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Biomedical subjects

J Lange

Publications and source records attributed to J Lange.

At least 55 records · Page 3Linked to original sources
PubMed2000

Medicare HMOs: the experience of older African Americans and whites.

This exploratory study of 205 older adults with chronic illness, of whom 55 enrolled in Medicare HMOs, examined the characteristics of those who enrolled, their experiences with managed care, and the differences between African Americans and whites in these domains. HMO enrollees were more likely to report their finances as inadequate; to have a high school education or less; and to have higher levels of social support. No significant differences by race were found in enrollment or in factors related to enrollment. Enrollees joined because of low premiums, enhanced HMO benefits, and pressure from employers providing retiree health benefits. The majority of enrollees reported positive experiences, however, more whites than African Americans reported negative experiences.

Black or African American↗
PubMed1999

Contribution of c-erbB-2 and topoisomerase IIalpha to chemoresistance in ovarian cancer.

Overexpression of the c-erbB-2 (HER-2/neu) oncogene, which encodes a transmembrane receptor tyrosine kinase, has been shown to be associated with poor prognosis in ovarian and breast cancer. Recent studies indicate that c-erbB-2 may also be involved in determining the chemosensitivity of human cancers. In the present study, we examined the role of c-erbB-2 for chemoresistance in ovarian cancer. Overexpression of c-erbB-2 mRNA in tumor tissue was associated with a shorter survival of patients with primary ovarian cancer (P = 0.0001; n = 77) and was an independent prognostic factor in the proportional-hazard model adjusted for International Federation of Gynecologists and Obstetricians stage, residual disease, chemotherapy, and age (P = 0.035). A significant association between expression of c-erbB-2 mRNA and survival was obtained for the subgroup of patients who received a standard chemotherapy with carboplatin or cisplatin and cyclophosphamide (P = 0.0003), whereas only a nonsignificant trend was observed for patients who did not receive a standard chemotherapy (P = 0.124). In addition, the application of a standard chemotherapy improved the survival of patients with relatively low c-erbB-2 expression (P = 0.013) but not of patients with overexpression of c-erbB-2 (P = 0.359). Expression of c-erbB-2 mRNA correlated with expression of topoisomerase IIalpha mRNA determined by a reverse semiquantitative PCR technique (P = 0.009), whereas expression of c-erbB-2 and topoisomerase IIbeta mRNA did not correlate (P = 0.221). To examine the hypothesis that coamplified and/or coregulated topoisomerase IIalpha contributes to the resistance of c-erbB-2-overexpressing carcinomas, we established a chemosensitivity assay using primary cells from an ovarian carcinoma that overexpressed both c-erbB-2 and topoisomerase IIalpha. The combination of carboplatin with nontoxic concentrations of the topoisomerase II inhibitors etoposide or novobiocin enhanced the toxicity of carboplatin. In contrast, the tyrosine kinase inhibitor emodin exhibited no chemosensitizing effect in cells of this individual carcinoma. In conclusion, overexpression of c-erbB-2 was associated with poor prognosis and poor response to chemotherapy. The data suggest that topoisomerase IIlalpha, which correlates with c-erbB-2 expression, contributes to the resistance of c-erbB-2-overexpressing carcinomas.

Antigens, Neoplasm↗
PubMed1999

Meropenem (1.5 g/day) is as effective as imipenem/cilastatin (2 g/day) for the treatment of moderately severe intra-abdominal infections.

This multicentre, open-label, randomised trial compared meropenem (0.5 g/8 h) and imipenem/cilastatin (at the commonly used dosage of 0.5 g/6 h) in monotherapy in patients with moderately severe intra-abdominal infections (IAIs). In total, 161 patients were randomised (82 meropenem, 79 imipenem/cilastatin). The mean APACHE II scores in the two groups were 5.8 and 6.4, respectively. At the end of therapy, 65/71 (91.6%) evaluable meropenem recipients were clinically cured or improved, compared to 60/64 (93.8%) imipenem/cilastatin recipients. This difference and that in an intention-to-treat analysis (82.1 vs 86.1%, respectively), were not statistically significant. Both drugs were generally well tolerated. Thus, meropenem 0.5 g/8 h is as clinically effective and well tolerated as imipenem/cilastatin 0.5 g/6 h in moderately severe IAIs.

APACHE↗
PubMed1999

A randomized, controlled trial of indinavir, zidovudine, and lamivudine in adults with advanced human immunodeficiency virus type 1 infection and prior antiretroviral therapy.

A randomized, double-blind, multicenter study of indinavir, zidovudine, and lamivudine was conducted in 320 adults with human immunodeficiency virus type 1 (HIV-1) infection, </=50 CD4 cells/mm3, and extensive prior zidovudine therapy. Patients received indinavir, 800 mg every 8 h; zidovudine, 200 mg every 8 h, and lamivudine, 150 mg twice daily; or all 3 drugs for 24 weeks. In an intention-to-treat analysis, proportions of patients with HIV-1 RNA <500 and <50 copies/mL, respectively, at week 24 were 56% and 45% in the indinavir-zidovudine-lamivudine group, 3% and 2% in the indinavir group, and 0% in the zidovudine-lamivudine group. Observed mean CD4 cell increases were 95, 78, and 6 cells/mm3 in the three-, one-, and two-drug arms, respectively. Regimens were generally well tolerated. Patients with advanced HIV-1 infection benefit from triple therapy with indinavir, zidovudine, and lamivudine, although the proportion with optimal response appeared to be lower in patients with low CD4 cell counts.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Binge drinking and bone metabolism in a young actively growing rat model.

BACKGROUND: Chronic alcohol consumption has been demonstrated to be deleterious to bone health. However, binge drinking is the prevalent form of drinking in young people, which was the impetus for the present study to determine the effect of week-end and week-long binge drinking on bone health in a young actively growing animal model. METHODS: Four-week-old, female, Sprague-Dawley rats were given the amount of 5% alcohol by gavage to be equivalent to a 63 kg woman drinking six beers a day for either 2 or 5 consecutive days per week. RESULTS: There were no changes in the 5-day binge animals, but the 2-day binge animals were hypocalcemic. Similarly, 2-day binge animals had slightly increased bone chemistry and histomorphometric values for both tibia and femur, but only femur length, dry weight, and ash weight as well as femur density, presented either as g/ml or ash weight per unit volume, were increased by a statistically significant level. Cross-section periosteal Mineral Apposition Rate (MAR) was significantly decreased in the 2-day alcohol fed animals. CONCLUSIONS: Actively growing rats given 5% alcohol by gavage for 2 days per week have an increased bone length, bone weight, and bone density. The interpretation of these results must be viewed with great caution because studies of chronic alcohol consumption, and many studies of acute drinking, clearly indicate deleterious effects of alcohol on bone health. Those fed alcohol for 5 days per week showed no change.

Animals↗
PubMed1999

[Therapeutic and prophylactic effect of LH-release in cattle].

In this study, LH release in response to the GnRH agonist buserelin and during treatment with a progesterone-releasing intravaginal device (PRID) was studied. A dose of 20 micrograms buserelin induced a more pronounced LH release than 4, 8, 40 and 80 micrograms. After injection of buserelin, pituitary response to a second buserelin injection was markedly reduced for at least 24 hours. Repeated buserelin injections at an interval of several hours therefore cannot be recommended. LH release was markedly suppressed by treatment with PRID. Two PRID tended to be more effective than one. After PRID removal, LH release increased significantly.

Administration, Intravaginal↗
PubMed1999

AVANTI 1: randomized, double-blind trial to evaluate the efficacy and safety of zidovudine plus lamivudine versus zidovudine plus lamivudine plus loviride in HIV-infected antiretroviral-naive patients. AVANTI Study Group.

The objective of this randomized double-blind, placebo-controlled trial was to investigate the effect of combination antiretroviral therapy on plasma HIV-1 RNA as measured by HIV RNA PCR and to assess the safety and tolerability of such regimens. The trial was carried out in seven European countries, Australia and Canada and involved antiretroviral-naive patients (n = 106) with CD4 counts between 150-300 cells/mm3 (CDC group A) and 150-500 cells/mm3 (CDC group B/C). Patients were randomly assigned to zidovudine (200 mg three times daily) plus lamivudine (300 mg twice daily) or to zidovudine plus lamivudine plus loviride (100 mg three times daily) for 52 weeks. The main outcome measures were degree and duration of reduction of plasma HIV-1 RNA as measured by RNA PCR and the development of drug-related toxicities sufficiently severe to warrant dose modification, interruption or permanent discontinuation. A mild, though statistically significant difference in favour of zidovudine plus lamivudine plus loviride for log10 plasma HIV-1 RNA (P = 0.022), as compared to zidovudine plus lamivudine, was observed using area-under-the-curve minus baseline (AUCMB). An increase in CD4 cell count in the zidovudine plus lamivudine plus loviride group was observed with a median improvement of 124 cells/mm3 at week 52 compared with 70 cells/mm3 in the zidovudine plus lamivudine group (P = 0.06). Both treatment regimens were well tolerated.

Acetamides↗
PubMed1998

Estimates of the virological benefit of antiretroviral therapy are both assay- and analysis-dependent.

OBJECTIVE: To assess the potential discrepancies in reported changes in plasma viral load (PVL) depending on how values below the detection limit of the assay are handled in the data analysis phase of a randomized controlled clinical trial. DESIGN: Data from a recently completed clinical trial comparing combinations of zidovudine, didanosine and nevirapine were analysed. In this trial, PVL was measured using an assay with a lower quantification limit of 400 HIV-1 RNA copies/ml initially. All PVL values less than 500 copies/ml were retested with a more sensitive assay with a lower quantification limit of 20 copies/ml. METHODS: Several summary measures for assessing change in PVL were calculated using three different methods to adjust for PVL values less than the quantification limit of the assay. The differences between these measures were evaluated. RESULTS: We found that the magnitude of the discrepancy between summary measures used to report changes in PVL depended on the proportion of subjects with PVL less than the quantification limit of the assay, how those observations were handled in the data analysis, and the relative difference between the quantification limits of the conventional and more sensitive assay. CONCLUSION: The lack of consensus in reporting of PVL data in the literature makes the interpretation of published trial results difficult. In the absence of agreement on the most appropriate summary measure of PVL data, we recommend that all summaries include information on the quantification limit of the assay used, the proportion of observations at or below the quantification limit and how these observations were handled in the data analysis.

Analysis of Variance↗
PubMed1998

Suppression of plasma viral load below 20 copies/ml is required to achieve a long-term response to therapy.

BACKGROUND: Current guidelines state that the goal of antiretroviral therapy for HIV-infected individuals is to suppress plasma viral load (pVL) to below 400 copies/ml. METHODS: Predictors of achieving and maintaining pVL suppression were examined in a randomized trial of combinations of zidovudine, nevirapine and didanosine in patients with CD4+ T cell counts of between 200 and 600 x 10(6) cells/l who were naive to antiretroviral therapy and AIDS-free at enrolment. RESULTS: One hundred and four patients had pVL > 500 copies/ml at baseline and a pVL nadir below 500 copies/ml. Of these, 77 patients experienced an increase in pVL above 500 copies/ml. The median number of days of pVL suppression to below 500 copies/ml was 285 (42) for patients with pVL nadir < or = (>) 20 copies/ml (P = 00.0001). The relative risk of an increase in pVL above 500 copies/ml associated with a pVL nadir below 20 copies/ml was 0.11 (P = 0.0001). The relative risks of an increase in pVL above 5000 copies/ml associated with a pVL nadir below 20 copies/ml or between 20 and 400 copies/ml were 0.05 [95% confidence interval (CI), 0.02-0.12] and 0.37 (95% CI, 0.23-0.61) respectively, compared with individuals with a pVL nadir > 400 copies/ml. Individuals with a pVL nadir < or = 20 copies/ml were at a significantly lower risk of virologic failure than individuals with a pVL nadir of between 21 and 400 copies/ml (P = 0.0001). CONCLUSIONS: Our results demonstrate that suppression of pVL below 20 copies/ml is necessary to achieve a long-term antiretroviral response. Our data support the need for a revision of current therapeutic guidelines for the management of HIV infection.

Anti-HIV Agents↗
PubMed1998

[Morbid obesity: 130 consecutive patients with laparoscopic gastric banding].

Morbid obesity causes co-morbidity such as diabetes mellitus, hypertensive heart disease, sleep apnoea, degenerative bone diseases and increased incidence of malignancy. Life expectancy and quality of life are reduced significantly. Without adequate weight loss, treatment of co-morbidity remains symptomatic only. Surgical treatment of morbid obesity is the one therapy promising long-term success, since conservative procedures normally lead to recurrence of overweight. We performed laparoscopic gastric banding on 130 patients between 1.11.95 and 31.10.97. Mean overweight was 63 +/- 12.7 kg (SD), and mean BMI was 46.5 +/- 4.6 kg/m2. The average hospital stay was 5.5 +/- 1.5 days. 4 patients with postoperative pulmonary embolism were treated with oral anticoagulation. We performed 9 (6.9%) reoperations because of pouch dilatation or dorsal slipping with food intolerance in the first series of 70, and none in the second series of 60 patients. Median weight loss after 3 months was 14.7 +/- 4.2 kg, after six months 24.0 +/- 6.6 kg and after 12 months 33.2 +/- 8.5 kg, corresponding to excessive weight loss (EWL) of 55.9 +/- 14.8% in the first year. 14 (70%) of 20 patients with diabetes mellitus normalised and 6 patients with diabetes mellitus normalised and 6 patients showed improved blood sugar levels. All 36 patients with hypertensive heart disease had normalised blood pressure, 60% of them without further medical antihypertensive treatment after median EWL of 36%. Cholesterol levels normalised in 30 (57%) patients and improved in 20 (38%) after 6 months. Laparoscopic gastric banding is a suitable method for reducing weight in morbid obesity patients and provides a better quality of life in a group of patients who are carefully evaluated and followed. Reducing co-morbidity and improving ability to work have a positive economic impact on health care costs.

Adult↗
PubMed1998

Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer.

Malignant rhabdoid tumours (MRTs) are extremely aggressive cancers of early childhood. They can occur in various locations, mainly the kidney, brain and soft tissues. Cytogenetic and molecular analyses have shown that the deletion of region 11.2 of the long arm of chromosome 22 (22q11.2) is a recurrent genetic characteristic of MRTs, indicating that this locus may encode a tumour suppressor gene. Here we map the most frequently deleted part of chromosome 22q11.2 from a panel of 13 MRT cell lines. We observed six homozygous deletions that delineate the smallest region of overlap between the cell lines. This region is found in the hSNF5/INI1 gene, which encodes a member of the chromatin-remodelling SWI/SNF multiprotein complexes. We analysed the sequence of hSNF5/INI1 and found frameshift or nonsense mutations of this gene in six other cell lines. These truncating mutations of one allele were associated with the loss of the other allele. Identical alterations were observed in corresponding primary tumour DNAs but not in matched constitutional DNAs, indicating that they had been acquired somatically. The observation of bi-allelic alterations of hSNF5/INI1 in MRTs suggests that loss-of-function mutations of hSNF5/INI1 contribute to oncogenesis.

Child↗
PubMed1998

Induction-maintenance antiretroviral therapy: proof of concept.

OBJECTIVE: To investigate the concept of aggressive initial combination therapy followed by reduction to a less demanding maintenance regimen with respect to its potential for sustaining viral suppression. DESIGN: Durable viral suppression to < 20 HIV RNA copies/ml plasma was achieved with zidovudine-nevirapine-didanosine (ZDV-NVP-ddl) therapy. Potential for sustained antiviral response was explored for patients who began with ZDV-NVP-ddl and subsequently interrupted ddl. METHODS: Antiretroviral-naive patients were treated with ZDV-NVP, ZDV-ddl, or ZDV-NVP-ddl. Viral load was measured with the Amplicor assay (limit of quantification 400 copies/ml) and by the Ultra Direct assay (limit of quantification 20 copies/ml) when the Amplicor result was < 500 copies/ml. Treatment adherence for each drug was recorded, including all dose adjustments. RESULTS: Five patients who had begun treatment with ZDV-NVP-ddl discontinued ddl for at least 6 weeks after achieving viral load levels below detection. All were documented to have sustained their viral load at < 20 copies/ml during the ddl interruption. Two patients permanently discontinued ddl, both with sustained viral load below detection for more than 1 year while treated with ZDV NVP. In contrast, no patient initially receiving ZDV-NVP was able to maintain viral load below detection for sustained periods; none had viral load below detection after week 12 of treatment. CONCLUSIONS: After induction with ZDV-NVP-ddl, patients were able to sustain viral suppression with a regimen (ZDV NVP) that was only transiently effective as initial therapy. There was no evidence of virologic escape, even with the most sensitive measure of plasma viral load.

Anti-HIV Agents↗
PubMed1998

Comparative gene expression profiling by oligonucleotide fingerprinting.

The use of hybridisation of synthetic oligonucleotides to cDNAs under high stringency to characterise gene sequences has been demonstrated by a number of groups. We have used two cDNA libraries of 9 and 12 day mouse embryos (24 133 and 34 783 clones respectively) in a pilot study to characterise expressed genes by hybridisation with 110 hybridisation probes. We have identified 33 369 clusters of cDNA clones, that ranged in representation from 1 to 487 copies (0.7%). 737 were assigned to known rodent genes, and a further 13 845 showed significant homologies. A total of 404 clusters were identified as significantly differentially represented (P < 0.01) between the two cDNA libraries. This study demonstrates the utility of the fingerprinting approach for the generation of comparative gene expression profiles through the analysis of cDNAs derived from different biological materials.

Animals↗
PubMed1998

Biodegradation of biphenyl by the ascomycetous yeast Debaryomyces vanrijiae.

Cells of the yeast strain Debaryomyces vanrijiae SBUG 770, grown with glucose, converted biphenyl to 4-hydroxybiphenyl as the major metabolite. In addition, 2-hydroxybiphenyl was formed in minor amounts. No further degradation of these substances was detected. However, these monohydroxylated derivatives were oxidised by alkane-grown cells in the presence of the co-metabolic substrate, tetradecane. Under these conditions 2-hydroxybiphenyl was oxidised to 2,5-dihydroxybiphenyl, and 4-hydroxybiphenyl was rapidly metabolised by formation of two major metabolites. One was identified as 3,4-dihydroxybiphenyl. Characterisation of the second product as 4-phenylmuconolactone points to a further metabolism of the initially formed dihydroxylated biphenyl via ortho-ring fission.

Ascomycota↗
PubMed1998

Cisplatin, doxorubicin and etoposide (PAV) in advanced gastric carcinoma: the SAKK experience. Swiss Group for Clinical Cancer Research (SAKK).

EAP (etoposide, doxorubicin, cisplatin), a chemotherapeutic combination given over 8 days, proposed by German investigators in cancer of the stomach, has been considered to be too toxic by others. A positive experience with a similar regimen (PAV) developed by the SAKK given over 3 days in small cell lung cancer led us to test it in gastric adenocarcinoma. 41 patients with metastatic gastric cancer were enrolled in the study and 38 were evaluable for response and toxicity. One complete response and 12 partial responses were recorded, giving a response rate of 34% (95% confidence interval (CI) 20-51%). Median progression-free and overall survival were 3.4 and 6.3 months, respectively. Haematotoxicity was the leading toxicity with 34 (90%) and 17 (45%) grade III-IV neutropenia and thrombocytopenia, respectively. Despite this high rate of granulocytopenia, only six episodes of non-fatal febrile neutropenia were observed. Other toxicities were relatively easy to manage with infrequent grade III-IV occurrences. We conclude that PAV is active in gastric cancer and seems to be better tolerated than EAP.

Adenocarcinoma↗