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Biomedical subjects

J Bucher

Publications and source records attributed to J Bucher.

At least 19 recordsLinked to original sources

A serine/alanine polymorphism in the nucleotide-binding fold-2 of the sulphonylurea receptor-1 (S1369A) is associated with enhanced glucose-induced insulin secretion during pregnancy.

The sulphonylurea receptor-1 (SUR-1) regulates glucose-induced insulin secretion by controlling K+-ATP channel activity of the pancreatic beta-cell membrane. In this study, we investigated the putative role of a T/G-polymorphism (exon 33, codon 1369; S1369A) in the adenosine diphosphate-sensing nucleotide-binding fold-2 (NBF-2) of the SUR-1 on glucose-induced insulin secretion during an oral glucose tolerance test in pregnant women (PW; n=182). Compared to PW with the T/T genotype, statistically significant elevated C-peptide concentrations were found 60 min after glucose intake in PW with the T/G and G/G genotype (T/T 9.0+/-0.4 ng/ml vs T/G 10.8+/-0.4 ng/ml or G/G 10.8+/-0.7 ng/ml, p=0.01). Furthermore, compared to PW with T/T genotype the deltaC-peptide (60/0 min) was significantly enhanced in PW with T/G or G/G genotype (T/T 6.7+/-0.3 vs T/G 8.9+/-0.4 or G/G 8.9+/-0.7, p=0.0009). A significant correlation of C-peptide concentrations with blood glucose (BG) 60 min after glucose intake was only found in PW with the T/T genotype (r=0.6, p<0.0004). Similarly, a significant correlation of insulin concentrations with BG 60 min after glucose intake was observed in PW with T/T genotype (r=0.5, p<0.0001) and T/G genotype (r=0.24, p<0.03) but not in PW with G/G genotype (r=0.01, p=0.9). From our data we conclude that in PW with the alanine substitution in the NBF-2 region, the insulin response of the pancreatic beta-cell after glucose intake is enhanced and does not correlate with actual BG levels.

ATP-Binding Cassette Transporters↗

Avoided and avoidable risks of cancer.

Despite the considerable efforts and funds devoted to cancer research over several decades, cancer still remains a mainly lethal disease. Cancer incidence and mortality have not declined at the same rate as other major causes of death, indicating that primary prevention remains a most valuable approach to decrease mortality. There is general agreement that environmental exposures are variously involved in the causation of the majority of cancer cases and that at least half of all cancers could be avoided by applying existing etiologic knowledge. There is disagreement, however, regarding the proportion of cancer risks attributable to specific etiological factors, including diet, occupation and pollution. Estimates of attributable risks are largely based today on unverified assumptions and the calculation of attributable risks involves taking very unequal evidence of various types of factors and treating them equally. Effective primary prevention resulting in a reduction of cancer risk can be obtained by: (i) a reduction in the number of carcinogens to which humans are exposed; or (ii) a reduction of the exposure levels to carcinogens. Exposure levels that could be seen as sufficiently low when based on single agents, may actually not be safe in the context of the many other concomitant carcinogenic and mutagenic exposures. The list of human carcinogens and of their target organs might be quite different if: (i) epidemiological data were available for a larger proportion of human exposures for which there is experimental evidence of carcinogenicity; (ii) more attention was paid to epidemiological evidence that is suggestive of an exposure-cancer association, but is less than sufficient, particularly in identifying target organs; and (iii) experimental evidence of carcinogenicity, supported by mechanistic considerations, were more fully accepted as predictions of human risk.

Carcinogenicity Tests↗

Endothelin and calcium antagonists in the skin microcirculation of patients with coronary artery disease.

BACKGROUND: Endothelin, a potent endothelium-derived vasoconstrictor peptide, is elevated in coronary artery disease (CAD); however, its pathophysiological role is uncertain. Calcium antagonists are widely used in patients with CAD. Using laser Doppler flowmetry, we investigated the influence of two endothelin antagonists and the calcium antagonist diltiazem on endogenous and exogenous endothelin in the skin microcirculation of CAD patients and healthy control subjects. METHODS AND RESULTS: Both endothelin antagonists and diltiazem applied intradermally induced vasodilation in CAD patients, which was more pronounced with the ETA/ETB antagonist than with the ETA antagonist or diltiazem. Exogenous endothelin led to profound vasoconstriction in CAD patients and healthy volunteers. Both endothelin antagonists and diltiazem blunted the vasoconstriction to exogenous endothelin in CAD patients and young healthy volunteers and less so in old healthy volunteers. However, compared with both endothelin antagonists, a 10-times-higher dose of diltiazem was required. Systemic diltiazem (240 mg, slow release) attenuated endothelin-induced vasoconstriction in CAD patients. Neurogenic vasodilation to exogenous endothelin was inhibited by both endothelin antagonists. CONCLUSIONS: This study demonstrates that endogenous endothelin of CAD patients contributes to the regulation of vascular tone in the skin microcirculation not only through ETA receptors but also possibly through ETB receptors. Diltiazem inhibited endothelin-induced vasoconstriction, but endothelin antagonists were slightly more effective. Thus, endothelin antagonists represent potent new tools to interfere with the vascular effects of endothelin in CAD patients. Future studies must confirm these findings in other areas of the circulation.

Administration, Oral↗

[Disulfiram in the treatment of alcoholic patients].

In a retrospective investigation we report our experience with alcohol-dependent patients who were hospitalized between 1987 and 1990. There were 58 patients, 29% of them were hospitalized several times. In the middle of 1991 and 1992 we interviewed the family doctors and the social workers who cared for the patients. In 48% of the patients there was improvement, in 24% there was a stabilization, and in 28% we noted a deterioration. There was no difference in patients treated by the family doctor alone or in patients treated by the social workers. Comparing patients taking Disulfiram with patients taking no drug, there was no difference in improvement (48% versus 50%). But the good results in patients not taking disulfiram were nearly exclusively noted for those who had been hospitalized in a special clinic for alcohol-dependent persons. Patients who were hospitalized several times for alcohol withdrawal had a worse chance to improve their situation (-20%). The therapy with disulfiram in alcohol-dependent patients is helpful to cure chronic alcoholics. Programs in a specialized clinic improve also the chance to be cured of the addiction.

Adult↗

Long-term exposure to the anti-inflammatory agent phenylbutazone induces kidney tumors in rats and liver tumors in mice.

Long-term toxicity and carcinogenicity of phenylbutazone, a nonsteroidal anti-inflammatory drug, were evaluated in F344/N rats and B6C3F1 mice. In 2-year studies, phenylbutazone was given in corn oil by gavage 5 days per week to groups of 50 rats of each sex at doses of 0, 50, or 100 mg/kg body weight, and to groups of 50 mice at doses of 0, 150, or 300 mg/kg body weight. Body weights and survival were similar among groups. Major target organs are kidneys in rats and liver in mice. Kidney: inflammation, papillary necrosis, and mineralization in both sexes of rats, and hyperplasia and dilatation of the pelvis epithelium, and cysts in female rats. Uncommon tubular cell tumors of the kidney were found in 13 exposed rats: 5 in the 50 mg group and 4 in the 100 mg group of males; 4 in dosed female rats; none in controls. In female rats, dose-related increases in hyperplasia of the pelvis transitional epithelium, and 2 carcinomas were discovered. Urinary bladder: papillomas of the transitional epithelium were seen in 2 low-dose male and in 1 low-dose female rats. Forestomach: ulcers in rats, with acanthosis, hyperkeratosis, and basal cell hyperplasia in female rats; however, no neoplasms were associated with these lesions. Liver: primarily in male mice exposed to phenylbutazone, hemorrhage, centrilobular cytomegaly and karyomegaly, fatty metamorphosis, cellular degeneration, and coagulative necrosis were seen; clear cell foci were observed in male mice. In summary, under the conditions of these 2-year oral intubation studies, phenylbutazone is associated with renal carcinogenicity in rats, as evidenced by increases in tubular cell neoplasms in both sexes. Evidence of carcinogenicity for male mice was shown by increased incidences and multiplicity of liver tumors. No carcinogenic activity was found for female mice.

Adenoma↗

Rubidium and cesium in spruce needles. Concentrations and biodynamics.

The endogenous concentrations of Rb and Cs have been determined in needles of 56 trees (Norway spruce, Picea abies) from eight different sites. Analysis was done by instrumental neutron activation. Concentrations were found to have a very large range (3-28,000 ng Cs/g and 1-190 micrograms Rb/g). The values on a given site have a tendency toward a log-normal distribution. There is a significant correlation between Rb and Cs, but the correlation is not linear. The concentrations of both elements are a function of the needle age. They decrease smoothly, approaching a constant value, when going from needle age class 1 to 5. It is shown that one algebraic function describes this biodynamic behavior on all sites and at all concentration levels. The function and its parameters are discussed.

Cesium↗

Is there a market for regional units in child and adolescent psychiatry?

BACKGROUND: An analysis of the demand for the services of a sub-regional Family and Young Persons Unit which offers both in-patient and out-patient treatment for children and adolescents with psychiatric, emotional or psychological problems was performed. METHODS: Interviews were held and questionnaires were sent to representatives of the principal and potential users of the service both within the local district and beyond. RESULTS: The results demonstrated unmet demand for outpatient services but only limited demand for in-patient services in some districts. The role of market research in the new National Health Service and some of the difficulties of applying it are discussed. The implications of the findings for both the Family and Young Persons Unit and for child and adolescent psychiatry are considered. CONCLUSION: It is concluded that the effect of the market may be to bring about the closure of regional units unless there is intervention to protect them.

Adolescent↗

Toxicity and carcinogenicity of hydroquinone in F344/N rats and B6C3F1 mice.

Toxicology and carcinogenesis studies were conducted by administering hydroquinone (more than 99% pure) by gavage to groups of F344/N rats and B6C3F1 mice of each sex for 14 days, 13 wk or 2 yr. 14-day studies were conducted by administering hydroquinone in corn oil to rats at doses ranging from 63 to 1000 mg/kg body weight and to mice at doses ranging from 31 to 500 mg/kg, 5 days/wk. In the 13-wk studies, doses for rats and mice ranged from 25 to 400 mg/kg. At those doses showing some indication of toxicity in the 14-day and 13-wk studies, the central nervous system, forestomach and liver were identified as target organs in both species and renal toxicity was observed in rats. Based on these results, 2-yr studies were conducted by administering 0, 25 or 50 mg hydroquinone/kg in deionized water by gavage to groups of 65 rats of each sex, 5 days/wk. Groups of 65 mice of each sex were given 0, 50 or 100 mg/kg on the same schedule. 10 rats and 10 mice from each group were killed and evaluated after 15 months. Mean body weights of high-dose male rats and high-dose mice were approx. 5-14% lower than those of controls during the second half of the study. No differences in survival were observed between dosed and control groups of rats or mice. Nearly all male rats and most female rats in all vehicle control and exposed groups had nephropathy, which was judged to be more severe in high-dose male rats. Hyperplasia of the renal pelvic transitional epithelium and renal cortical cysts were increased in male rats. Tubular cell hyperplasia of the kidney was seen in two high-dose male rats, and renal tubular adenomas were seen in 4/55 low-dose and 8/55 high-dose male rats; none was seen in vehicle controls or in female rats. Mononuclear cell leukaemia in female rats occurred with increased incidences in the dosed groups (vehicle control, 9/55; low dose, 15/55; high dose, 22/55). Compound-related lesions observed in the liver of high-dose male mice included anisokaryosis, syncytial alteration and basophilic foci. The incidences of hepatocellular neoplasms, primarily adenomas, were increased in dosed female mice (3/55; 16/55; 13/55). Follicular cell hyperplasia of the thyroid gland was increased in dosed mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

Survey of health promotion in Pennsylvania nursing homes.

Health promotion programs for residents represent a discretionary organizational response to increased demand for service differentiation within the nursing home setting. More than half (57%) of facilities in a systematic sample of Pennsylvania nursing homes reported offering one or more health promotion programs. This article describes the variety of topical categories of programs. Guided by two alternative explanations of medical technology adoption--the key professional model versus the institutional/environmental model--an explanation is offered about why some facilities offer such programs and others do not.

Evaluation Studies as Topic↗

The relationship between post-natal depression and mother-child interaction.

The study was based on an index group of 49 mothers who had had depressive disorders in the post-natal year, and 49 control mothers who had been free from any psychiatric disorder since delivery. Nineteen months after childbirth, the interaction between mother and child was assessed by blind assessors using defined observational methods. Compared with controls, index mother-child pairs showed a reduced quality of interaction (e.g. mothers showed less facilitation of their children, children showed less affective sharing and less initial sociability with a stranger). Similar but reduced effects were seen in a subgroup of index mothers and children where the mother had recovered from depression by 19 months. Social and marital difficulties were associated with reduced quality of mother-child interaction.

Adolescent↗

Carcinogenesis studies in rodents for evaluating risks associated with chemical carcinogens in aquatic food animals.

Fish and shellfish caught in polluted waters contain potentially dangerous amounts of toxic and carcinogenic chemicals. Public concern was heightened when a large percentage of winter flounder taken from Boston Harbor was found to have visible cancer of the liver; winter flounder outside the estuary area had no liver lesions. Long-term chemical carcinogenesis studies could be easily and feasibly designed using laboratory rodents offered diets containing fish caught in polluted waters. Induced cancers in rodents would corroborate field observations in fish; positive results from these studies would provide further evidence about potential human health hazards from eating substantial amounts of chemically contaminated fish. Nonetheless, fish and aquatic organisms should be viewed as environmental biological monitors of pollution or of potential human health hazards, and authorities responsible for assuring clean and safe rivers, bodies of water, and biota should give more attention to these valid biological indicators or sentinels of environmental pollution. Consequently, fish and other sea creatures alone should serve as alarms regarding whether water areas constitute public health hazards.

Animals↗

Chemicals associated with site-specific neoplasia in 1394 long-term carcinogenesis experiments in laboratory rodents.

The carcinogenicity data base used for this paper originated in the late 1960s by the National Cancer Institute and since 1978 has been continued and made more comprehensive by the National Toxicology Program. The extensive files contain among other sets of information detailed pathology data on more than 400 long-term (most often 24 month) chemical carcinogenesis studies, comprised of nearly 1600 individual experiments having at least 10 million tissue sections that have been evaluated for toxicity and carcinogenicity. Using the current data set of 379 studies made up of 1394 experiments, we have compiled listings of chemicals having like carcinogenic target sites for each of the 34 organs or systems for which histopathology diagnoses have been recorded routinely. The most common tumor site is the liver (15% of all experiments), followed in rank order by: lung, hematopoietic system and kidneys, mammary glands, forestomach, thyroid glands, Zymbal glands, urinary bladder, skin and uterus/cervix, and circulatory system and adrenal glands. These compilations are most useful for maintaining a historic perspective when evaluating the carcinogenicity of contemporary experiments. Equally important, the chemical-tumor-organ connection permits an evaluation of how well chemically induced cancers in a particular organ in one sex or species will predict or correlate with the other sex or species. Using liver cancers as an example, the overall interspecies concordance is 80%. Likewise target site predictions can be made for chemicals selected for study that may be similar to those already evaluated; thereby experimental protocols could be adjusted to allow, for example, more extensive pathology on preselected target organs (i.e., serial sections of the kidney). Further from these observations, one could decide to use two strains of mice to evaluate a short-chain chlorinated aliphatic compound or to study a human carcinogen in a sex-species known to develop chemically induced tumors in the same site observed in humans. Structural classes of chemicals having a propensity for certain organs can be easily identified from these data. Sex-species responders to particular induced cancers become clearly evident, such as in the ovary of female mice or in the kidney of male rats.

Animals↗

[Administration of prostaglandin E1 in diabetics and non-diabetic patients with severe Fontaine stage IIb arterial occlusive disease].

The success in therapy of prostaglandin E1 intra-arterially and intravenously applied to diabetics and non-diabetics with PAOD, stages IIb-IV according to Fontaine, was scrutinized in a city hospital primarily concerned with geriatrics, metabolism, and angiology. All the patients included were examined in retrospective studies with regard to the improvement of their situations during their stays in hospital and--in addition to that--a part of them prospectively some time after their stays in hospital. In all, 99 patients were included in the retrospective examination of which there were 60 diabetics and 39 non-diabetics. Of the 60 diabetics 53 were in stage IV, 5 in stage III, and 2 in stage IIb while in case of non-diabetics 26 were in stage IV, 10 in stage III, and 3 in stage IIb. 50 of the diabetics and 27 of the non-diabetics were treated intra-arterially. The prospectively orientated post-observation included 38 diabetics and 24 non-diabetics. The results of the retrospective examination revealed a significantly superior efficiency of intra-arterially applied PGE1 compared with the intravenous application, both, with regard to the reduction of needed analgesics and the improvement of the clinical situation. A comparison between intra-arterially treated diabetics and non-diabetics showed a significantly higher rate of success of the diabetics regarding to the improvement of the clinical situation. Concerning the prospective post-examination: due to their PAOD the diabetics took significantly more often analgesics at the time of their post-examination than the non-diabetics. Also concerning the development of their clinical situations the diabetics turned out to have worse results than the non-diabetics, however, the differences were not significant in this case.

Aged↗

Short-term group therapy for stroke patients in a rehabilitation centre.

Three groups of eight patients who had suffered strokes participated in short-term group therapy run by a psychiatrist and a social worker. A simple assessment was made by patients and therapists, further information being obtained by means of a follow-up questionnaire. The feasibility of this approach, and the indications that such groups might be beneficial, are discussed. Certain common themes emerged from all three groups, but it was interesting to note a different reaction was shown by men and women in response to their strokes. The provision of such groups for patients suffering from different illnesses and alternative ways of running these groups are suggested.

Adaptation, Psychological↗