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Photosensitive epilepsies and photoconvulsive responses in Arabs. The occurrence of photosensitivity (PS) was examined in 327 Arabs greater than or equal to 15 years of age with epilepsy by intermittent photic stimulation (IPS). A control group of 192 nonepileptic Arabs greater than or equal to 15 years of age were also examined by IPS. Of the epileptic patients, 24 (7.3%) were photosensitive, an incidence comparable to that in whites in contradistinction to the reported rarity among African blacks. This finding indicates that environmental factors, particularly excessive sunshine, does not appear to influence the occurrence of PS among epileptic patients. The occurrence of PS among epileptic patients may depend more strongly on the presence of an epileptic syndrome known to have association with PS.
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Pathophysiology of hypertension in blacks. The pathophysiology of hypertension in the black population differs to some extent from that of the nonblack population. Although black hypertensives exhibit enhanced sodium retention, expanded plasma volume, lower plasma renin activity, and a greater increase in blood pressure in response to high levels of Na+ intake compared with nonblack hypertensives, there is considerable heterogeneity in these studies. Alterations in ion transport mechanisms, such as a decrease in Na+K(+)-ATPase activity and Na+K+ cotransport, have been demonstrated in the black hypertensive population. Those features provide the physiologic basis for the differential response to monotherapy with diuretics and, perhaps, with calcium channel blockers, that is observed in black hypertensives, particularly when compared with responses to beta-blockers or angiotensin converting enzyme inhibitors.
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Spontaneous neurodegeneration in transgenic mice with mutant prion protein Transgenic mice were created to assess genetic linkage between Gerstmann-Straussler-Scheinker syndrome and a leucine substitution at codon 102 of the human prion protein gene. Spontaneous neurologic disease with spongiform degeneration and gliosis similar to that in mouse scrapie developed at a mean age of 166 days in 35 mice expressing mouse prion protein with the leucine substitution. Thus, many of the clinical and pathological features of Gerstmann-Straussler-Scheinker syndrome are reproduced in transgenic mice containing a prion protein with a single amino acid substitution, illustrating that a neurodegenerative process similar to a human disease can be genetically modeled in animals.
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Clinical and electrophysiologic determinants, treatment and survival of patients with sustained malignant ventricular tachyarrhythmias occurring late after myocardial infarction To assess the clinical and electrophysiologic determinants, treatment and survival of patients with sustained malignant ventricular tachyarrhythmias late after myocardial infarction, a total of 108 patients (mean age 61 +/- 10 years) were studied. Thirty-two patients (Group I) had sustained ventricular tachyarrhythmias 8 to 60 days (mean 13 +/- 9) after acute myocardial infarction. The remaining 76 patients (Group II), who served as a control group, had no sustained ventricular tachyarrhythmias less than or equal to 60 days after infarction. The most significant independent determinants of sustained ventricular tachyarrhythmias late after infarction were the presence of late potentials (chi square = 16.07, p = 0.0001), defined as an abnormal signal-averaged QRS complex in association with an abnormal root-mean-square voltage in the terminal 40 ms of the QRS complex, and an abnormal ejection fraction of less than 40% (chi square = 10.09, p = 0.001). Sustained ventricular tachycardia was induced in 27 (96%) of 28 Group I patients. Among the 32 patients in Group I, antitachycardia therapy included antiarrhythmic drug therapy as the sole preventive measure in 14 (44%); map-guided surgery or coronary artery bypass surgery, or both, in 14 (44%) and the automatic cardioverter-defibrillator in 4 (12%). The arrhythmias were rendered noninducible in 83% of patients after map-guided surgery and in 41% after drug therapy. During a follow-up period of 20 +/- 14 months, five Group I patients (15%) had an arrhythmic event and four (9.3%) had a cardiac-related death. All five patients who had an arrhythmic event were receiving antiarrhythmic drug therapy.
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Vimentin is preferentially expressed in high-grade ductal and medullary, but not in lobular breast carcinomas. Two hundred sixty-two invasive breast carcinomas dating from 1979 to 1984 were tested for vimentin and keratin on formaldehyde-fixed paraffin-embedded sections. None of 26 lobular carcinomas expressed vimentin. Vimentin expression in 10% or more of tumor cells was found in 78% of medullary (14 of 18), in 16% of ductal not otherwise specified (NOS) (35 of 214), and in two of four mucinous carcinomas. A further seven tumors showed vimentin expression in less than 1% to 10% of the cells. Vimentin was expressed in tumor cells of 30% (28 of 93) of grade III invasive ductal NOS carcinomas versus 7% (7 of 105) of grade II and 0% of grade I carcinomas (0 of 10). Vimentin was found to be preferentially expressed in tumors growing in broad, often anastomosing bands or sheets with extensive necrosis, scanty supportive stroma, high nuclear grade, and numerous mitoses. The authors conclude that vimentin is not detected in lobular carcinomas, but is preferentially expressed in medullary and in high-grade ductal NOS breast carcinomas.
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Benign cystic teratoma manifested as an umbilical hernia. We have reported a case of dermoid tumor manifested as an umbilical hernia. Resection led to complete recovery.
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The agent of bacillary angiomatosis. An approach to the identification of uncultured pathogens BACKGROUND. Bacillary angiomatosis is an infectious disease causing proliferation of small blood vessels in the skin and visceral organs of patients with human immunodeficiency virus infection and other immunocompromised hosts. The agent is often visualized in tissue sections of lesions with Warthin-Starry staining, but the bacillus has not been successfully cultured or identified. This bacillus may also cause cat scratch disease. METHODS. In attempting to identify this organism, we used the polymerase chain reaction. We used oligonucleotide primers complementary to the 16S ribosomal RNA genes of eubacteria to amplify 16S ribosomal gene fragments directly from tissue samples of bacillary angiomatosis. The DNA sequence of these fragments was determined and analyzed for phylogenetic relatedness to other known organisms. Normal tissues were studied in parallel. RESULTS. Tissue from three unrelated patients with bacillary angiomatosis yielded a unique 16S gene sequence. A sequence obtained from a fourth patient with bacillary angiomatosis differed from the sequence found in the other three patients at only 4 of 241 base positions. No related 16S gene fragment was detected in the normal tissues. These 16S sequences associated with bacillary angiomatosis belong to a previously uncharacterized microorganism, most closely related to Rochalimaea quintana. CONCLUSIONS. The cause of bacillary angiomatosis is a previously uncharacterized rickettsia-like organism, closely related to R. quintana. This method for the identification of an uncultured pathogen may be applicable to other infectious diseases of unknown cause.
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Effect of marked peripheral leukocytosis on the leukocyte count in ascites. Patients with high peripheral leukocyte counts are sometimes found to have high leukocyte counts in ascitic fluid in the presence of negative cultures. To determine if peripheral leukocytosis (greater than or equal to 20 x 10(9)/L) by itself can result in high leukocyte or neutrophil counts in ascites, 29 patients were studied. A total of 31 paracenteses were performed in these patients as soon as the high peripheral leukocyte count was determined. Culture of ascitic fluid was performed using blood-culture bottles. The mean peripheral leukocyte count was 29.3 +/- 9.3 x 10(9)/L, with a mean neutrophil count of 19.9 +/- 6.5 x 10(9)/L. The mean ascitic fluid neutrophil count was 0.064 +/- 0.054 x 10(9)/L (range, 0.007 to 0.197 x 10(9)/L). No significant correlation was found between peripheral neutrophil (or leukocyte) count and neutrophil (or leukocyte) count in ascitic fluid. Marked peripheral leukocytosis (or neutrophilia) does not seem to have an effect on the leukocyte or neutrophil count in ascitic fluid.
4
Congenital biliary tract disease. Jaundice in the pediatric patient requires prompt and directed evaluation. This dictum is highlighted in infants with biliary atresia, in whom the progressive sclerosing process results in complete obliteration of patent but microscopic hilar biliary structures by 4 months of age. Kasai's operation, if done before that time, will re-establish bile drainage in 90% of infants. One fourth to one third of patients achieve long-term jaundice-free survival. Complications of cholangitis, portal hypertension, and fat malabsorption are experienced by many patients. In children with early or late operative failure, liver replacement now offers legitimate hope for extended survival. Choledochal cyst is a conglomerate of pancreaticobiliary anomalies consisting of a choledochal cyst, a common-channel-type pancreaticobiliary junction, intrahepatic cystic disease, and partial obstruction of the distal common bile duct. Many patients have one or more of these malformations. It is now widely accepted that the preferred treatment of choledochal cyst is total excision of the diseased biliary duct with reconstruction by Roux-en-Y choledochojejunostomy. "Internal" excision avoids injury to other structures in the hepatoduodenal ligament, particularly if pericystic inflammation is present. Congenital perforation of the common bile duct responds in most cases to simple peritoneal drainage of the perforation. Retention of the tube cholecystostomy is useful for subsequent cholangiographic follow-up. Tube cholecystostomy may also be useful for irrigation of the biliary tract in infants with inspissated bile syndrome.
1
A topographical relationship between Helicobacter pylori and gastritis: quantitative assessment of Helicobacter pylori in the gastric mucosa. A topographical relationship between the number of Helicobacter pylori in the gastric mucosa and the histological severity of gastritis was studied in 902 pairs of biopsy specimens taken from 314 patients. A pair of biopsies were taken from the antrum, the lesser curvature of the middle body, and the greater curvature of the upper body of the stomach. The quantitative assessment of H. pylori was made based on smear, culture, and tissue section. The histological severity of gastritis was assessed as to the degrees of mononuclear cell and polymorphonuclear leukocyte infiltration. A positive correlation was confirmed between the number of H. pylori and the severity of polymorphonuclear leukocyte infiltration. The degrees of inflammatory cells infiltration in the specimens with H. pylori colonization were significantly lower in the upper body than in the antrum.
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Three staged approach to the surgical management of renal cell carcinoma extending into the right atrium. Case report. Left renal cell carcinoma extending into the right atrium was treated by angioinfarction, removal of right atrial tumour using cardiopulmonary bypass and ten days later abdominal radical nephrectomy and inferior vena cava thrombectomy. Twenty four months later the patient remains well with no evidence of tumour recurrence.
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Salt and hypertension--future directions. The comments that follow reflect the personal views of this author regarding some useful directions of research in the field of salt and hypertension. From a physiological perspective, salt sensitivity is defined, and the merits and limitations of certain animal models of hypertension used to study this issue are discussed. The need to more clearly define the mechanisms that detect sodium intake and control the renal excretion of sodium is discussed. Additionally, the need to better understand the relation between sodium homeostasis, volume regulation, and the consequences of dysfunction in these regulatory system on the arterial vasculature and interstitial matrix is emphasized. The necessity for the application of new tools and approaches in a number of investigative areas is discussed. Finally, the necessity of equally imaginative whole animal and cell/molecular research and efforts to merge and integrate the data obtained at the cellular level with that of intact systems is emphasized.
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Loss of heterozygosity on chromosomes 17 and 18 in breast carcinoma: two additional regions identified. The loss of heterozygosity (LOH) at specific regions of the human genome in tumor DNA is recognized as evidence for a tumor-suppressor gene located within the corresponding region of the homologous chromosome. Restriction fragment length polymorphism analysis of a panel of primary human breast tumor DNAs has led to the identification of two additional regions on chromosomes 17q and 18q that frequently are affected by LOH. Deletions of each of these regions have a significant correlation with clinical parameters that are associated with aggressive breast carcinomas. Previous restriction fragment length polymorphism analysis of this panel of tumors has uncovered several other frequently occurring mutations. LOH on chromosome 18q frequently occurs in tumors with concomitant LOH of loci on chromosomes 17p and 11p. Similarly, tumors having LOH on 17q also have LOH on chromosomes 1p and 3p. This suggests that certain combinations of mutations may collaborate in the development and malignant progression of breast carcinomas.
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Malignant fibrous histiocytoma of the conjunctiva. Malignant fibrous histiocytoma (MFH) of the conjunctiva is an extremely rare tumour, and only three previous cases have been reported. We describe two patients with MFH of the conjunctiva: a 58-year-old white male with epibulbar tumour who had exenteration and is alive after five years' follow-up, and a 3 1/2-year-old African girl with xeroderma pigmentosum and an MFH of her right eye conjunctiva, the first reported case of this association. The characteristics and the methods of diagnosis of MFH are discussed.
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Renal vein renins: inability to predict response to revascularization in patients with hypertension. To determine whether the captopril-stimulated renal vein renin ratio (CSRVRR) could enable identification of patients with hemodynamically significant renovascular lesions who would respond to revascularization, the authors measured CSRVRRs in 143 consecutive patients with hypertension who had been selected because of clinical features suggestive of renovascular hypertension. All patients underwent conventional renal arteriography. Renovascular hypertension was the final diagnosis if revascularization resulted in cure or improvement in blood pressure. Complete data were available for 133 patients. Twenty patients had renovascular hypertension; CSRVRR was greater than 1.5 in 13 of these 20 patients (sensitivity, 65%). However, it was also greater than 1.5 in 54 of the 113 patients without renovascular hypertension (false-positive rate, 47.8%). The positive predictive value of CSRVRR was 18.6%; the negative predictive value, 89.3%. It is concluded that CSRVRR is not sufficiently sensitive to enable prediction of which patients will respond to revascularization and is not specific enough to exclude patients who do not have renovascular hypertension.
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Daytime hypertension in obstructive sleep apnea. Prevalence and contributing risk factors. We examined the prevalence of daytime hypertension in a modern sample of patients with obstructive sleep apnea (OSA) and assessed the relative risk factors contributing to the development of hypertension in this disorder. Daytime hypertension was present in 92 (45 percent) of 206 male and female patients with OSA. Stepwise logistic regression revealed that only age and body mass index (BMI) were predictors of hypertension in this population. A subsample of 152 male patients with OSA was then compared to 904 men identified from a geographically and ethnically similar general population. When one controlled for age and BMI, the prevalence of hypertension in the two groups was the same except for those aged 25 to 44 years who were markedly obese (BMI greater than 31 kg/m2). In this group, 47 percent of the patients with OSA were hypertensive vs 26 percent of control subjects (p less than 0.05). Our data suggest that the high prevalence of hypertension in OSA is primarily related to age and the excess obesity seen in these patients. In morbidly obese young patients with OSA, factors directly related to OSA may also be contributing to the development of hypertension. With increasing age, other competitive risks may obscure any independent effect that OSA may exert.
2
Prevention of a false diagnosis of sexually acquired reactive arthritis by synovial lymphocyte responses. Three cases are reported in which a diagnosis of sexually acquired reactive arthritis might have been made erroneously from the history, but the enteric origin of the reactive arthritis was evident from synovial lymphocyte responses. The importance of making the correct diagnosis and the avoidance of unwarranted spousal dysharmony is stressed.
1
Prospective study on prevalence of esophageal chest pain in patients referred on an elective basis to a cardiac unit for suspected myocardial ischemia. The prevalence of esophageal chest pain was studied prospectively in patients referred on an elective basis to a cardiac unit for suspected myocardial ischemia. A group of 248 consecutive patients without previously documented heart disease was admitted for elective diagnostic coronary angiography. The clinical history classified 185 patients as having anginal pain and the coronary angiogram was normal in 48 of them. In 37 of these 48 patients full esophageal testing was performed including 24-hr intraesophageal pH and pressure recordings with indication of chest pain episodes as well as a number of esophageal provocation tests, ie, acid perfusion, edrophonium stimulation, balloon distension, and ergonovine stimulation, all performed under continuous esophageal manometric and electrocardiographic monitoring. In 19 of these 37 patients, the familiar chest pain could be reproduced by esophageal provocative testing without ischemic ST-T segment alterations; six of these 19 patients had also a positive 24-hr pH and pressure recording. These data strongly suggest an esophageal origin of chest pain in half the patients with typical angina and a normal coronary angiogram.
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The significance of gastrinomas found in peripancreatic lymph nodes. A patient with Zollinger-Ellison syndrome (ZES) was found to have a solitary, extrapancreatic, extraintestinal gastrinoma in a peripancreatic lymph node. Preoperative studies did not show the location of the tumor. After excision of the gastrinoma the patient's fasting serum gastrin level dropped from preoperative levels of 596 pg/ml to 120 pg/ml (normal, less than 200 pg/ml). Fasting and stimulated gastrin levels have remained within the normal range at 18 months follow-up. This patient had previously undergone antrectomy, so it could not be determined if this tumor represented a primary lymph node gastrinoma or metastasis from an unrecognized tumor that may have been present in the resected stomach or duodenum. The outcome of this case confirms the previous reports that ZES can be controlled after resection of gastrinomas that were contained within abdominal lymph nodes, even if a primary enteropancreatic tumor is not found. Our results also support the use of an aggressive operative search aimed at eradication of the tumor in patients with ZES even if preoperative localization studies fail to identify the site of the gastrinoma.
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Bronchial anomaly of the right upper lobe. This case report presents a rare anomaly of right upper lobe bronchial anatomy. During routine right upper lobe resection for carcinoma, a common right upper and middle lobe bronchus was found. The resection was completed as a right upper and middle bilobectomy. Knowledge of this uncommon variant was beneficial in performing the pulmonary resection. A review of the literature is presented.
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Limb reconstruction with vascularized fibular grafts after bone tumor resection. Limb-salvage operations are being used with increasing frequency for patients with malignant bone tumors. For children, when a biologic reconstruction is desired, the choice is often between conventional and vascularized fibular grafts. An experimental study was performed in dogs to compare the two types of fibular grafts for bridging segmental defects in the radius and ulna. Twenty-six adult dogs were divided into two groups and studied at intervals of two, three, four, six, and 12 months after transplantation. The conventional grafts healed by creeping substitution i.e., they were first partially resorbed before new bone was laid down. In contrast, the vascularized fibulae maintained their normal structure and hypertrophied by subperiosteal new bone formation. The conventional fibulae eventually hypertrophied but much later than the vascularized grafts. The vascularized grafts were stronger at four and six months. Between six and 12 months, both grafts remodeled to resemble the size and shape of the forearm bones they were replacing. These experimental results have influenced the treatment of patients. Vascularized fibular grafts are ideal for diaphyseal defects greater than 10 cm long, especially in very young children, a poorly vascularized bed, or when bone healing is delayed by chemotherapeutic agents. To maximize hypertrophy, an external fixator is used to immobilize the graft rather than a plate, which acts as a stress shield.
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The pathophysiology of anoxic injury in central nervous system white matter. White matter of the mammalian brain is susceptible to anoxic injury, but little is known about the pathophysiology of this process. We studied the mechanisms of anoxic injury in white matter using the isolated rat optic nerve, a typical central nervous system white-matter tract. Optic nerve function, measured as the area under the compound action potential, rapidly failed when exposed to anoxia. Postanoxic recovery was variable, depending on duration of the anoxic insult; after a standard 60-minute period of anoxia, the compound action potential recovered to 28.5% of control. Irreversible anoxic injury was critically dependent on extracellular Ca2+; maintaining the tissue in zero [Ca2+] solution throughout the anoxic period resulted in 100% compound action potential recovery. Increasing perfusate [Ca2+] during anoxia from zero to 4 mM resulted in progressively less recovery. Anoxic damage to the optic nerve appears to depend on the gradual accumulation (over tens of minutes) of Ca2+ in a cytoplasmic compartment. The inorganic Ca2+ channel blockers Mn2+ (1 mM), Co2+ (1 mM), or La3+ (0.1 mM) had no effect on recovery of the compound action potential after anoxia; only Mg2+ (10 mM) significantly improved recovery. Treatment with the dihydropyridine Ca2+ channel blockers nifedipine (1-10 microM) or nimodipine (1-40 microM) also had no effect on recovery from anoxia. Thus, Ca2+ influx during anoxia does not occur via conventional Ca2+ channels. Preliminary evidence suggests that this Ca2+ influx may occur via other cation channels that are imperfectly selective for Ca2+ or via the Na(+)-Ca2+ exchanger.
2
Fibrosing mediastinitis with coronary artery involvement. This case report describes a patient with chronic fibrosing mediastinitis involving the entire intrapericardial aorta, innominate artery, and the base of the heart with involvement of the proximal segments of the coronary arteries. This finding was unsuspected before emergency coronary artery bypass grafting. Coronary stenosis due to fibrosing mediastinitis is a rare complication of fibrosing mediastinitis. Owing to the extensive fibrosis, the normal bypass, cardiac preservation, and revascularization techniques required alteration and are discussed.
3
Clonal origin of pituitary adenomas. As the pathogenesis of pituitary adenomas remains unclear, the tumor clonal composition of these common neoplasms was studied. Clonality was determined in female patients by analysis of restriction fragment length polymorphisms of the X-chromosome genes hypoxanthine phosphoribosyl transferase and phosphoglycerate kinase in conjunction with their respective methylation patterns. Peripheral lymphocyte DNA was screened from 62 female patients undergoing transsphenoidal surgery for pituitary adenoma. Eleven patients were heterozygous for the BglI site on PGK, 4 for the BamHI site on HPRT, and 1 patient for both sites. Of these 16 patients, 3 had acromegaly, 4 had Cushing's disease, 7 had hyperprolactinemia, and 2 were clinically nonfunctional. After surgery, morphological study, including immunohistochemistry and electron microscopy of the pathological specimens, allowed a direct comparison between clonality and tumor cell type. Control fresh normal pituitary tissue was found to be polyclonal. The following tumors were monoclonal: all 3 somatotroph adenomas, 4 of 4 lactotroph tumors, 3 of 4 corticotroph cell adenomas, a gonadotroph adenoma, and a nonsecretory adenoma. A mixed plurihormonal adenoma was polyclonal, as were 2 tumors consisting of adenomatous lactotrophs interspersed with nontumorous adenohypophyseal pituitary tissue and one corticotroph adenoma mixed with normal pituitary tissue. Functional pituitary adenomas derived from somatotrophs, corticotrophs, or lactotrophs and nonsecretory tumors are monoclonal in nature, suggesting that somatic cell mutations precede clonal expansion of these cells and play a major role in pituitary tumorigenesis.
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Inflammatory pseudotumor of the liver. Inflammatory pseudotumor of the liver is an extremely rare entity. Because of its unusual clinical presentation and confusing histologic picture, a diagnosis of malignancy is frequently made. Thus the surgeon is closely involved with the case and extensive procedures are not uncommon. However, this lesion is benign and will even regress spontaneously, making radical surgical procedures contraindicated. The difficulty lies in establishing an accurate diagnosis and the histologic pitfalls of this particular process. Conservative therapy can then be applied, avoiding surgical morbidity.
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Eosinophilia-myalgia syndrome associated with ingestion of L-tryptophan: muscle biopsy findings in 4 patients. Muscle biopsies of 4 patients with the eosinophilia-myalgia syndrome associated with ingestion of L-tryptophan showed lymphocytic infiltrates with occasional eosinophils largely restricted to interstitial fibrous tissue and perivascular areas. There was inflammation and fibrosis of muscle spindle capsules in 3 patients. In the 2 sickest patients, there was profound muscle atrophy, affecting both muscle fiber types.
4
A phase I trial of cisplatin in hypertonic saline and escalating doses of 5-fluorouracil by continuous intravenous infusion in patients with advanced malignancies. Thirty-four patients with incurable solid tumors were treated in a Phase I trial with a fixed dose of high-dose cisplatin (CDDP) administered in hypertonic saline and escalating doses of infusional 5-fluorouracil (5-FU). Five treatment levels of 5-FU, ranging from 500 to 900 mg/m2/day for 5 days, were studied. Leukopenia, thrombocytopenia, and oral mucositis were the dose-limiting toxicities encountered. Nephrotoxicity was minimal. Ototoxicity and peripheral neuropathies were rare and mild in this patient group, but most patients received only a small number of treatment cycles. Diarrhea was not dose-limiting. Two complete responses (one non-small cell lung cancer and one sweat gland carcinoma) were observed. No other major responses were noted. With the dose of CDDP set at 35 mg/m2/day for 5 consecutive days, the maximum tolerated dose (MTD) of a concurrent 5-day 5-FU infusion was found to be 900 mg/m2/day. The recommended dosages for Phase II trials are 35 mg/m2/day CDDP and 800 mg/m2/day 5-FU for 5 consecutive days. Cancers of the lung, breast, gastrointestinal tract, and genitourinary tract would be reasonable targets for Phase II studies.
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Rigid fixation of internal orbital fractures. When large portions of the internal orbit are destroyed (two to four walls), standard bone-grafting techniques for immediate and late orbital reconstruction may not yield predictable eye position. Critical bone support is most often deficient inferomedially. CT analysis of orbital volume in cases where eye position was unsatisfactory reveals that displacement of bone grafts is one mechanism of the unsatisfactory result. Other mechanisms include undercorrection and bone-graft resorption. In order to minimize postoperative bone-graft displacement, titanium implants were used to span large defects in the internal orbit to provide a platform for bone-graft support. Twenty-six implants were placed in immediate and 12 were placed in late orbital reconstructions. More reliable bone-graft position resulted. Two late infections have occurred resulting in implant removal in a 3-year period.
2
Ischemic optic neuropathy. ION typically affects the older population with a sudden decrease in vision, altitudinal visual field loss, and a swollen optic nervehead. Systemic hypertension and diabetes mellitus are the most commonly associated medical problems. Occlusion of the posterior ciliary arterial blood supply to the retrolaminar optic nerve leads to axoplasmic stasis and further compromise of vessels in the nerve substance, which causes the typical funduscopic appearance. Although there is no recognized medical treatment that can reverse the visual loss, a recent report suggests optic nerve sheath decompression for a select group of patients with a gradual decline in vision due to ION may be beneficial. When ION occurs in persons less than 50 years of age, such etiologies as juvenile diabetes mellitus, antiphospholipid antibody-associated clotting disorders, collagen-vascular disease, and migraines should be considered. Rarely, complications of intraocular surgery or acute blood loss may cause an ischemic event in the optic nerve.
3
A phase II multi-institutional trial of low-dose N-(phosphonacetyl)-L-aspartate and high-dose 5-fluorouracil as a short-term infusion in the treatment of adenocarcinoma of the pancreas. A Southwest Oncology Group study. Adenocarcinoma of the pancreas is a highly lethal malignancy and chemotherapy has had little impact on the natural history of this disease. PALA, used to potentiate 5-fluorouracil (5-FU), has been shown to have synergy in vivo and in vitro. Twenty-seven patients were treated with an intravenous push dose of PALA (250 mg/m2) followed 24 hours later with a 24-hour infusion of 5-FU (2600 mg/m2). This regimen was repeated weekly. There was one partial response of 21 eligible patients with an estimated response rate of 5%. Toxicity was severe with one toxic death and four patients experiencing Grade 4 toxicity. 5-Fluorouracil and PALA, given in the schedule described, do not appear to be effective against adenocarcinoma of the pancreas.
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Mechanisms of hemolysis and anemia associated with acute antepartum pyelonephritis. Anemia develops in about a fourth of women whose pregnancy is complicated by pyelonephritis, although its exact mechanism has not been defined clearly. In this study of 18 women with antepartum pyelonephritis, although only a third had anemia (hematocrit less than 30 vol/dl), there was evidence for hemolysis in all 18. Specifically there was a mean decrease in hematocrit of 5 vol/dl from admission to discharge. With scanning electron microscopy, we compared erythrocyte morphologic aberrations that were found in women with renal infection with those of normally pregnant women, and the former had significantly increased proportions of echinocytes in particular, but schistocytes and spherocytes were increased also (total 10.3% vs 1.4%, p less than 0.0001). These changes, especially echinocytosis, have been induced in vitro by lipopolysaccharide, and they are known to lead to premature red blood cell destruction in vivo. We conclude that hemolysis with subsequent anemia in pregnant women with pyelonephritis is caused by lipopolysaccharide-induced red blood cell membrane damage.
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Reliability of stimulated and spontaneous growth hormone (GH) levels for identifying the child with low GH secretion. The reliability of stimulated and spontaneous GH levels for identifying the child with low GH secretion has been the subject of debate. We compared the ability of GH concentrations after pharmacological stimulation with levodopa and clonidine and of spontaneous peak and 12-h pooled GH concentrations during sleep on a single night to estimate the maximum spontaneous GH secretion from 2 nights in 55 children, aged 5-16 yr, with heights below the 3rd percentile and/or height velocities below the 25th percentile for age, who had two consecutive overnight GH secretory profiles. Maximum stimulated GH concentrations correctly categorized 80% of children who had maximum spontaneous GH concentrations above and below 4 micrograms/L using a double monoclonal immunoradiometric assay for GH (Tandem-R HGH, Hybritech). The remaining 20% of children had stimulated GH concentrations below but spontaneous GH concentrations above 4 micrograms/L. Using this cut-off, the maximum GH concentrations from the first and second nights correctly categorized 98% and 95% of the children, respectively. Night to night variation in GH secretion was low in children who had low spontaneous GH secretion (maximum spontaneous peak and pool GH concentrations, less than 4 and less than or equal to 0.7 micrograms/L, respectively), and pooled GH concentrations from the 2 nights were concordant in 98% of the cases. We conclude that it is not uncommon for stimulated GH concentrations to underestimate spontaneous GH secretion. Even without acclimatization to the hospital setting, measurement of spontaneous GH secretion on a single night was more reliable for identifying the child with low endogenous GH secretion than was GH stimulation testing alone.
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Decreased protein binding of salicylates in Kawasaki disease. Because patients with Kawasaki disease have low serum concentrations of salicylates despite high doses, and because the free (unbound) drug is responsible for the pharmacologic effects of salicylates, we assessed salicylate protein binding in patients with Kawasaki disease. During the acute phase of the disease, protein binding of salicylate in 36 children with Kawasaki disease was 73 +/- 12%, significantly lower than during the subacute phase (90.4 +/- 8.7%; p less than 0.0005). Mean serum albumin concentration was 29.2 +/- 6.4 gm/L during the acute phase and 36.7 +/- 7.8 gm/L during the subsequent subacute phase (p less than 0.005). Salicylate protein binding was affected independently by both serum albumin and total salicylate levels. During the acute phase of Kawasaki disease, children had an average twofold increase in free salicylate compared with normoalbuminemic control subjects. A nomogram has been devised to derive free salicylate levels from the known total salicylate and serum albumin concentrations.
4
Transoesophageal echocardiography in the longitudinal axis: correlation between anatomy and images and its clinical implications. Transoesophageal echocardiographic imaging in the longitudinal axis is a recent addition to the non-invasive evaluation of congenital and acquired heart disease. The technique provides unique images of intracardiac anatomy but their interpretation remains difficult. A heart specimen was therefore cut according to the echocardiographic imaging planes to elucidate the morphological details. The results suggested that longitudinal transoesophageal imaging complements the transverse axis approach. It gave new imaging information on the right ventricular outflow tract and the pulmonary trunk, the atrioventricular valves, the interventricular septum, the cardiac apex, and the thoracic aorta. In particular, it showed the entire length of the right ventricular outflow tract. When longitudinal imaging was used in combination with transverse imaging almost all the thoracic aorta could be examined. Imaging in the longitudinal axis may also allow better assessment of the mechanisms of atrioventricular valve regurgitation.
3
Sumatriptan in acute migraine: pharmacology and review of world experience. The introduction of sumatriptan, a novel abortive antimigraine agent, has generated a significant amount of preclinical and clinical interest during the past few years. At the scientific level, sumatriptan is unique in terms of its selective pharmacological properties. The effects of sumatriptan in various experimental paradigms have led to new insights into the pathophysiology of migraine. At the clinical level, sumatriptan appears to be an effective abortive anti-migraine agent with minimal side effects. Its ability to decrease, rather than exacerbate, the nausea and vomiting of migraine appears to be an important advance in the treatment of migraine.
4
Postoperative active specific immunization in colorectal cancer patients with virus-modified autologous tumor-cell vaccine. First clinical results with tumor-cell vaccines modified with live but avirulent Newcastle disease virus [published erratum appears in Cancer 1991 Apr 15;67(8):2124] Sixteen patients with colorectal carcinoma Dukes' Stage B2, C, or D were treated with an autologous virus-modified tumor-cell vaccine after potential curative tumor resection (R0-Resection). An inoculum of 1 X 10(7) cells incubated with 32 hemagglutination units of nonirradiated Newcastle disease virus (NDV) was given intracutaneously up to four times at 10-day intervals. The delayed-type hypersensitivity (DTH) skin reaction was measured. The vaccination was well tolerated. In 11 of 16 patients an increasing reactivity against the vaccine was observed during the vaccination procedure. A challenge test using autologous tumor cells without NDV after the vaccination cycle revealed a specific antitumor sensibilization in 12 patients. The DTH response was not due to bacterial contamination or sensibility to the virus. Histologic examination of the vaccination site showed a dense infiltration of predominantly helper T-lymphocytes. We conclude that in most of the patients treated active, specific immunization led to a specific antitumor sensitivity.
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Interleukin-6 (IL-6) is an intermediate in IL-1-induced proliferation of leukemic human megakaryoblasts. We have examined the in vitro effects of recombinant human (rh) interleukin-1 (IL-1) on the growth of purified megakaryoblasts obtained from patients with acute megakaryoblastic leukemia. We demonstrate that both IL-1 alpha and IL-1 beta treatment of these cells led to stimulation of DNA synthesis (as shown by increase of 3H-thymidine incorporation up to 35-fold) and also resulted in colony formation of leukemic megakaryoblasts. However, the stimulatory effect of IL-1 was dependent on endogenous production of IL-6, because addition of neutralizing monoclonal antibody (MoAb) to IL-6 abrogated the stimulatory activity of IL-1. In contrast, neutralizing MoAbs to granulocyte (G)-colony stimulating factor (CSF), granulocyte-macrophage (GM)-CSF, and macrophage (M)-CSF failed to counteract the growth-enhancing effects of IL-1. Leukemic megakaryoblasts accumulated IL-6 mRNA and released IL-6 protein into their culture supernatant when exposed to rh IL-1 but failed to disclose transcripts for G-, GM-, and M-CSF under these conditions. Analysis of IL-6 receptor (IL-6R) transcript levels demonstrated that megakaryoblasts constitutively expressed IL-6R mRNA and that these transcripts are down-regulated to undetectable levels upon exposure to IL-1 and IL-6. Increase of 3H-thymidine incorporation by megakaryoblasts could be duplicated by exogenous IL-6 that could be blocked by neutralizing MoAb to IL-6. In conclusion, our results suggest that leukemic megakaryoblasts could produce and secrete IL-6, and express IL-6R, and that the growth-enhancing effect of IL-1 on these cells is indirect, via production of IL-6 by leukemic cells.
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Recurrence of Crohn's disease after resection. Recurrent Crohn's disease develops in most patients after surgical resection if the patient is followed for sufficient time. This review examines various aspects of recurrent Crohn's disease. It is concluded that Crohn's disease is a diffuse condition of the gastrointestinal tract and that radical resection of Crohn's disease does not prevent recurrence. Assorted factors thought to be associated with recurrence are examined and the relevance of these factors to the surgeon treating Crohn's disease is discussed.
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Enlarged adenoid and adenoidectomy in adults: endoscopic approach and histopathological study. Adenoid enlargement is uncommon in adults and because examination of the nasopharynx by indirect posterior rhinoscopy is inadequate, many cases of enlarged adenoid in adults are misdiagnosed and accordingly maltreated. This study was conducted on 35 cases of enlarged adenoid aged between 20 and 42 years. The nasal endoscope was utilized to identify the adenoid mass. Adenoidectomy under transnasal endoscopic control was performed and all the excised material was sent for histopathological examination. Adenoidectomy resulted in marked improvement in 94 per cent of cases without major complications. Histopathological examination revealed non-specific inflammatory reaction in 15 cases (43 per cent), pure reactive changes, predominantly follicular hyperplasia, in two cases (6 per cent) and mixed pattern in 18 cases (51 per cent). Endoscopic follow-up for an average 17 months identified recurrence in only two patients. It was concluded that enlarged adenoid tissue in adults has some histopathological differences from that in children and adenoidectomy under transnasal endoscopic control is safe and reliable.
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Neuroendocrine activity in congestive heart failure. The increased neuroendocrine activity in patients with congestive heart failure appears to be a generalized attempt to maintain blood pressure at the expense of reduced cardiac performance and salt and water retention. It is likely that baroreceptor dysfunction contributes to increased sympathetic nervous system activity in patients with congestive heart failure. The usual tonic inhibitory messages emanating from baro- and mechanoreceptors in the great vessels and heart fail to adjust sympathetic traffic from the brain to the periphery, leading to uninhibited sympathetic tone. Arginine vasopressin and plasma renin activity may be increased secondarily; however, plasma renin activity activation could also be induced by a low-salt diet and diuretic use. Preliminary baseline data indicate that patients with left ventricular dysfunction (ejection fraction less than or equal to 35%) but no or very mild symptoms of heart failure have increased plasma levels of norepinephrine, atrial natriuretic factor and arginine vasopressin, while plasma renin activity is normal, suggesting that neuroendocrine activity contributes to the pathogenesis of congestive heart failure. Neurohormones such as angiotensin II may alter gene expression, leading to changes in the shape and size of the cell. Remodeling of the heart and blood vessels is associated with both heart failure and hypertension. Angiotensin-converting enzyme inhibitors have been demonstrated to retard or reverse the remodeling process under certain experimental conditions. Studies are currently under way to test this possibility in patients.
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Immune responses to allogeneic and xenogeneic implants of collagen and collagen derivatives. Whereas xenogeneic collagen has provided a safe and effective biomaterial for numerous medical applications, there are few instances in which data permit the correlation of the immunologic profile of well-defined devices with their clinical sequelae. A major exception is the use of injectable bovine dermal collagen for soft-tissue contour correction. The low incidence of hypersensitivity has been studied in the context of clinical efficacy and safety with several devices. The findings indicate that such immunity usually results in the manifestation of local symptoms of dermal inflammation at sites of treatment that resolve as the implant is resorbed by the host. In contrast, more immunogenic hemostatic agents may elicit a more frequent or vigorous immune response that is not clinically visible or relevant in that application. Recent experiences with collagen-based devices for the repair and regeneration of bone have also demonstrated that the presence of immunity to their collagenous or non-collagenous components does not necessarily predict adverse clinical sequelae. Indeed, numerous specific data indicate that this immunity can exist as an epiphenomenon with no effect on osteogenesis. To get a true composite picture of biocompatibility, significant steps must be taken to characterize biomaterials properly and to ensure that immunologic, clinical, histologic, and other pertinent laboratory data are viewed in relation to one another and not in isolation.
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Hemorrhoidectomy during pregnancy: risk or relief? Acute hemorrhoidal crisis can occur in the pregnant female. When medical therapy fails to relieve pain, operative intervention may be necessary. The surgeon, however, may be reluctant to operate due to potential complications to the mother and fetus. From July 1983 to July 1989, hemorrhoidectomy was performed in 25 of 12,455 pregnant women (0.2 percent) who delivered in our institution. Twenty-two women were in their third trimester, 80 percent were multiparous, and each had a remote history of hemorrhoidal symptoms, including intermittent pain, bleeding, and protrusion. Closed hemorrhoidectomy was performed under local anesthesia. The surgery was directed at removing only symptomatic disease, which included three quadrants in 14 patients, two quadrants in seven patients, and one quadrant in four patients. All patients experienced relief of intractable pain the day after surgery, except one patient who required a hemostatic packing during the immediate post-operative period. There were no other maternal or fetal complications. Subsequent follow-up for anorectal disease ranged from 6 months to 6 years. Six (24 percent) patients required additional hemorrhoid treatment. Hemorrhoidectomy in selected pregnant patients is safe in our experience.
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Anterior cervical discectomy and fusion. A retrospective review of 94 patients who had undergone anterior cervical discectomy and fusion was performed to analyze the result in patients who had a diagnosis of posterolateral spondylosis, disc herniation, or both. Although in 23 of 94 patients additional adjacent asymptomatic levels of spondylosis were noted, only the symptomatic levels were addressed in the 94 cases. Postoperatively two cases of dysphagia were noted, as well as a 4% pseudarthrosis rate. There was an 88% good or excellent result when no additional spondylosis was present, but only a 60% good or excellent result when just the symptomatic levels were addressed, leaving unoperated adjacent levels of spondylosis.
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Sedation for upper gastrointestinal endoscopy: results of a nationwide survey. A postal questionnaire inquiring about routine sedation and premedication practice for upper gastrointestinal endoscopy was sent to 1048 doctors. Of 665 appropriate returns, 81% were from consultant physicians and surgeons. Most endoscopists (90%) reported using an intravenous benzodiazepine for at least three quarters of endoscopies and 54% of physicians and 69% of surgeons always did so. Midazolam was the intravenous sedative used by a third of all respondents and 13% also used an additional intravenous agent, usually pethidine. Over the previous two years a total of 119 respiratory arrests, 37 cardiac arrests, and 52 deaths were identified. Adverse outcomes were reported more frequently by consultant physicians, by those who 'titrated' the intravenous sedative, and by those who used an additional intravenous agent, but were reported equally frequently by endoscopists using midazolam and endoscopists using diazepam. There is an urgent need for a prospective study to identify the circumstances and risk factors associated with adverse outcomes related to endoscopy.
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Noncoordinate regulation of alpha-1 adrenoreceptor coupling and reexpression of alpha skeletal actin in myocardial infarction-induced left ventricular failure in rats. To determine the effects of myocardial infarction-induced left ventricular failure on the regulation of surface alpha-1 adrenoreceptors and signal transduction, large infarcts were produced in rats and the animals killed seven days later. After the documentation of impaired left ventricular pump performance, radioligand binding studies of the alpha-1 adrenoreceptor, norepinephrine-stimulated phosphoinositol turnover, and ADP ribosylation of 41 kD substrate by pertussis toxin were examined in the hypertrophying unaffected myocardium. Moreover, the expression of sarcomeric actin isoforms was analyzed by Northern blots and hybridization with specific oligonucleotide probes. Alpha-1 adrenoreceptor density was found not to be altered in membranes obtained from the spared left ventricular tissue, whereas phosphoinositol turnover was increased 3.1-fold in the viable myocytes of infarcted hearts. Furthermore, pertussis toxin substrate was augmented 2.5-fold in membranes prepared from the surviving left ventricular myocardium. Finally, an upregulation of the skeletal actin isoform was detected in the tissue of the failing left ventricle. In conclusion, the possibility is raised that in the presence of severe myocardial dysfunction and ongoing reactive hypertrophy, effector pathways linked to the alpha-1 adrenoreceptor may stimulate the myocyte hypertrophic response which would tend to normalize cardiac hemodynamics. The reexpression of alpha skeletal actin may be a molecular indicator of the persistance of an overload on the myocardium.
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Analysis of the Medtronic Intact bioprosthetic valve. Effects of "zero-pressure" fixation. The long-term performance of current-design porcine xenograft valves has not been satisfactory. These valves are generally fixed at "low pressures" of about 3 to 5 mm Hg. The Medtronic Intact (Medtronic, Inc., Minneapolis, Minn.) valve is fixed at "zero pressure" and is proposed as a better alternative to existing xenograft valves. A mechanical analysis of this valve has been carried out to determine if the Intact valve differs significantly from the low-pressure fixed xenograft. Twelve circumferential strips of tissue 5 mm wide were cut from the leaflets of four clinical-grade Intact valves. Their stress/strain, stress relaxation, and flexural behavior were examined mechanically and histologically. The Intact valve was more extensible than the low-pressure fixed xenograft (22% versus 12% strain, p less than 0.001), relaxed faster (p less than 0.001), and was more pliable than the xenograft (p less than 0.05). It did not, however, buckle less than did the low-pressure fixed xenograft during enforced bending, and it buckled significantly more than did fresh porcine aortic valve tissue (p less than 0.001). The Intact valve also relaxed significantly more slowly than did the fresh tissue (p less than 0.05). Its bending stiffness had a stronger dependence on leaflet thickness than the bending thickness of fresh tissue had (p less than 0.001) but a weaker dependence than the bending thickness of the low-pressure fixed xenograft material had (p less than 0.001). The Intact valve demonstrated a very large variability in extensibility, bending stiffness, and buckling behavior, with little correlation between these parameters. Some valves appeared to have wrinkled leaflets; others were likely fixed at different pressures. The shrinkage of the leaflet material at these low fixation pressures is likely important, since it can modify the elastic behavior of the valve cusps. Overall, the Intact valve had a more "natural" elastic behavior than had low-pressure fixed xenograft, and it should therefore experience lower stresses during normal valve function. It can be concluded that zero-pressure fixation does preserve many of the desirable stress-reducing properties of aortic valve tissue.
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Left ventricular rupture complicating percutaneous mitral commissurotomy: salvage using percutaneous cardiopulmonary bypass support. Left ventricular rupture resulting in death has been reported to be a complication of percutaneous mitral commissurotomy. We report a 71-year-old man in whom a left ventricular rupture occurred during percutaneous mitral commissurotomy and resulted in hemodynamic collapse due to acute cardiac tamponade. The patient was stabilized using percutaneously instituted cardiopulmonary bypass support with subsequent repair of the left ventricle and successful mitral valve replacement. Three months later this patient remains in New York Heart Class I.
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Perianal appearances associated with constipation. The perianal appearances were studied prospectively of 136 constipated children (mean age 3.9 years, 67 boys, 69 girls). Anal dilatation, fissures, tags, warts, perianal oedema, redness, blueness, and veins were recorded. It was noted whether dilatation occurred immediately or at 30 and 60 seconds with the buttocks minimally separated, and on subsequent firm lateral traction of the buttocks. The degree of faecal loading was assessed in all children. Anal dilatation was found in 24 (18%) and first appeared on lateral traction in eight (6%). In three quarters of the children with dilatation faecal loading or perianal signs were present. Fissures were found in 35 (26%) children and tags in seven (5%). Perianal redness was more likely to be associated with fissures, and blueness with dilatation. We conclude that there are no pathognomonic perianal signs in childhood constipation and that the technique of anal examination should be standardised.
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Magnetic resonance imaging for ineffectual tarsal tunnel surgical treatment. Tarsal tunnel syndrome (TTS) is an entrapment neuropathy caused by compression of the posterior tibial nerve beneath the ankle flexor retinaculum. Treatment of TTS consists of surgical release of the retinaculum. The failure rate is 10%-20%. Magnetic resonance (MR) imaging was used to evaluate a patient with an unsatisfactory response. MR imaging demonstrated incompleteness of the surgical release of the flexor retinaculum.
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Analysis of base station morphine orders: assessment of supervising physician consistency. Paramedic contact with a base station should gemerate consistent recommendations reflecting a consensus of base station physician care. In our urban EMS system, paramedics must contact a single base station to provide morphine sulfate (MS) for a patient with chest pain. We performed a retrospective cohort analysis of all prehospital MS requests for chest pain to determine the consistency of the circumstances for which the paramedic team was refused MS. These MS requests represented 123 of the 1,715 (7%) on-line physician consultations during the 6-month study. Only 15 of the 123 (12%) MS requests were refused. Neither the mean patient age, sex distribution, or presenting vital signs correlated with MS refusal. A maximum estimate of transport time to the hospital of less than or equal to 5 minutes was noted for 7 of 15 (47%) medication refusals compared to only 11 of 96 (11%) approvals with documented estimated transport times (P less than or equal to 0.005). A simultaneous request for nitroglycerin (NTG) was noted for 6 of the 15 (40%) medication refusals and 15 of the 108 (14%) approvals (P less than 0.05). We found refusal of MS administration to be uncommon. Supervising physicians tended to refuse MS when the transport time was short and when NTG was requested for concomitant administration. We also noted physician inconsistencies in refusal scenarios. These findings can guide physician consensus development to avoid sending mixed messages to paramedics.
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Flow cytometric DNA-ploidy analysis of synchronously occurring multiple malignant tumors of the female genital tract. In this study the authors applied flow cytometric DNA-ploidy analysis to multiple female genital tract malignant tumors in 43 patients, most of whom (n = 37) had bilateral ovarian cancer. An algorithm was developed for calculation of the likelihood ratio of the probabilities that measured DNA index differences between multiple tumor localizations within the same patient could be attributed to measurement variation or to true biologic DNA content differences. The results of this statistical analysis show that in 72% of the cases (31 of 43) this probability ratio exceeded 1. Because the probability that two independent tumors will have a near-identical aneuploid DNA content is very low, this finding supports a metastatic process rather than the occurrence of multiple primary tumors in these patients. Thus, flow cytometric DNA-ploidy analysis can be helpful in the identification of metastatic disease in patients with multiple female genital tract malignant tumors.
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Successful mitral valvuloplasty using the Inoue balloon in a patient with mitral stenosis associated with subvalvular fibrosis and reduced left ventricular inflow cavity: a case report. Percutaneous transvenous mitral valvuloplasty (PTMV) was performed with two cylindric pigtail balloon catheters in a 52-year-old woman with symptomatic mitral stenosis. The subvalvular apparatus was fibrous with welded chordae and the subvalvular left ventricular space was markedly reduced. As a result of this distorted anatomy, during the inflations, the two balloons constantly slipped back into the left atrium before full inflation was obtained. After the procedure, the mitral valve area (MVA), as estimated by echo-doppler (ED), increased from 1.00 to 1.34 cm2. After 2 months of mild clinical improvement, the patient again became symptomatic and ED examination showed a MVA of 1.25 cm2. A second PTMV was performed with an Inoue balloon, the entire procedure taking less than 1 hour. A stable position of the Inoue balloon and complete dilatation were achieved. ED examination showed a mitral valve area of 2.30 cm2. There was no mitral regurgitation nor atrial septal defect. After 3 months, she has only N.Y.H.A. class I symptoms and MVA, as estimated by ED, was 2.40 cm2.
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Late complications in pediatric cardiac transplant recipients. Late complications occurring more than 3 months after cardiac transplantation were analyzed in 29 pediatric patients in whom 31 cardiac transplantations were performed. Age at transplantation ranged from 3 months to 18 years (mean, 11.3 years) with follow-up ranging from 3.5 to 54 months (mean, 21.6 months). There were seven late deaths and two patients with retransplantations. Of nine grafts lost, eight were due to acute rejection, and one was due to coronary disease. Four of the grafts lost were secondary to patient noncompliance with prescribed immunosuppression. The mean rejection frequency more than 1 year after cardiac transplantation was significantly higher in those patients who eventually lost their grafts; however, these patients could not be distinguished by their rejection frequency in the first year. Eight patients had coronary disease, with five diagnosed at autopsy, two at cardiac retransplantation, and one by angiography. All eight patients were on double immunosuppression; none of the 19 patients on triple therapy had coronary disease with similar follow-up. There were 12 serious infections in eight patients (four associated with OKT3) with no deaths. Five patients had arrhythmias requiring treatment including two pacemakers; four of the five were associated with rejection episodes. Twelve of 29 patients developed early hypertension, and five developed late hypertension (greater than 1 year). There were two malignancies; one patient with Hodgkin's lymphoma was cured with chemotherapy, and one patient with histiocytic lymphoma was discovered at autopsy. Two patients had cholecystectomies, and five patients required laser gingivectomies.
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Hepatic lesions in the rabbit induced by acoustic cavitation. Tissue damage during shock-wave lithotripsy is presumably secondary to cavitation phenomena involving the collapsus of gas bubbles in a fluid. To enhance shock-wave-related hepatic lesions, intravascular gas microbubbles were administered. Three groups of eight rabbits each received either 500 shock waves focused on the right hepatic lobe (group 1), gas microbubbles as a mixture of 50 cm3 of air with 50 cm3 of gelatin infused through an arterial catheter (group 2), or 500 shock waves and gas microbubbles simultaneously (group 3). In group 1, two animals had two to three subcapsular hepatic hematomas (diameter, less than 5 mm) and five had one to five intraparenchymal hematomas (less than 1 mm). In group 2, a moderate liver congestion was observed in three animals. In group 3, all animals had numerous subcapsular and intraperenchymal hematomas (2-30 mm). The hematomas were centered around the portal spaces, associated with lacunae (0.5-5 mm in diameter). Hematomas were also present on the anterior wall of intraabdominal organs. It was concluded that intravascular infusion of gas microbubbles into the path of a shock-wave generator dramatically enhances tissue damage. This technique, potentially useful in the treatment of hepatic tumors, needs refinement to confine lesions in a more uniform pattern to the targeted parenchyma.
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Multicenter trial of L-carnitine in maintenance hemodialysis patients. II. Clinical and biochemical effects. Since carnitine deficiency has been reported in some patients undergoing maintenance hemodialysis, we studied the effects of intravenous infusion of L-carnitine or placebo at the end of each dialysis treatment. The trial, which lasted seven months (one month baseline, 6 months treatment) was multicenter, double blind, placebo controlled, and randomized. Eighty-two long-term hemodialysis patients, who were given either carnitine (N = 38) or placebo (N = 44), completed this study. In each group, clinical and biochemical parameters during treatment were compared with baseline values. Intra-dialytic hypotension and muscle cramps were reduced only in the carnitine treated group, while improvement in post-dialysis asthenia was noticed in both carnitine and placebo groups. Maximal oxygen consumption, measured during a progressive work exercise test, improved significantly in the carnitine group (111 +/- 50 ml/min. P less than 0.03) and was unchanged in the placebo group. L-carnitine treatment was associated with a significant drop in pre-dialysis concentrations of serum urea nitrogen, creatinine and phosphorus (means +/- SEM, 101 +/- 4.5 to 84 +/- 3.9, 16.7 +/- 0.67 to 14.7 +/- 0.64, and 6.4 +/- 0.3 to 5.5 +/- 0.4 mg/dl, respectively, P less than 0.004). No significant changes in any of these variables were noticed in the placebo group. Mid-arm circumference and triceps skinfold thickness were measured in 11 carnitine and 13 placebo treated patients. Calculated mid-arm muscle area increased in the carnitine patients (41.37 +/- 2.68 to 45.6 +/- 2.82 cm2, P = 0.05) and remained unchanged in the placebo patients.
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Myocarditis simulating acute transmural myocardial infarction. A patient with cardiogenic shock had typical electrocardiographic findings of acute anterior transmural myocardial infarction. Cardiac catheterization revealed normal coronary arteries and severe biventricular failure. Postmortem examination confirmed normal coronary arteries; acute myocarditis, but no evidence for infarction, was found. Electrocardiographic changes of myocarditis may be indistinguishable from acute transmural infarction. In suspected cases, cardiac catheterization should be considered prior to thrombolytic therapy.
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Beta camera for static and dynamic imaging of charged-particle emitting radionuclides in biologic samples. A detection system based on microchannel plates has been constructed to image charged particles emitted by radionuclides in biomedical samples. This technique has significant advantages over conventional film autoradiography for investigating the distribution of radiolabeled compounds: shorter acquisition times due to the high sensitivity, easier sample handling, direct quantification and the ability to perform dynamic studies. The detector performance shows a spatial resolution of 0.9 mm for carbon-14 (14C) (0.156 MeV), good linearity and homogeneity. The noise level is below 50/(cm2.sec). Successful imaging with this system has been performed with beta-emitters 14C, sulfur-35 (35S), iodine-131 (131I), yttrium-90 (90Y), and positron emitters gallium-68 (68Ga), and fluorine-18 (18F). Dynamic studies of axonal transport of 35S-methionine in a nerve, and static images of 90Y-labeled monoclonal antibodies in slices of tumors are presented. The system shows promise for rapid quantitative imaging of charged-particle emitting radionuclides in small biologic samples.
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Endoscopic laser surgery for early glottic carcinoma: a clinical and experimental study. The purpose of this study is to define the indications for using the CO2 laser for the treatment of early glottic cancer. For this purpose, 52 consecutive laser resections of Tis to T2 vocal cord carcinomas were studied prospectively. In addition, laser resection was performed in eight human cadaver larynges, which were then examined histologically using whole organ sections. Both tumor size and tumor location had important influences on tumor resectability by laser. All of the Tis, 78% of T1, and one of four T2 carcinomas were successfully treated by laser surgery alone. Of the 10 carcinomas involving the anterior commissure, only four could completely be resected with the laser; of these four, two recurred in the anterior commissure. This finding is corroborated by the histologic study, which clearly shows that anterior commissure resection poses problems. The only laser resection complication of early glottic cancer was persistent hoarseness in one third of the patients. It is concluded that CO2 laser resection is a safe and effective alternative treatment for patients with Tis and T1 glottic carcinoma, provided the anterior commissure is free of tumor.
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A phase II clinical trial of carboplatin infusion in high-risk acute nonlymphoblastic leukemia. Carboplatin (CBDCA) is a second-generation platinum drug that has been shown to be useful when used as a continuous infusion in treatment of refractory adult leukemia. We report on the effectiveness of continuous infusion CBDCA, 300 mg/m2/d x 5 days, as evaluated in nine patients with secondary acute nonlymphocytic leukemia (ANLL) (seven previous myelodysplastic syndrome and two treatment-associated ANLL), three ANLL patients in first relapse, six refractory ANLL, and nine patients with blastic phase of chronic myelogenous leukemia (BP-CML). All patients were considered assessable. The response rate was 44% (eight complete remissions [CRs], four partial remissions [PRs]). Median duration of postchemotherapy neutropenia was 36 days (range, 18 to 45). Therapy was well tolerated, and toxicity was mainly hematologic and nondose-limiting. Despite prolonged neutropenia, severe infections were rarely seen, and most patients were managed as outpatients. Twelve patients had nausea and vomiting, two had symptomatic hypomagnesemia, and one patient showed reversible ototoxicity. Because of substantial antileukemic activity and unusual extrahematologic toxicity, CBDCA appears to be an effective second-line agent in the treatment of ANLL and should be considered for upgrading to first-line treatment regimens.
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Treatment of patients with advanced colorectal cancer with cisplatin, 5-fluorouracil, and leucovorin. Based on in vitro studies that have demonstrated synergy between 5-fluorouracil (5-FU), leucovorin (LV), and cisplatin (CDDP) against human colon cancer cell lines, a clinical trial was initiated to determine the effects of this combination in patients with advanced unresectable colorectal carcinoma. Fifty-nine patients were enrolled in the study and 12 of them had received prior conventional 5-FU chemotherapy. Treatment consisted of 4 weekly courses of high-dose LV (200 mg/m2) administered by intravenous (IV) bolus, followed by 5-FU (550 mg/m2) and CDDP (20 mg/m2) each administered as a 2-hour infusion on 4 consecutive days. After a median of 5.5 treatment cycles, objective tumor response was seen in 20 of 59 patients (34%) (this included 3 complete remissions). The response rate in the 47 previously untreated patients was 38% (95% confidence limits, 26% to 53%). Stable disease occurred in 16 (27%) patients, whereas the tumor progressed in 23 (39%) patients. The median survival time was 11.5 months, with 15% of the patients alive at 2 years. The regimen was well tolerated and the primary side effects were mild and reversible gastrointestinal symptoms and myelosuppression. There was no episode of life-threatening toxicity. Eastern Cooperative Oncology Group (ECOG) Grade III adverse reactions that required 25% dose reductions occurred in only 14% of the patients. The results of this trial suggest that 5-FU, LV, and CDDP is an active, safe, and well-tolerated combination regimen in patients with advanced colorectal cancer.
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Medicare Peer Review Organization preprocedure review criteria. An analysis of criteria for three procedures The Medicare Peer Review Organization (PRO) program includes preprocedure review using explicit criteria to assess the appropriateness of specific procedures. This study evaluates the variability in the PRO preprocedure criteria for the three procedures most frequently reviewed by PROs: carotid endarterectomy, cataract removal, and cardiac pacemaker implants. In August 1989, the PRO review criteria were received from the Health Care Financing Administration. To provide a reference point for reviewing the PRO criteria, national practice guidelines for these three procedures were identified. Wide variability was demonstrated in the PRO procedure-specific carotid endarterectomy and cataract removal review criteria among PROs, and the criteria differed significantly from the identified practice guidelines. The criteria for cardiac pacemaker implants were somewhat less variable, and were based, to varying degrees, on practice guidelines developed by the American College of Cardiology (ACC). Greater attention is needed to improve the development of review criteria, including the use of relevant practice guidelines, to ensure that review criteria are optimal.
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Natural history of progressive ischemic stroke in a population treated with heparin Data on the acute natural history of progressive stroke with or without heparin treatment are limited. To define the acute course of patients treated with heparin for progressive stroke, we examined the charts of 69 such patients identified through the Cornell Neurology Database from October 1979 to June 1985. Analysis included determining whether further clinical deterioration or hemorrhagic complications were associated with readily identifiable clinical or laboratory variables. Twenty-five patients (36%) continued to deteriorate while receiving heparin, another two (3%) worsened due to intracerebral hemorrhage, and a total of 10 patients (14%) had bleeding complications. No clinical features or heparin dosing regimens distinguished the patients likely to benefit from heparin. Clinical progression or hemorrhage did not correlate with the level of anticoagulation as measured by the average heparin dose per day or the mean partial thromboplastin time. Without unequivocal evidence demonstrating heparin's ineffectiveness for progressive stroke, many clinicians managing such patients will continue to use heparin. Our results suggest that this decision should not be governed by such clinical features as a patient's age or sex or by the vascular distribution of the stroke. Furthermore, frequent measurement of and overzealous efforts to adjust the partial thromboplastin time may be unnecessary since it does not correlate with outcome.
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Coronary ostial reconstruction: technical issues. Coronary ostial reconstruction may be the preferred alternative to reestablish antegrade myocardial revascularization in patients with isolated ostial stenosis. The technical steps of reconstruction are described. The ultrasonic aspirator is a helpful implement in the dissection of the left main and the proximal right coronary arteries. Satisfactory results of coronary ostial reconstruction in the current era seem to fulfill its promise.
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Autonomic nervous system and coronary blood flow changes related to emotional activation and sleep. Experimental models have been developed to investigate the influences of anger, fear, and sleep on coronary blood flow. Studies of anger in dogs with coronary stenosis indicate that the postarousal phase is particularly conducive to myocardial ischemia. Specifically, a delayed coronary vasoconstrictor response has been observed within 1-3 minutes after cessation of behavioral arousal. The response is prevented by bilateral stellectomy and can be elicited in anesthetized animals by electrical stimulation of the right or left stellate ganglion. The latter effect is averted by alpha-adrenergic blockade with prazosin. Although the basis for the protracted nature of the delayed vasoconstriction remains to be clarified, the current hypothesis is that the phenomenon results from a time-dependent imbalance between the vasoconstrictor effects of adrenergic input and the vasodilator influences of coronary pressure and/or cardiac metabolic activity. A behavioral model emulating the fear state has also been developed. When dogs that fail to exhibit anger are placed in a food-access confrontation protocol, the animals demonstrate a fearlike state evidenced by a cowering posture and somatic tremor. There is a distinct plasma catecholamine profile that is characterized by a predominant increase in epinephrine compared with norepinephrine. This is in contrast to the pattern observed during anger, in which a prevalent increase in norepinephrine is observed. Fear results in significant increases in heart rate, arterial blood pressure, and coronary arterial flow. Sleep is also associated with substantial alterations in coronary hemodynamic function.
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Heritability of symptoms in an experimental model of neuropathic pain. Male and female rats underwent transection and ligation of the sciatic and saphenous nerves, and the development of autonomy was monitored. The deafferented animals were then interbred, always selecting males and females that expressed relatively high and, alternatively, relatively low levels of autotomy. Offspring were similarly operated and interbred. By the sixth generation of selective breeding, lines were achieved in which autotomy was consistently high (HA) or consistently low (LA). There was no indication of sex linkage. Thermal and mechanical nocifensive responsiveness co-selected with propensity to express autotomy following nerve injury: response thresholds were lower in HA than in LA rats. F1 hybrids formed by crossing homozygous HA and LA animals showed low levels of autotomy, similar to LA stock. This indicates recessive inheritance of the autotomy trait. Backcrossing F1 hybrids onto the LA line yielded a low autotomy phenotype in almost all cases; backcrossing F1 hybrids onto HA stock yielded about 50% high autotomy and 50% low autotomy. These ratios are consistent with simple mendelian inheritance of a single gene. Taken together, the data suggest that autotomy is inherited as a single-gene autosomal recessive trait.
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Quantitative assessment of extradural bupivacaine analgesia. Bupivacaine (0.5%) 20 ml was administered extradurally to six healthy volunteers. It was found that simultaneous application of 10 needles to the skin could evoke pain when analgesia was obtained to one needle stimulation. In addition, a laser beam was used as a quantitative technique to activate simultaneously many cutaneous nociceptors. For 7 h, thresholds (sensory and pain) and pain-evoked brain potentials (amplitude and latency) to laser stimulation were monitored and used for quantitative assessment of onset, efficacy and duration of analgesia at various dermatomes (C7, T8, T10, T12, L1, L3, S1). The onset time of analgesia was shortest and conduction delay longest at the dermatome related to the site of injection (L3). Full analgesia was obtained at L1, L3 and S1, although the peak efficacy at S1 was delayed for 120-180 min after injection. A minor effect was found at dermatome C7 approximately 60 min after injection.
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Bacterial overgrowth and intestinal atrophy in the etiology of gut barrier failure in the rat. Bacterial translocation occurs in animal models of shock, trauma, sepsis, and parenteral or elemental enteral alimentation. Bowel atrophy and cecal bacterial overgrowth have both been implicated in the pathophysiology of bacterial translocation in many of these models. To further define the etiology of bacterial translocation resulting from dietary manipulations, rats were fed a elemental/defined-formula diet (DFD) for 2 weeks ad libitum and then randomized to either intestinal decontamination with a nonabsorbable antibiotic (neomycin) or no antibiotic treatment. Neomycin treatment significantly (p less than 0.01) reduced the incidence of bacterial translocation after DFD, in association with a significant reduction in the number of cecal gram-negative bacteria. Neither loss of bowel mass after DFD nor bowel composition was affected by oral neomycin. Bacterial translocation after DFD would thus appear to be the result of cecal bacterial overgrowth rather than a loss of a physical intestinal barrier due to atrophy.
4
Insulinomas: localization with selective intraarterial injection of calcium. To facilitate the noninvasive preoperative localization of islet cell tumors less than 15 mm in diameter, the authors examined the use of calcium as an insulin secretagogue in an arterial stimulation venous sampling (ASVS) technique. In four patients with episodic hypoglycemia, calcium gluconate (0.01-0.025 mEq Ca2+/kg) was injected directly into branches of the celiac plexus (gastroduodenal, splenic, and hepatic arteries) and the superior mesenteric artery. In all patients, serum levels of insulin rose abruptly in blood samples taken from the right hepatic vein 30 and 60 seconds after the infusion of calcium into the artery supplying the tumor; injection into an artery not supplying the tumor did not result in a similar rise. Accurate localization of the insulinomas was verified at surgery in three patients. In the fourth patient, who did not undergo surgery, arteriographic results were positive for insulinoma at the predicted site. On the basis of these results, the authors believe noninvasive ASVS may replace invasive portal venous sampling as the most effective method for the localization of occult insulinomas.
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Ultrastructural demonstration of peroxidase expression in acute unclassified leukemias: correlation to immunophenotype and treatment outcome. The lineage affinity of 57 cases of acute unclassified leukemias (AUL) was reevaluated by ultrastructural analysis of peroxidase expression (POEM) in combination with immunophenotyping and analysis of immunoglobulin gene configuration. Twenty-three cases of myeloid and three cases of megakaryocytic differentiation were identified by detection of ultrastructural myeloperoxidase (UMPO) and platelet peroxidase (UPPO). No significant correlation was noted between myeloid marker expression and POEM positivity, whereas presence of CD 19 or CD 24 antigen significantly correlated with POEM negativity (P = .001 and .023, respectively). Ig gene rearrangements including oligoclonal patterns were also recorded in 8 of 14 UMPO+ patients tested. Fourteen UMPO+ patients responded poorly to an ALL/AUL chemotherapy regimen with a low complete remission (CR) rate of 29% and a short median remission duration (MRD) of 5 months. The POEM- patients proved very heterogenous with respect to immunophenotype and Ig gene rearrangement. Seventeen of 21 patients tested had Ig gene rearrangements, including oligoclonal patterns. Combined data suggest that a proportion of these cases probably derive from a very immature lymphoid progenitor cell, particularly because 15 POEM- AUL patients showed a response to ALL/AUL chemotherapy comparable to that observed in patients with definitive acute lymphoblastic leukemia (ALL) (CR rate 80%, MRD 20 months). Thus, ultrastructural analysis of peroxidase expression can provide decisive prognostic information in AUL patients.
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Characterization of a rat pancreatic secretory protein associated with pancreatitis. A new protein was purified from the pancreatic juice of rats with acute pancreatitis. That protein, not detectable in control animals, was called "pancreatitis-associated protein." It was first observed 6 hours after induction of experimental pancreatitis with taurocholate or cerulein, reached maximal levels of 45 micrograms/mg protein in zymogen granules and 1.8 micrograms/mg protein in pancreatic tissue during the acute phase (48 hours), and disappeared during recovery (day 5). It was never detected in spleen, liver, kidney, heart, or lung. The detection limit of the assay system was 12 ng/mg protein, so that pancreatitis-associated protein levels increased at least 100-fold in pancreatic tissue during the acute phase. The molecular weight (12,000) and isoelectric point (8.2) were determined by two-dimensional gel electrophoresis. Subcellular fractionation and immunoelectron microscopy showed that the protein was synthesized on the rough endoplasmic reticulum and stored in zymogen granules before being secreted, similar to other pancreatic secretory proteins. Immunoblotting and two-dimensional gel electrophoresis revealed that the same protein was synthesized upon induction of pancreatitis by cerulein infusion, by retrograde injection of bile acids, or pancreatitis induced by pancreatic surgery. The pancreatitis-associated protein is therefore an acute-phase protein that differs from other proteins of that family because of its exocrine nature.
4
Altered waveform of plasma nocturnal melatonin secretion in premenstrual depression. The nocturnal secretion of plasma melatonin was determined under dim to dark conditions in eight patients with prospectively confirmed premenstrual syndrome and in eight age- and menstrual cycle phase-matched normal control subjects. Plasma samples for melatonin were collected every 30 minutes from 6 PM to 9 AM during the early follicular, late follicular, midluteal and late luteal phases of the menstrual cycle. Compared with normal controls, patients with premenstrual syndrome had an earlier (phase-advanced) offset of melatonin secretion, which contributed to a shorter secretion duration and a decreased area under the curve. No statistically significant differences were found between women with premenstrual syndrome and normal controls for melatonin onset or peak concentration, or for estradiol or progesterone levels. The data demonstrate that women with premenstrual syndrome have chronobiological abnormalities of melatonin secretion. The fact that these patients respond to treatments that affect circadian physiology, such as sleep deprivation and phototherapy, suggests that circadian abnormalities may contribute to the pathogenesis of premenstrual syndrome.
2
Cocaine babies: the scourge of the '90s. Six cases of cocaine-related deaths of infants have covered the spectrum of potentially devastating effects. They include an intrauterine death of a 35-week-old fetus following acute maternal cocaine abuse; anoxic encephalopathy at birth with 3 months' vegetative survival from a similar episode; traumatic compression asphyxia in a 4-month-old; infectious cardiomyopathy with heart failure in a twin at age 21 months following maternal cocaine abuse at birth; malnutrition and dehydration in a 7-week-old during continuing cocaine abuse by the parents; and a teenage sibling's cocaine lacing of a baby milk bottle ingested by his 6-week-old brother. All the cases had positive toxicological screening for cocaine or metabolites or both in the mother at delivery or in the infant at birth, or both. There were no instances of sudden infant death syndrome (SIDS, or "crib death"). Pathologic and toxicologic, as well as birth, developmental, and social data are presented. An integrated medical, public health, law enforcement, and educational policy to prevent or at least ameliorate these tragic cases, now approaching epidemic proportions, has yet to be developed. A careful obstetrical history and examination of the mother, indication on the birth certificate of maternal drug abuse, and notification of health authorities (by birth certificate checking, among other ways) may send an early warning message to providers for intercession. Active ingestion/injection and passive inhalation by older children and teenagers require more intensive monitoring and aggressive interaction by pediatricians, social workers, school authorities, and employers.
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Late postoperative episodic and constant hypoxaemia and associated ECG abnormalities. Twenty-two patients without cardiopulmonary disease and undergoing elective major abdominal surgery were monitored continuously with a Holter tape recorder and a pulse oximeter on one night before operation and the first two nights after operation (23:00 to 07:00), without oxygen therapy. Mean heart rate increased 16 beat min-1 (P less than 0.001) and mean oxygen saturation (SaO2) decreased 2.6% (P less than 0.001) after operation. Episodic oxygen desaturation to less than 80% occurred in four patients before operation, but in 13 patients after operation (P less than 0.05). ECG abnormalities were observed in 10 patients before operation and in 16 patients after operation (ns). Individual maximum ST depression was more pronounced after than before operation (P less than 0.05). Episodic desaturation was related closely to tachycardia in six patients before operation and one patient after operation; before operation to atrioventricular block in one patient, and after operation to ST depression in two patients. Mean SaO2 on the second night after operation correlated with total dose of opioid for pain relief (rs = -0.48; P less than 0.05), and postoperative decrease in SaO2 correlated with postoperative increase in heart rate (rs = -0.43; P less than 0.05). No patient had postoperative cardiac complications indicating treatment.
4
Image cytophotometric DNA analysis of atypical hyperplasias and intraductal carcinomas of the breast. With the use of image analysis, DNA content was quantified on paraffin-embedded tissue sections of 25 atypical hyperplasias and 35 intraductal carcinomas of the breast by comparison of integrated gray levels of Feulgen-stained control and ductal cell nuclei. The mean full-peak (G0/G1) control cell DNA histogram coefficient of variation was 5.5%. DNA aneuploidy was more common in intraductal carcinomas compared with atypical hyperplasias (71% of intraductal carcinomas vs 36% of atypical hyperplasias) and correlated with a lack of cytologic (nuclear) and architectural differentiation (63% moderate vs 93% poor and 38% cribriform vs 82% solid). In addition, multiple DNA stemlines were observed in 40% of intraductal carcinomas. We conclude that (1) some atypical hyperplasias demonstrate abnormal DNA content consistent with neoplastic transformation, (2) aggressive forms of intraductal carcinoma are more frequently associated with DNA content abnormalities, and (3) frequent DNA stemline heterogeneity in intraductal carcinoma supports the hypothesis that multiple genetic events occur in the development of mammary intraepithelial neoplasia.
4
The significance of Leu 8 negative T cells in lymphoid skin infiltrates: malignant transformation, selective homing or T-cell activation? The expression of Leu 8 was studied on skin biopsies from a large group of patients with benign and malignant skin disorders and correlated with the expression of T-cell differentiation antigens and activation markers. The effect of in vitro stimulation of peripheral blood T cells and T-cell subsets on the expression of Leu 8 antigen was also determined. In all the skin diseases studied an inverse relationship was found between the proportions of cells expressing Leu 8 and HLA-DR. A deficiency of Leu 8 positive cells was not specific for mycosis fungoides, but was also found in several reactive dermatoses. Stimulation of peripheral blood cells with phytohaemagglutinin (PHA), concanavalin A (Con A), and anti-CD3-PMA resulted in a considerable decrease of Leu 8 antigen expression on day 3 in both CD4+ and CD8+ T cells. These data suggest that the low proportion of Leu 8+ T cells in mycosis fungoides and several reactive skin disorders is not related to malignant transformation or selective homing of Leu 8- T cells, but probably results from local T-cell activation.
4
Plasma fatty acid profile in advanced cirrhosis: unsaturation deficit of lipid fractions. Fatty acid (FA) profile of plasma total lipids, phospholipids (PL), cholesteryl esters (CE), and triglycerides (TG) were measured in 101 patients with advanced liver cirrhosis and in 44 age- and sex-matched healthy controls. Plasma levels of lipidic phosphorus, esterified cholesterol, and TG also were measured, and the unsaturation index (UI) was calculated for each fraction. Total plasma concentrations of saturated FA, linoleate, and polyunsaturated FA (PUFA) were lower in cirrhotics than in controls. This profile was also found in plasma levels of PL- and CE-associated FA. No detectable amounts of C20:3n9 were found in cirrhotic patients. Percent FA distribution of lipid fractions showed a lower percentage of linoleate and PUFA and a higher relative amount of saturated and monoenoic FA in cirrhotics than in controls. As a consequence, the UI of PL and CE was diminished in liver cirrhosis. Linoleate and PUFA deficiency was more marked in CE than in PL, as shown by the number of patients with values below the 5th percentile of the control group, suggesting an attempt to maintain the unsaturation of PL as the most important component of cell membranes. Hepatic failure, poor essential FA intake, and malnutrition are some of the possible etiologic factors for PUFA deficiency in cirrhosis. Their relative contribution to plasma FA abnormalities, as well as the clinical and pathophysiological consequences of PUFA deficit in cirrhotic patients, requires further investigation.
1
Strokes in Asians and Pacific-Islanders, Hispanics, and Native Americans. Stroke in Asian and Pacific-Islander populations remains the principal cause of death among adults, but its incidence in the United States approximates that of Caucasians. Although controversial, uncontrolled hypertension in certain population groups (e.g., northern Japanese) and high dietary saturated fat in others (e.g, Pacific-Islanders) are believed to be responsible for the high stroke incidence rates. The recent reduction in stroke frequency rates in these areas is thought to be the result of better hypertension control. In the Ni-Hon-San Study, the level of hypertension and its frequency were similar in Hawaii and Japan, but ischemic infarction and intracerebral hemorrhage were less frequent in Hawaii. Reduced meat and fat intake may contribute to small vessel disease in Japan. Stroke is the third major cause of death among Hispanic-Americans and Native Americans, yet there is a paucity of information, especially about stroke, in subgroups of these populations. There is also considerable ignorance and controversy about risk factors for stroke in these populations. The need for additional research is urgent.
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Somatostatin-receptor imaging in the localization of endocrine tumors BACKGROUND AND METHODS. A number of different tumors have receptors for somatostatin. We evaluated the efficacy of scanning with 123I-labeled Tyr3-octreotide, a somatostatin analogue, for tumor localization in 42 patients with carcinoid tumors, pancreatic endocrine tumors, or paragangliomas. We then evaluated the response to octreotide therapy in some of these patients. RESULTS. Primary tumors or metastases, often previously unrecognized, were visualized in 12 of 13 patients with carcinoid tumors and in 7 of 9 patients with pancreatic endocrine tumors. The endocrine symptoms of these patients responded well to therapy with octreotide. Among 20 patients with paragangliomas, 8 of whom had more than one tumor, 10 temporal (tympanic or jugular), 9 carotid, and 10 vagal tumors could be visualized. One small tympanic tumor and one small carotid tumor were not seen on the scan. CONCLUSIONS. The 123I-labeled Tyr3-octreotide scanning technique is a rapid and safe procedure for the visualization of some tumors with somatostatin receptors. A positive scan may predict the ability of octreotide therapy to control symptoms of hormonal hypersecretion.
0
Changes in cardiac function during extracorporeal membrane oxygenation for persistent pulmonary hypertension in the newborn infant. The effects of extracorporeal membrane oxygenation (ECMO) on cardiac function and its determinants (preload, afterload, contractility, and heart rate) are largely unknown, although some evidence exists that function may decrease. To determine whether cardiac function decreases and what changes in the determinants take place during and after ECMO, we observed 26 newborn infants with persistent pulmonary hypertension. Serial echocardiograms were performed before ECMO, during maximum cardiopulmonary bypass, and after ECMO. Cardiac function was assessed by using standard echographic ejection phase indices (shortening fraction and cardiac output). Heart rate, preload (left ventricular end-diastolic dimension and area), afterload (left ventricular end-systolic wall stress), and contractility (relationship between velocity of circumferential fiber shortening and wall stress) were also measured. Ejection phase indices significantly decreased during ECMO (shortening fraction 33% to 25%, cardiac output 205 to 113 ml/kg/min; p less than 0.05) and returned to normal after ECMO (shortening fraction 26% to 34%, cardiac output 107 to 240 ml/kg/per minute; p less than 0.05). Heart rate also significantly decreased during ECMO (158 to 118 beats/min; p less than 0.05). Preload significantly increased after ECMO (left ventricular end-diastolic dimension 1.4 to 1.6 cm, left ventricular end-diastolic area 1.9 to 2.2 cm2; p less than 0.05). There were no significant changes in contractility and afterload during any study period. We conclude that, although left ventricular ejection phase indices and heart rate decreased during ECMO, these changes were transient and resolved when bypass was terminated. Contractility and afterload did not appear affected by bypass.
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Influence of organ environment on extracellular matrix degradative activity and metastasis of human colon carcinoma cells Orthotopic implantation of human colon carcinoma cells is useful for studying the behavior of metastatic subpopulations. We observed that the parental line and variants of human colon carcinoma KM12 cells were all tumorigenic following implantation into the subcutis or cecal wall of BALB/c nude mice. Their ability to metastasize to distant organ sites varied, however, with the site of growth. Subcutaneous (SC) tumors did not produce visceral metastases, whereas cecal tumors metastasized to the regional mesenteric lymph nodes and to the liver. To examine the influence of organ environment on the extracellular matrix-degrading activity of the tumors, we inoculated human colon carcinoma cells into the subcutis or cecal wall and after 7 weeks isolated and cultured the tumors in serum-free medium. The conditioned media of SC tumors contained very low levels of type IV collagenase (gelatinase) and heparanase (heparan sulfate-specific endo-beta-D-glucuronidase), whereas the media of the cecal wall tumors contained high levels of both. Zymograms of the media revealed that the intracecal human colon carcinomas secreted more than three times the amount of latent and active forms of 92-kd type IV collagenase than did the SC tumors. Moreover, only the conditioned media of intracecal tumors contained latent and active forms of 64-kd type IV collagenase. Histochemical analysis using rabbit antiserum raised against the synthetic peptides of 72-kd procollagenase type IV showed type IV collagenase in the intracecal tumors; human colon carcinoma growing SC, however, were not stained significantly. These results suggest that factors in the organ environment may affect production and secretion of tumor extracellular matrix-degrading enzymes, and these factors may modify the metastatic behavior of human colon carcinoma cells in nude mice.
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A comparative evaluation of the safety and efficacy of cefotetan and cefoxitin in surgical prophylaxis. Safety and efficacy were evaluated and compared retrospectively in 77 patients who received cefotetan (CTN) and 51 patients who received cefoxitin (CFX) for surgical prophylaxis. Both groups were similar with respect to age and gender. Surgical procedures were similar between groups (e.g., obstetric/gynecologic, renal transplant, colon, exploratory laparotomy, gastroduodenal, hernia repair). Postoperative infectious complications were more common in the CTN group (11.6 percent [9/77]) than in the CFX (7.8 percent [4/51]) group; however, this difference was not statistically significant. A higher incidence of wound infections was noted in the CTN group (5.2 percent [4/77]) than in the CFX group (2.0 percent [1/51]); this difference was also not significant. Patients receiving immunosuppressive therapy were more likely to develop infectious complications when CTN was used for prophylaxis (p = 0.0001). Clinically significant blood loss was not noted during surgery. Elevations in prothrombin times (greater than 1 sec) occurred in 27.3 percent (3/11) of CTN and 11.1 percent (1/9) of CFX patients (not significant). Except for the small subset of patients receiving concomitant immunosuppressive therapy, CTN appeared to be as safe and effective as CFX when used for surgical prophylaxis. Although not statistically significant, the increased incidence of wound infections in the CTN-treated patients requires further study in a prospective randomized comparison.
4
Effects of retrovenous myocardial drug delivery after coronary artery occlusion in sheep. Retrovenous (RV) myocardial delivery of blood and drugs into the coronary sinus (CS) through a 3 lumen balloon catheter was evaluated in sheep (no coronary collaterals) for protection from ventricular fibrillation (VF) during coronary artery occlusion. The balloon was asynchronously inflated (CS occlusion) for 5 sec and then deflated for 5 sec with 1 cc/sec of flow. The left anterior descending coronary artery was occluded with inflation of a percutaneous transluminal coronary angiography balloon and therapy started immediately. In a control group (no therapy, n = 4) all developed VF by 30 min after coronary artery occlusion. The drugs lidocaine (L), esmolol (E), adenosine (A), and deferoxamine (D) were evaluated for effects on eliminating developing VF with intravenous (i.v.) administration compared with RV administration with venous blood (VB) or arterial blood (AB). The percent survival after CA occlusion (no VF) was: L i.v., 0%; L RV with VB, 43%; L RV with AB, 17%; E i.v., 50%; E RV with VB, 70%; A. i.v., 29%; A RV with VB, 88%; D i.v., 17%; and D RV with AB, 80%. There was a trend toward lower myocardial necrosis (seen by tetrazolium stain and/or light microscopy) in the RV survivors (especially with VB) compared with the group i.v. survivors. These data suggest that RV antiarrhythmic drug delivery is a feasible alternative to i.v. administration during CA occlusion.
4
An analysis of abnormalities of the retinoblastoma gene in human ovarian and endometrial carcinoma. The altered expression of the human retinoblastoma (RB) gene has been demonstrated to play an important role in the pathogenesis of RB and other tumors. To determine whether the RB gene might be involved in the pathogenesis of human ovarian and endometrial cancer, DNA from 24 human ovarian tumors, 3 normal ovaries, 3 endometrial carcinomas, and 1 endometrial hyperplasia was examined with an RB complementary DNA probe. Evidence for homozygous deletion of the RB gene was observed in only one specimen. Interestingly, the specimen was an endometrioid tumor of the ovary of low malignant potential (LMP). This patient experienced rapid progression of the tumor and died 8 months after diagnosis. Abnormalities of the RB gene may be involved in the aggressive biologic behavior of certain forms of ovarian carcinoma, particularly those of LMP.
4
Giant eccrine acrospiroma. Four cases of large eccrine acrospiroma (three benign, one malignant) are reported. The benign tumors involved the lower extremities of two women and one man (73 to 89 years of age). The duration of the lesions ranged from 10 to 20 years. The malignant tumor involved the left side of the chest of a 60-year-old man. Its occurrence in a lesion that had been present for 40 years suggested malignant transformation of a pre-existing benign eccrine acrospiroma. Each tumor showed little to no cellular atypia. Mitotic rates (mitotic figures per 10 high-power fields) varied both between and within lesions. Average mitotic rates did not differentiate the benign from the malignant tumors. The most important distinguishing features of large benign eccrine acrospiromas are the relative circumscription, the lack of cellular atypia, and the absence of stromal, perineurial, and angiolymphatic invasion.
0
Platelet fatty acids and function in two distinct regions of Belgium: relationship to age and dietary habits. We compared the dietary habits, fatty acid composition of plasma and platelet phospholipids, and platelet function in two groups of healthy Belgian male subjects, known to differ in their mortality rate from coronary heart disease (CHD). In the Walloon subjects, there was a larger intake of saturated and a lower intake of (n-6) polyunsaturated fats, confirmed by the fatty acid composition of plasma and platelet phospholipids. While plasma HDL and total cholesterol were similar in the present samples of the two communities, platelet aggregation to epinephrine was significantly higher in the Walloon subjects. When the two populations were divided into younger (28-54 years) and older (55-73 years) age groups, the older Walloon subjects exhibited platelet hyper-aggregability to most of the agonists, compared to the other three groups. In addition to dietary fats, alcohol and smoking habits, age was an important determinant of platelet phospholipid fatty acids and platelet reactivity. The present results reinforce those of previous studies, indicating that platelet behaviour is significantly affected by the main risk factors for CHD.
3
Sustained increased cerebral blood flow with prophylactic hypertensive hypervolemic hemodilution ("triple-H" therapy) after subarachnoid hemorrhage. Delayed cerebral ischemia is the major cause of death and disability in patients who initially survive an aneurysmal subarachnoid hemorrhage (SAH). In the present study, a protocol for prophylactic hypertensive hypervolemic hemodilution ("triple-H" therapy) was utilized in the treatment of SAH, and the response of cerebral blood flow (CBF) was evaluated. Serial CBF measurements, f1 and CBF15, were performed using the xenon-133 inhalation technique to maximize therapy. Surgery within 24 hours of subarachnoid hemorrhage was preferred. In 43 patients with SAH, mean hemoglobin and hematocrit were lowered 3.0 +/- 0.3 g/dL and 8.9 +/- 0.5%, respectively, over the first 24 hours. Mean f1 and mean CBF15 over the same period increased 34.2 +/- 5.8% and 21.2 +/- 3.6%, respectively. The maximum mean increase in CBF was 47.2 +/- 4.7% for f1 and 30.1 +/- 3.2% for CBF15. Cerebral blood flow remained elevated during the 21 days after SAH, irrespective of neurological grade on admission, age, sex, or angiographic arterial narrowing. This is the first report of a consistent method for establishing sustained improvement in CBF after SAH. All patients managed in total compliance with the protocol remained neurologically stable or improved. Two patients developed delayed ischemia and infarction because of the inability to sustain protocol requirements. Thirty-six of the 43 patients (84%) were discharged capable of an independent lifestyle. Triple-H therapy is a safe and effective modality for elevating and sustaining CBF after SAH. In combination with early aneurysm surgery, it can minimize delayed cerebral ischemia and lead to an improved overall outcome.
3
Fenestrated atrial septal aneurysm: diagnosis by transesophageal echocardiography. The diagnosis of atrial septal defect by transthoracic echocardiography remains difficult in a small subset of patients because of either suboptimal acoustic windows or unusual anatomy, for example, fenestrated defects. We report the case of a 55-year-old woman with a fenestrated atrial septal aneurysm that was incompletely visualized by transthoracic echocardiography. Subsequent transesophageal echocardiography demonstrated three defects within the atrial septal aneurysm with left-to-right shunting across each defect. Normal pulmonary venous connections were also defined. All echocardiographic findings were confirmed at surgery. This case demonstrates the additional diagnostic accuracy of transesophageal echocardiography for detecting disease of the atrial septum.
3
Spinal glioblastomas: report of seven cases and review of the literature. Intramedullary glioblastomas are uncommon tumors. They occur chiefly in the cervicothoracic segments, have a slight tendency to occur in the early decades of life, and have a short clinical history before diagnosis. We report seven cases and discuss the salient features of these tumors, particularly the pathological features and treatment, in light of the relevant literature.
0
Dexamethasone inhibits the induction of monocyte chemotactic-activating factor production by IL-1 or tumor necrosis factor. Recently purified and molecularly cloned monocyte chemotactic and activating factor (MCAF) may play a major role in recruiting and activating monocytes in the inflammatory process. We examined the effects of a potent anti-inflammatory agent, dexamethasone (DXS), on the production of this factor. Over a wide range of concentrations (10(-5) to 10(-8) M), DXS inhibited the production of MCAF at the mRNA and protein level in a human fibrosarcoma cell line, which was stimulated with either IL-1 or TNF-alpha. We examined the turn-over of synthesized MCAF mRNA that showed DXS decreased the stability of MCAF mRNA. Furthermore, the addition of actinomycin D and cycloheximide abolished this effect of DXS, indicating that de novo mRNA and protein synthesis were required for this process. In addition, a nuclear run-off analysis revealed that DXS also inhibited the transcription of IL-1- or TNF-activated MCAF genes. Therefore, both the destabilization of MCAF mRNA and the inhibition of transcription of the gene contribute to the decrease in the MCAF mRNA steady state level by DXS.
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The validity of health risk appraisals for coronary heart disease: results from a randomized field trial. BACKGROUND: While health risk appraisals (HRAs) are becoming increasingly popular as tools for health assessment and health education, comparatively little is known about the accuracy of these risk estimates. METHODS: A field trial among 732 randomly selected adults ages 25 to 65 years was conducted to assess the validity of the risk scores produced by four widely used HRAs. RESULTS: Self-reported HRA risk scores for cigarette smoking and relative weight were generally accurate, but correlations between physiological measurements and scores for blood pressure, cholesterol, and physical activity were always lower than .51. Correlations between epidemiologic estimates of the probability of CHD death and HRA total risk scores ranged from .13 to .75; partial correlations adjusting for age, race, and gender ranged from .12 to .47. CONCLUSIONS: The HRAs chosen for the field trial exhibited modest correlations with the CHD mortality risk predicted by the epidemiologic model. Mathematical errors made by respondents completing self-scored instruments and lack of knowledge regarding physiologic status decrease the accuracy of HRA risk estimates.
3
Experience with Duraphase penile prosthesis: its use as replacement device. The Duraphase Penile Prosthesis is a new, articulating type of semirigid prosthesis which appears to have several advantages over other semirigid penile prostheses. This series describes the experience with this prosthesis in 12 patients and highlights the experience in 4 patients who underwent removal of other types of prostheses due to mechanical or functional problems and replacement with the Duraphase prosthesis. The device has been mechanically reliable during short follow-up, and there has been excellent patient satisfaction.
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Acetylsalicylic acid vs. metoprolol in migraine prophylaxis--a double-blind cross-over study. In a double blind cross-over study, 28 patients, 5 male and 23 female, aged 31 +/- 14 years, after a run-in period of 8 weeks, were treated for 3 months with acetylsalicylic acid and for another 3 months with metoprolol, both in a prophylactic mode. Attack frequency was reduced significantly with both therapeutic regimens (ASA p less than 0.001, metoprolol p less than 0.00005). Reduction of attacks below 50% was seen with metoprolol in 14 cases, and with ASA in three cases. Even though ASA was of statistically significant efficacy in migraine prophylaxis, it clearly is not the drug of first choice in migraine prophylaxis.
4
Changes in circulating norepinephrine with hemofiltration in advanced congestive heart failure. In congestive heart failure (CHF), hemofiltration is associated with an obvious decrease in circulating norepinephrine. This method was used for investigating the mechanisms whereby plasma norepinephrine is increased in chronic CHF. In 23 cases of advanced CHF, hemofiltration (2,983 +/- 1,228 ml) lowered plasma norepinephrine by 515 +/- 444 pg/ml. This effect was prompt, persisted or became greater in the next 24 hours. It was not associated with significant changes in cardiac output, aortic pressure or systemic vascular resistance. It did not appear to depend on variations in parameters related to the sympathetic activity, such as plasma renin, right atrial, wedge pulmonary artery and renal perfusion pressures, and was independent of duration and amount of hemofiltration. These observations did not support the concept that the norepinephrine decrease was the main consequence of a neural sympathetic inhibition. Hemofiltration increased diuresis by 606 +/- 415 ml; changes were prompt and correlated inversely (r = -0.7; p less than 0.01) with those in plasma norepinephrine. The same unknown mechanism of the increased urinary output might potentiate the norepinephrine removal from the blood by the kidney, or hemofiltration and the augmented diuresis might result in a regression of congestion of lungs and kidneys, leading to an improved extraction of norepinephrine. In CHF, a relation may exist between fluid retention and norepinephrine and in advanced stages, circulating norepinephrine, although strikingly increased, is devoid of important cardiovascular effects. At these stages, plasma norepinephrine is probably unreliable as an index of the sympathetic neural activity.
3
Effects of brief coronary occlusion and reperfusion on porcine coronary artery reactivity. The loss of coronary vasodilator reserve after ischemia-reperfusion may be due to endothelial injury, and this vascular dysfunction may contribute to functional alterations observed after ischemia. To determine whether endothelial dysfunction occurs after relatively brief periods of moderate low-flow ischemia in vivo, open-chest swine were subjected to 15 minutes of critical, subtotal left anterior descending coronary artery occlusion (80%) followed by 60 minutes of reperfusion. Serial measurements of regional coronary flow were made with the radiolabeled microsphere technique. After 60 minutes of reperfusion, the left anterior descending coronary artery was excised together with a section of the normally perfused left circumflex coronary artery to examine in vitro the relaxations to the endothelium-dependent dilators ADP and bradykinin and to the endothelial-independent dilators sodium nitroprusside and adenosine. Contractions to serotonin in quiescent rings were also examined. Endocardial and transmural blood flows recovered to preocclusion levels within 60 minutes of reperfusion, as did the epicardial-to-endocardial ratio. Vascular responses in isolated, reperfused left anterior descending coronary artery rings were significantly different from responses in control left circumflex coronary artery rings. Endothelium-dependent relaxations to adenosine diphosphate and bradykinin were significantly depressed in the left anterior descending coronary artery rings compared with left circumflex coronary artery rings (p less than 0.05). Serotonin-induced contractions were significantly greater in occluded-reperfused left anterior descending than in left circumflex coronary arteries (p less than 0.05). Relaxations to adenosine and sodium nitroprusside were not significantly different between the two groups.
3
Brain magnetic resonance imaging and neuropsychologic evaluation of patients with idiopathic dilated cardiomyopathy. We compared brain magnetic resonance imaging and neuropsychologic performance in 20 neurologically asymptomatic patients suffering from idiopathic dilated cardiomyopathy (mean age 41 [range 18-49] years) and 20 age-matched controls (mean age 38 [range 28-49] years). Patients exhibited a significantly higher rate of cerebral infarcts (20% versus 0%, p less than 0.05) and cortical (50% versus 5%, p less than 0.01) and ventricular (55% versus 15%, p less than 0.02) atrophy than controls. Accordingly, semiquantitative volumetric measurements yielded a significantly increased ventricular-to-intracranial cavity ratio in the patients (6.2 +/- 2.9% versus 4.1 +/- 1.3%, p less than 0.01). This ratio and the cortical atrophy ratings correlated positively with disease duration (r = 0.63 and 0.54, p less than 0.05). Cognitive test performance was significantly worse in patients than in controls and was most impaired in those patients with morphologic cerebral abnormalities.
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Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Three patients with hematologic relapse after bone marrow transplantation for chronic myelogenous leukemia were treated with interferon alpha and transfusion of viable donor buffy coat. All had complete hematologic and cytogenetic remission, which persisted 32 to 91 weeks after treatment. In two patients graft-versus-host disease developed and was treated by immunosuppression. These results are an example of adoptive immunotherapy without cytoreductive chemotherapy or radiotherapy in human chimeras.
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Maternal feeding behavior and child acceptance of food during diarrhea, convalescence, and health in the central Sierra of Peru. Feeding patterns by mothers and child acceptance of food were measured in a Peruvian village to determine changes on days when children had diarrhea as compared to days of convalescence and health. Morbidity surveillance identified 40 children, aged 4-36 months, with diarrhea. Children were followed using twelve-hour in-home structured observations during two to four days each of diarrhea, convalescence, and health. Using scales of maternal encouragement to eat and child acceptance of food and cumulative logistic regression analyses, maternal encouragement to eat decreased significantly during convalescence compared to diarrheal days (OR: 0.54, 90% CI: 0.35, 0.82) and health compared to diarrhea (OR: 0.65, 90% CI: 0.46, 0.93). In contrast, child acceptance of food increased during health compared to diarrhea (OR: 1.55, 90% CI: 1.02, 2.35). Results illustrate the importance of carefully examining the behavioral aspects of nutritional intake. Decreases in intake during diarrhea are due to anorexia and not withdrawal of food by mothers. In response to reductions in child appetite during illness, mothers are more likely to encourage children to eat, while they tend to become more passive feeders after the diarrhea has stopped. Program efforts should focus on messages to feed children more actively especially after diarrhea episodes, when appetite levels increase.
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Effects of mental stress on myocardial perfusion in patients with ischemic heart disease. The purpose of the present study was to determine whether and to what extent mental stress can reproduce the perfusion defects that are known to be induced by exercise. Twenty-four patients with recent myocardial infarction (New York Heart Association functional class I) and evidence of ischemic response were evaluated by means of SESTAMIBI scintigraphy performed once after exercise and then again within 2 days after mental arithmetic. Baseline, exercise, and mental stress planar scintigrams were divided into 15 segments, and each segment was reviewed and scored on a scale of 0 to 3 by experienced observers using circumferential profile analysis. Conflicting scores were resolved by consensus. Electrocardiographic abnormalities were found in 15 of 24 patients during exercise and in none during mental arithmetic. Chest pain was experienced by five patients during exercise and by none during mental stress. Twenty patients showed reversible perfusion defects during mental stress. Of the 360 pooled scintigram segments, 99 evidenced uptake defects during exercise, and 48 of these showed the same defects during mental stress. Twenty of the remaining 51 of 99 segments were adjacent to segments showing reversible hypoperfusion, suggesting milder hypoperfusion in these segments during mental arithmetic than during exercise. Furthermore, 10 segments showed reversible defects only during mental stress such that seven of these occurred in areas adjacent to those that had shown exercise-induced reversible perfusion defects, two occurred in areas that had shown fixed SESTAMIBI defects during exercise, and one occurred in a segment that had shown completely normal uptake during exercise.
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Proximal placement of the acetabular component in total hip arthroplasty. A long-term follow-up study. A retrospective review was undertaken of thirty-seven hips (thirty-four patients) that had had a complex cemented total hip arthroplasty. In these hips, circumstances had necessitated that the center of the hip be placed farther proximally, as measured from the interteardrop line, than the anatomical position that is normally used. The mean duration of clinical and roentgenographic follow-up was eleven years (range, seven to seventeen years), and the mean age of the patients was fifty-one years (range, sixteen to seventy-three years). Most of these hips had a major deficiency or defect of the acetabular bone stock, or both. Of the six acetabular components (16 per cent) that became loose and were followed for ten years, only one needed revision. Because this study was aimed specifically at assessment of the acetabular component, if the femoral component alone needed revision, the final clinical rating that was used was the one obtained after the femoral revision. Thirty-one hips (84 per cent) were rated as having a good or excellent result; they had an average Harris hip-rating score of 43 points preoperatively and 93 points postoperatively. Thirty-three of the thirty-seven acetabular components were not substantially displaced laterally as compared with the anatomical location that is normally used. Our findings suggest that, when circumstances dictate, proximal positioning of the acetabular component without lateral displacement can give an acceptable result in cemented total hip-replacement procedures.
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Sex differences in control of cutaneous blood flow. Women are far more likely than men to suffer from Raynaud's disease. The purpose of this study was to determine whether there are gender differences in local or central control of cutaneous blood flow that could account for the increased incidence of Raynaud's disease in women. To assess cutaneous blood flow, hand blood flow (HBF), finger blood flow (FBF), or skin perfusion (SP) was measured by fluid plethysmography, mercury strain-gauge plethysmography, or laser Doppler spectroscopy, respectively, in 47 volunteers. Basal HBF in men exceeded that of women (12.1 +/- 2.0 versus 6.2 +/- 1.5 ml/100 ml/min). Likewise, FBF in men surpassed that of women (19.5 +/- 4.1 versus 7.7 +/- 1.8 ml/100 ml/min). Similarly, SP in men was greater than that of women (270 +/- 42 versus 81 +/- 16 perfusion units). However, after total body warming (to induce a thermal sympatholysis), HBF in women exceeded that of men, suggesting that the lower basal HBF in women was due to increased sympathetic outflow to the extremities. Mental stress and deep inspiration reduced HBF and SP in men. Paradoxically, both of these maneuvers increased HBF and SP in women. To determine whether these paradoxical responses in women were due to the women's elevated basal sympathetic tone, these experiments were repeated after total body cooling in men to increase sympathetic tone and after total body warming in women to reduce sympathetic tone. Total body cooling reduced HBF and SP in men. Under these conditions, mental stress and deep inspiration induced vasodilation. In women, total body warming for 10 minutes increased HBF.
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