Acute and subchronic effects of Org 2305 and diazepam on psychomotor performance in man.

Three doses (15, 30 and 60 mg) of Org 2305 (O 15, O 30 and O 60 respectively), a novel anxiolytic drug chemically related to mianserin, were compared with placebo and 15 mg diazepam (DZ) on human psychomotor performance in a double-blind, cross-over study with 15 healthy volunteers. Objective measurements (choice reaction, tracking, flicker fusion, Maddox wing, digit symbol substitution, memory recall) and subjective assessments (visual analogue scales) were done at baseline and 2 and 13 h after the first dose. This testing procedure was repeated on day 7 when administering the seventh consecutive daily night-time dose. After the first dose O 15 did not differ from placebo and O 30 rarely differed from placebo. O 60 impaired various objective functions similarly to, or less than DZ. Subjectively, DZ and O 60 were felt as sedative. During subchronic treatment, DZ caused some impairment of baseline due to accumulation of bioassayable benzodiazepines, but significant responses to the last DZ dose were less than those to the first dose. DZ but not O 60 was reported to have caused lethargy and clumsiness during subchronic treatment. In the doses used Org 2305 impaired psychomotor performance less than diazepam did. A dose of 60 mg Org 2305 may offer some advantage over 15 mg diazepam, provided that their anxiolytic effects are about similar.     

Constrictive pericarditis following coronary bypass reoperation. Fibrotic pericardium and a foreign body reaction

A 65-year-old male patient underwent two bypass operations because of coronary artery disease. After the second operation he developed congestive heart failure with breathlessness, ankle swelling, hepatomegaly and poor exercise tolerance. Echocardiographic and haemodynamic findings were characteristic of constrictive pericarditis. Pericardiectomy was performed three months after the second operation. The retrosternal space was replaced with fibrotic, patchy hyalinic tissue, and the pericardium was thick and rigid. Histologically, the thickened pericardium showed dense fibrosis and foreign-body granulomas with large multinuclear giant cells and irregular crystals. This report indicates that foreign body reaction following coronary artery bypass operation may result in constrictive pericarditis with severe heart failure.     

The multifidus muscle in patients with lumbar disc herniation. A histochemical and morphometric analysis of intraoperative biopsies

Structural changes in the multifidus muscle were analyzed in 41 patients operated on for herniated intervertebral disc. Twelve cadavers served as controls. The two main findings follow: Both in the patients and in the controls the Type 2 muscle fibers were markedly and selectively smaller than the Type 1 fibers, which were of normal size for striated muscles, and the internal structure of Type 1 fibers showed so-called core-targetoid and/or moth-eaten change. Group atrophy or fiber-type grouping (indicators of denervation and reinnervation) were observed only in a few patients. The selective small size of the Type 2 fibers may indicate atrophy due to relative inactivity of the multifidus muscle both in the patients and in the controls, ie, it does not need to be related to the herniated disc. Definite proof for denervation of the multifidus muscle was not observed, but neither the possibility be excluded. The cause of the core-targetoid and/or moth-eaten changes cannot yet be determined with certainty, because these changes are not specific for any single entity but may be due, for example, to denervation, ischemia, or altered use of the muscles because of pain. In any case, because the changes were significantly more common in the patients than in the controls, they signal for a pathologic condition, the character of which remains to be elucidated.     

Cultured rat kidney parenchymal components are damaged by cytotoxic lymphocytes produced in MLC

Donor-specific cytotoxic lymphocytes (CTL) can be recovered from rejecting allografts both in animal models and in humans. These allograft infiltrating CTL expressing specific cytotoxicity to relevant MHC-restricted target cells in vitro most likely constitute the major effector arm during rejection. Effector cells with similar phenotype, specificity and function can be produced in mixed lymphocyte cultures (MLC). Despite the pivotal importance of CTL in allograft rejection, there is limited information about the susceptibility of different parenchymal graft cells to CTL-mediated damage. We used cultured rat glomerular epithelial cells (GEPC), glomerular mesangial cells (GMC), tubular cells (TC) and heart endothelial cells (HEC) as distinct parenchymal target components in 4 h Chromium release assays. All of these graft components were damaged by CTL produced in 6-day MLC (specific release: 10-25%). Three-day gamma-interferon (IFN-G) treatment enhanced MHC class I and II surface expression on all our targets and increased their susceptibility for CTL-mediated lysis in our experiments (specific release: 20-60%).     

Alcohol and drug interactions

Interactions of ethyl alcohol with various drugs are common. Their consequences vary depending on the effects of the drugs concerned, the doses of drugs and alcohol given and their mode of administration. Pharmacokinetic interactions refer to altered tissue concentrations of alcohol or drugs or both and their metabolites which sometimes lead to serious toxic reactions. The kinetic interactions take place in the absorption or metabolism of alcohol or the drug, whereas significant interactions in their distribution phase are rare. Pharmacodynamic interactions refer to the combined actions, even serious ones, which primarily take place at the tissue (receptor?) level, with or without an important pharmacokinetic component of interaction. Acute substantial doses of alcohol given quickly tend to inhibit microsomal drug metabolism and thus enhance the effects of drugs. Chronic administration of alcohol usually induces the synthesis of cytochrome P-450 isoenzyme P-450 II E1, thus accelerating the metabolism of its own and, depending on the circumstances, of various drugs as well. Reduced actions of the agents may then ensue. If the (toxic) effect of a drug (e.g., paracetamol) depends on the formation of active metabolites acute intake of alcohol may, paradoxically, reduce the drug effect, while chronic alcohol intake enhances it. Induction of hepatic enzymes by alcohol may affect the turnover of endogenous vitamins and hormones, or even produce carcinogenic substances.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use and knowledge of hormonal emergency contraception

Hormonal emergency contraception (EC) is an acceptable means of postcoital prevention of pregnancy, but potential users should have information and education about it before they need it. The aim of this study was to establish how many women and how many men's partners have used hormonal EC and how well the respondents know the correct time to take EC pills. Random samples (393 women and 395 men) were drawn from the Finnish population register. Response rates were 56% for women and 45% for men. Of all responding women and men, 12% had themselves or together with their partners used EC. The proportion of EC users was highest in the younger age group among both women and men. It was greater among single and cohabiting women than among married women. Only a minority of respondents knew that EC pills could be taken up to 72 h after unprotected intercourse. Women who had used EC were most knowledgeable, as were also the younger age groups among both women and men. Awareness of the availability of EC and of its correct use should be further promoted to avoid unwanted pregnancies.     

Bone Stress Injuries Are Common in Female Military Trainees: A Preliminary Study

Although bone stress injuries are common in male military trainees, it is not known how common they are in female trainees. It also is unclear whether asymptomatic bone stress injuries heal if intensive training is continued. We prospectively followed 10 female trainees of a military Reserve Officer Course. The subjects underwent clinical and MRI examinations of the pelvis, thighs, and lower legs at the beginning, once during, and at the end of their 3-month course. We identified two to five injuries in every female trainee, all of whom already had the injuries at the beginning of the officer course. None of these injuries increased their severity despite vigorous training. Two-thirds were asymptomatic and low grade. Femoral and tibial shafts were the most common locations. Higher-grade injuries were more likely symptomatic, but regardless of the MRI findings, female trainees expressed only mild to moderate symptoms. Asymptomatic, low-grade bone stress injuries of the femoral and tibial shaft are common in female recruits undergoing heavy physical training. Because these injuries seem to remain constant or even disappear despite continued heavy physical activity, we do not recommend routine screening of asymptomatic trainees. As some bone stress fractures may have severe consequences (eg, in the femoral neck), symptomatic bone stress injuries should be examined and treated.