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Code 9: a systematic approach for responding to medical emergencies occurring in and around a hospital. Members of the public expect to receive efficient and appropriate medical care if they become acutely ill or injured while in or around a hospital. Our institution became aware of the need for an organized system to respond to such emergencies involving patients, visitors, local community residents, and hospital employees, both inside the hospital and on the grounds surrounding the building. A search of the literature did not provide information regarding such a response; a survey of surrounding hospitals revealed no such plan in effect in other institutions. We therefore designed a plan to be superimposed onto our existing system for responding to in-house cardiac and respiratory arrests ("codes"). The results after one and one-half years appear encouraging. We recommend the establishment of such an emergency response system in all health care institutions.
4
Barotrauma associated with high-frequency jet ventilation for hypoxic salvage. Most reports describe reduction in proximal airway pressures with high-frequency jet ventilation. This led us to speculate that high-frequency jet ventilation might reduce barotrauma by providing alveolar ventilation at lower airway pressures. We describe a group of patients in whom a high incidence of barotrauma was observed after institution of high-frequency jet ventilation despite reduction in measured airway pressures. Fifteen hypoxic patients who could not be treated with conventional ventilation and who had no roentgenographic evidence of barotrauma were entered into the study. Airway pressures were measured during conventional ventilation and at 2 and 24 hours after high-frequency jet ventilation. Despite significant reduction in peak inspiratory and mean airway pressures, pneumothorax developed in seven of the 15 patients, an average of 21 hours after initiation of high-frequency jet ventilation. Five patients had bilateral pneumothorax and three developed tension pneumothorax. Despite reductions in proximal airway pressures, barotrauma is a significant potential complication of high-frequency jet ventilation in patients with noncompliant lungs. We currently place bilateral prophylactic thoracostomy tubes in patients with adult respiratory distress syndrome prior to initiation of high-frequency jet ventilation.
4
Fatigue. Fatigue is a pervasive, protective phenomenon affecting the totality of the individual. Assessment and management involve a wide range of activities to address the total human being's physical, psychological, cognitive, and spiritual dimensions. When elimination or neutralization of the effect of an antecedent condition is not an option, redesigning one's life-style may be the primary avenue of fatigue management. This protective mechanism, fatigue, may in fact herald the return of quality and purpose to one's life.
4
Abnormal baroreflex control of heart rate in decompensated congestive heart failure and reversal after compensation. Congestive heart failure (CHF) causes impairment of baroreflex control of heart rate (HR). To determine if this derangement is reversible, the cardiac chronotropic control was assessed in 10 patients with class IV chronic CHF of various etiologies before and after compensation achieved by bed rest, salt restriction, diuretics and vasodilators. Mean time between the 2 studies was 15 +/- 3 days. The management was modified 3 days before the second autonomic evaluation, so as to reestablish the same diet and pharmacologic conditions of the previous study. Compensation led to significant reduction in symptom-based class, body weight, and pulmonary and systemic congestion. Mean +/- standard error of the mean HR responses (beats/min) before and after compensation were, respectively: (1) to atropine (0.04 mg/kg): 10 +/- 2 and 27 +/- 2 (p less than 0.01); (2) to handgrip (30% maximum capacity, 1 minute): 9 +/- 2 and 19 +/- 3 (p less than 0.005); (3) to headup tilt (5 minutes): 4 +/- 3 and 20 +/- 4 (p less than 0.005). Mean +/- standard error of the mean baroreflex sensitivity (ms/mm Hg) of RR responses to phenylephrine and amyl nitrate-induced changes in systolic pressure was, respectively, in each condition: phenylephrine, 0.9 +/- 0.2 and 8 +/- 2.3 (p less than 0.05); amyl nitrate, 0.3 +/- 0.2 and 4.1 +/- 1.1 (p less than 0.05). A significant correlation between improvement in HR responses to atropine and tilt and changes in body weight was obtained. These findings show a reversible component of impaired baroreflex control of HR in severe CHF, possibly due to its congestive effects.
3
Retro-orbicularis oculus fat (ROOF) resection in aesthetic blepharoplasty: a 6-year study in 63 patients Sixty-three nonconsecutive patients have undergone resection of the retro-orbicularis oculus fat (ROOF) in conjunction with aesthetic blepharoplasty. In these patients, a consistent and useful ability to soften and flatten heaviness and bulkiness in the lateral upper orbital region was seen. Two patients developed postoperative hematoma, and two different patients had transient dry-eye symptoms following blepharoplasty. Twenty percent of patients had a transient degree of numbness in the lateral supraorbital nerve region, and all patients noted some transient numbness over the lateral upper brow region. No patient demonstrated significant paralysis of the orbicularis oculus or corrugator muscle. From this experience, retro-orbicularis oculus fat resection would appear to be a useful adjunct to standard blepharoplasty techniques in selected patients.
4
Neonatal small bowel atresia, stenosis and segmental dilatation. In 8 years, 44 neonates were treated for small bowel atresia, stenosis or segmental dilatation by one surgical team. There was a single lesion in 30 infants and 14 had two or more sites of intestinal obstruction. Associated gastrointestinal abnormalities were found in 23 (52 per cent) patients. Resection of the atresia(s) and primary anastomosis were performed in 34 infants and staged procedures were carried out in ten patients with complicated lesions. Patients undergoing staged procedures had a higher complication rate than those having primary repair (six out of ten and 11 out of 34 respectively). The overall initial survival rate was 93 per cent, rising to 100 per cent in those without associated anomalies or prenatal complications, but more than a quarter (27 per cent) of survivors have long-term disabilities.
4
Gracilis muscle transposition for faecal incontinence. Transposition of the gracilis muscle for faecal incontinence was performed in 13 patients. Six gained satisfactory continence, four were improved, two did not benefit from the operation and one patient died from intercurrent disease before closure of a pre-existing colostomy. Anal manometry compared with a control group showed no alteration in resting and pressure at a median of 35 mmHg (range 5-63 mmHg), whereas maximum squeeze pressure increased from a median of 38 mmHg (range 5-79 mmHg) to 59 mmHg (range 10-143 mmHg) (P = 0.041) which was, however, significantly lower than 130 mmHg (range 81-236 mmHg) in the control group. All patients who benefited from the operation had an increase in maximum squeeze pressure. The ability to retain a viscous fluid in the rectum was measured in seven patients, four of whom had gained satisfactory continence and three of whom had improved continence. They were able to retain a median volume of 200 ml (range 50-225 ml) without leakage compared with 325 ml (range 250-400 ml) in the control group. These patients could retain the maximum amount of viscous fluid for 5-8 min, whereas all control subjects could do so for more than 15 min. It is concluded that, although gracilis transposition never results in normal continence, acceptable continence may be achieved in selected patients provided careful attention is paid to the technical details of the procedure and provided that systematic postoperative exercises are performed.
1
Hepatocellular carcinoma within siderotic regenerative nodules: appearance as a nodule within a nodule on MR images. Large regenerative nodules in cirrhotic livers may accumulate iron and develop internal iron-poor foci of hyperplasia or malignancy. Magnetic resonance examinations were performed on 23 patients with biopsy-proved cirrhosis. A "nodule-within-nodule" appearance was noted in two patients. This appearance consisted of markedly low intensity of a large nodule on gradient-echo images, with one or two internal foci that were isointense to the liver. Each of the large nodules was 2 cm in diameter, and each of the internal foci was less than 1 cm. Serum alpha-fetoprotein levels were normal in both patients. Aspiration biopsy performed in one patient failed to show malignancy, but histologic confirmation of hepatocellular carcinoma was obtained eventually in both cases. The nodule-within-nodule sign, which reflects the unique histopathology of hepatocellular carcinoma in large siderotic regenerative nodules, is strongly suggestive of early hepatocellular carcinoma, even if serologic markers and biopsy results do not support this diagnosis.
1
Bipolar hemiarthroplasty for subcapital fracture of the femoral neck. A prospective randomised trial of cemented Thompson and uncemented Moore stems. We performed a randomised prospective trial to compare the results of 27 cemented and 26 uncemented bipolar hemiarthroplasties in active patients with displaced subcapital fractures of the femoral neck. After a mean follow-up of 17 months, significantly more of the uncemented group were experiencing pain in the hip and using more walking aids than the patients in the cemented group. The incidence of postoperative complications, the early mortality rate and the operating time and blood loss were not significantly different. Using otherwise identical prostheses the early results were much better with a cemented Thompson stem than with an uncemented Austin Moore stem.
4
Pharmacologic irreversible narrowing in chronic cerebrovasospasm in rabbits is associated with functional damage. We studied isolated basilar artery segments from a rabbit model of chronic cerebrovasospasm. Autologous blood placed around the basilar artery of rabbits killed 1, 2, 3, 4, 5, 6, 7, or 9 days later caused narrowing of the segments with a biphasic time course. The first (immediate) phase was reversed by intra-arterial papaverine; the second phase exhibited an increasing component of narrowing that was papaverine-insensitive. Based on the passive force/length curves, basilar artery segments became increasingly stiff over 9 days. By contrast, the segments' contractility decreased. Responses of the basilar artery segments were greater over the first few days, but then became less than that of saline-injected controls. Contractions in response to norepinephrine and potassium were reduced. Endothelium-based acetylcholine-induced vasodilation progressively diminished, as did the response to sympathetic nerve stimulation. There was a negative correlation between artery wall stiffness and contractility. The papaverine-insensitive component of angiographic narrowing correlated directly with loss of contractility and with artery wall stiffness. These results are consistent with the conclusion that increased artery wall stiffness is a primary determining factor in the arterial narrowing of chronic cerebrovasospasm.
3
Duodenal stricture: a complication of chronic fibrocalcific pancreatitis. Over the past 10 years, one of us (M.C.A.) has treated 92 patients who required operation for symptoms associated with alcohol-induced chronic fibrocalcific pancreatitis. Four of these patients had duodenal obstruction. All four had had lateral pancreaticojejunostomy to relieve pancreatic ductal obstruction and associated chronic abdominal pain; three of the four also required biliary diversion for stenosis of the intrapancreatic portion of the common bile duct. Each duodenal stricture required reoperation and gastrojejunostomy to bypass the site of obstruction. A review of the English language literature revealed that duodenal obstruction in patients with chronic fibrocalcific pancreatitis is uncommon, only 58 previous cases having been reported. All of those patients had pancreatic ductal obstruction, and more than half had concomitant distal biliary stenosis. Two thirds of the duodenal obstructions were treated by gastroenterostomy, and one third were resected. Duodenal obstruction in patients with chronic pancreatitis and biliary stricture appears to reflect an advanced form of the disease. Combined lateral pancreaticojejunostomy and biliary diversion has emerged as the preferred surgical procedure for this problem. Careful preoperative assessment for evidence of duodenal stenosis also is needed in this group of patients, and gastroenterostomy is indicated in appropriate cases.
1
Onset of induced atrial flutter in the canine pericarditis model To test the hypothesis that induced atrial flutter evolves from a transitional rhythm, the onset of 99 episodes of induced atrial flutter (mean cycle length 135 +/- 18 ms) lasting greater than 5 min in 40 dogs with sterile pericarditis was first characterized. In 85 (86%) of the 99 episodes, atrial flutter was preceded by a brief period (mean 1.4 +/- 0.9 s, range 0.4 to 42) of atrial fibrillation. Then, in 11 open chest studies, atrial electrograms were recorded simultaneously from 95 pairs of right atrial electrodes during the onset of 18 episodes of induced atrial flutter (mean cycle length 136 +/- 16 ms). Atrial flutter was induced by a train of eight paced atrial beats, followed by one or two premature atrial beats (7 episodes) or rapid atrial pacing (11 episodes). A short period of atrial fibrillation (mean cycle length 110 +/- 7 ms) induced by atrial pacing activated the right atrium through wave fronts, which produced a localized area of slow conduction. Then unidirectional conduction block of the wave front occurred for one beat in all or a portion of the area of slow conduction. This permitted the unblocked wave front to turn around an area of functional block and return through the area of slow conduction that had developed the unidirectional conduction block, thereby initiating the reentrant circuit. The location of the unidirectional block relative to the direction of the circulating wave fronts determined whether the circus movement was clockwise or counterclockwise. The area of slow conduction and unidirectional conduction block occurred where the wave front crossed perpendicular to the orientation of the atrial muscle fibers, suggesting a role for anisotropic conduction. These areas included the high right atrial portion of the sulcus terminalis (10 episodes), the low right atrial portion of the sulcus terminalis (4 episodes) and the pectinate muscle region (4 episodes). It is concluded that the development of a localized area of slow conduction in the right atrium followed by unidirectional conduction block in this area produced during a short period of atrial fibrillation or rapid atrial pacing is necessary for atrial flutter to occur in this model.
4
Mental stress as an acute trigger of ischemic left ventricular dysfunction and blood pressure elevation in coronary artery disease. Acute mental stress may be a frequent trigger of transient myocardial ischemia, myocardial infarction and sudden cardiac death. In an experimental setting, the effect of mental stress on hemodynamics and left ventricular wall motion abnormalities (as detected by radionuclide ventriculography) was measured in 29 patients with exercise-induced myocardial ischemia. Seventy-five percent of the patients demonstrated mental stress-induced wall motion abnormalities. Patients frequently exhibited greater increases in peak systolic arterial pressure during mental stress than during exercise. Personally relevant mental stress is the most potent type of mental stress, both in terms of frequency and magnitude of ischemia. Most mental stress-induced ischemic episodes are clinically and electrocardiographically silent and occur at heart rates significantly lower than those seen during exercise. Both systolic and diastolic blood pressure increased during mental stress-induced ischemia, suggesting that increased myocardial oxygen demand plays a role in the pathophysiology of mental stress-induced transient ischemia. The significant magnitude and acute onset of this mental stress-induced blood pressure elevation may in some manner contribute to atherosclerotic plaque rupture. These findings may provide a pathophysiologic link to the epidemiologic association between mental stress and acute ischemic coronary events. A new ambulatory radionuclide detector that can concurrently monitor left ventricular ejection fraction and electrocardiographic ST-segment change may enhance the detection and evaluation of transient myocardial ischemia in ambulatory coronary patients.
3
Use of the fistula assessment monitor to detect stenoses in access fistulae. Twenty-three unselected hemodialysis patients with functioning access arteriovenous fistulae were studied prospectively to determine the best technique for detecting stenoses within the fistulae. Combined clinical assessment and fistula assessment monitoring were compared with transbrachial angiography. Fistula assessment monitoring was more accurate (96%) than combined clinical assessment (accuracy, 52%) in stenosis detection. Complications of angiography occurred in 17% of patients; there were no complications of fistula assessment monitoring. Fistula assessment monitoring was better than combined clinical assessment in predicting clinical outcome for arteriovenous fistulae over 6 months and was as good as angiography. Routine fistula assessment monitoring could reduce inappropriate angiography and detect clinically significant silent stenoses. It is an ideal method for monitoring arteriovenous access fistulae.
3
Randomised, double-blind, placebo-controlled trial of nimodipine in acute stroke. Trust Study Group. The value of oral nimodipine 120 mg per day for acute stroke was assessed in a randomised, double-blind, placebo-controlled multicentre study of 1215 patients. The primary end-point was independence after 6 months, defined as a score of 60 or more on an activities of daily living (ADL) scale, the Barthel index. Patients were entered into the trial if they were aged over 40, became hemiparetic in the previous 48 h, were conscious, were able to swallow, and had been living independently before the stroke. At 6 months, 55% of the nimodipine group and 58% of the placebo group were independent, the odds ratio for independence on nimodipine being 0.88 (95% confidence limits 0.70-1.10). For mortality the odds ratio with nimodipine was 1.22 (95% confidence limits 0.95-1.57). ADL and neurological scores also suggested delayed recovery in the nimodipine group at 3 weeks. The results do not support the case for oral nimodipine therapy 120 mg per day starting within 48 h of the stroke, for patients with acute stroke.
2
Desmoplastic variant of ameloblastoma: report of a case and review of the literature. A case of desmoplastic variant of ameloblastoma is reported. The lesion, in a 36-year-old Japanese woman, was successfully treated by partial maxillectomy. Reconstruction was carried out with a block of hydroxyapatite about 7 years and 6 months later. Six cases, including our case, reported up to the present are summarized and reviewed.
0
Reduction of gastric ulcer recurrence after suppression of Helicobacter pylori by cefixime. The effect on the recurrence of gastric ulcers after suppression of Helicobacter pylori by combined treatment with cimetidine and the antimicrobial drug cefixime was investigated. Twenty one of 43 patients with endoscopically proved gastric ulcer and H pylori infection were randomly assigned to receive cimetidine 800 mg daily for 12 weeks; the remaining 22 patients received cimetidine 800 mg daily for 12 weeks plus cefixime 100 mg daily for the last two weeks. After treatment, 88% of 17 patients on cimetidine only remained H pylori positive, whereas combined administration of cimetidine and cefixime had suppressed H pylori in 78% of 18 patients (p less than 0.05). Seventeen patients in the former group whose ulcers healed but who remained H pylori positive and 18 patients in the latter group whose ulcers healed and who were no longer infected with H pylori continued to be followed after treatment. These patients underwent endoscopy to detect ulcer recurrence if symptomatic, or at 12 and 24 weeks if asymptomatic. At 12 weeks, recurrence was observed in seven of 15 (47%) patients in whom H pylori persisted, but in only one of 14 (7%) patients in whom H pylori had been suppressed (p less than 0.05). At 24 weeks, however, recurrence rates were similar between the two groups. These findings indicate that H pylori infection may be closely related to early ulcer recurrence.
1
Subarachnoid hemorrhage caused by a fungal aneurysm of the vertebral artery as a complication of intracranial aneurysm clipping. Case report. Intracranial aneurysms are an uncommon manifestation of fungal infection. A case is described in which the formation of an aneurysm followed an intracranial intraoperative Aspergillus infection attributable to a long period of preoperative antibiotic medication and immunosuppressive therapy with steroids.
4
Coronary collateral recruitment: functional significance and relation to rate of vessel closure. Studies in animals and humans have demonstrated the anatomic presence and functional significance of coronary collaterals. The extent of collateralization varies among species and among individuals. Collateral vessels are usually adequate for preserving resting regional and global ventricular function in the face of coronary obstruction. During stress, however, collateral supply may be inadequate. Collateral development is a time-dependent process during both the initial occlusion and following transient reflow and reclosure. Therefore when a previously collateralized coronary occlusion is recanalized and then recloses, the extent of the resulting collateral recruitment will depend, at least in part, upon the period of reflow between the two occlusions. The longer the reflow period, the less enhanced will be the collateralization. This is illustrated in the cases presented and has also been demonstrated in animal studies. The exact mechanisms for this recurrent collateral recruitment need further study.
4
Femorofemoral bypass: a profile of graft failure. We have reviewed our experience with 71 patients who had a femorofemoral bypass for unilateral iliac artery occlusion or stenosis. We analyzed morbidity, mortality, initial relief of symptoms, early patency, and long-term primary and secondary patency; and we attempted to identify the cause of graft failure. The overall hospital mortality after operative repair was 4%. One-year survival was 84% and 2-year survival was 81%. Early patency was 98.5% at 1 month, late patency was 91% at 1 year and 82% at 5 years. The major cause of graft failure was inadequate run-off and outflow disease progression.
4
Prediction of cognitive change as a function of preoperative ability status among temporal lobectomy patients seen at 6-month follow-up. The relationship between preoperative ability levels and postoperative changes in cognitive function was examined among 23 left (LTL) and 19 right (RTL) temporal lobectomy patients using a battery of memory, language, and visuospatial tasks administered approximately 3 months before surgery and at 6 months follow-up. Higher preoperative performances on the memory and language measures were associated with larger decrements in postsurgical scores among the LTL patients. The RTL group showed no consistent relationship between preoperative ability levels and subsequent postsurgical cognitive changes. Based on the present data, we constructed base-rate tables for the Wechsler Memory Scale-Revised indicating the likelihood of measurable gains or losses in memory as a function of presurgical ability level for patients undergoing LTL. While tentative, these data provide a useful and practical guide for counseling prospective epilepsy patients of the attendant cognitive risks of LTL.
4
Uptake of 2-deoxy, 2-(18F) fluoro-D-glucose in bladder cancer: animal localization and initial patient positron emission tomography. An orthotopically transplanted, locally metastasizing rat bladder tumor model was developed to evaluate the extent of uptake of fluoro-deoxy-glucose (FDG) in bladder cancer. Significant uptake of FDG in localized bladder tumors in rats was shown, with an average tumor-to-blood ratio of 39 at 2 hours after intravenous FDG administration. Metastases (3 nodal and 1 peritoneal) also showed significant uptake of FDG, with an average metastasis-to-blood ratio of 21.7, and tumor involved-to-normal lymph node ratio of 5.3. Because FDG is excreted in the urine, urinary FDG potentially could prevent the use of FDG/positron emission tomography (FDG/PET) scanning for localized bladder cancer. Bladder lavage successfully reduced the retention of FDG in the normal rat bladder, with an estimated uptake ratio of tumor-to-normal bladder of 13.1 after 5 ml. saline irrigation. Based on these data, we performed an FDG/PET scan of a patient with biopsy proved recurrent intravesical bladder cancer after radiation therapy. Computerized tomography (CT) of the pelvis showed abnormalities consistent with radiation scarring and extravesical tumor. Due to the scarring, the extent of tumor growth could not be determined. The patient also had pulmonary opacities seen on chest radiography. The FDG/PET scan of this patient showed significant extravesical uptake in the pelvis, confirming the abnormality noted on CT. Good images of the clinically apparent metastases in the chest also were obtained. These preliminary data indicate that FDG/PET imaging of bladder cancer is feasible and it may provide new information for the diagnosis and staging of patients with bladder cancer.
0
Familial hemifacial spasm associated with arterial compression of the facial nerve. Case report. This report of an 88-year-old woman with familial hemifacial spasm includes the first published postmortem description of hemifacial spasm with cross-compression of the seventh cranial nerve root exit zone by a redundant loop of the anterior inferior cerebellar artery and associated vascular plexus. Histological examination of the seventh and eighth cranial nerve complex suggested nerve degeneration because increased numbers of corpora amylacea were present just distal to the compression concavity. There was no evidence of demyelination or gliosis of the nerve. This case suggests that vascular compression of the nerve root exit zone is an important condition in the etiology of most of these cases. This is the third reported case of familial hemifacial spasm; to date, all such patients have had left facial involvement. The family pedigree in this case suggests a pattern of autosomal-dominant inheritance with partial penetrance. The genetic basis for familial hemifacial spasm may involve anatomical variants or anomalies of the posterior circulation, since both posterior inferior cerebellar arteries were congenitally absent in this case.
2
Patterns of acute respiratory tract infection in children: a longitudinal study in a depressed community in Metro Manila. The incidences of acute respiratory tract infection (ARI) and acute lower respiratory infection (ALRI) were 6.1 and 0.5 per child-year, respectively, in children less than 5 years old in a depressed urban community in Manila. The peak age-specific incidence occurred in those children 6-23 months old for ARI and 6-11 months old for ALRI. Age less than 2 years, malnutrition, household crowding, and parental smoking were associated with a statistically significant, though modest, increase in ARI morbidity. The crude mortality rate was 14.3 per 1,000 children 0-4 years old, with a corresponding ARI-specific mortality rate of 8.9 per 1,000. The prevalence of viral infection was 32.8 and that of bacteremic ALRI was 6.7 per 1,000 children with moderate ALRI. Respiratory syncytial virus was the predominant viral pathogen, while Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus were the most frequently isolated bacterial pathogens. Transmission of respiratory pathogens in depressed communities, facilitated by inadequate housing, inaccessible health services, and prevalent malnutrition, will continue unless meaningful socioeconomic improvement is realized.
4
Species-dependent effects of adenosine on heart rate and atrioventricular nodal conduction. Mechanism and physiological implications. This study 1) compares the negative chronotropic and dromotropic actions of adenosine in guinea pig, rat, and rabbit hearts; 2) investigates the mechanism(s) for the different responses; and 3) determines the physiological implications. Isolated perfused hearts were instrumented for measurement of atrial rate and atrioventricular (AV) nodal conduction time. Differences in metabolism of adenosine were determined in the absence and presence of dipyridamole (nucleoside uptake blocker) and erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA, adenosine deaminase inhibitor). Dipyridamole plus EHNA decreased adenosine's EC50 for the negative dromotropic effect by 14-fold in guinea pig heart and 1.6-fold in rat heart. This is consistent with the greater number of [3H]nitrobenzylthioinosine binding sites measured in membranes from guinea pig (1,231 +/- 68 fmol/mg protein) compared with rat (302 +/- 31 fmol/mg protein) and rabbit (260 +/- 28 fmol/mg protein) atria. The potency of adenosine to slow atrial rate and prolong AV nodal conduction time was greater in guinea pig than in rat or rabbit hearts. This rank order of potency correlated well with the number of binding sites for the specific adenosine receptor radioligand 125I-aminobenzyladenosine in guinea pig (102 +/- 13 fmol/mg protein), rat (11 +/- 0.5 fmol/mg protein), and rabbit (8 +/- 1 fmol/mg protein) atrial membranes. Hypoxia increased the rate of adenosine release by severalfold and caused slowing of heart rate and AV block. In spontaneously beating hearts, the main effect of hypoxia was a slowing of ventricular rate, which in the guinea pig heart was due to AV block and in the rat heart to atrial slowing. In atrial paced hearts, hypoxia caused a marked prolongation of AV nodal conduction time in guinea pig (39 +/- 4 msec) and rabbit (29 +/- 5 msec) hearts, but only small effect in rat hearts (10 +/- 2 msec). The differences in response to hypoxia could be accounted for by the species-dependent differences in the 1) amount of adenosine released and metabolized, 2) sensitivity of the hearts to adenosine, and 3) dependency of AV nodal conduction on atrial rate. The findings indicate that the results from physiological or pharmacological studies on adenosine in one species may not be applicable to others, and the ultimate effect of adenosine and hypoxia is to slow ventricular rate.
3
Cystic mesothelioma of peritoneum: occurrence in a man. We report a case of cystic mesothelioma of the peritoneum in a 54-year-old man in whom cystic masses were removed twice by surgery at an interval of 2 years. The patient died of cardiac arrest shortly after the second operation for a concurrent unresectable colonic cancer. The pathogenesis of the disease is uncertain, but we consider it neoplastic of low grade malignancy.
0
Diagnostic value of brush cytology in the diagnosis of bile duct carcinoma: a study in 65 patients with bile duct strictures. Malignant strictures of the extrahepatic bile ducts are difficult to distinguish from benign strictures, particularly in patients with primary sclerosing cholangitis. Because attempts at diagnosing small cancers with fine-needle aspiration biopsy are not possible in the absence of an associated mass lesion and because the sensitivity of exfoliative biliary cytology is controversial, brush cytology has been used as a potential means of establishing a specific diagnosis of bile duct carcinoma. Herein we report our experience with this technique when performed on 65 patients over a 5-yr period. Each had at least one brushing. Thirty-seven were found to have bile duct carcinoma and 28 were found to have benign strictures. Of these 37, the first brushing was positive for malignancy in 15 (40%), whereas four (11%) had cells suspected but not diagnostic of malignancy. Thirteen patients with bile duct carcinoma whose initial brushings were negative for malignancy had second brushings. Of these, five (38%) had malignant cells, whereas three (24%) yielded suspicious cells. Three of the eight whose first two brushings were negative for malignancy were found to have malignant cells on the third brushing. In contrast, of the 28 patients with benign strictures, malignant cells were never found. However, in two patients, suspicious cells were reported with the first but not the second brushing. A single negative or suspicious cytological finding decreased the probability of bile duct carcinoma to 43%. Two and three sequential negative tests reduced the probability to 32% and 0%, respectively.
4
Gastric lymphoma causing granulocytopenia and cold intolerance, with recovery after treatment. A 34-year-old man was found to have granulocytopenia with a white blood count of 2.3 x 10(9) l-1, consisting of 10% segmented neutrophils, 50% monocytes and 40% lymphocytes. A bone marrow aspirate showed 20% promyelocytes and 10% blasts with monoblastic features, and a smouldering myelomonocytic leukaemia was considered to be a possible diagnosis. In cold weather the patient experienced cold intolerance with acrocyanosis and small ulcerations on the ears. The test for heparin-precipitable protein ('cryofibrinogen') was strongly positive. During the following year, these signs and symptoms persisted, and the patient also developed constant moderate pain in the epigastric region. Gastroscopy revealed a large lymphoma of the stomach, which was a high-grade malignant centroblastic type of non-Hodgkin's lymphoma. After successful removal of the tumour, and six courses of potent cytostatic combinations, the patient recovered completely, and the granulocytopenia and cold intolerance disappeared.
3
Endogenous insulin-like growth factor (IGF) binding proteins cause IGF-1 resistance in cultured fibroblasts from a patient with short stature. The ED50 of insulin-like growth factor (IGF)-I-stimulated alpha-aminoisobutyric acid (AIB) uptake (mean +/- SD) in cultured fibroblasts from a child with short stature that we have reported (1.40 +/- 0.24 nM), is significantly higher than the ED50 of IGF-I-stimulated AIB uptake in fibroblasts from 11 normal subjects (0.42 +/- 0.12 nM) and from 127 short children (0.35 +/- 0.11 nM). Similarly, the ED50 of IGF-I-stimulated thymidine incorporation in fibroblasts from this child is 2.8 times higher than that in fibroblasts from four normal subjects. To minimize potential modulation of IGF-I action by endogenous IGF binding proteins in these assays, fibroblast responsiveness to [Q3,A4,Y15,L16]IGF-I, an IGF-I variant that has a 600-fold reduced affinity for serum IGF binding proteins, has been examined. The biological activity of this variant is comparable in the patient's and normal fibroblasts, suggesting that the resistance to IGF-I action cannot be attributed to a defective IGF-I receptor. To investigate directly the possibility that IGF-I sensitivity in the patient's fibroblasts is reduced by endogenous IGF binding proteins (IGFBP), binding proteins that are secreted into AIB assay buffer during a 3-h collection and that are cell-associated at the end of the collection have been analyzed. Ligand blot analysis of conditioned AIB assay buffer demonstrates that fibroblasts from the patient secrete 1.3-2.2 times more of Mr 46,400/42,900, 32,000, and 26,800 binding proteins than normal fibroblasts. The major difference between fibroblasts from the patient and from normal subjects is a striking 10-fold increase in the amount of a cell surface Mr 32,000 binding protein in the patient's fibroblasts. The Mr 32,000 binding protein is similar in size to IGFB-1 and different from IGFBP-2 and IGFBP-3, but it does not cross-react with an antibody against IGFBP-1. We conclude that the resistance to IGF-I action in the patient's fibroblasts is caused by an abnormal production and/or cell association of IGF binding proteins.
4
Intradural spinal cord tumor presenting as a subarachnoid hemorrhage: magnetic resonance imaging diagnosis. Negative findings on four-vessel angiography after a subarachnoid hemorrhage are seen in 5 to 30% of patients. A previously silent lesion in the spinal canal may be responsible for the ictus in a small percentage of this group. The etiological factors include tumors and arteriovenous malformations; however, investigations of such lesions have been limited to patients with signs and symptoms of spinal cord or nerve root pathological processes. This report describes the management of a 56-year-old woman with clinical findings typical of an aneurysmal subarachnoid hemorrhage and negative findings on cerebral angiography, in whom magnetic resonance imaging with gadolinium enhancement revealed an intradural extramedullary cervical schwannoma. For this reason, cervicothoracic magnetic resonance imaging with gadolinium enhancement should be considered as an adjunctive scanning examination in all patients with a subarachnoid hemorrhage and negative findings on angiography.
2
Chronic urticaria exacerbated by the antioxidant food preservatives, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). Two patients with chronic idiopathic urticaria in whom remissions were achieved with dye- and preservative-elimination diet had exacerbations of their urticaria when they were challenged under double-blind, placebo-controlled conditions with butylated hydroxyanisole and butylated hydroxytoluene. After elimination of butylated hydroxyanisole and butylated hydroxytoluene from their diets, there was marked abatement of the frequency, severity, and duration of their urticaria. These antioxidants appear capable of aggravating symptoms in certain patients with chronic urticaria.
4
Hepatocellular carcinoma presenting with pyrexia and leukocytosis: report of five cases. In the past 26 years we have encountered five patients with primary liver malignancy clinically characterized by high remittent fever and leukocytosis mimicking liver abscess. Two patients underwent exploratory laparotomy, and drainage was carried out in another. The clinical courses went rapidly downhill. The liver was cirrhotic in two patients. The interior of the main mass was almost totally necrotic in four cases. Histologically, the malignant cells in the main portion resembled sarcoma, but in some areas cells appeared epithelial with eosinophilic cytoplasm and were in a trabecular arrangement, except for one case not subjected to autopsy in which histological study was inadequate because of extensive necrosis. It seems that these neoplasms were very poorly differentiated hepatocellular carcinomas rather than combinations of sarcoma and hepatocellular carcinoma. These patients, therefore, may represent a distinct clinicopathological type of hepatocellular carcinoma that is very rare in Japan but perhaps more common in South Africa, where similar cases have been clinically described in larger numbers.
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Spontaneous electromyographic potentials in chronic spinal cord injured patients: relation to spasticity and length of nerve. Nine patients with complete cervical spinal cord injury (SCI) had their vastus medialis, tibialis anterior, and gastrocnemius muscles evaluated with an electromyographic (EMG) examination in the acute (four to eight weeks) and chronic (more than one year) phases. The hypothesis that spontaneous EMG activity changes with time was assessed. During the chronic phase evaluation, a conduction study was performed to rule out peripheral nerve damage, and the amount of reflex activity was assessed on a scale of 0 to 5 (0 = areflexia; 5 = greater than 5 beats of clonus) to estimate the amount of spasticity. Subjects demonstrated normal conduction through the sensory (sural nerve) and/or motor segments of the peroneal and tibial nerves. In the acute phase, each muscle had spontaneous activity with no significant variation between different muscles of the same patient. In the chronic phase, there was a positive correlation between the degree of spontaneous activity in a muscle and the length of its axon (p less than .01) and a negative correlation between the amount of spontaneous activity and the degree of reflex activity (p less than .01). Specifically, the lower motor neuron in the chronic phase of an SCI seems to behave much like an axonopathy where the degree of spontaneous EMG activity is dependent on the length of the axon, with the additional concept that spontaneous activity is inhibited by spasticity.
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Acute myeloid leukemia and background radiation in an expanded case-referent study. A case-referent study that investigated possible associations between environmental and occupational exposures and acute myeloid leukemia was performed on 86 cases and 172 referents, all of whom were living. Exposure information was obtained through a questionnaire mailed to each subject. An association was found between time spent in concrete buildings at home and work and leukemia morbidity. In addition, extensive x-ray examinations that occurred more than 5 y prior to diagnosis were more common among cases than referents.
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Paralytic shellfish poisoning--Massachusetts and Alaska, 1990 [published erratum appears in MMWR Morb Mortal Wkly Rep 1991 Apr 12;40(14):242] Paralytic shellfish poisoning (PSP) is a foodborne illness caused by consumption of shellfish or broth from cooked shellfish that contain either concentrated saxitoxin, an alkaloid neurotoxin, or related compounds. This report summarizes outbreaks of PSP that occurred in Massachusetts and Alaska in June 1990.
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A model to predict multivessel coronary artery disease from the exercise thallium-201 stress test. PURPOSE: The aim of this study was to (1) determine whether nonimaging variables add to the diagnostic information available from exercise thallium-201 images for the detection of multivessel coronary artery disease; and (2) to develop a model based on the exercise thallium-201 stress test to predict the presence of multivessel disease. PATIENTS AND METHODS: The study populations included 383 patients referred to the University of Virginia and 325 patients referred to the Massachusetts General Hospital for evaluation of chest pain. All patients underwent both cardiac catheterization and exercise thallium-201 stress testing between 1978 and 1981. RESULTS: In the University of Virginia cohort, at each level of thallium-201 abnormality (no defects, one defect, more than one defect), ST depression and patient age added significantly in the detection of multivessel disease. Logistic regression analysis using data from these patients identified three independent predictors of multivessel disease: initial thallium-201 defects, ST depression, and age. A model was developed to predict multivessel disease based on these variables. As might be expected, the risk of multivessel disease predicted by the model was similar to that actually observed in the University of Virginia population. More importantly, however, the model was accurate in predicting the occurrence of multivessel disease in the unrelated population studied at the Massachusetts General Hospital. CONCLUSION: It is, therefore, concluded that (1) nonimaging variables (age and exercise-induced ST depression) add independent information to thallium-201 imaging data in the detection of multivessel disease; and (2) a model has been developed based on the exercise thallium-201 stress test that can accurately predict the probability of multivessel disease in other populations.
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Nasal augmentation with split calvarial grafts in Orientals. This study reports on my experience with autogenous split calvarial grafts in nasal augmentation in 62 Orientals. In 78 percent of patients, the procedure was performed under local anesthesia in an outpatient setting. Total operating time for harvesting of split calvarial grafts ranged from 20 to 55 minutes, with a mean of 32 minutes. Patients ranged in age from 16 to 48 years, with a mean of 27 years. Follow-up was from 6 months to 8 years, with an average of 3.1 years. Intraoperative discomfort was uniformly low and well tolerated when local anesthesia was used. The complication rate was 8.0 percent, with three cases of minor seroma-hematoma formation at the bone-graft donor site. These were treated with aspiration. There were two recipient-site complications, with one case of complete bone resorption that occurred in a densely fibrotic nose with preexisting septal perforation and a case of overcorrection that was successfully rasped 1 year later. Because of their easy accessibility beneath the scalp, split calvarial grafts to the nose are useful in various types of nasal augmentation, and the technique is offered as a practical alternative to the use of alloplastic materials.
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Effects of treatment on long-term survivors with malignant astrocytomas. We reviewed the records of 160 consecutive patients with glioblastoma and anaplastic astrocytoma to evaluate the long-term consequences of radiation therapy and chemotherapy. We defined long-term survivors as those patients with glioblastoma or anaplastic astrocytoma who lived at least 100% longer than median survival of historical controls, for example, 2 years for patients with glioblastoma and 4 years for patients with anaplastic astrocytoma. There were 9 (5.6%) long-term survivors. Three (30%) became demented and died without evidence of tumor recurrence. One, after survival of 10 years, died of tumor recurrence. Of the remaining survivors, 2 (22%) have significantly impaired short-term memory function and other neurological deficits such as gait apraxia. Three (30%) can function independently. It is likely but cannot be proved that it is radiotherapy and not chemotherapy that is the causal factor of this dismal therapeutic outcome. Our study suggests restraint in the use of radiotherapy for patients with brain tumors that have more favorable prognoses than glioblastomas and anaplastic astrocytomas, such as low-grade astrocytomas and oligodendrogliomas.
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Cutaneous T-cell lymphoma (parapsoriasis en plaque). An association with pityriasis lichenoides et varioliformis acuta in young children. Pityriasis lichenoides et varioliformis acuta (PLEVA) and pityriasis lichenoides chronica (PLC) are related benign disorders without recognized association with cutaneous T-cell lymphoma (CTCL). We report the cases of two children with documented PLEVA evolving into CTCL over several years. One child had the clinical lesions of PLC but the dermatopathologic findings of PLEVA at age 2 years. At age 12 years, he had skin changes of poikiloderma atrophicans vasculare and dermatopathologic findings consistent with parapsoriasis en plaque. The second child presented at age 7 years with scaling dermatitis and dermatopathologic findings of PLEVA. At age 12 years, the histologic diagnosis was parapsoriasis. Monoclonal antibody studies performed on biopsy specimens from both patients revealed 70% to 100% cells staining with CD5, 80% to 90% staining with CD4, 30% to 50% staining with CD8, and an increase in CD1-staining cells in the papillary dermis, indicating a predominantly helper T-cell infiltrate. We believe that PLC and PLEVA may be part of the spectrum of CTCL. Furthermore, CTCL may be more common in young children than once thought.
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A phase I clinical, plasma, and cellular pharmacology study of gemcitabine. A novel deoxycytidine analog, gemcitabine (2',2'-difluorodeoxycytidine [dFdC]), has been studied in a phase I clinical and pharmacology trial. Doses ranging from 10 to 1,000 mg/m2 were administered over 30 minutes weekly times 3 weeks every 4 weeks. The maximum-tolerated dose (MTD) was 790 mg/m2. The dose-limiting toxicity was myelosuppression, with thrombocytopenia and anemia quantitatively more important than granulocytopenia. Nonhematologic toxicity was minimal. Two responses in patients with adenocarcinomas of the colon and lung were documented. The maximum dFdC plasma concentration, reached after 15 minutes of infusion, was proportional to the total dose administered. Elimination, due mainly to deamination, was rapid (terminal half-life [t1/2], 8.0 minutes) and dose independent. The deamination product 2',2'-difluorodeoxyuridine (dFdU) was eliminated with biphasic kinetics characterized by a long terminal phase (t1/2, 14 hours); it was the sole metabolite detected in urine. The concentration of dFdC 5'-triphosphate in circulating mononuclear cells increased in proportion to the dFdC dose at infusions between 35 and 250 mg/m2. No further increment in dFdC 5'-triphosphate (dFdCTP) was observed at higher doses, which resulted in plasma dFdC concentrations greater than 20 mumol/L (350 to 1,000 mg/m2), suggesting saturation of dFdC 5'-phosphate accumulation. The recommended dose for phase II clinical trials in solid tumors is 790 mg/m2/wk.
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Unusual haemostasis for an unusual tumour. Catastrophic bleeding from a tactile neurofibroma affecting the thoracic vertebrae. Case report. The symptomatology of a typical acute descending thoracic aorta dissection was imitated by profuse haemorrhage caused by a benign tumour composed almost exclusively of Wagner-Meissner like tactile corpuscles and fatty tissue. The tumour caused extensive destruction of the bodies of the fifth and sixth thoracic vertebrae at the level of the vertebro-costal articulation. Emergency cross clamping of the descending aorta and haemostasis of the bleeding from osteal defects by tamponade with bone polymethyl methacrylate appeared the only way to control the life threatening haemorrhage. It seems that an intrathoracic tactile neurofibroma with a similar case history has not been reported till now.
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AIDS enteropathy: occult enteric infections and duodenal mucosal alterations in chronic diarrhea OBJECTIVE: To investigate occult enteric infections and morphologic changes in the small intestine in patients with advanced human immunodeficiency virus (HIV) infection and chronic diarrhea of undefined cause. DESIGN: Case-control study. SETTING: Referral-based clinic and hospital in tertiary care center. PATIENTS: Twenty-two patients with advanced HIV infection (19 with the acquired immunodeficiency syndrome [AIDS], 3 with AIDS-related complex) with chronic diarrhea, selected because of previously negative stool evaluations for bacterial or parasitic pathogens, were compared with 13 patients with advanced HIV infection (9 with AIDS, 4 with AIDS-related complex) without diarrhea by analysis of endoscopic biopsies using light and electron microscopy, viral culture, and morphometric studies. Both groups were convenience samples and had at least 7 months follow-up. MEASUREMENTS AND MAIN RESULTS: Eleven of twenty-two patients with HIV infection and chronic diarrhea but only 1 of 13 patients without diarrhea showed occult enteric pathogens (that is, undetected by routine studies) after extensive evaluation of duodenal and colorectal biopsies. Mycobacterium avium-intracellulare and microsporidia were the most common occult agents in study patients with diarrhea (5 each). Patients with diarrhea and occult enteric infections had greater weight loss (mean, 14.3 kg compared with 6.2 kg; P less than 0.05) and shorter survival (1 of 11 compared with 8 of 11 still alive; P less than 0.004) than those with diarrhea but no identified pathogens (defined as "AIDS enteropathy"). Duodenal morphometry showed decreased villus-to-crypt ratios because of villus atrophy and crypt elongation in HIV-infected patients both with and without diarrhea compared with normal controls (P less than 0.001 for each). All three groups showed comparable frequencies of epithelial mitoses. CONCLUSIONS: Further endoscopic biopsy evaluation of patients with AIDS who had unexplained chronic diarrhea showed an occult infectious cause in half of the cases. However, altered villus and crypt architecture in advanced HIV infection was independent of the presence of diarrhea or enteric infection and therefore did not correlate with AIDS enteropathy. Subnormal epithelial proliferation in response to injury could be a factor, but the underlying cause of the architectural changes remains obscure. We suggest that T-cell dysfunction may play a role.
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Transthyretin receptors on human astrocytoma cells. Transthyretin (TTR), a transport protein for T4 and retinol-binding protein, is the principal T4-binding protein of cerebrospinal fluid. Its function in regard to the delivery of its ligands and in other respects is unclear. The binding of [125I] TTR to cultured human astrocytoma cells was studied to determine whether these cells carry receptors for TTR. Scatchard analysis was consistent with a single class of binding sites with a Kd of 3 nM. No significant cross-reactivity with transferrin or serum albumin was observed. Internalization of TTR was temperature dependent and proportional to receptor occupancy. Dilutions of cerebrospinal fluid displaced [125I]TTR in proportion to their content of radioimmunoassayable TTR and in parallel with purified TTR. The uptake and internalization of TTR increased in the presence of high T4 or T3 concentrations. These results demonstrate that TTR binds to specific high affinity receptors on human astrocytoma cells. Receptor binding of TTR provides a potential mechanism for the delivery of its ligands within the central nervous system.
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Oral manifestations of HIV infection and their management. I. More common lesions. Oral lesions are common at all stages of HIV infection. This first of two articles reviews the clinical features and pathogenesis of common oral manifestations of HIV disease (candidiasis, hairy leukoplakia, Kaposi's sarcoma, and HIV-related periodontal disease) and considers current treatment measures.
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Effect of extracorporeal membrane oxygenation on survival of infants with congenital diaphragmatic hernia. To determine the effect of extracorporeal membrane oxygenation (ECMO) on the survival of infants with congenital diaphragmatic hernia, we undertook a retrospective review of 31 infants with congenital diaphragmatic hernia treated at Children's National Medical Center. Infants were categorized by means of the Bohn quadrant analysis to determine the impact of ECMO on infants with congenital diaphragmatic hernia and a "poor prognosis." All infants assigned to the Bohn 100% mortality quadrant required ECMO. The survival rate in this group was 86% (6/7) when assessed preoperatively and 67% (6/9) when assessed postoperatively. Comparison of the change occurring in ventilation index and arterial carbon dioxide pressure demonstrated that after repair the clinical condition of 48% of infants deteriorated, 40% improved, and 12% remained unchanged. Of the 12 infants whose condition was worse after surgery, 11 eventually required ECMO. Our review demonstrates that ECMO improved survival significantly in infants with congenital diaphragmatic hernia who had a "poor prognosis" by the criteria of Bohn et al. We recommend consideration of ECMO for all infants with congenital diaphragmatic hernia for whom maximal medical therapy has failed.
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Etoposide in the management of non-small cell lung cancer. Etoposide is a phase-specific, schedule-dependent derivative of podophyllotoxin that appears to act by inhibiting DNA-topoisomerase II. Early preclinical work demonstrated sharp activity in mouse leukemias and possible synergy with cisplatin. As a single agent (either orally or intravenously), it demonstrated limited benefit in non-small cell lung cancer (NSCLC), with response rates around 10%. In combination with cisplatin, it has become a mainstay of chemotherapeutic efforts, either as primary therapy or in conjunction with radiation. Response rates in advanced disease average around 30%, climbing to more than 50% in patients with Stage IIIA or IIIB disease. More recent work suggests that the issue of the true synergy of etoposide with cisplatin in NSCLC needs reassessment. The relative roles of etoposide and cisplatin in the combination are unclear, as several studies conflict. Pharmacokinetic data suggest that multiple daily fractions of etoposide are superior to prolonged infusions, warranting several future trials. The current major role for etoposide plus cisplatin would appear to be in multimodality therapy where the combination can be readily combined with radiation and/or surgery. Several other agents have been studied with etoposide or etoposide plus cisplatin (mitomycin, vindesine, doxorubicin, cyclophosphamide, ifosfamide, and carboplatin), but it is unclear whether the addition of any of them offers any response or survival advantage.
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Regulation of the truncation of luteinizing hormone receptors at the plasma membrane is different in rat and mouse Leydig cells. Regulation of the truncation of LH receptors was investigated in two types of mouse tumor Leydig cells (MA10 and MLTC-1), rat testis Leydig cells (RTL), and a rat tumor Leydig cell (R2C). Receptor numbers were measured by binding [125I]hCG to the cells cultured in monolayers. Addition of 3.3 nM LH for 2 h at 34 C had no detectable effect on binding sites in RTL or R2C cells, but in MA10 and MLTC-1 cells it caused a loss in binding sites. The effect on MA10 and MLTC-1 cells could be mimicked by inhibiting receptor internalization with 5 mM NaN3 and prevented by the addition of protease inhibitors. Incubating RTL and R2C cells with protease inhibitors caused a 2- to 3-fold increase in binding sites and a 2- to 3-fold increase in LH (0.033 and 0.33 nM)-stimulated cAMP production. When RTL and MA10 cells were incubated in the presence of [125I]hCG, a radioactive protein complex with an approximate mol wt of 80,000-90,000 was released into the incubation medium. We conclude that LH receptors are regulated by proteolysis at the plasma membrane in both mouse and rat Leydig cells. Furthermore, truncation of the LH receptor in the mouse Leydig cells is involved in down-regulation, whereas in the rat it is a continuous process.
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Regulation of insulin-like growth factor II gene expression by hepatitis B virus in hepatocellular carcinoma. In this study we investigated the regulation of insulin-like growth factor II gene expression to explain a role for this growth factor in concert with hepatitis B virus involvement in the development of hepatocellular carcinoma from cirrhosis. Sections of normal liver and tumor and non-tumor-bearing liver disease tissue were hybridized in situ with [35S]-labeled insulin-like growth factor II oligonucleotide probe. Parallel sections were tested for presence of insulin-like growth factor II polypeptide using immunohistochemistry. To investigate a possible role for hepatitis B virus in insulin-like growth factor II gene expression in hepatocellular carcinoma, results were analyzed against patient seropositivity for hepatitis B virus. Levels of insulin-like growth factor II transcripts in normal liver (n = 4) sections and in those from non-tumor-bearing individuals (n = 10) were so low that specific signal was not detectable above homogeneous tissue background. In contrast, 4 of 8 (50%) of the sections of hepatocellular carcinoma arising from cirrhosis or noncirrhotic chronic liver disease with hepatitis B virus involvement showed increased expression of insulin-like growth factor II messenger RNA transcripts. Up-regulation was observed in cell foci in the hepatocellular regions of the surrounding cirrhotic lobular cells and the fibrous septa. Numerous cell foci were observed in patch distribution in the tumor areas. The level of insulin-like growth factor II messenger RNA transcripts in sections of hepatocellular carcinoma arising from cirrhotic and noncirrhotic tissues obtained from patients seronegative for hepatitis B virus was similar to that of normal liver.
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Premenstrual syndromes defined by symptom-sets. An analysis is made of the pattern of presenting premenstrual symptoms in randomly selected general practice patients from the Wellington region, New Zealand. Participants, 1826 healthy women 16-54 years old whose characteristics were reasonably representative of the adult female population, were asked about their general, obstetrical and gynaecological health. For the 1456 women who had menstruated within the last month or so, detailed questions were asked about the last menstrual cycle. Each woman was assigned to one of seven premenstrual symptom sets. Three groups had 'pure' symptoms, ie a predominant single symptom (breast tenderness, bloating or irritability). Three groups had 'mixed' symptom-sets. The largest of the 'mixed' groups was formed by the women who reported breast tenderness, bloating and irritability together with tension and depression. Women in this group were most likely to rate their symptomatology as severe. The last group contains a large number of women with miscellaneous symptoms. Characteristics of these groups are outlined. The study highlights the importance of distinguishing among premenstrual syndromes as this can foster more effective clinical management.
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Bilateral phrenic nerve palsy associated with open-heart surgery. The incidence of phrenic nerve palsy after open-heart surgery has been estimated at 10%, but it is usually unilateral and does not cause symptoms. Bilateral phrenic nerve injury after coronary artery bypass surgery is a rare complication. This case report describes a patient who developed bilateral phrenic nerve palsies and required prolonged ventilatory support. Denervation of both hemidiaphragms was documented by needle electromyography four weeks after bypass surgery. The patient required total ventilatory support for three months and partial ventilatory support for an additional three months. This case demonstrates the usefulness of electromyographic screening for documentation and prognostication after phrenic nerve injury. The cause of the lesion was unclear, but hypothermia and stretch were leading hypotheses. This patient developed the phrenic nerve palsies despite using a cardiac insulation pad.
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Nevus flammeus. Discordance in monozygotic twins. Nevus flammeus has been described as an inherited vascular anomaly. We report two cases of nevus flammeus, each appearing in one of two monozygotic twins. This finding supports the idea that nevus flammeus results from embryologic mishap rather than genetic transmission.
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Idiopathic intracranial hypertension. A prospective study of 50 patients. Management of patients with idiopathic intracranial hypertension (IIH) should be based on the presence and progression of visual loss. To characterize the clinical course of IIH more completely, we monitored the clinical status, especially visual function, in 50 consecutive newly-diagnosed patients over a period of 2 to 39 months (average follow-up 12.4 months). The mean age at onset of symptoms was 31 (range 11-58) yrs; 46 (92%) were women and 47 (94%) were obese (mean weight 90 kg). Common symptoms were headache (92%), transient visual obscurations (72%) and intracranial noises (60%); 13 of the patients (26%) initially had complaints of sustained visual loss. There was visual loss as determined by Goldmann perimetry in 96% and by automated perimetry in 92%. Contrast sensitivity testing was abnormal in 50% and Snellen acuity in 22%. Two patients (4%) became blind in both eyes. The Goldmann visual field grade improved in 60% of patients but visual function deteriorated in 5 (10%). Deterioration of visual field grade was significantly associated only with weight gain during the year before diagnosis. Visual loss in patients with IIH is common and is often reversible. Patients should be evaluated by perimetry using an appropriate strategy and contrast sensitivity testing, along with careful examination of the optic discs.
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Effects of epidural anesthesia on the incidence of deep-vein thrombosis after total knee arthroplasty [published erratum appears in J Bone Joint Surg [Am] 1991 Jul;73(6):952] Epidural anesthesia has been reported to reduce the prevalence of deep-vein thrombosis after total hip arthroplasty compared with the prevalence after general anesthesia. However, the effect of epidural anesthesia on the rate of thrombosis after total knee arthroplasty has not been reported previously, to our knowledge. A review was conducted of 705 total knee arthroplasties (541 patients) that had been performed by a single surgeon between September 1984 and December 1988. During this period, the operative technique, the protocol for rehabilitation, and the regimen for prophylaxis against thromboembolism did not change meaningfully. The patients received either epidural or general anesthesia. Preoperative and postoperative perfusion scans of the lungs and a venogram of the lower limb or limbs that had been operated on were done for all patients. For the 227 patients who had received epidural anesthesia, the over-all rate of deep-vein thrombosis was 48 per cent, which was significantly lower than the 64 per cent incidence in the 264 patients who had received general anesthesia (p less than 0.0001). The greatest reduction was in the occurrence of proximal thrombosis, which was identified in 9 per cent of the patients who had had general anesthesia but in only 4 per cent of those who had had epidural anesthesia (p less than 0.05). The use of epidural anesthesia reduced the incidence of proximal thrombosis after both unilateral and one-stage bilateral arthroplasty.
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Internuclear ophthalmoplegia in the Chiari type II malformation. We describe 3 cases of Chiari type II malformation presenting with bilateral internuclear ophthalmoplegia (INO). Although prominent, the INO was not an isolated sign in any of the patients; superimposed abduction paresis was present in 2, and deficits in smooth pursuit, optokinetic nystagmus, and vestibulo-ocular responses were present in 3. Two had hydrocephalus: 1 was clinically unchanged without therapy after 5 years; the other did not improve with shunting. Findings in our 3 patients, along with the 4 previously reported, confirm that INO is 1 manifestation of widespread brainstem or cerebellar dysfunction. Its origin is probably multifactorial, related to hydrocephalus, vascular compromise, direct neuronal distortion, or congenital neural malformation.
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Repair of O6-ethylguanine in DNA protects rat 208F cells from tumorigenic conversion by N-ethyl-N-nitrosourea. O6-Ethylguanine (O6-EtGua) is one of about a dozen different alkylation products formed in the DNA of cells exposed to the alkylating N-nitroso carcinogen N-ethyl-N-nitrosourea (EtNU). We have evaluated selectively the relative capacity of cells for the specific enzymatic repair of O6-EtGua as a determinant for the probability of malignant conversion. Eleven O6-EtGua-repair-proficient (R+) variant subclones were isolated from the O6-EtGua-repair-deficient (R-) clonal rat fibroblast line 208F by selection for resistance to 1,3-bis-(2-chloroethyl)-1-nitrosourea (frequency, approximately equal to 10(-5). Contrary to the 208F wild-type cells, all variants expressed O6-methylguanine-DNA methyltransferase activity, while both kinds of cells were deficient for repair of the DNA ethylation products O2- and O4-ethylthymine. After exposure to EtNU (less than or equal to 500 micrograms/ml; 20 min), cells were analyzed for the formation of piled-up foci in monolayer culture and of anchorage-independent colonies in semisolid agar medium. Depending on the EtNU concentration, the frequencies of piled-up foci and agar colonies, respectively, in the R+ variants were as low as 1/28th and 1/56th of those in the R- wild type. Contrasting with the cells from R+ variant-derived agar colonies, cells from 208F (R-) agar colonies gave rise to highly malignant tumors when implanted subcutaneously into syngeneic rats. No significant differences in the frequencies of piled-up foci were found between wild-type and variant cells after exposure to the major reactive metabolite of benzo[a]pyrene, (+)-7 beta, 8 alpha-dihydroxy-9,10 alpha-epoxy-7,8,9,10 alpha-tetrahydrobenzo[a] pyrene, for which stable binding to guanine O6 in cellular DNA has not been observed. The relative capacity of cells for repair of O6-alkylguanine is, therefore, a critical determinant for their risk of malignant conversion by N-nitroso carcinogens.
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Long-term results of surgical resection of locally advanced colorectal carcinoma. This study was undertaken to review the long-term results of multivisceral resection of locally advanced colorectal carcinoma. Between 1964 and 1980, 1042 patients underwent exploratory surgery for colorectal cancer. Of these, 58 patients (5.5%) underwent curative multivisceral resection for suspected contiguous invasion by the primary tumor. Follow-up was complete for all patients. The primary tumors were located in the rectum (38 patients), sigmoid (9 patients), left colon (6 patients), and right colon (5 patients). En bloc resection of other viscera included uterus, adnexa, bladder, vagina, small intestine, abdominal wall, liver, stomach, kidney, and ureter. The operative morbidity and mortality rates were 31% and 1.7%, respectively. Resection margins were free of tumor in 54 patients. In the four patients with tumor-positive resection margins, recurrence of disease was evident between 8 and 22 weeks after surgery (mean survival time, 8.2 months). Carcinomatous invasion of the resected contiguous organ was confirmed in 49 patients (84%). The mean survival time for patients without lymph node metastases was 100.7 months, but it was only 16.2 months (p less than 0.01) for patients with lymph node metastases. Actuarial 5-year disease-free survival rate for patients without lymph node metastases was 76% (36 of 47 patients). None of the patients (0 of 11) with lymph node metastases survived for 5 years. Three of 36 of the 5-year survivors experienced recurrence of disease before the seventh postoperative year; no cancer-related deaths occurred between 7 and 25 years. These data suggest that survival in locally advanced colorectal carcinoma is more dependent on lymph node status than on the extent of local invasion. Effective disease control associated with survival in the long term can be achieved by multivisceral resection.
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Recurrence of resected esophagogastric adenocarcinoma: results of re-resection. Isolated local recurrence following potentially curative resection for carcinoma of the esophagus or esophagogastric junction does not necessarily imply pending systemic disease and early demise. While radiation alone or in combination with chemotherapy is standard treatment for such patients, resection is another available option. Resection may also be a consideration should localized disease persist after non-operative therapy in the absence of metastases. A 5 year retrospective review was performed examining 204 resections performed prior to 1989. Only 5 patients underwent resection of locally recurrent esophagogastric (EG) adenocarcinoma during this period. No squamous carcinoma recurrences were resected. One patient is well 15 months later while another died at 18 months of other causes without recurrence. Recurrence after re-resection occurred at 8, 11, and 24 months in the 3 other patients. Although there were no postoperative deaths, major complications occurred in 4 patients. All 5 patients swallowed normally after operation.
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Sucralfate used as adjunctive therapy in patients with severe erosive peptic esophagitis resulting from gastroesophageal reflux. A total of 36 patients with grade 2 or greater erosive esophagitis and an abnormal 24-h pH monitor study, were treated in a randomized, double-blind fashion to assess the efficacy of sucralfate suspension as adjunctive therapy to cimetidine for severe esophagitis secondary to gastroesophageal reflux. Treatment consisted of cimetidine, 300 mg qid and either sucralfate suspension (1 g/10 ml) or an identical placebo suspension, 10 ml after meals and 20 ml hs. Patients were treated for 12 wk unless endoscopic healing occurred earlier. Initial evaluation and monthly follow-up consisted of symptom monitoring, endoscopic evaluation and pre- and post-therapy esophageal manometry, Bernstein test, and 24-h pH monitoring. The combination of cimetidine and sucralfate suspension was superior to cimetidine alone in improving daytime heartburn symptoms (p less than 0.05) but not nighttime heartburn, dysphagia, or regurgitation. Sucralfate plus cimetidine improved the overall endoscopic outcome of esophagitis more than cimetidine alone (p less than 0.05). More patients exhibited endoscopic healing in the adjunctive sucralfate group than in the cimetidine-only group. Endoscopic healing, however, was not statistically different between groups. We conclude that sucralfate used as adjunctive therapy to cimetidine resulted in improvement of some of the symptoms of reflux, and probably increases the likelihood of complete healing of esophagitis, compared with cimetidine alone.
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Antibodies to Epstein-Barr virus in iridocorneal endothelial syndrome. Antibody titers to Epstein-Barr virus were determined in 13 patients with iridocorneal endothelial syndrome and in 13 healthy race-, age-, and sex-matched controls. Both the geometric mean titer of IgG antibodies to the Epstein-Barr virus capsid antigen and the proportion with high titers of IgG antibodies to the Epstein-Barr virus capsid antigen (greater than or equal to 1:640) were significantly higher in 12 seropositive patients with iridocorneal endothelial syndrome than in 12 seropositive controls (1/761:1/202, P = .001; 83.3%:8.3%, P less than .001). Ten of 12 seropositive patients with iridocorneal endothelial syndrome and five of 12 seropositive controls had antibodies to Epstein-Barr virus-induced early antigens (greater than or equal to 1:10) (Fisher's Exact Test, P less than .05), while four seropositive patients with iridocorneal endothelial syndrome and one seropositive control had low to undetectable levels of antibodies to Epstein-Barr virus-associated nuclear antigen (less than or equal to 1:5) (P greater than .1). Antibody levels to cytomegalovirus or measles virus were not different between patients with iridocorneal endothelial syndrome and controls. Additional studies showed no evidence of humoral immune disorder or collagen vascular disease in the patients with iridocorneal endothelial syndrome. The serologic profiles suggest that the patients with iridocorneal endothelial syndrome examined had a cellular immune abnormality sufficient to permit reactivation of latent Epstein-Barr virus infection and imply, but do not establish, a role for Epstein-Barr virus infection in the pathogenesis of some cases of the iridocorneal endothelial syndrome.
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Use of the levator scapulae muscle flap in head and neck reconstruction. There are numerous techniques available for reconstruction of defects following composite resection of oral cavity and oropharyngeal tumors. No single technique is applicable in all situations. The levator scapulae muscle flap is well known for its application in carotid protection. Little attention is paid to its usefulness in other aspects of head and neck reconstruction. We have been using the levator scapulae muscle flap for a variety of reconstructive problems. The flap is useful for buttressing intraoral suture lines, closing intraoral defects, and providing soft tissue to fill in dead spaces and bulk out lateral and anterior oral defects. The levator flap was found to be easy to elevate, safe, and reliable with a minimum of wound complications. A review of 18 patients, representative case studies, and a discussion of surgical technique and relevant anatomy and blood supply is presented.
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Transcatheter oily chemoembolization in the management of advanced hepatocellular carcinoma in cirrhosis: results of a Western comparative study in 60 patients. Transcatheter oily chemoembolization is widely used as palliative therapy for inoperable hepatocellular carcinoma in high-incidence Asiatic areas. To assess its usefulness in the Western form of this cancer, 30 French patients were treated between 1987 and 1990 by intraarterial hepatic injection of a Lipiodol-doxorubicin emulsion followed by embolization with 0.5 to 1 mm gelatin sponge particles. The number of procedures ranged from one to five. All patients had advanced, symptomatic and inoperable hepatocellular carcinoma (Okuda's staging: I, n = 8; II, n = 14; III, n = 8); none was found under systematic screening. All had underlying cirrhosis (Child-Pugh's class: A, n = 15; B, n = 12; C, n = 3) that was alcoholic in origin in 27 cases and posthepatitic B in origin in 3 cases. The results of the treatment were assessed by comparison with a group of 30 untreated patients admitted to the same unit between 1984 and 1987. Patients of both groups were closely matched for clinical presentation, global disease staging and precise anatomical extension. The overall 1- and 2-yr survival rate was 59% and 30%, respectively, for the treated patients vs. 0% at 1 yr for the untreated patients. The latter all died from local disease with end-stage liver failure and/or uncontrollable variceal bleeding. In the former, the three patients with Child's class C cirrhosis died after the first procedure. During the follow-up (range = 3 to 26 mo), 11 additional patients died, 8 from metastatic generalization.
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Hyperkalaemia during rapid blood transfusion and hypovolaemic cardiac arrest in children. A morbidity and mortality review documented a high occurrence of hyperkalaemia in cardiac arrests associated with rapid blood transfusion, which resulted in further study. In order to stimulate events during rapid blood transfusion and cardiac arrest, the central circulation was modeled as a linear one compartment, and used to stimulate a child who suffered a hypovolaemic cardiac arrest and was resuscitated with rapid blood transfusion (RBT). The simulation suggested that the combination of RBT and a low cardiac output state could be associated with hyperkalaemia, if the potassium concentration in the plasma fraction of the transfused blood was greater than or equal to 10 mmol.L-1. In an associated clinical study the plasma potassium concentration during cardiac arrest was documented from a retrospective review of 138 cardiac arrests in a paediatric population. Patients were divided into two groups. The RBT-group received a rapid blood transfusion during resuscitation. The non-RBT group did not receive blood during resuscitation. During cardiac arrest the plasma [K] in the non-RBT group was 5.63 +/- 2.39 mmol.L-1 compared with 8.23 +/- 1.99 mmol.L-1 in the RBT-group (P less than 0.05). The hyperkalaemia during cardiac arrest in the RBT-group could be explained as a consequence of RBT to a hypovolaemic child with a low cardiac output.
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Defects in the precore region of the HBV genome in patients with chronic hepatitis B after sustained seroconversion from HBeAg to anti-HBe induced spontaneously or with interferon therapy. Hepatitis B virus DNA clones were propagated from sera of six patients with chronic hepatitis B who seroconverted from HBeAg to antibody to HBeAg either spontaneously or after administration of alpha-interferon. Defects in the precore region blocking synthesis and secretion of HBeAg were detected in all 46 hepatitis B virus DNA clones from three patients who remained positive for antibody to HBeAg and in whom hepatitis resolved. Defective clones had point mutations from guanine to adenine at nucleotide 83 in the precore region, converting codon 28 from tryptophan (TGG) to a stop codon (TAG). In contrast, this defect was not found in any of 39 hepatitis B virus DNA clones from three patients who seroconverted to antibody to HBeAg but then redeveloped HBeAg with reactivation of hepatitis. Using these results, the G-to-A point mutation at nucleotide 83 in the precore region would predict sustained positivity for antibody to HBeAg and remission of hepatitis in patients who have seroconverted either spontaneously or with interferon therapy.
1
Early complications in the operative treatment of ankle fractures. Influence of delay before operation. We have reviewed the early complications of 121 surgically treated closed ankle fractures; the complication rate was 30%, with 14 major and 22 minor complications. Fractures with skin blisters or abrasions had more than double the overall complication rate. Fracture-dislocations had three times as many major complications as simple fractures, and those not fixed within 24 hours had a 44% major complication rate compared to 5.3% in those operated upon as emergencies. Patients transferred from another medical facility had high complication rates, especially if they had fracture-dislocations. We conclude that operative treatment of ankle fractures must be delivered in a timely fashion, especially in severe fractures. We would caution against the practice of transferring patients with serious ankle fractures before completion of definitive care.
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Does somatostatin analogue prevent experimental acute pancreatitis? Because somatostatin is a potent inhibitor of pancreatic secretion, we hypothesized that pretreatment with somatostatin analogue octreotide (SMS 201-995) might prevent cerulein-induced edematous pancreatitis. We studied 18 rats prepared with jugular vein catheters. The following agents were administered intravenously to groups of four rats for 6 hours: 1 mL/h (control) crystalloid solution; 1-microgram/kg bolus then 1 microgram/kg per hour of octreotide; and 5 micrograms/kg per hour of cerulein; also, in a fourth group of six rats, octreotide and cerulein were administered simultaneously. At the end of experiments, blood was drawn for plasma amylase determinations; rats were killed and pancreata were examined. Supramaximal cerulein administration to conscious rats induced hyperamylasemia and edematous pancreatitis, confirming previous observations; in both groups of rats receiving cerulein, there was prominent interstitial edema, acinar vacuolization, and mild-to-moderate acute inflammation. While octreotide pretreatment of rats with cerulein-induced acute pancreatitis was associated with a lesser increase of wet pancreas weight and plasma amylase concentration, there was little overall benefit of octreotide pretreatment in this form of experimental acute pancreatitis.
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Effects of a multidisciplinary management program on neurologically impaired patients with dysphagia. Dysphagia is a major problem in patients with neurologic disorders. Aspiration pneumonia and impaired nutritional status are consequences of dysphagia that result in high morbidity and mortality rates. Assessment and treatment of the dysphagic patient by a multidisciplinary team have been advocated but to date the effects of such an approach have not been demonstrated quantitatively. This prospective study was conducted to determine if a dysphagia program would improve patients' caloric intake and body weight, decrease the instances of aspiration pneumonia, or improve patients' feeding ability. Patients were referred from a 26 bed neurology/neurosurgery unit. A time series design was utilized. The control group consisted of 15 patients (mean age = 46.1 years), managed according to the existing ward routine. Subsequently, nursing staff attended a dysphagia training program. Following this, the treated group of 16 patients, (mean age = 49.3 years) was assessed by the dysphagia team, using bedside and videofluoroscopic examinations to determine the specific swallowing disorder. An individualized treatment program was designed for each patient. The groups were compared on the basis of deviation from their baseline weight, deviation from ideal energy intake, and the incidence of aspiration pneumonia. Statistical analysis revealed that the groups were comparable in age, number of days on the study, and Glasgow Coma Scale score; and that a significant weight gain and increase in caloric intake occurred in the treated group. No incidence of aspiration pneumonia was reported in either group. We speculate that this may have been influenced by the meticulousness of the care delivered in an acute unit as well as greater attention to prevention given in both groups.
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Intraabdominal hemorrhage as a result of segmental mediolytic arteritis of an omental artery: case report. This article describes the fifth reported case of segmental mediolytic arteritis and the second in a survivor. The patient had intraabdominal bleeding as a result of a ruptured omental artery. The pathologic and arteriographic findings are described. The pathology is characterized by segmental disruption of the medial smooth muscle cells and the initiation of mediolysis. Mediolysis is associated with marked segmental thinning of the vessel wall, often with only the adventitia intact. Fibrin is deposited at the adventitial and medial surfaces, and hemorrhage into the media may occur. As in this reported case, lysis of the adventitia leads to sudden, often catastrophic intraabdominal hemorrhage. Little associated adventitial inflammation occurred. Segmental mediolytic arteritis seems to involve the intra-abdominal muscular arteries in elderly patients with nonspecific abdominal symptoms. An angiogram showed patchy areas of narrowing involving ileal, gastroduodenal, and renal arteries that correlated with the pathologic findings observed in the excised omental arteries.
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Temporoparietal cortex in aphasia. Evidence from positron emission tomography. Forty-four aphasic patients were examined with (F18)-fluorodeoxyglucose positron emission tomography in a resting state to determine whether consistent glucose metabolic abnormalities were present. Ninety-seven percent of subjects showed metabolic abnormalities in the angular gyrus, 89% in the supramarginal gyrus, and 87% in the lateral and transverse superior temporal gyrus. Pearson product moment correlations were calculated between regional metabolic measures and performance on the Western Aphasia Battery. No significant correlations were found between the Western Aphasia Battery scores and right hemisphere metabolic measures. Most left hemisphere regions correlated with more than one score from the Western Aphasia Battery. Temporal but not frontal regions had significant correlations to the comprehension score. The left temporoparietal region was consistently affected in these subjects, suggesting that common features in the aphasias were caused by left temporoparietal dysfunction, while behavioral differences resulted from (1) the extent of temporoparietal changes, and (2) dysfunction elsewhere in the brain, particularly the left frontal and subcortical areas.
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Estrogen deficiency in adolescents and young adults: impact on bone mineral content and effects of estrogen replacement therapy. Because the long-term effects of estrogen replacement in adolescents with ovarian failure and hypothalamic amenorrhea have not been previously studied, we conducted a 2-year study of 35 patients to determine factors contributing to baseline bone density measures (bone density, bone mineral content, and bone width) and the response to estrogen therapy. Estrogen-deficient patients were often profoundly osteopenic by single-photon absorptiometry of the radius and dual-photon absorptiometry of the spine, despite estrogen replacement. Variables that were significant predictors of better initial single-photon absorptiometry measurements included increased age, increased body mass index, spontaneous pubertal development, lack of radiation therapy, and lower serum osteocalcin. Patients treated with estrogen/progestin had stable cortical bone mineral content and bone density at the distal one-third of the radius, a slight improvement in bone density at the distal one-tenth of the radius, and on encouraging, but marginal, improvement in the z score (standard deviation from the mean) of bone mineral content at the distal one-tenth. The z scores for cortical bone width and bone density decreased, suggesting a possible relative worsening over time. In untreated estrogen-deficient girls, bone mineral content and bone density decreased (but not significantly); the z score of cortical bone width showed a significant decrease. Using dual-photon absorptiometry, a history of radiation therapy was found to be a predictor of lower bone density compared with age-matched controls. Estrogen progestin therapy did not result in changes in serum levels of lipids and antithrombin III, weight, or blood pressure.
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Psychological reaction to hospitalization and illness in the emergency department. Each personality type presents with different methods of coping. Physicians should be aware of the impact on a patient's psychological functioning and ability to cope with illness and hospitalization, to understand and more effectively manage the patient. The physician must try to assess the patient's baseline personality from their past and present behavior. Establishing a good physician-patient relationship is important as a source of information about behavior of patients and how they will respond to their illness. Depending on the specific personality type, each patient will respond differently to the stress of illness. The effort of the emergency physician to identify personality types will aid in medical management of the patient and enable the physician to help each patient cope effectively with the illness and the hospitalization. The specific issues that seem to be threatening to traumatized patients include the following: helplessness, humiliation, blurring of body image, and gaps in memory filled with distortions. The traumatized patient experiences an altered state of consciousness which is either due to a physiologic cause or an emotional cause. Emotional causes are usually based on defensive dissociation. People who have been in an auto accident characteristically report loss of memory of the intense pain that the accident produces initially. Oftentimes, the core experience for the traumatic patient is not somatic, it is unconscious. The interesting feature is that so many patients do not remember the accident. The mind seems to be filled with all kinds of distortions and irrelevant and perhaps totally inconsistent fantasies, such as imprisonment, confinement, or deathlike experiences. Some report that they are being incarcerated, others recall being in a featureless cubicle with no contact with the normal world in which there are no windows, no pictures, no flowers. Others remember only being surrounded by masked, hatted, uniformed wardens who are standing over them with nasogastric tubes, intravenous lines, Foley catheters, arterial blood gases, subclavians, and dermal cut-downs. This is an overwhelming nightmare that can be relieved only by the empathic and caring physician and emergency department staff. The stress of medical illness and/or hospitalization can be overwhelming for some patients and is usually followed by some form of psychological response. Current understanding of the psychological impact of illness is based upon psychological defenses, coping mechanisms, and individual personality. It is the ability of the emergency physician to identify defenses, coping skills and personality types that will aid him or her in the medical management of the patients in their time of illness and hospitalization.
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Comparisons of diet and biochemical characteristics of stool and urine between Chinese populations with low and high colorectal cancer rates. In an investigation of the roles of diet and stool biochemistry in human colorectal carcinogenesis, 24-hour food, urine, and stool samples were collected from randomly selected participants from two populations with a fourfold difference in colorectal cancer risk: Chinese in Sha Giao, People's Republic of China (low risk), and Chinese-Americans of similar ages in San Francisco County, Calif, in the United States (high risk). The findings supported the hypotheses that colorectal cancer risk is increased by the consumption of high-fat, high-protein, and low-carbohydrate diets and is associated with high levels of cholesterol in stool as well as increased daily outputs of 3-methyl-histidine and malonaldehyde in urine. However, risk does not increase with low stool bulk and low total stool fibers.
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Pelvic pain: lessons from anatomy and physiology. Pelvic pain is often a difficult differential diagnosis in the emergency department. For physiologic reasons, pain in the pelvis is difficult to localize to a specific organ, and pelvic peritonitis is hard to recognize. On the other hand, differences in types of pain can be very useful in arriving at a correct diagnosis. The clinician must learn to recognize superficial and deep somatic pain, and differentiate between various types of visceral pain which originate from inflammation, ischemia, or colic. A review of the anatomy and physiology of pelvic pain helps identify some of the problems as well as potential aids in approaching the patient with pelvic pain.
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Metastatic carcinoma to the retina. Clinicopathologic findings in two cases. Two cases of metastatic carcinoma to the neuroretina are reported. One patient had an oat cell carcinoma of the lung that was metastatic to the brain and retina; this was confirmed postmortem. The other patient had metastatic breast carcinoma with seeding of tumor cells into the vitreous from a focus of retinal embolism. The diagnosis was confirmed from a vitrectomy specimen.
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Role of systemic therapy in advanced non-small-cell lung cancer. Increasing evidence supports the investigation of chemotherapy in patients with non-small-cell lung cancer (NSCLC). Randomized studies in patients with stage IV disease have shown increased survival in chemotherapy-treated patients compared to best supportive care and indicate the ability of chemotherapy to alter the natural history of this disease. Randomized studies involving adjuvant and neoadjuvant chemotherapy have also shown encouraging results. These studies and results of recent pilot studies utilizing neoadjuvant chemotherapy and concomitant chemoradiotherapy indicate a potential benefit from the use of chemotherapy in patients with NSCLC and call for its continued intensive investigation in clinical trials.
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Role of mast cells in ion transport abnormalities associated with intestinal anaphylaxis. Correction of the diminished secretory response in genetically mast cell-deficient W/Wv mice by bone marrow transplantation. To investigate the role of mast cells in transport abnormalities during intestinal anaphylaxis, we examined responses to antigen in isolated intestinal preparations from ovalbumin-sensitized genetically mast cell-deficient WBB6F1-W/Wv (W/Wv) mice and congenic normal WBBGF1(-)+/+ (+/+) mice. Changes in ion transport (primarily secretion of chloride ions) were indicated by increases in short-circuit current (Isc). In tissues from +/+ mice, antigen caused increases in Isc which were significantly inhibited by antagonists to histamine (diphenhydramine) and serotonin (ketanserin), by a cyclooxygenase inhibitor (piroxicam) and by a neurotoxin (tetrodotoxin). In preparations from W/Wv mice, antigen-stimulated responses were approximately 30% of that in +/+ mice and were inhibited only by piroxicam. Responses to electrical transmural stimulation of nerves were approximately 50% in W/Wv versus +/+ mice, and were inhibited by antagonists of mast cell mediators in +/+ but not W/Wv mice. Reconstitution of mast cells in W/Wv mice by intravenous injection of +/+ bone marrow cells restored the normal responses to both antigen and nerve stimulation. Our results indicate that mast cell-dependent mechanisms are primarily responsible for the ion secretion associated with intestinal anaphylaxis, but that other cells are also involved. In addition, our data provide evidence for the functional importance of bidirectional communication between nerves and mast cells in the regulation of ion transport in the gastrointestinal tract.
1
Dexamethasone effects on the hospital course of infants with bronchopulmonary dysplasia who are dependent on artificial ventilation. A randomized double-blind placebo-controlled trial was conducted to evaluate the effects of enterally administered dexamethasone on the hospital course of infants with bronchopulmonary dysplasia. A total of 23 infants with a birth weight less than 1500 g who were dependent on artificial ventilation 3 to 4 weeks of age received dexamethasone (n = 12) or saline placebo (n = 11). Dexamethasone (0.5 mg/kg per day) was given in tapering doses for 7 days followed by hydrocortisone (8 mg/kg per day) which was progressively reduced for a total of 17 days of therapy. Infants who received dexamethasone required less oxygen on days 8 and 17 (P less than .05) and were more likely to extubate 8 days after therapy than infants in the control group (respectively 8/12 vs 3/11 infants, P less than .05; P = .12 after Yates correction). The use of dexamethasone significantly shortened median duration of mechanical ventilation (4 vs 22 days, P less than .05) but had no effect on length of oxygen therapy, hospitalization, home oxygen therapy, occurrence and severity of retinopathy of prematurity, rate of growth, and mortality. No significant complications resulted from dexamethasone therapy. Measurements of plasma dexamethasone levels confirmed the absorption of drug from the gastrointestinal tract (23.7 ng/mL in dexamethasone vs 4.6 ng/mL in the control group, P less than .05). Dexamethasone administration resulted in short-term improvements in pulmonary function but did not ameliorate the hospital course of infants with bronchopulmonary dysplasia.
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Scintigraphic assessment of leukocyte infiltration in acute pancreatitis using technetium-99m-hexamethyl propylene amine oxine as leukocyte label. The infiltration of leukocytes has been linked to the pathophysiology of complicated or severe pancreatitis. We have tested the ability of leukocyte scintigraphy using technetium-99m-hexamethyl propylene amine oxine (HM-PAO) as label to demonstrate the localization of leukocytes in the pancreas during acute pancreatitis. Twenty-eight patients with acute pancreatitis (eight with biliary, 13 with alcoholic, and seven with unknown origin) were studied with leukocyte scintigraphy using planar imaging and single photon emission computed tomography (SPECT). Fourteen patients had a mild (group I), II a severe (group II), and three a lethal outcome (group III) of pancreatitis. All patients of group III, six of group II, and two of group I had a positive leukocyte scan. Thus, the sensitivity of leukocyte scintigraphy for the detection of a lethal course of acute pancreatitis was 100%, of a severe course 54%, and of a severe or lethal course 64%. The specificity of a negative scan for a mild pancreatitis was 86%. Comparison of the results of leukocyte scintigraphy with those of contrast enhanced CT showed that six of eight patients with pancreatic necrosis in CT had a positive leukocyte scan, but only five of 20 patients without detectable pancreatic necrosis in CT. In summary, leukocyte infiltration into the pancreas during pancreatitis can be demonstrated by noninvasive leukocyte scintigraphy using technetium-99m-HM-PAO as label. A correlation between the severity of the disease and leukocyte infiltration exists.
1
Fluorescence assays to monitor membrane fusion: potential application in biliary lipid secretion and vesicle interactions. Membrane fusion constitutes an essential, intermediate step in numerous cell biological processes, occurring for example during endocytosis, membrane recycling and exocytosis. Also less desirable events such as the infection of cells by animal viruses are mediated by membrane fusion during which the viral envelope merges with a cellular membrane, causing the expulsion of the viral nucleocapsid into the cytoplasm of the cell as an initial step in virus replication. Much of our current knowledge concerning the mechanism of membrane fusion has been derived from studies using simple artificial membranes, such as liposomes or phospholipid vesicles, as model systems. A most essential feature of these studies has been the development of membrane fusion assays that register in a sensitive and continuous fashion the mixing of membranes or the aqueous volumes initially enclosed by these membranes. Not only do these assays allow one to readily detect and quantify fusion, but they also provide the possibility to relate the kinetics of fusion to the rate by which certain molecular changes in membranes take place. Obviously, this insight is of relevance for understanding the mechanism of membrane fusion. The principles and applications of some representative assays that rely on the use of fluorescence spectroscopy will be discussed. Assays that monitor membrane mixing are commonly based on the detection of changes in resonance energy transfer efficiency or the relief of fluorescence self-quenching of appropriate fluorescent lipid analogs. Contents mixing assays rely on either the formation of a (aqueous-soluble) fluorescent complex or quenching of a fluorophore, encapsulated in one vesicle population, by a suitable quencher, entrapped in a second population.
1
Enhanced anaphylatoxin and terminal C5b-9 complement complex formation in patients with the syndrome of hemolysis, elevated liver enzymes, and low platelet count. Complement activation was studied in ten consecutive pregnant women developing hemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome) and ten other women with normal pregnancies. Blood samples for anaphylatoxin (C3a/C3a desArg and C5a/C5a desArg) and terminal C5b-9 complement complex determinations were drawn at delivery and 24 hours and 7 days later. Women developing HELLP syndrome had higher plasma levels of anaphylatoxins with delivery than did women with uneventful pregnancies. The plasma levels of terminal C5b-9 complement complexes at the time of delivery were increased as compared with levels 1 and 7 days after delivery in women with HELLP syndrome. The plasma concentrations of the anaphylatoxins and the terminal C5b-9 complement complexes returned to normal levels within 1 week after delivery in the HELLP group. The formation of C5b-9 complement complex indicates that the terminal part of the complement cascade has been activated and that C5a has been formed and eliminated. Complement activation with release of anaphylatoxins and terminal C5b-9 complement complexes may be one etiologic factor behind the elevated blood pressure, hemolysis, liver insufficiency, and platelet consumption seen in these patients.
4
Atrial activation sequence during atrial flutter in the canine pericarditis model and its effects on the polarity of the flutter wave in the electrocardiogram. Stable atrial flutter induced in both conscious and open chest states was studied in 30 mongrel dogs after production of sterile pericarditis. During the conscious state studies, induced atrial flutter (mean cycle length 128 +/- 15 ms) was always sustained greater than 15 min and was stable. Three types of flutter wave polarity were noted in electrocardiogram (ECG) lead II: positive in 16 dogs, negative in 3 and flat or slightly positive in 11. Sequential site atrial mapping during atrial flutter (mean cycle length 133 +/- 18 ms) in the open chest state showed either clockwise (18 dogs) or counterclockwise (12 dogs) circus movement in the right atrium. In 19 of 30 dogs, the circus movement clearly did not require any naturally existing anatomic obstacle; in 11, the orifice of the superior vena cava probably was also involved. Double potentials were recorded from the center of the reentrant circuit during atrial flutter, and fractionated electrograms were recorded from a pivot point of the reentrant wave front. A positive flutter wave in ECG lead II (12 dogs with counterclockwise circus movement) was associated with early activation of the Bachmann's bundle region compared with the posteroinferior left atrium and activation of the left atrium mainly in a superoinferior direction. A negative flutter was associated with the early activation of the posteroinferior left atrium compared with Bachmann's bundle and activation of a considerable portion of the left atrium in an inferosuperior direction. A flat or slightly positive flutter wave (14 of 18 with clockwise circus movement) was associated with activation of the left atrium almost simultaneously by two wave fronts coming from both these sites. In conclusion, atrial flutter in this dog model is due to circus movement in the right atrium, the center of which does not necessarily require an anatomic obstacle. Although atrial flutter is generated by circus movement in the right atrium, the flutter wave polarity in the ECG is determined primarily by the activation sequence of the left atrium.
4
Squamous carcinoma of the distal esophagus: a survival study. A survival study for squamous carcinomas of the distal esophagus treated by the Southern California Permanente Medical Group in the interval of 1954 to 1988 was undertaken. We found radiation therapy and surgery equally efficacious in terms of cure for patients without distant disease and performance status sufficient to tolerate treatment. We did not find survival benefit for patients treated with palliative surgery, and plan less invasive endoscopic means along with chemotherapy and radiation for palliation, reserving surgery for special circumstances.
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Hemodynamic basis of stasis ulceration--a hypothesis. Approximately 25% of patients with stasis ulceration have normal or below normal ambulatory venous pressures. A reflux index was calculated by multiplying postexercise pressures by Valsalva-induced foot venous pressure elevation. In patients with stasis ulceration, reflux index was found to have an excellent negative predictive value with a clear discriminant line between normal limbs and those with ulcers. Increasing incidence of stasis ulceration was demonstrated with increasing reflux index value. Even when ambulatory venous pressure was within the normal range, the index was found to be abnormal in ulcerated limbs because Valsalva-induced foot venous pressure was elevated in these limbs. Conversely, some patients with stasis ulceration and normal Valsalva foot venous pressure elevation were found to have abnormal ambulatory venous pressure values, yielding an elevated reflux index. Preliminary analysis indicates that reflux index may be a better predictor of surgical outcome after valve reconstruction procedures than either ambulatory venous pressure or Valsalva-induced foot venous pressure elevation. The concept of reflux index is a hypothesis that attempts to explain inconsistencies observed in implicating ambulatory venous hypertension as the sole determinant of venous reflux.
3
Hypoxanthine levels in vitreous humor: evidence of hypoxia in most infants who died of sudden infant death syndrome. Postmortem changes of the hypoxanthine in vitreous humor in humans were investigated. Hypoxanthine is formed from hypoxic degradation of adenosine monophosphate. Repeated sampling was performed in 13 deceased adults. Keeping the bodies at +6 degrees C, the increase of the hypoxanthine levels was estimated to 3.5 mumol/L per hour when sampling was started more than 12 hours after death (range 2.8 to 5.6 mumol/L per hour). Results of hypoxanthine measurements from vitreous humor in 73 infants with sudden infant death syndrome, 17 infants and children who died sudden violent deaths, and 6 neonates who died suddenly without hypoxemia prior to death were corrected according to the expected postmortem hypoxanthine increase. The time between death and autopsy was similar in the three groups studied. The corrected median hypoxanthine level in the group with sudden infant death syndrome was 227 mumol/L, which is significantly higher than in the other groups; 22 mumol/L in the group who had violent deaths (P less than .01), and 0 mumol/L in the neonate group (P less than .01). The findings seem to confirm that sudden infant death is preceded by a relatively long period of tissue hypoxia in most cases.
4
Characteristics of a new angiotensin converting enzyme inhibitor: delapril. Delapril, a nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor, which has an indanylglycine moiety differing from the proline moiety of captopril or enalapril, is an esterified prodrug that is converted in vivo to its active metabolites. Delapril effectively inhibits rabbit lung ACE activity and lowers blood pressure in spontaneously hypertensive rats. Delapril has several characteristics that differ from captopril and enalapril, including high lipophilicity and weak bradykinin potentiating action. Delapril is a more potent inhibitor of vascular wall ACE activity than enalapril or captopril. It also shows a weaker potentiating action on the citric acid-induced cough in the guinea pig model compared with captopril and enalapril. In 12 out of 150 patients with essential hypertension who complained of cough during treatment with enalapril, changing to delapril resulted in resolution of the cough in 6 out of 12 of these patients: the percentage of patients in the total population with cough decreased from 8% to 4%.
3
Coronary angioplasty after coronary bypass surgery: initial results and late outcome in 422 patients. From 1978 to 1988, coronary angioplasty was performed in 422 patients with prior coronary artery bypass surgery (264 patients with native coronary artery angioplasty and 158 patients with graft angioplasty). Angioplasty was successful in 84%, unsuccessful but uncomplicated in 11% and complicated by one or more major cardiac events in 5% (myocardial infarction 5%, emergency bypass surgery 2% and death 0.2%). Follow-up data were obtained in 99% of 356 patients with successful angioplasty. At a mean of 33 +/- 26 months, 92% were alive, 73% had improvement in angina and 61% were free of angina. One or more of the following late events occurred in 67 patients (19%): myocardial infarction (6%), elective reoperation (13%) and cardiac death (6%). Repeat angioplasty was performed in 27%, with a success rate of 89% and no deaths. Initial success rates were equal in native vessel versus graft angioplasty, but late outcome was less favorable with the latter because of a higher rate of infarction (11% versus 4%, p less than 0.05) and need for reoperation (19% versus 10%, p less than 0.05). The initial success rate was higher in vein grafts less than 1 year old compared with grafts 1 to 4 years or greater than 4 years after operation (92% versus 85% versus 83%, respectively) and adverse late events were less frequent after angioplasty in recent vein grafts (less than 1 year 13%, 1 to 4 years 35%, greater than 4 years 29%; less than 1 versus greater than 1 year, p less than 0.05).
3
Factors influencing survival after pancreaticoduodenectomy for pancreatic cancer. Eighty-nine patients with carcinoma of the head of the pancreas underwent pancreaticoduodenectomies. The actuarial 5-year survival for all 89 patients was 19%, with a median survival of 11.9 months. The 81 hospital survivors were analyzed in an effort to determine factors influencing long-term survival. Negative lymph nodes and the absence of blood vessel invasion both favored long-term survival. The strongest predictive factor was negative lymph node status with a median survival of 55.8 months, compared with 11 months with lymph nodes involved with tumor (p less than 0.05). Blood transfusions were also predictive, with patients receiving two or fewer units having a median survival of 24.7 months, compared with 10.2 months for those receiving three or more units (p less than 0.05). The most important determinant of long-term survival after pancreaticoduodenectomy for pancreatic cancer is biology of the tumor (lymph node status, blood vessel invasion). However, performance of the resection (units of blood transfused) also appears to be an important factor influencing survival.
0
The effect of continuous epidural analgesia on postoperative pain, rehabilitation, and duration of hospitalization in total knee arthroplasty. Efficacies of three alternate methods of postoperative analgesia were studied in 156 patients who had total knee arthroplasty (TKA). Forty-two of these patients received parenteral meperidine hydrochloride or morphine (Group 1), 58 patients received periodic epidural injections of morphine (Group 2), and 56 patients received continuous epidural infusions of bupivacaine hydrochloride and Duramorph (Group 3). The postoperative course of all patients was documented in terms of the incidence and severity of pain, range of joint motion, duration of hospitalization, and occurrence of complications. Although epidural analgesia increased the cost and duration of the operation, good-to-excellent pain relief was attained in 86% (Group 2) and 88% (Group 3) of cases with epidural analgesia compared with 61% of patients (Group 1) receiving conventional analgesia. Moreover, 67% of patients in Group 1 experienced frequent episodes of moderate-to-severe postoperative pain in contrast to 40% of patients in Group 2 and only 10% of patients in Group 3. As a result of diminished pain, greater joint motion was obtained within the first 72 hours in Groups 2 and 3. They also had shorter hospitalization (9.6 days versus 11.2 days for Group 1 and 10.8 days for Group 2). However, the use of epidural analgesia did not reduce the incidence of complications, including nausea. Continuous infusion of epidural bupivacaine and Duramorph provided good-to-excellent control of postoperative pain after TKA. However, better analgesics are needed to reduce the high incidence of side effects associated with various treatment methods.
4
Pneumomediastinum, pneumothorax and subcutaneous emphysema following the measurement of maximal expiratory pressure in a normal subject. Mediastinal and subcutaneous emphysema have been reported as a consequence of deliberate manipulations of the breathing pattern producing a Valsalva-like maneuver in healthy subjects. We present a case of pneumomediastinum, pneumothorax and subcutaneous emphysema occurring in a normal volunteer after repeated measurements of the PEmax.
4
Multimodality cisplatin treatment in nonresectable alpha-fetoprotein-positive hepatoma. Twenty-eight patients with alpha-fetoprotein-positive (AFP+) nonresectable hepatoma have been enrolled in a new multimodality Phase I, II program. Induction therapy consisted of 50 mg/m2 intravenous cisplatin followed by 2100 cGy irradiation to the tumor volume in seven fractions over 10 days. Hepatic arterial infusion of 50 mg/m2 cisplatin (IA-CDDP) was then administered at monthly intervals. Twenty-one patients have completed induction and at least two cycles of IA-CDDP. Twelve-month cumulative survival was 52% for all 28 patients and 69% for the 21 patients completing induction and IA-CDDP. Median survival has not yet been reached. Response rate (complete and partial) was 36% overall and 48% among the 21 patients who completed treatment. The improved survival of the present series of patients as well as the minimal hematologic toxicity suggests possible further integration of new modalities for therapy.
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Role of ultrasonic tissue characterization to distinguish reversible from irreversible myocardial injury. Tissue characterization reflects structural and functional integrity of tissues. Inasmuch as reversible ischemia causes no structural damage and irreversible ischemia results in persistent structural myocardial damage, we postulated that ultrasonic tissue characterization can distinguish the two types of injuries. Anesthetized open chest dogs underwent 15 minutes (group 1, n = 5) and 90 minutes (group 2, n = 8) of acute total occlusion of the left anterior descending coronary artery, followed by 3 hours of reperfusion. Myocardial ischemia-infarction was confirmed with segment shortening, electronmicroscopic examination, and triphenyl tetrazolium chloride staining. Integrated backscatter Rayleigh 5 (IBR5), a measure of ultrasonic backscatter, and Fourier coefficient of amplitude modulation (FAM), an index of cardiac cycle dependent variation in backscatter, were measured at baseline, during ischemia, and after reperfusion. Group 1 (reversible ischemia) showed an increase in IBR5 from -48 +/- 1.2 dB at control to -45 +/- 1.0 dB (p less than 0.01) during ischemia, which returned to baseline after reperfusion (-47 +/- 1.3 dB). FAM was blunted during ischemia (6.2 +/- 1.0 dB during control versus 1.2 +/- 1.0 dB during ischemia, p less than 0.01) and recovered completely during reperfusion. Segment shortening was abolished during ischemia (18% +/- 3% during control versus -12% +/- 5% during ischemia, p less than 0.01) and recovered partially during reperfusion (4% +/- 5%). The group 2 animals with irreversible myocardial injury showed an increase in IBR5, from -49 +/- 1.2 dB during control to -44 +/- 1.0 dB during ischemia (p less than 0.01) and paradoxical bulging of the ischemic region (17% +/- 3% to -7% +/- 3%, p less than 0.01) during ischemia.
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Nonseminomatous germ cell tumor with very high serum human chorionic gonadotropin. Most patients with disseminated nonseminomatous germ cell tumor (NSGCT) have an excellent prognosis with modern chemotherapy, although certain subgroups with a worse prognosis have been described. One such subgroup includes patients with high serum levels of the tumor marker, human chorionic gonadotropin (HCG). Sixteen patients of 104 treated for NSGCT at the CRC Wessex Medical Oncology Unit (Southampton, UK) presented with serum HCG greater than 25,000. Most of these patients exhibited features of the "choriocarcinoma syndrome" with bulky, rapidly progressive disease; frequent pulmonary, hepatic, and central nervous system complications; and a generally poorer response to standard NSGCT chemotherapy. Histologic identification of trophoblastic tumor was not made in all patients and is not essential for the diagnosis of the syndrome; indeed, closed biopsy may be contradicted in some circumstances because of the risk of hemorrhage. The NSGCT patients with poor prognosis, including patients with the choriocarcinoma syndrome, must be clearly identified in order to improve management and, eventually, cure rates.
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The effect of glucose administration on carbohydrate metabolism after head injury. The role of intravenous infusion of glucose in limiting ketogenesis and the effect of glucose on cerebral metabolism following severe head injury were studied in 21 comatose patients. The patients were randomly assigned to alimentation with or without glucose. Systemic protein wasting, arterial concentrations of energy substrates, and cerebral metabolism of these energy substrates were monitored for 5 days postinjury. Both groups were in negative nitrogen balance, and had wasting of systemic proteins despite substantial protein intake. Blood and cerebrospinal fluid (CSF) glucose concentrations were highest on Day 1, but remained higher than normal fasting levels on all days of study, even in the patients who received no exogenous glucose. Although there were no differences in blood or CSF glucose concentrations in the two groups of patients, the glucose group had higher plasma insulin levels, with a mean +/- standard deviation of 14.8 +/- 7.3 microU/ml compared to 10.3 +/- 4.2 microU/ml in the saline group. The blood concentrations of beta-hydroxybutyrate, acetoacetate, pyruvate, glycerol, and the free fatty acids were higher in the saline group than in the glucose group. Cerebral oxygen consumption was similar in the two groups, while the cerebral metabolism of glucose and of the ketone bodies was dependent on whether glucose was administered. In the glucose group, glucose was the only energy substrate utilized by the brain. In the saline group, the ketone bodies beta-hydroxybutyrate and acetoacetate replaced glucose to the extent of 16% of the brain's total energy production. Cerebral lactate production and CSF lactate concentration were lower in the saline group. These studies suggest that administration of glucose during the early recovery period of severe head injury is a major cause of suppressed ketogenesis, and may increase production of lactic acid by the traumatized brain by limiting the availability of nonglycolytic energy substrates.
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Experience with esmolol for the treatment of cocaine-associated cardiovascular complications. The authors report their experience using esmolol, an ultra-short acting beta-adrenergic antagonist, for the treatment of seven patients with cocaine-associated cardiovascular complications. No consistent hemodynamic benefit was found with the use of this drug. Although there was a decline in mean heart rate of 23% (range 0% to 35%), they were unable to show a consistent antihypertensive response. Adverse effects occurred in three patients. This included one patient with a marked exacerbation of hypertension and one who became hypotensive. Another patient developed emesis and lethargy during esmolol therapy and required endotracheal intubation. They do not recommend the routine use of esmolol for cocaine cardiotoxicity.
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Synchronous carcinoma of the colon and rectum. Reports on the incidence of synchronous carcinoma of the colon and rectum have varied from 2 to 11 per cent. The variability is a result of a lack of uniformity in criteria of diagnosis, differences in the population studied and differences in time period used. In this study, we evaluated the incidence and distribution of synchronous lesions during a recent time period before the use of colonoscopy became widespread. We reviewed the records of all patients with newly diagnosed adenocarcinoma of the colon and rectum who were operated upon at our institution between 1976 and 1981. In a total group of 1,000 patients of which 52 per cent were men, there were 54 patients or 5.4 per cent who had synchronous carcinomas. The group of patients with synchronous carcinomas were older than the group with nonsynchronous carcinomas (72.4 versus 68.8 years). There was also a higher incidence of associated benign polyps in the group with synchronous carcinomas (70 versus 30 per cent for a nonsynchronous carcinomas). The anatomic distribution of carcinomas of the colon and rectum in the group with synchronous lesions (111 in total) revealed a higher percentage of carcinomas located on the right side (29.7 versus 22.5 per cent), although the difference did not reach statistical significance. Synchronous carcinomas were located in nonadjacent segments of the colon in 37 per cent. There was no difference in stage between the groups with and without synchronous carcinomas. The preoperative identification of synchronous lesions by either colonoscopy or barium enema is important for the proper treatment of patients with carcinoma of the colon and rectum. Failure to locate these tumors may lead to the demise of the patient.
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Successful control of bleeding from gastric antral vascular ectasia (watermelon stomach) by laser photocoagulation. We report a case of gastric antral vascular ectasia in a patient with primary biliary cirrhosis in whom chronic blood loss was a major problem. She required repeated blood transfusions that were complicated by reactions and still had persistent anaemia. She was treated with laser phototherapy in the form of quadrantic photocoagulation with a neodynium yttrium-aluminium-garnet laser. This greatly improved the endoscopic appearance of the gastric lesions and effectively controlled blood loss. She required no further transfusions. Bleeding recurred after 11 months which was controlled by further laser photocoagulation.
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Long-term effect of dopaminergic drugs in restless legs. A 2-year follow-up. Thirty patients with restless legs syndrome, who initially had all responded well to treatment with levodopa and benserazide, were studied as to the long-term effect of the drugs (at least 2 years). During the 2-year period, two patients were switched from levodopa to bromocriptine. Two patients no longer needed levodopa; one of them had developed paraplegia and in the other the symptoms of restless legs syndrome had disappeared completely. The remaining 26 patients continued to use levodopa. Eight patients maintained the original dose, nine had to use an increased dose, and nine found a decreased dose to be sufficient. The only side effect was transient nausea reported by two of the 30 patients. The study showed that the relief of symptoms of restless legs syndrome by dopaminergic drugs does not wear off with the passage of time, that side effects are minimal even with long-term use, and that the dose needed to obtain relief may increase as well as decrease.
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Acute leukemia and related entities. Impact of new technology. Twenty-seven cases of acute leukemia and related entities were evaluated by morphologic examination, cytochemical study, terminal deoxynucleotidyltransferase study, immunophenotyping, cytogenetic analysis, ultrastructural cytochemical study, and gene rearrangement analysis to determine the impact on the determination of the French-American-British (FAB) classification and the definitive diagnosis. The definitive diagnosis contained prognostic, diagnostic, and treatment information beyond the FAB classification that affected the disease course and patient management. All diagnostic variables were evaluated in each case and were labeled essential, ambivalent, supportive, or noncontributory. Except for gene rearrangement analysis, all variables we studied contributed essential data to establish the definitive diagnosis. Ambivalent findings were rare but could be explained with the knowledge of the total data. All variables, except cytochemical study, whose results were almost always essential, contributed supportive data. Noncontributory data only occurred with cytogenetic analysis in cases that demonstrated normal karyotypes. The FAB classification was established in 20 (74%) of the cases by use of morphologic examination, cytochemical study, and terminal deoxynucleotidyltransferase study. With use of the same variables, however, the definitive diagnosis, whose determination required all data, was established in only 15 (55.5%) of the cases. The addition of immunophenotyping increased the definitive diagnosis to 25 (92.5%) of the cases. The use of ultrastructural myeloperoxidase and platelet peroxidase analysis enabled us to definitively diagnose the remaining two cases (27 cases [100%]). Cytogenetic analysis revealed four cases in which essential information was added to the diagnosis. However, because the cytogenetic information usually was not immediately available, the result did not affect the immediate diagnosis or treatment. Surprisingly, the gene rearrangement studies did not yield essential data in any case and in a few cases contributed ambivalent data. This finding should not exclude gene rearrangement analysis in selected cases; however, the data should always be interpreted in light of all clinical and laboratory findings. This study clearly demonstrates the importance of a multifaceted approach to the understanding of the acute leukemias and related entities and shows the impact of newer technologies on reaching a definitive diagnosis.
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Leucine kinetics in patients with benign disease, non-weight-losing cancer, and cancer cachexia: studies at the whole-body and tissue level and the response to nutritional support. We have performed intraoperative isotopic infusions of carbon 14-labeled leucine in 65 patients to define the abnormalities in protein metabolism at both the whole-body and tissue level in patients with weight-losing and non-weight-losing cancer. Eighteen patients had benign disease, 26 had non-weight-losing cancer, and 21 had cancer cachexia. Samples of plasma and expired breath were taken to determine rates of whole-body protein synthesis (WBPS), whole-body protein catabolism (WBPC), net protein catabolism, and albumin fractional synthetic rates. Tissue samples were taken to determine the fractional synthetic rates (FSR) of protein in muscle, liver, cancer, and the tissue in which the cancer arose. In addition, in 14 patients the effect of nutritional support on protein metabolism was assessed. In all parameters examined we were unable to detect any significant differences between patients with no cancer and the patients with non-weight-losing cancer. In contrast, patients with cancer cachexia had a significant elevation (p less than 0.005) in WBPC compared with the other two groups. WBPS was also elevated (to a lesser extent) in the patients with cancer cachexia, and the rate of net protein catabolism was increased significantly (p less than 0.05). Patients with cancer cachexia also had significantly higher values of FSR of protein in muscle (p less than 0.05), liver (p less than 0.05), and albumin (p less than 0.01) compared with the other two groups. In addition, the protein FSR in the cancer rose progressively when the values for the primary cancer were compared with those for nodal and systemic metastases. Further, although nutritional support resulted in an increase in host muscle protein synthesis (p less than 0.04), there was no promotion of FSR of protein in cancer. We conclude that patients with cancer cachexia are actively losing protein as a result of an increase in WBPC that is only partially compensated for by an increase in WBPS. There are compensatory increases in protein synthesis in muscle and liver, but these increases in host protein synthesis are insufficient to keep pace with the combined effect of the accelerated rate of protein synthesis in the cancer per se and the accelerated rate of net protein catabolism at the whole-body level. In response to nutritional support, there is a significant increase in the muscle protein synthesis, but we could not demonstrate any increase in cancer protein synthesis.
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Prospective randomized multicenter comparison of in situ and reversed vein infrapopliteal bypasses. We have performed a prospective, randomized, multicenter study to compare in situ and reversed vein grafts for long limb salvage bypasses from the proximal thigh to an infrapopliteal artery. Three hundred eighty-four patients required an infrapopliteal bypass for critical lower extremity ischemia. Of these, 259 were excluded because a short vein bypass was performed or because the vein was considered inadequate. The remaining 125 patients had a randomized vein bypass, 63 reversed, 62 in situ. The two groups were similar with regard to risk factors, indications, graft dimensions, and outflow. Secondary patency at 30 months was similar for both techniques: reversed 67% +/- 9% (+/- SE); in situ 69% +/- 8%. For veins less than or equal to 3.0 mm in minimum distended diameter 24-month patency rates were 61% +/- 22% for 12 in situ veins and 37% +/- 29% for 10 reversed veins (p greater than 0.05). Angiographic evaluation of failing grafts revealed lesions similar in type and frequency in both types of grafts. These included focal (in situ, n = 4; reversed, n = 7) and diffuse vein hyperplasia (in situ, n = 2; reversed, n = 1), and inflow and outflow stenoses (in situ, n = 4; reversed, n = 3). The incidence of wound complications and the mortality rate were similar for the two groups. These data show no significant difference in overall patency rates for the two types of vein grafts at 2 1/2 years.
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Variability in DNA measurements in multiple tumor samples of human colonic carcinoma. The DNA ploidy and cell-cycle distribution of three separate fresh tissue samples of 60 colorectal adenocarcinomas were analyzed by flow cytometry. DNA ploidy was concordant among the three samples in 38 cases (63.3%). In the remaining 22 cases (36.6%), the DNA histograms of two of the three multiple samples were similar; however, the ploidy of the third sample was discordant. No relationship was observed between Dukes' stage and histologic grade with concordance or discordance among samples. Thus, in about one third of the colonic carcinomas, a single sample showing either a diploid or diploid-cycling DNA histogram would not detect aneuploid DNA patterns. Comparison of scrapes and fine-needle aspirates of tumors as alternative sampling methods of tumors for DNA ploidy analysis indicated a strong association with the tumor ploidy (84% and 96%, respectively) only when the ploidy of the multiple samples was concordant. In about 25% of the cases, tumor scrapes and fine-needle aspirates did not correlate with the "most abnormal" ploidy observed in one of the three tissue samples. The data suggest that single or even double tissue samples may not show aneuploid DNA patterns in a substantial proportion of colorectal cancers.
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