Benzodiazepine Dependence

Benzodiazepines, the most widely used of all drugs, are powerful anxiolytics, anticonvulsants and muscle relaxants. Dependence is difficult to induce in animals but has been induced by high doses in man. Case reports of benzodiazepine dependence are rare compared with the usage of these drugs, but do not provide a proper epidemiological framework for the estimation of risk. Patients taking these drugs for four months or more may develop a physical withdrawal syndrome, characterized by anxiety, dysphoria, malaise, depersonalization, and by perceptual changes such as hyperacusis and unsteadiness. In our experience drawn from over 20 patients, withdrawal from therapeutic doses of a benzodiazepine may be attended by a fully-developed physical withdrawal syndrome.     

Aminosugar derivatives as potential anti-human immunodeficiency virus agents.

Recent data suggest that aminosugar derivatives which inhibit glycoprotein processing have potential anti-human immunodeficiency virus (HIV) activity. These inhibitory effects may be due to disruption of cell fusion and subsequent cell-cell transmission of the acquired immunodeficiency syndrome (AIDS) virus. Free virus particles able to bind CD4-positive cells are still produced in the presence of these compounds with only partial reduction of infectivity. We now report a method to score in parallel both the degree of antiviral activity and the effect on cell division of aminosugar derivatives. We find that (i) the compounds 1,4-dideoxy-1,4-imino-L-arabinitol and N-(5-carboxymethyl-1-pentyl)-1,5-imino-L-fucitol partially inhibit the cytopathic effect (giant cell formation, etc.) of HIV and yield of infectious virus; (ii) the compounds N-methyldeoxynojirimycin and N-ethyldeoxynojirimycin reduce the yield of infectious HIV by an order of four and three logarithms, respectively; and (iii) one compound, N-butyldeoxynojirimycin, of the 47 compounds previously screened reduces infectious viral particles by a logarithmic order greater than five at noncytotoxic concentrations. In addition, long-term growth of infected cells in the presence of N-butyldeoxynojirimycin gradually decreases the proportion of infected cells, leading to eventual elimination of HIV from culture. This result suggests that replication is associated with cytolysis. The ability to break the cycle of replication and reinfection has important implications in the chemotherapy of AIDS.     

Patients with a history of diabetes have a lower survival rate after in-hospital cardiac arrest

AIM: To describe the association between a history of diabetes and outcome among patients suffering an in-hospital cardiac arrest. METHOD: All patients suffering an in-hospital cardiac arrest in whom cardiopulmonary resuscitation (CPR) was attempted at Sahlgrenska University Hospital in G?teborg between 1994 and 2006 and at nine further hospitals in Sweden between 2005 and 2006. RESULTS: In all, 1810 patients were included in the survey, 395 (22%) of whom had a previous history of diabetes. Patients with a history of diabetes differed from those without such a history by having a higher prevalence of previous myocardial infarction, stroke, heart failure and renal disease. They were more frequently treated with anti-arrhythmic drugs during resuscitation. Whereas immediate survival did not differ between groups (51.7% and 53.1%, respectively), patients with diabetes were discharged alive from hospital (29.3%) less frequently compared with those without diabetes (37.6%). When correcting for dissimilarities at baseline, the adjusted odds ratio for being discharged alive (diabetes/no diabetes) was 0.57 (95% CL 0.40-0.79). CONCLUSION: Among patients suffering an in-hospital cardiac arrest in Sweden in whom CPR was attempted, 22% had a history of diabetes. These patients had a lower survival rate, which cannot simply be explained by different co-morbidity.     

Eye movement deficits in schizophrenia

BACKGROUND: Deficits in antisaccade (AS) and smooth pursuit eye movements (SPEM) are promising endophenotypes in genetic studies of schizophrenia. The Icelandic population lends itself ideally to genetic studies due to its ethnic homogeneity and well-documented genealogy. The primary aim of this study was to assess AS and SPEM performance in a large Icelandic sample. Additional aims were to investigate the relationship between AS and SPEM task performance and to assess internal consistency, within-session performance changes and effects of SPEM target velocity on performance. METHOD: Patients with schizophrenia (N = 118) and healthy controls (N = 109) matched for age and gender underwent infrared oculographic assessment of AS and SPEM (at target velocities of 12 degrees , 24 degrees and 36 degrees /s). RESULTS: On the AS task patients displayed significantly more reflexive errors, longer latency, increased intra-individual latency variability, and reduced amplitude gain compared to controls. On the SPEM task, patients had significantly lower velocity gain and more frequent saccades during pursuit at all velocities, but group differences in velocity gain increased with increasing target velocity. Internal consistency of performance was high for all variables in both groups (Cronbach's alpha >0.77 for AS and >0.85 for SPEM) except for AS spatial error in patients (alpha = 0.38). A moderate association was found between AS and SPEM performance. By and large, patients and controls showed similar patterns of systematic within-session performance changes. CONCLUSIONS: Our findings confirm the existence of robust eye movement deficits in schizophrenia in a large sample. These measures may be studied as endophenotypes in future studies of potential schizophrenia risk genotypes in the genetically homogenous Icelandic population.     

Additive effects of moderate dietary salt reduction and captopril in hypertension

In a randomized, cross-over study 27 patients had diastolic blood pressure of greater than or equal to 96 mmHg during four visits without treatment. Following captopril 25 mg b.i.d. nine patients' blood pressure was less than or equal to 90 mmHg. The remaining 18 were randomized into two treatment modalities, captopril and moderate dietary salt reduction, and captopril and hydrochlorothiazide 25 mg daily. Following a wash-out period the groups crossed over to the alternative treatment. At the end of the control period the average blood pressure was 151/100 +/- 12/6 mmHg recumbent and 140/91 +/- 11/7 standing, following captopril 144/94 +/- 13/5 and 132/92 +/- 12/6, respectively, with low salt diet added to captopril 140/91 +/- 12/6 and 128/89 +/- 11/6 and with hydrochlorothiazide and captopril 133/86 +/- 12/7 and 120/84 +/- 11/7 mmHg supine and erect, respectively. It is concluded that moderate dietary salt reduction, which is easily advised, will significantly potentiate the blood pressure fall following captopril treatment in moderate arterial hypertension.     

Pathogenesis of visna. III. Immune responses to central nervous system antigens in experimental allergic encephalomyelitis and visna.

Experimental allergic encephalomyelitis (EAE) was induced in sheep in pursuit of the hypothesis that an immune response against central nervous system antigens might play a role in the pathogenesis of visna. Nine to 12 days after sensitization with whole sheep brain and complete Freund's adjuvant, approximately 50% of sheep developed a fulminating lethal form of EAE. Following a second sensitization, another 20% of animals developed EAE whereas a residual 30% failed to develop any signs or histologic evidence of disease. A histologic comparison of EAE and visna indicated considerable similarity in the nature of the pathologic process. However, the distribution of lesions was quite different, suggesting cellular responses to two different antigens, Cell-mediated immunity to myelin basic protein, as measured by lymphocyte blast transformation, was minimally elevated in sheep sensitized with whole brain suspension in complete Freund's adjuvant, whereas no response could be detected in visna-infected sheep. Complement-fixing antibody titers to basic protein and to a lipid antigen of brain, probably galactocerebroside, rose briskly after sensitization. In visna-infected sheep, on the other hand, there was no increase in either antibody. A large proportion of both Hampshire and Icelandic sheep had low levels of complement-fixing antibody to central nervous system antigens prior to induction of EAE or infection with visna virus. The origin of this antibody is undetermined, but it appeared to have no effect on the course of either disease. Immunosuppression of sheep with antilymphoid serum prevented induction of EAE. Acute EAE was, thus, successfully induced in sheep and used as a model to measure immune responses to central nervous system antigens and as an index of immunosuppression. However, these comparative studies did not provide any evidence for the role of an autoimmune response, to the two central nervous system antigens tested, in the pathogenesis of visna.     

Decreased libido--a side effect of carbonic anhydrase inhibitor

Thirty-nine cases of decreased libido in glaucoma patients on carbonic anhydrase inhibitors are reported. This symptom completely reversed or markedly improved after discontinuation of the drug in all cases. Twelve of these patients restarted their carbonic anhydrase inhibitor medication which resulted in a recurrence of decreased libido symptoms. There were 3 cases of impotency which reversed after discontinuation of the drug. Most likely, these symptoms are a result of the malaise and depression occurring in some patients on carbonic anhydrase inhibitor therapy.     

Pathogenesis of visna. II. Effect of immunosuppression upon early central nervous system lesions.

It was hypothesized that the lesions of visna might represent an immunopathologic process. To test this hypothesis, a 1-month schedule of immunosuppressive treatment was devised, using horse anti-sheep thymocyte serum. In Hampshire sheep, this regime was shown to protect against experimental allergic encephalomyelitis, to inhibit development of tuberculin hypersensitivity, to retard rejection of skin homografts by 3 weeks, and to markedly reduce the number and mitogenic responsiveness of peripheral blood lymphocytes. Two groups of Icelandic sheep received intracerebral inoculations of visna virus, and one group was treated with horse antisheep thymocyte serum supplemented by a short terminal course of cyclophosphamide. Central nervous system lesions were seen in only one of eight suppressed animals at sacrifice 25 days after infection, whereas definite lesions were present in eight of eight infected control animals. The frequency of central nervous system virus isolation was similar in the two groups, indicating that treatment suppressed the cellular proliferative response without preventing the central nervous system phase of infection. Sheep receiving horse antisheep thymocyte serum had a reduced number of virus isolations from peripheral lymphoid tissue, presumably reflecting the lympholytic effect of treatment. These observations are consistent with the immunopathologic hypothesis and suggest several different ways in which suppression could modify the immune response to visna virus.     

Genetic linkage analysis of manic depression in Iceland.

Genetic linkage analysis has been used to study five Icelandic pedigrees multiply affected with manic depression. Genetic markers were chosen from regions which had been implicated by other studies or to which candidate genes had been localized. The transmission model used was of a dominant gene with incomplete penetrance and allowing for a large number of phenocopies, especially for unipolar rather than bipolar cases. Multipoint analysis with linked markers enabled information to be gained from regions spanning large distances. Using this approach we have excluded regions of chromosome 11p, 11q, 8q, 5q, 9q and Xq. Candidate genes excluded include those for tyrosine hydroxylase, the dopamine type 2 receptor, proenkephalin, the 5HT1A receptor and dopamine beta hydroxylase. Nevertheless, we remain optimistic that this approach will eventually identify at least some of the genes predisposing to manic depression.     

Psychiatric court reports in Iceland 1970-1982

This paper looks closely at psychiatric court reports in criminal cases in Iceland. Psychiatric court reports are in the great majority of cases requested by the State Criminal Investigation Police (SCIP) on behalf of the court in major criminal cases (e.g. homicide, sexual offences, arson, physical assault). Reports are very rarely requested by the defence. During the 13-year period 1970-1982 there were 97 requests for psychiatric reports by the police/court (i.e. an annual rate of about 7.5 reports). About two-thirds of the defendants were found to have some psychiatric abnormality, although only a minority (8%) were considered criminally insane at the time of the offence. Psychiatric reports were most often requested to assess criminal responsibility, and, to a much lesser extent, sentencing issues. Psychiatric experts almost never have to present their evidence in person in court, nor are they cross-examined on their evidence. This paper discusses some of the strengths and limitations of psychiatric evidence in Iceland, and the need for an organized forensic service.