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Biomedical subjects

R Moser

Publications and source records attributed to R Moser.

At least 55 records · Page 3Linked to original sources
PubMed1995

Effects of lead administration on developing rat kidney. II. Functional, morphologic, and immunohistochemical studies.

The effects of chronic lead administration on renal function and cytoarchitecture and on the immunohistochemical localization of glutathione S-transferase (GST) isoenzymes were determined. Pregnant rats were given 250 ppm lead acetate in drinking water from conception until weaning and mothers and pups received 500 ppm of lead acetate from weaning until termination at either 3 or 7 weeks of age. Light and electron microscopic studies after 3 weeks of lead administration showed tubular injury with frequent mitoses noted in proximal tubular cells and, after 7 weeks of treatment, interstitial fibrosis, characteristic intranuclear inclusions, and tubular injury characterized by both nuclear and cytoplasmic pleomorphism. Rats treated with lead for 7 weeks showed significantly lower body weights and creatinine clearances than age-matched control animals. Immunohistochemical studies of glutathione transferase subunits in control rats showed unique isoform localization in each segment of the nephron; treatment with lead caused large increases in immunoreactive protein of Yc, Yk, Yb1, and Yp GST subunits in proximal tubules. No increases in the antioxidant enzymes copper-zinc superoxide dismutase, catalase, and glutathione peroxidase were found in lead-treated rats, but there was a diffuse lead-related increase in immunoreactive protein for manganese superoxide dismutase throughout the renal cortex. Our results demonstrate large lead-induced increases of specific isoforms of glutathione S-transferase in specific kidney cell types and show that these increases preceded irreversible renal damage.

Aging↗
PubMed1995

Neutrophil activation in response to immune complex-bearing endothelial cells depends on the functional cooperation of Fc gamma RII (CD32) and Fc gamma RIII (CD16).

Leukoclastic vasculitis is thought to be initiated by deposition of immune complexes (ICs) in the vascular wall. To study the neutrophil response in a related in vitro model, we primed human umbilical vein endothelial cell (HUVEC) monolayers with antibodies against human fibronectin. The resulting respiratory burst to the immobilized ICs depended on the antibody concentration used to prime the monolayers and included a marked release of primary and secondary granule constituents. On IC-bearing HUVEC monolayers, but not on ICs directly bound to tissue culture dishes, blocking monoclonal antibodies (mAbs) to crystallizable fragment-gamma receptor II (Fc gamma RII) and Fc gamma RIII markedly inhibited the respiratory burst and the release of elastase. However, on both surfaces the neutrophil response was strongly inhibited by mAbs against CD18. Regardless of whether we used neutrophils from a patient with severe paroxysmal nocturnal hemoglobinuria (PNH) lacking the Fc gamma RIII, or whether the Fc gamma RII-mediated signal transduction was blocked by pertussis toxin, the respiratory burst to the IC-bearing HUVECs was essentially unchanged. With PNH neutrophils, the respiratory burst was predominantly blocked by an anti-Fc gamma RII mAb. In contrast, the response of pertussis toxin treated neutrophils was strongly inhibited by a mAb against Fc gamma RIII. Together these data indicate that the answer of neutrophils to ICs immobilized at the endothelial barrier depends on the cooperative function of both low-affinity Fc gamma Rs.

CD18 Antigens↗
PubMed1995

Aviators at risk.

Human error has been found to cause or contribute to most aviation accidents. Excess emotional stress may have an adverse effect on pilot performance and is known to increase the risk of an aircraft mishap. Family problems, social stressors, career instability, worry, aircraft accidents, and difficult flight schedules are a few of the many potential sources of emotional stress in aviation. Pilots who fail at stress coping may become depressed or even self-destructive. They may externalize their feelings, act out, or blame others for their misfortunes. The aviator at risk may demonstrate "warning signs" such as defensiveness, arrogance, hostility, financial irresponsibility, excesses in routine habits, fatigue, deteriorating pilot performance, or increased risk taking. The aeromedical practitioner's role is to educate aircrew members and help them understand stress and its effect on pilot performance. The time may come when an aviator is confronted by multiple stressors, and inadequate stress coping or failure on the part of the aviation community to recognize the "warning signs" may have disastrous results.

Accidents, Aviation↗
PubMed1995

[Infections caused by Campylobacter jejuni in the pediatric department of the Leoben district hospital 1983-1993].

Over the period 1983-1993 10,344 stool cultures were undertaken in children with gastrointestinal symptoms at the pediatric department of the Landeskrankenhaus Leoben. Campylobacter jejuni was diagnosed as pathogen in 238 cultures taken from 196 patients aged one month to 16 years. Thus, Campylobacter jejuni infections (2.3% of all stool cultures) were second in frequency to various forms of salmonella (6.1% of all stool cultures; 332 patients). Apart from diarrhea (92% of cases), the most frequent clinical features were fever exceeding 38 degrees C (61%), abdominal pain (58%), blood in the stools (48%) and vomiting (34%). Treatment was based on appropriate diet. Fluid replacement with glucose-electrolyte infusions was required in 24% of the patients and erythromycin was administered orally in 30% of cases.

Adolescent↗
PubMed1994

Weekly 5-fluorouracil and high-dose folinic acid in combination with epidoxorubicin as first-line therapy in advanced breast cancer: a phase II study.

A total of 25 patients with advanced breast cancer were treated weekly with i.v. 5-fluorouracil at 350 mg/m2, folinic acid at 500 mg/m2, and epidoxorubicin at 35 mg/m2 as first-line chemotherapy for a maximum of 18 cycles. In all, 24 patients were evaluable for response. Overall, 1 patient achieved a complete response and 11 patients showed a partial response, for an objective response rate of 50%; the median duration of response was 18.3+ months and median survival amounted to 18.8+ months. Side effects were generally mild, with grade II leukopenia occurring in 10 patients and grade III leukopenia, in 1 patient. Other toxicity included nausea and vomiting (82%), diarrhea (48%), stomatitis (48%), and alopecia (92%), all of which were mainly restricted to WHO grades I and II. Our results suggest that leucovorin modulation of 5-fluorouracil can safely be incorporated into combination chemotherapy with epidoxorubicin on the investigated schedule. The observed response rate appears comparable with that obtained with other first-line regimens.

Adult↗
PubMed1994

A phase I/II study of 4'-O-tetrahydropyranyl-doxorubicin, 5-fluorouracil, and high-dose leucovorin as first-line therapy in advanced breast cancer patients.

A total of 50 patients were treated weekly with 5-fluorouracil (FU), leucovorin (LV), and 4'-O-tetrahydropyranyl-doxorubicin (THP) as first-line chemotherapy for advanced breast cancer (ABC). In phase I the doses of LV (500 mg/m2, day 1) and FU (350 mg/m2, day 1) were held constant, while the dose of THP (day 1) was escalated, from the initial dose of 10 mg/m2 up to the maximum tolerated dose (MTD). Twenty-eight patients entered phase I, and MTD for THP was defined as 35 mg/m2 in this combination. Dose-limiting toxicities were myelosuppression and hepatotoxicity. In phase II, another 22 patients were treated with THP at a dose level of 30 mg/m2. Including 4 patients already treated at this dose in the first part, 25 patients were evaluable for response: 1 patient obtained a complete response (CR) and 13 showed a partial response (PR), giving an objective response rate of 56%. The median duration of response was 9.1+ months and median survival, 15.5+ months. Side effects were generally mild, with ECOG grade I and II leukopenia in 51% of all cycles and grade III in 3% of the courses. Other toxicity included nausea and vomiting (54% and 8%, respectively) and alopecia (24%), all restricted to ECOG grade I and II. Our results suggest that weekly THP/LV-FU represents an active regimen for first-line treatment of ABC with relative low toxicity.

Adult↗
PubMed1994

Development of four donor-specific phenotypes in human long-term lymphokine-activated killer cell cultures.

A series of 62 lymphokine-activated killer cell (LAK) cultures from 44 different donors was investigated for the distribution of various CD markers during a cultivation period of 3 weeks. Great differences in the phenotypic pattern were found between different donors, but similar changes of the subset pattern of various donors allowed a classification of the LAK cultures into four distinct LAK types. LAK type 1 was characterised by low numbers of CD3+ cells and high values for CD56+ cells. In LAK type 2 cultures gamma/delta TCR+ cells extensively proliferated, whereas in LAK type 3 cultures the CD57 and CD8 values increased considerably. LAK type 4 cultures did not show any of these characteristics. The resulting phenotype of a LAK culture was donor-specific, as LAK cultures established from the same peripheral blood mononuclear cells (PBMC), fresh or after cryopreservation, or from PBMC obtained from the same donor at different venous punctures, always developed the same phenotype. A clear correlation between phenotype and killing activity could only be found for LAK type 1 cultures, which always developed high lytic activity. Long-term IL-2 stimulation induced high levels of perforin-positive cells in LAK cultures but the perforin content did not correlate with the cytotoxicity. The transcription pattern for various cytokines only varied slightly between the cultures. Messenger RNA for granulocyte/macrophage- colony-stimulating factor, interferon gamma, tumour necrosis factor alpha, interleukin-4 (IL-4) and IL-5 were found in almost all cultures during the entire cultivation period, whereas mRNA for IL-2 was never detected. Most variations in the transcription pattern were observed for IL-6 and IL-7. However, no correlation could be found between the endogenous cytokine production and the phenotype or lytic activity of the LAK cultures. Further studies are required to determine the factors that cause lymphocyte subsets from a specific donor to proliferate preferentially under long-term IL-2 stimulation.

Animals↗
PubMed1994

Neonatal allo-immune thrombocytopenia due to fetomaternal HPA-1 incompatibility of a homozygous HPA-1a mother and a homozygous HPA-1b father. A case report.

We report a case of neonatal allo-immune thrombocytopenia due to fetomaternal human platelet antigen (HPA)-1 incompatibility. Anit-HPA-1b antibodies were detectable in maternal serum. Repeated treatment of the infant with high-dose IgG effectively raised platelet counts transiently, but the patient remained thrombocytopenic for more than 6 weeks. Serological and DNA analysis revealed that the mother was homozygous HPA-1a and the father homozygous HPA-1b.

Antigens, Human Platelet↗
PubMed1994

Bed occupancy due to HIV/AIDS in an urban hospital medical ward in Uganda.

OBJECTIVE: To determine the proportion of patients with HIV-related illness admitted to a medical ward. DESIGN: A prospective study. SETTING: Rubaga Hospital, the third largest hospital in Kampala, the capital of Uganda. PARTICIPANTS: A total of 449 patients admitted to the medical ward between September and November 1992. RESULTS: Of the 449 patients, 390 (86.8%) agreed to provide a blood sample for HIV serology. Of these, 55.6% (95% confidence interval, 50.7-60.5%) were positive for HIV. Eighty-six (22.2%) of all patients [71 (33%) of the seropositives and six (3.5%) of the seronegatives] met the World Health Organization case definition for AIDS in Africa. The HIV-seropositives had a mortality rate of 17.4%, significantly higher (P = 0.00057) than the 5.8% rate observed in the seronegative group. The overall mortality rate was 13.7% and was significantly associated with HIV infection (P = 0.0005). CONCLUSION: HIV infection is a major contributor to morbidity and mortality in Uganda. Over 50% of the medical admissions were HIV-positive revealing the serious impact of HIV on the health-care system.

Acquired Immunodeficiency Syndrome↗
PubMed1994

[Breast cancer in the man: a report of 30 patients].

A retrospective review of male patients suffering from breast cancer seen over an 18-year period was carried out at the Department of Clinical Oncology of the University Hospital of Graz. Thirty evaluable cases were analysed. Eight patients had Stage I, 11 had Stage II, 8 had Stage III, and 3 had Stage IV disease. Local control was achieved in the majority, 29/30 (97%), by either surgery alone or combined surgery and radiation therapy. Local recurrence developed in 2 (7%) patients. Further 7 (23%) patients developed distant metastases and were treated in accordance with policies developed for the appropriate stage of the disease in females, with hormonal manipulation for hormone receptor-positive and -unknown patients and chemotherapy for hormone receptor-negative patients. The corrected five-year survival (Kaplan-Meier) is 83% for the entire group, 100% for patients with Stage I disease, 86% in Stage II, and 67% in Stage III and IV disease, respectively. This corresponds well with the results in recently published series. Stage of disease at initial presentation was a significant factor determining survival in our investigation. Our own data as well as recent data from literature suggest that with respect to TNM Stages in mammary carcinoma, there is no prognostic difference between men and women. To what extent improved local control by adequate local therapy or systemic adjuvant treatment modalities may improve overall survival remains to be discussed.

Adult↗
PubMed1993

Low density lipoprotein subfractions increase thromboxane formation in endothelial cells.

Correlations between dyslipidemia and high blood pressure have been shown. It is unclear whether there is a causal relationship but there are indications that blood lipids might have a direct effect on mechanisms regulating the vascular tone. As secretory products of endothelial cells (EC) have been suggested to be involved in blood pressure regulation, we studied the influence of low density lipoprotein subfractions on thromboxane (T) synthesis in human umbilical vein endothelial cells (HUVEC). LDL can be separated into at least three major subfractions. In the present study, subfractions LDL1 (d = 1.030-1.033 g/ml), LDL 2 (d = 1.033-1.040 g/ml), and LDL 3 (d = 1.040-1.045 g/ml) were obtained by density gradient ultracentrifugation. T was measured by a radioimmuno-assay. LDL subfractions induced a dose dependent (10-100 micrograms/ml) increase in T synthesis. Control T concentration was 96 +/- 12 pg/ml. LDL 3 (205 +/- 17 pg/ml, p < 0.01) and LDL 2 (194 +/- 13 pg/ml, p < 0.05) caused a significantly higher T concentration compared to the LDL 1 subfraction (152 +/- 11 pg/ml). These results indicate that LDL 2 and 3- the subfractions with the higher density-might have a more pronounced effect on T synthesis by EC than the other LDL subfractions.

Cells, Cultured↗
PubMed1993

Chemotaxins inhibit neutrophil adherence to and transmigration across cytokine-activated endothelium: correlation to the expression of L-selectin.

Non-activated neutrophils strongly adhere to cytokine-activated human umbilical vein endothelial cells (HUVE). However, activation of neutrophils by different chemotactic mediators led to potent inhibition of this endothelial-dependent interaction. For different formylated peptides, concentrations leading to maximal adherence inhibition coincided with those known for inducing maximal chemotactic migration of neutrophils. In terms of maximal adherence inhibition, a rank list was found in the order of N-formyl-Met-Leu-Phe > C5adesArg > interleukin-8 > C5a > or = leukotriene B4, whereas platelet-activating factor, and lipopolysaccharide showed no inhibition. This rank order was congruent to that of down-regulation of neutrophil L-selectin detected by the monoclonal antibody Leu-8. Moreover, the dose-dependent increase of neutrophil adherence inhibition corresponded to the loss of L-selectin expression. Concentrations higher than that required for maximal inhibition led to a dose-dependent decrease of inhibition, which was accompanied by increasing expression of neutrophil CD11/CD18. In contrast to the capacity of non-activated neutrophils to migrate across interleukin-1-activated HUVE monolayers, transmigration was significantly impaired after chemotactic activation.

Antigens, CD↗
PubMed1993

Occupational medicine training program surveys.

Although the quantity of Occupational Medicine (OM) residents in training programs has risen in the past 15 years, there remains a significant shortage of OM physicians in the United States. A survey of OM residency program directors and residents and fellows (trainees) was accomplished to answer questions relevant to recruiting and supplying OM trained physicians. Twenty-six of 29 program directors (89.7%) replied. One hundred forty-three of 174 (82.2%) trainees responded. Fifty percent of responding program directors were satisfied with the current quantity of program applicants. Medical students were provided a median of 3 hours (range, 0 to 20 hours; mean, 5.35 hours) of formal OM teaching by the responding programs. Almost half of trainees, 68 (48.6%), did not receive formal OM instruction in medical school. An average of 5.4 +/- 13.3 hours of OM was taught to OM trainees in medical school. Disproportionate numbers of trainees were taught OM as fourth-year medical students and in other residencies. Reasons for pursuing OM training were diverse and often related to postgraduate clinical experience with OM. Only a total of 84 primary care residents (0.32%) rotate through the OM residency programs in an average year. We conclude that an insufficient quantity of qualified applicants, combined with limited exposure to OM in medical schools and low levels of contact with residents in primary care programs, will continue to hinder efforts to reduce the shortage of OM residents and physicians. Further training specifically targeting the fourth year of medical school and the primary care residencies may have the most impact on recruitment.

Certification↗