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Biomedical subjects

K Mayer

Publications and source records attributed to K Mayer.

At least 91 records · Page 5Linked to original sources

Sexual practices in a cohort of US women with and without human immunodeficiency virus. HERS Study. HIV Epidemiology Research Study.

OBJECTIVES: To compare the frequency and pattern of sexual activities of women infected with human immunodeficiency virus (HIV) relative to uninfected women at the time of enrollment into a multisite cohort study. METHODS: The HIV Epidemiology Research Study (HERS) is a prospective study following 873 HIV-infected and 438 HIV-uninfected women. The baseline protocol included interviews about sexual practices, sociodemographic information, and drug and alcohol use, as well as clinical and laboratory studies. Multiple logistic regression models estimated differences between infected and uninfected women in relation to sexual activity and practice. RESULTS: 77% of infected women and 89% of uninfected women reported at least one sexual partner in the six months before study entry. Among sexually active women, specific practices varied little by HIV serostatus, with the exception of oral sex, which was more frequently performed and received by uninfected women. Despite the high prevalence of sexual activity, infected women were 2.5 times as likely not to have had any recent sexual partners as uninfected women (95% CI = 1.77-3.44). CONCLUSIONS: Women who decrease or altogether stop engaging in sexual partnerships may benefit from direct counseling in relation to underlying loss of sexual affection.

Adolescent↗

Simultaneous analysis of 4- and 5-series lipoxygenase and cytochrome P450 products from different biological sources by reversed-phase high-performance liquid chromatographic technique.

Quantification of lipoxygenase and cytochrome P450 products of both arachidonic acid (AA) and eicosapentaenoic acid (EPA) is of broad interest due to the multiple biological activities of these compounds. We developed a method combining (i) solid-phase extraction, (ii) isocratic reversed-phase high-performance liquid chromatographic separation, and (iii) online photodiode array detection with spectrum analysis for identification and measurement of all main 4- and 5-series eicosanoids (leukotrienes, hydroxyeicosatetraenoic acids/hydroxyeicosapentaenoic acids, epoxyeicosatrienoic acids) within one run. With these procedures, standard mixtures of AA- and EPA-derived lipid mediators were recovered from different biological liquids, like lung perfusate, human bronchoalveolar lavage fluid, and cell supernatant with linear characteristics for each compound. Recoveries of the different lipid mediators exceeded 80% showing excellent reproducibility. Application of the method to isolated, perfused, and ventilated human lungs challenged with the calcium ionophore A23187 and to human neutrophils stimulated in the presence of arachidonic acid and eicosapentaenoic acid with N-formyl-methionyl-leucyl-phenylalanine demonstrated the generation of a large array of lipoxygenase and cytochrome P450 products. Thus, convenient quantification of 4- and 5-series eicosanoids in fluids of biological interest is achieved by a technique comprising solid-phase extraction, isocratic reversed-phase high-performance liquid chromatography, and photodiode array-based online spectrum analysis of eluting compounds.

Arachidonate 5-Lipoxygenase↗

Readiness of high-risk populations in the HIV Network for Prevention Trials to participate in HIV vaccine efficacy trials in the United States.

OBJECTIVE: To determine the willingness of populations at high risk of HIV-1 infection to participate in HIV vaccine efficacy trials, determine factors influencing decision-making, and evaluate knowledge levels of vaccine trial concepts. DESIGN: Cross-sectional study. METHODS: HIV-1-negative homosexual men, male and female injecting drug users and non-injecting women at heterosexual risk were recruited in eight cities in the United States (n=4892). RESULTS: A substantial proportion of the study population (77%) would definitely (27%) or probably (50%) be willing to participate in a randomized vaccine efficacy trial. Increased willingness was associated with high-risk behaviors, lower education level, being uninsured or covered by public insurance, and not having been in a previous vaccine preparedness study. Altruism and a desire for protection from the vaccine were major motivators for participation. Major concerns included positive HIV-1 antibody test due to vaccine, safety of the vaccine, and possible problems with insurance or foreign travel. Baseline knowledge of vaccine trial concepts was low. CONCLUSIONS: It is likely that high-risk volunteers will be willing to enroll in HIV vaccine efficacy trials. A variety of participant and community educational strategies are needed to address participant concerns, and to ensure understanding of key concepts prior to giving consent for participation.

AIDS Vaccines↗

[Effects of limited mouth opening capacity (trismus) on lung function].

In the present study pulmonary function test data were obtained from 15 healthy volunteers and 15 patients with slightly impaired ventilation during both normal and maximally reduced opening of the mouth (trismus, intercuspid position). The aim of the study was to examine the effects of complete trismus on pulmonary function using objective and subjective parameters. In maximally reduced mouth opening, both groups showed an impairment of all subjective and objective pulmonary function test data. In healthy volunteers, the significant changes in the test data (p < 0.05) simulated mild to moderate pulmonary impairment, whereas patients with an already impaired pulmonary function showed a marked deterioration of their initial respiratory condition. The results of the subjective and objective parameters examined indicate that an intercuspid position (trismus) further aggravates pulmonary functional impairments. Complete trismus can be considered a risk factor to pulmonary function in patients using mouth-breathing as primary or supportive mode of respiration.

Adult↗

Prognosis of medically treated patients referred for cardiac transplantation.

OBJECTIVES: To assess prognosis and factors influencing survival of transplant candidates in whom continued medial therapy was recommended in comparison to that of immediately listed patients. METHODS: Retrospective analysis of clinical, echocardiographic and hemodynamic data as related to survival or listing for transplantation of medically treated transplant candidates. PATIENTS: 160 patients considered 'too well' for cardiac transplantation and 133 patients immediately listed for transplantation. RESULTS: Forty-one of the medically treated patients deteriorated clinically and were listed after 10.7+/-12.3 months after initial evaluation. Mid-term prognosis (2 years) of patients never listed was comparable to that of immediately listed patients (74% vs. 70%) but long-term prognosis (5 years) was worse (41% vs. 54%, p<0.001). Cardiothoracic ratio and pulmonary capillary wedge pressure were independent predictors of survival (multivariate analysis) in patients whose NYHA class and physical working capacity improved and cardiothoracic ratio decreased significantly after adjustment of medical therapy. CONCLUSIONS: Mid-term prognosis of selected patients considered 'too well' for transplantation is comparable to patients immediately listed. Lower left ventricular filling pressures, smaller hearts on chest X-ray on initial evaluation, and improvement of symptoms during follow up may identify a subgroup of patients who do well on optimized therapy.

Actuarial Analysis↗

Omega-3 fatty acid-based lipid infusion in patients with chronic plaque psoriasis: results of a double-blind, randomized, placebo-controlled, multicenter trial.

BACKGROUND: Profound changes in the metabolism of eicosanoids with increased concentrations of free arachidonic acid (AA) and its proinflammatory metabolites have been observed in psoriatic lesions. Free eicosapentaenoic acid (EPA) may compete with liberated AA and result in an antiinflammatory effect. OBJECTIVE: Our purpose was to assess the efficacy and safety of intravenously administered fish-oil-derived lipid emulsion on chronic plaque-type psoriasis. METHODS: A double-blind, randomized, parallel group study was performed in eight European centers. Eighty-three patients hospitalized for chronic plaque-type psoriasis with a severity score of at least 15 according to the Psoriasis Area and Severity Index (PASI) participated in a 14-day trial. They were randomly allocated to receive daily infusions with either a omega-3 fatty acid-based lipid emulsion (Omegavenous; 200 ml/day with 4.2 gm of both EPA and docosahexaenoic acid (DHA); 43 patients) or a conventional omega-6-lipid emulsion (Lipovenous; EPA+DHA < 0.1 gm/100 ml; 40 patients). The groups were well matched with respect to demographic data and psoriasis-specific medical history. Efficacy of therapy was evaluated by changes in PASI, in an overall assessment of psoriasis by the investigator, and a self-assessment by the patient. In one center neutrophil 4- versus 5-series leukotriene (LT) generation and platelet 2- versus 3- thromboxane generation were investigated and plasma-free fatty acids were determined. RESULTS: The total PASI score decreased by 11.2 +/- 9.8 in the omega-3 group and by 7.5 +/- 8.8 in the omega-6 group (p = 0.048). In addition, the omega-3 group was superior to the omega-6 group with respect to change in severity of psoriasis per body area, change in overall erythema, overall scaling and overall infiltration, as well as change in overall assessment by the investigator and self-assessment by the patient. Response (defined as decrease in total PASI of at least 50% between admission and last value) was seen in 16 of 43 patients (37%) receiving the omega-3 emulsion and 9 of 40 patients (23%) receiving omega-6 fatty acid-based lipid emulsion. No serious side effects were observed. Within the first few days of omega-3 lipid administration, but not in the omega-6 supplemented patients, a manifold increase in plasma-free EPA concentration, neutrophil leukotriene B5 and platelet thromboxane B3 generation occurred. CONCLUSION: Intravenous omega-3-fatty acid administration is effective in the treatment of chronic plaque-type psoriasis. This effect may be related to changes in inflammatory eicosanoid generation.

Adult↗

Clinical use of lipids to control inflammatory disease.

Selective dietary supplementation with lipids has long been used to influence the course of chronic inflammatory diseases. This review describes new aspects of the molecular mechanism of lipids to modulate leukocyte activity and highlights some recent clinical studies on therapeutic lipid administration. New promising advances in parenteral application of lipids as well as the impact on acute inflammatory disorders are discussed.

Animals↗

Nitric oxide biosynthesis in an exotoxin-induced septic lung model: role of cNOS and impact on pulmonary hemodynamics.

Nitric oxide (NO) is an important vasodilator that is produced by constitutive (cNOS) as well as inducible (iNOS) isoforms of nitric oxide synthase. The pore-forming hemolysin of Escherichia coli (HlyA), an important virulence factor in extraintestinal E. coli infections, was found to be a potent stimulator of NO liberation in isolated endothelial cells, and that it also causes thromboxane generation and related vasoconstriction in rabbit lungs. We investigated the effect of different concentrations of HlyA on pulmonary NO synthesis in buffer-perfused rabbit lungs. NO release into the alveolar as well as the intravascular compartment was monitored on-line by chemiluminescence detection of expired NO and by measurement of (peroxy-)nitrite/nitrate release into the perfusate. HlyA induced a pressor response and an immediate dose-dependent increase of exhalative and intravascular NO liberation, further enhanced by the addition of the NOS substrate L-arginine. The nonspecific NOS inhibitor N(G)-monomethyl-L-arginine (L-NMMA), but not the iNOS selective inhibitors aminoguanidine and 2-(2-aminoethyl)-2-thiopseudourea-dihydrobromide, blocked the HlyA-evoked NO liberation into both the alveolar and the intravascular compartments. Enhancement of NO formation (L-arginine) slightly reduced, and inhibition of NO synthesis (L-NMMA) amplified greatly, the HlyA-elicited vasoconstrictor response. Inhibition of the pressor response by a thromboxane receptor antagonist did not interfere with the exotoxin-elicited NO formation. We conclude (1) that marked NO biosynthesis occurs in this model of the septic lung, (2) that the signal transduction in response to HlyA proceeds via activation of cNOS directly related to exotoxin activity and not to secondary changes in shear stress, and (3) that this vasodilator release mitigates the HlyA-induced pulmonary vasoconstriction. These findings may have important implications for therapeutic approaches using NOS inhibitors in sepsis.

Animals↗

Abnormalities of gastric mucosal oxygenation in septic shock: partial responsiveness to dopexamine.

Splanchnic mucosal perfusion abnormalities have been implicated in the development of sepsis and multiorgan failure. We employed reflectance spectrophotometry for direct assessment of the microvascular hemoglobin oxygen saturation (HbiO2) and hemoglobin concentration (rel Hb(conc)) in the mucosa of the upper gastrointestinal tract. Owing to the high recording frequency together with a small catchment volume, assessment of spatial heterogeneity is enabled. Results were as follows: In healthy controls (n = 7), mean HbiO2 was 70.3 +/- 2.1%, with narrow dispersion and near-Gaussian distribution of the histogram. In patients presenting with hyperdynamic septic shock (n = 15) mean HbiO2 was reduced to 51.0 +/- 1.6% in spite of high normal whole-body oxygen delivery, with tailing of the histogram to severely hypoxic values (18.4 % of data < 40%). In parallel, markedly reduced rel Hb(conc) values were recorded and the standardized intramucosal pH (pHi) was lowered to 7.25 +/- 0.01. Short-term infusion of dopexamine (2 microg/kg/min) caused a significant rise in HbiO2 and rel Hb(conc), whereas whole-body oxygen uptake and standardized pHi values were not altered. In conclusion, decreased oxygenation and tissue hemoglobin concentration, with the appearance of severely hypoxic microdomains, were noted in patients with hyperdynamic sepsis, strongly suggesting pronounced microcirculatory disturbances in this compartment. The partial responsiveness of these abnormalities to dopexamine warrants further elucidation.

Adult↗

Women HIV sexual risk takers: related behaviors, interpersonal issues, and attitudes.

HIV and AIDS is a growing health risk for heterosexual women, particularly women of color (Centers for Disease Control and Prevention, 1997). Our research identified 5 types of HIV sexual risk taking in 3 independent samples of adult women from a New England Community: Group A women were noted by low to moderate levels of the 4 risk markers (i.e., unprotected vaginal sex, perceived partner-related risk, number of sexual partners, and unprotected anal sex); Group B women reported very high frequency of unprotected vaginal sex; Group C women were characterized by unprotected anal sex; Group D women had high perceived partner risk; and Group E women reported extremely high levels on all 4 HIV risk markers. Sexual risk groups were validated by demonstrating significant differences among groups on relevant behaviors, interpersonal experiences, and attitudes. Compared to other women, higher risk types reported greater behavioral risk practices (substance use, prostitution, diverse sexual experience), interpersonal risk experiences (sexual abuse, violence), initiation sexual assertiveness, and attitudinal risks (psychosocial distress). They reported less interpersonal assurance (surety of own and partner's HIV status), sexual assertiveness (for condom use and partner communication), psychosocial strengths (sexual self-acceptance), and transtheoretical readiness for change (condom use efficacy, readiness to consider condoms). Results provide additional support for the multifaceted model of HIV risk and the transtheoretical model. Suggestions for specifically focused interventions are given, depending on the pattern of sexual risk taking.

Adolescent↗

Ectopic activation of lymphoid high mobility group-box transcription factor TCF-1 and overexpression in colorectal cancer cells.

Physical interaction between the lymphoid high mobility group (HMG)-box architectural transcription factors TCF/LEF and beta-catenin is associated with translocation of the heteromeric complex to the nucleus and regulation of target gene expression. Since formation of molecular complexes among beta-catenin, E-cadherin, p300apc and TCF/LEF depends on balanced expression of these constituents, we investigated the biosynthesis of TCF-1 in colorectal cancer. Here we report detailed analyses of activation and overexpression of lymphoid transcription factor TCF-1 in human colorectal cancer-derived cell lines. Northern blot analyses revealed considerable steady-state expression levels of TCF-1 mRNA of normal size. Genomic rearrangement of the 5' flanking region of the TCF-1 gene was excluded as a cause of ectopic expression. By contrast, CAT-reporter constructs depending on a 515-bp T-cell-regulated TCF-1 genomic upstream region were significantly activated in epithelial tumor cells. RT-PCR analyses revealed a heterogeneic population of mRNA isoforms due to alternative splicing in the TCF-1 gene. On Western blots of colorectal cancer cells, the TCF-1-specific monoclonal antibody 7H3 detected a similar heterogeneous spectrum of TCF-1 specific polypeptide chains. Interestingly, overexpression of TCF-1-specific splice forms correlated with the metastatic behavior of the analyzed cells and with overproduction of lymphoid tyrosine protein kinase p56(lck). We conclude that ectopic expression of the HMG-box factor TCF-1 is associated with late events in tumor progression.

Alternative Splicing↗

[May-Hegglin anomaly: further studies on thrombocyte dysfunction].

The May-Hegglin anomaly is an extremely rare, autosomal dominant inherited disorder characterized by alterations in white cells and in blood platelets. The granulocytes show basophilic inclusion bodies of no clinical importance. Usually moderate thrombocytopenia with variable platelet size, including giant platelets, is also found. Clinically a mild hemorrhagic diathesis may occur. We report on a so far asymptomatic patient from the second family described by Hegglin et al. in 1964 [1] who had to be treated for repeated life-threatening bleedings. A moderate prolongation of bleeding time was found, corresponding to the reduced platelet count; platelet aggregation induced by ADP, collagen, ristocetin or arachidonic acid was not impaired. Therefore, there is at present no evidence of a congenital platelet function defect in the May-Hegglin anomaly. The bleeding time improved temporarily in our patient on administration of DDAVP (Minirin); platelet substitution is indicated in special situations only.

Adult↗