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Biomedical subjects

P Sedgwick

Publications and source records attributed to P Sedgwick.

17 recordsLinked to original sources

Mortality in people with learning disability: risks, causes, and death certification findings in London.

Two thousand people with learning disabilities registered as service users in two London districts were followed up for 8 years to ascertain, in those who died, age and cause of death and significant associations with early death. Respiratory disease was documented as the leading cause of death in 52% of the study population compared with only 15% of males and 17% of females in the whole population. People with learning disabilities have an increased risk of early death. Although the majority of deaths (83%) in the whole population occur in people aged 65 years and over, less than 50% of deaths in the study population were in this age group, and the risk of dying before the age of 50 was 58 times higher than in England and Wales generally. Early death was significantly associated with cerebral palsy, incontinence, problems with mobility, and residence in hospital. Death certificates were not found to be a reliable source of data about factors contributing to cause of death, and learning disabilities were rarely mentioned. The authors recommend an extension to the current format of the Medical Certificate of Death to include recording of chronic disabling conditions.

Adolescent

Subjective sleep-wake parameters in treatment-seeking opiate addicts.

We investigated subjective sleep parameters and sleep difficulties of opiate addicts undertaking methadone detoxification and identified their sleep profile. Using the St Mary's Sleep Questionnaire, we compared the subjective sleep parameters of 27 consecutively consenting patients (16 males, 11 females) with a mean age of 33 years (S.D. = 7.5) undertaking in-patient methadone detoxification with those of 26 drug-free controls (9 males, 17 females) with a mean age of 35 years (S.D. = 8.0). Our findings reveal that subjective sleep parameters of opiate addicts and controls are quantitatively and qualitatively different. The patients are more likely than controls to report difficulty initiating sleep (OR = 5.42; 95% CI = 1.43, 20.47); difficulty maintaining sleep (OR = 16.50; 95% CI = 3.81, 71.47); inadequate sleep quality (OR = 8.56; 95% CI = 2.04, 35.81); and inadequate sleep quantity (OR = 9.00; 95% CI = 2.49, 32.57).

Adult

Kinetics of endotoxin-induced acute-phase protein gene expression and its modulation by TNF-alpha monoclonal antibody.

The kinetics of cytokine release and acute-phase protein gene expression in liver were investigated in rats receiving a single intraperitoneal bolus dose of Escherichia coli lipopolysaccharide (LPS). Transient elevation of plasma tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were detected. Hepatic messenger RNAs for two acute-phase proteins, alpha 1-acid glycoprotein and alpha 2-macroglobulin, were measured by Northern blotting and were found to increase to a maximum at 24 h, returning to normal by 72 h; plasma concentrations showed a slower but more sustained rise. For albumin, hepatic mRNA was reduced, being minimum at 24 h with a similar but more prolonged fall in plasma concentration. Pretreatment of rats with TNF-alpha monoclonal antibody 4 h before LPS ameliorated weight loss and anorexia, partially suppressed the rise in IL-6 and reduced the increase in hepatic mRNA and plasma concentrations of alpha 1-acid glycoprotein and alpha 2-macroglobulin. For albumin, however, such pretreatment had no effect on the fall in either hepatic mRNA or plasma concentration. Thus we have defined an in vivo role of TNF-alpha in the control of endotoxin-induced acute-phase protein generation.

Acute-Phase Proteins

Double-blind placebo-controlled trial of amitriptyline among depressed patients in general practice.

Depressed patients in general practice were included in a double-blind placebo-controlled six-week trial of amitriptyline (median dose 125 mg). The patients were relatively mildly ill and satisfied diagnostic criteria for depression and treatment with antidepressants in routine practice. Amitriptyline was found to be considerably superior to placebo after six weeks and significantly so as early as two weeks after the start of treatment. The effects of the antidepressant were on the core symptoms of depression, and were apparent in all but the most mildly ill patients. The findings suggest that tricyclic antidepressants are of considerable therapeutic benefit to depressed patients in general practice.

Adolescent

The use of brain digoxin concentrations to confirm blood digoxin concentrations.

Recent research suggests that the cardiotoxic as well as the neurotoxic effects of digitalis may be mediated by the central nervous system. Therefore brain regions implicated in the genesis of cardiac rhythm disorders were assayed for digoxin. An 125I-labeled radioimmunoassay was used to determine blood and tissue digoxin concentrations. Digoxin was found in the optic tract and optic chiasm in each of four persons who had been taking digoxin regularly. Digoxin is apparently concentrated from blood by the choroid plexus of the fourth ventricle but not by the choroid plexus of the lateral ventricle. However, digoxin was present in the area postrema and nucleus of the vagus only in the two digoxin overdose cases. Digoxin was not detected in any of the other brain regions analyzed. The presence of digoxin in the area postrema (the chemoreceptor trigger zone) and the nucleus of the vagus in the toxic but not in the therapeutic cases suggests a mechanism for the emesis and cardiac arrest brought about by digoxin toxicity in humans. The digoxin content of the medulla, especially the surface of the medulla under the obex, may be useful in confirmation of elevated blood digoxin concentrations.

Aged

Predictors of therapeutic benefit from amitriptyline in mild depression: a general practice placebo-controlled trial.

General practice depressives were treated for 6 weeks with amitriptyline or placebo in a controlled trial. Overall, drug was found strongly superior to placebo. Interactions were examined between drug effects and a number of variables, principally reflecting demographic characteristics, history of illness, severity of illness, and endogenous depression separately in symptoms and stress. Only in the area of severity were significant interactions found. Amitriptyline was superior to placebo in probable or definite major depression on the Research Diagnostic Criteria, but not in minor depression. It was also superior to placebo in subjects with initial scores on the Hamilton Depression Scale of 13-15, and 16 or more, but not with lower scores. Findings indicate that tricyclic antidepressants are of considerable benefit in relatively mild depressions, except in the mildest range.

Adolescent

Serum propoxyphene concentrations in a cohort of opiate addicts on long-term propoxyphene maintenance therapy. Evidence for drug tolerance in humans.

Propoxyphene, norpropoxyphene, and cyclic dinorpropoxyphene concentrations in the sera of eight opiate addicts were measured by gas chromatography. The addicts were enrolled in a propoxyphene maintenance program and had received 800-1600 mg of propoxyphene napsylate daily for 13-50 months. Serum propoxyphene and norpropoxyphene ranged from 127 to 1070 ng/mL and 814 to 2638 ng/mL, respectively, and their ratio ranged from 0.1 to 0.4. A roughly linear dose-to-serum-concentration relationship was found for serum propoxyphene and norpropoxyphene in the cohort. Cyclic dinorpropoxyphene was detected in three of the subjects' sera. Because tolerance to propoxyphene occurs, knowledge of prior drug exposure is necessary to determine whether an elevated propoxyphene or norpropoxyphene concentration is toxic to patients or decedents with apparent propoxyphene overdose. Serum norpropoxyphene concentration exceeds that of propoxyphene following chronic propoxyphene use. Measurable cyclic dinorpropoxyphene implies chronic propoxyphene use but its absence does not exclude chronic use.

Adult

Toxicological findings in amoxapine overdose.

Tissue concentrations of amoxapine, a new antidepressant with antipsychotic properties, were determined in two cases in which amoxapine was taken in overdose. Two extractions and GLC procedures, UV spectra, and TLC properties of amoxapine are described. The concentrations of amoxapine are described. The concentrations of amoxapine in brain tissue (52 micrograms/g and 53.2 micrograms/g) were about equal to concentrations found in liver (77 micrograms/g and 50 micrograms/g) and higher than blood concentrations (6 micrograms/mL and 1.5 micrograms/mL). The two metabolites of amoxapine, 8-hydroxyamoxapine and 7-hydroxyamoxapine, were not detected by TLC or GLC.

Adult

Radioimmunoassay screening and GC/MS confirmation of whole blood samples for drugs of abuse.

From 1981 to 1984, an average of 300 radioimmunoassay screens on whole blood were performed each week in the authors' laboratory. Most samples were screened for opiates, phencyclidine and its analogs, barbiturates, and cocaine or its metabolite benzoylecgonine. A commercially available radioimmunoassay was used with modifications to facilitate screening of whole blood. Increasing sample size increased the sensitivity of the assay. Changing reagent concentration (1:1 dilution), incubation time, sample matrix (water, urine, or blood), or fraction counted (precipitate or supernatant) did not affect the utility of the standard curve or the sensitivity of the assay. All positive results for phencyclidine, opiates, cocaine, and related compounds were confirmed by GC/MS. Barbiturate positives were confirmed by UV spectrophotometry. The rate of confirmation in postmortem bloods from coroner's cases for 1981-84 was: cocaine/benzoylecgonine, 57%; opiates, 79%; phencyclidine, 49%; and barbiturates, 58%.

Ammonium Sulfate

Sleep disorders.

Sleep disorders carry a high risk of morbidity and mortality, yet they receive little medical attention. This article outlines the clinical features, aetiology, diagnosis and management of some common sleep disorders.

Cognitive Behavioral Therapy