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Biomedical subjects

R M Hamer

Publications and source records attributed to R M Hamer.

At least 19 recordsLinked to original sources

Olanzapine and haloperidol in first episode psychosis: two-year data.

Few studies have assessed the comparative efficacy and safety of atypical and typical antipsychotic medications in patients within their first episode of psychosis. This study examined the effectiveness of the atypical antipsychotic olanzapine and the typical antipsychotic haloperidol in patients experiencing their first episode of a schizophrenia-related psychotic disorder over a 2-year treatment period. Two hundred and sixty-three patients were randomized to olanzapine or haloperidol in a doubleblind, multisite, international 2-year study. Clinical symptoms and side effects were assessed at baseline and longitudinally following randomization for the duration of the study. Olanzapine and haloperidol treatment were both associated with substantial and comparable reductions in symptom severity (the primary outcome measure) over the course of the study. However, the treatment groups differed on two secondary efficacy measures. Patients were less likely to discontinue treatment with olanzapine than with haloperidol: mean time (in days) in the study was significantly greater for those treated with olanzapine compared to haloperidol (322.09 vs. 230.38, p<0.0085). Moreover, remission rates were greater in patients treated with olanzapine as compared to those treated with haloperidol (57.25% vs. 43.94%, p<0.036). While extrapyramidal side effects were greater in those treated with haloperidol, weight gain, cholesterol level and liver function values were greater in patients treated with olanzapine. The data from this study suggest some clinical benefits for olanzapine as compared to haloperidol in first episode patients, which must be weighed against those adverse effects that are more likely with olanzapine.

Adult↗

Limited influence of olanzapine on adult forebrain neural precursors in vitro.

We evaluated the activity of the atypical antipsychotic drug olanzapine on differentiation and gene expression in adult neural precursor cells in vitro. Neural precursors obtained from forebrain subventricular zone (SVZ)-derived neurospheres express a subset (13/24) of receptors known to bind olanzapine at high to intermediate affinities; in contrast, all 24 are expressed in the SVZ. In the presence of 10 nM, 100 nM or 1 microM olanzapine, there is no significant change in the frequency of oligodendrocytes, neurons, GABAergic neurons and astrocytes generated from neurosphere precursors. In parallel, there is no apparent change in cell proliferation in response to olanzapine, based upon bromodeoxyuridine incorporation. There are no major changes in cytological differentiation in response to the drug; however, at one concentration (10 nM) there is a small but statistically significant increase in the size of glial fibrillary acidic protein-labeled astrocytes derived from neurosphere precursors. In addition, olanzapine apparently modulates expression of one serotonin receptor -- 5HT2A -- in differentiating neurosphere cultures; however, it does not modify expression of several other receptors or schizophrenia vulnerability genes. Thus, olanzapine has a limited influence on differentiation and gene expression in adult neural precursor cells in vitro.

Animals↗

Treatment of somatization disorder with nefazodone: a prospective, open-label study.

Somatization disorder (SD) is commonly seen in medical clinics and is associated with significant impairment in functioning as well as excessive utilization of health care. While antidepressants have been studied in some functional somatic syndromes such as fibromyalgia and chronic fatigue, there are no pharmacologic treatment studies of SD itself. In this prospective, 8-week, open-label study, 15 patients diagnosed with either full SD or abridged somatization, by Escobar's criteria (four unexplained physical symptoms for men or six for women), were given nefazodone, titrated to 150 mg bid. The primary outcomes included measures of physical symptom severity (visual analogue scale), functioning (SF-36), and overall improvement (CGI). Fourteen of the 15 patients achieved the target dose of 300 mg/day and completed the trial. 73% of the patients were rated as improved on the CGI, 79% improved on the self-rated visual analogue scale and 73% of the patients improved on the SF-36. There was significant improvement for the whole group (prepost) on the SF-36, as well as on the HAM-D and the HAM-A. Of the nine patients with a categorical depression diagnosis, 55% of them were rated as improved on the CGI, and 67% improved on both the VAS and the SF-36. Of the six nondepressed patients, 67% were rated as improved on the CGI, 83% improved on the SF-36, and 50% improved on the VAS. Adverse events were generally mild and resulted in only one discontinuation. Although these data need to be confirmed in a larger, double-blind, placebo-controlled trial, they suggest that patients with SD will accept and tolerate therapy with nefazodone and that nefazodone may be a useful treatment for these patients.

Adult↗

Sildenafil effects on sexual and cardiovascular responses in women with spinal cord injury.

OBJECTIVES: Sexual dysfunction is common in women with spinal cord injuries (SCIs) and other neurologic conditions. Sildenafil has previously been shown to be safe and effective in the treatment of erectile dysfunction due to SCI. This study is the first to evaluate the sexual and cardiovascular effects of sildenafil in women with SCIs in a controlled, laboratory setting. METHODS: Nineteen premenopausal women with SCIs were randomly assigned to receive either sildenafil (50 mg) or placebo in a double-blind, crossover design study. Physiologic and subjective measures of sexual response, heart rate, and blood pressure were recorded during baseline and sexual stimulation conditions. Adverse events were also recorded. RESULTS: Significant increases in subjective arousal (SA) were observed with both drug (P <0.01) and sexual stimulation conditions (P <0.001), and a borderline significant (P <0.07) effect of drug administration on vaginal pulse amplitude (VPA) was noted. Maximal responses occurred when sildenafil was combined with visual and manual sexual stimulation. Cardiovascular data showed modest increases in heart rate (+/-5 bpm) and mild decreases in blood pressure (+/-4 mm Hg) across all stimulation conditions, consistent with the peripheral vasodilatory mechanism of the drug. Sildenafil was well tolerated with no evidence of significant adverse events. CONCLUSIONS: Findings suggest that sildenafil may partially reverse the sexual dysfunction commonly associated with SCI in women. Consistent with previous findings in men, the sexual effects of the drug were most evident under conditions of optimal stimulation. Mild, clinically insignificant cardiovascular effects were also noted. Further large-scale studies of sildenafil's effects in women with neurogenic sexual dysfunction are strongly indicated.

Adult↗

Odor perception: multiple chemical sensitivities, chronic fatigue, and asthma.

Patients with multiple chemical sensitivities (MCS) often report heightened sensitivity to odors. Odor detection thresholds to phenyl ethyl alcohol (PEA) and pyridine (PYR) were evaluated as a measure of odor sensitivity for 33 MCS subjects, 13 chronic fatigue syndrome subjects, 16 asthmatic subjects, and 27 healthy controls. Odor identification ability (based on University of Pennsylvania Smell Identification Test results) and ratings in response to four suprathreshold levels of PEA and PYR were also assessed. Odor detection thresholds for PEA and PYR and odor identification ability were equivalent for all groups; however, when exposed to suprathreshold concentrations of PEA, MCS subjects reported significantly more trigeminal symptoms and lower esthetic ratings of PEA. No group differences were found in response to suprathreshold concentrations of PYR. In summary, MCS subjects did not demonstrate lower olfactory threshold sensitivity or enhanced ability to identify odors accurately. Furthermore, they were differentiated from the other groups in their symptomatic and esthetic ratings of PEA, but not PYR.

Adult↗

Association of a serotonin transporter gene promoter polymorphism with harm avoidance behaviour in an elderly population.

A polymorphic 44-nucleotide insertion/deletion in the promoter region of the serotonin transporter gene (5-HTTLPR) has been shown to affect the level of expression of the serotonin transporter protein. An association between anxiety-related behavioural traits and the short form of the 5-HTTLPR has been reported. We determined the 5-HTTLPR genotype in genomic DNA samples from 84 subjects (47 Parkinson's disease patients and 37 controls) with a mean age of 67.4 years. The TPQ of Cloninger was used to obtain values for harm avoidance (HA), reward dependence and novelty seeking for all subjects. Analysis of variance showed a significant influence of the s-allele of the 5-HTTLPR on HA in both subject groups, with no significant interaction between diagnosis and genotype. Subjects with the l/l-genotype had significantly lower mean HA scores than the l/s subjects (P < 0.04) and s/s subjects (P < 0.003). A linear change in HA with genotype was observed, indicating a gene dose effect of the 5-HTTLPR s-allele on this personality dimension. Based on these findings it is suggested that there may be increased influence of the 5-HTTLPR short allele on anxiety-related traits during aging.

Aged↗

Association of long variants of the dopamine D4 receptor exon 3 repeat polymorphism with Parkinson's disease.

The dopamine D4 receptor (D4DR) has a highly polymorphic region in the third exon which has been associated with novelty seeking (NS) behavior. Due to the central position of dopamine and the documented low NS in Parkinson's disease (PD), the frequency of the exon 3 variants of D4DR in 95 PD patients and 47 controls was investigated. A significantly higher frequency of exon 3 alleles with six or more repeat units was found in the PD group (p = 0.039). This provides evidence that some forms of the highly polymorphic D4DR may represent a genetic susceptibility factor for PD.

Adult↗

The Lie/Bet Questionnaire for screening pathological gamblers: a follow-up study.

This study follows up one in which was derived a two-item screening questionnaire for pathological gambling. In the previous study, the two-item screening questionnaire had sensitivity of .99 and specificity of .91. In this study, testing 295 men (116 pathological gamblers and 179 controls) and 128 women (30 pathological gamblers and 98 controls), sensitivity was 1.00 and specificity .85. In the previous study, the predictive value of a positive result was .92 and of a negative result .99. In this sample, the predictive value of a positive result was .78 and of a negative result 1.00. These results indicate the two questions represent a useful screening device for a DSM-IV diagnosis of pathological gambling.

Deception↗

Psychiatric consultation in the nursing home. A survey of six states.

The authors examined availability, characteristics, and perceived adequacy of psychiatric consultation in nursing homes, as reported by directors of nursing, who returned 899 questionnaires. Thirty-eight percent of nursing home residents were judged to need a psychiatric evaluation; current frequency of consultation was rated as adequate by half of nursing directors. Nearly two-thirds reported that psychiatrists adequately provided diagnostic and medication recommendations; however, advice on nonpharmacologic management techniques, staff support, and dealing with staff stress and family conflicts was largely viewed as inadequate. Findings suggest that perceived need for psychiatric services is far greater than the level actually provided. Overall, more attention must be directed to identifying incentives for psychiatrists to practice in nursing homes, determining clinical effectiveness of mental health services, and examining effects of alternative payment mechanisms on level of care.

Humans↗

Psychopathology and pain in medical in-patients predict resource use during hospitalization but not rehospitalization.

The authors investigated the relationship between psychopathology and resource use in general medical in-patients during hospitalization and rehospitalization. Between 1 July 1987, and 30 April 1989, 1020 in-patients were prospectively screened for depression, anxiety, cognitive dysfunction, and pain. Overall, the screen identified 47% of patients as having high psychopathology or pain, including 25.7% depressed, 21.8% anxious, 17.6% with cognitive dysfunction, and 5.2% with high pain. There were no measured differences in demographics or disease severity between high and low psychopathology groups. High psychopathology patients had longer stays and higher costs during the index hospitalization but there were no differences during subsequent hospitalizations. Length of stay declined overall during the study period, but there were no changes over time in the association between high psychopathology or pain with increased resource use. The measured symptoms of psychopathology and pain we measured are associated with increased short-term utilization of health care resources, but the increase does not extend to subsequent hospitalizations. Outcome studies aiming to reduce psychopathology in medical in-patients should pay particular attention to short term costs.

Anxiety Disorders↗

A randomized controlled study of psychiatric consultation guided by screening in general medical inpatients.

OBJECTIVE: The purpose of the study was to test the hypothesis that psychiatric consultation would reduce health care utilization during and after medical hospitalization. METHOD: A randomized, double-controlled clinical trial of psychiatric consultation was conducted on the general medical inpatient services of a university hospital. After meeting inclusion criteria, 1,541 patients were screened for depression, anxiety, confusion, and pain over a period of 21 months. The 741 patients with high levels of psychopathology or pain were subdivided into baseline control subjects (N = 232), contemporaneous control subjects (N = 253), and an experimental consultation group (N = 256). The major outcome measures were length of hospital stay and hospital costs. Secondary outcome measures were posthospital health status, rehospitalization rates, and use of outpatient medical care. RESULTS: This study did not demonstrate an effect of experimental psychiatric consultation on hospital resource use or posthospital medical care utilization after adjustment was made for disease severity. Hospital resource use decreased in the entire sample over the 21-month duration of the study. CONCLUSIONS: The brief, efficient screen for anxiety, depression, confusion, and pain identified a group of patients who also used more hospital resources, but a single experimental psychiatric consultation did not reduce costs. The double-controlled nature of the design proved essential to avoid being misled by background changes in hospital resource use.

Adult↗

Symptom report in orofacial pain patients: relation to chronic pain, experimental pain, illness behavior, and personality.

A study was conducted to determine symptom report patterns in a heterogenous population of orofacial pain patients and to evaluate how symptom patterns relate to various dimensions of the human pain experience. Results indicated that symptoms frequently associated with chronic orofacial pain disorders can be described by four indices related to the temporomandibular joint (TMJ) and its movement; discomfort of and parafunctional activities related to the masticatory muscles; interference of pain with activities of daily living; and presence of orofacial pain unrelated to myogeneous or arthrogenous TMJ disorders. Of these four symptom indices, only the pain interference (symptom) index was related to clinical pain and illness behavior. None was related to personality. Two of the indices were influenced by diagnosis. Biomechanical symptoms and parafunctional activities appear to be insignificantly related to perceived pain intensity, pain responsiveness, illness behavior, or personality, but are related to diagnosis. The results indicated that relatively simple symptom checklists have potential utility in screening orofacial pain patients and in evaluation of treatment outcome.

Adolescent↗

Effects of buspirone and alprazolam on the cognitive performance of normal elderly subjects.

OBJECTIVE: To increase understanding of the potential in elderly persons for disability related to behavioral side effects of anxiolytic medications, cognitive and psychomotor effects of clinical doses of buspirone and a popular intermediate-acting benzodiazepine, alprazolam, were examined in carefully screened, healthy elderly subjects. METHOD: Sixty subjects recruited through community organizations and newspaper advertisements and screened on the basis of history, physical examination, and laboratory studies were randomly assigned to one of three drug treatment groups. After 2 days of washout placebo, subjects were given 0.25 mg t.i.d. of alprazolam, 5 mg t.i.d. of buspirone, or placebo three times a day for a total of 14 days in a double-blind design. Behavioral assessments were completed beginning 1 hour after ingestion of medication on the second washout placebo day, day 1 of the treatment period, and day 14 of the treatment period. Tests included the continuous performance test, recall memory for word lists, digit-symbol substitution, retention of pictorial stimuli over 1 hour, the Profile of Mood States, and subjective ratings of mental status. RESULTS: Buspirone did not affect reaction time, vigilance, psychomotor speed, or memory function. Alprazolam had minimal effects on vigilance, psychomotor speed, and memory on the first treatment day and had no effects after repeated doses. CONCLUSIONS: Buspirone did not produce behavioral side effects that could lead to disability, and alprazolam had minimal side effects. Because the patients were carefully screened, it is unclear whether these medications in the doses used would have more side effects in less healthy elderly patients.

Aged↗