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Biomedical subjects

J B Williams

Publications and source records attributed to J B Williams.

At least 163 records · Page 9Linked to original sources

Substance-use disorders in DSM-III-R. Evidence for the dependence syndrome across different psychoactive substances.

Using the newly revised DSM-III-R criteria for substance-abuse diagnoses, we examined dependence syndrome elements among 83 psychiatric patients. The sample included 14 with no history of substance abuse. The remainder abused alcohol (52), sedatives (31), hallucinogens (12), stimulants (33), cannabis (44), cocaine (52), or opiates (47). Many patients (52) had abused more than one type of drug. Ten items assessing the proposed dependence symptoms for each type of drug were factor-analysed. The dependence syndrome items formed a single factor for opiates, cocaine, and alcohol, but not for other drugs. When the items were combined into cumulative scales, they had excellent internal consistency. Furthermore, they formed good approximations of unidimensional Guttman scales on which higher scores indicated greater syndrome severity. The items associated with higher scores differed across drugs, with opiates having the most striking differences from the other substances. Medical-psychosocial consequences were relatively independent of the dependence syndrome, although alcohol and cocaine dependence had some association with other problem areas. These findings support the utility of a common dependence syndrome concept for drugs of abuse as well as alcohol, and provide empirical support for the current revision of the DSM-III diagnostic criteria.

Adult↗

Clinical and biochemical correlates of bradyphrenia in Parkinson's disease.

Bradyphrenia is considered the mental equivalent of bradykinesia in Parkinson's disease. Patients are described as inattentive and "slow thinking," but not demented. We compared the performance of three groups: parkinsonians age-matched controls, and mildly impaired patients with probable Alzheimer's disease in tests of general intellect, memory reaction time, and in a continuous performance task measuring attention and vigilance. Metabolites of the major biogenic amine in CSF were also measured. The parkinsonians formed two distinct groups. In one, intellectual function and CSF measures were similar to that of controls. The other group of parkinsonians had significantly more omission errors and fewer correct response on the continuous performance task than did controls or patients with Alzheimer's disease. We considered this second group to have bradyphrenia. Their performance on measures of general intellectual and memory function was similar to that of the patients with Alzheimer's disease. CSF-MHPG, the major metabolite of norepinephrine, correlated with the continuous performance task and reaction time in all parkinsonians, and those with bradyphrenia had the highest CSF-MHPG levels. Our data suggest that bradyphrenia is an impairment of attention and vigilance, unique to Parkinson's disease, that may be associated with dementia and with an alteration in norepinephrine metabolism.

Aged↗

Comparison of mammalian luteinizing hormone releasing hormone (LH-RH), and of an analog (ICI 118630), on luteinizing hormone and ovarian steroid (progesterone, oestradiol) secretions in laying hens. (Gallus domesticus).

This experiment was conducted to compare the luteinizing hormone (LH), progesterone (P4) and oestradiol (E2) release in response to injections of various doses of synthetic mammalian luteinizing hormone-releasing hormone (LH-RH) and of an LH-RH agonist, ICI 118630, administered to laying hens 4 to 9 hours after a mid-sequence ovulation. Plasma LH increased significantly within 10 minutes of injection of either compound whereas any increases in plasma steroid concentrations were discerned later, at approximately minutes post-injection. No dose-response relationship was found for either compound with respect to LH release, but ICI 118630 appeared more potent than LH-RH. This analog also produced a greater mean incremental rise in plasma progesterone, but not oestradiol, than LH-RH, and this was found in animals injected at a time when the largest ovarian follicle was not mature. These result suggest that ICI 118630 is a more potent releasing hormone in the hen at the level of the pituitary, and that it may have a stimulating effect on ovarian progesterone secretion.

Animals↗

Rat liver NAD(P)H:quinone reductase. Construction of a quinone reductase cDNA clone and regulation of quinone reductase mRNA by 3-methylcholanthrene and in persistent hepatocyte nodules induced by chemical carcinogens.

We have used polysomal immunoabsorption techniques to purify rat liver quinone reductase mRNA (NAD(P)H:quinone oxidoreductase, EC 1.6.99.2, formerly called DT-diaphorase). Using the purified mRNA as template, cDNA clones complementary to quinone reductase mRNA have been constructed. One cDNA clone, pDTD55, has a 1900-base pair insert which has been demonstrated by hybrid-select translation experiments to be complementary to quinone reductase mRNA. Clone pDTD55 has been used in RNA and DNA blot hybridizations to show that quinone reductase mRNA is approximately 1900 nucleotides in length and is encoded by a gene which spans approximately 7000-8000 base pairs. We have also shown that quinone reductase mRNA is markedly elevated by 3-methylcholanthrene administration and in persistent hepatocyte nodules induced by chemical carcinogens. The elevation of quinone reductase mRNA in persistent hepatocyte nodules is not due to either gene amplification of DNA rearrangement. Rather, the quinone reductase gene is hypomethylated in persistent hepatocyte nodules compared to the gene in either liver tissue surrounding the nodule or normal liver. These data suggest that hypomethylation of specific gene sequences occurs at early stages during chemical carcinogenesis.

Animals↗

The logistic regression analysis of psychiatric data.

Logistic regression is presented as the statistical method of choice for analyzing the effects of independent variables on a binary dependent variable in terms of the probability of being in one of its two categories vs the other. The method, which must be applied by computer, is illustrated on data from the DSM-III field trials. The dependent variable is treatment with behaviourally-oriented psychotherapy vs treatment with psychoanalytically-oriented psychotherapy, and the independent variables are several patient and clinician characteristics. Like ordinary multiple regression, the method is shown capable of analyzing categorical as well as continuous independent variables. Unlike ordinary multiple regression when applied to binary data, logistic regression analysis necessarily yields estimated probabilities that lie between 0 and 1. The measure of association derived from logistic regression analysis, the odds ratio, is defined. Methods for making inferences about it are presented and illustrated.

Attitude of Health Personnel↗

Use of a membrane-bound fluorophore to characterize diffusion boundary layers around human erythrocytes.

A novel method is used to demonstrate the presence of diffusion boundary layers around erythrocytes following rapid mixing in a stopped-flow spectrophotometer and to estimate the apparent dimensions of the diffusion boundary layers. Pink erythrocyte ghosts labeled on their external surfaces with tetramethyl rhodamine isothiocyanate (TRITC) were mixed in a stopped-flow apparatus with 50 mM NaI in Ringer's solutions. I- is an effective collisional quencher of TRITC fluorescence. TRITC fluorescence after flow stopped decreased monoexponentially with time. The concentration of I- at the cell surface as a function of time was estimated from the dependence of TRITC fluorescence on I- concentration in steady-state experiments. The kinetics of the increase in I- concentration at the cell surface was fit to two diffusional models: a planar erythrocyte ghost bounded by planar diffusion boundary layer and a spherical erythrocyte surrounded by a spherical shell diffusion boundary layer. The planar model best fits the experimental data with a diffusion boundary layer 4.68 microns thick. Using the spherical model the experimental data is best fit by a 6.9 microns diffusion boundary layer.

Diffusion↗

Proposed changes in DSM-III substance use disorders: description and rationale.

The authors describe changes in DSM-III substance use disorders to be included in the revised version, DSM-III-R. Major revisions include removal of the distinction between "abuse" and "dependence" and broadening the definition of "dependence" to a syndrome of clinically significant behaviors that indicate a serious degree of involvement with psychoactive drugs; creation of a new category of "psychoactive substance neuroadaptation syndrome" for individuals whose physiological adaptations to high doses of psychoactive substances did not arise from their own behavior; use of an identical set of symptoms and behaviors to determine dependence on all different classes of psychoactive substances; and provision of a system for rating severity of dependence.

Drug Tolerance↗

Clinical and biochemical features of depression in Parkinson's disease.

Among 49 consecutive patients with Parkinson's disease, 40% were depressed according to DSM-III; they had major depression or dysthymic disorder accompanied by sleep disturbance, fatigue, psychomotor retardation, loss of self-esteem, and excessive guilt. During a 10-day dopamine-free period, lumbar puncture was performed to measure the metabolites of dopamine, serotonin, and norepinephrine. Patients were given an overnight dexamethasone suppression test, and the effects of thyrotropin-releasing hormone and L-dopa on plasma growth hormone and prolactin were examined. Level of CSF 5-hydroxyindoleacetic acid was lowest in parkinsonian patients with major depression and was related to psychomotor retardation and loss of self-esteem.

Aged↗

The MCMI and DSM-III: a brief rejoinder to Million (1985).

Millon (1985) presented eight criticisms of the article by Widiger, Williams, Spitzer, and Frances (1985) on the MCMI as a measure of DSM-III. This article is a brief rejoinder. The major point we wish to make is that one should be cautious in interpreting the MCMI as a measure of DSM-III disorders because there has not yet been any research published on the relationship between the MCMI and DSM-III. We believe this position has not been refuted by Millon's critique.

Comment↗

Luteinizing hormone releasing activity of [Gln8]-LHRH and [His5, Trp7, Tyr8]-LHRH in the cockerel, in vivo and in vitro.

The luteinizing hormone (LH)-releasing activity of two distinct chicken luteinizing hormone releasing hormones ([Gln8]-LHRH and [His5, Trp7, Tyr8]-LHRH) were evaluated in white Leghorn cockerels. In the first study, thirty birds were randomly allotted to five groups and injected, i.v., with 0.9% saline, [Gln8]-LHRH (cLHRH I, 1 microM or 10 microM) or [His5, Trp7, Tyr8]-LHRH, (cLHRH II; 1 microM or 10 microM). Blood samples were drawn prior to and through 60 min following the injection, and plasma was collected for LH determination. In the second study, anterior pituitary cells from cockerels were dispersed and preincubated for 1 hr. Approximately 1.5 X 10(5) cells per tube were incubated with either Medium 199 buffer (control), 8-bromo-cAMP or various doses of cLHRH I or cLHRH II at final concentrations ranging from 0.02 to 100.0 nM. At the end of a two hour incubation, supernatant was collected and the concentration of LH determined. Injection of cLHRH I or cLHRH II at 1 microM and 10 microM levels caused a significant increase in blood LH concentrations which peaked 5 min following injection. There were, however, no differences between the stimulatory effect of cLHRH I compared to cLHRH II at either dose. On the other hand, cLHRH II was found to be 4.7 times more potent than cLHRH I in stimulating LH release from dispersed pituitary cells. It is suggested that cLHRH II may have greater affinity for the gonadotroph receptor, greater uptake by the cell, and/or that it may be more resistant to in vitro degradation than cLHRH I. On the other hand, an extra pituitary site of degradation may be more effective in metabolizing cLHRH II, resulting in its equipotency with cLHRH I, in vivo.

Animals↗

The multiaxial system of DSM-III: where did it come from and where should it go? I. Its origins and critiques.

The multiaxial system for evaluation is widely regarded as one of the most important contributions of DSM-III. The concept of multiaxial evaluation, that an individual is evaluated in terms of several different domains of information that are assumed to be of high clinical value, was introduced in the United States in the mid-1970s. Its value for clinical and research work was quickly recognized, and in the first year of the development of DSM-III, in 1976, a decision was made to incorporate such a system in the manual. This report reviews both the background of the development of the DSM-III multiaxial system and critiques that have been made of each of the axes since its publication in 1980. A companion report reviews empirical studies of the system and offers suggestions for its further development.

Attitude of Health Personnel↗

The multiaxial system of DSM-III: where did it come from and where should it go? II. Empirical studies, innovations, and recommendations.

In a companion report, the development of the DSM-III multiaxial system was described, as well as critiques that have been made of each of its five axes. In this report, empirical studies that provide information about the reliability and validity of the system are reviewed. In addition, suggestions that have been made for changes in the system are critically examined. Finally, this material is synthesized into specific proposals for improvements in the multiaxial system that will be considered by the recently constituted Work Group to Revise DSM-III.

Attitude of Health Personnel↗

Pharmacokinetic studies of ivermectin: effects of formulation.

Studies are reported which describe the effects of formulation, animal species, and route of administration on the pharmacokinetics of ivermectin. Biological half-life t1/2 increases in the order: swine (0.5 day) less than dogs (1.8 day) less than cattle approximately equal to sheep (2.8 day). Formulation modifications, based upon the solubility properties of the drug, have been directed towards the development of a nonaqueous injectable formulation for cattle and an aqueous vehicle for horses. Bioavailability following subcutaneous injection in cattle can be regulated by control of injection solvent composition: a vehicle composed of a mixed aqueous-organic solvent exhibits pharmacokinetic properties (i.e., Cp, t1/2, AUC, and F) intermediate between those furnished by an aqueous formulation and via a purely nonaqueous solvent. The longer apparent biological half-life from this latter vehicle (t1/2 = 8.3 days) confirms that a slow absorption process dominates the pharmacokinetics in the nonaqueous injectable product to produce an effective controlled-release formulation. These bioavailability results illustrate the increase in the concentration of an organic solvent and a concomitant decrease in surfactant concentration in a micellar aqueous system for prolonged drug delivery via injection.

Animals↗

Validation of the doubly labeled water technique for measuring energy metabolism in starlings and sparrows.

I have tested the idea that doubly labeled water (DLW) can accurately predict CO2 production in savannah sparrows, song sparrows, white-throated sparrows, starlings, and a single house sparrow by comparing DLW estimates with those obtained simultaneously by capturing expired CO2 in Ascarite. In addition I used the energy balance method to see if metabolic rates generated from DLW measurements accurately reflected the actual metabolic rates of these birds. I found close agreement in DLW and the gravimetric and energy balance methods, with DLW underestimating CO2 production on average by -3.5% in sparrows, and -7.1% in starlings. Similarly, the energy balance method indicated a -3.1% underestimate by DLW for sparrows and a -5.1% for starlings. The DLW method can yield reasonable estimates of CO2 production in a variety of passerine birds.

Animals↗