shukoor65/lab-rag-model huggingface dataset:
Oestrogen receptor D5 antibody is an independent negative prognostic factor in gastric cancer. Recent studies have demonstrated oestrogen receptors in tissues other than those considered to be sex hormone responsive, for instance in gastric cancer. In vitro experiments have shown oestradiol to be trophic to gastric cancer cell lines. The effect of D5 (an oestrogen receptor-related protein) status on survival was therefore studied in a group of 188 consecutive patients undergoing surgery for gastric cancer. Ninety-two patients (49 per cent) were positive for the D5 antibody. There were no differences between the D5-positive and D5-negative groups for age or adverse prognostic features such as high grade tumours or advanced stage. The D5-negative patients had a significant survival advantage over the D5-positive patients. The 95 per cent confidence interval for survival in the patients with D5-negative tumours was 63-101 weeks compared with 39-66 weeks for the patients with D5-positive tumours (Mantel-Cox statistic = 4.15, P = 0.042). Prognostic factor analysis with a Cox proportional hazards model showed tumour stage (P = 0.001) and D5 status (P = 0.003) to be significant independent factors in gastric cancer. Lauren type, grade and gender were not significant independent factors in this small series.
Intracellular calcium transients and arrhythmia in isolated heart cells. Intracellular calcium ([Ca2+]i) elevation may mediate cardiac arrhythmias. However, direct measurement of the rapid alterations of [Ca2+]i on a beat-to-beat basis using fast temporal resolution and without signal averaging in the spontaneously beating in vivo heart is lacking. Furthermore, data from an isolated spontaneously beating myocyte preparation that develops arrhythmia similar to that in the in vivo heart are unavailable. We measured rapid changes of [Ca2+]i with fast temporal resolution in isolated spontaneously beating neonatal rat ventricular myocytes with cell-to-cell communication and characterized the interrelation between [Ca2+]i and arrhythmia. An elevated extracellular calcium ([Ca2+]o) concentration of 10.8 mM induced premature beats, a rapid beating rate (tachyarrhythmia), and chaotic or fibrillatory beating activity in a small group of myocytes. [Ca2+]i levels during systole increased from the nanomolar to micromolar concentration range before arrhythmia development. Spontaneous oscillations of [Ca2+]i during diastole could evoke a spontaneous tachyarrhythmia. In the presence of [Ca2+]i elevation, a spontaneous tachyarrhythmia could induce severe [Ca2+]i overload. Reduction of [Ca2+]i with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid AM (5 microM) in the presence of 10.8 mM [Ca2+]o reversed the arrhythmia. In single ventricular myocytes superfused with 10.8 mM [Ca2+]o, oscillations of membrane potential characteristic of transient inward current occurred that were prevented by ryanodine (0.1 microM), an inhibitor of Ca2+ flux across the sarcoplasmic reticulum. This study characterizes 1) an isolated multicellular myocyte model of arrhythmia similar to that evident in in vivo hearts, 2) elevation of [Ca2+]i with systolic [Ca2+]i levels of 1-3 microM and diastolic [Ca2+]i oscillations before the initiation of arrhythmia, 3) tachyarrhythmia as a cause of severe [Ca2+]i overload, which may be important in the perpetuation and degeneration of arrhythmias, and 4) reversal of arrhythmia with reduction of [Ca2+]i. The results in the isolated myocyte model may have relevance to the generation and perpetuation of certain cardiac arrhythmias associated with calcium overload.
Idiopathic scrotal calcinosis is idiopathic. The appearance of calcific masses within the dermis of scrotal skin is generally referred to as idiopathic scrotal calcinosis. There has been some debate about the pathogenesis of these calcium deposits. This debate centers on the question of whether the calcium deposition is truly idiopathic or whether it occurs as a result of preexisting epidermal cysts. We have performed immunohistochemical staining for keratin in nine patients with apparent idiopathic scrotal calcinosis and have found no evidence of keratin in the dermal tissue immediately adjacent to the calcium deposits. We conclude that idiopathic scrotal calcinosis is idiopathic.
Benign familial neonatal convulsions: evidence for clinical and genetic heterogeneity. The gene for autosomal dominant "benign" familial neonatal convulsions, a transient, primary epilepsy of infancy, has recently been assigned to chromosome 20q. To determine whether this disorder is genetically heterogeneous, we performed linkage analysis in two previously unreported pedigrees with benign familial neonatal convulsions in which clinical heterogeneity was evident. There were 14 affected persons in the first family, and none had seizures (febrile or afebrile) after the age of 2 months. The second family had 13 affected individuals and 2 obligate carriers; seizures frequently did not remit until 6 to 24 months, febrile convulsions occurred in at least 2 patients, apparent audiogenic seizures occurred in 4 patients, and 1 individual had refractory epilepsy until late adolescence. Linkage studies with the chromosome 20 markers D20S19 and D20S20 were performed in both families. The resulting data favored linkage of the disease and marker loci in Family 2 by a maximum odds ratio of 45:1 at 6% recombination. In Family 1, however, the odds were greater than 20,000:1 against linkage at 10% recombination or less. We conclude that the syndrome of benign familial neonatal convulsions is clinically and genetically heterogeneous. Further study will be necessary to clarify the relationship between phenotype and genotype in this disorder.
The risks of metastases from shunting in children with primary central nervous system tumors. The authors reviewed the hospital charts of 415 pediatric patients treated for benign or malignant primary brain tumors over the past 20 years at the Children's Hospital Medical Center, Seattle. Patients' ages ranged from the neonatal period to 18 years. A shunt was placed in 152 patients (37%), 45 before and 94 after surgery. Confirmation of extraneural metastases was based on clinical and diagnostic examination. Factors analyzed as possibly influencing the occurrence of extraneural metastases were: 1) the shunt: type, valve, location, filter, and revisions; 2) extent of resection; 3) pathology; and 4) treatment regimen. Eight of the 415 patients developed extraneural metastases during life. All eight patients had a medulloblastoma (cerebellar primitive neuroectodermal tumor). These eight patients were separated into Group A (without a shunt) and Group B (with a shunt). In Group A (five patients), the mean interval from primary diagnosis to metastasis was 15 months. Two children had gross total resection of the tumor. The predominant location of metastases in Group A was: bone (two cases); cervical lymph nodes (one); lung/bone (one); and retroperitoneal pelvic mass (one). Three Group A patients had a simultaneous central nervous system (CNS) recurrence. Of the three Group B patients, two had a ventriculoperitoneal (VP) shunt and one a ventriculoatrial (VA) shunt; all were placed postoperatively. One Group B patient had a simultaneous CNS recurrence. No shunt revisions were performed in these three patients. The mean time from primary diagnosis to metastasis was 25 months. One patient had a total tumor resection. The predominant location of metastases was bone (one case), retroperitoneal pelvic mass (one), and abdominal cavity with ascites (one case). Only one patient in the entire series had a filter placed; this resulted in shunt obstruction and was removed 1 month following placement. It is concluded that cerebrospinal fluid shunts, regardless of type, location, revision rate, or filter insertion, do not predispose pediatric patients with brain tumors to develop extraneural metastases. A diagnosis of shunt-related metastases should be based on the development of intra-abdominal (VP shunt) or pulmonary (VA shunt) dissemination primarily with or without additional sites. The diagnosis of medulloblastoma is an important factor related to metastasis occurrence while the extent of resection and postoperative therapy are not influential.
Prognostic factors in advanced head and neck cancer patients undergoing multimodality therapy. A retrospective analysis was performed to investigate potential prognostic factors for complete remission to neoadjuvant chemotherapy and overall survival in patients with previously untreated stage III and stage IV head and neck cancer. Eighty consecutive patients were treated in one of two studies investigating three or four courses of neoadjuvant chemotherapy. Before local therapy and surgery and/or radiotherapy, 29% attained a complete remission. No strong significant and independent predictor of complete remission was identified. Only nodal stage (N) was found moderately associated with complete remission (p = 0.06). Node-negative patients had higher remission rates. Less important predictors were tumor stage (T) and site of disease; nasopharyngeal patients had superior remission rates (56%). With a median followup of 45 months and estimated 3-year survival rate of 38% (median 23.7 months), individual factors predictive of survival included pretherapy weight loss, performance status, alcohol use, pretherapy serum albumin level, site of disease, and N stage. In multivariate testing weight loss was identified as the strongest independent predictor of survival (p less than 0.0001) and surpassed other health status measures, such as performance status and serum albumin level. In addition, N stage (p = 0.019) and alcohol use (p = 0.017) were found to be predictive. A cross-classification by N stage and weight loss revealed risk groups with distinctly different prognoses, which may be useful for design and analysis in future trials.
Aspirin does not inhibit cholesterol cholelithiasis in two established animal models. The effect of aspirin on cholesterol cholelithiasis was examined in the hamster and the prairie dog. In the prairie dog, diets were composed of semipurified components of chow, plus cholesterol (1.2%), with and without aspirin. Animals were studied for either 2 weeks or 4 weeks. Cholesterol gallstones were present in all groups at the end of each period; aspirin did not alter the incidence of cholelithiasis. All animals studied had cholesterol crystals in the bile when they were killed. Liver cholesterol levels in prairie dogs with and without aspirin tended to be lower in animals fed chow than in animals fed semipurified diets. There were no significant differences in cholesterol levels in the plasma or bile. The cholesterol saturation index of all biles approached unity when animals were fed chow with aspirin; animals fed the semipurified diets had cholesterol saturation indices of less than 1.0. The prairie dogs fed aspirin plus cholesterol in the semipurified diet showed increased levels of biliary chenodeoxycholic acid amidates and concomitant decreased levels of cholic acid amidates compared with animals fed the same diet without aspirin. Hamsters fed aspirin plus cholesterol in a semipurified diet tended to have a greater incidence of gallstones than animals given no aspirin (80% vs. 55%). Liver and bile cholesterol levels were similar with and without aspirin; plasma cholesterol levels increased significantly with aspirin [14.20 vs. 7.80 mmol/L (549 vs. 301 mg/dL)]. Lithogenic indices in all hamsters were above unity; biliary lipids, total lipid concentration, and biliary bile acid composition were similar. These results show that the addition of aspirin to a lithogenic diet does not reduce the incidence of cholelithiasis.
Azoospermia: a complication of hydrocele repair in a fertile population. Although minor complications have been reported, hydrocelectomy generally is considered to be a safe procedure. We recently treated 3 patients who became azoospermic after hydrocele repair. Of the patients 2 underwent bilateral and 1 unilateral hydrocelectomy. All 3 patients had iatrogenic injury to the vas deferens or epididymis after hydrocele repair.
Cholesterol screening and life assurance. OBJECTIVES--To examine how insurance companies assess proposals for life assurance from applicants with raised cholesterol concentrations and to determine the excess mortality rating applied. DESIGN--Survey of 49 companies underwriting term life assurance. SETTING--United Kingdom. SUBJECTS--Four fictional men aged 30 seeking 20 year term policies paying benefit only on death. Two had total cholesterol concentrations of 6.4 and 8.1 mmol/l but no other cardiovascular risk factors; one was overweight, hypertensive, smoked 20 cigarettes daily, and had a total cholesterol concentration of 8.1 mmol/l; and one had possible familial hypercholesterolaemia and a total cholesterol concentration of 10.7 mmol/l after treatment. MAIN OUTCOME MEASURE--Percentage excess mortality rating. RESULTS--All companies used explicit criteria to assess the mortality risk associated with hyperlipidaemias, and 47 companies applied the same criteria to men and women. No excess mortality rating was imposed on an applicant with a total cholesterol concentration of 6.4 mmol/l, but a small excess was applied to an applicant with a concentration of 8.1 mmol/l (median excess 50%, range 0-75%). When multiple cardiovascular risk factors were present the same concentration of 8.1 mmol/l resulted in a substantial excess (median 135%, range 50-200%). A smaller but more variable excess was applied to an applicant with possible familial hypercholesterolaemia (median 75%, range 0-200%). CONCLUSIONS--Despite considerable differences among companies in the excess mortality ratings applied, increases in term life assurance premiums are likely to be restricted to patients with severe hypercholesterolaemia, in particular those with familial hypercholesterolaemia. In the absence of other cardiovascular risk factors milder hypercholesterolaemia is unlikely to result in higher premiums.
Cyclophosphamide plus cisplatin versus cyclophosphamide, doxorubicin, and cisplatin chemotherapy of ovarian carcinoma: a meta-analysis. The Ovarian Cancer Meta-Analysis Project. Four randomized clinical trials comparing cyclophosphamide plus cisplatin (CP) versus cyclophosphamide, doxorubicin, and cisplatin (CAP) individually failed to show a significant survival difference in the treatment of ovarian carcinoma. However, by pooling 1,194 patients from these trials in a meta-analysis, there is a statistically significant survival benefit for CAP (P = .02); in addition, there is a significant advantage for CAP in frequency of negative second-look laparotomy (CAP, 30%; CP, 23%; P = .01). Because the dose intensity of CAP was greater than CP in three of the trials, it remains unresolved to what extent the benefit of CAP is from greater dose intensity and to what extent it is from the doxorubicin itself. Either interpretation suggests directions for improving the chemotherapy of ovarian carcinoma.
Response of newly established mouse myeloid leukemic cell lines to MC3T3-G2/PA6 preadipocytes and hematopoietic factors. Some mouse myeloid leukemias induced by X-irradiation and serially transplanted into syngenic mice do not proliferate in vitro even in the presence of hematopoietic factors. To examine whether such leukemic cells can proliferate in response to stromal cells, we cocultured them with MC3T3-G2/PA6 (PA6) preadipocytes, cells that can support the growth of hematopoietic stem cells. All leukemias developed into in vitro cell lines, showing a dependence on contact with the PA6 cells. Two cell lines responded to none of the known hematopoietic factors including interleukin-3 (IL-3), IL-4, IL-5, IL-6, GM-CSF, G-CSF, M-CSF, and Epo. These results demonstrate that the mechanism of the action of PA6 cells is different from that of any of the known hematopoietic factors, and that, because these two leukemic cell lines retained the ability to grow in vivo, responsiveness to the known hematopoietic factors is not essential for the leukemic cell growth in vivo. Furthermore, all leukemic cell lines could respond also to the preadipocytes fixed with formalin, paraformaldehyde, or glutaraldehyde, suggesting that some molecule(s) associated with the surface of PA6 cells or with extracellular matrix secreted by the preadipocytes is responsible for the leukemic cell growth.
Syringoid eccrine carcinoma. Eccrine carcinomas are locally aggressive and have an infiltrative growth pattern. They have a variable clinical appearance and a diversity of histologic findings that often make the diagnosis difficult. The histologic findings, together with immunoperoxidase and enzyme histochemical studies, usually allow differentiation between eccrine carcinomas, other cutaneous neoplasms, and visceral adenocarcinomas with skin metastases. Provided there is no evidence of distant metastases, surgical excision is the treatment of choice. We report a case of syringoid eccrine carcinoma that was treated with Mohs micrographic surgery.
Reinforced sternal closure. A technique of reinforced sternal closure with stainless steel struts is described. Stable sternum avoids severe complications such as mediastinitis and sternal dehiscence.
Recurrent varicella-zoster virus infections in apparently immunocompetent children. Fourteen generally healthy children (5 females, 9 males, ages 18 months to 13 years) who have developed 2 to 5 attacks of chickenpox are described. Herpes zoster also occurred in 2 of 14 children. No case of chickenpox was severe or associated with complications. General studies of immunoglobulins, specific antibodies to immunization agents, complement and lymphocyte subpopulation number and function indicated that 1 of 14 had low serum IgA and 3 of 14 lacked antibody to 1 (n = 2) or 2 (n = 1) immunization agents. Varicella-zoster virus (VZV)-specific immune studies showed that the children developed VZV-antibody titers by enzyme-linked immunosorbent assay of 1:640 to 1:10 240. By immunoblot assay all appeared to develop a normal spectrum of antibodies to individual VZV proteins. All but one developed VZV cellular immune responses with stimulation indices ranging from 3.6 to 174. Sequential follow-up of 8 patients revealed 1 who became seronegative and 2 who lost VZV cell-mediated immune responses. Chickenpox may recur more frequently than is generally recognized. General and VZV-specific immune investigations are unlikely to indicate a reason.
Cervical implantation metastasis by endometrial adenocarcinoma. A distinct type of cervical involvement by endometrial cancer is reported and termed cervical implantation metastasis. It is believed to result from implantation of endometrial cancer on the denuded endocervix after fractional dilatation and curettage (D & C). The histologic criteria for diagnosis are: (1) the cervical implantation metastasis must be imbedded in the endocervical epithelium or superficial stroma surrounded by an implantation site of inflammatory cells and granulation tissue (free-floating cancer cells above the cervical mucosa are not acceptable as implantation tissue), (2) the histologic findings of the cervical implantation metastasis must be similar to those of the endometrial adenocarcinoma in the uterine corpus, (3) the cervical implantation metastasis must be separate from the primary tumor with no evidence of direct extension, and (4) the cervical implantation metastasis should be surrounded by nonneoplastic endocervical glands with no transition between the two. Of the 176 patients who underwent fractional D & C before hysterectomy, nine (5%) were found to have cervical implantation metastasis. No patients had cervical implantation metastasis who did not undergo fractional D & C before hysterectomy. When stratified according to stage, grade, and myometrial invasion, there was no statistically significant difference in the recurrence rate between patients with or without cervical implantation metastasis. It appears that cervical implantation metastasis does not alter prognosis or require specific treatment.
Osteoid osteoma: CT-guided percutaneous treatment. Seven patients with presumed osteoid osteoma were treated with percutaneous destruction or drill resection with computed tomographic (CT) guidance. The diagnosis of osteoid osteoma was made on the basis of findings in the clinical history and results at plain radiography, bone scintigraphy, and CT. In four patients, histologic confirmation was obtained. Hospital stay lasted from 1 to 3 days. After 11-38 months of follow-up examinations, all patients were asymptomatic. The authors report this simple procedure as an alternative to the more traditional open surgery technique.
New potent verapamil derivatives that reverse multidrug resistance in human renal carcinoma cells and in transgenic mice expressing the human MDR1 gene. Multidrug resistance in human renal cell carcinoma is mainly caused by expression of the MDR1 gene and is characterized by a broad spectrum cross resistance to many natural product chemotherapeutic agents. This resistance can be overcome by applying chemosensitizers which inhibit the function of the MDR1 gene product P-glycoprotein. The development of new reversing agents with fewer side effects and a higher potency in modifying resistance is a high priority of research on drug resistance. We have evaluated four new verapamil derivatives on 21 primary human renal cell carcinomas in vitro, and also tested them in an MDR-transgenic mice model. These mice express the human MDR1 gene in their bone marrow cells and measurement of their white blood counts provides a simple, rapid and reliable system to screen for the potency of MDR-reversing agents in vivo. We demonstrate here that all four drugs are effective in reversing multidrug resistance in primary cultures of human renal cell carcinomas when used in combination with vinblastine chemotherapy, and to a lesser extent with doxorubicin or daunomycin chemotherapy. Our in vivo data indicate that two of these reversing agents display low toxicity at high concentrations and are more effective at low, clinically achievable concentrations, than the other two drugs and R-verapamil. These results make the two new drugs attractive candidates to be taken into clinical trials.