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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
PubMed1995

The Ib phase of ventricular arrhythmias in ischemic in situ porcine heart is related to changes in cell-to-cell electrical coupling. Experimental Cardiology Group, University of North Carolina.

BACKGROUND: This study was designed to test the hypothesis that the loss of cell-to-cell electrical interaction during ischemia modulates the amplitude of ischemia-induced TQ-segment depression (ie, the injury potential) and the occurrence of ventricular fibrillation (VF) during the so-called Ib phase of ventricular arrhythmias. METHODS AND RESULTS: Regional ischemia was induced by 60 minutes of mid-left anterior descending coronary artery ligation in open-chest swine (n = 10). Cell-to-cell electrical uncoupling was defined as the onset of the terminal rise in whole-tissue resistivity (Rt). Local activation times and TQ-segment changes (injury potential) were determined from unipolar electrograms. Extracellular K+ ([K+]e) and pH (pHe) were measured with plunge-wire ion-selective electrodes. VF occurred in 6 of 10 pigs during regional no-flow ischemia between 19 and 30 minutes after the arrest of perfusion. The occurrence of VF was positively correlated to the onset of cell-to-cell electrical uncoupling (R2 = .885). Cell-to-cell electrical uncoupling superimposed on changes of [K+]e and pHe contributed to the failure of impulse propagation between 19 and 30 minutes after the arrest of perfusion. During ischemia, maximum TQ-segment depression was -10 mV at 19 minutes, after which TQ-segment depression slowly recovered. The onset of the TQ-segment recovery was correlated to the second rise in Rt (R2 = .886). CONCLUSIONS: In the regionally ischemic in situ porcine heart, loss of cell-to-cell electrical interaction is related to the occurrence of VF and changes in the amplitude of the injury current. Cellular electrical uncoupling contributes to failure of impulse propagation in the setting of altered tissue excitability as a result of elevated [K+]e and low pHe. These data indicate that Ib arrhythmias and ECG changes during ischemia are influenced by the loss of cell-to-cell electrical interaction.

Animals↗
PubMed1995

The impact of vaccination against invasive Haemophilus influenzae type b disease in the Sydney region.

OBJECTIVE: To evaluate the incidence of invasive Haemophilus influenzae type b (Hib) disease relative to rates of Hib vaccination in a well defined population. DESIGN AND SUBJECTS: Cases of invasive Hib disease were identified by active laboratory surveillance for the period 1989-1994, and retrospectively for 1985-1987. Vaccination rates were determined by telephone interview of families with children aged 0-4 years, identified in a random telephone directory sample of 4000 households. The receipt and time of vaccination were validated from general practitioner records for a 50% subsample of children. SETTING: Sydney Statistical Division, with a population of 263,758 children aged 0-4 years in 1990. RESULTS: Hib vaccination rates were relatively low before the introduction of government-funded vaccination programs in May 1993, especially for children under 18 months for whom multiple doses are required. Rates rose from fewer than 9% (95% CI, 4%-13%) in May 1993 to 48% (CI, 40%-56%) in August 1993 for children under 18 months, and from 31% (CI, 26%-36%) to 45% (CI, 40%-51%) for children aged 19-60 months. The age-specific incidence of Hib disease was inversely related to the vaccination rate. Forecasting of Hib disease incidence by the Box-Jenkins method showed that from September 1993, when about a 50% vaccine uptake was achieved in the eligible age group, overall incidence was substantially lower than expected. CONCLUSIONS: These data provide good evidence that the decrease in Hib disease incidence in 1993-1994 is an effect of vaccination, and not annual or seasonal variation. The impact of Hib vaccination appears to have been greater than would be expected from protection of vaccinated children alone. Invasive Hib disease is likely soon to become a rare cause of serious childhood infection in Australia.

Child, Preschool↗
PubMed1994

The implications of underreporting in dietary studies.

Dietary data from the Western Sydney Dietary Survey 1989-90 (n = 512) was used to investigate: 1. the prevalence and predictors of underreporting of energy intake, 2. the effects on results of excluding data from underreporters for analysis of mean nutrient intakes, and 3. the proportion of energy intake supplied by macronutrients and proportions of subjects who met dietary goals. The proportion whose measured energy intakes from a Food Frequency Questionnaire (FFQ) were below cutpoints for biologic plausibility was 28.5 per cent; it was higher for subjects who had BMI > 25 and were female. Point estimates for mean intakes of energy and nutrients were all greater when data from underreporters were excluded, but nutrient intakes expressed as percentages of energy intake remained largely unchanged. Increases in estimated mean population intake for each nutrient ranged from 7 per cent to 14 per cent for males, and 12 per cent to 17 per cent for females. Estimates of the percentages of the sample who did not meet dietary goals were significantly lower for a number of nutrients when underreporters were excluded. We conclude that: 1. results expressed as a percentage of energy intake are not affected by the exclusion of energy underreporters, and 2. estimates of the proportion of populations meeting some nutrient goals and associations between diet and disease are likely to change meaningfully and significantly with the exclusion of data from underreporters.

Adult↗
PubMed1994

Discriminating placebo and drug in generalized anxiety disorder (GAD) trials: single vs. multiple clinical raters.

A multisite, double-blind, placebo-controlled study was made of 177 patients with the diagnosis of generalized anxiety disorder. After a 1-week placebo lead-in, they were randomized to 4 weeks of treatment by placebo or one of two doses of a novel, nonsedating compound that had demonstrated reduction of fear-avoidance behavior in animals. Efficacy was not demonstrated at a significant level. A further analysis of 142 patients who completed the treatment was undertaken to test the hypothesis that efficacy might be demonstrated by the single-rater procedure (SRP), which eliminates interrater error variance. The 80 patients who were examined by the same clinical rater for all six visits were compared with the 62 patients who had the multiple-rater procedure (MRP), ratings by two or more clinicians sequentially over the six visits. A two-way analysis of variance showed significantly greater discrimination of placebo and drug for the MRP group. The results provided no support for the frequent preference for the SRP. The MRP may include less psychotherapeutic interaction with the patient and less researcher bias in ratings.

Adult↗
PubMed1993

A comparison of paroxetine and placebo in depressed outpatients.

To compare the safety and efficacy of paroxetine (n = 167) and placebo (n = 169), data from 4 centres using the same protocol were pooled. A double-blind parallel group design was used, with therapy lasting 6 weeks. Significant differences between paroxetine- and placebo-treated patients were found on the major efficacy outcome variables by week 2 and on all efficacy variables by week 4 of the study. Improvement on the sleep factor of the Hamilton Rating Scale for Depression was found after 7 d. Observer and patient global efficacy ratings were in agreement by week 4. No serious adverse events occurred, and paroxetine had no clinically significant effects on vital signs or laboratory safety data. Side effects were more common on paroxetine and were similar to other serotonin reuptake inhibitors. In general, these were well tolerated and did not lead to dropout. Symptoms of increased arousal were not seen during early therapy.

Adolescent↗
PubMed1993

Selective application of cardiopulmonary resuscitation improves survival rates.

This study is a retrospective review of all patients who died without cardiopulmonary resuscitation (CPR) or who sustained a sudden cardiopulmonary arrest in the hospital and received CPR during a 2-yr period at a large medical center. Based on a review of Current Procedural Terminology codes, patients were classified into one of the ten disease categories: multiple medical problems, acute disease, procedure-related, congenital disease, neoplasm, metastatic neoplasm, trauma, burn, acquired immunodeficiency syndrome, and dementia. A total of 1206 patient deaths without a CPR effort were identified. CPR was administered to another 550 patients who had a sudden cardiopulmonary arrest, of which 71% survived the resuscitative attempt initially, but only 25% survived CPR until discharge from the hospital. CPR was applied less frequently than the mean in the metastatic neoplasm (P < 0.0001), trauma (P = 0.013), and dementia (P = 0.0003) groups and more frequently in the acute disease (P < 0.0001) and procedure-related (P < 0.0001) groups. Survival to discharge from the hospital was more frequent than the mean in the congenital disease group (P = 0.0004) and less frequent in the neoplasm group (P = 0.0425). The other groups had survival rates comparable to the mean. Patients 70 yr of age and older were less likely to receive CPR than those younger than 70 (P < 0.0001). However, if they did receive CPR, they were just as likely to survive to discharge from the hospital as the younger patients (P = 0.3404).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1986

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↗
PubMed1985

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↗