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Biomedical subjects

W T Smith

Publications and source records attributed to W T Smith.

At least 19 recordsLinked to original sources

Rabies case in New South Wales, 1990: public health aspects.

OBJECTIVES: To identify the source of rabies in the recent case in New South Wales, and to determine the need for post-exposure rabies prophylaxis among contacts of the patient. DESIGN: Information was obtained by face-to-face interview of the dead girl's family and face-to-face and telephone interviews using a questionnaire of health care workers. Other information was gathered from overseas and local sources through telephone and facsimile contact. RESULTS: The girl had migrated from Vietnam in 1984 to Hong Kong, and from there in 1986 to Australia. No evidence of contact with a rabid animal in Australia or Hong Kong was found. There had also been no organ donations from the girl. Four health care workers were given post-exposure rabies prophylaxis. CONCLUSIONS: Because of the lack of evidence of animal contact in Australia and the fact that extremely long incubation periods for rabies have been documented, it was considered that the most likely source of the rabies virus was North Vietnam. Genetic studies of the virus also supported a South-East Asian source. Nevertheless the presumed incubation period--at least six years and four months--is one of the longest recorded.

Animals

Use of buspirone in patients with generalized anxiety disorder and coexisting depressive symptoms. A meta-analysis of eight randomized, controlled studies.

This report presents the results of a retrospective analysis of pooled efficacy data from eight studies in which buspirone was compared to placebo in 520 patients with generalized anxiety disorder (GAD). In addition to evaluating overall efficacy in the composite patient data base, four criteria were used to identify subsets of patients with GAD who had coexisting depressive symptoms of at least moderate intensity: (1) a score of > or = 2 on the Hamilton Anxiety (HAM-A) Rating Scale item 6 (depressed mood), (2) a score of > or = 2 on the Hamilton Depression (HAM-D) Rating Scale item 1 (depressed mood), (3) a HAM-D total score of > or = 18, or (4) a HAM-D Retardation Factor value (items 1, 7, 8, and 14) greater than the median for the group. Overall, patients treated with buspirone demonstrated significant (p < or = 0.001) improvement over baseline in total HAM-A scores compared to patients who received placebo. Buspirone also produced significant (p < or = 0.001) global improvement compared to placebo as assessed by the attending physician. Of the GAD patients stratified according to the four criteria for coexisting depressive symptoms, a substantial percentage (44-64%) of the total patient sample exhibited significant depressive symptoms as part of their anxiety disorder. Patients with GAD and coexisting depressive symptoms of at least moderate intensity exhibited significantly greater improvement with buspirone compared to placebo treatment regardless of the stratification criterion used. They also responded at least as well or better to buspirone therapy as did those with GAD who had less intense depressive symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Paroxetine versus placebo: a double-blind comparison in depressed patients.

BACKGROUND: Paroxetine is a potent and selective serotonin reuptake inhibitor (SSRI). The present study assessed the efficacy and tolerability of paroxetine against placebo in depressed outpatients. METHOD: A double-blind, parallel-group study was undertaken in four stand-alone centers. Patients aged 18-65 years, meeting DSM-III criteria for major depression, and having a Hamilton Rating Scale for Depression (HAM-D) score > or = 18 on the first 17 items of the HAM-D-21 were randomized to paroxetine or placebo for 6 weeks of treatment. Efficacy outcome variables included the HAM-D, the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impressions Scale (CGI), and the Covi Anxiety Scale. Tolerability was assessed by asking a non-leading question. Routine laboratory safety and vital sign data from all four centers were pooled. The primary analysis used the intention-to-treat sample and for efficacy variables the last-observation-carried-forward data set was employed. Statistical methods included one-way analysis of variance for parametric and Fisher exact test for nonparametric variables. RESULTS: Significant differences (p < or = .05) were found between paroxetine and placebo on the HAM-D and CGI by Week 2 and on all efficacy outcome variables by Week 4. Improvement on the HAM-D sleep factor occurred 2 weeks prior to that seen on the retardation factor. Similar results were obtained when an adequate treatment group (therapy for > or = 28 days) was considered. A full clinical response (CGI-severity of illness score 1 or 2) was seen in over 40% of subjects. Adverse events were more common for paroxetine compared with placebo (p < or = .01). Somnolence was twice more common than nervousness. Dropout due to adverse events was similar between therapies. Paroxetine had no clinically significant effect on laboratory safety data or vital signs. CONCLUSION: Paroxetine was an effective, well tolerated, and safe antidepressant. Side effects were typical of the SSRI class of drugs. Symptoms indicative of a nonalerting profile were more common than those associated with alerting effects.

Adolescent

A placebo-controlled trial of paroxetine in the treatment of major depression.

Paroxetine is a phenylpiperidine compound that selectively inhibits neuronal serotonin uptake in man. In this study, the efficacy of paroxetine was compared with that of placebo in the treatment of 66 outpatients with the diagnosis of moderate-to-severe major depression. The research was a 6-week, prospective, double-blind design after a 1-week placebo baseline phase. Paroxetine was associated with a consistent pattern of greater improvement on the primary efficacy scales, but the differences were not statistically significant. Paroxetine did produce significantly greater improvement than placebo for patients whose illness had lasted more than 1 year, and there was a significant reduction in suicidal ideation. Significantly fewer dropouts were due to lack of efficacy in those patients treated with paroxetine compared with those in the placebo group. Paroxetine was well tolerated. There was no difference between paroxetine and placebo in the rate of adverse effects or in the number of patients who dropped out because of adverse effects.

Adult

Acute stimulation of ornithine decarboxylase in neonatal rat brain regions by nicotine: a central receptor-mediated process?

Nicotine exposure during development alters central nervous system structure and function. In the current study, we examined the acute effects of nicotine (3 mg/kg) on developing rat brain by monitoring ornithine decarboxylase (ODC), a marker for perturbed cell development; ODC controls polyamine biosynthesis and thus regulates cell differentiation. Three brain regions were selected that differ both in their timetables for maturation and in nicotinic receptor concentrations: midbrain + brainstem (earliest development, highest receptor concentration), forebrain (intermediate profiles) and cerebellum (latest development and lowest receptor concentration). Nicotine caused stimulation of ODC within 1 h after drug administration, an effect that displayed both age- and region-dependence corresponding to the development of central nicotinic receptors: effects appeared earliest and were largest in magnitude in midbrain + brainstem and forebrain, and appeared last and with smaller magnitude in the cerebellum. Central receptor involvement was confirmed at 8 days postpartum by demonstrating desensitization of the response after repeated nicotine administration, and by evoking equivalent effects with direct introduction of a small dose of nicotine into the central nervous system. Later in development, acute stimulation of ODC by nicotine became less selective, reflecting secondary actions mediated through systemic hypoxia caused by the drug; this conclusion was confirmed by the absence of desensitization after repeated nicotine administration, and by the failure of centrally administered nicotine to evoke a full stimulatory response. Nicotine-induced ischemia did not contribute to stimulation of ODC seen at the 1 h time point: pretreatment with chlorisondamine, a ganglionic nicotinic antagonist, failed to alter the central stimulatory response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Undergraduate education about cancer.

The quality, quantity and balance of undergraduate cancer teaching in Australian Medical Schools were investigated by a survey, using a self-administered questionnaire, of recent graduates from all Australian medical schools. Stratified random cluster sampling was used and a response rate of 84% (389 respondents) was achieved. The results revealed substantial differences in knowledge, experience in, and rating of teaching between the medical, surgical, radiotherapeutic and palliative components of cancer management. The proportions of graduates who had never attended radiotherapy and palliative care clinics or units (42.3% and 49.9%, respectively) were more than double the proportion who had never attended medical and surgical cancer clinics or units (17.5% and 10.9%, respectively). More than twice as many graduates rated their instruction in the palliative management of cancer as poor or very poor (29.4%) compared with those rating their instruction as poor or very poor in both cancer prevention (8.4%) and treatment for cure (14.6%). The respondents displayed a considerable lack of knowledge about radiotherapy treatment options, and reported a lack of perceived competence in doing cervical smears. Their answers to questions about 5-year survival of selected cancers, about the existence of screening tests validly shown to reduce mortality, and the ages at which breast and cervical cancers are likely to develop all revealed worrying levels of incorrect knowledge. There was some important disturbing variation in levels of knowledge, experience and rating of cancer instruction between states and between universities.

Australia

Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder.

Patients (n = 150) were randomized to a 6-week, double-blind study to evaluate the relative efficacy and safety of mirtazapine, amitriptyline, and placebo in the treatment of major depressive disorder symptoms. Average daily modal doses were mirtazapine, 18 mg; amitriptyline, 111 mg; and placebo, 4.6 capsules. Mirtazapine- and amitriptyline-treated patients had statistically significantly greater mean Hamilton Rating Scale for Depression (HAM-D) score reductions (weekly visits 1, 2, 4, and endpoint) compared to placebo. These findings were supported by the Montgomery-Asberg Depression Rating Scale (MADRS); the Zung Self-rating Depression Scale (SDS); and the Clinical Global Impressions (CGI) scales. Somnolence and weight gain were the only adverse clinical experiences (ACEs) reported substantially more often by mirtazapine-treated patients than by those in the placebo group. However, more amitriptyline-treated patients reported decreased visual accommodation, dry mouth, dyspepsia, constipation, tachycardia, hypertension, hypotension, discoordination, dizziness, and tremor than mirtazapine- or placebo-treated patients. Results of this study indicate that mirtazapine is more effective than placebo in the treatment of these patients, and superior to amitriptyline in respect to anticholinergic and cardiovascular effects.

Adult

Double-blind efficacy and safety study comparing adinazolam mesylate and placebo in depressed inpatients.

In a 6-week, randomized, double-blind study, adinazolam mezylate (Deracyn Tablets, The Upjohn Company) was compared with placebo for the treatment of depression in 80 inpatients who met the criteria for single episode or recurrent DSM-III Major Depression. Subjects were admitted to the hospital 3 days before the start of the study and remained hospitalized for at least the first week of treatment. Efficacy was evaluated after 2, 4, 7, 14, 28, and 42 days of treatment. Adinazolam was significantly superior to placebo on all observer-rated and all global patient-rated measures of efficacy. Twenty-five subjects (63%) completed 6 weeks of adinazolam treatment and of these, 88% responded within 7 days. Only 15 placebo-treated subjects (38%) completed the study. Drowsiness and mild to moderate cognitive complaints were the only side effects observed more frequently with adinazolam, and both were transient. The results show that adinazolam is safe and more effective than placebo for the treatment of major depression.

Adult

Stereospecificity of 2-methylpiperidine binding to a nicotinic up-regulatory site in the rat brain P2 preparation.

(+/-)-2-Methylpiperidine has a high degree of specificity in enhancing the binding of (-)-[3H]nicotine in the rat brain P2 preparation. (-)- and (+)-2-Methylpiperidine have been resolved. The (+) but not the (-) isomer increased the binding of (-)-[3H]nicotine. The two isomers were equally effective in inhibiting the binding of (-)-[3H]nicotine in high concentrations. These data provide additional support for a stereospecific nicotinic up-regulatory site.

Animals

Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression.

Five hundred four outpatients suffering from a major depressive episode were randomly assigned to receive either amitriptyline, doxepin, alprazolam, or placebo. The study was conducted in three treatment centers during a six-week period. All three active medications produced significantly more clinical improvement than did placebo, irrespective of the patient's initial anxiety, depression, and psychomotor retardation and irrespective of the patient's assignment to various subtypes of depression, including the DSM-III melancholia subtype. Compared with placebo, sedation was reported more frequently with all three medications, whereas anticholinergic effects were reported more frequently only for the two tricyclic antidepressants, but not for alprazolam.

Adult

Comparison of two dosage regimens of fluoxetine in major depression.

The effect of dose frequency on fluoxetine efficacy and safety was evaluated in a double-blind study in patients with major depressive disorder. The patients received fluoxetine once a day (in the morning) or twice a day (in the morning and at noon). There were no significant differences between the two groups in the mean measures of efficacy, all of which showed significant improvement over baseline (p less than .001). Adverse experience profiles were not significantly different, with nervousness/anxiety predominating in both groups. In the subsequent 48-week open-label study, the percentage of patients reporting adverse experiences decreased greatly.

Adult

Comparison of alprazolam, imipramine, and placebo in the treatment of depression.

Alprazolam is the first of the triazolobenzodiazepines to be studied in a large population of depressed patients. In a six-week, double-blind multicenter comparison of alprazolam, imipramine hydrochloride, and placebo in the treatment of 723 patients with depression, the two active drugs were statistically more effective than placebo. Alprazolam was at least as effective as imipramine in relieving depressive symptoms, significantly more effective in relieving somatic symptoms, and showed an earlier onset of activity in some measurements. Anticholinergic side effects were reported most often by patients receiving imipramine, while drowsiness was the only side effect reported most often in the alprazolam group. The Feighner Diagnostic Criteria and prestudy and poststudy intercenter conferences with videotaped patient interviews ensured interrater reliability.

Adolescent

Subcortical arteriosclerotic encephalopathy (Binswanger's type) and cortical infarcts in a young normotensive patient.

A 49-year-old normotensive man died after a series of strokes, slowly evolving dementia and personality change occurring over a period of 23 years. CT scan showed large infarcts involving the cortex and white matter of the temporo-occipital areas, small subcortical infarcts and low attenuation in the white matter of the frontal and parietal lobes. Neuropathological examination revealed large cortical and small subcortical infarcts corresponding to the radiological findings as well as degeneration/demyelination of central white matter corresponding to the areas of low attenuation seen on CT. The basic underlying pathological process was hyaline arteriosclerosis and atheroma which diffusely affected the small intracerebral arteries and to a lesser extent the arteries of the circle of Willis. Though usual because of the absence of hypertension, the very early age at onset of the syndrome and the presence of large cortical infarcts this case illustrates the clinical, radiological and neuropathological features of subcortical arteriosclerotic encephalopathy (Binswanger's type).

Arteriosclerosis

The neuropathology of intervertebral discs removed for low-back pain.

Thirty lower lumbar intervertebral discs (IVDs) removed for low-back pain were examined. There is a profuse non-myelinated axonal network and abundant free nerve terminals in the outer (lateral) half of the annulus fibrosus. The inner annulus and the nucleus pulposus did not contain nerve terminals. No significant changes in the nerve networks could be demonstrated in degenerate IVDs: in particular, ingrowth of nerve terminals into foci of granulomatous tissue was not seen. Early foci of degeneration are clearly shown by Marshall's silver method for metalophil cells. Mucinous filaments are argyrophilic and can be mistaken for axonal structures in the nucleus pulposus.

Back Pain

Effects of low cobalamin diet and chronic cyanide toxicity on cobalamin distribution in baboons.

This paper reports the bodily distribution of total cobalamin and individual cobalamins at the termination of an experiment on the effects of a low cobalamin diet and chronic cyanide or thiocyanate administration in baboons. The results show that the distribution of cobalamins in the tissues of the baboon can be altered by a low cobalamin diet and also by chronic intoxication with cyanide, whether or not the animals are on a low cobalamin diet. All animals on the low cobalamin diet showed a reduction in total and individual cobalamins. In blood plasma and erythrocytes, kidney, spleen, testis and brain, the proportion of methylcobalamin tended to be disproportionately reduced in cobalamin-depleted animals. This reduction was lessened or prevented by the administration of cyanide. Neither cyanide not thiocyanate produced a significant increase in the proportion of cyanocobalamin in plasma, though thiocyanate produced a large increase in cyanocobalamin in erythrocytes. In liver, cyanocobalamin was more than doubled by the administration of cyanide to cobalamin-depleted animals.

Animals