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Penetration of the pericardium by a gastric ulcer--survival after pericardiocentesis. Elderly patients often have unusual manifestations of common illnesses. We describe a geriatric patient having a pneumopericardium from pericardial penetration by a gastric ulcer. Benign gastric ulceration causing perforation of the pericardium or other cardiac structures was recognized as early as 1854; however, until 1964, the condition was invariably fatal. Our patient survived the episode after early pericardiocentesis and medical treatment. Aspects of this uncommon clinical entity and a brief review of the literature are described. | 3 |
Effects of hypovolemia and transfusion on tumor growth in MCA-tumor-bearing rats. Pretransplant blood transfusion has been shown to significantly affect the outcome of renal transplantation. Evidence regarding the association of blood transfusions with growth or recurrence of solid tumors is still conflicting both in clinical and in experimental studies, although diminished survival has been suggested in several studies. To determine the influence of blood transfusions and hypovolemia, as separate or combined factors, on tumor growth, we evaluated the weight of a subcutaneously implanted sarcoma (methylcholanthrene-induced) in 35 rats. After reaching 1% tumor burden (day 0), the animals were separated into two groups: hypovolemia (shed volume, 15 ml/kg) or normovolemia. These groups were further divided according to resuscitation: OO (no resuscitation), BL (receiving syngeneic blood stored in citrate phosphate dextrose for 4 days, 15 ml/kg), SL (receiving 0.9% sodium chloride, 45 ml/kg). Tumor dimensions were determined daily by external measurement, and tumor weight was calculated. Hypovolemia exerted a significant influence on tumor growth, independent of the resuscitation modality. The rats that received blood transfusions showed an increased rate of tumor growth, compared to the animals that received saline solution or no treatment. No interaction was noted between the effects produced by hypovolemia and blood transfusion. We conclude that the hypovolemic event enhanced tumor growth independently of the resuscitation, and transfusion of citrate phosphate dextrose-blood stored for 4 days did influence tumor growth in this model. We suggest that the effect of blood transfusion in patients with cancer has to be redefined to account for the influence of possible hypovolemic events. | 4 |
Early beneficial effect of streptokinase on left ventricular function in acute myocardial infarction. The effect of intravenous streptokinase therapy on the time course of functional recovery was investigated in a controlled study of 64 patients randomized within 3 hours after the onset of acute myocardial infarction (AMI). Contrast ventriculography was performed 1 to 4 days after AMI and repeated 5 weeks later. Wall motion was analyzed by the centerline method in the central infarct, peripheral infarct and noninfarct regions. In patients with ventriculographic data at the early catheterization, streptokinase-treated patients had less severe hypokinesia in the central infarct region than control patients (-2.9 +/- 0.9 [n = 29] vs -3.4 +/- 0.7 standard deviations below normal [n = 21], p less than 0.05). The benefit of streptokinase was more marked in the peripheral infarct region (-1.5 +/- 0.7 vs -2.1 +/- 0.6, p less than 0.001). As a result, the ejection fraction was slightly higher in treated versus control groups (46 +/- 10 vs 43 +/- 7%, respectively; difference not significant). At 5 weeks, function in the streptokinase and control groups had diverged further because of continued improvement in the streptokinase-treated patients. This study shows that streptokinase benefits left ventricular (LV) function by 1 to 4 days after AMI, earlier than previously reported. The benefit was not limited to the peripheral infarct region, where ischemia might have been less severe, but was also seen in the central infarct region. The implication is that thrombolytic therapy can improve LV function during the period of myocardial stunning, while myocardial function is still recovering. | 3 |
Repetitive intraoperative mapping and cryotherapy improve the results of endocardial resection for ventricular tachycardia. Patients with recurrent ventricular tachycardia or a history of a sudden cardiac death episode and ventricular tachycardia inducible in the electrophysiology laboratory have a high incidence of recurrence and a high mortality despite medical therapy. Map-guided endocardial resection has improved treatment results, but is associated with a 10-30% failure rate. In our initial experience with endocardial resection (Group I) we incurred a 30% treatment failure rate. In the present study we have found the addition of sequential intraoperative mapping and routine use of cryotherapy (Group II) improved our results of ventricular tachycardia control without significant additional morbidity or mortality. | 3 |
Subscapular elastofibroma in a young pitcher. A case report. Subscapular elastofibromas and scapulothoracic bursitis can cause symptomatic masses in baseball pitchers. Both processes appear to represent reactive soft tissue responses to repetitive stress at the inferior border of the scapula. It is assumed that most masses in the subscapular area represent scapulothoracic bursitis rather than an elastofibroma. However, it is possible that some of the masses treated conservatively as scapulothoracic bursitis may be elastofibromas. A study is currently under way to evaluate the incidence of subscapular masses in college and professional pitchers in the United States. A follow-up report is anticipated when the study has been completed. The author requests information concerning any confirmed cases of elastofibroma in baseball pitchers. | 0 |
Coexisting thymic carcinoid tumor and thymoma. Thymic carcinoid tumors are unusual neoplasms that are different from thymomas. We report a case of coexisting thymic carcinoid tumor and thymoma associated with myasthenia gravis. The clinicopathological findings are discussed with a review of the literature. | 0 |
Ataxia and peripheral neuropathy: a benign variant of peroxisome dysgenesis. A 5-year-old boy with panperoxisomal dysfunction is described. Clinical features included hypotonia, areflexia, and ataxia. Cognition, vision, hearing, and hepatic function were normal. A panel of peroxisomal markers, including very-long-chain fatty acids, phytanic acid, pipecolic acid, and catalase compartmentalization, were abnormal. This is a uniquely benign syndrome of disordered peroxisome biogenesis. | 2 |
Resection and reconstruction for soft-tissue sarcomas of the extremity. Soft-tissue sarcomas are uncommon malignant tumors, and when a diagnosis is made early, the patient has up to an 80% chance of surviving. In treating soft-tissue sarcomas, the goal of the surgeon is the prolongation of patient survival, the total eradication of local disease, and the minimization of functional deficits. In addition to treatment, this article discusses evaluation, histology, and staging. | 0 |
Fatigue failure of noncemented porous-coated implants. A retrieval study. The causes of mechanical failure of five noncemented porous-coated components were studied. There were two cobalt-chromium alloy and three titanium alloy implants which fractured after 12 to 48 months. The implants included one acetabular component, and one femoral condylar, one patellar and two tibial components. Examination of the fractured surfaces revealed fatigue to be the mechanism of failure in all cases. The porous coating and the processes required for its fabrication had resulted in weakening and reduction of substrate thickness. Additional factors were stress concentration due to limited, localised bone ingrowth, and some features of the design of the implants. | 4 |
Biliary pain in postcholecystectomy patients without biliary obstruction. A prospective radionuclide study. Biliary pain without obvious biliary obstruction is common in postcholecystectomy patients. We studied 20 symptomatic patients with episodes of biliary-type pain after cholecystectomy (all having undergone endoscopic retrograde cholangiography), and in 18 asymptomatic postcholecystectomy controls. We performed quantitative hepatobiliary radionuclide analysis with dimethyl-imidodiacetic acid. From a series of 90 dynamic images at 1-min intervals using a gamma camera coupled to a computer, time-activity curves were produced in regions of interest in the liver, intrahepatic biliary tree, common duct, and heart, from which quantitative biliary excretion indexes were obtained. The results demonstrate a biliary kinetic dysfunction in patients with postcholecystectomy pain without morphological abnormalities. | 4 |
Effects of acute hypermagnesemia on the threshold for lidocaine-induced seizures in the rat. The effects of acute changes in plasma magnesium concentration on the threshold for lidocaine-induced seizures were evaluated in mechanically ventilated rats receiving 70% nitrous oxide and 30% oxygen. In experiment 1, male rats were intravenously administered either 0.9% sodium chloride (group I) or 5.0% magnesium sulfate to elevate plasma magnesium levels to 5.8 +/- 0.1 (group II) or 10.5 +/- 1.0 mg/dl (group III). In experiment 2, pregnant rats were intravenously administered either 0.9% sodium chloride (normomagnesemia) or magnesium sulfate, resulting in a plasma magnesium concentration of 7.8 +/- 1.4 mg/dl. Thirty minutes later, a continuous intravenous infusion of lidocaine (2.3 mg/kg per minute) was begun in both experiments. Biparietal electroencephalographic activity was monitored continuously. At the onset of electroencephalographic seizure activity, arterial plasma magnesium and lidocaine concentrations were measured. In groups I and III (experiment 1), brain parenchymal magnesium was also assayed. There were no differences in plasma lidocaine concentrations (in experiments 1 or 2) between saline solution and hypermagnesemic groups at onset of seizures. Brain magnesium level was unaltered by magnesium sulfate infusion. We conclude that acute administration of magnesium sulfate alters neither brain magnesium level nor the plasma lidocaine concentration associated with onset of electroencephalographic seizures. | 2 |
A study of the effectiveness of the iron-chelating agent deferoxamine as vasospasm prophylaxis in a rabbit model of subarachnoid hemorrhage. The pathogenesis of cerebral vasospasm occurring after subarachnoid hemorrhage (SAH) is unknown. Several lines of experimentation have suggested a free radical mechanism in the etiology of vasospasm. Iron is an important catalyst in the generation of free radicals and lipid peroxides in response to tissue injury. We hypothesize that the elaboration of iron from the subarachnoid clot might result in enhanced generation of free radicals and lipid peroxidation. If so, then treatment with deferoxamine, an iron-chelating compound, might reduce the formation of free radicals and thereby ameliorate vasospasm. This hypothesis was examined in a rabbit model of experimental cerebral vasospasm. New Zealand White rabbits were divided into the following experimental groups: control (normal) animals (n = 7), control animals treated with deferoxamine (n = 3), animals subjected to SAH and killed on Day 2 (n = 7), animals subjected to SAH on Day 2 and treated with deferoxamine (n = 9), animals subjected to SAH killed on Day 3 (n = 7), and animals subjected to SAH on Day 3 and treated with deferoxamine (n = 7). Deferoxamine treatment (50 mg/kg/8 hours) was begun 16 hours before the induction of SAH and continued until the animals were killed by perfusion fixation. The basilar artery caliber was assessed using morphometric techniques. The diameter of the basilar arteries in the control animals was 0.64 +/- 0.02 mm. Deferoxamine treatment alone did not alter the artery diameter. | 3 |
Acute angiographic and clinical outcome of high speed percutaneous rotational atherectomy (Rotablator). Percutaneous rotational atherectomy (Rotablator), a high speed (greater than 100,000 RPM) rotational burr, was used successfully in 38 of 43 patients (88%) (mean age: 65 +/- 7 years) with 82 lesions (71 stenoses and 11 occlusions). The clinical indications were claudication (84%), nonhealing ulcer (7%), and renovascular hypertension (7%). Rotablation was successful in 78 of 82 lesions (95%): 68 of 71 (96%) stenoses (12 of 12 iliac, 11 of 11 femoral, 7 of 8 popliteal, 36 of 37 tibial, and 2 of 3 renal arteries; 60% of lesions were diffuse, i.e., greater than or equal to 4 cm in length), and 10 of 11 (91%) occlusions (5 of 6 femoral, 1 of 1 popliteal, 3 of 3 tibioperoneal, 1 of 1 brachial artery). The Rotablator significantly (p less than 0.001) reduced the arterial obstruction (stenoses: 85 +/- 11% to 12 +/- 12%); occlusions: 100% to 25 +/- 10%). The effective final burr size for arteries varied at 3.5-4.5 mm for renal, 3.0-3.5 mm for femoral, and 2.0-3.0 mm for brachial and tibial. Complications included gross hemoglobinuria without sequelae in 27 patients (63%), groin hematoma in 10 (23%), arterial spasm in 10 (23%), and arterial bypass in 2 (5%). The Rotablator was successfully used, without concomitant conventional balloon angioplasty, to open arterial lesions with excellent angiographic results in both diffuse and segmental peripheral vascular disease. There was gratifying patient clinical improvement. | 4 |
Concordance for dyslipidemic hypertension in male twins. Sixty cases of dyslipidemic hypertension were identified in the 1028 middle-aged, white, male twin participants in the first examination of the National Heart, Lung, and Blood Institute Twin Study (1969 to 1973). The prevalence of dyslipidemic hypertension was similar by zygosity but proband concordance was three times greater in monozygotic than dizygotic twins (0.44 [seven concordant and 18 discordant pairs] vs 0.14 [two concordant and 24 discordant pairs]), suggesting a genetic effect on the condition. Low high-density lipoprotein cholesterol level was the most common lipid abnormality in concordant pairs. Mortality from ischemic heart disease was significantly higher in individuals with dyslipidemic hypertension. Obesity and glucose intolerance were closely associated with the syndrome. Moreover, within the 18 discordant monozygotic twin pairs, the twins with dyslipidemic hypertension had gained significantly more weight as adults and were significantly heavier than their unaffected cotwins. Thus, although genetic factors may influence development of dyslipidemic hypertension, nongenetic, potentially modifiable aspects of obesity are also closely related to expression of this clinically important syndrome. | 4 |
Dilatation in the duplex kidney: 3 unusual cases. Dilatation in the upper limb of a duplex ureter is usually secondary to obstruction and may be associated with a ureterocele. By contrast, vesicoureteric reflux is the usual cause of a dilated lower moiety ureter. We report 3 cases in which unusual or complex causes of dilatation of 1 limb of a duplex ureter were demonstrated. | 4 |
Transcriptional regulation of ferritin messenger ribonucleic acid levels by insulin in cultured rat glioma cells. Recent data have shown that ferritin, a ubiquitous protein, has a role as a regulator of cellular differentiation. In the present study we have investigated the expression of ferritin mRNAs in cultured C6 cells, a rat glioma cell line, in response to insulin, which has an important role in cellular growth and differentiation. Insulin stimulated steady state levels of both ferritin heavy chain and ferritin light chain mRNAs. An increase in the level of ferritin heavy or light chain mRNA was detected after 2 h of incubation with insulin, and a plateau was reached after 48 h for heavy chain mRNA and after 72 h for light chain mRNA. The responses were dose-dependent and were maximal at 100 nM for both mRNAs. Treatment of cells with actinomycin-D showed that insulin had no effect on the posttranscriptional stability of these mRNAs. Actinomycin-D inhibited insulin-induced accumulation of both mRNAs, suggesting transcriptional stimulation of ferritin genes by insulin. A nuclear run-on assay showed that the insulin-induced increase in ferritin heavy chain mRNA was due to an increase in the rate of gene transcription. We also demonstrated that insulin-like growth factor-I (IGF-I) increased ferritin heavy and light chain mRNA levels in a dose-dependent fashion, and that the maximum effect was obtained at a concentration of 10 nM on both mRNA levels. IGF-I was not only 10-fold more potent, but the absolute level of maximum stimulation was also about 2-fold greater than that for insulin. The combination of insulin (100 nM) and IGF-I (10 nM) showed no additive effect. The results suggested that the ferritin heavy and light chain genes are transcriptionally regulated by insulin and influenced by IGF-I. | 0 |
Psychogenic purpura (autoerythrocyte sensitization): an unsolved dilemma. Experience at University Hospitals of Cleveland with 71 cases of Gardner and Diamond's syndrome of autoerythrocyte sensitization is reviewed. Gardner and Diamond attributed the pathogenesis of the inflammatory bruises typical of this syndrome to sensitization to the stroma of the patients' own erythrocytes, as demonstrated by reproduction of the lesion on intracutaneous injection of erythrocytic stroma. Nearly all the cases my colleagues and I have seen were in adult women, in whom the onset of inflammatory bruising could often be precisely dated, frequently some weeks after an injury or surgical procedure or, more often, severe emotional stress. Bouts of bruising were often preceded by sensations localized to the affected site. Cutaneous responses to the injection of erythrocytes were erratic. The patients described a wide range of both hemorrhagic and nonhemorrhagic complaints, including, among others, severe headaches, paresthesias, repeated syncope, diplopia (sometimes monocular), and "nervousness." Psychiatric studies indicated that patients had overt depression, sexual problems, feelings of hostility, and obsessive-compulsive behavior. The patients had traits that can be described as typical of a hysterical character disorder. Therapy of autoerythrocyte sensitization--that is, psychogenic purpura--has been difficult; in younger individuals, psychiatric therapy has appeared to be beneficial. | 4 |
Alpha 1-acid glycoprotein and the binding of lidocaine in children with congenital heart disease. The purpose of this study was to evaluate the effect of congenital heart disease (CHD) on the serum concentrations of alpha 1-acid glycoprotein (alpha 1-AGP) and the serum binding of lidocaine. Thirteen children with acyanotic CHD and 12 children with cyanotic CHD were studied and compared with 28 children without heart disease (control). The mean (+/- SD) serum concentration of alpha 1-AGP, as determined by radial immunodiffusion, did not differ significantly among the three groups. Five minutes after administration of 1.5 mg.kg-1 intravenous lidocaine, the free fraction of lidocaine correlated inversely and linearly with the serum concentration of alpha 1-AGP in children with acyanotic CHD (r2 = 0.74; P less than 0.001) cyanotic CHD (r2 = 0.57; P less than 0.005), and control (r2 = 0.63; P less than 0.001). The slopes and intercepts of the linear regressions did not differ significantly among the three groups. We conclude that the serum concentration of alpha 1-AGP in children with CHD does not differ quantitatively or qualitatively from that in children without CHD. | 4 |
Malignant melanoma of the biliary tract: a case report. A 58-year-old man was seen with obstructive jaundice and discomfort in the upper abdomen. Computed tomographic and ultrasound examinations revealed a soft-tissue mass in the gallbladder. Cholecystectomy and choledochotomy revealed a soft black mass in the gallbladder and a second one in the intrapancreatic portion of the common bile duct. Each was diagnosed as malignant melanoma. Subsequently, a Whipple resection of the pancreas, duodenum, and distal bile duct revealed a melanoma circumferentially invading and obstructing the distal common duct. No lymph node or distant metastasis was identified. Repetitive searches for another primary site have been negative. The tumor apparently originated in the biliary tract. The patient remains almost well 2 years after diagnosis. | 0 |
Spontaneous alterations in coronary blood flow velocity before and after coronary angioplasty in patients with severe angina. Cyclic coronary artery flow variations with a spontaneous decline in coronary blood flow to very low levels have been documented in stenosed canine coronary arteries with endothelial injury. These flow variations are associated with transient platelet aggregation and dislodgment and the release of selected mediators, including thromboxane A2 and serotonin. However, cyclic or spontaneous flow variations have not been demonstrated in stenosed coronary arteries in humans. In this study, the hypothesis was tested that spontaneous coronary blood flow velocity variations occur in some patients with stenosed coronary arteries before or after coronary artery angioplasty. Thus, 13 patients with severe and limiting angina underwent intracoronary pulsed Doppler velocimetry of their dilated artery immediately before and after percutaneous transluminal coronary angioplasty, whereas 9 control patients underwent velocimetry of an angiographically normal coronary artery. A 3F catheter with a 20 MHz Doppler crystal was positioned to achieve a maximal stable signal, and the flow velocity signal was recorded continuously for 20 min. Spontaneous flow velocity variations (greater than or equal to 38% change in Doppler frequency shift with wide morphologic changes) were present in 3 of the 13 patients tested. Spontaneous flow velocity variations occurred before angioplasty in one patient, after angioplasty in another and both before and after angioplasty in a third. In addition, 2 of the 13 patients, 1 with spontaneous coronary artery flow velocity variations before angioplasty, had frank vasospasm in an adjacent area just distal to the area of coronary dilation immediately after balloon inflation. These data establish that spontaneous coronary artery flow velocity variations occur in some patients with severe and limiting angina before and after coronary angioplasty. These variations may be related to platelet aggregation or coronary vasoconstriction, or both, at sites of endothelial injury resulting from plaque fissuring or ulceration and endothelial and medial injury occurring during coronary angioplasty. | 3 |
Stereotactic radiosurgery of meningiomas. Stereotactic radiosurgery has an expanding role in the management of selected intracranial tumors. In an initial 30-month experience using the 201-source cobalt-60 gamma knife at the University of Pittsburgh, 50 patients with meningiomas were treated. The most frequent site of origin was the skull base. Previously, 36 patients (72%) had undergone at least one craniotomy and four patients (8%) had received fractionated external beam radiation therapy. Stereotactic radiosurgery was the primary treatment modality in 16 patients (32%) with symptomatic tumors demonstrated by neuroimaging. Computer imaging-generated isodose plans (with one to five irradiation isocenters) for single-treatment irradiation gave optimal (greater than or equal to 50% isodose line) coverage in 44 patients (88%). The proximity of cranial nerves or vascular, pituitary, and brain-stem structures to the often convoluted tumor mass was crucial to dose selection. Serial imaging studies were evaluated in all 50 patients. Twenty-four patients were examined between 12 and 36 months after treatment; 13 (54%) showed a reduction in tumor volume while nine (38%) showed no change. Of 26 patients evaluated between 6 and 12 months after treatment, four showed a decrease in tumor size while 22 showed no change. Two patients (both with large tumors that received suboptimal irradiation) had delayed tumor growth outside the radiosurgical treatment volume. The actuarial 2-year tumor growth control rate was 96%. Between 3 and 12 months after radiosurgery, three patients developed delayed neurological deficits that gradually improved, compatible with delayed radiation injury. Although extended follow-up monitoring over many years will be necessary to fully evaluate treatment, to date stereotactic radiosurgery has proved to be a relatively safe and effective therapy for selected patients with symptomatic meningiomas, including those who failed surgical resection. Radiosurgery was an effective primary treatment alternative for those patients whose advanced age, medical condition, or high-risk tumor location mitigated against surgical resection. | 2 |
Nitrite from inflammatory cells--a cancer risk factor in ulcerative colitis? Elevated levels of luminal nitrite and a lowered luminal pH were found in 77 percent of patients with acute ulcerative colitis. No luminal nitrite was found in healthy control subjects. Nitrites are a secretory product of activated macrophages and neutrophils of the lamina propria, whereas the lowered luminal pH is due to diminished bicarbonate formation by impaired colonocytes. A hypothesis is put forward that nitrites, lowered pH, and bacterial amines are conducive to formation of carcinogenic n-nitroso compounds, which reflect a cancer risk in patients with ulcerative colitis dependent on the type and extent of inflammatory cell activation as well as metabolic impairment of colonic epithelial cells. | 1 |
A randomized comparison of manipulation of the fractured nose under local and general anaesthesia. Reduction of simple nasal fractures may be performed under local or general anaesthesia: the latter is by far the most popular method in Britain, though why is hard to define. We have attempted to compare the 2 approaches by means of a randomized, prospective trial. Fifty consecutive, adult patients with radiologically proved fractures of the nasal bones were randomized to a local or general anaesthesia group and underwent manipulation with Asch's and Walsham's forceps between 7 and 15 days post-injury. Analysis of results at 4 h and 8 weeks post-operatively showed no significant benefit conferred by fracture reduction under general anaesthesia as opposed to local anaesthesia with respect to post-operative airway patency or cosmesis. It is suggested that significant benefits can be obtained in terms of patient convenience and cost effectiveness if nasal fractures are reduced under local anaesthesia as an outpatient procedure. | 2 |
Recurrent cyanotic episodes with severe arterial hypoxaemia and intrapulmonary shunting: a mechanism for sudden death The pathophysiology of recurrent cyanotic episodes has been investigated in 51 infants and children. Episodes began at a median age of 7 weeks (range 1 day to 22 months, 39 at less than 4 months). They were characterised by the rapidity of onset and progression of severe hypoxaemia with early loss of consciousness from cerebral hypoxia. The most common precipitating factor was a sudden naturally occurring stimulus from pain, fear, or anger. In uncontrolled trials, cyanotic episodes were reduced in frequency and severity by tetrabenazine (n = 15) and additional inspired oxygen (n = 10). Eight patients died suddenly and unexpectedly (four during cyanotic episodes). Twenty eight patients underwent physiological studies during cyanotic episodes. There was no evidence of seizure activity at the onset and although prolonged absence of inspiratory effort with continued expiratory efforts was common, breathing sometimes continued. Episodes were not caused by upper airway obstruction and sometimes occurred during positive airway pressure ventilation. The rapidity of fall in arterial oxygen pressure and continued breathing suggested a right to left shunt of sudden onset. The results of contrast echocardiography and lung imaging studies confirmed that this was occurring within the lungs. These cyanotic episodes included both intrapulmonary shunting and prolonged expiratory apnoea. They are best explained by interactions between central sympathetic activity, brainstem control of respiration and vasomotor activity, reflexes arising from around and within the respiratory tract, and the matching of ventilation to perfusion in the lungs. They are a cause of sudden unexpected death in infancy and early childhood. | 4 |
Immunohistochemical detection of abnormal cell proliferation in colonic mucosa of subjects with polyps. Previous studies have shown the presence of increased proliferation in the large bowel epithelium of those at high risk of developing colon cancer. An in vitro technique for labelling large bowel mucosa with the thymidine analogue bromodeoxyuridine (Brdu) was therefore developed and its ability to distinguish differences in mucosal proliferation between subjects with colorectal adenomas and normal controls was assessed. Sigmoid biopsy specimens from 15 subjects with polyps and 15 age and sex matched controls were labelled and the incorporated Brdu visualised with an immunohistochemical technique. Mean labelling index (LI) was significantly higher in those with polyps than in controls. Differences in the pattern of labelling in colonic crypts were compared by the generation of cumulative labelling distributions. Analysis showed a significant expansion of the proliferative compartment in the colon crypts of those with polyps. It is concluded that in vitro labelling with Brdu provides a useful method for the assessment of mucosal proliferation in subjects at high risk of developing colon cancer. | 1 |
The placebo effect in heart failure. Many patients who are enrolled in controlled clinical trials of new drugs for the treatment of heart failure show favorable hemodynamic and clinical responses to placebo therapy. This "placebo effect" results from both the creation of a supportive therapeutic environment and the spontaneous improvement that is commonly seen when measurements of symptoms and cardiac function are repeated frequently over long intervals of time. Three months of treatment with a placebo produces a reduction in symptoms in 25% to 35% of patients, an increase in cardiac output and a decrease in pulmonary wedge pressure, and an increase in exercise tolerance of up to 90 to 120 seconds. Physicians commonly seek to maximize the "placebo effect," since the goal of treatment in the clinical setting is to improve the quality of the patient's life. On the other hand, clinical investigators seek to minimize the "placebo effect," since the goal of a research study is to test the hypothesis that the new drug is superior to a placebo. | 3 |
Molecular genetic basis of maple syrup urine disease in a family with two defective alleles for branched chain acyltransferase and localization of the gene to human chromosome 1. Maple syrup urine disease in humans results from inherited defects in branched chain alpha-ketoacid dehydrogenase, a mitochondrial multienzyme complex. A variety of genetic changes may produce this phenotype by affecting the function of any of the three complex-specific subunits. The varied clinical expression observed in patients may be partially explained by the defects in the involved subunit. Here we report localization of the gene for the branched chain acyltransferase component of the complex to human chromosome 1 and describe a proband who is a compound heterozygote at this locus. One allele, inherited from the father, produces transcripts with 124 nucleotides deleted from the coding region. The deletion is not found in the branched chain acyltransferase gene, implying that the deleted transcripts arise by an error in transcript processing. Cells from the patient's mother contain 50% of the normal amount of mRNA for the subunit, and the proband has inherited this nonexpressing allele from her. As a result, the proband produces no acyltransferase protein and therefore has greatly impaired complex activity. A phenotypically normal sibling is shown to be genetically similar to the mother having inherited the mother's nonexpressing allele and the father's normal allele. | 2 |
Exercise thallium-201 scintigraphy in the diagnosis and prognosis of coronary artery disease. OBJECTIVE: To determine the discriminant accuracy of exercise thallium-201 myocardial perfusion scintigraphy for the diagnosis and prognosis of patients with known or suspected coronary artery disease. DATA IDENTIFICATION: A survey of the National Library of Medicine MEDLINE database. STUDY SELECTION: The key medical subject headings used were coronary disease, myocardial infarction, radionuclide imaging, and thallium. A total of 122 retrieved studies were considered relevant and were reviewed in depth. DATA EXTRACTION: Only studies reporting both the sensitivity and specificity of thallium scintigraphy were analyzed. RESULTS: Discriminant accuracy for diagnosis and prognosis was summarized in terms of pooled sensitivity and specificity. CONCLUSIONS: Exercise thallium scintigraphy is useful in the noninvasive diagnosis of coronary artery disease, especially in patients with abnormal resting electrocardiograms, restricted exercise tolerance, and intermediate probability of having disease at the time of testing as well as of defining the prognosis of patients with known or suspected coronary artery disease, especially in those with previous myocardial infarction. Because of various shortcomings in the published record, however, the marginal discriminant accuracy and cost effectiveness of thallium scintigraphy compared with conventional clinical assessment and exercise electrocardiography remain controversial. | 3 |
Antibodies directed against neutrophils (C-ANCA and P-ANCA) are of distinct diagnostic value in systemic vasculitis. In a prospective study, sera from over 700 patients with suspected vasculitis, including over 200 patients undergoing renal biopsy, were examined for antibodies to neutrophil cytoplasmic antigen (ANCA). An indirect immunofluorescence assay on ethanol fixed human neutrophils identified two types of autoantibody: C-ANCA, which produces diffuse cytoplasmic staining and P-ANCA, which produces an artefactual nuclear/perinuclear staining pattern. The diagnosis of patients in whom ANCA of either form was found was established following case note review according to defined diagnostic criteria. Forty of 45 patients whose sera contained C-ANCA at a titre of greater than or equal to 1/40 satisfied the diagnostic criteria for Wegener's granulomatosis or microscopic polyarteritis. Twelve of 30 patients with P-ANCA at a titre of greater than or equal to 1/40 were also classified as having one of these disorders. Seventeen of the remaining 18 patients had immune-mediated disorders with deep organ damage. Of 47 ANCA-positive patients who underwent renal biopsy, 21 had glomerulonephritis associated with Wegener's glomerulonephritis and a further 22 had a necrotizing or crescentic glomerulonephritis. Ethanol fixation is important for discrimination of C-ANCA and P-ANCA. C-ANCA are highly specific for Wegener's granulomatosis and microscopic polyarteritis. In patients undergoing renal biopsy, the presence of these antibodies is highly specific for a necrotizing or crescentic glomerulonephritis. | 3 |
Serum keratan sulfate. Quantitative and qualitative comparisons in inflammatory versus noninflammatory arthritides. The concentration of keratan sulfate (KS) epitope was measured in the serum of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) by enzyme-linked immunosorbent assay and compared with that in the serum of patients with primary fibromyalgia syndrome (PFS) and of controls who had no joint disease. By Student's tau-test, the mean serum KS concentrations in OA and RA patients measured with monoclonal antibodies (MAb) 5-D-4 and 2-D-3 were significantly increased over those in the PFS and normal groups; similar findings were observed using a nonparametric test, except that levels in RA patients showed no difference from those in PFS patients and normal subjects. There was no significant correlation between joint scores or disease duration and KS levels in OA or RA patients. Gel filtration of sera revealed mainly large, polydisperse KS-bearing fragments which eluted in a broad profile. KS purified from sera by immunoaffinity chromatography consisted mainly of high-density proteoglycans. Electrophoresis of pooled high-density KS fractions in polyacrylamide-agarose gels followed by Western blotting with MAb 5-D-4 showed diffuse bands with relative mobilities corresponding to large proteoglycans. These findings are consistent with attachment of KS to protein core fragments of various sizes; KS in patient sera is comparable in size with that in normal sera. Elevations of serum KS levels occur in the presence of cartilage degradation, but do not quantitatively define the extent or duration of articular involvement. | 2 |
Progressing cerebral infarction in relation to plasma glucose in gerbils. We studied neurologic morbidity and its evolution during hyperglycemia induced immediately after permanent unilateral common carotid artery ligation in Mongolian gerbils. A total of 60 animals were divided into five groups: one experiencing severe hyperglycemia for 1 hour after the onset of ischemia (brief hyperglycemia group, n = 13), a normoglycemic control group for the brief hyperglycemia group (n = 12), a group with severe hyperglycemia for 4 hours after the onset of ischemia (prolonged hyperglycemia group, n = 11), a normoglycemic control group for the prolonged hyperglycemia group (n = 13), and a hyperosmolar normoglycemic control group for the prolonged hyperglycemia group (n = 11). Neurologic morbidity and mortality were higher in the two hyperglycemic groups than in the three normoglycemic control groups. The neurologic deficit progressed according to the duration of severe hyperglycemia. In the three normoglycemic control groups neurologic status stabilized 120 minutes after the onset of ischemia, in the brief hyperglycemia group stabilization occurred at 210 minutes, and in the prolonged hyperglycemia group neurologic deficit progressed for approximately 360 minutes, coinciding with the death of all but one gerbil, in which the neurologic deficit remained stable until death 23 hours after ischemia. We suggest that hyperglycemia is another cause of progressing cerebral infarction. | 2 |
Stiff-man syndrome. Stiff-man syndrome (Moersch-Woltman syndrome) is a rare disorder of motor function characterized by involuntary stiffness of axial muscles and superimposed painful muscle spasms, which are often induced by startle or emotional stimuli. The standard treatment has been benzodiazepines. An association has been reported between stiff-man syndrome and epilepsy, insulin-dependent diabetes, and a variety of organ-specific autoimmune disorders. Antibodies directed against glutamic acid decarboxylase and against pancreatic islet cells have been detected in the serum and cerebrospinal of patients with stiff-man syndrome. These findings suggest that stiff-man syndrome may be an autoimmune disease. Preliminary reports indicate that patients with stiff-man syndrome have a favorable response to plasma exchange and corticosteroid therapy. | 4 |
Comparison of thallium-201 and technetium-99m hexakis 2-methoxyisobutyl isonitrile single-photon emission computed tomography for estimating the extent of myocardial ischemia and infarction in coronary artery disease. Single-photon emission computed tomography (SPECT) using thallium-201 (Tl-201) was compared with technetium-99m hexakis 2-methoxyisobutyl isonitrile (Tc-99m MIBI) in 24 patients with coronary artery diseaes. Patients exercised to the same work load as each isotope was studied. Normal and hypoperfused left ventricular mass was determined with an automated method. Estimated total left ventricular mass was similar for both stress/redistribution Tl-201 and stress/rest Tc-99m MIBI images. The mean estimated defect size in the redistribution Tl-201 images was 32 +/- 34.7 vs 33 +/- 38.4 g in the resting Tc-99m MIBI studies (difference not significant). The individual determinations of defect mass were highly correlated (r = 0.93; p less than 0.0001). Estimated defect size in the stress Tl-201 images (52 +/- 46.2 g) was significantly larger than the exercise Tc-99m MIBI estimates of defect mass (42 +/- 39.9 g; p less than 0.05). A linear correlation existed between stress thallium and technetium estimates of defect size (r = 0.85) but 15 of 24 Tc-99m MIBI defects were smaller than the Tl-201 defects. Partial redistribution of Tc-99m MIBI could explain the discordance. Stress Tc-99m MIBI SPECT defect size determined by visual interpretation or by the use of isocount analysis may be smaller than what is seen with stress Tl-201 SPECT. | 3 |
Eight and 12 week courses of cyclophosphamide in nephrotic syndrome Seventy-three children with steroid dependent minimal change nephrotic syndrome were randomly allocated to receive treatment with cyclophosphamide (2 mg/kg/day) for either eight or 12 weeks, in combination with prednisolone. All patients had previously relapsed while the dosage was being reduced or within 14 days of discontinuing prednisolone in the six months before receiving cyclophosphamide treatment (steroid dependent), and had severe steroid toxicity. Thirty two patients were treated with cyclophosphamide for eight weeks, and 41 for 12 weeks. There were no differences between the two groups in age at onset of nephrosis or entry into the study, sex ratio, duration of nephrosis, number of relapses before entry, and follow up period after entry. The relapse free rate of patients treated for eight weeks (25%) was similar to that of those treated for 12 weeks (24%) five years after stopping the treatment, and the mean relapse free interval and the sparing effect of cyclophosphamide (if any) on subsequent treatment with steroids did not differ between the groups. We conclude that cyclophosphamide should be used for no longer than eight weeks at a dose of 2 mg/kg/day in children with steroid dependent minimal change nephrotic syndrome. | 4 |
Effect of antileukemia chemotherapy on marrow, blood, and oral granulocyte counts. This study was designed to elicit the effects of antileukemia chemotherapy on marrow production, blood carriage, and oral extravasation of granulocytes, and on the phagocytic activity of those harvested from the mouth. Fifteen adult patients with various morphologic forms of acute leukemia were followed through one to four courses of chemotherapy. Oral saline rinse samples were obtained thrice weekly and prepared for enumeration in a hemocytometer. The oral granulocyte counts were compared with concurrent counts in the bone marrow and peripheral blood. Phagocytic activity of the oral granulocytes was measured by the method of Smith and Rommel. The 15 patients were followed through 30 courses of chemotherapy and recovery. During each, there was a drug-induced decrease in marrow, blood, and oral granulocytes that was reversed when therapy was discontinued and bone marrow activity was restored. Phagocytic activity of the oral granulocytes was not perceptibly affected by the antileukemic drugs. Oral granulocyte counts provide a noninvasive method for monitoring the onset and recovery of chemotherapy-induced myelosuppression and granulocytopenia in patients with leukemia. | 4 |
Treatment planning for internal radionuclide therapy: three-dimensional dosimetry for nonuniformly distributed radionuclides. A calculational approach is described that provides the spatially varying radiation absorbed dose, presented as isodose contours superimposed on CT images, from nonuniform and/or irregular cumulated activity distributions. CT images are read from magnetic tape and are displayed on a high-resolution color graphics display monitor. Source tissue geometries are defined on a series of contiguous CT images automatically (by an edge detection algorithm) or manually (using a trackball), thereby obtaining a three-dimensional representation of the various source volumes of activity. Dose calculations are performed using a radionuclide-specific absorbed dose point kernel in the form of a lookup table. The method described yields the spatially varying dose delivered to tumor and normal tissue volumes from a patient-specific cumulated activity distribution in a clinically implementable manner. This level of accuracy in determining normal tissue and tumor doses may prove valuable in the evaluation and implementation of radionuclides and radiolabeled compounds for therapeutic purposes. | 0 |
Late metastases of cutaneous melanoma: case report and literature review. The development of delayed metastases, although rare, is well documented in patients with invasive cutaneous melanoma. Only 24 cases, including ours, are clearly documented in the literature. We describe a 56-year-old woman who had an acral lentiginous melanoma of the right hand (thickness 1.2 mm). Thirteen years after excision and postoperative irradiation, a subcutaneous metastasis developed in the right arm. One year later the patient died with disseminated bone metastases. This case, as with most of those with delayed metastases, has typical features: female sex; location at a site other than the back, arm, neck, or scalp; and primary tumor thickness between 1.2 and 2.5 mm. | 0 |
Ponderal index as a predictor of postoperative complications. Four hundred sixty-eight patients undergoing elective surgery were prospectively followed for the development of postoperative complications. There was a trend toward increasing complication rate with a lower ponderal index. However, lower ponderal indices were associated with increasing rates of diabetes mellitus and hypertension. Of these patients, forty cases with postoperative complications were matched to 40 control cases for sex, age, concomitant illness and operation performed. The cases of postoperative complications had a statistically significantly lower ponderal index than the controls (11.98 versus 12.43). The increased risk of postoperative complications in those patients with a ponderal index of less than 11 was 3.36, and less than 13 was 3.44. Surgeons who treated patients with lower ponderal indices need to have a high index of suspicion for the development of postoperative complications in these patients. | 4 |
A new method for mapping hepatic subsegment: counterstaining identification technique. Hepatic subsegmentectomy requires identification of the borders of tumor-bearing subsegment, usually achieved by injecting dye into the portal veins feeding the domain. We describe an alternative technique for performing systematic subsegmentectomy in patients with cirrhosis and hepatocellular carcinoma, in whom hepatic arterial and portal venous embolizations were already performed as a preoperative adjuvant. Under ultrasonic guidance, each of the neighboring portal units is sequentially stained, thus defining the avascular subsegment to be resected as the nonstaining area. This allows the subsegment to be totally resected. This counterstaining identification technique can be used for all subsegments undergoing complete embolization and for other situations in which the usual staining method is impossible because of the presence of arterioportal shunting or portal tumor thrombus. | 0 |
Kidney function and cardiovascular risk factors in non-insulin-dependent diabetics (NIDDM) with microalbuminuria. Microalbuminuria in non-insulin-dependent diabetes (NIDDM) is a strong predictor of increased mortality. The major causes of death are cardiovascular, whereas end-stage renal failure is of low frequency. To define kidney function and the presence of some assumed cardiovascular risk factors, we compared a group of 19 microalbuminuric NIDDM patients (M), of mean age (+/- SD) 65 +/- 4 years, and known duration of diabetes 8 +/- 7 years, with 19 randomly selected matched normoalbuminuric patients (N). Seven microalbuminuric patients (P) were also studied. Glomerular filtration rate (GFR) did not differ between N and M, whereas kidney volume was increased in M (260.3 +/- 54.1 ml 1.73 m-2) compared to N (220.4 +/- 44.8 ml 1.73 m-2; P = 0.018). The frequency of cardiac disease increased with increasing albuminuria. Glycaemic control did not differ between the groups, but fasting plasma C-peptide levels increased from 2.8 +/- 1.1 micrograms l-1 in N, to 3.7 +/- 1.7 micrograms l-1 in M (P = 0.08), and to 4.2 +/- 1.9 micrograms l-1 (P = 0.03) in P. The lipoprotein profile showed no significant differences, although the LDLcholesterol/HDLcholesterol (LDL-C/HDL-C) ratio tended to rise. A significant correlation was found between C-peptide and LDL-C/HDL-C (r = 0.5; P less than 10(-3]. In conclusion, GFR was not increased, and did not differ between N and M, whereas kidney volume was enhanced in M. Several assumed cardiovascular risk factors showed values of M intermediate between those of N and P. | 3 |
Malignant glandular triton tumor. A case of left brachial plexus-related malignant peripheral nerve sheath tumor showing neoplastic, glandular, and rhabdomyoblastic elements in a 39-year-old Chinese man is reported. The authors suggested that this tumor be termed a malignant glandular triton tumor in view of the presence of the adenocarcinomatous component. The patient had extensive local recurrence comprising mainly the Schwann spindle cells within a year after complete piecemeal removal and died 15 months later after the initial presentation. The natural behavior of this tumor, as in other reported cases of malignant triton tumor, is extremely aggressive, unlike malignant schwannoma or glandular malignant schwannoma. The histogenesis of this tumor is likely to be from primitive neural crest cells, Schwann's cell precursors, or metaplastic malignant Schwann's cells. | 0 |
Pressure threshold for shock wave induced renal hemorrhage. Studies were performed with an interest in determining a pressure threshold for extracorporeal shock wave induced renal damage. Histological evidence of intraparenchymal hemorrhage was used as an indicator of tissue trauma. Depilated C3H mice were anesthetized and placed on a special frame to enhance visualization and treatment of the kidneys in situ. A Wolf electrohydraulic generator and 9 French probe designed for endoscopic use were utilized to expose the kidneys to 10 double spherically divergent shock waves. Measurements of the shock waves revealed two positive pressure peaks of similar magnitude for each spark discharge. The kidneys were exposed to different peak pressures by choice of distance from the spark source and were removed immediately after treatment for histologic processing. A dose response was noted with severe corticomedullary damage apparent following 15 to 20 MPa shocks. Hemorrhage was more apparent in the medulla where evidence of damage could be seen following pressures as low as three to five MPa. When a latex membrane was interposed to prevent possible collapse of the initial bubble from the spark source against the skin surface, histological evaluation revealed substantial reduction of severe tissue damage associated with the highest pressures tested, 20 MPa. However, the threshold level for evidence of hemorrhage remained about three to five MPa. Hydrophonic measurements indicated that the membrane allowed transmission of the acoustic shock waves and suggested that collapse of the bubble generated by electrohydraulic probes may have local effects due to a cavitation-like mechanism. | 4 |
Oral dissolution therapy for cholelithiasis: mix and match. The authors conducted a prospective, randomized trial of chenodeoxycholic and ursodeoxycholic acid versus ursodeoxycholic acid alone in patients with cholelithiasis to determine their efficacy for dissolution of gallstones. One hundred and twenty patients with radiolucent gallstones, less than or equal to 15 mm and who had a functioning gallbladder were enrolled. The patients were divided into two groups based on the diameter of their largest stones. Seventy patients had stones larger than 5 mm but less than 15 mm, whereas 50 patients had stones that measured 5 mm or less. The patients were randomly assigned to treatment with chenodeoxycholic acid plus ursodeoxycholic acid (5 mm/kg of each) or ursodeoxycholic acid (10 mm/kg) alone. Oral cholecystography, plain abdominal x-rays, and ultrasonography of the gallbladder were done at 6, 12, and 24 months. Dissolution was deemed to be complete if not stones were visualized on two examinations. partial dissolution was defined as a 50% reduction in stone size and/or number. Stones that were not detected by cholecystography but still detected during ultrasonography were considered to be partially dissolved. Plasma triglycerides, serum cholesterol, HDL, and serologic liver function tests were determined at 1, 3, 6, 12, 18, and 24 months. In a select group of patients, bile-rich duodenal aspirates were aspirated and analyzed for biliary lipid contents. In the group with small stones, defined as less than or equal to 5 mm, complete stone dissolution occurred significantly more often utilizing combination therapy at 6 months (52% vs 24%), and this trend persisted, although no longer significant, at 12 and 24 months. Combination therapy also achieved an improved rate of dissolution for large stones within 6 months; however, this did not persist at 12 and 24 months. Although not statistically significant, stone calcification occurred less often with combined therapy. All treatment regimens were well tolerated, with only minor changes in bowel habits and mild elevations in serum transaminase levels. Serum lipid levels did not change with either therapy. The authors concluded that the combination of chenodeoxycholic acid and ursodeoxycholic acid was the preferred therapy for gallstone dissolution, because it dissolves stones more rapidly, with a lower incidence of stone calcifications, and thus might reduce the long-term cost of treatment. | 1 |
Cerebrospinal fluid neopterin in human immunodeficiency virus type 1 infection. We evaluated cerebrospinal fluid (CSF) concentrations of neopterin, a putative marker of activated macrophages, in 97 subjects infected with human immunodeficiency virus type 1 who had a spectrum of neurological complications. The highest CSF neopterin concentrations occurred in those with neurological opportunistic infections, primary central nervous systems lymphoma, and acquired immunodeficiency syndrome (AIDS) dementia complex. In general, the CSF concentration of neopterin was independent of CSF cell count and blood-brain barrier disruption to albumin. In the patients with AIDS dementia complex, CSF neopterin concentrations correlated with severity of disease and decreased in conjunction with clinical improvement following treatment with zidovudine. These results suggest that CSF neopterin, although not disease-specific, may be useful as a surrogate marker for the presence of AIDS dementia complex and its response to antiviral therapy. | 0 |
Interferon activation of latent natural killer cells and alteration in kinetics of target cell lysis: clinical implications for oral precancerous lesions. Reduced natural killer cell activity was observed in patients with oral leukoplakia and submucous fibrosis compared with normal control subjects. However, the number of target binding lymphocytes was found to be normal in these precancers. Treatment of effector cells with interferon-alpha resulted in highly elevated active killer cell activity, although no change was observed in target binding lymphocyte counts. This finding could imply that precytotoxic cells that are activated by interferon exist in peripheral blood or that direct recruitment of a new cell population takes place. In addition, altered target lysis kinetics was observed, with interferon-activated killer cells demonstrating a tremendous lytic activation that is completed so quickly that a statistical kinetic analysis could not be accurately done. Because natural killer cell activity is an important effector system in immunosurveillance against tumors, its modulation with interferon may be an exciting clinical possibility in the control of malignant transformation or oral precancers. | 0 |
Incidental demonstration of pericardial fistula during hepatobiliary scintigraphy. Biliary vomiting developed 16 mo after resection of adenocarcinoma of the esophagus in a patient with a complex postoperative course. A biliary scan revealed an outline of the pericardium, suggesting a fistula. The potential role of radionuclide imaging in this rare and potentially fatal complication is discussed. | 4 |
Neonatal monosodium glutamate abolishes corticotropin-releasing factor-induced epileptogenic activity in rats. Intracerebroventricular (i.c.v.) injection of rat corticotropin-releasing factor (rCRF) at doses of 5-20 micrograms in rats induces epileptogenic activity characterized by pacemaker-like spikes localized in the hippocampal leads. Such an effect was still present in rats neonatally treated with saline but was absent in those neonatally treated with monosodium glutamate (MSG), a treatment that caused marked changes in the concentration of several brain neurotransmitters and neuropeptides in hypothalamic nuclei where CRF is highly concentrated and is believed to induce endocrinologic and behavioral effects. The present results suggest the rCRF-induced spiking activity is mediated by activation of neuronal pathways sensitive to MSG neurotoxic effect. | 2 |
Spontaneous splenic rupture following infectious mononucleosis. Four cases of spontaneous splenic rupture after infectious mononucleosis (IM) have been treated at this institution since 1978. The condition is rare, occurring in 0.1-0.5 per cent of patients with proven infectious mononucleosis. Splenectomy is considered the treatment of choice for these patients. However, because recent trends in the management of traumatic splenic rupture are moving towards nonoperative treatment with selected patients, a similar approach has been considered for the patient with spontaneous splenic rupture following IM. The major reason for avoiding splenectomy is the increased incidence of sepsis in splenectomized patients. Yet, splenic rupture is accompanied by hemorrhage and the risks associated with blood transfusion for ongoing hemorrhage are of similar magnitude as those of sepsis following splenectomy. In addition, the grossly abnormal spleens seen at operation tend to include large, contained hematomas that may also be prone to rupture. Therefore, operative management still appears to be the preferred treatment for spontaneous splenic rupture following IM. Splenectomy is curative, safe, and obviates the need for transfusion, extended hospitalization, and activity restriction. | 4 |
High hemoglobin A2 beta 0-thalassemia due to a 532-basepair deletion of the 5' beta-globin gene region. We identify and characterize a novel beta 0-thalassemia mutation that is associated with an unusually high level of hemoglobin (Hb) A2 in the heterozygote. This newly discovered mutation is caused by a 532-basepair deletion that extends from positions -454 to + 78 relative to the mRNA cap site of the beta-globin gene. The propositi are 9-month-old fraternal twins. One of the twins is a compound heterozygote for the deletion and Hb S, the other is a compound heterozygote for the deletion and Hb C. | 4 |
Characterization of LY233569 on 5-lipoxygenase and reperfusion injury of ischemic myocardium. LY233569 produced concentration-dependent inhibition of isolated guinea pig 5-lipoxygenase (5-LPO) and 5-LPO activity of human polymorphonuclear leukocytes in vitro; IC50 values were 0.4 and 0.1 microM, respectively. LY233569 also inhibited (IC50 approximately 1.8 microM) zymosan-stimulated production of leukotriene B4 in canine whole blood but had little or no concomitant effect on the production of thromboxane B2. Concentrations of LY233569 as high as 10 microM did not inhibit production or scavenge superoxide from activated human neutrophils. In normal anesthetized dogs, infusion of LY233569 (0.11 mg/kg/min, i.v.) for 6 hr produced persistent inhibition (approximately 80%) of leukotriene B4 production in blood challenged ex vivo with zymosan; the plasma concentration (approximately 4 microM) of LY233569 was consistent with in vitro data illustrating selective and maximal inhibition of 5-LPO. In subsequent experiments, myocardial infarct size was measured after 1 hr of occlusion of the circumflex coronary artery and 5 hr of reperfusion. Continuous infusion of LY233569 (0.11 mg/kg/min, i.v.) had little or no effect on base-line systolic arterial pressure, cardiac rate and the pressure rate product when compared with time-related changes observed in control dogs. LY233569 infusion also did not alter the degree of ST-segment deviation or the intensity and duration of cardiac arrhythmias associated with coronary artery occlusion and reperfusion. Resultant myocardial infarct sizes were 45 +/- 5% of the left ventricle placed at risk in control dogs and 43 +/- 4% in dogs given LY233569. Myeloperoxidase activity of infarcted myocardium did not differ between groups. | 3 |
The combination of prednisone and colchicine in patients with primary sclerosing cholangitis. Primary sclerosing cholangitis is a cholestatic liver disease characterized by inflammation and fibrosis of the biliary tract. The cause of the disease is unknown, and no effective medical treatment exists. In this study, 12 patients received a combination of low-dose prednisone (10 mg/day) and colchicine (0.6 mg bid). Their course was compared with that of a group of concurrent historical controls. At 6 and 12 months, there was significantly more improvement in liver test results over baseline values in patients receiving prednisone and colchicine than in the untreated controls. At 24 months, however, no significant differences in biochemical tests were appreciated between treated and untreated patients. Analysis of serial liver biopsies showed no differences in histologic change in the two groups. During the 2 yr of follow-up, there were two deaths in the control group but none in the treated group. Four untreated patients developed ascites; gastrointestinal bleeding developed in three untreated patients, one of whom developed ascites. In contrast, in the treated group, ascites and bleeding developed in only one patient. We conclude that the combination of colchicine and prednisone does not retard histologic progression or progression of standard liver tests after 2 yr of therapy. There is a trend toward less clinical deterioration and improved survival after 2 yr of treatment. On the basis of these findings, we would not advocate empiric use of these drugs for patients with primary sclerosing cholangitis, but suggest that, if they are to be used at all in PSC, they be evaluated in a controlled clinical trial as treatment for this as yet incurable disease. | 1 |
A three-dimensional system for long-term culture of human colorectal adenomas. Studies of the adenoma-carcinoma sequence in the colon and rectum have been limited by the paucity of experimental models of adenoma growth and progression. Progress recently was reported in the development of monolayer culture systems. The principal objective of this study was to develop a primary culture system for colorectal adenomas that would simulate three-dimensional in vivo growth. We used a calcium alginate encapsulation technique that was previously described for established tumor cell lines. Briefly, fresh resected specimens were washed, minced into small multicellular particles called microadenomas, and encapsulated in 1% calcium alginate pellets. The pellets were maintained in minimum essential medium containing 10% fetal bovine serum at 37 degrees C in humidified atmosphere of 95% air, 5% CO2. Ten of eleven adenomas, including six tubular, three tubulovillous, and one villous have been successfully cultured for 34 to 162 days. Cell viability was confirmed histologically by light and electron microscopy. The cells were characterized as epithelial by morphologic features and ultrastructural studies, which showed a high degree of cellular differentiation, including villous brush borders and many desmosomes. Both tubular and villuslike structures have been observed in vitro, correlating in some cases with the histology of the parent adenoma. Measurements of proliferative activity by [3H]thymidine autoradiography or immunohistochemical staining with the monoclonal antibody Ki-67 demonstrated growth fractions of 9% to 25%. A simple, highly efficient primary culture system was developed for the long-term maintenance of adenomas that promotes three-dimensional growth patterns and growth rates analogous to those seen in vivo. This model provides an opportunity to develop an experimental system for longitudinal studies of pathologic and molecular parameters in adenoma progression to carcinoma. | 0 |
Diagnostic utility of lower extremity radiographs of young children with gait disturbance. The diagnostic utility of lower extremity radiographs was evaluated using 84 outpatients 1 to 5 years of age with gait disturbance whose lower extremities appeared physically normal. Chief complaints included limp (65 children [77%]), refusal to walk or stand (37 children [44%]), and frequent falling (6 children [7%]). A total of 43 children (51%) had more than one complaint. The mean age of patients was 26 months and the median duration of symptoms was 1 day. Trauma was reported in 43 (51%) cases and fever in 14 (17%). Results of radiographical studies appeared normal in 81 children (96%), demonstrated soft tissue swelling in 2 children, and revealed a bony island in 1 child. In 1 patient admitted to the hospital for failure to thrive and irritability, and whose radiographic results appeared normal, findings consistent with osteomyelitis later developed. Of the remaining children, 68 (81%) were available for follow-up observation 4 to 28 months after the initial visit and all reported spontaneous resolution of the initial complaint. It was concluded that in a well-appearing child with an otherwise normal physical examination results, an acute gait disturbance is likely to be a self-limiting condition and radiographs are unlikely to contribute to the diagnosis. | 2 |
Tethered cord syndrome from a choristoma of mullerian origin. Case report. The authors report a case of tethered cord syndrome due to a choristoma of mullerian origin located in the spinal cord at the lumbosacral junction. Two similar cases were found upon review of the literature. The embryology of this lesion is discussed. | 0 |
The internist in the management of head and neck cancer. The general internist has an important role in the management of head and neck squamous cell cancers. This heterogeneous group of cancers must be accurately diagnosed and staged before planning treatment. Curability is directly related to stage at presentation and, because most patients with such cancers present to internists first, these physicians must be familiar with presenting symptoms and must be suspicious enough to refer patients with symptoms for appropriate evaluation. The work-up of patients with suspected unknown primary cancer presenting as adenopathy is detailed, and the physician is cautioned not to immediately proceed to open biopsy. As many as 10% of such primary cancers remain undetected, although, with proper therapy, the 5-year survival rate for squamous cell cancer of the head and neck is 60%. Those patients cured of head and neck cancer still face significant psychosocial and medical problems, including hypothyroidism, xerostomia, and a 20% rate of second primary cancer. Head and neck cancer is highly preventable; 75% of cases are related to tobacco and alcohol use. Smokeless tobacco has gained popularity among young Americans and is associated with an increased incidence of head and neck cancer at several sites. Education is crucial, and internists must seek strategies to stop patients from using tobacco products. Other etiologic factors include industrial carcinogens, Epstein-Barr virus, and diet. Retrospective serologic and dietary recall studies of vitamin A suggest an etiologic role of diet; vitamin A analogs have been tested in preneoplastic lesions. To reduce mortality from head and neck cancers, the general internist must play a central role in prevention and early detection. | 0 |
Nerve growth factor binding domain of the nerve growth factor receptor. A structural analysis of the rat low-affinity nerve growth factor (NGF) receptor was undertaken to define the NGF binding domain. Mutant NGF receptor DNA constructs were expressed in mouse fibroblasts or COS cells, and the ability of the mutant receptor to bind NGF was assayed. In the first mutant, all but 16 amino acid residues of the intracellular domain of the receptor were removed. This receptor bound NGF with a Kd comparable to that of the wild-type receptor. A second mutant contained only the four cysteine-rich sequences from the extracellular portion of the protein. This mutant was expressed in COS cells and the resultant protein was a secreted soluble form of the receptor that was able to bind NGF. Two N-terminal deletions, in which either the first cysteine-rich sequence of the first and part of the second cysteine-rich sequences were removed, bound NGF. However, a mutant lacking all four cysteine-rich sequences was unable to bind NGF. These results show that the four cysteine-rich sequences of the NGF receptor contain the NGF binding domain. | 4 |
The role of the physician in the late diagnosis of primary malignant tumors of the small intestine. Survival from primary malignancies of the small intestine has not improved during the last four decades. One reason for this is the advanced stage of disease at the time of surgery. In order to determine why diagnosis is made late, we reviewed the records of all patients with small bowel malignancy diagnosed between 1967 and 1988. The time from the onset of symptoms to the first medical contact and the time from medical contact until diagnosis were evaluated in 77 patients. The average delay in diagnosis attributable 1) to the patient failing to report symptoms was less than 2 months, 2) to the physician not ordering the appropriate diagnostic test was 8.2 months, and 3) to the radiologist failing to make the diagnosis was 12 months. Thus, the major delay in diagnosis was after medical help was sought and not from the onset of symptoms to first medical consultation. Physicians must increase their sensitivity to the subtle but persistent symptoms that necessitate a small bowel evaluation. | 0 |
Morphological changes in unmyelinated nerve fibres in the sural nerve with age. Quantitative changes in unmyelinated nerve fibres in sural nerves obtained at autopsy were evaluated in 28 normal adults. The following conclusions were reached. (1) The density of unmyelinated axons showed no significant correlation with age, but the densities of (2) Schwann cell subunits with axons, (3) Schwann cell subunits without axons, (4) single protrusions of Schwann cells and (5) collagen pockets, and (6) the mean number of Schwann cell profiles per axon, all showed positive correlations with age. Additionally, (7) the percentage of subunits containing unmyelinated axons and (8) the mean number of axons in single axon-containing Schwann cell subunits demonstrated negative correlations with age. The density of Schwann cell nuclei related to unmyelinated fibres did not show a significant change with age. The age-dependent changes in unmyelinated nerve fibres thus mainly consist of an increased production of processes by Schwann cells in the absence of cell multiplication. A decrease in unmyelinated nerve fibre density or a compensatory increase of small unmyelinated axons did not occur in these normal adults. In terms of relative sensitivity for the detection of the earliest changes in unmyelinated fibres, the indices (6) and (7) are considered to be useful and superior to the conventional assessment of unmyelinated axon density and diameter distribution. These two indices are not influenced by postmortem swelling of the axons and Schwann cells. Measurements of unmyelinated axon density and size distribution will continue to be useful in the assessment of more advanced pathological conditions. | 4 |
Interleukin-6 mRNA and protein increase in vivo following induction of acute thrombocytopenia in mice. Induction of experimental thrombocytopenia in rodents results in the enhancement of megakaryocytic growth and differentiation. Interleukin-3 (IL-3) and IL-6, cytokines with a broad spectrum of biologic activities, stimulate megakaryocytopoiesis in vitro. To determine if expression of these factors might increase in response to experimental thrombocytopenia, we measured steady-state levels of IL-3 and IL-6 mRNA following rabbit antiplatelet serum (APS) injection. Groups of mice were injected intravenously with 0.2 mL APS while control animals received rabbit antilymphocyte serum (ALS), normal rabbit serum (NRS), or phosphate-buffered saline (PBS). At various times up to 72 hours after injection mice were exsanguinated and splenectomized. Platelet counts in the experimental animals were less than 12% of controls. Splenic RNA was hybridized in solution to 32P-UTP-labeled cRNA probes for IL-3 and IL-6. RNase-resistant hybrids were resolved on denaturing gels and visualized autoradiographically. IL-3 hybrids were undetectable at all time points tested, irrespective of the film exposure time or specific activity of the probe. Conversely, IL-6 hybrids were easily visualized and showed peak expression at 1.5 to 2.0 hours. By 3 hours, IL-6 mRNA had returned almost to the level of the controls. Similar results were observed in the bone marrow, although maximal IL-6 mRNA in that tissue was observed 4 hours following APS administration. To determine if this mRNA increment was associated with a concomitant increase in bioactive protein, serum was tested for its ability to stimulate IL-6-dependent B9 cells. At 1.75 hours following injection, experimental animals showed a small but significant increment in IL-6 activity compared with controls (200 +/- 30 U/mL IL-6 compared with 129 +/- 17 U/mL in ALS-injected controls, 106 +/- 17 U/mL in NRS-injected controls and 84 +/- 17 U/mL in PBS-injected controls). The data show that IL-6 mRNA and bioactive protein increase in response to acute immunothrombocytopenia, while no increment in IL-3 is detectable. These results suggest that IL-6 may play a role in the physiologic response to acute immunothrombocytopenia. | 4 |
Spatial dispersion of magnetic stimulation in peripheral nerves. To assess the longitudinal dispersion of the stimulus induced by the magnetic coil, collision experiments were performed in seven normal ulnar nerves. A supramaximal electrical stimulus S1 was delivered at the wrist, and followed by a supramaximal stimulus S2 in the upper arm, which was either electrical (electrical collision studies), or magnetic (magnetic collision studies). The interstimulus interval was varied by 0.2 msec increments from the time of complete cancellation of the S2 evoked motor response onwards, to include the entire span of recovery of that compound motor action potential. Collision curves were obtained for both magnetic and electrical stimuli by plotting the amplitude of the motor response elicited by S2 as a function of the interstimulus interval. In all seven normal ulnar nerves, comparison of the collision curves showed that the S2 evoked motor response is restored significantly more slowly when magnetic stimulation is used. This finding is best explained by longitudinal dispersion of the stimulus induced by the magnetic coil relative to conventional electrical stimulation, the large fibers being stimulated further away from the coil than the small ones. This interpretation is confirmed by the findings obtained with the same method in two cases of ulnar neuropathy, and by comparison of different intensities of magnetic stimulation. | 2 |
Distinguishing malignant mesothelioma from pulmonary adenocarcinoma: an immuno-histochemical approach using a panel of monoclonal antibodies. A panel of six monoclonal antibodies (MAbs) was employed to evaluate antigen expression in pulmonary adenocarcinomas and mesotheliomas. Monoclonal anti-human milk fat globulin (HMFG-2), anti-carcinoembryonic antigen (NP-2), anti-epithelial membrane antigen (EMA), anti-cytokeratin (PKK-1), anti-tumor-associated antigen 72 (B72.3), and anti-human myelomonocytic antigen (Leu M-1) antibodies were used to localize their respective antigens in formalin-fixed, paraffin-embedded tumors by using the avidin-biotin-complex immunoperoxidase technique. In all, 28 mesotheliomas obtained from Ohio State University Anatomic Pathology files and from a Southwest Oncology Group (SWOG) protocol were compared to 22 pulmonary adenocarcinomas by using this MAb panel. None of the mesotheliomas demonstrated positive staining with MAbs NP-2 (anti-CEA) or Leu M-1. However, 95% (21/22) of adenocarcinomas stained with one of these two antibodies. Although neither of these two MAbs stained all adenocarcinomas, each antibody demonstrated positive immunostaining in more than 90% of the adenocarcinomas studied. Therefore, MABs NP-2 and Leu M-1 are, individually, quite useful for distinguishing mesothelioma from adenocarcinoma. However, in our study, no single MAb could be used to distinguish these two tumor types in every case. MAb B72.3 stained 91% (20/21) adenocarcinomas but also stained 7% (2/28) of mesotheliomas. MAb HMFG-2 reacted positively with 95% of adenocarcinomas, but also stained 39% of the mesotheliomas, usually in a membranous pattern. MAbs EMA and PKK-1 were not found useful in distinguishing mesothelioma from adenocarcinoma. We conclude that MAbs Leu M-1 and NP-2 were both useful in distinguishing mesothelioma from pulmonary adenocarcinoma in that positive staining was demonstrated in adenocarcinomas and not mesotheliomas. | 0 |
A computerized laboratory alerting system. A computerized laboratory alerting system (CLAS) has been developed as part of an ongoing effort to improve the quality of care at LDS Hospital. The system identifies potentially life-threatening conditions on the basis of laboratory findings and then generates appropriate warnings and transmits them to clinicians. Use of the system has led to a significant increase in the proportion of patients in life-threatening situations who have received appropriate care (50.8% before implementation vs. 62.5% afterward, P less than 0.05). Among patients with hypokalemia, falling potassium levels, hyperkalemia, hypokalemia during treatment with digoxin, hyponatremia, falling sodium levels, hypernatremia, hypoglycemia, or hyperglycemia, the average length of time spent in the life-threatening situation has decreased from 30.4 to 15.7 hours (P less than 0.05) and the average length of stay has decreased from 14.6 to 8.8 days (P less than 0.05). There has been little change in the proportion of patients with findings indicating metabolic acidosis who have received appropriate care (32.3 vs. 34.6%). We conclude that CLAS has an important role in patient care at our hospital. | 4 |
Embolization with particles in thoracic intramedullary arteriovenous malformations: long-term angiographic and clinical results. To evaluate the long-term results of endovascular treatment with particles in the management of thoracic intramedullary arteriovenous malformations (AVMs), the authors retrospectively reviewed the angiographic and clinical findings in 35 patients. Follow-up was 1-15 years (mean, 6 years) in 28 patients and 6-10 months (mean, 7 months) in seven. A total of 158 embolization procedures were performed in 35 patients. Revascularization occurred frequently, necessitating multiple endovascular sessions. Long-term clinical evaluation showed clinical improvement, compared with the initial status before treatment, in 63% of the patients. Clinical aggravation due to embolization was observed in seven patients (20%) after 12 of the 158 endovascular sessions (8%). These results are better than those reported after surgery and indicate that embolization with particles is an efficient and safe tool in the treatment of thoracic intramedullary AVMs. | 3 |
Left ventricular pseudoaneurysm complicating mitral valve replacement in a 4-year-old child with acute bacterial endocarditis. A 4-year-old child with acute bacterial endocarditis required mitral valve replacement. A left ventricular pseudoaneurysm developed following surgery. The etiology and diagnosis of this complication are discussed. | 3 |
Enhanced alpha 1-adrenergic responsiveness in cardiomyopathic hamster cardiac myocytes. Relation to the expression of pertussis toxin-sensitive G protein and alpha 1-adrenergic receptors. The pathogenesis of the myopathy occurring in the heart of the cardiomyopathic strain of the Syrian hamster is not well understood but is believed to be associated with abnormal calcium handling by myopathic cells. The purpose of this study was to determine whether the cardiomyopathy occurring in strain BIO 14.6 animals is associated with an enhanced alpha 1-adrenergic receptor-mediated rise in cytosolic calcium, whether a pertussis toxin-sensitive G protein is involved in coupling the alpha 1-adrenergic receptor to changes in intracellular calcium and whether enhanced alpha 1 responsiveness is associated with an increase in the level of expression of the alpha 1-adrenergic receptor or in the pertussis toxin-sensitive G protein or proteins. To test the hypothesis that the cardiomyopathic state is associated with a greater alpha 1-receptor-mediated rise in cytosolic calcium, we studied the effect of phenylephrine (in the presence of propranolol) on time-averaged cytosolic calcium concentration ([Ca2+]i) in isolated cardiac myocytes from cardiomyopathic and age-matched control hamsters. Phenylephrine caused a greater increase both in time-averaged [Ca2+]i (an increase of 48 +/- 8% versus 12 +/- 3%, p less than 0.01) and in contractility (+181 +/- 22% versus +35 +/- 9%, p less than 0.01) in cardiomyopathic than in normal cardiac myocytes. Exposure to pertussis toxin (200 ng/ml for 3 hours) attenuated the alpha 1-adrenergic receptor-mediated increase in contractility and time-averaged [Ca2+]i in both cardiomyopathic and normal cells. The level of pertussis toxin-sensitive G protein, as determined by pertussis toxin-mediated [32P]ADP-ribosylation, was 1.6-fold higher in cardiomyopathic versus normal hamster hearts. The density of alpha 1-adrenergic receptors, as measured by the antagonist radioligand [3H]prazosin and the affinity of the receptor for agonist and antagonist were similar in myopathic and normal heart membranes. Thus, in cardiac myocytes from hamsters, the alpha 1-adrenergic receptor-mediated effects on [Ca2+]i and contractility appear to be mediated by a pertussis toxin-sensitive G protein or proteins. In myocytes from cardiomyopathic hamsters, these alpha 1-adrenergic effects were increased in magnitude, as was the level of pertussis toxin-sensitive G protein, but there was no measurable alteration in the density or ligand binding properties of alpha 1-adrenergic receptors. | 3 |
Chronic pain. Understanding of the etiology of chronic pain is growing rapidly as researchers seek to integrate physiologic and psychosocial mechanisms. When nurses assess clients with chronic pain, they should make their assessments using both verbal and nonverbal methods and realize that no one instrument is comprehensive enough to be used alone. The key to successful treatment of these difficult clients lies in the use of a comprehensive approach that takes the client seriously and integrates both physiologic and psychosocial approaches. | 4 |
Long-term results of submandibular duct transposition for drooling. This study examines the long-term results and morbidity of submandibular duct transposition in drooling children. Twenty-two patients, aged 3 to 18 years, with neurological dysfunction and excessive drooling underwent submandibular duct transposition between 1984 and 1987. In January 1990, 20 patients were reviewed. Their degree of drooling pre-operatively, immediately post-operatively and currently was assessed. The rate of improvement and the occurrence of complications were noted. Drooling was 'much better' in the early post-operative period in 17 of the 20 patients, and this improvement was invariably noted within three weeks. In the three other patients drooling was 'better'. Deterioration occurred in only three patients over the entire follow-up period. Complications all occurred in the first 18 months following surgery; they consisted of salivary retention cysts in four and transient submandibular gland swelling in a fifth patient. | 4 |
Mucin production by human colonic carcinoma cells correlates with their metastatic potential in animal models of colon cancer metastasis. Patients with mucinous colorectal cancers characteristically present with advanced disease, however, the relationship between mucin production by colon cancer cells and their metastatic potential remains unclear. We therefore sought to define the relationship between mucin production by human colon cancer cells and metastatic ability by employing animal models of colon cancer metastasis. LS LiM 6, a colon carcinoma cell line with high liver metastasizing ability during cecal growth in nude mice produced twofold more metabolically labeled intracellular mucin and secreted four- to fivefold more mucin into the culture medium compared to poorly metastatic parental line LS174T. This was accompanied by a similar elevation in poly(A)+ RNA detected by blot hybridization with a human intestinal mucin cDNA probe, and increases in mucin core carbohydrate antigens determined immunohistochemically. Variants of LS174T selected for high (HM 7) or low (LM 12) mucin synthesizing capacity also yielded metastases after cecal growth and colonized the liver after splenic-portal injection in proportion to their ability to produce mucin. Inhibition of mucin glycosylation by the arylglycoside benzyl-alpha-N-acetyl-galactosamine greatly reduced liver colonization after splenic-portal injection of the tumor cells. These data suggest that mucin production by human colon cancer cells correlates with their metastatic potential and affects their ability to colonize the liver in experimental model systems. | 0 |
The natural history of lumbar intervertebral disc extrusions treated nonoperatively. The purpose of this study was to evaluate the natural history of morphologic changes within the lumbar spine in patients who sustained lumbar disc extrusions. All patients in this study were treated nonoperatively for radicular pain and neurologic loss. The following questions were addressed: 1) Does perithecal or perineural fibrosis result when extrusions are not removed surgically, and 2) Do disc extrusions spontaneously resolve, and, if so, how rapidly? The study population consisted of 11 patients with extrusions and radiculopathy. All patients were successfully treated nonoperatively. All had a primary complaint of leg pain and all had positive straight leg raising reproducing their leg pain at less than or equal to 60 degrees. Additionally, 87% had muscle weakness on a neurologic basis in a root level distribution corresponding to the site of disc pathology. Computed tomographic (CT) examinations were obtained on all patients at the inception of treatment. These studies were compared with follow-up MRI studies. The initial CT scans were evaluated for the following criteria: disc size and position, thecal sac effacement, nerve root enlargement or displacement, and evidence of central or intervertebral canal stenosis. In addition to the pathomorphology evaluated on the CT scans, follow-up MRI studies also evaluated disc hydration at the herniated and contiguous levels, and the presence of perithecal or perineural fibrosis. The following grading system was used to evaluate change in fragment size on the follow-up studies: Grade 1-0 to 50% decrease in size; Grade 2-50 to 75% decrease in size; Grade 3-75 to 100% decrease in size. | 4 |
The chest radiograph appearances seen following high dose chemotherapy and autologous bone marrow transplantation for resistant malignant lymphoma. The objective of this study was to review and analyse the chest radiograph (CXR) appearances seen following high dose chemotherapy and autologous bone marrow transplantation (ABMT), and to identify any characteristic patterns. Thirty-one patients underwent ABMT between 1984 and 1989 for high grade lymphoma resistant to conventional chemotherapy. Their case notes and CXRs were reviewed in conjunction with the clinicians. In this small sample of patients, an acute interstitial pattern was seen with pulmonary oedema following bone marrow reinfusion in two cases of the 13 patients showing CXR changes (15%). Otherwise, the CXR changes following ABMT were not specific, although they did alert the clinician to the possibilities of recurrent lymphoma or opportunistic infection, enabling appropriate investigations and treatment to be instituted at an early stage. The complications and CXR changes did not differ greatly from those seen following allogeneic bone marrow transplantation. | 4 |
Toxicity of high-dose cytosine arabinoside in the treatment of advanced childhood tumors resistant to conventional therapy. A Pediatric Oncology Group study. Experience with high-dose cytosine arabinoside (HDAC) in pediatric solid tumors is limited. Sixteen children with solid tumors resistant to conventional therapies were registered in a pilot Pediatric Oncology Group (POG) study that required the administration of HDAC at 3 g/m2 every 12 hours for four doses. There were four cases of rhabdomyosarcoma, two cases of fibrosarcoma, four cases of neuroblastoma, and one case each of germ cell tumor, Wilm's tumor, retinoblastoma, hepatocellular carcinoma, Ewing's sarcoma, and Burkitt's lymphoma. All eligible patients had advanced diseases and had previously received extensive chemotherapy. Thirteen patients received one course of HDAC and three patients received two courses of HDAC. Due to prior treatments, patients had less than normal marrow reserves. Short-term toxicity included nausea, vomiting, suppression of hemopoiesis, drug fever, and increased blood urea nitrogen (BUN), creatinine, and liver enzymes. All evaluable patients recovered from their toxicities. There were no drug-related deaths. None of the patients had neurologic problems, including the only patient with prior irradiation to the skull. With the above schedule, HDAC appears to have manageable toxicity. | 0 |
Influences of angiotensin on renal function in renal vascular hypertension. The scope and the magnitude of the roles which angiotensin plays in the generation and maintenance of elevated blood pressure in models of renal vascular hypertension are continuing to expand. It is now clear that specific angiotensin dependent mechanisms contribute importantly to the pathophysiology of hypertension and altered renal function in models of two-kidney, one clip hypertension in rats. The generation of angiotensin in the local intrarenal environment of the kidney is a new and potentially important mechanism contributing to altered renal function in these models. Application of antagonists of the renin-angiotensin system to rat models of renal vascular hypertension indicate that the effects of angiotensin attenuate renal hemodynamic and excretory behavior, particularly in the nonclipped kidney. Further, angiotensin may attenuate the efficiency of autoregulation of renal hemodynamics in the nonclipped kidney. Evidence that inhibition of angiotensin reverses or improves these altered hemodynamic and excretory functions indicate that angiotensin may contribute importantly to the pathophysiology of hypertension in these models by altering or impairing the ability of the nonclipped or normal kidney to excrete sodium and volume. | 3 |
Ventilatory effect of acute pulmonary hypothermia. The isolated effect of cooling the pulmonary circulation on ventilation was quantified in nine anesthetized dogs. The right pulmonary artery (RPA) was cannulated within the pericardium, and systemic blood was pumped from the left atrium to the RPA between, but not during, periods of cooling. Cooled blood boluses were injected into the RPA under conditions in which either bolus temperature (5-35 degrees C) or volume (0-1.5 ml/kg body wt) varied. Inspiratory time (TI), expiratory time (TE), breath duration (TT), and peak integrated activity (PEAK) were determined from diaphragm EMG. Results for five postinjection breaths were converted to a percent of the values from five preinjection breaths. There was a linear relationship between bolus temperature and TI [r = 0.61, slope (x) = 0.59%/degrees C, P less than 0.001), TE (r = 0.73, x = 1.43%/degrees C, P less than 0.001] as well as TT (r = 0.74, x = 1.10%/degrees C, P less than 0.001), whereas PEAK was unaffected (n = 9). When injection temperature was 5 degrees C, an inverse linear relationship existed between bolus volume and TI (r = 0.75, x = -15.2%.ml-1.kg-1, P less than 0.001) and TE (r = 0.78, x = -23.4%.ml-1.kg-1, P less than 0.001) (n = 4). In two dogs tested the effect of bolus injection was minimal at residual volume and progressively increased with lung volume. The effect of cold bolus injection was eliminated after right vagotomy in three dogs. Results indicate that cooling of some vagal receptor in the lung increases breathing frequency primarily by shortening TE. | 4 |
Portal venous gas in a patient with Crohn's disease. Portal venous gas usually occurs in the setting of an acute abdomen. Several causes for benign portal venous gas (PVG) have been reported. We describe the finding of PVG by computed tomography in a febrile patient with Crohn's disease and discuss the clinical implications of such a finding. | 3 |
Seizure outcome from anterior and complete corpus callosotomy. Eighty patients underwent anterior corpus callosotomy for treatment of generalized seizures. The patients' mean age was 18.3 years (range 4 to 53 years); the mean age at seizure onset was 5.27 years (range 0.1 to 27 years). The mean intelligence quotient (IQ) of 41 testable patients was 71.12 (range less than 30 to 114). The seizure outcome was as follows: 13% were seizure-free, 65% were significantly improved, and 22% were unchanged. Ten patients subsequently underwent a second operation to complete the callosal sectioning which resulted in additional seizure improvement in only five of them. Five complications resulted from 90 operations: two epidural hematomas, one delayed subdural hematoma, one bone-flap infection, and one postcallosotomy disconnection syndrome; two patients died. A younger age at onset of seizures, a higher IQ, and generalized tonic-clonic, atonic, complex-partial, and mixed seizure types were associated with improved seizure outcome. | 2 |
Erythrocyte fatty acids, plasma lipids, and cardiovascular disease in rural China. Cardiovascular disease (CVD) mortality (coronary heart disease, hypertensive heart disease, and stroke), plasma lipids, and red blood cell fatty acid composition were examined in an ecologic study in 65 rural counties in the People's Republic of China. Means of plasma total cholesterol, triglyceride, low-density-lipoprotein (LDL) cholesterol, and high-density-lipoprotein (HDL) cholesterol concentrations were substantially lower and the ratio of HDL cholesterol to total cholesterol was higher in this Chinese population than in Western populations. Mortality rates for CVD in China were well below Western values. Within China neither plasma total cholesterol nor LDL cholesterol was associated with CVD. A strong inverse correlation between red blood cell oleate concentrations and CVD was observed. However, red blood cell oleate concentrations were not associated with plasma cholesterol but were strongly negatively associated with arachidonate concentrations, suggesting potential diminution of CVD by oleate through reduced platelet aggregability. The results indicate that geographical differences in CVD mortality within China are caused primarily by factors other than dietary or plasma cholesterol. | 3 |
New treatment for frontal sinus hypertrophy A new treatment of frontal sinus hypertrophy is described. The anterior wall is removed, inverted, and attached again. The resulting depression is filled with bone dust. Details are discussed, and a case is presented. | 4 |
Recurrent rhabdomyolysis in association with cocaine use. As the popularity of cocaine increases in our society, so does the frequency and variety of medical complications associated with its use. A growing number of cases have implicated cocaine use in the development of rhabdomyolysis and its complication, acute renal failure. We have reported the first case of recurrent rhabdomyolysis and acute renal failure directly associated with cocaine use. Although adulterants might cause muscle damage, we believe cocaine should be added to the list of drugs that are capable of producing rhabdomyolysis. | 4 |
Eosinophilia-myalgia syndrome (L-tryptophan-associated neuromyopathy). Histopathologic study of skeletal muscle biopsy in a patient with eosinophilia-myalgia syndrome following L-tryptophan use showed prominent lymphocytic perineuritis, neuritis, and perimysial fasciitis. The presence of perineuritis and neuritis provides a histopathologic basis for clinical features of neuropathy in eosinophilia-myalgia syndrome and occurred in conjunction with a fasciitis or interstitial myositis that was predominantly perimysial and focally endomysial. | 4 |
The pattern of intrathoracic Hodgkin's disease assessed by computed tomography. Computed tomography (CT) was used to define the sites of intrathoracic abnormality in Hodgkin's disease, determine a pattern of progression of disease in the thorax, and establish the place of this pattern of spread in the differential diagnosis of thoracic abnormalities. One hundred eight patients with newly diagnosed Hodgkin's disease were studied by chest CT. Seventy-seven patients had intrathoracic abnormalities. The pattern seen was one of contiguous spread from the anterior mediastinal/paratracheal area to the other mediastinal lymph node groups (aortopulmonary, subcarinal, posterior mediastinal, and internal mammary), to the hila, and then into the lung by extension or as discrete nodules. Involvement of the pleura, pericardium, or chest wall occurred only after the anterior mediastinal/paratracheal mass had enlarged to greater than 30% of the thoracic diameter. The probability that this pattern of contiguous lymph node spread occurred by chance alone was very small. Hodgkin's disease spreads from the anterior mediastinal/paratracheal area in a contiguous manner. Exceptions are unusual enough that when they occur, diagnoses other than Hodgkin's disease are more likely. | 0 |
The J-curve phenomenon and the treatment of hypertension. Is there a point beyond which pressure reduction is dangerous? We critically appraised the medical literature to evaluate whether there is a point beyond which blood pressure reduction in hypertensive subjects is no longer beneficial and possibly even deleterious. Thirteen studies that stratified cardiovascular outcomes by level of achieved blood pressure in treated hypertensive subjects who had been followed up for at least 1 year were critiqued by four independent reviewers. Data addressing population, protocol, and methodological characteristics were evaluated. Studies did not show a consistent J-shaped relationship between treated blood pressure and stroke, but they did demonstrate a consistent J-shaped relationship for cardiac events and diastolic blood pressure. The beneficial therapeutic threshold point was 85 mm Hg. We conclude that low treated diastolic blood pressure levels, ie, below 85 mm Hg, are associated with increased risk of cardiac events. | 2 |
Cone cerclage in pregnancy. We report a technique of cone cerclage and the results and outcome in 17 patients who required a diagnostic cone biopsy in pregnancy. The mean age of the patients was 30.6 years (range 21-41). The mean gestational age was 18.8 weeks (range 10-32) at the time of the procedure. There were no major complications and hemorrhage was not a significant problem. There were no second-trimester abortions. Two patients required beta-sympathomimetics to suppress uterine activity for longer than 24 hours after the procedure. Six patients had invasive carcinoma, nine had cervical intraepithelial neoplasia (CIN) III, and two had CIN II. In 14 cases, the endocervical and ectocervical margins were negative; two patients with CIN and one with multifocal microinvasion had positive margins. Cone cerclage is a safe and easy method for performing diagnostic cervical conization during pregnancy. | 0 |
Effective surgical adjuvant therapy for high-risk rectal carcinoma BACKGROUND. Radiation therapy as an adjunct to surgery for rectal cancer has been shown to reduce local recurrence but has not improved survival. In a previous study, combined radiation and chemotherapy improved survival significantly as compared with surgery alone, but not as compared with adjuvant radiation, which many regard as standard therapy. We designed a combination regimen to optimize the contribution of chemotherapy, decrease recurrence, and improve survival as compared with adjuvant radiation alone. METHODS. Two hundred four patients with rectal carcinoma that was either deeply invasive or metastatic to regional lymph nodes were randomly assigned to postoperative radiation alone (4500 to 5040 cGy) or to radiation plus fluorouracil, which was both preceded and followed by a cycle of systemic therapy with fluorouracil plus semustine (methyl-CCNU). RESULTS. After a median follow-up of more than seven years, the combined therapy had reduced the recurrence of rectal cancer by 34 percent (P = 0.0016; 95 percent confidence interval, 12 to 50 percent). Initial local recurrence was reduced by 46 percent (P = 0.036; 95 percent confidence interval, 2 to 70 percent), and distant metastasis by 37 percent (P = 0.011; 95 percent confidence interval, 9 to 57 percent). In addition, combined therapy reduced the rate of cancer-related deaths by 36 percent (P = 0.0071; 95 percent confidence interval, 14 to 53 percent) and the overall death rate by 29 percent (P = 0.025; 95 percent confidence interval, 7 to 45 percent). Its acute toxic effects included nausea, vomiting, diarrhea, leukopenia, and thrombocytopenia. These effects were seldom severe. Severe, delayed treatment-related reactions, usually small-bowel obstruction requiring surgery, occurred in 6.7 percent of all patients receiving radiation, and the frequencies of these complications were comparable in both treatment groups. CONCLUSIONS. The combination of postoperative local therapy with radiation plus fluorouracil and systemic therapy with a fluorouracil-based regimen significantly and substantively improves the results of therapy for rectal carcinoma with a poor prognosis, as compared with postoperative radiation alone. | 0 |
Traumatic diaphragmatic hernia and intestinal obstruction due to penetrating trunk wounds. We have reported two cases of intestinal obstruction due to traumatic diaphragmatic hernia, both resulting from apparently trivial knife wounds. When TDH is due to a penetrating injury, it tends to produce symptoms of intestinal obstruction. A high index of suspicion, a chest x-ray film, and barium studies of the gastrointestinal tract are usually needed to make the diagnosis, though CT scans, ultrasonography, laparoscopy, and radionuclide scanning may also be useful. Surgeons and emergency physicians should be aware of the potential for TDH when there is a history of a penetrating wound of the chest or abdomen. | 1 |
Major histocompatibility complex antigen expression in the affected tissues in amyotrophic lateral sclerosis. Monoclonal antibody immunocytochemistry was used to examine spinal cord and muscle in amyotrophic lateral sclerosis for changes that would indicate ongoing or potential immune activity. Increased expression of class I and II major histocompatibility complex (MHC) antigens was seen in the affected areas of spinal cord. New MHC expression was concentrated in phagocytes, particularly in degenerating white matter in which they were dispersed in the tissue and also packed around blood vessels. MHC antigen was not revealed in motor neurons or skeletal muscle fibers. An anti-pan-T-cell monoclonal revealed small numbers of T cells in degenerating white matter. Similar changes have been seen in other neurodegenerative disorders. They suggest a potential for (secondary) cell-mediated activity in the affected areas rather than an ongoing MHC-restricted T-cell response. Vessel-associated phagocytes may be a source of antigen to peripheral lymphoid tissue, stimulating production of the autoantibodies that have been described. | 2 |
A positron emission tomographic comparison of pulmonary vascular permeability during the adult respiratory distress syndrome and pneumonia. We measured extravascular density (EVD) and the pulmonary transcapillary escape rate (PTCER) for 68Ga-transferrin using positron emission tomography in 14 normal volunteers and 29 patients with radiographic infiltrates, including six patients with congestive heart failure (CHF), eight patients with the adult respiratory distress syndrome (ARDS), and 15 patients with focal pneumonia. Contralateral, radiographically normal regions were also evaluated in the patients with focal pneumonia. Mean EVD was elevated in the patients with CHF, ARDS, and pneumonia in regions of radiographic infiltrate compared with values from normal subjects (p less than 0.05), but it was not significantly different among the three patient groups. PTCER in normal subjects and in patients with CHF was not significantly different (21 +/- 11 versus 44 +/- 16 x 10(-4) min-1, respectively, p = NS). PTCER was elevated in regions of infiltrate because of either pneumonia (173 +/- 99) or ARDS (170 +/- 79). PTCER was also elevated in regions contralateral to those with focal infiltrate during pneumonia, even though these regions were radiographically normal and had normal EVD values. These results suggest that PTCER is a sensitive but nonspecific index of abnormal pulmonary vascular permeability, which may be useful for classifying patients in clinical studies of pulmonary edema. | 3 |
Is liver transplantation justified for the treatment of hepatic malignancies? Twenty-eight patients received orthotopic liver transplants for malignant disease between February 1, 1984, and December 31, 1989. Preoperative diagnoses included hepatocellular carcinoma (n = 16), cholangiocarcinoma (n = 3), other primary hepatic tumors (n = 6), and metastatic diseases to the liver (n = 3). Overall actuarial survivals at 6 months, 1 year, and 5 years were 67.3%, 51%, and 31%, respectively. Long-term survival longer than 5 years was achieved in 3 patients. The recurrence rate in patients surviving longer than 3 months is 48% (median, 7 months). Hepatocellular carcinoma and cholangiocarcinoma had the poorest survival and highest recurrence rates. Specific prognostic factors correlating with survival or recurrence could not be elucidated. These results indicate that orthotopic liver transplants can provide long-term cure and palliation for malignant disease; however, patient selection is extremely important in predicting outcome. | 0 |
Prostate-specific antigen and external beam radiation therapy in prostate cancer. This study of 133 patients with localized prostate cancer (Stages A2 to C), treated by external beam radiation therapy (XRT), was undertaken for two reasons: (1) to investigate the usefulness of pretreatment serum prostate-specific antigen (PSA) levels in evaluating patients before XRT; and (2) to investigate post-XRT changes in PSA values and their likely clinical significance. It was found that pretreatment PSA values in patients with localized disease exhibit wide patient to patient variability with a greater than 100-fold difference between the lowest and highest values. Although mean PSA values were significantly higher in Stage C disease (51 patients; mean PSA, 17.3 ng/ml) than in Stage A2 disease (31 patients; mean PSA, 9.0 ng/ml), Stage B1 disease (23 patients; mean PSA, 9.1 ng/ml), or Stage B2 disease (28 patients; mean PSA, 10.6 ng/ml), individual values were of virtually no help in assigning individual patients to a clinical stage. PSA levels did not correlate with grade. After XRT, PSA values fell significantly and dramatically in virtually all patients (98%) by 3 months follow-up. Mean PSA fell from 12.5 to 2.6 ng/ml, and median PSA fell from 6.6 to 1.9 ng/ml. In most patients, PSA continued to fall up to 12 months after XRT and then stabilized at 21 months. Although PSA values fell dramatically after XRT, PSA was detectable in the serum of all patients. PSA values tended to transiently and mildly elevate during XRT. In a small proportion of patients, rising PSA values were observed after 6 months. The full significance of this requires further follow-up, of four such patients, one has relapsed. PSA is a more sensitive marker of prostatic radiation than prostatic acid phosphatase. | 0 |
Perioperative monitoring of blood flow in femoroinfragenicular vein grafts with Doppler ultrasonography: a preliminary report. A system for monitoring blood flow in femorodistal vein grafts with Doppler ultrasonography in the immediate postoperative period has been developed. Twenty-three grafts have been monitored for periods of up to 72 hours. Seventeen grafts have remained patent at minimum follow-up of 6 months, and six grafts occluded in the immediate postoperative period. Successful Doppler recordings were obtained in 16 successful and all failed grafts. Fast Fourier transform analysis of the Doppler signals was performed, and pulsatility index and time-averaged mean velocity were derived from the spectral information. Successful grafts displayed hyperemic flow with pulsatility index less than 2 and time-averaged mean velocity greater than 10 cm/sec. Failed grafts could be classified in two groups: those that occluded less than 24 hours after operation and those that occluded after 24 hours after operation. Short-term failure was categorized by highly pulsatile flow, with pulsatility index rising rapidly and time-averaged mean velocity falling correspondingly before actual cessation of flow. Delayed failure was less well defined but was suggested by failure to develop, or early deviation from, the hyperemic flow seen in successful grafts. Occlusion was heralded by development of the pulsatile pattern seen in the short-term failure group. | 4 |
The role of lasers in hemorrhoidectomy. Eighty-eight patients who received treatment for hemorrhoids were randomized into two groups. Group A received the Nd-YAG laser phototherapy for internal hemorrhoid combined with the CO2 laser for external hemorrhoid. Group B was treated with closed Ferguson hemorrhoidectomy. The need of narcotic injections for pain relief was 11 percent in group A vs. 56 percent in group B (P less than 0.001). The incidence of postoperative urinary retention was 7 percent in group A, vs. 39 percent in group B (P less than 0.05). No enema was required postoperatively in group A, vs. 9 percent in group B; 84 percent of the patients in group A were discharged on the second postoperative day, vs. 83 percent of the patients in group B discharged on the fifth postoperative day. The cost was 20 percent less in the former group. The overall complications in both groups were insignificant in difference, except prolonged wound healing in group A was noted. One year follow-up showed satisfactory results. Laser treatment is considered one of the alternatives to conventional treatment, but the surgeon needs to be aware of laser hazards. | 3 |
Late deaths after treatment for childhood cancer. An investigation of 749 deaths occurring among 4082 patients surviving at least five years after the diagnosis of childhood cancer in Britain before 1971 has been undertaken. Of the 738 with sufficient information the numbers of deaths attributable to the following causes were: recurrent tumour, 550 (74%), a second primary tumour, 61 (8%), a medical condition related to treatment of the tumour, 49 (7%), an traumatic death unrelated to the tumour or its treatment, 34 (5%), finally, any other cause unrelated to the tumour or its treatment, 44 (6%). Less than 10% of five year survivors of non-Hodgkin lymphomas, neuroblastoma, retinoblastoma, Wilms' tumour, or a soft tissue sarcoma died of recurrent tumour during the next 15 years, while more than 25% of five year survivors of Hodgkin's disease, ependymoma, medulloblastoma, and Ewing's tumour died of recurrent tumour during the corresponding period. Almost 50% of five year survivors of acute lymphoblastic leukaemia died of recurrent disease during the corresponding 15 years, a large proportion of deaths being due to central nervous system relapse in an era before central nervous system prophylaxis was routinely given. Comparison of the mortality observed with that expected from mortality rates in the general population indicated three times the expected number of deaths from non-neoplastic causes. Five times the expected number of deaths from cardiovascular causes were observed, these were predominantly myocardial infarction and cerebrovascular accidents. There was no evidence of an excess in the number of suicides observed, but there were three times the expected number of deaths from accidents observed after central nervous system tumours. | 4 |
Acute phase reactants and risk of bacterial meningitis among febrile infants and children. STUDY OBJECTIVE: To test the hypothesis that quantitation of either C-reactive protein (CRP) or the total peripheral WBC count can improve clinical detection of underlying bacterial meningitis among young febrile children. DESIGN: Cross-sectional survey of selected symptoms of central nervous system infection, signs of meningeal irritation and/or elevated intracranial pressure, levels of CRP in serum, and total peripheral WBC counts among unselected pediatric patients undergoing lumbar punctures for evaluation of acute febrile illnesses. SETTING: Emergency department and acute care "walk-in" clinic of an urban, university-affiliated general hospital. PARTICIPANTS: 160 previously well, acutely febrile infants and children (median age, 6 months). RESULTS: The prevalence of bacterial meningitis was 6%. Sensitivity of symptoms was 1.00 and specificity was 0.17. Sensitivity of signs was 0.70 and specificity was 0.81. Of the acute phase reactants, sensitivity of a CRP level of more than 1.0 mg/dL was 0.80, while that of a total peripheral WBC count of more than 15,000/mm3 was 0.40. The presence of signs and/or a CRP level of more than 1.0 mg/dL correctly identified all children with bacterial meningitis (sensitivity, 1.00). The absence of signs and a CRP level of 1.0 mg/dL or less correctly identified 71 of 150 children without bacterial meningitis (specificity, 0.47). Of 125 children without meningeal signs, the combination of symptoms and a CRP level of more than 1.0 mg/dL correctly identified all three children with bacterial meningitis (sensitivity, 1.00). The absence of these symptoms and/or a CRP level of 1.0 mg/dL or less correctly identified 80 of 122 children without bacterial meningitis (specificity, 0.66). CONCLUSION: Quantitation of CRP but not the total peripheral WBC count can increase the sensitivity of physical examination findings and the specificity of symptoms for the diagnosis of bacterial meningitis. Measurement of CRP in serum is useful as an adjunct to history and physical examination for the detection of acute bacterial meningitis in the acutely febrile child. | 2 |
Glomus tumor of the coccyx. A curable cause of coccygodynia. A 30-year-old woman presented with recurrent severe coccygodynia. She underwent exploration for a possible pilonidal sinus and was found to have a precoccygeal glomus tumor that also involved bony trabeculae of the coccyx. To our knowledge, a glomus tumor involving the coccygeal bone has not been previously documented. In view of the relief of this patient's pain following the surgical excision of coccyx and tumor, a causal role is suggested. | 0 |
Determinants of cell type in patients with cancer of the lungs. In order to evaluate the determinants of cell type in patients with primary lung cancer, we compared smoking characteristics in 1,939 patients (1,474 men and 465 women). Patients with squamous cell carcinomas, adenocarcinomas, or small-cell carcinomas were eligible. This study did not consider smoking as a risk factor for lung cancer, as all subjects had a confirmed diagnosis. We were interested in smoking history and the pattern of smoking among those whose risk was 100 percent. Among these patients, we confirmed that a larger subset of nonsmoking individuals developed adenocarcinomas than squamous cell or small-cell carcinomas; however, the duration and intensity of cigarette smoking, as measured by pack-years, were not determinants of tumor cell type in male patients. Small-cell carcinomas in women were more strongly associated with cigarette smoking than either squamous cell carcinomas or adenocarcinomas. More than 3,500 different substances have been measured in tobacco smoke, including tumor initiators, promoters, and those involved in tumor progression. These data confirm the hypothesis that factors other than cigarette smoking are more likely to be involved in the initiation of adenocarcinomas than other cell types. Endogenous and exogenous factors related to gender may be more important than the duration or intensity of cigarette smoking. | 0 |
Metoprolol versus thiazide diuretics in hypertension. Morbidity results from the MAPHY Study. The present study in hypertensive men (40-64 years old) with untreated diastolic blood pressure above 100 mm Hg was aimed at investigating whether metoprolol (n = 1,609) given as initial treatment would lower the risk for coronary events (sudden death and myocardial infarction) more effectively than thiazide diuretics (n = 1,625). A substantial part of this study was the metoprolol arm of the Heart Attack Primary Prevention in Hypertension (HAPPHY) study. The HAPPHY study was a pooling of the effect of different beta-blockers, mainly metoprolol and atenolol, in which no favorable effect in relative risk was observed for atenolol as compared with diuretics. In the present study, 255 patients suffered definite coronary events during follow-up; 25% of these events were fatal, 39% were acute myocardial infarctions, and 36% were silent myocardial infarctions. The risk for coronary events was significantly lower in patients on metoprolol than in patients on diuretics (111 versus 144 cases, p = 0.001, corresponding to 14.3 versus 18.8 cases/1,000 patient years and a relative risk of 0.76 at the end of the trial; 95% confidence interval 0.58-0.98). This difference in risk has potentially important implications for clinical practice because of the large number of hypertensive patients who are at increased risk for coronary events. Because a placebo group, for ethical reasons, could not be included, relative risk can only be expressed in relation to diuretics. There was no difference between the two treatment groups in baseline characteristics, blood pressure during follow-up, or stroke rates. Thus, the difference in risk for coronary events is probably mediated via mechanisms other than blood pressure control. However, present data might suggest that different beta-blockers may have different efficacy in preventing coronary events. The reasons for this possibility are as yet unknown. | 3 |
Recurrent childhood myoglobinuria. Recurrent heritable childhood myoglobinuria is a potentially fatal entity (mortality up to 35%) in which prompt diagnosis and treatment are critical. Sixty childhood cases have been reported between 1910 to 1988, most with undiagnosed etiologies. We have studied an additional 40 cases referred to CPMC (1980-1988), suggesting that this condition is largely underdiagnosed or unreported. We have found important differences between the childhood and adult-onset cases. Of 77 cases of adult-onset recurrent myoglobinuria, 45% have been diagnosed biochemically. In contrast, only 30% of the 60 childhood cases from the literature have been diagnosed; 11 with CPT deficiency and 7 with various glycolytic defects, and only 5 of our 40 childhood cases have been diagnosed, all with CPT deficiency. The 100 combined childhood cases can be divided into an exertional group (type I) with exertion as the leading precipitating factor (46 literature and 10 CPMC cases), a toxic group (type II) with infection and/or fever as the primary precipitant (14 literature and 23 CPMC cases), and 7 undefined cases. The type I group resembles the adult-onset group in which exercise is also the leading precipitating factor. There is a slight female predominance (male/female = 1:1.3) in the toxic group vs. a marked male predominance in the exertional and adult groups (4:1). Only 4 of 37 cases (11%) of the toxic group are diagnosed (all with CPT deficiency) vs. 19 of 56 cases (34%) of the exertional group (12 CPT, 7 glycolytic) and 45% of the adult group. The toxic group is also differentiated by a higher mortality rate and by the presence of additional clinical features, including ictal bulbar signs (8 of 18), encephalopathy (4 of 19), and seizures (2 of 7), as well as persistent cardiac abnormalities, developmental delay (4 of 17), and dysmorphic features (2 of 9). These clinical characteristics clearly differentiate the childhood from the adult cases and suggest the presence of more generalized disease processes and different biochemical etiologies. A study of the heritable causes of myoglobinuria is important because identification of the biochemical defect may elucidate the pathogenetic mechanism of the myoglobinuria and facilitate the development of rational treatment strategies aimed at circumventing or correcting the metabolic block. | 4 |
Blue rubber bleb nevus syndrome with oral hemangiomas. A case of blue rubber bleb nevus syndrome with oral hemangiomas is reported. Attention is directed to this syndrome because, although rare, it is usually associated with oral lesions. The blue rubber bleb nevus syndrome should always be considered a possibility in patients with oral hemangiomas and bluish skin nodules. | 0 |
Ultrasonography in the differentiation of complicated and uncomplicated acute pyelonephritis. Differentiation of uncomplicated pyelonephritis versus complicated pyelonephritis has always been problematic. No clear physical signs or symptoms are diagnostic. To study differences between the two, we retrospectively reviewed charts of patients admitted to Charity Hospital, New Orleans, with febrile urinary tract infections. Criteria for inclusion were pyuria, positive urinary culture, and signs or symptoms of pyelonephritis. All patients underwent renal ultrasonography (US) before other diagnostic tests. US identified a potential emergency (hydronephrosis or abscess) in 11 of 98 patients (11.2%). The only significant contributing factor was the presence of diabetes mellitus, which was present in five of 11 emergent conditions and eight of 73 of the remainder (P = 0.003). US is inexpensive, easily obtainable in the emergency room, and sensitive enough to screen patients with pyelonephritis for complications. However, we believe it is mandatory in diabetics, because of the high incidence of abnormalities in this population. | 4 |
Mechanism of surgical stress impairment of human perioperative natural killer cell cytotoxicity. Natural killer (NK) cells are an important defense against intravascular tumor dissemination. Tumor embolization can occur at surgery, so we tested whether surgical stress decreased perioperative NK cell cytotoxicity, and examined the underlying mechanism of suppression. Patients with solid tumors underwent NK cell cytotoxicity assay just before and 24 hours after surgery in a 3-hour chromium 51 release assay. The NK cell cytotoxicity was significantly decreased postoperatively. We considered that surgical NK cell impairment might be due to (1) NK cell redistribution, (2) presence of suppressor cells, or (3) direct "toxic" effects on NK cells. Impaired NK cell cytotoxicity was not due to NK cell redistribution, because differential counts showed no significant changes in the percentage of large granular lymphocyte NK morphology. To isolate possible suppressor cells, postoperative cells from patients were selectively depleted of NK cells using anti-Leu-11b monoclonal antibody plus complement; these cells were then mixed with autologous preoperative cells. Postoperative NK cell cytotoxicity was markedly impaired, but the postoperative NK depleted cells did not suppress preoperative NK cells. We conclude that NK cell functional impairment from surgical stress is due to direct "toxic" effects on NK cells rather than either NK cell redistribution or the generation of NK-directed suppressor cells. | 4 |
Surgical and prosthesis-related complications using the Groningen button voice prosthesis. Prosthesis-assisted tracheoesophageal speech has advanced speech rehabilitation appreciably. However, the surgical technique and the use of a prosthesis may give rise to complications. In a retrospective study on 132 consecutive patients rehabilitated with a Groningen button voice prosthesis, the complications were assessed, the average follow-up being 21 months. Surgical complications were not observed. Prosthesis-related complications, which were encountered in 28%, were all of a minor nature and mainly consisted of granulation formation and hypertrophic scarring; these appeared to be easily treatable. The complications found were few and insignificant in comparison with reports in the literature. This may be attributed to the uncomplicated surgical procedure for the insertion of the Groningen button. Moreover, the prosthesis is self-retaining and requires hardly any care from the patient. Permanent removal of the prosthesis usually requires surgical closure, which is a simple procedure performed under local anaesthesia. | 1 |
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