123rc/medical_text huggingface dataset:
Frequent mutation of the p53 gene in human esophageal cancer. Sequence alterations in the p53 gene have been detected in human tumors of the brain, breast, lung, and colon, and it has been proposed that p53 mutations spanning a major portion of the coding region inactivate the tumor suppressor function of this gene. To our knowledge, neither transforming mutations in oncogenes nor mutations in tumor suppressor genes have been reported in human esophageal tumors. We examined four human esophageal carcinoma cell lines and 14 human esophageal squamous cell carcinomas by polymerase chain reaction amplification and direct sequencing for the presence of p53 mutations in exons 5, 6, 7, 8, and 9. Two cell lines and five of the tumor specimens contained a mutated allele (one frameshift and six missense mutations). All missense mutations detected occurred at G.C base pairs in codons at or adjacent to mutations previously reported in other cancers. The identification of aberrant p53 gene alleles in one-third of the tumors we tested suggests that mutations at this locus are common genetic events in the pathogenesis of squamous cell carcinomas of the esophagus.
Desmopressin and antifibrinolytics. Desmopressin appears to be a safe and effective hemostatic agent for use during surgery in patients with mild to moderate hemophilia or von Willebrand disease. Uremic patients also benefit from substitution of desmopressin for cryoprecipitate to control bleeding. The highly variable response to desmopressin by individual patients with hemophilia or von Willebrand disease dictates that each patient receive a trial administration prior to surgery; surgery should proceed only following verification of a therapeutically effective increase in Factor VIII and vWF after desmopressin. Use of desmopressin in patients with normal baseline hemostatic function is not clearly advantageous, although certain patient subgroups might benefit, and prospective studies have documented the drug's safety in these cases. Data are lacking to clarify a role for desmopressin during surgery in patients taking aspirin. Antifibrinolytic therapy appears to decrease bleeding without increased risk after cardiac surgery. In addition, specific use after urological surgery may be beneficial in the absence of upper urinary tract bleeding. In the last ten years, other applications for antifibrinolytic therapy have been found--both surgical (intracranial aneurysms, oral and lacrimal surgery) and nonsurgical (in cancer patients and for gastrointestinal bleeding). Although anecdotal reports have fueled fears of increased thrombosis with antifibrinolytics, controlled studies indicate no increased risk.
Patients' observations of bioprosthetic valve failure: "my heart is honking, doctor". Audible cardiac murmurs are uncommon and may indicate severe native valve dysfunction. In six patients with bioprosthetic mitral valves audible honking systolic murmurs suddenly developed. Doppler echocardiography showed characteristic striated regurgitant signals. At operation each prosthesis had torn cusps. New audible murmurs and striated Doppler signals originating from mitral bioprosthetic valves are indicators of cusp tears. Recognition of this is important because early detection of prosthetic valve dysfunction may improve subsequent surgical outcome.
Attenuation of alcohol-induced hepatic fibrosis by polyunsaturated lecithin. Characteristic features of alcoholic liver injury include fibrosis and striking membrane alterations, with associated phospholipid changes. To offset some of these abnormalities, a 10-yr study was conducted in baboons: 12 animals (eight females, four males) were fed a liquid diet supplemented with polyunsaturated lecithin (4.1 mg/kcal) for up to 8 yr, with either ethanol (50% of total energy) or isocaloric carbohydrate. They were compared with another group of 18 baboons fed an equivalent amount of the same diet (with or without ethanol), but devoid of lecithin. In the two groups, comparable increases in lipids developed in the ethanol-fed animals, but striking differences in the degree of fibrosis were seen. Whereas at least septal fibrosis (with cirrhosis in two) and transformation of their lipocytes into transitional cells developed in seven of the nine baboons fed the regular diet with ethanol, septal fibrosis did not develop in any animals fed lecithin (p less than 0.005). They did not progress beyond the stage of perivenular fibrosis (sometimes associated with pericellular and perisinusoidal fibrosis) and had a significantly lesser activation of lipocytes to transitional cells. Furthermore, when three of these animals were taken off lecithin, but continued on the same amount of the ethanol-containing diet, they rapidly (within 18 to 21 mo) progressed to cirrhosis, accompanied by an increased transformation of their lipocytes to transitional cells. These results indicate that some component of lecithin exerts a protective action against the fibrogenic effects of ethanol. Because we had previously found that choline, in amounts present in lecithin, has no comparable action, the polyunsaturated phospholipids themselves might be responsible for the protective effect.
Association of expression between N-myc gene and major histocompatibility complex class I gene in surgically resected human neuroblastoma. Amplification of the N-myc gene in neuroblastoma correlates with advanced stage and poor prognosis. Association of the expression between N-myc and major histocompatibility complex (MHC) class I genes in 33 neuroblastomas obtained from Japanese children was investigated. Amplification of the N-myc gene was observed in two of five cases in Stage III, six of 11 cases in Stage IV, and one of five cases in Stage IV-S. In each case, the expression of N-myc gene was significantly increased. The expression was also increased in cases without amplification of the N-myc gene, the origin being from the suprarenal region. Expression of the MHC class I gene was significantly decreased in five of these nine with a high level of N-myc expression with amplification. These results suggest that the down-modulation of the MHC class I expression may be associated with the high level of expression and amplification of N-myc gene in the advanced stage of neuroblastoma.
Orocaecal transit time in Duchenne muscular dystrophy. Smooth muscle degeneration may occur in Duchenne muscular dystrophy. We measured fasting orocaecal transit time in patients with advanced Duchenne muscular dystrophy and other muscular dystrophies and in healthy controls. No significant differences were found. In contrast to reports of gastric hypomotility in Duchenne muscular dystrophy, we found no evidence of impaired small intestinal motility.
Azathioprine in the treatment of children with inflammatory bowel disease. During a 6-year period, we treated 21 patients with azathioprine, 2 mg/kg/day, as an adjunct to their customary regimen. Nine patients had ulcerative colitis and 12 patients had Crohn disease; the patients' ages ranged from 3 to 17 years. The median duration of disease before the start of azathioprine therapy was 2 years, and median follow-up was 2 years. Sixteen patients seemed to respond to azathioprine therapy: six patients in each disease group had complete responses and four patients (one with ulcerative colitis and three with Crohn disease) had partial responses. Two patients with ulcerative colitis and three patients with Crohn disease did not respond. The median time until patients responded was less than 3 months for patients with ulcerative colitis and 4 months for those with Crohn disease. Reduction of corticosteroid dose was possible for all patients who responded to azathioprine therapy. Only minimal side effects were attributable to the drug. We conclude that azathioprine is an effective adjunctive agent for the treatment of inflammatory bowel disease in childhood, but because questions remain regarding its long-term safety, its use should be reserved for children with refractory disease or severe and unacceptable side effects of corticosteroids.
Mitral valve repair by replacement of chordae tendineae with polytetrafluoroethylene sutures. Expanded polytetrafluoroethylene sutures have been used for replacement of diseased chordae tendineae during reconstructive procedures on the mitral valve in 43 patients. There were 28 men and 15 women whose mean age was 55 years, range 21 to 76. Three fourths of the patients were in New York Heart Association class III or IV. Replacement of primary chordae tendineae of the anterior leaflet was performed with 4-0 or 5-0 polytetrafluoroethylene sutures. A double-armed suture was passed twice through the fibrous portion of the papillary muscle head and tied down. Each arm of the suture was brought up to the free margin of the leaflet and passed through the area where the native chorda was attached. After the lengths of the two arms were adjusted, the ends were tied together on the ventricular side of the leaflet. Thirty patients had degenerative disease of the mitral valve; the incompetence was due to prolapse of the anterior leaflet in 14 patients and prolapse of the anterior and posterior leaflets in 16. Eleven patients had rheumatic mitral valve disease: four had stenosis, three had regurgitation, and four had mixed lesions. Two patients had ischemic mitral regurgitation caused by rupture of a papillary muscle head. There were no operative deaths. Patients have been followed up from 5 to 61 months, mean 13. Doppler echocardiographic studies were performed at regular intervals after the operation and revealed normal mitral valve function in most patients There were two failures that necessitated mitral valve replacement: one because of acute mitral regurgitation and the other because of hemolysis. There have been two late deaths, neither one valve related. Replacement of chordae tendineae with polytetrafluoroethylene sutures is simple and allows for reconstruction of the mitral valve in many patients who would otherwise require mitral valve replacement. Because our patients have been followed up for a limited time, the long-term results of this procedure remain unknown.
Blue rubber bleb nevus syndrome with oral hemangiomas. A case of blue rubber bleb nevus syndrome with oral hemangiomas is reported. Attention is directed to this syndrome because, although rare, it is usually associated with oral lesions. The blue rubber bleb nevus syndrome should always be considered a possibility in patients with oral hemangiomas and bluish skin nodules.
Vasopressin response in collecting ducts of rats resistant to mineralocorticoid hypertension. In previous studies we found that vasopressin stimulation of both cyclic AMP (cAMP) formation in cortical collecting tubules (CCT) and sodium reabsorption in isolated perfused kidneys was markedly exaggerated in rats with mineralocorticoid hypertension. In the present study, we tested the response (cAMP accumulation) of cortical and outer medullary collecting tubules (OMCT) to vasopressin in two rat models that are resistant to deoxycorticosterone acetate (DOCA)-induced hypertension, the Wistar-Furth strain and NaCl-deficient rats. The blood pressure of normal outbred Wistar rats rose to hypertensive levels (systolic pressure more than 165 mm Hg) during a 5-week treatment with DOCA (10 mg/week) and 1% saline to drink. Significant hypertrophy of the heart and kidneys was also observed. Vasopressin (10(-8) M)-induced cAMP formation was enhanced 3.4-fold in the CCT (OMCT unchanged) of hypertensive rats compared with normotensive controls. Significant hypertrophy (as indexed by tubule diameter) of the CCT but not the OMCT was also observed in DOCA-salt hypertensive rats. Restriction of dietary NaCl (0.13% in chow, tap water to drink) completely prevented DOCA-induced hypertension, organ and CCT hypertrophy, and enhancement of vasopressin-stimulated cAMP formation in the CCT. In Wistar-Furth rats, DOCA-salt treatment did not alter blood pressure or cause significant organ hypertrophy. However, DOCA-salt treatment enhanced vasopressin-stimulated cAMP formation by 4.1-fold in CCT of Wistar-Furth rats, with significant tubular hypertrophy in the CCT but not the OMCT. We conclude that DOCA-induced hypertension and changes in CCT function are dependent on excess dietary NaCl.
Experimental retinal branch vein occlusion in miniature pigs induces local tissue hypoxia and vasoproliferative microangiopathy. In miniature pigs, retinal veins were experimentally occluded using argon laser coagulation. Microvascular modifications leading to retinal hemorrhages and retinal edema were observed some hours after the occlusion. These lesions resolved progressively within 3 weeks after the occlusion, but in most cases ischemic retinal territories persisted. Preretinal partial pressure of oxygen (PO2) measurements, using double barrelled O2-sensitive microelectrodes, showed that all the ischemic areas were indeed hypoxic. In half of the experiments, preretinal and intravitreal new vessels grew on the ischemic territories. Tissue hypoxia appears to be a key step in triggering neovascularization. However, the critical level of hypoxia was not determined.
Laparoscopic guided cholecystectomy. Cholecystectomy remains the most effective form of therapy for patients with symptomatic cholelithiasis. An alternative method of gallbladder removal, laparoscopic guided cholecystectomy, was attempted in 100 patients. Five patients required conversion of the laparoscopic procedure to an open laparotomy for the following reasons: discovery of a pancreatic malignancy in one patient, extensive adhesions in one, presence of an aberrant accessory right hepatic duct in one, common hepatic duct injury in one, and avulsion of the cystic duct in one. Both ductal injuries occurred during the early phase of the clinical program. In those patients undergoing laparoscopic cholecystectomy, 93 were discharged within 24 hours of surgery and 94 returned to normal activity within 1 week. Laparoscopic guided cholecystectomy appears to offer a number of advantages in patient care as well as a significant reduction in health care expenses for gallbladder disease. Appropriate training in laparoscopic surgery is necessary in order to avoid operative complications.
Parenteral illegal drug use and limb loss. The problem of illegal drug abuse and extremity loss was identified in 27 patients-22 men and 5 women, with a mean age of 26 years. Associated medical problems included: smoking in 27, cardiac disease in 2, diabetes in 3, and hypertension in 3. Six femoral pseudoaneurysms, 2 with distal emboli and all with sepsis and thrombosis, directly contributed to limb loss along with 2 patients with progressive phlegmasia dolens. There were 3 below-the-elbow, 7 above-the-knee, 11 below-the-knee, and 6 transmetatarsal amputations. Eight patients received prostheses; 8 patients subsequently died in follow-up.
Omeprazole 20 mg three days a week and 10 mg daily in prevention of duodenal ulcer relapse. Double-blind comparative trial. In a double-blind, parallel-group clinical trial of 195 patients with duodenal ulcers who after a short-term study had relief of pain and healed ulcers proved endoscopically, 65 were randomized to receive 20 mg omeprazole 3 days a week (once in the morning from Friday to Sunday), 64 to receive 10 mg omeprazole once daily in the morning, and 66 to receive placebo for up to 6 months. The patients underwent repeat endoscopy with biopsy of the gastric fundic mucosa (qualitative assessment of argyrophilic cell population), assessment of symptoms, and laboratory screening with measurement of basal serum gastrin concentrations at 3 and 6 months or more often if indicated by recurrence of symptoms. At 3 months, endoscopically proved ulcer relapse occurred in 16% receiving 20 mg omeprazole 3 days a week; 21% receiving 10 mg omeprazole daily; and 50% receiving placebo. At 6 months, corresponding rates were 23%, 27%, and 67% with 95% confidence intervals of difference between the placebo group and omeprazole groups of 28%-60% and 24%-56% (P less than 0.00001), respectively, and between omeprazole groups of -19%-11% (NS). No major clinical or laboratory side effects were noted. Thus both omeprazole regimens are effective and safe in preventing duodenal ulcer relapse.
Elevated serum levels of soluble interleukin-2 receptors in small cell lung carcinoma. The presence of the soluble form of the interleukin-2 receptors (sIL-2R) was evaluated in the serum of 21 patients with small cell lung carcinoma (SCLC) and 37 patients with non-small cell lung carcinoma (non-SCLC) by means of an enzyme-linked immunosorbent assay. The sIL-2R level was measured serially in patients with SCLC both during and after therapy. The mean serum level of sIL-2R in patients with SCLC was 3.8 times higher than that of 47 healthy controls and was 1.9 times higher than in 37 patients with non-SCLC. Six patients with SCLC had very high levels of sIL-2R, ranging from five to 52 times the mean level observed in normal controls. Tumor cells in the pleural fluid of the patient with highest levels were positive with monoclonal antibodies to IL-2R (CD25), NKH-1, OKDR, and OKT9. A longitudinal study in this patient showed a good correlation between tumor activity and sIL-2R levels. Also, the sIL-2R levels decreased in patients responding to therapy. These results suggest that some SCLCs secrete sIL-2R and that the serial measurements of the serum sIL-2R levels can be used as a noninvasive tumor marker in this disease.
Stimulation of cAMP and phosphomonoester production by melanotropin in melanoma cells: 31P NMR studies. A major part of the present understanding of the molecular basis of signal transduction has been gained from in vitro studies using classical biochemical methods. In this study, we used 31P NMR spectroscopy to investigate the response of live M2R mouse melanoma cells to stimulation by melanocyte-stimulating hormone (MSH; melanotropin). In the presence of 3-isobutyl-1-methylxanthine and a synergistic dose of forskolin (1.67 microM), MSH induced a transient (approximately 60-min) rise in the cellular concentration of 3',5'-cyclic adenosine monophosphate (cAMP), which coincided in time with an equivalent decrease (approximately 40%) in ATP. However, no detectable change in phosphocreatine concentration was observed. Concomitantly, MSH induced a striking and unexpected increase in the concentration of three phosphomonoester (PME) metabolites (approximately 2-fold increase in total PME signal area); one signal has been assigned to phosphoethanolamine. The levels of the PMEs remained high for 2-4 hr and declined slowly (approximately 10 hr) to basal level, following perfusion with fresh culture medium. The increase in PME was also observed after stimulation with MSH alone. In contrast, stimulation with a high dose of forskolin (50 microM) and isobutylmethylxanthine (0.2 mM), although effective in stimulating the production of cAMP, did not induce the PME response. Evaluation of the cells' energetics indicated that the enhanced production of phosphoethanolamine is probably not due to ethanolamine phosphorylation. Therefore, it is likely to result from hydrolysis of phosphatidylethanolamine by a specific phospholipase C. The response of the PMEs appears to be regulated by a cAMP-independent process, suggesting the existence of an alternative transduction pathway controlled by MSH.
Serial magnetic resonance imaging in neonatal hypoxic-ischemic encephalopathy. We prospectively performed magnetic resonance imaging (MRI) studies during the neonatal period, and at 4 and 8 months of age, on 15 term infants with hypoxic-ischemic encephalopathy, and compared the results with their neurodevelopmental outcome at 18 months of age. Cerebral palsy developed in nine infants, two infants were classified as having abnormalities of tone and delayed motor milestones that were suggestive of cerebral palsy, and four infants were normal. Structural abnormalities, delayed myelination, or a combination of the two were detected with MRI at 8 months of age in all nine infants with later development of cerebral palsy. Three of the four normal infants and one infant with suggestive abnormalities had normal serial MRI findings. Each of the remaining two infants (one normal, one with suggestive abnormalities) had isolated persistent ventricular dilation on all three MRI studies. Our results suggest that 8 months appears to be the earliest time at which MRI findings correlate well with later adverse neurodevelopmental outcome in this population.
Definitive mandibular replacement using reconstruction plates. Mandibular defects following radical cancer surgery continue to provide challenges to head and neck surgeons. Twenty-seven patients with advanced oral cancer underwent primary mandibular replacement with metal reconstruction plates without the use of bone. Twenty-one patients (78%) had successful reconstruction with primary soft tissue healing. Six patients required removal of the plate in the postoperative period. Two of these patients had their reconstruction plates replaced as a secondary procedure following soft tissue healing. Thus, 23 of 27 patients (85%) had final mandibular reconstruction and were followed for an average of 19 months. Functional and cosmetic results were satisfactory. For patients with advanced disease, this technique compares favorably with microvascular transfer in terms of operating time and donor defect. Despite problems with plate exposure, the initial and overall success rates of 78% and 85%, respectively, make the use of these plates a reasonable choice for immediate reconstructive needs in patients with difficult tumors.
Effects of vasopressin on portal pressure during hemorrhage from esophageal varices. Vasopressin is often used to treat variceal hemorrhage. However, its efficacy is uncertain, and its portal hemodynamic effects in this setting are unknown. Eleven patients with alcoholic liver disease and bleeding varices were given vasopressin (0.2 U/min for the first hour, then 0.4 U/min for 24 hours). Portal pressure was monitored using an indwelling hepatic vein balloon catheter. Seventeen patients with variceal bleeding who remained stable over 26 hours of initial treatment with crystalloid and blood products served as a comparison group. Vasopressin infusion (0.2 U/min) produced a significant decrease in wedged hepatic venous pressure, hepatic venous pressure gradient (wedged minus free hepatic venous pressure), and heart rate. Increases in the rate of infusion did not produce further decreases in the parameters measured, but the changes were sustained over the course of the infusion. Hemodynamics remained stable in the control group. Portal pressure did not increase when vasopressin was abruptly discontinued in the 3 patients in whom postinfusion measurements were made. Vasopressin retains its portal hypotensive effects in the setting of variceal hemorrhage. Tachyphylaxis does not develop over 26 hours, and a "rebound" increase in portal pressure probably does not occur when the infusion is discontinued.