Influence of nicotine on myocardial stiffness and fibrosis during chronic ethanol use.

Cardiomyopathy related to ethanol abuse is often accompanied by cigarette use. To examine if the major cardioactive component may intensify the abnormal function and composition induced by chronic ethanol, nicotine was administered orally, 2.5 mg bid, to a canine model receiving 36% of calories as ethanol for 6 months (group III). These animals were compared with group II receiving ethanol alone, group IV on nicotine alone, and controls (group I). In the intact, ventilated, anesthetized dog, left ventricular pressures and volumes were measured before and after dextran infusion and related to left ventricular collagen alterations. Basal heart rate, aortic pressure, and ejection fraction were comparable with controls. End-diastolic pressure and diastolic chamber stiffness (KPV) were significantly higher in the basal state and during dextran infusion in the three experimental groups, compared with group I. The increment was largest in the ethanol-nicotine group. Analysis of left ventricular myocardium revealed a rise of collagen concentrations in all three experimental groups, with an interstitial distribution on histochemical examination. Moreover, determination of advanced glycosylation endproducts, as a measure of alterations in collagen cross-links, revealed higher concentrations versus controls. The greater increase of diastolic stiffness in the nicotine-ethanol group occurred despite a similar concentration of fluorescent products as group II. Because the former had a larger increase of collage concentration, total cross-linked collagen content was presumably greater after the combined use of nicotine-ethanol. Thus, nicotine in relatively high dose when combined with ethanol, elicited a modest further increase in the left ventricular chamber stiffness and collagen concentration.

Tyrosylprotein sulfotransferase activity is increased in human gastric mucosa of alcoholics.

Sulfation plays a major role in the processing of secretory proteins. We report here on tyrosylprotein sulfotransferase activity in human gastric mucosa of normal and alcoholics. The tyrosylprotein sulfotransferase was identified in the Golgi-enriched fraction. In alcoholics, the activity of sulfotransferase was 2- to 3-fold higher than in normals. However, no change in the activity of UDP-glucose-ceramide glucosyltransferase, a marker for Golgi, between alcoholics and normals was observed. The tyrosylprotein sulfotransferase enzyme required Triton X-100, MnCl2 and 5'-AMP, and obtained optimum activity at pH 6.8 in the presence of 0.5% Triton X-100, 20 mM MnCl2, 50 mM NaF, and 2 mM 5'-AMP. The apparent Km for poly-Glu6, Ala3, Tyr1 (EAY; 47,000) was 1.9 x 10(-6) M and for 3'-phosphoadenosine 5'-phosphosulfate (PAPS), 1.4 x 10(-6) M. The results suggest that alcohol abuse causes enhancement in the expression of gastric mucosal tyrosylprotein sulfotransferase activity.

Psychiatric screening of admissions to an accident and emergency ward.

One hundred medical and surgical patients admitted to an accident and emergency ward were screened for psychiatric disorder. A psychiatric diagnosis was made in 37 patients, 32 of whom were correctly identified by the GHQ. Psychiatric morbidity was associated with being single, lower social class, unemployment, homelessness and living in Bloomsbury Health District or north-east London. It was also associated with not being registered with a GP. The 14 overdose patients were no more likely to receive a psychiatric diagnosis than other patients, yet constituted most of the psychiatric referrals. Few patients were asked by medical staff about emotional worries or problems. A desire to be asked such questions and a past psychiatric history were associated with a psychiatric diagnosis. Routine screening of psychiatric morbidity in both medical and surgical patients and appropriate psychiatric referral of identified patients is recommended. A system of facilitating GP registration is necessary, as much of the morbidity identified could be contained within primary care.

Protection against alcohol-induced gastric mucosal injury by nitecapone.

1. The mechanism of gastric mucosal protection by an anticular agent, nitecapone, against injury was investigated in rats with and without indomethacin pretreatment. 2. Animals received intragastrically either a dose of nitecapone or vehicle alone, followed by ethanol given at various intervals up to 5 hr, and their gastric mucosa subjected to histologic and physicochemical assessment. 3. Ethanol caused extensive gastric hemorrhagic lesions which were essentially prevented by nitecapone at doses of 30 mg and higher per kg body weight. The maximal protection was achieved by 1.5 hr which persisted up to 4 hr and was not thwarted by indomethacin. 4. Physicochemical measurements revealed that nitecapone evoked 78% increase in mucus gel dimension, and showed 21% increase in phospholipids, and the content of sulfo-(22%) and sialomucins (72%). This was accompanied by 1.6-fold increase in mucus viscosity, 31% increase in H+ retardation capacity and 2.2-fold increase in hydrophobicity. 5. The results suggest that the gastroprotective action of nitecapone occurs through the enhancement of the physicochemical characteristics of mucus layer.

Screening for psychiatric morbidity in an accident and emergency department.

One hundred and twenty A&E Department daytime attenders were screened for psychiatric disorder in a two stage procedure. Thirty-three patients were identified as General Health Questionnaire (GHQ) 'cases' of whom 28 agreed to a psychiatric interview using the Clinical Interview Schedule. Twenty-eight GHQ 'non-cases' were also interviewed. A psychiatric diagnosis was made in 24 patients, 21 of whom were GHQ cases. Patients were more likely to suffer from psychiatric morbidity if the presenting complaint was other than minor trauma. There were trends for psychiatric morbidity to be associated with not being married and living in Bloomsbury Health District (No Fixed Abode or resident) or Northeast London. Sixty-nine percent of cases had a positive past psychiatric history. Ten of 12 cases (83%) requiring primary care intervention were not registered with a GP. It is suggested that appropriate intervention would be for A&E Departments to routinely facilitate such registration. In addition, resources need to be released to make 9am to 5pm walk-in psychiatric services commonplace.