Treatment of osteoporosis in men

Osteoporosis in men is recognised worldwide as an important and increasing public health problem. The causes are more heterogeneous than those in women. About 50% are diagnosed as secondary cases. In some secondary forms of osteoporosis the specific diagnosis results in additional therapeutic options (e.g. androgen therapy in proven hypogonadism). The basic therapy for osteoporosis in men is no different to that in postmenopausal women, namely recommendations for counteracting modifiable risk factors, especially with regard to diet, physical exercise, and calcium and vitamin D supplementation. Concerning specific drug medications, however, even today there is still a therapeutic dilemma in male osteoporosis. While older substances (e.g. calcitonin, fluoride, alfacalcidol) are approved for both sexes, all newer medications have primarily been approved for the treatment of postmenopausal osteoporosis. Health authorities request studies in purely male populations. For new drugs, fracture data are necessary while for new substances within a class (e.g. bisphosphonates), at the very least consistent effects on bone mineral density (BMD) and bone turnover markers are requested. Due to these regulatory rules, ibandronate, teriparatide and strontium ranelate are not approved in the European Union. Some years ago, alendronate was the first bisphosphonate that was approved for the treatment of men with osteoporosis, based on consistent results from two independent male studies using a daily 10 mg dosage. Very recently risedronate was approved by the FDA and EMEA. A randomised, placebo-controlled multicentre trial of 285 male patients showed, after 2 years, a 5.8% increase in lumbar spine BMD in the risedronate 35 mg once weekly group vs 1.2% in the placebo group. In a prospective controlled study on 316 men with primary or secondary osteoporosis we found, after 12 months, a lumbar spine BMD of +4.7% vs +1.0% in controls. The number of patients with one or more new vertebral fractures was 8 in the risedronate group and 20 in the placebo group (a fracture reduction of 60%). Furthermore, we found a significantly smaller decrease in height and a steeper decrease in back pain in the risedronate group. Risedronate is the first oral bisphosphonate available for men with the more comfortable once weekly dosage.     

The Ab-Adductometer: a new device for measuring the muscle strength and function of the thumb.

The purpose of this study was to present normative values for thumb abduction and adduction and also to present measures of reliability of the measuring system arising from the use of the Ab-Adductometer. With the Ab-Adductometer, we obtained abductor and adductor measurements of intrinsic muscle strength of the healthy hand thumb in 600 volunteers. Handgrip strength values were obtained with the Jamar dynamometer. Age and male-female specific reference ranges for the Ab-Adductometer and the Jamar dynamometer are presented. This study, with a very large number of volunteer subjects, 600, presents reference ranges for pure palmar adduction and abduction of the thumb. The results indicate that the Ab-Adductometer is a clinically useful device for the purpose of quantitatively measuring thumb adduction and abduction strength at various starting angles of thumb abduction relative to the plane of the palm. The device may be especially helpful in the evaluation of compressive neuropathies of the median or ulnar nerves such as carpal tunnel syndrome or cubital tunnel syndrome as well as for primary disease of the peripheral nerves that affect intrinsic muscles and for thumb function in proximal conditions such as tetraplegia and brachial plexopathy.     

A human amphotropic retrovirus receptor is a second member of the gibbon ape leukemia virus receptor family.

Retrovirus infection is initiated by binding of the viral envelope glycoprotein to a cell-surface receptor. The envelope proteins of type C retroviruses of mammals demonstrate similarities in structural organization and protein sequence. These similarities suggest the possibility that retroviruses from different interference groups might use related proteins as receptors, despite the absence of any relationship between retrovirus receptors isolated to date. To investigate this possibility, we have identified a human cDNA clone encoding a protein closely related to the receptor for gibbon ape leukemia virus and have found that it functions as the receptor for the amphotropic group of murine retroviruses. Expression of this protein (GLVR-2) is likely to be a requirement for infection of human cells by amphotropic retroviral vectors for purposes of gene therapy.     

A 2-year prospective follow-up study of children and adolescents with disruptive behavior disorders. Prediction by cerebrospinal fluid 5-hydroxyindoleacetic acid, homovanillic acid, and autonomic measures?

A 2-year prospective follow-up study of 100% (N = 29) of a sample of children and adolescents with disruptive behavior disorders found that the baseline lumbar cerebrospinal fluid monoamine metabolite concentration and autonomic nervous system activity predicted some subsequent outcomes. The 5-hydroxyindoleacetic acid concentration significantly predicted severity of physical aggression during follow-up. The skin conductance level significantly predicted institutionalization. Correlations were in predicted directions with lower cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations and autonomic activity correlated with poor outcome. Moreover, in multivariate analyses, which included nonlaboratory measures as predictors, cerebrospinal fluid and autonomic measures still contributed significantly to the prediction. However, hypothesized predictions of cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations for suicide attempts and of low autonomic nervous system activity for arrests were not supported thus far. Patients are still at risk; consequently, these results must be considered preliminary. Nonetheless, the results suggest that further investigation of relationships between biological factors and outcome of children with disruptive behavior disorders is warranted.     

Statistical issues in long-term followup studies

The thesis of this article is that since followup studies of patients with schizophrenia have provided a rich body of informative knowledge, emphasis should now be on hypothesis testing in future studies. The consumer of research needs to have a general appreciation of statistical thinking, design, and methods to make an informed synthesis of results presented. This article presents a brief discussion of relevant statistics and statistical issues, as free of jargon as possible. Given the multivariable nature of psychiatric research, the natural focus is on multivariate statistics. A strong background in statistics is not required to understand the methods described and how and why they might be applied. Reference material for more detailed discussions is provided. It is a truism to say that the highest quality scientific work is dependent on an intimate collaboration with the expert in statistics and the expert in clinical methods, and this merits repeating only because it is so often ignored.     

Entwicklung einer neuen Säuglingsnahrung mit Thermobacterium bifidum. Ein Beitrag zum Problem der Sauermilchnahrung

Ohne Zusammenfassung     

Phase I trial of the polyelectrolyte carbetimer administered i.v. once every four weeks

Summary Carbetimer, a new synthetic low molecular weight polyelectrolyte with a novel structure displayed antitumor activiy in a number of animal tumor model systems and in vitro investigations. Based on these findings it was brought to a phase I clinical trial in patients with advanced malignant disease after failure of conventional treatment or with no conventional treatment available. Forty-eight patients received 98 courses. The schedule was a one hour i.v. infusion every four weeks. The starting dose was 180 mg/m² and dose escalation was performed according to a modified Fibonacci formula up to 16,690 mg/m². At least three patients were treated at each dose level and each patient was eligible to receive repeat courses at the same dose, until progressive disease or dose-limiting toxicity intervened. No hematological toxicity was encountered. Some adverse effects such as reversible proteinuria, hypercalcaemia, pain at infusion site, nausea and vomiting and fatigue were seen partly in a dose-related manner but did not represent the maximum tolerated dose (MTD). The limiting toxicity at the highest dose level of 16,690 mg/m² consisted of ocular symptoms (light flashes) accompanied by a modest decrease of blood pressure and nausea or vomiting during a one hour infusion. 16,690 mg/m²/1 hour was considered the MTD. There were four deaths on study, all considered diseaserelated. Fourteen patients had stable disease for more than two courses, which, however, could also be explained by the natural course of disease. No clear-cut antitumor responses were noted in our study center.The recommended dose for phase II trials derived from our results is 12,550 mg/m²/2 hours. However, with regard to experiences in other phase I studies, the subsequent phase II studies will be performed with a dose of 6,500 mg/m².