Chemical investigation of hassium (element 108).

The periodic table provides a classification of the chemical properties of the elements. But for the heaviest elements, the transactinides, this role of the periodic table reaches its limits because increasingly strong relativistic effects on the valence electron shells can induce deviations from known trends in chemical properties. In the case of the first two transactinides, elements 104 and 105, relativistic effects do indeed influence their chemical properties, whereas elements 106 and 107 both behave as expected from their position within the periodic table. Here we report the chemical separation and characterization of only seven detected atoms of element 108 (hassium, Hs), which were generated as isotopes (269)Hs (refs 8, 9) and (270)Hs (ref. 10) in the fusion reaction between (26)Mg and (248)Cm. The hassium atoms are immediately oxidized to a highly volatile oxide, presumably HsO(4), for which we determine an enthalpy of adsorption on our detector surface that is comparable to the adsorption enthalpy determined under identical conditions for the osmium oxide OsO(4). These results provide evidence that the chemical properties of hassium and its lighter homologue osmium are similar, thus confirming that hassium exhibits properties as expected from its position in group 8 of the periodic table.

Clozapine-related seizures.

Clozapine is an atypical antipsychotic drug with minimal extrapyramidal toxicity recently approved by the Food and Drug Administration for hard-to-treat schizophrenic patients. We reviewed information on 1,418 patients treated with clozapine in the United States between 1972 and 1988. Forty-one of 1,418 (2.8%) patients had generalized tonic-clonic seizures during treatment with clozapine. Life-table analysis predicts a cumulative 10% risk of seizures after 3.8 years of treatment. Clozapine-related seizures appear to be dose-related. High-dose therapy (greater than or equal to 600 mg/day) was associated with a greater risk of seizures (4.4%) than medium (300 to 600 mg/day; 2.7%) or low doses (less than 300 mg/day; 1.0%). Also, rapid upward titration may increase seizure risk. Thirty-one of 41 patients were successfully continued on clozapine despite seizure occurrence, either with reduction of dose or addition of an antiepileptic medication. Recognition and treatment of clozapine-related seizures will become increasingly important as its use grows in the 1990s.

The first double-blind, placebo-controlled trial of a partial benzodiazepine agonist abecarnil (ZK 112-119) in generalized anxiety disorder.

This is the first reported controlled trial of a partial benzodiazepine agonist, abecarnil, utilized in the treatment of generalized anxiety disorder (GAD). It was a sequential dose-finding study comparing 15-30 mg/day, 7.5-15 mg/day, and 3-9 mg/day to placebo for 3 weeks of treatment followed by abrupt discontinuation through placebo substitution. Although the two higher dose groups had high incidence of central nervous system (CNS) sedative adverse effects, the 3-9 mg/day group tolerated the medication well with no dropouts. The 3-9 mg/day group, in comparison to the two higher doses and placebo, demonstrated efficacy in global improvement ratings and Hamilton Anxiety Scale (HAM-A) scores. At Week 3, 61 percent of the abecarnil 3-9 mg/day group was rated as at least 50 percent improved on the HAM-A, compared to 30 percent of the placebo group. With abrupt discontinuation there were mild to moderate withdrawal symptoms and loss of efficacy in the two higher dose groups. However, in the 3-9 mg/day abecarnil group, there were few withdrawal symptoms and almost no loss of efficacy following discontinuation.

A two-year clinical and economic follow-up of patients on clozapine.

The long-term efficacy of clozapine therapy and its effect on health care costs were examined over a two-year period. Patients on clozapine showed marked clinical improvement as measured by the Brief Psychiatric Rating Scale. They also had significantly lower rates of rehospitalization and hospitalization costs than a comparison group of schizophrenic patients who received standard neuroleptic treatment and who were considerably less psychotic at hospital admission. By the second year of the study, savings on mental health care costs averaged $20,000 for each patient on clozapine therapy. The savings were due largely to the patients' change in residence from costly inpatient facilities to less expensive settings in the community.

Predictors of response to clozapine therapy.

Multiple regression analysis and discriminant function analyses were applied to the question of prediction of therapeutic success or failure to clozapine therapy, using a non-biological predictor pool of 46 items. This effort was not successful, accounting for less than 25% of outcome variance under optimal conditions. However, it does appear that while clozapine efficacy in treatment-resistant schizophrenic patients in general is superior to such neuroleptics as chlorpromazine or haloperidol, the "paranoid" subgroup appears to benefit most.

Coagulation factor concentrate usage and the risk of lymphadenopathy: a prospective study.

A prospective evaluation of 115 patients with hemophilia was performed between July 1982 and July 1983. During that period, 24 patients were seen with unexplained, generalized lymph node enlargement. The date lymphadenopathy occurred was recorded. No lymphadenopathy was found in 22 patients who did not receive coagulation factor concentrate. Factor usage was most closely related to the risks of lymphadenopathy (p = 0.004) even after controlling for age. A patient's age affected the risk of lymphadenopathy when the data were analyzed categorically (p = 0.008). A tendency was seen for heavily treated patients to develop lymph node enlargement earlier in the study period. Twenty-one of twenty-four (88%) patients with lymphadenopathy eventually developed HTLV-III/LAV antibodies and had abnormal T4/T8 ratios. These studies emphasize a close relationship between patients with hemophilia using coagulation factor concentrates and those with other risks for immune deficiency and lymphadenopathy. Close follow-up, optimal use of blood products, and further efforts to understand the importance of such changes are indicated in patients with hemophilia.

Replicated evidence on the construct validity of the SCAG (Sandoz Clinical Assessment-Geriatric) scale.

Factor analysis procedures, applied to a data bank of 1165 senile patients from 21 double-blind studies, yielded 5 factors: cognitive dysfunction (4 items), interpersonal relationships (4 items), apathy (4 items), affect (3 items) and somatic function (3 items). A retrospective review of the 1165 case histories revealed that patients fell into three distinct diagnostic classes: (a) patients whose symptoms of dementia were likely associated with multiple infarcts; (b) patients with other medical disorders such as metabolic imbalances, pulmonary diseases, etc. which may have induced dementia-like symptoms; and (c) primary degenerative dementia for patients with no evidence of other intervening causes. Factor analysis applied independently to the SCAG data of each of the three groups produced similar factor constructs, thereby suggesting that results reported with this instrument are valid across different geriatric diagnostic categories.

[Sandoz Clinical Assessment Geriatric Scale: a transcultural factor-analytic study]. / Sandoz Clinical Assessment Geriatric Scale (SCAG): Eine transkulturelle faktorenanalytische Studie.

To date only a few scales claimed to be valid and reliable exist that are designed to assess symptoms and signs of mental deterioration in the aging patient. One such scale, the SCAG, was presented by Venn et al. in the early seventies in the USA as an instrument designed to provide a picture of the cognitive, affective, social and somatic functions of the patient and to measure the effects induced by geriatric drugs on this picture. It consists of 18 items that have to be rated on a scale from 1 to 7. Along with the English original, German and French translations of this scale have been widely used in clinical trials in Europe. Their properties would not be assumed to be the same, especially when they are used in countries with different cultural backgrounds. Thus, a comparative study of the construct validity (by means of factor analyses) of the English, German and French versions of the SCAG, using 5 samples from different European countries, has been performed. As reference served a factor analysis of the SCAG based on 1165 pre-treatment values from 21 American trials. In all but one sample essentially the same structure with five factors emerged (in one case two factors were confounded).