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Biomedical subjects

J M Davis

Publications and source records attributed to J M Davis.

At least 487 records · Page 27Linked to original sources

The natural course of schizophrenia and effective maintenance drug treatment.

The natural course of schizophrenia is poor; in the absence of consistently effective and broadly applied treatment, about two thirds of schizophrenic patients remain symptomatic. Antipsychotic drugs dramatically improve the prognosis of these patients, and there is limited evidence that the use of these drugs during an acute episode may improve a patient's long-term outcome. Continued administration of antipsychotic drugs significantly attenuates the relapse rate among schizophrenic patients; however, compliance with oral antipsychotic medication remains a problem in this population. Long-acting depot antipsychotic drugs have an obvious advantage in improving patient compliance, and there are some data that suggest that relapse rates may be lower in patients receiving depot drugs compared with oral drugs. Because of the greater assurance long-acting depot drugs provide about medication compliance, these drugs clearly have a significant role in the maintenance treatment of schizophrenic patients.

Antipsychotic Agents↗

The pathogenicity of long versus short fibre samples of amosite asbestos administered to rats by inhalation and intraperitoneal injection.

For many years it has been accepted that fibre dimensions are the most important factor in the development of asbestos related disease with long fibres being more dangerous than short for all types of asbestos. This information has been derived from in vitro experiments and injection or implantation experiments since the kilogramme quantities of specially prepared dusts that are necessary for long term inhalation have not been available. The present study has taken advantage of the availability of a sample of amosite produced so that almost all fibres were less than 5 micron in length. The effects of this dust were compared to dust prepared from raw amosite that contained a very high proportion of long fibres. Previous data from studies with UICC amosite, which was intermediate in length, were also available for comparison. At the end of 12 months of dust inhalation, significantly more short fibre amosite was present in the lung tissue compared to the long but while the long fibre dust caused the development of widespread pulmonary fibrosis, no fibrosis at all was found in animals treated with short fibre. One third of animals treated with long fibre dust developed pulmonary tumours or mesotheliomas but no pulmonary neoplasms were found in animals treated with short fibre dust. Following intraperitoneal injection, the long fibre amosite produced mesotheliomas in 95% of animals with a mean induction period of approximately 500 days. With short fibre dust, only a single mesothelioma developed after 837 days. In previous inhalation studies with UICC amosite, relatively little pulmonary fibrosis had developed and only two benign pulmonary tumours. This would suggest that to produce a significant carcinogenic response in rat lung tissue amosite fibres must be longer than those in the UICC preparation. Following the injection of UICC amosite, however, mesotheliomas developed in the same proportion of animals and with the same mean induction period as with long fibre dust. From this it would appear that while very short fibres exhibit little carcinogenicity to either lung or mesothelial tissues, mesotheliomas can be produced by dust preparations consisting of shorter fibres than are needed to produce tumours.

Animals↗

Inhalation and injection studies in rats using dust samples from chrysotile asbestos prepared by a wet dispersion process.

Long term inhalation studies and intraperitoneal injection studies in rats were undertaken with a series of chrysotile asbestos dusts. Three dust samples were generated from chrysotile modified by the wet dispersion process (WDC) and one was from unmodified chrysotile. Following a 1 year inhalation period, all the chrysotile samples proved extremely fibrogenic and carcinogenic and there were no significant differences between the WDC dusts and normal chrysotile. In all experimental groups approximately 25% of animals developed pulmonary carcinomas and in the oldest rats advanced interstitial fibrosis occupied on average 10% of all lung tissue. In the injection studies all the dust samples produced mesotheliomas in over 90% of animals. Very little chrysotile remained in the lungs of the animals that survived longest following dust inhalation and what there was was present as individual chrysotile fibrils. It is suggested that chrysotile is potentially the most harmful variety of asbestos as shown in these and other animal studies but that it is removed from lung tissue quite rapidly. In the long lived human species this may mean that except where exposure levels are very high and of long duration, chrysotile should be less hazardous than other asbestos types.

Animals↗

Monaural auditory adaptation of reaction times at .5, 1, and 3 kc/s.

All procedures to measure auditory adaptation depend at least indirectly upon some subjective judgment of loudness, with the exception of the reaction-time (RT) study of Davis and Weiler (Brit. J. Audiol., 1976, 10, 102-106). We used a variant of the Davis-Weiler RT method to measure monaural adaptation at the end of tones of 7 min duration at .5, 1, and 3 kc/s at 60 db SPL, in 62 normal-hearing young adults. Adaptation was expressed as an increase in RT in msec post- vs pre-adaptation in response to a 1-sec probe tone at 10 kc/s at 70 db SPL presented simultaneously with the adapting tone, either (1) in the middle of a 2-sec burst of the adaptation tone prior to the beginning of the 7-min adaptation session (pre-adaptation measure), or (2) during the last seconds (S alerted) of the continuing adaptation tone (post-adaptation measure). Significant pre-post RT differences, collapsed over pre-post measures and over ears, were found at all 3 frequencies (p less than .0001), indicating that the Monaural Heterophonic RT (MHRT) procedure can indeed be used as an objective measure of auditory adaptation. The mean RTs across pre- and post-adaptation measures were 221.9, 217.6, and 228.0 msec in the usual frequency order, significantly different (p less than .0001). Adaptation (i.e., increased RT after 7 min of adaptation) at .5, 1, and 3 kc/s was 36.9, 28.5, and 21.6, respectively. This effect introduced a significant interaction between frequency and adaptation (p less than .001). To transfer from auditory adaptation in reduced RT in msec by the MHRT method to adaptation in reduced phons in db, it will be necessary to construct, perhaps for every S, a table of RTs for a sufficient selection of levels at the relevant frequencies.

Acoustic Stimulation↗

A review of experimental evidence for the carcinogenicity of man-made vitreous fibers.

This paper reviews experimental studies on the carcinogenicity of man-made vitreous fibers. Long-term inhalation studies using several animal species and dust preparations of fibrous glass, rock wool or slag wool have produced little evidence of pulmonary fibrosis or pulmonary tumors. While some intratracheal injection studies found almost no pathological changes in lung tissue, some showed that pulmonary fibrosis can occur. Only one intratracheal injection study has reported that vitreous fibers can be carcinogenic; in contrast, many workers have reported that, following intrapleural or intraperitoneal injection, man-made vitreous fibers are highly carcinogenic, and tumor production appears to be closely related to fiber size. In vitro tests confirm that vitreous fibers can be toxic and can cause neoplastic transformation of cultured cells. The discrepancies between some experimental studies probably result from the relatively high solubility of most vitreous fibers. It seems likely that, while these fibers can survive in body cavities long enough to cause tumor production, they dissolve in lung tissue fast enough to have relatively little harmful effect. Rock-wool fibers appear more durable than glass- or slag-wool fibers, and, with similar fiber numbers and sizes in any dust cloud, this material is the most likely to have harmful potential.

Animals↗

The effect of alcoholism on membrane lithium transport.

Red cell lithium efflux rates in major affective disorder and alcoholic patient groups were studied. Current alcoholism was associated with significant elevation of lithium transport in white but not black subjects. This effect of alcoholism on the characteristics of membrane ion transport was independent of the blood pressure elevating effects of alcoholism and the diagnosis of major affective disorder. A model to explain the mechanism of this race-specific membrane effect of alcoholism is proposed and discussed.

Alcoholism↗

Uptake and/or binding of tricyclic antidepressants in human red cells.

The factors affecting the red blood cells (RBC) uptake and/or binding of tricyclic antidepressants imipramine (IMI) and desmethylimipramine (DMI) were investigated under in vitro conditions. The time course of drug distribution indicated that equilibrium between RBC and medium is reached rapidly. The uptake and/or binding of IMI and DMI to RBC was not saturable and RBC/medium ratio was unaffected by pH, nature of monovalent cations or by the presence of therapeutic concentrations (5-50 ng/ml) of antipsychotic drugs. In the protein-free medium, RBC/medium ratio of DMI was X +/- SE = 2.58 +/- 0.08 (n = 5) and that of IMI was 7.38 +/- 0.12 (n = 6). However, RBC/plasma ratio of DMI was 0.78 +/- 0.04 (n = 7) and IMI ratio was 0.64 +/- 0.03 (n = 9). The RBC/medium ratio was linearly related to free fraction of IMI in a buffer containing 60 mg/ml of human serum albumin with various concentrations of alpha 1-acid glycoprotein (r = 0.971, n = 7). These results suggest that in the absence of proteins the lipid solubility of antidepressants is the main determinant factor in RBC uptake and/or binding, whereas, in the presence of proteins, free fraction of the drug plays the major role. Hence, the RBC/plasma ratio of antidepressants may correlate with treatment outcome in clinical studies better than total drug concentration in plasma.

Buffers↗

Pharmacologic evidence for specificity of pursuit dysfunction to schizophrenia. Lithium carbonate associated with abnormal pursuit.

Conflicting findings regarding the prevalence of abnormal smooth-pursuit eye movements in patients with major affective disorders call into question the specificity of impaired smooth-pursuit eye movements to schizophrenia. We report that pursuit is impaired in 88% of lithium carbonate-treated affective disorder patients whose pursuit was normal prior to receiving this drug. Over half of lithium carbonate-treated affective disorder patients in remission also showed impairment of smooth-pursuit eye movements. In conjunction with recent prevalence data on family members of psychiatric patients, the findings support the specificity of abnormal pursuit as a biological trait associated with schizophrenia, but not with the major affective disorders. The mechanisms by which lithium carbonate impairs pursuit are discussed.

Adult↗

Somatic symptoms in primary affective disorder. Presence and relationship to the classification of depression.

The incidence and severity of somatic symptoms were determined in 132 patients with major depressive disorder and 80 normal controls. The role of somatic symptoms was analyzed in relation to the unipolar-bipolar division, Research Diagnostic Criteria (RDC) subtypes, hypersomnia, and appetite increase. The data suggest that the rate and level of somatic symptoms increased with the severity of depression and age, only appetite loss differentiated unipolar from bipolar patients, and the classic somatic symptoms of depression were present in most RDC subtypes and not exclusively associated with the "endogenous" subtype. Hypersomnia or increased appetite identified two overlapping depressive subgroups; patients in both groups were young and characterized by high interpersonal sensitivity. Hypersomniac depressed patients were less anxious and agitated; patients with increased appetite were more hostile and showed a greater decrease in libido than age-matched and sex-matched patients with neither symptom.

Adult↗

Plasma levels of fluphenazine during fluphenazine decanoate treatment in schizophrenia.

The authors measured plasma fluphenazine levels in 20 schizophrenic patients receiving 25 or 50 mg fluphenazine decanoate (FPZ-D) by IM injection every 2 weeks. The plasma levels were determined by a sensitive gas-liquid chromatographic (GLC) assay with a nitrogen detector device developed in their laboratory. Using this chemical assay method, they replicated the finding of a sharp initial plasma peak within 24 h after the injection followed by a low but rather stable plasma level as previously reported by nonchemical assay methods. The interval plasma levels (averages of day 4-10 after injection) ranged from 0.17-0.61 ng/ml in 10 patients who received 25 mg; and 0.20-0.93 ng/ml in 7 patients who received 50 mg FPZ-D every 2 weeks. This four-fold variation in plasma levels during FPZ-D injection was smaller than previously reported levels achieved with oral antipsychotic drug treatment. Based on the study of plasma levels achieved with FPZ-D injection and oral FPZ-H (fluphenazine HC1) in 6 patients, the dosage requirement of FPZ-D appeared to be difficult to predict from the oral dosage of FPZ-H in the same patient. Two weeks past injection, fluphenazine was undetectable in approximately half the samples with the GLC method. Thus, radioimmunoassay or radioreceptor assay, which also measures metabolites, might be more suitable for the study of plasma levels in patients receiving FPZ-D injection.

Adolescent↗

Application of modern psychometric theory in psychiatric research.

This paper describes the general statistical theory of item-response modeling as developed in the fields of statistics and education. Generalization of these procedures for application in the analysis of psychiatric rating scales is the focus of this paper. Questions of unidimensionality vs multidimensionality and choice of distributional transform (logistic vs normal) are both discussed and statistically examined using data on the Beck Depression Inventory (BDI). Application of these models to the BDI revealed two subscales that maximally differentiate high and low levels of depression in psychiatric and medically ill patients respectively. There was considerable but not complete overlap between the two subscales. These statistical models are found to have desirable properties when used to analyze psychiatric rating scales and provide a refinement over existing techniques of classical test theory and factor analysis.

Adult↗

Opioid modulation of feeding behavior following forced swimming exercise in male rats.

Adult male rats were subjected to an acute bout of swimming exercise for 50 min during the early morning or late afternoon. Compared to nonexercised controls, all exercised groups showed an initial approximately 2-hr period of increased feeding (period I hyperphagia). A 50-min period of sham swimming (wading in water) was followed by period I hyperphagia but not period II hypophagia. Opioid modulation of period I hyperphagia was indicated by the ability of naltrexone to antagonize, in a dose-dependent manner, the postexercise hyperphagia. Furthermore, plasma concentrations of immunoreactive B-endorphin (Ir-B-ep) were increased during period I following exercise. Opioid modulation of the period II hypophagia was equivocal. Plasma Ir-B-ep was not altered in period II, and naltrexone did not modify period II hypophagia. The ability of 2-deoxy-D-glucose to induce feeding was slightly depressed (p less than 0.05) during period II after exercise, and the ability of exogenous insulin to induce feeding was not changed. These differential feeding responses to 2-deoxy-D-glucose (opioid-mediated) and insulin (relatively opioid-independent) suggest that an opioid deficiency may exist during period II and contribute to the hypophagia.

Animals↗

Opioid modulation of feeding behavior following repeated exposure to forced swimming exercise in male rats.

Patterns of normal and stimulated food intake (FI) as well as its possible endogenous opioid (EO) modulation were investigated in male rats given regular swimming exercise (trained; TR) and compared with nonexercised sedentary (SED) controls. Rats in the TR group had lower body weights as well as reduced 24 hr FI due to lower nocturnal FI. TR rats also ate less food in response to injections of 2-deoxy-D-glucose (2-DG) but not insulin (INS) when injections were given during the first 4-5 weeks of training. However, this difference between TR and SED rats in the 2-DG induced feeding was not demonstrable after 10 or more weeks of training. Plasma concentrations of immunoreactive B-endorphin (IR-B-ep) were elevated, as expected, in TR rats (10-12 weeks) during nocturnal sampling whereas the nocturnal increase of IR-B-ep was absent in SED controls. However, these SED rats did increase daytime IR-B-ep in response to 2-DG and acute exercise, albeit somewhat less in magnitude when compared to TR rats. Injection of naltrexone (NTX) decreased feeding in TR rats (10-12 weeks) but not in contemporary SED controls. In summary, exercise training modified feeding behavior, and at 4 weeks of training, TR rats ate less in response to opioid-related feeding stimulus of 2-DG, but responded similarly to insulin (relatively opioid independent) treatment. At later stages of training this difference between TR and SED rats disappeared. Moreover, SED rats had atypical profiles of IR-B-ep and reduced hypophagic responses to NTX suggesting that TR rats might have greater EO modulation of feeding at this stage.

Animals↗