Alcohol placebos: you can only fool some of the people some of the time.
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Biomedical subjects
Publications and source records attributed to C Taylor.
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This paper considers the impact of the first consultation at a specialist alcohol clinic on patients' perceptions of their drink problem and on their expectations of help from three sources: an alcohol clinic, general practitioners and Alcoholics Anonymous. At intake, males had higher expectations than females of help from the alcohol clinic while people in manual occupations and those in the 'less heavy' drinking category had higher expectations of general practitioner help than other patients. Change was found to occur during the first clinic consultation so that by the end of the session patients had raised their rating of problem severity and their expectations of help from the three sources examined. Overall, patient perceptions of the clinic assessment session were positive. The study highlights the importance of obtaining a full understanding of the process of engagement in treatment and indicates the potential of a clinical assessment to effect change in patient attitudes.
A method for producing placebo drinks that are hard to discriminate from alcoholic drinks is described. Subjects received a series of paired comparisons, each involving a distinctively flavoured alcoholic drink and one of six different placebo versions of it. Following each such comparison, rating scales were used to record the 'alcoholic strength' and 'sensory intensity' of a placebo drink relative to the alcoholic drink. The procedure was replicated using another distinctive alcoholic drink and another set of placebos. Based upon a multivariate analysis of subjects' ratings, the version of the placebo that was most difficult to discriminate from it's corresponding alcoholic drink was identified for both alcoholic drinks. The method is intended to be a general one for producing placebo versions of alcoholic drinks which do not differ on any dimensions which can be shown to be important in producing a response.
Pharmacokinetic and coagulation studies were carried out over a 12-week period with 11 asymptomatic hemophilia patients with human immunodeficiency virus infection receiving zidovudine (ZDV). The patients received 300 mg every 4 h while awake (the accepted dose at the time of this study); consecutive 24-h intravenous (i.v.) and 12-h oral pharmacokinetic studies were conducted at weeks 1, 6, and 12. Coagulation studies were conducted at weeks 0, 4, 8, and 12. The numbers of units of factors VIII and IX and cryoprecipitate transfused during the 12-week periods before, during, and after ZDV treatment were recorded. Following i.v. and oral ZDV administration, the concentration in plasma declined rapidly over the first 4 h, and in some patients, ZDV was still detectable at 4 to 10 h. The i.v. total clearances (means +/- standard deviations) were 14.9 +/- 7.3, 11.2 +/- 3.7, and 15.1 +/- 4.7 ml/min/kg of body weight. The i.v. distribution volumes were 1.08 +/- 0.5, 1.0 +/- 0.4, and 1.65 +/- 1.4 liters/kg. The bioavailabilities were 0.54 +/- 0.22, 0.46 +/- 0.19, and 0.59 +/- 0.13 at weeks 1, 6, and 12, respectively. The pattern of ZDV-glucuronide (GZDV) disposition was similar to that of ZDV, and the peak plasma GZDV-to-ZDV ratio was higher after oral dosing, consistent with first-pass metabolism. In some individuals, up to 33% of an i.v. dose was excreted unchanged. At weeks 6 and 12, greater than 300 mg of total ZDV (GZDV plus ZDV) was recovered in the urine of some patients, suggesting tissue redistribution. Concentration in plasma after oral ZDV administration were variable, both within and between patients. The von Willebrand antigen level consistently decreased throughout the study but was not accompanied by a parallel change in ristocetin cofactor A activity, and no clinical adverse effects on coagulation were noted. This study demonstrates that ZDV can be used in hemophilia patients without worsening of their bleeding tendencies. The clinical significance of decreased ZDV clearance and the prolonged terminal elimination phase of ZDV will require further study with patients receiving chronic ZDV.
Evidence for a pseudoautosomal locus for a schizophrenia susceptibility gene was sought by two forms of analysis of 25 multiply affected families. Firstly, in the sample as a whole there was an excess of same-sex over mixed-sex siblings compared with that expected. Secondly, linkage analysis was performed in six of the families. The genotypes were studied for DXYS14, a highly polymorphic marker in the telomeric pseudoautosomal region. No evidence for positive linkage was found with two-point analysis under eight different genetic models for the mode of transmission. A non-parametric, sibling-pair analysis also failed to detect linkage. Our findings provide no evidence for linkage within the pseudoautosomal region; same-sex concordance must arise from some other mechanism.
Analysis of seven strains designated as Rickettsia conorii for reactivity with a panel of 12 monoclonal antibodies to surface-protein epitopes of spotted fever group rickettsiae and by Western immunoblotting with standard serotyping sera revealed remarkable antigenic diversity. Rickettsial strains from France, Morocco, Ethiopia, Kenya, South Africa, India, and the USSR differed from one another in reactivity with at least one and as many as five monoclonal antibodies. Simko and Indian strains were similar to one another and differed substantially from other R. conorii strains. All seven strains reacted with three R. conorii-specific monoclonal antibodies. Western immunoblotting demonstrated a major 120-kD protein and a major 135-kD protein in all strains. The principal differences were the presence of a major undenatured 130-kD protein in all strains except Indian and Simko, which had an analogous protein of 124 kD. Immunodominant antigenically related, heat-denatured protein bands of 170 kD (Malish 7 strain), 175 kD (Manuel strain), and 190 kD (Kenya tick typhus, Indian, and Simko strains) were not detected in the M-1 and Moroccan strains. This antigenic diversity is greater than that previously reported for other spotted fever group rickettsial species, suggesting that R. conorrii is an older species than R. rickettsii with a longer period of time for evolutionary divergence.
A nonhuman primate model of ocular histoplasmosis was developed that enabled the authors to define the choroidal cellular immunopathology of both the acute and chronic phases of experimental histoplasmic choroiditis. Anti-human monoclonal antibodies were used to identify the inflammatory cell subsets and to calculate their relative percentages in the choroidal inflammatory lesions. Comparison of the acute (less than or equal to 65 days) and chronic (greater than or equal to 1 yr) phases suggested possible variations in the evolution of these lesions, resulting in the development of immunopathologically distinct chronic lesions. In this model, these late lesions could be differentiated by the presence or absence of dense lymphocytic foci, comprised predominantly of mature B-lymphocytes, located within the more diffuse inflammatory cell background. The chronic lesions containing these B-cell foci had significantly higher percentages of both mature B-cells (P less than 0.0001) and helper-inducer T-cells (P less than 0.05) than did the chronic lesions without B-cell foci. The increase in helper-inducer T-cells in the chronic lesions with B-cell foci resulted in a higher mean helper-suppressor T-cell ratio (mu = 0.60) than that seen in lesions lacking foci (mu = 0.33). These findings suggest that, even in the same eye, individual chronic histoplasmic choroidal lesions, which clinically resemble "histo spots" in humans, may have different immunopotentials.
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A total of 752 individuals from The Gambia, west Africa who are representative of the major ethnic groups in the capital, Banjul, were serologically typed for HLA-A, -B, and -C antigens. Although all were typically "African" in their antigenic profiles, some marked frequency differences were found between the ethnic groups. Genetic distance comparisons with several other African populations showed that, although these west African populations clustered closely together, the positions of the various ethnic groups in The Gambia were consistent with historical and linguistic evidence of their affinities with one another and with other African populations. Despite the potential confounding effects both of selection by infectious diseases and of genetic drift caused by local differences in population structure, HLA frequencies appear to be of value in measuring inter- and intraregional population affinities in sub-Saharan Africa.
We compared the Social Security Administration's (SSA) judgment of disability with uninvolved rheumatologists' evaluations of ability to work. With the cooperation of the SSA, 52 new disability claimants who alleged rheumatoid arthritis, osteoarthritis, or systemic lupus erythematosus were identified at the beginning of their claim. At the same time that their claim was being formally reviewed, they had a standardized examination by an independent rheumatologist who was not involved with their care, and they had a standardized test of observed performance. Rheumatologists' judgments of ability to work were compared with the SSA judgments. Rheumatologist and SSA judgments were in agreement for 35 of the 52 claimants (67%). All 11 claimants who met or equaled the SSA medical evaluation criteria were judged work-disabled by the rheumatologist. Of 27 judged able to work by the SSA, the rheumatologist judged 11 to be unable. Agreement between the SSA judgment of residual functional capacity and observed performance was no more than would be expected by chance. Most SSA judgments agree with a clinician's evaluation but a standardized physical evaluation by a rheumatologist and performance-based tests appear to add important information.
The Kernel Density Estimator (KDE) is a versatile nonparametric technique with very good theoretical properties. It is used to obtain "smoothed histograms," which allows several distributions to be presented and analyzed more easily on one graph, and direct combination into average distributions. The application of the KDE method as a visual aid for the analysis of distributions of muscle fiber areas is presented here.
The accuracy of clinical diagnosis for pelvic inflammatory disease was determined in 95 women who presented with pelvic pain to primary care physicians and then were referred to gynecologists. Laparoscopy or laparotomy with endometrial biopsy and fimbrial minibiopsy revealed that prevalence of pelvic inflammatory was 46% (44/95) and positive and negative predictive values of gynecologists were 74% (23/31) and 67% (43/64) (p = 0.0002). If histopathologic diagnosis was the standard, clinical accuracies of the gynecologists were no better than chance (p = 0.43), suggesting an expectation bias for visual diagnosis. Laparoscopy had a sensitivity of 50% (12/24) and a specificity of 80% (40/50) for salpingitis if the standard was fimbrial histopathologic diagnosis (p = 0.01). These results support the routine use of laparoscopy, supplemented when negative by endometrial and fimbrial minibiopsy, to accurately diagnose pelvic inflammatory disease.
The hospital records of 30 patients with isolated fractured mandibles treated by intermaxillary fixation (IMF) were compared to 30 patients treated by miniplate osteosynthesis. The treatment variables assessed were the period of hospitalisation, the operating time, the use of intensive care or nurse specialing services, the number of outpatient visits, and the cost of materials. The cost of each facility was calculated from six sources, so that the average cost of each method of treatment could be determined. The results showed that the average cost for managing a fractured mandible with IMF was 1000 pounds if the intensive therapy unit (ITU) was used and 919 pounds if ward specialing services (a single nurse looking after the patient) were used. This compared with an average cost of 794 pounds for miniplate osteosynthesis. The extra cost of the materials if miniplates were used could be discounted by the longer period of hospitalisation, the use of ITU or nurse specialising services, and the greater number of outpatient visits that were required for patients treated with IMF. In addition the use of IMF significantly increased the time patients spent off work.
One of the most precise methods of determining hydrogen peroxide (H2O2) formation by biological systems is based on measuring the rate of enzyme-substrate complex formation between H2O2 and cytochrome c peroxidase (CCP). The main problem with this method is that CCP is not commercially available and has to be prepared in the laboratory. We have modified some currently available methods for purifying a highly active preparation of CCP in about 4 d. It includes a batch extraction of protein using DEAE-sepharose followed by concentration either by lyophilization or by passing the extract through a small DEAE-sepharose column instead of by ultrafiltration. The concentrated preparation is passed through a Sephadex G-75 column and the final CCP crystallized against water. The final preparations had a purity index (PI, ratio of absorbance at 408 nm/280 nm, equivalent to heme/protein ratio) above 1.2. These changes make the overall procedure very simple, preserving enzyme activity and spectral properties. In addition, we point out that special care has to be taken to eliminate cytochrome c from crude CCP extracts. Cytochrome c not only introduces an artifact when determining PI, but is also may act as a hydrogen donor for CCP when monitoring H2O2 formation, thus decreasing the sensitivity of this method.
Two groups of patients have been studied in order to investigate the relationship between age and the effect of oral anticoagulant therapy. The first group comprised 364 patients aged 23-89 years who showed a stable anticoagulant effect on medium- or long-term warfarin therapy; in this group the elderly subjects were found to require, on average, a lower drug dose to maintain the same degree of anticoagulation. The second group comprised 130 patients aged 15-83 years who had received an initial standard oral dose of 10 mg of warfarin. No significant difference was found in the degree of anticoagulation achieved by 16 hours. Although the maintenance dose in elderly patients is somewhat lower than in younger, the same protocols can be used for the introduction of therapy.
BACKGROUND AND METHODS: To determine the effects of reduced cerebral perfusion pressures produced by hemorrhage alone or in combination with intracranial hypertension on thromboxane A2 (TxA2) production, we undertook a randomized study in 38 anesthetized, mongrel dogs. Animals were subjected to 30 mins of hemorrhagic shock with normal (group 1) or increased (group 2) intracranial pressure (ICP). Group 1 animals (n = 22) were hemorrhaged to reduce cerebral perfusion pressure to 40 mm Hg for 30 mins. In group 2 (n = 16), cerebral perfusion pressure was reduced by the combination of less severe hypotension and intracranial hypertension (20 mm Hg). Cerebral and systemic hemodynamic measurements were recorded, including cerebral blood flow (sagittal sinus outflow method); ICP; cerebral perfusion pressure; and arterial and cerebral venous concentrations of TxB2 (double-antibody radioimmunoassay technique), the major metabolite of TxA2. Data were obtained at baseline and at the beginning and end of the 30-min shock period. RESULTS: Hemorrhagic shock significantly (p less than .05) decreased cerebral blood flow in both groups. At the beginning of the shock period, cerebral blood flow was higher in group 1 than in group 2 (p less than .05) and venous-arterial differences in TxB2 increased significantly (p less than .05) in group 2, but not in group 1. At the end of the 30-min shock period, venous-arterial levels of TxB2 remained significantly (p less than .05) higher in group 2. CONCLUSIONS: Increased cerebral production of TxA2 during hypotension accompanied by intracranial hypertension may contribute to the severity of neural damage produced by the combination of head trauma and shock.
Information was abstracted from the hospital notes of 144 doctors who had received treatment for drug and alcohol dependency. These problems affect those in every specialty, and at all degrees of seniority. Over half came into treatment following medical referral. Social morbidity was an important contributory reason for seeking help. The mean age at presentation was 43.1 years; the mean duration of problematic use prior to this was 6.4 years for drug misusers and 6.7 years for alcohol misusers. Alcohol was the current problem for 41.6% and drug misuse for 26.4%; 31.3% were misusing both alcohol and drugs at presentation. Of the 83 subjects who were misusing drugs, only four had ever used blackmarket supplies. Psychotropic agents are readily available to doctors, but the consequences of this are not addressed. Those who develop dependency suffer a delay of years before reaching help.
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