123rc/medical_text huggingface dataset:
Maple syrup urine disease caused by a partial deletion in the inner E2 core domain of the branched chain alpha-keto acid dehydrogenase complex due to aberrant splicing. A single base deletion at a 5'-splice donor site of an intron of the E2 gene disrupts the consensus sequence in this region. We have studied the molecular bases of maple syrup urine disease by analyzing the activity, subunit structure, mRNA sequence, and the genome of the affected enzyme. The branched chain alpha-keto acid dehydrogenase (BCKDH) activity in the patient was 4.2-4.5% of the control level. Immunoblot analysis revealed that the E2 subunit of BCKDH (Mr 52,000) was absent and another protein band with an Mr of 49,000 was present. We amplified the cDNA of the E2 subunit obtained from the patient's cell using the polymerase chain reaction method, then sequenced the amplified cDNA, in which a 78-bp deletion was identified. The consanguineous parents and a sister had two species of mRNA; the one corresponding to the normal E2 subunit and the other with a 78-bp deletion, whereas findings in a brother were normal. The molecular size of the translation products as deduced from the abnormal mRNA sequence was compatible with an abnormal protein band (Mr 49,000) detected in the patient's cells by immunoblot analysis. Analysis of genomic DNA of BCKDH-E2 subunit revealed that the 78-bp deletion in the mRNA was caused by an exon skipping due to a single base deletion in the 5'-splice donor site. As a result of the mutation, part of the inner E2 core domain was omitted. The specified region of the inner E2 core domain was highly homologous to the region of the E2 subunit of pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase. These observations imply the biological importance of the region in the inner E2 core domain of BCKDH to maintain normal function of the activity.
Primary carcinoma of the upper urinary tract. Effect of primary and secondary therapy on survival. The pathologic material and medical records of 76 patients with primary upper urinary tract carcinomas were reviewed to identify the role of grade and stage in predicting survival; to determine any differences in survival between ureteral and renal pelvic carcinoma; to understand the role of local therapy in low grade, low stage tumors; and to establish the usefulness of adjuvant therapies in metastatic disease. Kaplan-Meier survival curves with Cox-Mantel analysis for statistical significance revealed both grade and stage to be excellent predictors of survival. No differences in survival were noted between renal pelvic and ureteral carcinomas for equivalent stage tumors. For low grade, low stage tumors, although there was an increased risk of local recurrence with local therapy, there were no differences in survival between patients treated with local therapy or radical surgery. Finally, cisplatin-based chemotherapy seemed to improve survival in patients with metastatic disease.
Use of computed tomographic scanning and aortography in the diagnosis of acute dissection of the thoracic aorta. Before the introduction of computed tomographic (CT) scanning, aortography was the investigation of choice for acute aortic dissection. Between 1978 and 1982, 24 patients were referred to the Brompton Hospital with suspected acute thoracic aortic dissection; all had aortography with diagnosis confirmed at surgery (n = 12) or necropsy (n = 2) or supported by clinical outcome (n = 8). One patient in whom aortography was negative had type B dissection at necropsy and another patient was lost to follow up. CT scanning became available in this unit in 1983 and between 1983 and 1987 was used as the only imaging investigation in 32 patients with suspected acute dissection of the thoracic aorta while in a further 22 patients aortography was used alone. Results were confirmed at surgery (n = 18), necropsy (n = 3), or supported by clinical outcome (n = 31). Two patients were lost to follow up. In an additional 16 patients both aortography and CT scanning were performed with concordant findings in 10. In six in whom the results were discordant, aortography was normal in three in whom subsequent CT scanning showed type B dissection and CT scanning was normal in three patients in whom aortography showed type A dissection. Both CT scanning and aortography are reliable techniques for assessment of suspected acute dissection of the thoracic aorta. Both techniques misdiagnose occasionally and the frequency of misdiagnosis will be minimised by performing both investigations in patients where the level of clinical suspicion is high and the initial investigation negative. CT scanning tends to miss type A dissection and in view of the success of surgery in this condition this failing has the more serious clinical consequences.
A risk-benefit analysis of elective bilateral oophorectomy: effect of changes in compliance with estrogen therapy on outcome. A bilateral oophorectomy at the time of elective hysterectomy is often performed to prevent ovarian cancer. The assumption that endogenous estrogen can be easily replaced with supplemental medication fosters the decision for routine oophorectomy. Published reports on the use of postmenopausal estrogen indicate that compliance is less than perfect. This fact could affect the overall outcome. Decision analysis techniques with Markov cohort modeling were used to evaluate the policy of elective bilateral oophorectomy. Results from studies judged methodologically sound were combined to determine values representing the influence of estrogen on coronary heart disease, breast cancer, and osteoporotic fracture. The decision tree also explicitly incorporated patient compliance. When compliance with estrogen therapy is assumed to be perfect, oophorectomy yields longer life expectancy than retaining the ovaries. When actual drug-taking behavior is considered, retaining the ovaries results in longer survival. This analysis highlights the importance of including the effects of patient compliance with treatment recommendations when the impact of a health policy decision such as prophylactic surgery is assessed.
Impact of echocardiography on the management of patients with mitral valve prolapse OBJECTIVE: To determine whether echocardiography affects the decisions to use beta blockers or to recommend bacterial endocarditis prophylaxis in patients suspected of having mitral valve prolapse (MVP). DESIGN: Retrospective review of echocardiograms and clinical records. SETTING: Military tertiary care hospital. PATIENTS: 127 patients with clinically suspected MVP (105) or incidentally discovered MVP (22). MAIN RESULTS: Beta blockers were used more often in patients with suspected MVP and positive echocardiograms (45%) than in patients with normal echocardiograms (13%, p less than 0.001). Bacterial endocarditis prophylaxis was recommended more often in patients with suspected MVP and positive echocardiograms (65%) than in patients with normal echocardiograms (11%, p less than 0.001). Presence or absence of a murmur did not influence the decision to recommend bacterial endocarditis prophylaxis. Patients in whom MVP was incidentally discovered were unlikely to receive either beta blockers or the recommendation for bacterial endocarditis prophylaxis. CONCLUSIONS: The results of echocardiography affect the decisions to use beta blockers or to recommend bacterial endocarditis prophylaxis in patients with suspected MVP.
The surprising kidney-fluid mechanism for pressure control--its infinite gain! In this short paper, I have tried to explain the elation that we felt when we first realized that the kidney-fluid mechanism for controlling the arterial pressure has an infinite feedback gain property. Because of this, all the other pressure control mechanisms, none of which has ever been shown to have a similar infinite gain property, must themselves alter the kidney-fluid mechanism if they are to succeed in causing long-term changes in the arterial pressure. We have not been able to refute this principle despite many experiments over the last 2 decades. For this reason, our first understanding of the infinite gain property of the kidney-fluid mechanism was like a light at the end of the tunnel. I hope that I can explain to the reader the excitement of those few seconds when we first recognized the principle in 1966.
Crohn's disease: what about the pancreas? [editorial] Crohn's disease (CD) is now accepted as a systemic illness. The importance of extraintestinal manifestations is underlined by the fact that such "complications" can be more prominent and even more difficult to control than the intestinal disease itself. Lately, evidence for a more than accidental association of pancreatitis and exocrine pancreatic insufficiency with CD is growing. This might have a significant impact on the treatment of abdominal pain and diarrhea in CD, symptoms which have so far been attributed exclusively to the intestinal rather than the extraintestinal manifestations of the disease.
Molecular analysis of acute promyelocytic leukemia breakpoint cluster region on chromosome 17. Acute promyelocytic leukemia (APL; FAB M3) is characterized by a predominance of malignant promyelocytes that carry a reciprocal translocation between the long arms of chromosomes 15 and 17, t(15;17) (q22;q11.2-q12). This translocation has become diagnostic for APL, as it is present in almost 100 percent of cases. A Not I linking clone was used to detect this translocation initially on pulsed-field gel electrophoresis and subsequently with conventional Southern (DNA) analysis. The breakpoints in ten APL cases examined were shown to cluster in a 12-kb region of chromosome 17, containing two CpG-rich islands. The region is the first intron of the retinoic acid receptor alpha gene (RARA).
Progressive coronary luminal narrowing after cardiac transplantation. Accelerated coronary disease is a major factor limiting long-term survival in cardiac transplant recipients. Coronary angiography was obtained a mean of 5.1 weeks posttransplantation and annually thereafter. Replicate projections recorded after nitroglycerine administration were quantitated using computer-assisted edge detection. Five hundred and fifteen coronary segments in 25 patients having 1-year follow-up and 353 segments in 18 patients reaching 2-year follow-up were compared with baseline angiograms. Significant change was defined as +/- 0.10 mm, equal to 3.8% change in diameter based on three standard deviations obtained from estimation of measurement error. Mean coronary diameter fell from 2.44 +/- 0.26 mm at baseline to 2.21 +/- 0.34 mm (p less than 0.001) at 1-year follow-up. This rate of diameter decline was 20-fold more rapid during the initial posttransplantation year than the rate of change of visually normal segments in nontransplant patients with coronary atherosclerosis elsewhere. There was no significant drop in mean diameter between the first and second year in those patients who had second-year studies. Decrease in absolute diameter for vessels greater than 2.9 mm significantly exceeded diameter reduction for smaller vessels but did not differ when considered as a ratio of vessel diameter. In 21 of 25 patients, mean coronary diameter reduction exceeded the three-standard deviation threshold at their last angiogram, but only two of these patients had visually detectable transplant coronary disease.
Gynecologic vascular abnormalities: diagnosis with Doppler US. The authors describe the use of duplex and/or color Doppler ultrasonography of the pelvis in three women to demonstrate the presence of venous malformations. One patient with a pulsatile vaginal mass was shown to have an arteriovenous malformation of the vaginal wall. The second patient was shown to have an unsuspected venous angioma in the endometrial cavity. The third patient was shown to have adnexal varices that closely mimicked hydrosalpinx. In the latter two cases, the duplex and color flow capabilities of an endovaginal probe were especially important.
Which clinical variables predict an abnormal double-contrast barium enema result? OBJECTIVE: To determine the relations among patient history, symptoms, objective indicators, and abnormal double-contrast barium enema results in outpatients. PATIENTS AND SETTING: Seven hundred and ninety-four patients receiving care in a large multispecialty medical group. DESIGN: Physicians completed a form before ordering a double-contrast barium enema, listing information about patient history, symptoms, and objective findings, including the results of a complete blood count, stool hemoccult, and sigmoidoscopy. MEASUREMENTS AND MAIN RESULTS: Outcome measures were colon cancer and any abnormal finding. The results of 18.6% of the barium enemas were abnormal. The most frequent positive findings were of polyps (8.8%) and colon cancer (2.9%). Over 50% of the barium enemas were ordered solely on the basis of symptoms, yet there was no statistical correlation between symptoms and colon cancer or any positive finding. Using logistic regression, four variables were shown to be significant predictors of colon cancer (P less than 0.05): abnormal sigmoidoscopy, iron deficiency anemia, positive stool hemoccult results, and relevant history. The respective odds ratios of these variables were 3.76 (95% CI, 2.89 to 4.90); 2.86 (CI, 2.13 to 3.74); 1.87 (CI, 1.46 to 2.39); and 1.91 (CI, 1.44 to 2.52), respectively. In a patient without any of these indicators, the predicted probability of having colon cancer was only 0.7%. In a patient with at least two objective indicators, the probability of having colon cancer was greater than 15%. CONCLUSIONS: Symptoms without objective indicators or pertinent risk factors do not correlate with an abnormal double-contrast barium enema result. Objective indicators are useful predictors of an abnormal barium enema result, particularly when looking for colon cancer.
Clinical and electrophysiologic characteristics of patients with antidromic circus movement tachycardia in the Wolff-Parkinson-White syndrome. Antidromic circus movement tachycardia was documented in 36 of 345 consecutive patients with Wolff-Parkinson-White syndrome undergoing detailed electrophysiologic evaluation. Twenty-six patients were men and 10 were women (mean age +/- standard deviation 26 +/- 12 years [range 12 to 45]). Multiple accessory pathways were identified in 12 of these 36 patients (33%). Ten of the patients (67%) with clinically documented antidromic tachycardia had multiple accessory pathways. Dizziness and syncope occurred in 61 and 50% of patients with antidromic circus movement tachycardia. Six patients had clinical documentation of atrial fibrillation, and 4 patients (11%) were resuscitated from ventricular fibrillation. In the 36 patients, 56 distinct antidromic tachycardias were recorded and several different pathways were observed. Orthodromic tachycardia was the most frequently associated arrhythmia (72%). Dual atrioventricular nodal pathways were present in 12 patients (33%); however, atrioventricular nodal tachycardia could be initiated in only 2 of them. Interruption of the accessory pathway was successfully performed in all 20 patients undergoing surgery.
Achieving pH control in the critically ill patient: the role of continuous infusion of H2-receptor antagonists. Stress-related gastric mucosal damage is a common occurrence in intensive care unit (ICU) patients. Because of the significant morbidity and mortality associated with this mucosal damage, many ICU patients routinely receive prophylactic therapy, usually with histamine H2-receptor antagonists (H2RAs). Gastric acid secretion occurs in a circadian pattern, with late afternoon and evening surges. H2RAs by continuous infusion may control this uneven pattern of secretion more effectively than H2RAs given by bolus injection. More studies are needed to identify the target ICU population for prophylactic treatment.
The use of angiotensin converting enzyme inhibitors in combination with other antihypertensive agents. Angiotensin converting enzyme (ACE) inhibitors have additive effects with most other antihypertensive agents, but the mechanisms of these interactions vary. With diuretics the interaction with ACE inhibitors can be explained by their contrasting effects on the renin-angiotensin system, while with calcium antagonists it may be attributed to independent mechanisms of action. With beta-blockers there is a variable additive effect, which has been proposed to be due to more complete blockade of the renin-angiotensin system than can be obtained with either type of agent alone.
Technetium-99m(v) dimercaptosuccinic acid planar scintigraphy in head and neck cancer: clinical, scintigraphic and radiological study. Technetium-99m (Tc99m)(v) Dimercaptosuccinic Acid (DMSA) is an imaging agent which has been proposed as a scintigraphic marker for head and neck squamous cell carcinoma. Fifty-four patients were studied of whom 51 had a head and neck tumour. All patients were examined and then imaged using Tc99m(v) DMSA scintigraphy and computerized tomography. Scintigraphy was less sensitive than clinical examination in the detection of patients with cancer, patients with primary tumours and patients with metastatic neck disease. CT was as sensitive and as accurate as clinical examination but more sensitive than Tc99m(v) DMSA in detecting patients with cancer and with primary tumours. CT was more sensitive and more accurate than both clinical examination and Tc99m(v) DMSA scintigraphy in predicting which patients had metastatic neck disease. Although Tc99m(v) DMSA is accumulated by squamous cell carcinoma, its inability to detect low volume disease and apparent low specificity means it has no role to play in the management of patients with head and neck squamous cell carcinoma.
The isolation and characterization of a Norwalk virus-specific cDNA. Norwalk virus, an important cause of epidemic, acute, nonbacterial gastroenteritis in adults and children, has eluded adaptation to tissue culture, the development of an animal model, and molecular cloning. In this study, a portion of the Norwalk viral genome encoding an immunoreactive region was cloned from very small quantities of infected stool using sequence-independent single primer amplification. Six overlapping complementary DNA (cDNA) clones were isolated by immunologic screening. The expressed recombinant protein from a representative clone reacted with six of seven high titer. Norwalk-specific, postinfection sera but not with corresponding preinfection sera. Nucleic acid sequence for all clones defined a single open reading frame contiguous with the lambda gt11-expressed beta-galactosidase protein. Only oligonucleotide probes specific for the positive strand (defined by the open reading frame) hybridized to an RNaseA-sensitive, DNaseI-resistant nucleic acid sequence extracted from Norwalk-infected stool. Furthermore, RNA extracted from serial postinfection, but not preinfection, stools from three of five volunteers hybridized to a Norwalk virus cDNA probe. Clone-specific oligonucleotide probes hybridized with cesium chloride gradient fractions containing purified Norwalk virion. In conclusion, an antigenic, protein-coding region of the Norwalk virus genome has been identified. This epitope has potential utility in future sero- and molecular epidemiologic studies of Norwalk viral gastroenteritis.
Hepatic arterial embolization in cases of extensive celiac arterial stenosis. Transarterial hepatic embolization was attempted in 10 and succeeded in nine patients with hepatocellular carcinoma accompanied by extensive celiac arterial stenosis. All catheterization was done through the femoral artery. In six cases, the tip of the catheter (2.5-F ball-tip microcatheter in three cases, 4-F ball-tip supple catheter in three cases) was placed in the proper hepatic artery through the pancreaticoduodenal collaterals. In three cases, a ball-tip microcatheter was injected from the guiding catheter, which was placed in a pinhole of the celiac trunk. These techniques involving flow-guided ball-tip catheters are of great value for hepatic arterial catheterization in cases of extensive celiac arterial stenosis.
Low diacylglycerol values in colonic adenomas and colorectal cancer. The biochemical events that make colonic epithelial cells proceed along the adenoma-carcinoma sequence are not well understood. The phosphoinositol signal transduction pathway is involved in the regulation of cell growth and differentiation. To determine its role in colonic neoplasias we performed mass measurements of its second messenger sn-1,2-diacylglycerol in biopsy specimens from normal mucosa and neoplasias of the colon. Normal colonic mucosa was also investigated in patients without colonic abnormalities (n = 10). Compared with pooled diacylglycerol values from five colonic sites (100%), values in patients with a normal colon were highest in the ascending colon (120 (5)%, p less than 0.05) and lowest in the rectum (81 (5)%, p less than 0.01). Absolute diacylglycerol values in patients with normal colons (2.62 (0.16) nmol/mg protein) were not significantly different from those found in the normal mucosa of patients with colorectal neoplasias (2.45 (0.17) nmol/mg protein). Both colonic adenomas (n = 15) and colorectal carcinomas (n = 14) showed significantly decreased diacylglycerol values compared with the adjacent normal mucosa of each patient (72 (4)%, p less than 0.001, and 71 (4)%, p less than 0.001 respectively). The appreciable decrease in mass diacylglycerol values clearly distinguishes adenomas and carcinomas of the colon from the surrounding normal mucosa. This finding suggests that profound metabolic changes of the phosphoinositol signal transduction pathway occur early in the adenoma-carcinoma sequence and may be important in colonic carcinogenesis.
Spontaneous and steroid-induced recurrence of endometriosis after suppression by a gonadotropin-releasing hormone antagonist in the rat. Recurrent endometriosis in women is difficult to study because of the ethical consideration of performing repeated surgeries. Previously in the rat model we described therapeutic regression of endometriosis with the gonadotropin-releasing hormone antagonist antide. Presently we report the spontaneous and steroid-induced recurrence of endometriosis after withdrawal from antide therapy. Rats with endometriosis received antide or vehicle on days 0 (proestrus), 3, 6, and 9 and were killed on days 0, 6, 12, 18, 24, 30, and 42 (n = 4 antide-treated and 4 vehicle-treated rats killed per day). Additional antide-treated rats (n = 4 per treatment) received estrogen, progesterone, both estrogen and progesterone, cholesterol, and no steroid on day 9 and were killed on day 12. Antide significantly suppressed endometriotic implant size on days 12, 18, and 24. However, implant size spontaneously returned to pretreatment values by day 30. Administration of steroids on day 9 elicited regrowth of antide-suppressed endometriosis (estrogen plus progesterone greater than estrogen, progesterone, or cholesterol greater than no steroid) by day 12. This resilience of endometriosis offers an explanation for treatment failure and recurrence of the disease in women.