shukoor65/lab-rag-model huggingface dataset:
Course of brittle diabetes: 12 year follow up. OBJECTIVE--To determine the course of brittle diabetes. DESIGN--12 year follow up of patients identified in 1977-9 as having brittle diabetes; retrospective review of the case notes. SETTING--Nottingham health district. SUBJECTS--25 brittle diabetic patients were identified in 1979-9; 11 (five men) had three or more admissions with ketoacidosis between June 1977 and 1979 and 14 (eight men) had three or more attendances at the accident and emergency department with hypoglycaemia in 1978. Two controls from our diabetic register were matched to each patient for age, sex, and duration of diabetes. MAIN OUTCOME MEASURES--Frequency of ketoacidosis and severe hypoglycaemia in the 12 years after ascertainment; diabetic control and complications in 1988-90; retrospective attribution of the cause of brittleness. RESULTS--Patients with recurrent ketoacidosis had had a median (range) of 28 (8-67) episodes. One man died of a cerebral tumour but five of the surviving nine patients had not been admitted in the past two years, although diabetic control remained poor (median haemoglobin A1 concentration 14%). Seven patients had pure hypoglycaemic brittleness, and five had also had eight or more admissions with ketoacidosis (mixed brittleness). Two died of uraemia within a year after ascertainment and two others in hypoglycaemic coma seven and 12 years later. Brittle diabetes was in most cases related to a specific situation, usually unhappiness at home or school. CONCLUSIONS--Brittle diabetes is often episodic and almost always related to stressful life circumstances. Once the underlying cause is removed it tends to improve. Recurrent hypoglycaemic brittleness of psychological origin has a poor prognosis.
Twenty five years of case finding and audit in a socially deprived community. OBJECTIVE--To evaluate audit and case finding (whole population care) in a community over 25 years. DESIGN--Contemporary screening for and audits of care of chronic disease and risk factors; retrospective review of computerised practice records; and comparisons of mortality and social indices with neighbouring communities. SETTING--One general practice in Glyncorrwg, West Glamorgan. SUBJECTS--1800 people registered with the practice in 1987 and 558 people who died from 1964 to 1987, whose records had been retained. MAIN OUTCOME MEASURES--Detection of high blood pressure, smoking, airways obstruction, obesity, diabetes, and alcohol problems in adults aged 20-79; prevalence of smoking in this population and in hypertensive and diabetic groups; age standardised mortality ratios in relation to indices of social deprivation. RESULTS--In the population aged 20-79 (1207 patients) 249 (21%) had peak expiratory flow rate less than 50% of expected value or which improved by 15% or more with an inhaled beta agonist, 207 (17%) had body mass index at or over 30 kg/m2, 118 (10%) had untreated mean arterial pressures greater than 159/104 mm Hg (three readings), 80 (7%) (65 (16%) men, 15 (4%) women) had recognised alcohol problems, and 35 (3%) had diabetes. The proportion of men aged 20-64 who said they smoked fell from 61% (290/476) in 1968-70 to 36% (162/456) in 1985 whereas that of women who smoked was unchanged (43%, 187/436 v 42%, 190/448 respectively). In 116 screened hypertensive patients group mean blood pressure fell from 186/110 mm Hg before treatment to 146/84 mm Hg at 1987 audit, as did the proportion of smokers (56% v 20%), but body mass index and total cholesterol concentration showed no significant change. In 34 diabetic patients mean blood pressure and the proportion of smokers fell (171/93 mm Hg v 155/81 mm Hg; 44% v 12%). The age standardised mortality ratio in 1981-6 was lower than in a neighbouring village without a developed case finding programme (actual to expected deaths less than 65 = 21 to 22 in Glyncorrwg, 48 to 30 in control village). CONCLUSIONS--Whole population care through organised case finding and audit is feasible but only with a labour intensive approach combining accessibility, flexibility, and continuity, as well as a planned and structured approach, which requires substantial expansion of staff numbers and assiduous recording. It may reduce risks for at least some high risk groups. Despite their shortcomings the available data are consistent with the hypothesis that whole population care helps reduce mortality. Incentives in the new contract, which encourage the uncritical development of structured process, may diminish health outputs.
Cell-cycle-related staining patterns of anti-proliferating cell nuclear antigen monoclonal antibodies. Comparison with BrdUrd labeling and Ki-67 staining. Monoclonal antibodies (MAbs) to nuclear antigens are increasingly used as tools to obtain valuable information concerning the proliferative characteristics of various types of cancer. Prerequisite for the application of these MAbs in surgical pathology is establishment of the level of expression and/or cellular distribution of the antigens in relation to distinct cell-cycle compartments. In this study the topologic distribution of proliferating cell nuclear antigen (PCNA), an auxiliary protein of DNA polymerase delta, as recognized by human autoantiserum (AK) and two recently developed MAbs (19A2 and 19F4), was evaluated. Using cultured human cancer cells as a model system, and providing optimal fixation/permeation procedures are applied, these antibodies display a high affinity for PCNA bound to nuclear replicon clusters, resulting in distinct granular staining patterns. A more diffuse nucleoplasmic PCNA staining was mainly restricted to non-S-phase cells; in methanol-fixed cells, staining intensity of this form relative to the replicon-bound form appeared higher after staining with 19A2 than with 19F4 or AK. Comparing PCNA expression (detected with 19A2) with the expression of the Ki-67 antigen, PCNA-negative cells are also Ki-67 negative. In MCF-7 human breast cancer cells treated with 10(-6) mol/l (molar) tamoxifen, the fraction of nuclei showing replication patterns decreased from 42% to 8% within 8 days, but PCNA and Ki-67 antigens remained detectable in most cells during this interval, indicating a relatively slow decrease of antigen expression in cells that have entered a quiescent state. Treatment of MCF-7 cells with 10(-6) mol/l methotrexate resulted in a rapid accumulation of cells with an early S-phase DNA content; PCNA replication patterns showing a frequency distribution reflecting this DNA content were observed up to 48 hours after treatment. This indicates that the presence of replication patterns as visualized with anti-PCNAs is not a measure of replicative activity per se. It is concluded that, providing nuclear non-S-phase PCNA staining is faint relative to staining of replicon clusters, anti-PCNA antibodies may be excellent markers to detect in situ cells with S-phase DNA contents.
Acute myocardial infarction associated with prostaglandin E2. Prostaglandin E2 is rarely associated with serious maternal side effects when used for second-trimester pregnancy termination. Acute myocardial infarction complicating therapeutic pregnancy termination with prostaglandin E2 in a patient with chronic glomerulosclerosis and severe hypertension is reported.
Submaximal endurance exercise performance during enalapril treatment in patients with essential hypertension. In a double-blind randomized crossover study of 10 patients with mild essential hypertension, the influence of antihypertensive treatment with the angiotensin-I converting enzyme inhibitor enalapril (a single dose of 10 mg.day-1) on submaximal endurance exercise performance at a work rate eliciting a heart rate of 150 beats/min was studied. Resting and exercise blood pressure were significantly reduced during enalapril therapy. Heart rate was unaffected. Submaximal endurance exercise performance was reduced by 12% (p = 0.06). Plasma lactate concentrations were significantly increased and serum nonesterified fatty acid concentrations were decreased during exercise in patients receiving enalapril treatment. Plasma glucose and potassium levels and serum glycerol concentrations were not influenced by enalapril treatment. Because the impairment of endurance performance during enalapril treatment is relatively small compared with the reductions caused by other antihypertensive agents, such as beta-adrenoceptor blocking agents or diuretics, it is of minor clinical importance for most physically active patients with hypertension.
Stage distribution of breast cancer: a basis for the evaluation of breast screening programmes. Stage at presentation can be predictive of future mortality rates. A change in stage distribution will be indicative of the effect of a programme. All registrations for 1985 aged over 50 years were staged from case notes and, to assess whether a stage drift is already occurring, cases that presented in 1975 were also staged. The accuracy and completeness of the Wessex Cancer Register for this particular cancer was assessed and further sources of registration identified. There was a significant difference between 1975 and 1985 stage distributions. If the Southampton and Salisbury service achieves the same success as the Gavleborg County trials, 4.61 deaths will be prevented at 5 years for each annual cohort of cases. For individual breast screening programmes, effectiveness is better monitored by analysis of stage distribution than of mortality rates.
Transfalcine approach to a callosomarginal artery aneurysm. We describe a transfalcine approach to clipping and subsequently excising an expanding mycotic callosomarginal aneurysm. The patient had a devastating dominant (left) hemispheric spontaneous intracranial hemorrhage and was neurologically improving at the time of surgery nearly 2 months later. To avoid retracting the left hemisphere, we approached this left callosomarginal aneurysm from the nondominant side through the falx. The approach was straight-forward, and the result was satisfactory.
Pagetoid carcinomatous involvement of the penile urethra in association with high-grade transitional cell carcinoma of the urinary bladder. We present a case of pagetoid carcinomatous involvement of the penile urethra and periurethral glands following cystoprostatectomy for high-grade transitional cell carcinoma of the urinary bladder. Previously reported cases with involvement of the urethra are reviewed. This condition is believed to be a rare variant of transitional cell carcinoma in situ.
Localized Aspergillus infestation in primary lung carcinoma. Clinical and pathological contrasts with post-tuberculous intracavitary aspergilloma. Saprophytic infestation with Aspergillus was observed in pathologic specimens of primary squamous cell lung carcinoma. In one case, the fungus grew in cystic scarred parenchyma and bronchi distal to an obstructing carcinoma of a segment bronchus. In the other, fungi colonized the inner surface of a peripheral cavitary carcinoma. Neither patient had roentgenographic evidence of aspergilloma and neither experienced severe pulmonary hemorrhage or other complications attributable to the presence of fungus. Although both specimens showed colonizing growth within the abnormal air spaces, in neither had the colonies detached to form a separate intracavitary fungus ball. These patients, and eight patients with similar lesions reported in the literature, demonstrate that Aspergillus colonization of a lung neoplasm frequently lacks one or both of the features characteristic of post-inflammatory intracavitary aspergilloma, a loose fungus ball and antifungal serum antibodies. No patient, to date, has developed massive hemorrhage as a complication of this lesion.
Recurrence risk of a new dominant mutation in children of unaffected parents. Extensions to models originally described by Hartl for predicting the recurrence risk of new dominant mutations are developed in this paper. Additions to the models are (1) possible somatic mosaicism in a parent in some families, (2) the possibility that the parental origin of the mutation may or may not be known, and (3) mutation rates which change as a function of sex and/or time. The models indicate that recurrence risks are most critically affected by (a) the amount of somatic mosaicism which can be tolerated in the parent without manifesting disease and (b) knowledge of the parental origin of the mutation. In addition, there is a moderate effect on recurrence risks if mutation rates increase in the father as a function of time. Recurrence risks are at least as large as the risk of trisomy 21 in a child of a mother of age 35 years or older, probably much higher (5%-10%) when the mutation is known to be of maternal origin or if substantial somatic mosaicism in the parent is compatible with a normal phenotype. The recurrence risk of a new mutation is high because of a very high ascertainment bias of families with substantial germ-line mosaicism.
Purtscher's-like retinopathy after childbirth. Severe bilateral visual loss attributable to multiple retinal arteriolar occlusions occurred in four young women within 24 hours after childbirth. In two patients, labor was complicated by preeclampsia requiring cesarean section. One patient was suffering from pancreatitis. None had connective tissue disease or antecedent trauma. Ophthalmoscopy and fluorescein angiography revealed evidence of multiple superficial peripapillary and macular patches of ischemic retinal whitening simulating Purtscher's retinopathy. By 8 weeks, the white patches were resolving in all eyes and visual acuity had significantly improved in three of the four patients. The pathogenesis of this disorder is unknown but may involve arteriolar obstruction by complement-induced leukoemboli formed during parturition.
Seronegative symmetric polyarthritis in Sezary syndrome. We describe a patient with Sezary syndrome and seronegative symmetric polyarthritis. Detailed analysis of the synovial membrane, including T lymphocyte subset delineation, demonstrated that malignant synovial infiltration was the direct cause of arthritis in this patient.
Cyclophosphamide cardiotoxicity in bone marrow transplantation: a prospective evaluation of new dosing regimens. Cyclophosphamide (CY) cardiotoxicity may be a lethal complication of bone marrow transplantation. Previous echocardiographic studies have reported that left ventricular dysfunction due to CY occurs in over 50% of patients undergoing transplantation. To evaluate the cardiotoxicity of new dosing protocols that included twice-daily rather than once-daily CY, 44 bone marrow transplantation patients were prospectively evaluated with serial ECGs and echocardiograms. Twenty-six patients received a once-daily lower-dose protocol (mean total 87 +/- 11 mg/kg), and 18 patients received a twice-daily higher-dose (mean total 174 +/- 34 mg/kg) CY regimen. In the higher-dose CY group, significant reductions in summed ECG voltage (-20%) (P less than .01) and increases in left ventricular mass index (LVMI) (+10%) (P less than .05) were detected in the first week following therapy. These changes resolved by the third week following CY and were significantly greater than the changes noted in the lower-dose group. However, left ventricular ejection fraction (EF) did not change significantly in either group. Five patients developed clinical cardiotoxicity (four, pericarditis; one, congestive heart failure); four of the five patients were in the higher-dose group (P = .14). Only a prior history of congestive heart failure or a baseline EF less than 50% was an independent correlate of clinical cardiotoxicity (P less than .05). Thus, dose-dependent cardiotoxicity following the use of CY for bone marrow transplantation is evident as reversible decreases in ECG voltage and increases in left ventricular mass, possibly reflecting myocardial edema or hemorrhage. However, systolic dysfunction is much less common with these new twice-daily dosing regimens when compared with earlier studies of high-dose once-daily CY.
Engraftment after infusion of CD34+ marrow cells in patients with breast cancer or neuroblastoma. The CD34 antigen is expressed by 1% to 4% of human and baboon marrow cells, including virtually all hematopoietic progenitors detectable by in vitro assays. Previous work from our laboratory has shown that CD34+ marrow cells can engraft lethally irradiated baboons. Because the CD34 antigen has not been detected on most solid tumors, positive selection of CD34+ cells may be used to provide marrow cells capable of engraftment, but depleted of tumor cells. In seven patients with stage IV breast cancer and two patients with stage IV neuroblastoma, 2.5 to 17.5 x 10(9) marrow cells were separated by immunoadsorption with the anti-CD34 antibody 12-8 and 50 to 260 x 10(6) positively selected cells were recovered that were 64 +/- 16% (range 35% to 92%) CD34+. The patients received 1.0 to 5.2 x 10(6) CD34-enriched cells/kg after marrow ablative therapy. Six patients engrafted, achieving granulocyte counts of greater than 500/mm3 at 34 +/- 10 (range 21 to 47) days and platelets counts of greater than 20,000/mm3 at 46 +/- 14 (range 28 to 66) days posttransplant. Five of these patients showed durable engraftment until the time of death 82 to 386 days posttransplant. One patient failed to sustain engraftment associated with metastatic marrow disease. Three patients died at days 14, 14, and 17 posttransplant, two of whom had evidence of early engraftment. These studies suggest that CD34+ marrow cells are capable of reconstituting hematopoiesis in humans.
Vasopressin levels in infants during the course of aseptic and bacterial meningitis. We measured urine vasopressin (VP) once daily on days 1 through 3 in 18 patients hospitalized with meningitis. Urine VP values were 215 +/- 100, 116 +/- 44, and 69 +/- 23 pg/mL on days 1 through 3, respectively, for children with bacterial meningitis and 34 +/- 14, 20 +/- 4, and 15 +/- 4 pg/mL for those with aseptic meningitis. Urinary VP levels of infants with bacterial meningitis were significantly greater than those of healthy ambulatory subjects (n = 18) on all three study days; VP values of infants with bacterial meningitis were also greater than those of infants with aseptic meningitis on study days 2 and 3. The VP levels for the subjects with aseptic meningitis were significantly greater than those of the controls on day 1 only. None of the infants exhibited the clinical syndrome of inappropriate antidiuretic hormone secretion.
Disseminated malignant melanoma and recombinant interferon: analysis of seven consecutive phase II investigations. We have performed seven phase II trials with recombinant interferons (IFN) involving 191 patients with biopsy-proved, measurable disseminated malignant melanoma. The regimens and numbers of patients have included IFN-alpha 2A, 50 X 10(6) U/m2 subcutaneous (SQ) TIW (regimen A, 31 patients); IFN-alpha 2A, 12 X 10(6) U/m2 SQ TIW (regimen B, 30 patients); IFN-alpha 2A with cimetidine as an immunorestorative agent (regimen C, 35 patients); IFN-gamma (regimen E, 29 patients); IFN-alpha 2A with IFN gamma (Regimen E, 20 patients); IFN-alpha 2A with bis-chloroethylnitrosourea (BCNU) (regimen F, 30 patients); and IFN-alpha 2A with the biochemical modulator, difluoromethylornithine (DFMO) (regimen G, 16 patients). The objective regression rates were as follows: A, 23%; B, 20%; C, 23%; D, 10%; E, 5%; F, 7%; G, 0%. Despite the higher response rate from regimen A, there appeared to be no survival advantage from any of these programs. The median time to progression was 1 month with a median survival time of 6 months. Most regressions involved soft tissue disease, were partial, and occurred within 2-3 months of treatment. Four patients received IFN for approximately 6 months and have manifested extraordinarily durable regressions of greater than 4+ years. The alpha-regimens produced a flu-type illness and anorexia which were dose-related. Leukopenia was most noteworthy with regimens containing gamma-interferon. Ongoing trials involving alternative and improved immune-related modalities are awaited with keen interest.
The prophylactic use of cyclooxygenase inhibitors in recurrent herpes simplex infections. In an open study, continuous oral therapy with cyclooxygenase inhibitors (ibuprofen or indomethacin) reduced the incidence and frequency of recurrent eruptions in nine of 16 patients with herpes simplex virus infection. Retrospective analysis of seven cases indicated that natural killer cell enhancement assays might allow us to predict the clinical outcome of such treatment.
Fusiform dilatations of the carotid artery following radical surgery of childhood craniopharyngiomas. Between 1982 and 1990, a series of 31 children with craniopharyngiomas underwent initial surgery at the Children's Hospital of Philadelphia with an attempt at total tumor removal. Nine (29%) of them were found to have fusiform dilatation of the supraclinoid carotid artery either at the time of surgery for recurrence (one patient) or on routine surveillance with enhanced computerized tomography 6 to 18 months postoperatively (eight patients). The finding of carotid enlargement was confirmed in seven cases with magnetic resonance angiography and in one case with a formal arteriogram. Eight of the nine patients remain alive at a mean of 3.7 years after diagnosis. None have experienced hemorrhage or other symptoms referrable to fusiform dilatation of the carotid artery, which is believed to result from surgical manipulation of the carotid artery.
Adenoid cystic carcinoma: DNA as a prognostic indicator. A retrospective study was performed on 20 patients with adenoid cystic carcinomas of major salivary glands to see if DNA patterns correlated with their prognoses. Fourteen tumors were found to be DNA diploid; 6 were DNA aneuploid. Histologically, all DNA-aneuploid tumors had solid components, compared with only 5 of the DNA-diploid tumors. All of the DNA-aneuploid tumors recurred, in contrast to only 2 of the DNA-diploid tumors; the difference was highly significant (P less than 0.001). All of the patients with no recurrences had DNA-diploid tumors. In our study, DNA measurements of adenoid cystic carcinomas gave statistically significant information about prognosis and correlated to histological grading. We propose that evaluation of DNA content may be performed before planning the treatment of adenoid cystic carcinomas.
Computed tomography of cranial metastatic malignant melanoma: features, early detection and unusual cases. The cranial computed tomographic (CT) scans reported as showing metastatic disease in patients with malignant melanoma (MM) seen at the Westminster Hospital over a 5 year period were reviewed. Ninety-eight patients with intracranial metastatic MM were identified. Twelve had an initial scan which was reported as normal and particular attention was given to these to see if, in retrospect, any early features of metastatic disease were discernible. Fifty-eight cases showed the "typical" features of intracranial MM; the remainder were unusual in appearance, behavior, or site. Radiological regression was shown in only seven cases on follow-up scans; all but one of these patients had one or two large metastases. No significant lesion was thought to have been missed on a scan after the administration of intravenous contrast medium, but the lesions of three patients were difficult to discern on plain scans. Thus when MM metastasis is suspected, the use of the contrast-only scan is advocated.