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Biomedical subjects

M Gerber

Publications and source records attributed to M Gerber.

At least 55 records · Page 3Linked to original sources

Epidemiological survey in hay fever patients: symptom prevalence and severity and influence on patient management.

The prevalence and severity of symptoms of self-reported hay fever were assessed in 509 symptomatic patients not currently receiving treatment who consulted their physicians in Switzerland during the 1994 pollen season. Conjunctivitis was diagnosed in 93.3% of cases (in 8% isolated), rhinitis in 92% (isolated in 6.7%). 24.2% suffered from current asthma symptoms. The severity of the asthma symptoms was mild in 43.9%, moderate in 48% and severe in 8.1%. When the main symptomatology of hay fever (excluding asthma) was taken into account (the diagnosis with the severest symptomatology), 22.4% of patients suffered predominantly from conjunctivitis, 24.6% from rhinitis and 53% from both. Onset of symptoms typically occurred between March and May and lasted on average 2.7 +/- 1.8 months. Severe symptoms were most common in the rhinitis group and least common in the rhinoconjunctivitis group. Conjunctivitis was more common than rhinitis in younger patients, whilst asthma prevalence increased with age (so-called "Etagenwechsel"). Topical therapy was the preferred treatment for all three symptomatologies and particularly for conjunctivitis. Overall, topical therapy was recommended for 50.5% of patients and in a further 33% in combination with oral therapy. In conclusion, conjunctivitis symptoms are at least as severe as rhinitis symptoms in approximately 70% of patients with hay fever. This would appear to influence clinical management as indicated by a preference for topical therapy.

Administration, Oral↗

Uncoupling of muscarinic cholinergic phosphoinositide signals in senescent cerebral cortical and hippocampal membranes.

Muscarinic-cholinergic signals in brain are mediated in part through the hydrolysis of phosphoinositides (PtdIns) by phospholipase C (PLC). To test the hypothesis that muscarinic PtdIns signals change during aging, membranes were prepared from the cerebral cortex and hippocampus of young (4-6 months old), middle aged (8-10 months old) and senescent (24-26 months old) Fisher 344 rats. Carbachol dose-dependently increased [3H]-PtdIns hydrolysis in both brain regions in all three age groups, however, in senescent rats the maximal response was decreased to 69.26 +/- 4.33% (p < 0.01) in cortex and to 48.29 +/- 2.55% (p < 0.01) in hippocampus of young rat values. In contrast to the decrease in carbachol-stimulated phosphoinositide hydrolysis, calcium-stimulated phosphoinositide hydrolysis was not altered. GTP gamma S also dose-dependently increased [3H]-PtdIns hydrolysis in membranes from all three age groups through G-protein-PLC activation. Similar to carbachol, GTP gamma S-activated [3H]-PtdIns hydrolysis was reduced approximately 40% in senescent rats membranes. Muscarinic receptor (mAChR) density, as determined by [3H]-QNB binding decreased slightly in cortical membranes, but not in hippocampal membranes. These data suggest that muscarinic stimulated [3H]-PtdIns responses are decreased in senescent brain primarily due to an uncoupling of the receptor-G-protein and/or G-protein-PLC link, although decreases in receptor density may also contribute to reduced muscarinic [3H]-PtdIns signaling.

Aging↗

The effects of interaction between familial and reproductive factors on breast cancer risk: a combined analysis of seven case-control studies.

In this paper, a combined analysis was performed to study the interaction between familial risk and reproductive life factors. In particular, the interaction between familial risk and breast cell mitotic activity (BCMA), as assessed by duration of ovarian activity, was investigated because of the potential importance of mitotic activity on genetically susceptible cells. The present analysis included 3152 cases and 4404 controls in seven case-control studies from four countries. The interaction effect was estimated in each study separately, then combined using two different methods: a multivariate weighted average and a Bayesian random-effects model. The main effects of reproductive life factors on the risk of breast cancer were in agreement with the previous findings. In particular, an increased duration of BCMA before the first childbirth and over life was found to increase the risk of breast cancer (P < 0.001). Slightly increasing but non-significant, familial risks were observed with increasing number of children (P = 0.17), increasing age at first childbirth (P > 0.2) and increasing duration of BCMA (P > 0.2). There was no modification in familial risk with age at menarche and no clear pattern with menopause characteristics. A weak influence of reproductive and menstrual factors on the familial risk emerged from the present study.

Adult↗

Return of olfaction after gross total resection of an olfactory groove meningioma: case report.

Patients with olfactory, groove meningiomas may present with anostnia, Surgery in patients with intact olfaction can also lead to anosmia when the olfactory nerves are sacrified. Olfaction can be preserved by using the prerional approach and microsurgical technique. To our knowledge; however, the recovery of olfaction after resection of an olfactory groove meningroma has not been reported. We therefore describe a patient who presented with anosmia whose evaluation revealed a large olfactory groove meningioma. She underwent a bifrontal approach for microsurgical gross bilateral excision of the tumor. At her 6-month follow-up examination, her olfaction, as measured by formal testing, had recovered.

Case Reports↗

Fibre and breast cancer.

The strength of the hypothesis that fibre reduces the risk of breast cancer is its biological plausibility, which is supported by experimental and interventional findings and by the coherence of observational studies. However, at least half the available epidemiological studies have failed to show a decreased risk in breast cancer for an increased fibre intake. But intervention studies taking the plasma concentration of oestrogens as an end-point showed significantly lower levels of breast cancer in women with a high-fibre and low-fat diet than in women with usual Western diets. Any reduction in breast cancer risk appears to be significantly dependent on the level of fibre intake. Several explanations can be proposed, including measurement errors in food intake, the insufficiency of food-composition tables, the difficulty of allowing for the diversity of fibre intake and the complexity of the natural history of breast cancer. More research is needed, not only better nutritional surveys for the different types of fibre intake and improvements in food-composition tables, but also epidemiological studies with the power to control for all the eventual confounding risk factors. Although the scientific evidence is not complete, recommendations for a fibre-rich diet should be made, both for cereals and for fruit and vegetables, in part because such diets at least do no harm, but also because fibre is known to be protective against other pathological conditions.

Breast Neoplasms↗

Antioxidant supplementation and respiratory functions among workers exposed to high levels of ozone.

Ozone exposure has been related to adverse respiratory effects, in particular to lung function decrements. Antioxidant vitamins are free-radical scavengers and could have a protective effect against photo-oxidant exposure. To evaluate whether acute effects of ozone on lung functions could be attenuated by antioxidant vitamin supplementation, we conducted a randomized trial using a double-blind crossover design. Street workers (n = 47) of Mexico City were randomly assigned to take daily a supplement (75 mg vitamin E, 650 mg vitamin C, 15 mg beta carotene) or a placebo and were followed from March to August 1996. Pulmonary function tests were done twice a week at the end of the workday. During the follow-up, the mean 1-h maximum ozone level was 123 ppb (SD = 40). During the first phase, ozone levels were inversely associated with FVC (beta = -1.60 ml/ppb), FEV1 (beta = -2.11 ml/ppb), and FEF25-75 (beta = -4.92 ml/ppb) (p < 0.05) in the placebo group but not in the supplement group. The difference between the two groups was significant for FVC, FEV1, and FEF25-75 (p < 0.01). During the second phase, similar results were observed, but the lung function decrements in the placebo group were smaller, suggesting that the supplementation may have had a residual protective effect on the lung. These results need to be confirmed in larger supplementation studies.

Adolescent↗

Tumor progression and oxidant-antioxidant status.

We previously reported on a paradoxical oxidant-antioxidant status in breast cancer patients, more so in pre-menopausal than menopausal women. In this study, measurements were performed on 146 patients with various carcinomas. Vitamin E/total cholesterol increased and plasma malondialdehyde decreased with tumor size and progression. To investigate the difference between young pre-menopausal and aged menopausal breast cancer patients, the same measurements were performed in 365 breast cancer patients according to pathology, tumor size and estrogen receptors. The oxidant-antioxidant status varied with these prognosis factors in the same pattern, and was more pronounced in young than aged women.

Adult↗

Phase I study of 3'-deamino-3'-(2-methoxy-4-morpholinyl)doxorubicin (FCE 23762, PNU 152243) administered on a daily x3 schedule.

BACKGROUND: 3'-Deamino-3'-(2-methoxy-4-morpholinyl)doxorubicin (FCE 23762, PNU 152243) is a highly lipophilic doxorubicin derivative which possesses potent in vitro and in vivo antitumor activity. Previous phase I studies had been conducted using a single bolus every 28 days. PATIENTS AND METHODS: We conducted a phase I study of FCE 23762 on a daily x3 every 28 days schedule. Thirty patients received 68 cycles of therapy at 5 dose levels (200-600 micrograms/m2/d). RESULTS: Prolonged neutropenia and thrombocytopenia were the dose-limiting toxicities. Other nonhematological toxicities included nausea and vomiting, anorexia, fatigue and transient elevations of serum creatinine and hepatic transaminases. No cardiac toxicity was demonstrated. There were no partial or complete antitumor responses. CONCLUSION: The recommended phase II dose using the schedule defined in this study is 500 micrograms/m2/dx3.

Adult↗

Complete remission of lichen-planus-like graft-versus-host disease (GVHD) with extracorporeal photochemotherapy (ECP).

A 45-year-old female patient with CML underwent allogeneic BMT and developed two episodes of acute GVHD. The first episode of acute cutaneous GVHD grade II (day +17) responded well to systemic CsA and steroids. During the second episode (around day +60) the patient developed erythroderma (grade III), and subsequently signs of lichen-planus-like GVHD. The patient did not respond to increased dosages of prednisolone and CsA. On day +89 extracorporeal photochemotherapy (ECP) was initiated. After four cycles, a significant improvement of erythroderma and lichen-planus-like lesions was documented, and after 12 cycles, a lasting complete remission was achieved. To our knowledge this is the first report of successful treatment of early-onset, lichen-planus-like GVHD after allogeneic BMT with ECP.

Acute Disease↗

Comparison of dietary assessment methods in a southern French population: use of weighed records, estimated-diet records and a food-frequency questionnaire.

OBJECTIVE: The main objective of the study was to develop appropriate dietary assessment instruments for the French Mediterranean region and to validate the measurements they provide. SUBJECTS AND METHODS: Three different assessment methods were submitted to a sample of 150 male and female volunteers. 98 completed the protocol, which consisted of a 4 d weighed dietary record (PETRA) and a 7 d estimated-diet record (S7) based on a check list and a set of photographs, both these records being completed once in each season of the year, and a semi-quantitative (standard portion) food-frequency questionnaire (FFQ) including questions eliciting socio-demographic and anthropometric data, which was completed once only. The days when PETRA was used to evaluate food consumption coincided with the first 4 d of S7 (S4). RESULTS: Validation was based on nutrients and foods. Energy-adjusted Pearson correlation coefficients between S4 and PETRA ranged from 0.32 for vitamin E to 0.81 for vitamin C (mean: 0.65 for 21 nutrients). There was practically no misclassification in opposite extreme quartiles. Spearman correlation coefficients ranged from 0.63 for fish and sea-food to 0.90 for wine (mean: 0.76 for 16 food groups). There was practically no misclassification in opposite extreme quartiles. De-attenuated energy-adjusted Pearson correlation coefficients between FFQ and S7 ranged from 0.22 for proteins and monounsaturated fatty acids to 0.80 for iron (mean: 0.45). 10% or less of subjects were misclassified in opposite extreme quartiles (except for vitamin C, 12%). Spearman correlation coefficients ranged from 0.25 for green-yellow-red raw vegetables to 0.76 for wine (mean: 0.42). 8% or less of subjects were misclassified in opposite extreme quartiles (except for citrus fruit, 11%). CONCLUSIONS: Portion estimation using the set of photographs was validated by the correlation between S4 and PETRA for both nutrients and foods. The FFQ provides a reasonably reliable measure of macronutrient intake and a good measure of micronutrient intake when compared with the data in the literature. It performs less well for food intake. Better results can be achieved for FFQ: (i) by using the set of photographs instead of standard portions and (ii) by adding further questions on foods which are insufficiently covered.

Adult↗

Age-related loss of cholinergic-muscarinic coupling to PLC: comparison with changes in brain regional PLC subtypes mRNA distribution.

Activation of phospholipase C (PLC) coupled to phosphoinositide (PtdIns) hydrolysis occurs through one of the two pathways. One of the major pathways for the neurotransmitter signaling involves phosphoinositide (PtdIns) specific and G-protein dependent PLC-beta, which stimulates the formation of inositol triphosphate (IP3) and inositol tetraphosphate (IP4). Another pathway through the stimulation of calcium influx can directly activate all of the PLC isozymes. At least three isozymes of PLC have been characterized in the brain; PLC-A (alpha), PLC-I (beta) and PLC-II (gamma), which are shown to be localized differentially in brain regions. Muscarinic-cholinergic signals are mediated in large part through the hydrolysis of PtdIns by PLC. To investigate changes in muscarinic coupling to PLC during aging, we examined carbachol stimulated and calcium stimulated PtdIns hydrolysis in cerebral cortical membranes in young, middle aged and old rats. In order to determine whether PtdIns hydrolysis changes correspond to PLC isozyme expression in these animals, we examined three subtypes of PLC mRNA expression in brain sections of young and old rats using in situ hybridization technique. Our study indicated decreased carbachol-induced PLC activity in the cerebral cortex and, in contrast, increased PLC-beta mRNA in the frontal cortex and superficial cortical layer of aged rats. PLC-alpha mRNA was decreased in hippocampal regions of older rats. These studies suggest that during aging there is an uncoupling of muscarinic stimulated PtdIns hydrolysis, which is accompanied by an increased PLC-beta mRNA and decreased PLC-alpha mRNA that may represent compensatory changes in PLC expression.

Aging↗

Comparison of idarubicin to daunomycin in a randomized multidrug treatment of childhood acute lymphoblastic leukemia at first bone marrow relapse: a report from the Children's Cancer Group.

The outcome of children with acute lymphoblastic leukemia (ALL) and bone marrow relapse has been unsatisfactory largely because of failure to prevent subsequent leukemia relapses. Ninety-six patients were enrolled and received vincristine, prednisone, L-asparaginase, and an anthracycline as reinduction therapy. Ninety-two patients were randomized to receive either daunomycin (DNR) or idarubicin (IDR). After achievement of second complete remission (CR2), maintenance chemotherapy included the same anthracycline, IDR or DNR, high-dose cytarabine, and escalating-dose methotrexate. Compared to DNR (45 mg/m2/week x 3), IDR (12.5 mg/m2/week x 3) was associated with prolonged myelosuppression and more frequent serious infections. Halfway through the study, the dose of IDR was reduced to 10 mg/m2. Overall, second remission was achieved in 71% of patients. Reinduction rate was similar for IDR and DNR. Reasons for induction failure differed; none of 15, 1 of 5, and 5 of 7 reinduction failures were due to infection for DNR, IDR (10 mg/m2), and IDR (12.5 mg/m2), respectively. Two-year event-free survival (EFS) was better among patients who received IDR (12.5 mg/m2) (27 +/- 18%) compared to DNR (10 +/- 8%, P = 0.05) and IDR (10 mg/m2) (6 +/- 12%, P = 0.02). However, after 3 years of follow-up, late events in the high-dose IDR group result in a similar EFS to the lower-dose IDR and DNR groups. In conclusion, IDR is an effective agent in childhood ALL. When used weekly at 12.5 mg/m2 during induction, the EFS outcome during the first 2 years of treatment appears better than lower-dose IDR or DNR (45 mg/m2), although this difference was not sustained at longer periods of follow-up. Increased hematopoietic toxicity seen at this dose might be reduced through the use of supportive measures, such as hematopoietins and intestinal decontamination.

Antibiotics, Antineoplastic↗