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Biomedical subjects

M Adler

Publications and source records attributed to M Adler.

At least 163 records · Page 9Linked to original sources
PubMed1990

Identification of a new site of conformational heterogeneity in unfolded ribonuclease A.

The results presented here indicate that there are two slowly exchanging conformational isomers in unfolded bovine pancreatic ribonuclease A (RNase A) in the vicinity of Lys-41. The conformational heterogeneity is not observed in the fully folded protein. Therefore, one of the isomers may correspond to one of the slow-folding forms of the protein observed when refolding is initiated. These results were obtained from a chemically modified form of the protein, CL(7-41) RNase A, that has a dinitrophenyl cross-link between the epsilon-amino groups of Lys-7 and Lys-41. Extensive physical studies have shown that the cross-link does not significantly perturb the structure or the folding pathways of the protein. Therefore, the results obtained from this modified form of the protein are relevant to intact RNase A. The one-dimensional (1D) NMR spectrum of heat-unfolded CL(7-41) RNase A reveals that the singlet resonance for the C3H ring proton of the dinitrophenyl cross-link has been split into two unequal peaks in a 3:1 ratio, indicating that there are two distinct environments for the dinitrophenyl group. Variations in temperature, and the addition of urea, do not affect the relative peak intensities. The two peaks collapse into one after the protein is refolded. The observed splitting must originate from a slow reversible isomerization (greater than 100 msec) in a neighboring bond. The two most likely candidates are either the cis/trans isomerization of the Lys-41-Pro-42 peptide bond or hindered rotation about the disulfide bond between Cys-40 and Cys-95.

Disulfides↗
PubMed1990

Factors influencing survival at one year in patients with nonbiliary hepatic parenchymal cirrhosis.

Transplantation may be considered for patients with advanced cirrhosis, however, adequate criteria for evaluating survival in those patients are ill-defined. The aim of the present study was to select, among several clinical and functional variables those that could best predict survival at one year. The data collected from 91 consecutive patients with parenchymal cirrhosis hospitalized in our center from February 1984 to January 1986 were subjected to stepwise logistic regression analysis. Death occurring during the first year following entry into the study was considered as a failure. During that period, there were no censored patients. Of 19 variables that entered into the analysis, only two were significant (P less than 0.01): presence (1: moderate; 2: severe) or absence (0) of ascites (A) and breath test (BT: % aminopyrine activity of administered dose at 2 hr). The logistic equation was: 1n (P/1 - P): - 1.95 A + 1.64 BT - 0.393, where P represented the probability of survival at one year. For each patient, P was calculated according to his A and BT values. Using a 0.7 probability cut-point to separate success from failure, 93% (70/75) of successes, 81% (13/16) of failures, and 91% (83/91) of both successes and failures could be correctly predicted. Predictive equations like the present preliminary one can be used in the future to better assess the risk of mortality in patients with parenchymal cirrhosis in whom liver transplantation is considered.

Breath Tests↗
PubMed1990

Efficacy of interferon alfa-2b with or without prednisone withdrawal in the treatment of chronic viral hepatitis B. A prospective double-blind Belgian-Dutch study.

A prospective, double-blind study was carried out to assess the efficacy of interferon alfa-2b, with or without pre-treatment prednisone withdrawal, in patients with chronic hepatitis B. A total of 57 Belgian and Dutch patients were included in the study. Patients were divided into four treatment groups: Group A, prednisone withdrawal followed by interferon 5 million units per day; Groups B and C, placebo followed by interferon 5 or 1 million units, respectively; and Group D, untreated controls followed for 1 year. All treated patients received interferon for 16 weeks. Two of the 14 control patients lost hepatitis B e antigen during the year of study, and only one of 15 patients in the interferon 1 million units group. Among the 28 patients receiving 5 million units of interferon (with or without prednisone withdrawal), ten (36%) cleared hepatitis B e antigen during the study or within 6 months of the end of therapy. This was associated with a marked improvement in serum transaminase levels. When comparing Groups A and B, it was found that prednisone withdrawal therapy enhanced the response to interferon in patients with pre-treatment serum alanine aminotransferase levels below 100 IU/l, bringing the seroconversion rate up to 50%, compared to 17% on interferon alone. This effect was not seen in patients with high pre-treatment transaminase levels. All treatment responders showed a marked improvement in Knodell index score, whereas in the 15 non-responders from groups A and B, overall inflammatory activity remained the same in six, improved in five and worsened in four.(ABSTRACT TRUNCATED AT 250 WORDS)

Belgium↗
PubMed1990

High-dose epirubicin in combination with cyclophosphamide (HD-EC) in advanced breast cancer: final results of a dose finding study and phase II trial.

In the dose finding study we were able to demonstrate that an increase of the epirubicin dose to 120 mg/m2 in combination with cyclophosphamide (600 mg/m2) is possible. The phase II trial had to check the efficacy and the toxicity of this combination with a therapy interval of 21 days. 34 patients with metastatic breast cancer previously not treated with chemotherapy for metastatic disease entered this phase II trial, which tested the efficacy and toxicity of the chemotherapy combination epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 (HD-EC regimen) i.v. every three weeks. Excluded from the trial were patients at risk of anthracycline toxicity and those with bone or brain metastases. Results compare favourably with best data reported in the literature for chemotherapy of metastatic breast cancer: overall remission rates of 73% (35% CR, 38% PR), median TTP of 58 weeks for CR (range 32-168 weeks) and 52 weeks for the PR group (range 24-110 weeks); median survival time for CR 71+ weeks (range 52-196+), for PR 74+ weeks (range 40-134+ weeks). No therapy was given for remission maintenance after a stable remission was obtained. This results in a very favourable ratio of time with chemotherapy to maintenance time without chemotherapy, which is 10 weeks/62 weeks for CR and 12 weeks/49 weeks for PR. Evidence of tumor remission was found in 80% of the patients who already responded to chemotherapy after the first cycle. The early onset of tumor response as well as the short induction chemotherapy period necessary to obtain best response are considered major advantages of the HD-EC regimen.

Adult↗
PubMed1990

[Long-term results of the anti-emetic effectiveness of the 5-HT3 antagonist ondansetron].

40 patients with metastatic breast cancer, under treatment with epirubicin (greater than 50 mg/m2) and cyclophosphamide (greater than 500 mg/m2), had an antiemetic therapy with Ondansetron 3 x 8 mg day, for a maximum of 10 cycles. A total of 128 treatment cycles were analysed. There was no reduction in antiemetic efficacy, regarding vomits/day and grade of nausea. 77% (31/40) had a steady or better control of vomiting during the whole treatment period. Only 23% experienced a reduction in the antiemetic efficacy in repeated therapy. 60-100% of the patients also had control of nausea (mild or none). Generally, there were no signs for a reduction of the antiemetic efficacy of Ondansetron in repeated therapy. There were neither clinically relevant side effects nor changes in laboratory values related to Ondansetron.

Antiemetics↗
PubMed1990

Use of somatostatin for complications occurring after liver transplantation.

Somatostatin can be helpful after liver transplantation in some well-defined indications. In uncontrolled digestive haemorrhage, a short course of somatostatin therapy can be of great help in controlling the acute bleeding and to avoid emergency laparotomy. Somatostatin could also be helpful in bilio-pancreato-intestinal fistula, but in this case its advantage over elective surgical treatment remains to be confirmed.

Acyclovir↗
PubMed1990

Macroscopic and microscopic gut lesions in seronegative spondyloarthropathies.

A retrospective study by ileocolonoscopy and multiple biopsies was performed on 96 patients with seronegative spondylarthropathy, 17 patients with osteoarthritis (OA) and 19 patients with chronic abdominal discomfort. Under these conditions, inflammatory gut lesions were detected in 66.7% of the patients with spondyloarthropathy, 12.5% with OA and 15.8% with chronic abdominal discomfort. In 10 patients treated by sulfasalazine (Salazopyrine), pathologic lesions disappeared simultaneously with an improvement of the rheumatic conditions. comparison between patients treated and untreated with nonsteroidal inflammatory drugs (NSAID) demonstrated that NSAID did not enter into the etiopathology of the intestinal lesions. Our study therefore confirms the high incidence of inflammatory gut lesions among patients with spondylarthropathy which seems not to be related to NSAID therapy.

Abdominal Pain↗
PubMed1990

[Spastic colon: a multi-factorial pathology, a polyvalent therapy].

Irritable bowel syndrome represent the most common gastrointestinal disease. It is characterized by abdominal pain, distension and abnormalities of intestinal transit. It is a functional disorder determined by emotional stress and by diet. The treatment is polyvalent, dietary, medicinal and psychological. In the medicinal domain the anti-spasmodics (anti-nicotinic and musculotropic), represent the first choice weapons in association or not with an anxiolytic, an anti-depressor, even an antalgic in the acute phase.

Adult↗
PubMed1990

[The radiotherapy of epidemic Kaposi's sarcomas in AIDS patients].

From August 1986 to May 1989, 15 patients suffering from Kaposi's sarcoma and serologically proven HIV infections were treated in the Department of Radiotherapy, University of Cologne, Medical Hospital. All patients were male and homosexual. Therapeutic objectives were palliation of pain and functional impairment as well as elimination of the cosmetically disturbing Kaposi's sarcoma. 68 localizations (facial skin, torso, extremities, sole of the foot, penis, oral mucosa and oropharynx) were irradiated. Depending on the individual therapy regimen, photons or high-energy electrons up to a total dose of 26 to 40 Gy, with single doses of 1.8 to 2.5 Gy were applied four to five times a week. In 66% of the cases, complete remission was achieved within the area of irradiation at the dermal or mucosal level, with at most a discrete residual pigmentation of the cluster remaining. Partial remission with at least 50% regression or a distinctive residual pigmentation was achieved in 31%. In 3% of the cases, a less than 50% regression of the Kaposi's lesions were achieved after radiotherapy. There were five local recurrences. Treatment with radiation is an effective local therapy in epidemic Kaposi's sarcoma and yields good functional and cosmetic results and also provides relief from pain.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Aggressive osteoblastoma of the temporal bone: a case report.

Osteoblastoma is a rare tumor of bone which is usually present in the long bones and vertebrae. Occasionally, they present in the head and neck, and only very rarely will they have a locally aggressive clinical course. We report a case of the aggressive subtype of benign osteoblastoma and its histologic and radiologic presentation.

Adult↗
PubMed1990

[Lack of predictive factors for symptomatic recurrence of Crohn disease at the site of surgical anastomosis].

Recurrence of Crohn's disease at the ileocolonic anastomosis after curative surgery is frequent. Prognostic value of several parameters at the time of surgery was studied in 37 patients to detect early symptomatic recurrence of Crohn's disease after surgery. These included patient age at the time of surgery, sex, disease duration before surgery, clinical activity index, length of resected bowel, presence of granulomas in resected bowel segment, indication for surgery, type of medical treatment before surgery, and biochemical parameters at the time of surgery (ESR, C reactive protein and serum albumin level). Symptomatic recurrence associated with endoscopic lesions at the anastomotic site was observed in 10 of 37 patients (27 percent), within one year after surgery. None of the studied parameters were able to differentiate the patients with recurrence or not.

Adolescent↗
PubMed1990

Liver transplantation for fulminant and subacute viral hepatic failure in adults.

In our early experience, orthotopic liver transplantation was found to be successful in fulminant and subacute hepatic failure due to viral hepatitis in adults, with 66% 1-year survival rate. In the future, more accurate prognostic criteria would probably improve overall survival rate in acute hepatic failure, by allowing better and earlier selection of patients requiring liver transplantation.

Adult↗
PubMed1989

The actions of a red tide toxin from Ptychodiscus brevis on single sodium channels in mammalian neuroblastoma cells.

The actions of brevetoxin (PbTX-3) were studied on single, voltage-dependent sodium channels and whole-cell currents from the neuroblastoma x glioma cell line NG108-15. Purified PbTX-3 shifted the activation of sodium channels to membrane potentials negative to normal. PbTX-3 did not alter the single-channel mean open lifetime, suggesting that the toxin does not change the rate of sodium channel inactivation from the open state. There was also no change in single-channel conductance. These results indicate that brevetoxin increases sodium current at rest by shifting the voltage dependence of channel activation and that the resulting depolarization is limited by channel inactivation.

Animals↗
PubMed1989

Risk factor adapted treatment of Hodgkin's lymphoma: strategies and perspectives.

In a national multicenter trial in the Federal Republic of Germany, patients with Hodgkin's lymphoma in stages I, II and IIIA presenting with large mediastinal tumor (MT), extranodal (E), or massive spleen (S) involvement received a combined modality treatment with 2x (COPP + ABVD) followed by 20 or 40 Gy EF radiation (HD1 protocol). By October 1987, 89 patients aged 15-60 years had finished therapy and were evaluable for response. Of these 74 (83%) achieved complete remission (CR). After 3 years freedom from treatment failure (FFTF) is 80% (+/- 8%, 95% confidence interval) and survival (SV) 92% (+/- 6%, 95% confidence interval). In a univariate and multivariate analysis using FFTF as endpoint we could not identify any particularly prominent prognostic risk factor among the following examined: stage, constitutional symptoms, MT, E stage, S involvement, age, sex, histology, laparotomy, erythrocyte sedimentation rate (ESR), leukocytes, lymphocytes, and alkaline phosphatase (AP). These data suggest that the inclusion criteria have selected a fairly homogeneous group of patients with respect to prognosis. In a separate trial (HD3 protocol) patients in stages IIIB/IV received induction chemotherapy with 3x (COPP + ABVD). Patients in complete remission (CR) received consolidation therapy by either radiotherapy (20 Gy IF) or further chemotherapy (COPP + ABVD). Patients not in CR received salvage therapy (40Gy in the case of persisting nodal disease, or else 4x CEVD chemotherapy). By October 1987, 137 patients had finished therapy and were evaluable for response. Of these 86 (63%) achieved CR after induction chemotherapy. Including salvage therapy a total of 104 patients (76%) achieved CR. After 3 years FFTF is 56% (+/- 10%, 95% confidence interval) and SV 84% (+/- 8%, 95% confidence interval). Univariate and multivariate prognostic risk factor analyses were performed using FFTF as endpoint. Sex, age, stage, splenectomy, bone marrow, and liver and bone involvement had no prognostic impact. In contrast, a pretreatment erythrocyte sedimentation rate (ESR) above 80 mm/h and a serum alkaline phosphatase (AP) above 230 IU/ml each appeared as significant prognostic factors (P less than 0.01; relative risk, 2.3). The two parameters can be combined to separate two groups (A: ESR and AP both low; B: ESR and/or AP high) which differ significantly for FFTF (P less than 0.001) and survival (P less than 0.04). The decision for risk-adapted treatment requires identification of groups of patients in the frame of specified diagnostic and therapeutic strategies.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1989

Intracellular calcium and hormone secretion in clonal AtT-20/D16-16 anterior pituitary cells.

Intracellular ionized Ca2+ concentration was measured in clonal mouse anterior pituitary tumor cells with the fluorescent Ca2+ indicator Quin-2. In control physiological solution, free cytoplasmic Ca2+ concentration was found to be 139 +/- 11 nM. Replacement of 50 mM NaCl by 50 mM KCl in the extracellular fluid caused a 29 mV depolarization and a 4.2-fold increase in the concentration of free cytoplasmic Ca2+. Under comparable depolarizing conditions, a specific influx of 2.66 nmole of 45Ca2+ per mg protein was detected 1 min after addition of high K+, accompanied by a marked increase in the initial rate of beta-endorphin secretion. In the absence of external Ca2+, depolarization by K+ produced little or no increase in either intracellular free Ca2+ or hormone release. Incubation of AtT-20/D16-16 cells in the secretagogue norepinephrine led to a depolarization accompanied by an increase in spontaneous action potential frequency and a marked elevation in cytosolic Ca2+ concentration. Exposure of cells to somatostatin, an inhibitor of hormone release, led to only transient decreases in burst frequency and no significant reduction in intracellular Ca2+ levels. These results indicate that in addition to intracellular Ca2+, other factors also control secretory activity in AtT-20/D16-16 anterior pituitary cells.

Action Potentials↗