[Adaptation to intermittent hypoxia-hyperoxia improves cognitive performance and exercise tolerance in elderly].

For improvements in exercise tolerance and cognitive function in geriatric patients Multimodal training programs (MTP) are used as combination of physiotherapy, occupational therapy and cardiovascular training. Intermittent Hypoxic-Hyperoxic Training (IHHT), a modified type of intermittent hypoxic training (IHT) is proposed to be included in MTP to elicit more pronounced beneficial effects in exercise tolerance and cognitive functions of geriatric patients likely by an additional pathway than a single MTP. Thirty four patients of the Geriatric Day Clinic aged between 64 and 92 years participated in the placebo controlled clinical trial. They were randomly assigned to receive MTP plus IHHT (experimental group - EG) or MTP plus placebo-breathing through a machine face mask (control group - CG) in a double blind fashion. Before and after the interventions course cognitive performance was assessed by the Dementia-Detection-Test (DemTect) and the Clock-Drawing-Test (CDT), and functional exercise capacity - by the total distance of 6-Minute-Walk-Test (6MWT). After IHHT combined with MTP cognitive performance (DemTect) increased significantly when compared to NG (+16,7 % vs. +0,39 %, p<0,001). The CDT indicated similar results with a significant increase in the EG while the score of the CG even decreased (+10,7 % vs. -8%, p=0,031). Concerning the functional exercise capacity, both groups improved the total distance in the 6MWT but with a significantly larger increase in the EG compared to the CG (+24,1 % vs. +10,8 %, p=0,021). In addition, there was a significant relationship between the changes of the 6MWT and the DemTect Scores and the CDT. IHHT contributed significantly to improvements in cognitive performance and exercise capacity in elderly performing MTP. IHHT sessions are considered to be easily applicable to and well tolerated by geriatric patients up to 92 years.

GER1, a GDSL motif-encoding gene from rice is a novel early light- and jasmonate-induced gene.

The reaction of the rice mutant HEBIBA differs from that of wild-type rice in that the mutant responds inversely to red light and is defective in the light-triggered biosynthesis of jasmonic acid (JA). Using the wild type and the HEBIBA mutant of rice in a differential display screen, we attempted to identify genes that act in or near the convergence point of light and JA signalling. We isolated specifically regulated DNA fragments from approximately 10 000 displayed bands, and identified a new early light- and JA-induced gene. This gene encodes an enzyme containing a GDSL motif, showing 38 % identity at the amino acid level to lipase Arab-1 in Arabidopsis thaliana. The GDSL CONTAINING ENZYME RICE 1 gene (GER1) is rapidly induced by both red (R) and far-red (FR) light and by JA. The results are discussed with respect to a possible role for GER1 as a negative regulator of coleoptile elongation in the context of recent findings on the impact of JA on light signalling.

Exogenous or endogenous reservoirs of nosocomial Pseudomonas aeruginosa and Staphylococcus aureus infections in a surgical intensive care unit.

OBJECTIVE: A 4 month prospective study was performed to assess the incidence and routes of endogenous or exogenous colonization and nosocomial infection caused by Staphylococcus aureus and Pseudomonas aeruginosa in surgical critically ill patients. DESIGN: A total of 4634 specimens were obtained. Patient's nasal, scalp, and rectal swabs as well as tracheal secretion (TS) were cultured every second day beginning on the day of admission. Nasal swabs and hand cultures of the personnel as well as cultures from gowns were also taken. All isolates of S. aureus were phage typed and 116 of these isolates were also plasmid typed. P. aeruginosa isolates were sero- and pyocin typed. Resistance patterns were determined in all isolates. SETTING: The study was carried out in the surgical intensive care unit (SICU) of an teaching hospital. PATIENTS: During the study period each patient (a total of 153 patients) admitted to the SICU entered the study. RESULTS: P. aeruginosa and S. aureus colonisation rate on admission were 5% and 36.5% respectively. Only 10 patients (6.5%) were colonized with P. aeruginosa during hospitalization, and only 7 patients (4.5%) acquired S. aureus in the surgical intensive care unit (SICU). The most common primary colonisation site of P. aeruginosa was the rectum, whereas S. aureus was predominantly found in nasal cultures. Horizontal transmission of S. aureus occurred in only 2 patients. CONCLUSION: The study suggests that colonisation with P. aeruginosa and S. aureus occurs from endogenous rather than from exogenous sources and that the endogenous acquisition of both bacteria play a more important role in development of nosocomial infections than the exogenous route of transmission.

Enhancement of benzo(a)pyrene-induced sister chromatid exchanges as a consequence of glutathione depletion in vivo.

Pretreatment of Chinese hamsters with phorone (diisopropylidene acetone) decreased hepatic glutathione (GSH) content to about 20% of the control level after 2 hours. The GSH S-transferase activities were not affected. As a consequence of reduced detoxication by GSH the potency of 3,4-benzo(a)pyrene to induce sister chromatid exchanges in vivo in bone marrow cells was significantly enhanced. Chemically induced distinct alterations in metabolism of mutagens/carcinogens are proposed as experimental models for pharmacogenetic and toxigenetic studies.

The in vivo induction of sister chromatid exchanges in the bone marrow of the Chinese hamster. II.N-nitrosodiethylamine (DEN) and n-isopropyl-alpha-(2-methyl-hydrazino)-p-toluamide (Natulan), two carcinogenic compounds with specific mutagenicity problems.

N-Nitrosodiethylamine (DEN) and N-isopropyl-alpha-(2-methylhyadrazino)-p-toluamide (Natulan) were examined with the in vivo SCE method of Vogel and Bauknecht. Only Natulan showed a positive effect with a significant increase of induced SCE between 10 and 25 mg/kg b.w. The six-point curve of the dose effect was of the plateau type. With DEN only a slight increase with high doses could be obtained, which was not significant when 50 or 100 cells were counted. Compared with the results of other tests published, Natulan gives positive results preferentially with in vivo mammalian tests but not with microorganisms. On the other hand, DEN is inactive in vivo on the chromosomal level, but preferentially induces point mutations at the molecular level in microorganisms and Drosophila. It is recommended to include in a battery of true mutagenicity tests also cytogenetic tests (in vivo SCE test and micronucleus test).

The application of mitotic gene conversion in Saccharomyces cerevisiae in a pattern of four assays, in vitro and in vivo, for mutagenicity testing.

The induction of mitotic gene conversion of the nitrofuran derivatives nitrofurantoin (N-(5-nitro-2-furfuryliden)-1-aminohydantoin), nifurprazinum (1-(5-nitro-2-furyl)-2-(6-amino-3-pyridazyl)-ethylenehydrochloride) and FANFT (2-formylamino-4-(5-nitro-2-furyl)thiazole) was investigated in the D4-RDII strain of Saccharomyces cerevisiae (heteroallelic at the gene loci ade2 and trp5, respiration-deficient). A battery of tests was applied: direct action of the substance to yeasts, the liver microsome test in vitro, the host-mediated assay and the urinary assay. From the various combinations of positive and negative results, additional pharmacokinetic conclusions were drawn. The three nitrofuran derivatives gave positive results by direct action and in the urine of rats. The additon of liver microsomes of mice in the test in vitro reduced the number of induced convertants. In the first hours, a great deal of nitrofurantoin given orally to rats was excreted in the urine, as shown by a high genetic activity. Nifurprazinum and FANFT were excreted to a lesser extent or more slowly. Addition of glucuronidase/arylsulfatase reduced the genetic activity in the urine in the case of nitrofurantoin, had an increasing effect with nifurprazinum and was without any effect in the case of FANFT. In the host-mediated assay, only nitrofurantoin gave positive results. These results seem to be a consequence of the quick but different excretion of the nitrofuran derivatives.

Bilateral, tumorlike diabetic mastopathy-progression and regression of the disease during 5-year follow up.

Diabetic mastopathy is a recently described collection of radiographical and histological features found in dense fibrous masses of the breast in long standing Type I diabetes. We describe the first case of bilateral disease with the alternate progression and regression of the disease over a 5 year period. A 45-year-old woman has been affected of insulin dependent diabetes mellitus (IDDM) for 21 years. She developed palpable mass retromamillar of the right side, indistinguishable radiographically from cancer. The histology showed a diabetic mastopathy (DMP) with B-lymphocytic ductitis and lobulitis, a discrete monocellular vasculitis and a keloid-like fibrosis. After 22 months she developed a suspicious palpable mass contralateral on the left side. The FNAB presented an identical morphology on histology. Additionally 10 months later there were no palpable masses of both mammae. Mammographically no suspect alterations were observed. One year later the clinical and mammographical examination showed similar findings, mentioned before. The pathogenesis is still obscure and includes the hypothesis of extracellular accumulation, secondary to prolonged hyperglycemia in IDDM, production of alternated non-enzymatic glycosylated end products with neoantigen formation, B cell predominant inflammation with autoimmune response against neoantigens and cytokine release secondary to the autoimmune response.

Sex hormone therapy and functional brain plasticity in postmenopausal women.

Several studies have shown that fluctuating levels of sex hormones (estrogen and progesterone) can affect fundamental principles of brain organization, including functional cerebral asymmetries (FCAs) and interhemispheric interactions. The majority of findings come from studies investigating younger women tested during distinct hormonal phases of the menstrual cycle, an approach that does not necessarily allow for conclusions about the causal relationship between hormonal changes and functional brain organization. An alternative approach is to manipulate the hormonal status of participants directly. This research focuses on the effects of hormone therapy (HT) on FCAs and interhemispheric interactions in postmenopausal women. Functional brain organization was tested in postmenopausal women using either estrogen therapy or combined estrogen plus gestagen therapy. The results are then compared to age- and IQ-matched postmenopausal women not taking HT. The results indicate HT-related modulations in both FCAs and interhemispheric interaction. In contrast to normally cycling women, however, it seems that HT, and especially estrogen therapy, after menopause affects intrahemispheric processing rather than interhemispheric crosstalk. The findings indicate a faster and more pronounced age-related decline in intrahemispheric relative to interhemispheric processing which seems to be accompanied by a higher sensitivity to HT. Aging processes together with differences in the hormonal status (exogenous changes as a result of HT vs. endogenous changes during the menstrual cycle) may also explain divergent (cognitive) behavioral outcomes in postmenopausal women and younger women. Taken together, the findings suggest that the female brain retains its plasticity even after reproductive age and remains susceptible to the effects of sex hormones throughout the lifetime. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.

Computer-assisted teaching and learning in medicine.

Induced mainly by the increased spreading of personal computers in the last few years computer-assisted instruction (CAI) systems for medicine have been developed on a large scale. Proven structure principles are above all the simulation of patient management in a problem-orientated approach, the mathematical simulation of (patho-) physiological functions independent of particular patients and the separation of educational mode and scoring mode. There exists already a large choice in programs dealing with topics of internal medicine--especially cardiology--while operative disciplines are less represented so far. Programs accredited in the US for continuing medical education (CME) are usually of high quality as to medical contents. Other important quality criteria to be mentioned concerning simulation programs are algorithms of medical decision making, completeness and refinement of the medical knowledge base, software design and user interface. CAI is a unique tool to enhance clinical problem solving skills although--of course--it can by no means replace bedside teaching.

Genotoxic activity of the aminophenols as evidenced by the induction of sister chromatid exchanges.

1 Most hair dyes contain the structural isomers ortho-, meta- and para- aminophenol which were investigated concerning their ability to induce sister chromatid exchanges (SCE) in cultured human lymphocytes in vitro and in Chinese hamster bone marrow cells in vivo. 2 In vitro only ortho-aminophenol significantly induced SCE in a dose-dependent manner. 3 In vivo none of the structural isomers increased significantly the SCE frequency. 4 It is concluded that ortho-aminophenol is a weak directly acting compound which is detoxified during its metabolism.

[Formation and treatment of pathologic scars--clinical and micromorphologic investigations (author's transl)]. / Uber die Entstehung und Behandlung pathologischer Narben -- Klinische und mikromorphologische Untersuchungen.

The results of treatment with Calmurid and Calmurid-HC in patients with hypertrophic scars and keloids of various causes are reported. Histochemical and ultrastructural investigations were performed in individual cases before and after treatment. The following results were found: 1. In the context of keloid prophylaxis and scar care, application of Calmurid and Calmurid-HC has proved very effective. The results of treating hypertrophic scars with urea preparations are also to be evaluated optimistically. 2. The local treatment with Calmurid or Calmurid-HC generally does not have a substantial influence on cosmetically disturbing keloids. However, the skin becomes smoother, more elastic and more resistant under Calmurid or Calmurid-HC therapy; a reduction in the size of the keloid mass is observed only in individual cases. 3. In short, the results are consistent with those which can be obtained with other external preparations which are specially recommended for treatment of scars and keloids. Success of treatment is especially dependent on the age of the lesion. 4. Disturbances in glycosaminoglycan (GAG) and collagen metabolism as well as enzyme defects are the most significant factors in the pathogenesis of pathological scars. The histochemical and electron microscopic studies reveal (of course with the necessary caution in the interpretation) that Calmurid and Calmurid-HC show an effect on distribution of GAG and on the enzyme pattern of the fibroblasts. The preparations may possibly affect the disturbed processes of collagen and GAG synthesis. The reduction of the mast cells in keloids and hypertrophic scars under Calmurid treatment is noteworthy.

Bone marrow genotoxicity of N-methyl, N-nitrosourea (NMU): n-alkanols as sister chromatid exchange (SCE) anti-inducers.

The in vivo SCE test was used to demonstrate significant inhibition of NMU bone marrow genotoxicity by pretreatment of Chinese hamsters with n-alkanols. Our findings exclude a loss of intracellular DNA alkylation potential through a competitive direct reaction of NMU with the weakly nucleophilic polar end of the n-alkanols, but not through methylations of nucleophilic membrane sites possibly liberated by structural modifications which the membrane-active amphiphilics induce.

Comparative in vivo mutagenicity testing by SCE and micronucleus induction in mouse bone marrow.

The treatment of mice with repeated injections of BUdR and FUdR allows for the demonstration of differentially stained metaphases from bone marrow after FPG (fluorescence plus Giemsa; Perry and Wolff, 1974) treatment. Thus, it is possible to determine the number of SCE's under in vivo conditions, which appears as a very promising system for mutagenicity testing. We studied the response of this system in comparison to the micronucleus test using six mutagenic agents: triaziquone, cyclophosphamide (CP), dimethylphenyltriazene (PDMT), methylnitronitrosoguandine (MNNG), dimethylnitrosamine (DMNA), and diethylnitrosamine (DENA). With the exception of MNNG and DENA, all these agents induce both, SCE and micronuclei, MNNG and and DENA being ineffective in both systems. The most potent SCE-inducing agent was triaziquone, followed by PDMT, CP, and DMNA. The quantitative comparison indicates that SCE are induced at 1/10-1/100 of the concentrations which are required for the detection of micronuclei.