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Biomedical subjects

M Gross

Publications and source records attributed to M Gross.

At least 181 records · Page 10Linked to original sources
PubMed1999

Acceptability of a bioadhesive nonoxynol-9 gel delivered by an applicator as a rectal microbicide.

BACKGROUND AND OBJECTIVES: Potential rectal microbicides, as an adjunct to condoms for HIV/STD prevention, have not been studied previously. GOAL OF THIS STUDY: Advantage 24 (1.5 ml of a bioadhesive gel containing 52.5 mg nonoxynol-9 administered by single-use applicator)-under investigation as a vaginal microbicide-was evaluated for acceptability among male couples. STUDY DESIGN: Twenty-five HIV-negative and 10 HIV-positive male couples participated in a frequency use escalation trial. Diaries and self-administered questionnaires assessed product use, acceptability, sexual behavior, and gastrointestinal and urologic side effects. RESULTS: Excluding participants who felt no need for an HIV prevention method, 58% said they would use Advantage 24 if approved for rectal use; 69% of receptive users reported rectal fullness and related side effects after insertion of the gel, and 68% reported applicator-related discomfort; 59% of insertive participants found the gel too sticky. CONCLUSIONS: Acceptability remains inconclusive and warrants further study of redesigned applicators and ways to minimize rectal side effects.

Adult↗
PubMed1999

Formation of amyloid fibrils by peptides derived from the bacterial cold shock protein CspB.

Three peptides covering the sequence regions corresponding to the first two (CspB-1), the first three (CspB-2), and the last two (CspB-3) beta-strands of CspB, the major cold shock protein of Bacillus subtilis, have been synthesized and analyzed for their conformations in solution and for their precipitation behavior. The peptides are nearly insoluble in water, but highly soluble in aqueous solutions containing 50% acetonitrile (pH 4.0). Upon shifts of the solvent condition toward lower or higher acetonitrile concentrations, the peptides all form fibrils resembling those observed in amyloid associated diseases. These fibrils have been identified and characterized by electron microscopy, binding of the dye congo red, and X-ray fiber diffraction. Characterization of the peptides in solution by circular dichroism and NMR spectroscopy shows that the formation of these fibrils does not require specific preformed secondary structure in the solution state species. While the majority of the soluble fraction of each peptide is monomeric and unstructured, different types of structures including alpha-helical, beta-sheet, and random coil conformations are observed under conditions that eventually lead to fibril formation. We conclude that the absence of tertiary contacts under solution conditions where binding interactions between peptide units are still favorable is a crucial requirement for amyloid formation. Thus, fragmentation of a sequence, like partial chemical denaturation or mutation, can enhance the capacity of specific protein sequences to form such fibrils.

Amino Acid Sequence↗
PubMed1999

Lamotrigine monotherapy in newly diagnosed untreated epilepsy: a double-blind comparison with phenytoin.

PURPOSE: Lamotrigine is an effective add-on therapy against a range of epileptic seizure types. Comparative studies with carbamazepine (CBZ) as monotherapy in newly diagnosed epilepsy suggest similar efficacy. In this study, lamotrigine (LTG) and phenytoin (PHT) are compared. METHODS: In a double-blind parallel-groups study, 181 patients with newly diagnosed untreated partial seizures or secondarily or primary generalised tonic-clonic seizures were randomised to two treatment groups. One group (n = 86) received LTG titrated over 6 weeks from a starting dose of 100 mg/day. The other (n = 95) received PHT titrated from 200 mg/day. Treatment continued for < or =48 weeks. RESULTS: The percentages of patients remaining on each treatment and seizure free during the last 24 and 40 weeks of the study, and times to first seizure after the first 6 weeks of treatment (dose-titration period), did not differ significantly between the treatment groups. These were measures of efficacy. Time to discontinuation, a composite index of efficacy and safety, likewise did not distinguish between treatments. Adverse events led to discontinuation of 13 (15%) patients from LTG and 18 (19%) from PHT. The adverse-event profile for LTG was dominated by skin rash [discontinuation of 10 (11.6%) patients compared with five (5.3%) from PHT] rather than central nervous system side effects: asthenia, somnolence, and ataxia were each significantly more frequent in the PHT group. The high rate of rash with LTG was probably due to the high starting dose and may be avoidable. A quality-of-life instrument, the SEALS inventory, favoured LTG. Patients taking PHT showed the biochemical changes expected of an enzyme-inducing drug, whereas those taking LTG did not. CONCLUSIONS: LTG and PHT monotherapy were similarly effective against these seizure types in patients with newly diagnosed epilepsy. LTG was better tolerated, more frequently causing rash, but with a lower incidence of central nervous system side effects.

Adolescent↗
PubMed1999

Use of reality "female condoms" for anal sex by US men who have sex with men. HIVNET Vaccine Preparedness Study Protocol Team.

OBJECTIVES: This study assessed use of Reality "female condoms" for anal sex by HIV-seronegative men who have sex with men and are at high risk for HIV infection. METHODS: Self-administered questionnaires were completed by 2277 participants in a 6-city prospective cohort study. RESULTS: Of the 1084 (48%) men who had heard of using the female condom for anal sex, 145 (13%) reported using it in the prior 6 months. Users were at greater risk than nonusers: 47 receptive and 35 insertive users reported problems, including bleeding by the receptive partner (4). CONCLUSIONS: Redesign of the female condom could increase acceptability and use by men who have sex with men and could address possible safety concerns.

Adult↗
PubMed1999

Venous thromboembolism prophylaxis after total hip or knee arthroplasty: a survey of Canadian orthopedic surgeons.

OBJECTIVE: To determine the pharmacologic and physical modalities used by orthopedic surgeons in Canada to prevent venous thromboembolism (deep venous thrombosis and pulmonary embolism) after total hip or knee arthroplasty. DESIGN: Mail survey sent to all members of the Canadian Orthopaedic Association. SETTING: A nation-wide study. METHODS: A total of 828 questionnaires, designed to identify the type and frequency of prophylaxis against venous thromboembolism that were used after hip and knee arthroplasty were mailed to orthopedic surgeons. OUTCOME MEASURES: Demographic data and the frequency and type of thromboprophylaxis. RESULTS: Of the 828 surveys mailed 445 (54%) were returned, and 397 were included in this analysis. Of the respondents, 97% used prophylaxis routinely for patients who undergo total hip or knee arthroplasty. Three of the 397 (0.8%) did not use any method ofprophylaxis. Warfarin was the most common agent used (46%), followed by low-molecular-weight heparin (LMWH) (36%). Combination therapy with both mechanical and pharmacologic methods were used in 39% of patients. Objective screening tests were not frequently performed before discharge. Extended prophylaxis beyond the duration of hospitalization was used by 36% of physicians. CONCLUSION: Prophylaxis for venous thromboembolism with warfarin or LMWH has become standard care after total hip or knee arthroplasty in Canada.

Anticoagulants↗
PubMed1999

Distribution and concordance of N-acetyltransferase genotype and phenotype in an American population.

Polymorphic arylamine N-acetyltransferase 2 (NAT2) status varies widely between individuals and ethnic groups and has been associated with susceptibility to several cancers. Few studies have reported the distribution of NAT2 status for Caucasian-American populations or evaluated the concordance between methods of assessment for cancer cases and controls. In our study, distribution of NAT2 status was classified by genotype and phenotype measurements in PANCAN, a population-based case-control study of pancreatic cancer, and concordance between measurements was evaluated for 33 cases and 222 controls. Major genotypes and alleles among controls were *5B/*6A, *5B/*5B, *4/*6A, and *5B/*4. One putative new allele was found in a single individual. Genotypes and phenotypes were classified as rapid or slow, according to a bimodal model. Presence of the *4 (wild-type) allele defined a NAT2 genotype as rapid. The NAT2 phenotype was analyzed by the caffeine assay. Ratios of 5-acetylamino-6-formylamino-3-methyluracil to 1-methylxanthine were determined, and individuals with values of > or =0.66 were identified as having a rapid phenotype. In our population, 58.1 and 59.5% of control subjects were classified as slow acetylators by phenotype and genotype, respectively. Concordance of NAT2 genotype and phenotype classification was 97.8% in the bimodal model. A similar analysis was completed for a trimodal model. Concordance of genotype and phenotype was high in cases (90.9%) and similar to controls; genotyping alone provided an efficient, accurate method of analysis for acetylator status. A comparison with two previous reports revealed subtle differences in genotype and allele distribution but exhibited overall similarity with other Caucasian-American populations.

Aged↗
PubMed1998

Effect of ribose on cardiac adenine nucleotides in a donor model for heart transplantation.

Preservation time of explanted hearts is short. Cardiac function after transplantation declines dramatically in hearts that have been preserved for more than 4 to 6 hours. This has been linked to a critical decrease in high energy phosphates (HEP) after explantation. Ribose has previously been shown to stimulate HEP synthesis and to improve cardiac function. In this study, ribose was infused into 20 rats for 24 hours continuously before explantation (donor treatment) and also added to the solutions used for preservation. Saline was used in the control group. Myocardial tissue biopsies were taken after 24h of infusion and after 4h of preservation. High energy phosphates were determined by HPLC. Adenosine triphosphate content (ATP), energy charge and total adenine nucleotides (TAN) were significantly lower after 4h of preservation in both the ribose-treated and the control group compared to hearts before preservation. The difference in mean ATP concentrations between the 4 hours preserved ribose group and the control group was not significant. Single case analysis however revealed a minimum ATP level of 12.3 micromol/g dry weight in 10 ribose treated hearts whereas 2 out of 11 control hearts showed ATP levels below 10 micromol/g dry weight. - This study supports the hypothesis that ribose treatment is capable of maintaining ATP at a higher level in preserved rat hearts. Donor treatment and metabolic support with ribose during organ preservation may be suitable to prolong preservation time of donor hearts.

Adenine Nucleotides↗
PubMed1998

Hearing screening in at-risk neonate cohort.

OBJECTIVE: This prospective study reports on the prevalence of hearing impairment in an at-risk neonatal intensive care unit (NICU) population. DESIGN: From 1990 to 1997, 942 neonates were screened with transient evoked otoacoustic emissions (TEOAE) and brainstem evoked response audiometry (BERA). RESULTS: 835 Infants passed the primary screen for both ears, 57 for one ear, adding up to 94.7%. Seventeen infants (1.9%) were lost to follow-up. In thirteen infants (1.4%), bilateral hearing impairment above 30 dB was confirmed. While all children with hearing impairment belonged to the group of 820 children receiving aminoglycosides, only one presented no other risk factors. In 11 of the hearing impaired children other anamnestic factors, i.e. dysmorphism, prenatal rubella or cytomegaly, family history of hearing loss or severe peri- and postnatal complications seem to be more probable causes of the identified hearing loss. CONCLUSIONS: From our data, aminoglycosides seem not to be an important risk factor for communication related hearing impairment, when serum levels are continuously monitored, as occurred in our cohort. After adjustment for other risk factors, birth weight between 1000 and 1500 g and a gestational age between 29 and 31 weeks were no predictive markers for hearing impairment. It might be speculated that the improved medical treatment in a Neonatal Intensive Care Unit (NICU) reduces the probability of hearing impairment for those two groups. Conductive hearing loss as a possible additional cause for hearing impairment was not studied in detail, but the high percentage of malformations detected (four out of 13 hearing impaired infants) demands further monitoring, close follow-up, counselling and adequate treatment.

Acoustic Stimulation↗
PubMed1998

The gamma134.5 protein of herpes simplex virus 1 has the structural and functional attributes of a protein phosphatase 1 regulatory subunit and is present in a high molecular weight complex with the enzyme in infected cells.

The carboxyl-terminal domain of the gamma134.5 protein of the herpes simplex virus 1 binds to protein phosphatase 1alpha (PP1) and is required to prevent the shut-off of protein synthesis resulting from phosphorylation of the alpha subunit of eIF-2 by the double-stranded RNA-activated protein kinase. The corresponding domain of the conserved GADD34 protein homologous to gamma134.5 functionally substitutes for gamma134.5. This report shows that gamma134.5 and PP1 form a complex in the infected cells, that fractions containing this complex specifically dephosphorylate eIF-2alpha, and that both gamma134.5 and GADD34 proteins contain the amino acid sequence motif common to subunits of PP1 that is required for binding to the PP1 catalytic subunit. An oligopeptide containing this motif competes with gamma134.5 for binding to PP1. Substitution of Val193 and Phe195 in the PP1-binding motif abolished activity. These results suggest that the carboxyl-terminal domain of gamma134.5 protein has the structural and functional attributes of a subunit of PP1 specific for eIF-2alpha, that it has evolved to preclude shut-off of protein synthesis, and that GADD34 may have a similar function.

Amino Acid Sequence↗
PubMed1998

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↗
PubMed1998

Protein folding: think globally, (inter)act locally.

Protein folding appears to be almost too complex for a complete description or for accurate structure prediction from sequence data. A simple way of analysing local interactions, however, bears promise of linking theory with experiment and cutting through some of the complexities.

Models, Biological↗
PubMed1998

The social context of drinking, drug use, and unsafe sex in the Boston Young Men Study.

The objective of this study was to evaluate the relation between drinking, drug use, and unprotected anal intercourse in young men who have sex with men. A cross-sectional analysis of first-visit data from a prospective cohort of 508 young gay men recruited from 1993 through 1994 from bars, college campuses, and the Fenway Community Health Center in Boston was performed. The major outcome measures were any unprotected anal intercourse, after drinking and when sober, stratified by type of sexual partner (steady or nonsteady) during the previous 6 months and during the most recent sexual encounter. The average age of the cohort was 23.3 years; 77.6% were white, and 76.4% were in college. These young men had a median of 10.5 male sexual partners in their lifetimes, and 3 sexual partners in the previous 6 months before enrollment. One hundred and thirty-four (26%) reported unprotected anal intercourse during the previous 6 months. Individuals who had unprotected anal intercourse were more likely to have a drinking problem (odds ratio [OR] = 1.95; 95% confidence interval [CI] = 1.26-3.01) and drank more (20.4 ml/day versus 13.9 ml/day; p < or = 0.01), compared with individuals who did not engage in unprotected anal intercourse. Overall, men were significantly less likely to have unprotected anal intercourse after alcohol or drug use, based on a series of paired analysis (OR = 0.27; 95% CI = 0.15-0.48). However, when we stratified by type of sexual partner, men were significantly more likely to have unprotected anal intercourse with their nonsteady sexual partners after drinking than when sober (OR = 4.33; 95% CI = 1.37-13.7), but were significantly less likely to have unprotected anal intercourse with steady partners (OR = 0.27; 95% CI = 0.15-0.48). The patterns observed as already mentioned for drinking were also found for substance use in general. Men who were more likely to have unprotected anal intercourse after substance use were significantly more likely to have a drinking problem (OR = 7.65; 95% CI = 2.34-24.59). These results suggest that the role of alcohol and unsafe sex in young gay men is complex, with the role of situational factors of paramount importance. Alcohol and substance use interventions designed to reduce HIV risk need to specify the role of substance use in the sexual context to be successful.

Adult↗