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Biomedical subjects

S M Weiss

Publications and source records attributed to S M Weiss.

At least 19 recordsLinked to original sources
PubMed2006

Influencing sexual practices among HIV-positive Zambian women.

This study assessed and compared the efficacy of culturally tailored behavioral interventions to increase use and acceptability of sexual barrier products among HIV-positive women in Zambia. It also sought to evaluate cultural preferences as facilitators or impediments to potential use of vaginal chemical barriers for sexual risk reduction within the Zambian context. Women (N=240), recruited from the University Teaching Hospital HIV Voluntary Counseling and Testing Center, were randomized into group or individual intervention arms. Participants attended a baseline assessment, three intervention sessions and follow up assessments at six and 12 months. All participants increased use and acceptability of female condoms and vaginal products and maintained male condom use at six and 12 months. Preliminary data indicated that group participants increased male condom use at six months and trial use and acceptability of female condoms and lubricants predicted their use in the group condition. Results support group interventions to increase sexual barrier use and acceptability in HIV-positive women within the Zambian context. From a public health standpoint, groups may represent a cost-effective and culturally congruent intervention.

Adult↗
PubMed2003

Discovery of nonxanthine adenosine A2A receptor antagonists for the treatment of Parkinson's disease.

During a program to investigate the biochemical basis of side effects associated with the antimalarial drug mefloquine, the authors made the unexpected discovery that the (-)-(R,S)-enantiomer of the drug is a potent adenosine A2A receptor antagonist. Although the compound was ineffective in in vivo animal models of central adenosine receptor function, it provided a unique nonxanthine adenosine A2A receptor antagonist lead structure and encouraged the initiation of a medicinal chemistry program to develop novel adenosine A2A antagonists for the management of Parkinson's disease (PD). The authors have synthesized and screened more than 2,000 chemically diverse and novel adenosine A(2A antagonists. Early examples from two distinct chemical series are the thieno[3,2-dy]pyrimidine VER-6623 and the purine compounds VER-6947 and VER-7835, which have high affinity at adenosine A2A receptors (K(i) values 1.4, 1.1, and 1.7 nmol/L, respectively) and act as competitive antagonists. In particular, VER-6947 and VER-7835 demonstrate potent in vivo activity reversing the locomotor deficit caused by the D2 receptor antagonist haloperidol, with minimum effective doses comparable with that of KW6002 (0.3 to 1 mg/kg). In conclusion, the authors have discovered potent, selective, and in vivo active nonxanthine adenosine A2A antagonists that have considerable promise as a new therapy for PD.

Adenosine↗
PubMed2003

Influencing medication adherence among women with AIDS.

This study examined the effects of a ten-session cognitive-behavioural stress management/expressive supportive therapy (CBSM+) intervention on adherence to antiretroviral medication. Although the intervention was not designed to influence adherence, it was theorized that improved coping and social support could enhance adherence. Women with AIDS (N = 174) in Miami, New York and New Jersey, USA, were randomized to a group CBSM+ intervention or individual control condition. Participants were African American (55%), Latina (18%) and Caribbean (18%) with drug (55%) and/or alcohol (32%) histories. Participants were assessed on self-reported medication adherence over seven days, HIV-related coping strategies and beliefs regarding HIV medication. Baseline overall self-reported adherence rates were moderate and related to coping strategies and HIV medication beliefs. Low adherent (80%) participants in the intervention condition increased their mean self-reported medication adherence (30.4% increase, t44 = 3.1, p < 0.01), whereas low adherent women in the control condition showed a non-significant trend (19.6% increase, t44 = 2.0, p > 0.05). The intervention did not improve adherence in this population; conditions did not differ significantly on self-reported adherence. Low adhering intervention participants significantly decreased levels of denial-based coping (F1,88 = 5.97, p < 0.05). Results suggest that future interventions should utilize group formats and address adherence using coping and medication-knowledge focused strategies.

Acquired Immunodeficiency Syndrome↗
PubMed2001

A brief sexual barrier intervention for women living with AIDS: acceptability, use, and ethnicity.

Interventions aimed at reducing sexual transmission of human immunodeficiency virus/sexually transmitted diseases (HIV/STDs) have focused primarily on male condom use among seronegative men and women. However, female-controlled sexual barriers (female condoms and vaginal microbicides) offer women living with acquired immunodeficiency syndrome (AIDS) alternative methods to protect themselves and others from disease transmission. A pilot behavioral intervention was conducted to increase sexual barrier use and enhance and assess factors related to acceptability. Participants (N = 178) were drawn from the Stress Management and Relaxation Training with Expressive Supportive Therapy (SMART/EST) Women's Project, a multisite phase III clinical trial for women living with AIDS (Miami, FL; New York City, NY; Newark, NJ). Intervention participants (n = 89) were matched for age and ethnicity with control condition participants (n = 89). Women were African American (52%), Haitian (15%), Hispanic (19%), Caucasian (10%), and other ethnicities (4%). The intervention condition received barrier products (male and female condoms and spermicides based on nonoxynol-9 in the form of vaginal gel, film, and suppositories) during three sessions held over 3 months. Data on barrier use and acceptability were analyzed at baseline and 3 and 9 months postintervention. Use of N-9 spermicides on a trial basis increased significantly by 3 months in the intervention conditions (22%-51%, P <.05). Cultural differences in acceptability were greatest between Haitian women and women in other ethnic groups. Exposure to this pilot behavioral intervention was associated with increased acceptability and use of chemical barriers without decreased use of male condoms.

Acquired Immunodeficiency Syndrome↗
PubMed2001

KW-6002 (Kyowa Hakko Kogyo).

Kyowa Hakko is developing KW-6002, an adenosine A2A receptor antagonist, for the potential treatment of Parkinson's disease (PD) [183211]. The company subsequently began evaluating the compound for depression, and in June 2000 initiated a phase II trial for this indication. Good results have been obtained in a preclinical depression model and Kyowa Hakko hopes that KW-6002 will be representative of a new class of antidepressants [376107]. KW-6002 is undergoing phase II trials for PD in Japan [343257] and in Europe, including the UK 1271929], [321641], [402754]. As expected, KW-6002 entered phase II trials for PD in the US in October 1999 [321640], [342643], [360980], [402754]. The drug is of particular interest due to the absence of the involuntary movement adverse effects characteristic of L-DOPA therapy [271929]. Roche was to codevelop KW-6002 with Kyowa in the US and Europe, but withdrew from the development of this drug in April 1999 [321640]. Kyowa will continue with the drug's development in the US [321640]. NDAs are estimated to be filed around the end of 2001 and the drug is expected to be launched in Western Europe during 2002. An NDA is expected to be filed in Japan approximately three to four years later than in Western Europe [271929].

Animals↗
PubMed2001

The muscarinic receptor agonist xanomeline has an antipsychotic-like profile in the rat.

The muscarinic receptor agonist xanomeline was examined and compared with the antipsychotics clozapine and/or haloperidol in the following in vivo rat models: apomorphine-induced disruption of prepulse inhibition (PPI), amphetamine-induced hyperlocomotion, and the conditioned emotional response (CER) test. The effects of xanomeline were also assessed ex vivo on dopamine turnover in the rat medial prefrontal cortex. Under conditions of varying dose and prepulse intensity, xanomeline, like haloperidol, had no effect on PPI. In contrast, the muscarinic receptor antagonist scopolamine and the muscarinic receptor agonist pilocarpine both induced significant dose-dependent deficits in PPI. Haloperidol and xanomeline, but not pilocarpine, dose dependently reversed apomorphine-induced disruption of PPI. Thus, xanomeline induced a clear antipsychotic-like effect in PPI, whereas pilocarpine appeared to induce a psychotomimetic-like effect. Xanomeline attenuated amphetamine-induced hyperactivity at doses that had no effect on spontaneous activity, possibly indicating a separation between attenuation of limbic hyperdopaminergic function and the induction of hypolocomotion. Haloperidol and clozapine also reversed amphetamine-induced hyperlocomotion, but at similar doses to those that reduced spontaneous locomotion. Clozapine, but not haloperidol had an anxiolytic-like effect in the CER test. The effects of xanomeline in the CER test were similar to those of clozapine, although at the anxiolytic dose it tended to disrupt baseline levels of lever pressing. Finally, haloperidol, clozapine, pilocarpine, and xanomeline, all induced an increase in dopamine turnover in medial prefrontal cortex. The antipsychotic-like effects of xanomeline in the animal models used here suggest that it may be a useful treatment for psychosis.

Amphetamine↗
PubMed2000

Improved sensitivity proteomics by postharvest alkylation and radioactive labelling of proteins.

We describe approaches to improve the detection of proteins by postharvest alkylation and subsequent radioactive labeling with either [3H]iodoacetamide or 125I. Database protein sequence analysis suggested that cysteine is not suitable for detection of the entire proteome, but that cysteine alkylating reagents can increase the number of proteins able to be detected by iodination chemistry. Proteins were alkylated with beta-(4-hydroxyphenyl)ethyl iodoacetamide, or with 1,5-l-AEDANS (the Hudson Weber reagent). Subsequent iodination using the Iodo-Gen system was found to be most efficient. The enhanced sensitivity obtainable by using these approaches is expected to be sufficient for visualization of the lowest copy number proteins from human cells, such as from clinical samples. However, we argue that significantly improved methods of protein separation will be necessary to resolve the large number of proteins expected to be detectable with this sensitivity.

Acetamides↗
PubMed2000

Measurement of anxiety in transgenic mice.

A wide range of approaches has been used to study anxiety in mice. All presuppose that aversive stimuli, such as foot shock or novelty, induce a central state of fear, which can be quantified through specific behavioural and physiological measures. This review discusses the validity of the various approaches in terms of their similarity to different human anxiety disorders, their ability to detect compounds which modulate human anxiety, and their relevance to animal defensive processes. The most commonly used models of anxiety suitable for screening transgenic and knockout mice are discussed, with an emphasis placed on controlling for factors which could confound results. As all models used to date have limitations and no single paradigm adequately models all aspects of anxiety, this review recommends the use of a broad range of anxiety models in order to provide a comprehensive characterisation of the behavioural phenotype of transgenic mice.

Animals↗
PubMed1999

A comparison of maladaptive behaviors of athletes and nonathletes.

A comparison of maladaptive behavior tendencies of men and women who were athletes and nonathletes was undertaken. Participating students (N = 200) were divided into four groups: male athletes, male nonathletes, female athletes, and female nonathletes. Maladaptive behavior tendencies were determined from responses on C. MacAndrew's (1965) Alcoholism Scale. The statistical analysis used was an independent groups 2 x 2 analysis of variance to determine significant main effects and interaction effects. The mean maladaptive behavior score (MBS) for athletes (M = 21.87) was significantly higher (p < .05) than the MBS for nonathletes (M = 20.24). The MBS for the men (M = 21.68) was significantly higher (p < .05) than the MBS for the women (M = 20.43). No significant interaction (p > .05) between gender and athletic status was found. Male athletes are more likely than the other 3 groups to have maladaptive behavior tendencies. Research directed toward greater understanding and the development of preventive and coping techniques for this population is needed.

Adaptation, Psychological↗
PubMed1999

Infantile hypertrophic pyloric stenosis: delays in diagnosis and overutilization of imaging modalities.

Infantile Hypertrophic Pyloric Stenosis (IHPS) can usually be diagnosed by the detection of a pyloric olive on examination performed by an experience examiner. In babies with typical symptoms and a palpable olive, no further confirmation of diagnosis is required. We retrospectively reviewed the diagnostic evaluations of 93 consecutive patients with proven IHPS. Many patients who had the diagnosis confirmed on physical examination underwent one or more unnecessary and redundant studies. The performance of these studies was associated with delayed diagnosis and possibly with adverse clinical health problems. An algorithm for management of patients with suspected IHPS is proposed. Prompt examination by an experienced examiner is key to the evaluation of such patients.

Algorithms↗
PubMed1998

Utility of ethological analysis to overcome locomotor confounds in elevated maze models of anxiety.

The elevated plus-maze is a commonly used model to identify putative anxiolytic and anxiogenic drugs. However, the validity of elevated plus-maze and other recently developed variants such as the elevated zero-maze has recently been questioned on the grounds that both the reference anxiolytic drug chlordiazepoxide and the psychostimulant d-amphetamine increase open arm exploration and stimulate locomotor activity. These findings suggest that measures of "anxiety" in the elevated maze cannot be adequately dissociated from simple changes in locomotor activity, which may confound the interpretation of results obtained using these models. A variety of approaches to assess drug effects on locomotor activity in the elevated maze have been suggested, including the use of total and closed arm entries, as well as supplementary tests such as exploration of the holeboard apparatus. However, all these approaches utilise the measurement of exploration in a novel environment, and as such, could potentially be influenced by either changes in anxiety or locomotor activity. Recently, it has been shown that ethological measures of "risk assessment", such as stretched-attend postures and head-dipping, are sensitive indicators of drug-effects in the elevated maze. The present study assessed the utility of ethological analysis in dissociating locomotor activity from "anxiety" by comparing the effects of d-amphetamine to those of chlordiazepoxide in the rat elevated zero-maze. The results showed that both chlordiazepoxide and d-amphetamine increase the amount of time spent in the open arms and reduce "risk assessment" without increasing line crossing or rearing. These results confirm that under certain test conditions, psychostimulants are capable of producing "false-positives" in elevated maze models, and that both traditional methods and the ethological measures used in this study fail to unequivocally dissociate drug effects on anxiety from effects on locomotor activity. Further studies using other species and different classes of psychostimulants are warranted to determine the generality of these findings.

Animals↗
PubMed1997

Effects of diazepam and buspirone on the behaviour of wild voles (Microtus socialis) in two models of anxiety.

Exploration models of anxiety rely almost universally on the use of laboratory species. Furthermore, the spontaneous patterns of locomotion displayed are often interpreted as being an expression of antipredator defense. However, there is no direct link between the experience of these animals and the proposed motivation for their behaviour. To address this problem, the behaviour of wild trapped voles (Microtus socialis), a small-rodent species that is heavily predated upon, was examined in the elevated plus-maze and the black/white exploration model. It was hypothesised that the patterns of locomotion in these exploration models of anxiety should be similar to those reported for laboratory animals if the reactions of the laboratory animals are related to antipredator defense. Data revealed that voles show a similar preference for the protected areas in these models (closed arms or dark section) and that this preference can be modified by buspirone and diazepam. Interestingly, although the effective doses of each drug was the same within each model, it differed between models, with the minimum effective doses of these compounds being lower in the black/white exploration model (1 mg/kg) than in the elevated plus-maze (4 mg/kg). These data provide valuable information concerning the actions of anxiolytic compounds in wild trapped animals as assessed by formal laboratory models and provide useful verification that findings in these models may be generalised to species other than laboratory rodents.

Animals↗
PubMed1996

Patient satisfaction with decision-making for breast cancer therapy.

BACKGROUND: Many sources have suggested that mastectomy is inappropriately performed too frequently for breast cancer, leading to excessive patient dissatisfaction and unnecessary mutilation. Hurried decision-making based on inadequate information has been proposed as an explanation. METHODS: After confirming the diagnosis of breast cancer, patients were informed of the diagnosis, prognosis, and treatment options according to a standard protocol. The protocol was similar to that used by many surgeons in similar circumstances. Six months after completion of either mastectomy or breast conservation therapy, patients were surveyed about their satisfaction with the decision-making process and choice of treatment. RESULTS: The majority of patients, whether they had undergone mastectomy or breast conservation, thought they had been adequately informed of treatment options and that they had made the appropriate choice of therapy. A significant percentage of mastectomy patients found that procedure more disfiguring than anticipated, but still thought they had made the appropriate choice of therapy. Despite having been informed to the contrary, most patients said their chosen treatment provided the best chance for cure. CONCLUSIONS: When informed of the diagnosis and treatment options in an unhurried, supportive setting, and when encouraged to seek further consultations as desired, breast cancer patients make appropriate therapeutic choices about mastectomy or breast conservation therapy.

Breast Neoplasms↗
PubMed1996

Exploration and predation models of anxiety: evidence from laboratory and wild species.

The current article addresses several issues within the context of issues within the context of modeling human anxiety disorders in the laboratory. First, evidence is presented to support the suggestion that behavior in exploration models of anxiety may be motivated by apprehension relating to intraspecific encounters rather than interspecific, predator/prey interactions, which has consequences for the interpretation of findings generated using these tests. Second, data are reviewed concerning the use of stimuli indicating the presence of a predator in the context of anxiety modeling, and it is suggested that tests involving the reactions of animals following exposure to such stimuli may be more closely related to pathologic anxiety mechanisms than tests employing observations during contact with these stimuli. Third, comparative studies, using wild-caught rodents, are outlined that show that, although there are similarities in the defensive strategies adopted by these animals in response to the call of an owl, there are also important differences. Finally, the suggestion is made that the distance-dependent-defense-hierarchy may be of important heuristic value in the interpretation of these data and that, perhaps more significantly, it may also provide a mechanism that allows animal defensive strategies and human anxiety disorders to be placed within the same conceptual framework.

Animals↗
PubMed1996

Failure to detect Chlamydia pneumoniae in coronary atheromas of patients undergoing atherectomy.

To further investigate a proposed relationship between Chlamydia pneumoniae and coronary heart disease, coronary atheromas were collected from patients undergoing percutaneous atherectomy. Fifty-eight atheroma specimens were examined by culture and polymerase chain reaction (PCR) and 22 by electron microscopy. All were negative for C. pneumoniae, except a single specimen that was PCR-positive. These results differ from studies in other populations, in which this organism was identified by nonculture methods within coronary atheromas obtained at autopsy. Anti-C. pneumoniae antibody titers from 65 of the patients were compared with those of 28 asymptomatic controls. IgG titers were higher in controls than in patients. There is no evidence that C. pneumoniae exists within atheromas in this study population, nor does seroprevalence correlate with the presence of coronary disease in these patients.

Adult↗
PubMed1996

Neuralgia after inguinal hernia repair.

Severe chronic pain after groin hernia repair is uncommon but potentially debilitating. Fifteen patients with this condition were retrospectively reviewed. All patients had severe pain, which prevented their working or normal activity and was refractory to nonoperative treatment. Essentials of therapy included 1) a preoperative attempt to identify the involved nerve and 2) high ligation and division of the involved nerve identified at exploration. Twelve patients obtained excellent results and were able to return to normal activity with no requirement for analgesia. Understanding of the typical nerve anatomy, as well as the individual variation in nerve anatomy, can help prevent this complication and is essential for correction if the complication does develop.

Adult↗
PubMed1995

Visible burrow system as a model of chronic social stress: behavioral and neuroendocrine correlates.

In mixed-sex rat groups maintained in visible burrow systems (VBS), consistent asymmetries in offensive and defensive behaviors of male dyads are associated with the development of dominance hierarchies. Subordinate males are characterized by particular wound patterns, severe weight loss, and a variety of behavioral changes, many of them isomorphic to target symptoms of clinical depression. In two VBS studies, subordinate males showed increased basal levels of plasma corticosterone (CORT), and increased adjusted adrenal and spleen weights compared to controls, and often, to dominants as well. Thymus weights and testosterone levels of subordinates were not reliably different in one study using highly aggressive males, but were reduced, along with testes weights, in a second study using unselected males. Glucocorticoid receptor binding levels in hippocampus, hypothalamus, and pituitary were not different, nor were aldosterone levels. When tested in a restraint stress procedure, subordinates had higher basal CORT levels, but about 40% of these animals showed a reduced, or absent, CORT response to restraint. These findings indicate that subordination may be reflected in high magnitude changes consistent with physiological indices of prolonged stress. Dominant rats of such groups may also show physiological changes suggesting stress, particularly when the groups are comprised of highly aggressive males only. The VBS colony model thus appears to enable rat groups to produce natural, stress-engendering, social interactions that constitute a particularly relevant model for investigating the behavioral, neural, and endocrine correlates of chronic stress.

Adrenal Glands↗