shukoor65/lab-rag-model huggingface dataset:
Prognostic factors in invasive bladder carcinoma in a prospective trial of preoperative adjuvant chemotherapy and radiotherapy Clinical and pathologic factors were analyzed in 40 patients with localized muscle-invasive bladder carcinoma treated in a prospective bladder-preserving program consisting of transurethral tumor resection, neoadjuvant chemotherapy (methotrexate, cisplatin, and vinblastine [MCV]), and 4,000 cGy radiotherapy with concurrent cisplatin. Patients with biopsy-proven complete response after chemotherapy and 4,000 cGy radiation received full-dose radiotherapy (6,480 cGy) with cisplatin. Cystectomy was recommended to patients with residual disease. Distant metastasis rate was associated with tumor stage and size: 0% in T2 patients, 39% in T3-4 patients (P = .035), 6% for tumors less than 5 cm, and 59% for tumors greater than or equal to 5 cm (P = .002). Risk of bladder tumor recurrence was higher in patients with tumor-associated carcinoma in situ (CIS; 40%) than those without CIS (6%; P = .075). Papillary tumors and solid tumors both had similar treatment outcomes. By multivariate analysis, tumor stage T2 (P = .04) and absence of CIS (P = .03) were significant predictors of complete response; CIS was predictive of local bladder recurrence (P = .07); and tumor size (P = .03), response after chemoradiotherapy (P = .02), and vascular invasion (P = .08) were associated with distant metastasis. Six of eight local bladder tumor recurrences were superficial tumors. The low actuarial distant metastasis rate of T2 patients (0% at 3 years), the 3-year actuarial overall survival rates for T2 (89%) and T3-4 (50%) patients, and the similar treatment outcomes for papillary versus solid tumors are encouraging when compared with published historical controls. These results provide preliminary evidence (median follow-up, 30 months) that the current chemoradiotherapy regimen may have beneficial effects in the treatment of muscle-invasive bladder carcinoma. The true efficacy of neoadjuvant chemotherapy remains to be proven by ongoing randomized trials.
N-(fluorenyl-9-methoxycarbonyl) amino acids, a class of antiinflammatory agents with a different mechanism of action [published erratum appears in Proc Natl Acad Sci U S A 1991 Mar 15;88(6):2612] Several members of a series of N-(fluorenyl-9-methoxycarbonyl) amino acids were found to possess a broad spectrum of antiinflammatory activity. The compounds were active against oxazolone dermatitis in mice and adjuvant arthritis in rats, models in which activated T lymphocytes are implicated. The compounds also inhibited T-lymphocyte activation in vitro, assessed by using the mixed lymphocyte reaction. The compounds inhibited the reversed passive Arthus reaction in rats and arachidonic acid-induced dermatitis in mice, models in which leukocyte infiltration is responsible for the inflammatory reaction. More complete evaluation was made of one compound, N-(fluorenyl-9-methoxycarbonyl)leucine (NPC 15199). On histologic examination after arachidonic acid administration, NPC 15199 was found to block recruitment of neutrophils into the inflammatory site. The compound was not a general myelotoxin. Prolonged treatment of animals did not alter bone-marrow progenitor number or the numbers of circulating white blood cells. Further, several white cell functions were not inhibited in vitro, including neutrophil respiratory burst and macrophage phagocytosis. NPC 15199 was effective in blocking antigen arthritis in rabbits and was effective in a therapeutic protocol, reversing oxazolone edema. These studies suggest that N-(fluorenyl-9-methoxycarbonyl) amino acids may be valuable therapeutic agents for inflammatory diseases.
10 year review of invasive aspergillosis detected at necropsy. Between 1980 and 1989, 32 cases of invasive aspergillosis were identified out of 2315 consecutive necropsies, an incidence of 1.4%. The incidence in immunosuppressed "high risk" patients was 10.7%. Twenty out of 32 cases showed spread beyond the lungs, with the brain the most common site. There was an increase in cases in the second half of the decade, attributable to the start of a liver transplantation programme. Liver transplant recipients and patients with haematological malignancies were at significantly greater risk of acquiring aspergillosis than kidney transplant recipients or those with solid malignancies treated with chemotherapy. There was also a greater risk of haematogenous dissemination in liver transplant recipients than in all other groups, and this was significantly associated with the use of high dose steroids as anti-rejection treatment. Aspergillus was isolated during life in only eight cases, which indicates a continuing need for and emphasises the value of necropsy.
Antibodies to cytoplasmic sequences of cloned liver growth hormone (GH) receptors recognize GH receptors associated with tyrosine kinase activity. GH stimulates tyrosyl phosphorylation of GH receptors in 3T3-F442A fibroblasts, and highly purified GH receptor preparations exhibit tyrosine kinase activity. Paradoxically, however, the GH receptor cloned from liver exhibits no sequence similarity to receptors with known signal transduction mechanisms, including those exhibiting ligand-activated tyrosine kinase activity. These observations raise the possibility that there are two kinds of receptors for GH: the first represented by the cloned liver GH receptor, and the second by a tyrosine kinase-containing GH receptor. To inquire into the possibility of two distinct GH receptors, we determined whether the cloned liver GH receptor shares structural similarities with the tyrosine kinase-associated GH receptor. When the cloned rabbit liver GH receptor is expressed in human kidney 293 cells, it migrates with a mol wt appropriate for the tyrosine kinase-associated GH receptor, despite the calculated mol wt of the cloned GH receptor being 60,000 smaller than that of the tyrosine kinase-associated GH receptor. The recognition of tyrosine kinase-associated GH receptor by antipeptide antibodies to three different epitopes on the cytoplasmic domain of the cloned liver GH receptor was also tested. Tyrosyl phosphorylated [125I]human GH-receptor complexes were prepared by immunoprecipitation with phosphotyrosyl-binding antibody; this subpopulation of GH-receptor complexes was recognized by all three antipeptide antibodies. The antibodies also recognized similarly isolated tyrosyl phosphorylated GH-receptor complexes, which had been further phosphorylated in solution on tyrosyl residues upon addition of [gamma 32P] ATP. Furthermore, highly purified GH receptors prepared by sequential immunoprecipitation using phosphotyrosyl-binding antibody and any one of the three antipeptide antibodies incorporated 32P into tyrosyl residues upon the addition of [gamma 32P] ATP. These results provide evidence that tyrosine kinase-associated GH receptors share sequence similarity in the cytoplasmic domain with the cloned liver GH receptor. The cloned GH receptor and the tyrosine kinase-associated GH receptor, therefore, are likely to be the same receptor or related receptor isoforms.
An analysis of sequential physiologic changes in hypoxic cor pulmonale during long-term oxygen therapy. Physiologic changes were studied retrospectively in 37 patients with hypoxic cor pulmonale who died during long-term oxygen therapy (LTOT). The subjects were assessed during periods of clinical stability for each year on LTOT. At the onset of treatment, their mean age (+/- SEM) was 60.0 +/- 1.3 years, and at the time of death, they were aged 65.0 +/- 1.3 years. The median duration of LTOT was five years. For each year leading up to death, mean values of FEV1, PaO2, and PaCO2 were obtained. A rate of decline of FEV1 of 73 +/- 10 ml/yr was observed, and this was accompanied by a decline in PaO2 of 0.47 +/- 0.01 kPa/yr. Patients died with a mean FEV1 of 0.55 +/- 0.04 L and a PaO2 of 5.1 +/- 0.2 kPa. A small rise in PaCO2 occurred, on average 0.25 +/- 0.09 kPa/yr, throughout the study, but accelerating in many cases during the three years before death. Hypoxic cor pulmonale appears to be associated with a rapid deterioration in airway function, a steady decline in PaO2, and a slow rise in PaCO2 during the years leading up to death. These physiologic changes measured in a stable clinical state while breathing air appear to occur in spite of LTOT. The LTOT may merely prevent death from episodes of severe hypoxemia while the pathophysiologic changes in the lung progress. Hence the benefit to be expected from LTOT is only temporary. Generally, those patients with lower levels of FEV1 will obtain diminishing clinical benefit, inversely related to the severity of airflow obstruction at the time of commencement of LTOT.
Non-infective verrucous endocarditis in a patient with 'primary' antiphospholipid syndrome. A 27-year-old women with 'primary' antiphospholipid syndrome, who developed a haemodynamically significant non-infective verrucous endocarditis is reported. Her mother suffered from antiphospholipid syndrome associated with systemic lupus erythematosus. A pathogenetic role of antiphospholipid antibodies in heart valve lesions is suggested.
Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease [published erratum appears in Nature 1991 Aug 8;352(6335):547] The human prion diseases, Creutzfeldt-Jakob disease (CJD) and Gerstmann-Straussler syndrome (GSS), are neurodegenerative diseases that are unique in being both infectious and genetic. Transmission of both diseases and the animal spongiform encephalopathies (for example, scrapie and bovine spongiform encephalopathy) to experimental animals by intracerebral inoculation with brain homogenates is well documented. Despite their experimental transmissibility, missense and insertional mutations in the prion protein gene are associated with both GSS and familial CJD, demonstrating that the human familial cases are autosomal dominant diseases. More than 80% of CJD cases occur sporadically, however, and are not known to be associated with mutations. Here we report that 21 of 22 sporadic CJD cases and a further 19 of 23 suspected sporadic CJD cases are homozygous at the polymorphic amino-acid residue 129; 51% of the normal population are heterozygous at this site. We argue that homozygosity predisposes towards sporadic CJD and that this directly supports the hypothesis that interaction between prion protein molecules underlies the disease process.
Correlation of the antiproliferative effect and the Mx-homologous protein induction by IFN in patients with malignant melanoma. The human interferon-induced intracellular protein homologous to the murine Mx-protein has recently been identified by means of a specific monoclonal antibody. Three of six melanoma cell lines elicited this intracellular human Mx-homolog upon incubation with IFN-alpha or IFN-gamma, yet all six melanoma cell lines tested were susceptible to the antiproliferative effect of IFN-alpha and IFN-gamma. Compared per antiviral unit, IFN-gamma had weaker Mx-inducing but stronger antiproliferative activity than IFN-alpha. These data suggest that the IFN-induced Mx-homologous protein is not involved in the antiproliferative action of IFN on malignant melanoma cell lines. Furthermore, 51 patients with advanced malignant melanoma were treated thrice weekly with 10 x 10(6) IU rIFN-alpha-2b and 6 x 10(6) nIFN-alpha, respectively. Nine of the 51 patients experienced systemic objective tumor responses (3 complete response, 6 partial response), but had Mx concentrations in their mononuclear cells equal to the Mx levels of non-responders during IFN-alpha therapy. Therefore, the level of Mx-homologous protein induced during IFN therapy is not a predictive marker for an antitumor response in malignant melanoma.
A preliminary report of ticarcillin and clavulanate versus triple antibiotic therapy in children with ruptured appendicitis. Standard therapy for childhood ruptured appendicitis includes combination antibiotic therapy with ampicillin, gentamicin and clindamycin. Complicated dosing schedules and the possibility of aminoglycoside toxicity make alternatives desirable. One such alternative is Timentin (a combination agent of ticarcillin disodium and clavulanate potassium). This agent has a more convenient dose schedule than standard therapy and eliminates the possibility of aminoglycoside ototoxicity and nephrotoxicity. It is active in vitro against most pathogens associated with ruptured appendicitis in children. The preliminary results of an ongoing prospective, open label, randomized trial comparing ticarcillin and clavulanate with ampicillin, gentamicin and clindamycin in childhood ruptured appendicitis are reported herein. While further evaluation is necessary, we have found single agent therapy with ticarcillin and clavulanate to be equivalent in safety and efficacy to standard combination therapy. Also discussed are the relative merits of immediate versus delayed primary closure of the abdominal wound after appendectomy.
Spondyloepiphyseal dysplasia congenita. Caesarean section under epidural anaesthesia. Spondyloepiphyseal dysplasia congenita is a rare condition with several features of concern to the anaesthetist. The patients are of extremely short stature and the presence of kyphoscoliosis may lead to significant respiratory impairment. Cervical vertebral body changes can result in spinal cord compression and laryngotracheal stenosis may be present. The management of such a patient presenting for elective Caesarean section under epidural anaesthesia is described.
Peripheral odontogenic fibroma: a clinicopathologic study. The clinicopathologic features of 30 cases of peripheral odontogenic fibroma are reviewed. The age distribution is wide (11 to 76 years), and there is a slight predilection for males. The majority of the lesions (93%) occurred in blacks on the attached gingiva, and with equal frequency in the maxilla and mandible. Size varied between 1 and 3 cm in diameter. One case recurred after 14 months. Histologically, the lesions are nonencapsulated and poorly delineated. The amount of odontogenic epithelium varies considerably and consists usually of small islands or strands, although larger follicles are sometimes present. In one case the epithelial cells had a clear cytoplasm, whereas in another it was granular and eosinophilic. Origin from the surface oral mucosa can sometimes be seen. The connective tissue component is usually cellular, but collagenous, myxomatous, and mixed forms occur. Calcifications were present in 22 cases and consisted of tissue interpreted as either dentinoid, cementum, bone, or dystrophic calcific material.
Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis. A model of Wilson's disease. Long-Evans Cinnamon (LEC) rats, an inbred strain of a mutant rat isolated from Long-Evans rats, develop hereditary hepatitis. To elucidate the role of copper metabolism in the development of the hepatitis in LEC rats, we examined the copper concentration in the tissues and serum levels of copper and ceruloplasmin. Copper concentration in the liver of LEC rats was over 40 times that of normal Long-Evans Agouti (LEA) rats, while the serum ceruloplasmin and copper concentrations in LEC rats decreased significantly. The hepatocytes of LEC rats show steatosis in cytoplasm and pleomorphism of mitochondria, resembling the histologic features of the liver in Wilson's disease. These findings suggest that the hereditary hepatitis in LEC rats is closely associated with copper toxicity, and may be dealing with a rat form of Wilson's disease. Thus the LEC rats will provide a unique and useful animal model for clarifying the mechanism and for developing treatment strategies for Wilson's disease and other abnormal copper metabolism in humans.
Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus. To clarify the relationship between hepatitis C virus infection and the development of hepatocellular carcinoma as sequelae of non-A, non-B posttransfusion hepatitis, 231 patients with chronic non-A, non-B hepatitis (96 with chronic hepatitis, 81 with cirrhosis and 54 with hepatocellular carcinoma) were analyzed for antibody to hepatitis C virus and were compared with 125 patients with chronic hepatitis B (50 with chronic hepatitis, 46 with cirrhosis and 29 with hepatocellular carcinoma). Antibody to hepatitis C virus was detected in 89.6%, 86.4% and 94.4% of patients with non-A, non-B hepatitis-related chronic hepatitis, cirrhosis and hepatocellular carcinoma, respectively, compared with 6%, 17.4% and 34.5% with similar diseases related to hepatitis B. A history of transfusion was documented in 52%, 33% and 42% of anti-hepatitis C virus-positive cases of chronic hepatitis, cirrhosis and hepatocellular carcinoma. The mean intervals between the date of transfusion and the date of diagnosis of anti-hepatitis C virus-positive chronic hepatitis, cirrhosis and hepatocellular carcinoma were 10, 21.2 and 29 yr, respectively. In 21 patients with transfusion-associated hepatocellular carcinoma, anti-hepatitis C virus was present in each serial sample available for testing, including samples obtained up to 14 yr before the diagnosis of hepatocellular carcinoma. These data suggest the slow, sequential progression from acute hepatitis C virus-related non-A, non-B hepatitis through chronic hepatitis and cirrhosis to hepatocellular carcinoma and support a causal association between hepatitis C virus and hepatocellular carcinoma.
Safety of alcohol after viral hepatitis. To test the validity of the generally held belief that moderate consumption of alcohol during convalescence from acute viral hepatitis adversely affects outcome, 87 adults recovering from acute viral hepatitis (hepatitis A in 36, hepatitis B in 34, hepatitis non-A, non-B in 17) were studied. Criteria for entry to the study attempted to ensure that no patient was a chronic hepatitis B carrier. Patients were randomised either to a moderate alcohol intake, or to continued complete abstention. Drinkers consumed 26 g alcohol daily (mean) and none remained abstinent. At 3 months all patients were well, with normal liver function tests. There were no significant differences between the two groups at anytime. The findings suggest that moderate alcohol intake during convalescence from acute viral hepatitis does not seem to be harmful.
Involvement of the retinoblastoma gene in primary osteosarcomas and other bone and soft-tissue tumors. The retinoblastoma (Rb) gene, thought by some to be associated with tumor formation of retinoblastoma as a recessive human oncogene, was investigated in 57 cases using DNA and RNA from primary osteosarcomas and other bone and soft-tissue tumors. Eight of 23 osteosarcoma cases (35%) showed structural alterations of the Rb gene. Three of the eight demonstrated homozygous deletions, and the remaining five cases showed heterozygous deletions. Seven out of eight cases represented deletion of a 7.5-kb HindIII fragment. Northern blot analysis of five cases of osteosarcoma showed that four demonstrated no detectable Rb gene transcription, and one case had a truncated 3.5-kb fragment with a faint 4.7-kb band. In the other 34 cases of bone and soft-tissue tumors, two cases of three malignant fibrous histiocytomas showed an Rb gene abnormality by Southern blot analysis. These results strongly suggest that Rb gene alteration is pertinent to the tumorigenesis of most osteosarcoma cases and some other bone and soft-tissue tumors.
Identification of alloimmunized patients: use of radiolabeled allogeneic platelet kinetic measurements and platelet antibody tests. In a group of stable, nonthrombocytopenic leukemia patients awaiting bone marrow transplantation, results of paired allogeneic radiolabeled platelet kinetic measurements were correlated with the results of several different platelet and lymphocytotoxic antibody tests to determine which parameters could be used to identify patients who were alloimmunized to platelets. Seven patients with acute leukemia who had been transfused during induction therapy were used as the test group, and, as a control group, five untransfused patients with chronic myelogenous leukemia were also studied. Concurrent fibrinogen survival measurements were performed in all patients to assess whether hemostatic factor consumption (ie, disseminated intravascular coagulation) was present. Allogeneic platelet survival measurements were reduced from normal in all 12 study patients. In 8 of 12 patients, fibrinogen and platelet survival measurements were comparably reduced, suggesting disease-related platelet consumption. In four heavily transfused patients with acute leukemia, allogeneic platelet survivals were markedly reduced to less than or equal to 2.1 days, compared with the 3.5- to 7.4-day platelet survival measurements found in the other eight patients. The disproportionately short platelet survivals compared with fibrinogen survival measurements in these four patients, combined with documented positive antibody tests to their donors' platelets in the three patients with evaluable tests, suggested that these patients had become alloimmunized to platelets because of their prior transfusions. There was substantial concordance between the two radiolabeled allogeneic donor platelet survival measurements performed in each of these patients, suggesting that host rather than donor factors have a major influence on transfusion outcome (r = .93, P less than .001). The platelet cross-match tests, using the radiolabeled protein Staph A assay combined with the IgG enzyme-linked immunosorbent assay test, had the best correlation with the posttransfusion recovery and survival of the donors' platelets.
Comparison of IgG antibody profiles by immunoblotting in patients with acute and previous Toxoplasma gondii infection. The IgG antibody profile to Toxoplasma gondii proteins of less than 37 kilodaltons in sera from patients with acute and previous infection was studied by immunoblotting. Bands at 28, 29, and 36 kilodaltons were more common in acute infection (10 out of 10, nine out of 10, and nine out of 10, respectively) compared with previous infection (five out of 10, four out of 10, and one out of 10, respectively). The 6 kilodalton band was present in 10 out of 10 sera from patients with acute infection and five out of 10 sera from those with previous infection. A new observation is a doublet of bands of 22-25 kilodaltons present only in sera from patients with acute infection. This doublet may be a more reliable indicator of acute infection than the 6 kilodalton band.
Effect of enteral nutrition on exocrine pancreatic function. Twelve patients with chronic pancreatitis underwent a pancreatoduodenectomy in which the pylorus was preserved. The effects of parenteral and enteral nutrition on pancreatic secretion were compared. Postoperative nutrition was administered by needle-catheter jejunostomy in seven patients and by total parenteral nutrition in five patients. Pancreatic juice, drained directly from the pancreatic duct, was collected in 4-hour fractions. Volume, bicarbonate, protein, amylase, and chymotrypsin were measured. In the first two postoperative days, there was a slow increase in all measured indices. On the third postoperative day, an abrupt rise occurred, after which pancreatic secretion stabilized. No differences in exocrine pancreatic secretion were observed between the enteral and parenteral methods of feeding.