shukoor65/lab-rag-model huggingface dataset:
Progression and regression of minor coronary arterial narrowings by quantitative angiography after fenofibrate therapy. To study the effects of fenofibrate, a lipid-lowering medication, on patients with coronary artery disease, 191 minor coronary narrowings in 42 patients with coronary artery disease were analyzed by quantitative coronary angiography using computer-assisted contour detection. Computed parameters were percent diameter reduction and percent plaque area. A prospectively formed intervention group of 21 patients treated with special diet and fenofibrate (200 to 400 mg/day) was checked every 6 weeks with regard to risk factors. After a mean interval of 21 months, coronary angiography was repeated, using the same x-ray system and nearly identical projections. The intervention group was angiographically compared at follow-up with an untreated comparison group, also comprising 21 patients. Both groups had high initial serum cholesterol (mean 311 mg/dl) and low-density lipoprotein (LDL) cholesterol levels (mean 235 mg/dl). Only among the treated patients did lipid levels change significantly: cholesterol, -19%; LDL cholesterol, -20%; high-density lipoprotein cholesterol, +19%; and triglycerides, -30%. At angiographic follow-up, the changes in percent diameter reduction and percent plaque area correlated positively with the mean serum and LDL cholesterol levels of the intervention group. Significant differences were found in the change in percent plaque area between both groups. The intervention subgroup with angiographic regressions (11 patients) had significantly lower serum and LDL cholesterol levels than the intervention subgroup with angiographic progressions (10 patients). These results indicate the beneficial effect of fenofibrate on minor coronary narrowings. Because of its high reproducibility in measuring minor narrowings, quantitative coronary angiography proved to be a suitable method for angiographic follow-up.
Early results of aortic valve replacement with or without concomitant coronary artery bypass grafting. Early results of aortic valve replacement were reviewed in 962 unselected patients, 659 without concomitant coronary bypass surgery (AVR group) and 303 with combined valve replacement and coronary artery bypass grafting (AVR + CABG). The early (less than 30-day) mortality was 4.6% in the AVR, and 5.9% in the AVR + CABG group. Multivariate analysis showed coronary artery stenoses and NYHA functional class to be independent predictors of early mortality in the AVR group, and the number of distal anastomoses as the strongest predictor in AVR + CABG. The incidence of peroperative technical complications in the cases with fatal outcome was 27% in the AVR and 6% in the AVR + CABG group. The incidence of myocardial injury (new Q wave or evidence of increased enzyme leakage) was 11% in AVR and 21% in AVR + CABG. Independent predictors of postoperative myocardial injury were aortic cross-clamp time, year of surgery, coronary artery stenoses and NYHA class in AVR and aortic cross-clamp time and year of surgery in AVR + CABG. The study suggests that coronary artery disease increases risk in aortic valve replacement with or without CABG. Replacement should be undertaken before endstage of the disease (NYHA IV), with CABG if significant coronary disease is present, and in multivessel disease the number of distal anastomoses should be restricted in order to shorten aortic cross-clamp time.
The nature of the naming deficit in Alzheimer's and Huntington's disease. A comparison of naming performance, on the Boston Naming Test, of 52 patients with dementia of Alzheimer's type (DAT), 16 patients with Huntington's disease (HD) and 52 normal control subjects was performed using a comprehensive classification of error types. Spontaneous and cued naming scores were significantly impaired both in the DAT and HD groups, but performance in the DAT patients was significantly worse than that of the HD patients. Normal controls made predominantly semantic-category and circumlocutory errors. The HD group differed from normal only in the proportion of visually based errors, which was greater in the patient group. By contrast, the DAT patients made a significantly greater proportion of semantic-superordinate and semantic-associative errors. The same pattern of naming errors was found when a group of DAT and HD patients matched for overall naming ability was compared. A subgroup of 22 DAT patients was followed longitudinally over 3 y. Their deterioration in overall naming performance was accompanied by a consistent change in the profile of naming errors: the proportion of semantic-associative errors increased significantly as did the proportion of visual errors. These results are considered in the light of current cognitive models of naming. They suggest that in HD, naming deficits initially involve disruption of perceptual analysis, whereas in DAT such impairments in the early stages reflect a breakdown in semantic processes. However, as DAT progresses, perceptual problems also begin to contribute to the patients' naming difficulties. Postlexical (phonemic) processes remain relatively intact throughout in both diseases.
Immunohistology of temporal arteritis: phenotyping of infiltrating cells and deposits of complement components. Deposition of complement factors, immunoglobulins and infiltrating cells was evaluated by immunohistochemical staining in 30 temporal artery biopsy specimens from patients suffering from temporal arteritis and/or polymyalgia rheumatica and in controls. In the temporal arteritis group infiltrating cells, classic complement, alternative complement and lytic complex activation were detected. In specimens from patients suffering from only polymyalgia rheumatica there was unexpected evidence of classic complement and lytic complex activation. We conclude that immuno-histochemistry provides support for the concept of temporal arteritis and polymyalgia being based on the same pathological process.
Anti-MY9-blocked-ricin: an immunotoxin for selective targeting of acute myeloid leukemia cells. The use of immunotoxins (IT) to selectively destroy acute myeloid leukemia (AML) cells in vivo or in vitro is complicated by both the antigenic similarity of AML cells to normal progenitor cells and the difficulty of producing a sufficiently toxic conjugate. The monoclonal antibody (MoAb) anti-MY9 is potentially ideal for selective recognition of AML cells because it reacts with an antigen (CD33) found on clonogenic AML cells from greater than 80% of cases and does not react with normal pluripotent stem cells. In this study, we describe an immunotoxin that is selectively active against CD33+ AML cells: Anti-MY9-blocked-Ricin (Anti-MY9-bR), comprised of anti-MY9 conjugated to a modified whole ricin that has its nonspecific binding eliminated by chemical blockage of the galactose binding domains of the B-chain. A limiting dilution assay was used to measure elimination of HL-60 leukemic cells from a 20-fold excess of normal bone marrow cells. Depletion of CD33+ HL-60 cells was found to be dependent on the concentration of Anti-MY9-bR and on the duration of incubation with IT at 37 degrees C. More than 4 logs of these leukemic cells were specifically depleted following short exposure to high concentrations (10(-8) mol/L) of Anti-MY9-bR. Incubation with much lower concentrations of Anti-MY9-bR (10(-10) mol/L), as compatible with in vivo administration, resulted in 2 logs of depletion of HL-60 cells, but 48 to 72 hours of continuous exposure were required. Anti-MY9-bR was also shown to be toxic to primary AML cells, with depletion of greater than 2 logs of clonogenic cells following incubation with Anti-MY9-bR 10(-8) mol/L at 37 degrees C for 5 hours. Activity of Anti-MY9-bR could be blocked by unconjugated Anti-MY9 but not by galactose. As expected, Anti-MY9-bR was toxic to normal colony-forming unit granulocyte-monocyte (CFU-GM), which expresses CD33, in a concentration- and time-dependent manner, and also to burst-forming unit-erythroid and CFU-granulocyte, erythroid, monocyte, megakaryocyte, although to a lesser extent. When compared with anti-MY9 and complement (C'), Anti-MY9-bR could be used in conditions that provided more effective depletion of AML cells with substantially less depletion of normal CFU-GM. Therefore, Anti-MY9-bR may have clinical utility for in vitro purging of AML cells from autologous marrow when used at high IT concentrations for short incubation periods. Much lower concentrations of Anti-MY9-bR that can be maintained for longer periods may be useful for elimination of AML cells in vivo.
Postoperative analgesic requirements following flumazenil administration. The effect of flumazenil (RO 15-1788) on postoperative analgesic requirements was evaluated in 30 postoperative patients. This prospective investigation was a double-blind, placebo-controlled trial in patients undergoing general anesthesia supplemented by midazolam and fentanyl or sufentanil. Patients received either flumazenil (n = 20) or placebo (n = 10) by random assignment. Analgesic requirements were measured in morphine equivalents (MEs) and were recorded for a three-hour period following the administration of flumazenil. All patients received the assigned treatment within five minutes of arrival to the postanesthesia room. Total ME requirements were 4.1 +/- 3.8 mg for the flumazenil group and 4.5 +/- 4.6 mg (p = 0.71) for the placebo group. Patient analgesic requirements were also assessed when patients were adequately alert. For the flumazenil group this time period was 6.2 +/- 12.7 minutes versus 52.9 +/- 28.4 minutes for placebo (p less than 0.01). MEs (flumazenil 4.1 +/- 3.8 mg vs. placebo 3.7 +/- 3.2 mg) were not significantly different (p = 0.57) when similar levels of consciousness were compared. The onset of pain was more rapid with flumazenil patients as evidenced by the first analgesic dose at 15.7 +/- 25.1 minutes for the flumazenil group versus 34.7 +/- 43.7 for the placebo group; however, these data were not statistically different (p = 0.144). These results suggest that flumazenil does not increase postoperative analgesic requirements during the immediate postanesthesia period; however, patients receiving flumazenil may experience an earlier onset of postoperative pain.
Echocardiographic evidence for the existence of a distinct diabetic cardiomyopathy (the Framingham Heart Study). Although several reports have described early changes of cardiac structure and function in diabetic patients, controversy persists regarding the existence of a clinically distinct diabetic cardiomyopathy. To this end, sex-specific linear regression analyses were used to examine the contribution of diabetes mellitus and glucose intolerance to age-adjusted echocardiographic parameters in 1,986 men (mean age 48 years) and 2,529 women (mean age 50 years) from the original Framingham Study cohort and the Framingham Offspring Study. Subjects with evidence of cardiovascular disease at the time of echocardiogram were excluded. Diabetics had higher heart rates than nondiabetics (67.9 vs 64.0 beats/min (p = 0.002) in men, and 73.1 vs 68.3 beats/min (p = 0.004) in women). Diabetic women had increased left ventricular (LV) wall thickness (18.7 vs 17.1 mm, p less than 0.001), relative wall thickness (0.403 vs 0.377, p = 0.008), LV end-diastolic dimension (46.9 vs 45.7 mm, p = 0.03) and LV mass corrected for height (100.4 vs 82.2 g/m, p less than 0.001). Women with glucose intolerance showed similar, less significant trends (p = 0.007 for wall thickness, p less than 0.01 for LV mass). In diabetic men, fractional shortening was slightly reduced (0.355 vs 0.360, p less than 0.05). In a multivariate model that included potentially confounding factors, diabetes remained an independent contributor to LV mass (p = 0.004) and wall thickness (p = 0.008) in women. In a separate linear regression model, which assessed the association of age with LV mass, the age-coefficient for diabetic women was much higher than that for nondiabetics (13.6 vs 6.6 g/m per 10-year increment in age).
A population-based study of bronchial asthma in adult twin pairs. Aggregation of cases of bronchial asthma in adult twin pairs was studied in the nationwide Finnish twin cohort consisting of 13,888 adult monozygotic (MZ) and same-sex dizygotic (DZ) pairs. Cases of asthma were ascertained by record-linkage from three sources of data: death certificates from the Central Statistical Office; hospital discharges from the nationwide hospital registry; and the nationwide registry for fully reimbursed medications of the Social Insurance Institution. A diagnosis of bronchial asthma in one or more of these registers was obtained for 525 (236 men and 289 women) out of 27,776 twin individuals. Among MZ pairs, ten concordant and 138 discordant pairs were identified, while among DZ pairs, 12 concordant and 343 discordant pairs were found. In the whole sample the observed-expected ratio for the number of pairs concordant for bronchial asthma was 4.30 (95 percent confidence interval [CI], 2.06 to 7.90) in MZ pairs and 2.61 (95 percent CI, 1.35 to 4.56) in DZ pairs. Using a multifactorial threshold model, we estimated the correlation in liability to asthma as 0.425 (SE = 0.07) in MZ twins and 0.247 (SE = 0.06) in DZ twins, and we obtained a heritability estimate of 35.6 percent. The data also showed a gender difference in asthma heredity, which may, however, be due to chance events affecting the distribution of concordant pairs.
Lack of efficacy of tranexamic acid in thrombocytopenic bleeding. A controlled, randomized, double-blind study was performed to assess the effect of the oral antifibrinolytic agent tranexamic acid in patients with amegakaryocytic thrombocytopenia as regards their need for platelet transfusions and the number of bleeding episodes experienced. Each patient served as his or her own control and received sequential, randomized courses of either tranexamic acid or an identical placebo. The need for platelet transfusions due to bleeding and the total number of bleeding episodes were compared for tranexamic acid and placebo courses. Patients received platelet transfusions at the discretion of their personal physician and kept detailed records of bleeding episodes. Of three patients who completed the full study, none had a reduction in the need for platelet transfusions. Moreover, in the eight patients who participated in the study, there was no reduction in number of bleeding episodes during tranexamic acid treatment as compared to the number with placebo. Our data indicate that the prophylactic administration of tranexamic acid does not decrease dependence on platelet transfusions or decrease bleeding episodes in patients with bleeding due to amegakaryocytic thrombocytopenia.
Neoplastic disease of the spine. In summary, MR imaging has become the single most effective modality for the evaluation of spinal neoplasms by virtue of its ability to image the spinal cord directly and noninvasively. In this fashion, one can localize mass lesions relative to the spinal cord; in conjunction with the patient's clinical history, it is thus possible to provide a brief yet accurate differential diagnosis. Intravenous paramagnetic contrast enhancement also may prove extremely useful in further delineating such lesions. In addition, it has demonstrated a high sensitivity to primary and secondary tumors of the bony spine through its ability to detect subtle T1 signal changes in the vertebral marrow space.
Retroviral-mediated gene therapy for the treatment of hepatocellular carcinoma: an innovative approach for cancer therapy. An approach involving retroviral-mediated gene therapy for the treatment of neoplastic disease is described. This therapeutic approach is called "virus-directed enzyme/prodrug therapy" (VDEPT). The VDEPT approach exploits the transcriptional differences between normal and neoplastic cells to achieve selective killing of neoplastic cells. We now describe development of the VDEPT approach for the treatment of hepatocellular carcinoma. Replication-defective, amphotrophic retroviruses were constructed containing a chimeric varicella-zoster virus thymidine kinase (VZV TK) gene that is transcriptionally regulated by either the hepatoma-associated alpha-fetoprotein or liver-associated albumin transcriptional regulatory sequences. Subsequent to retroviral infection, expression of VZV TK was limited to either alpha-fetoprotein- or albumin-positive cells, respectively. VZV TK metabolically activated the nontoxic prodrug 6-methoxypurine arabinonucleoside (araM), ultimately leading to the formation of the cytotoxic anabolite adenine arabinonucleoside triphosphate (araATP). Cells that selectively expressed VZV TK became selectively sensitive to araM due to the VZV TK-dependent anabolism of araM to araATP. Hence, these retroviral-delivered chimeric genes generated tissue-specific expression of VZV TK, tissue-specific anabolism of araM to araATP, and tissue-specific cytotoxicity due to araM exposure. By utilizing such retroviral vectors, araM was anabolized to araATP in hepatoma cells, producing a selective cytotoxic effect.
Clinical genetics and genetic counseling in Alzheimer disease. Because of growing evidence for genetic causes of Alzheimer disease, clinicians are often asked about risks for this disorder among relatives of patients. This paper briefly reviews the evidence for genetic and other causes of Alzheimer disease, including specifically its typical late-onset variant. Several recent developments in the molecular genetics of early-onset Alzheimer disease are described briefly. These findings, however, may not apply to more typical, late-onset Alzheimer disease. Genetic studies of the latter disorder are complicated by the censorship of any inherited predisposition to disease by death from other causes. Hence, heritable disease may be apparent only in families with large numbers of elderly relatives at risk. Relying on empiric observations of risk among relatives from several recent studies of pooled Alzheimer families, curves are presented describing theoretic age-specific risks in relatives of patients and unaffected controls. Real (current) lifetime risks of Alzheimer disease are then estimated by modification of the theoretic figures with corresponding current age-specific mortality characteristics of the U.S. population. The lifetime incidence among relatives of patients with Alzheimer disease is estimated to be 19%, or three to four times the risk among control relatives. Because both mortality of and risk for Alzheimer disease change rapidly with advancing age, it may be possible to reduce the current morbidity from Alzheimer disease by 50% if onset can be postponed by only 5 years.
Symptomatic gastro-oesophageal reflux, abnormal oesophageal acid exposure, and mucosal acid sensitivity are three separate, though related, aspects of gastro-oesophageal reflux disease. The Bernstein test has been used as a test of oesophageal acid sensitivity for over 30 years but its clinical value has been challenged by the advent of ambulatory pH monitoring. Furthermore, the relation between mucosal acid sensitivity, symptomatic reflux, and abnormal oesophageal acid exposure time is unclear. This study examined the relation between these three parameters in patients referred for pH monitoring with unexplained chest pain or heartburn. Fifty consecutive patients were studied - nine with non-cardiac chest pain and 41 with a history of heartburn. Symptomatic reflux was defined as a greater than or equal to 50% temporal association between pain episodes and reflux events (pH less than 4) during pH monitoring. A positive acid perfusion test (in which the patient's usual symptoms were evoked by acid, though not saline) had a 100% sensitivity, 73% specificity, and 81% accuracy for the detection of symptomatic reflux. All 10 patients with symptomatic reflux during pH monitoring had evidence of mucosal acid sensitivity. A negative acid perfusion test made symptomatic reflux unlikely. However, symptomatic reflux or a positive acid perfusion test, or both, were found in some patients with a normal oesophageal acid exposure time during pH monitoring. Mucosal acid sensitivity, abnormal oesophageal acid exposure time, and symptomatic reflux should be regarded as separate, though related aspects of reflux disease. The Bernstein test is simple, safe, and easily performed. A positive test helps to identify an oesophageal cause of symptoms, particularly in patients in whom other aspects of 'gastro-oesophageal reflux disease' are absent, or who do not have symptoms during pH monitoring.
Cytomegalovirus epididymitis following renal transplantation. Cytomegalovirus infection is an important cause of morbidity and mortality in immunocompromised individuals. The disease is usually systemic in expression although localized infection can occur, particularly in the lung, liver, retina and gastrointestinal tract. We report a case of cytomegalovirus epididymitis with limited systemic manifestations occurring 2 months after renal transplantation in a patient immunosuppressed with azathioprine, prednisone and cyclosporine. Diagnosis was confirmed by observation of typical cytopathic changes in epididymal cells. Clinical resolution occurred with epididymo-orchiectomy and 9-(1,3-dihydroxy-2-proproxymethyl)guanine therapy. To our knowledge this presentation has not been described previously in the transplant literature and it is extremely rare in other forms of inherited or acquired immune deficiency.
Surgical strategies in the treatment of pancreatic necrosis and infection. Controversy still surrounds the management of necrotic and septic complications of acute pancreatitis. A review of the literature of the past decade dealing with the surgical treatment of pancreatic necrosis, pancreatic abscess and infected pancreatic necrosis has been undertaken. Three main patterns of management could be identified: (1) 'conventional treatment', consisting of pancreatic resection or necrosectomy with drainage; (2) 'local lavage', consisting of necrosectomy followed by regional lavage; and (3) 'open management', with resection or necrosectomy followed by planned multiple re-explorations. From this review it appears that local lavage and open management offer better survival prospects than conventional treatment. Open abdomen techniques, however, are associated with an increased risk of complications, such as colonic necrosis, intestinal fistula, and intra-abdominal bleeding. Excellent results can be achieved in specialized centres with any of the three methods, provided adequate debridement and prompt reoperations are undertaken if the septic state persists.
High-signal-intensity rim surrounding uterine leiomyomas on MR images: pathologic correlation. A high-intensity rim surrounding uterine leiomyomas was identified on T2-weighted magnetic resonance (MR) images in five of 13 patients with histopathologically confirmed leiomyomas. These peripheral high-intensity rims were not associated with subject age or with size, location, or degeneration of the leiomyomas. Histologic examination revealed markedly dilated lymphatic vessels, dilated veins, edema, or a combination of these features to correspond to the location of the high-intensity rims. These benign causes of high intensity in the myometrium should not be confused with clinically important processes such as adenomyosis or invasion by endometrial carcinoma.