Pharmacokinetics and pharmacodynamics of cicaprost in healthy volunteers after oral administration of 5 to 20 μG

Summary In a Phase I study, the tolerability, pharmacodynamics and pharmacokinetics of cicaprost have been investigated in 6 male volunteers given 5, 10, 15 and 20 g as tablets of the -cyclodextrin clathrate.Individual inhibition of platelet aggregation and changes in facial colour (measured by chromametry) were dose-dependent and reached a maximum 30 to 60 min post-dose. The maximum inhibition of platelet aggregation was about 40%. After 3 to 4 h pre-treatment values had returned. Blood pressure remained within the normal range. The peak plasma level of cicaprost was reached within 15 to 90 min after drug intake. Both C_max-and AUC were individually dose-dependent. The terminal half-life in plasma of cicaprost was approx. 1 h, and its total clearance amounted to 4–7 ml·min^–1·kg^–1. The time courses of the plasma levels and of the pharmacodynamic actions were in agreement. Interindividual differences were observed in the occurrence of unwanted effects (e.g. headache).Thus, cicaprost is an orally available PGI₂-mimetic, for which effects on platelet aggregation and vascular perfusion have been demonstrated in healthy volunteers after doses of 5 to 15 g.The results will form part of the M.D. thesis of T.Staks. Some of the findings were presented at the CPT meeting, Mannheim/Heidelberg, 1989     

Adverse childhood experiences and the development of Down syndrome regression disorder

Down syndrome regression disorder (DSRD) is a clinical symptom cluster of acute or subacute neurocognitive regression in otherwise health persons with Down syndrome. The objective of this study was to evaluate if adverse childhood experiences (ACEs) were more prevalent in children with DSRD than those with DS alone. A survey-based, cohort-based study was performed. Caregivers of individuals with DSRD with onset of symptoms between age 10 and 30 years and DS alone were administered the ACEs questionnaire via an online REDCap survey. A total of 159 responses were collected after excluding incomplete surveys and those not meeting criteria for DSRD. Individuals with DSRD were not more likely to experience ACEs (p = 0.18, 95% confidence interval [CI]: 0.43–1.17). In those with ACEs prior to the onset of symptoms, the median time prior was 7 months (interquartile range: 5–10). Individuals with DSRD were more likely to report three or more ACEs (52, 33%) compared to those with DS alone (39, 22%) (p = 0.02, 95% CI: 1.08–2.87). Exposure to ACEs were not predictive of response to particular therapeutic interventions although those with multiple ACEs 3 months prior to the onset of symptoms was associated with lower response rates to benzodiazepines and immunotherapy (p = 0.02, 95% CI: −3.64–−1.13). This study provides preliminary data that individuals with DSRD experience ACEs at a similar rate to individuals with only DS alone, although three or more ACEs, often preceding the onset of symptoms, was more prevalent in individuals with DSRD.     

单用国产紫杉醇治疗乳腺癌

目的评价国产紫杉醇（特素）对乳腺癌的治疗效果和不良反应。方法自１９９５年３月至１９９５年７月,采用紫杉醇治疗乳腺癌２２例。紫杉醇１７５ｍｇ／ｍ２（１７０．９～２１０．８ｍｇ／ｍ２）,２１天为１个周期,共１～４次（中位数３次）。结果紫杉醇近期客观疗效：完全缓解３例,部分缓解１１例,总有效率６３．６％（１４／２２）,有效患者的病情已全部再度进展,缓解期２～７个月（中位３．５个月）。特素化疗的主要不良反应为白细胞下降（９６．２％）、脱发（１００％）和肌肉疼痛（８４．９％）。结论国产紫杉醇治疗乳腺癌有效,不良反应可以耐受。     

Route of administration and adverse effects of amphetamine use among young adults in Syndney, Australia

The relationship between route of administration and the adverse effects of amphetamine use (dependence symptoms, treatment-seeking, adverse psychological symptoms and violence) were examined among 231 Australian amphetamine users, half of whom usually injected amphetamine. Although 87% of users were recruited from non-treatment sources, a third had experienced symptoms of dependence on amphetamine, and a third had experienced an amphetamine-related health problem for which one in four had sought medical attention. There was also a high prevalence of psychological symptoms, such as depression, anxiety, paranoia, hallucinations and violence which were related to frequency of amphetamine use, and use by injection. Amphetamine users need to be better informed about the potential adverse effects of amphetamine use, and about ways in which they can reduce their risks of experiencing these harms by avoiding injecting use, and the regular use of high doses of amphetamines.     

The human toxicity of marijuana: a critique of a review by Nahas and Latour

A review entitled “The human toxicity of marijuana” was published in 1992 in the Medical Journal of Australia. The authors claimed that the adverse effects of cannabis use have been trivialized and that the effects are much more serious than earlier reported. We have made a careful study of this review and examined the claims made. We compared the claims of the authors with the information contained in the documents they cited and found that at least 28 of the 35 citations in this article were cited inaccurately. Five of these publications were misquoted, or the findings of the study were not fully reported. Twenty-three citations contained other errors, leaving only six to eight (two citations could not be retrieved because of their obscurity) accurate citations among 35. All of these inaccuracies operate in the direction of finding an adverse effect of marijuana.     

Cost-benefit analysis of transesophageal echocardiography in cardiac surgery

This article evaluates the costs and outcomes associated with TEE during and after cardiac surgery. The costs include the direct and indirect costs--the complications of TEE. The outcomes include the positive consequences or the benefits: money and lives saved. The article uses liberal (high) estimates of the direct and indirect costs of TEE and conservative (low) estimates of the benefits. The exact cost or benefit depends on the number of cases performed. The analysis shows that patients having surgery for congenital heart disease derive the greatest overall benefit: around $600 per case studied. Patients having valvular repair surgery derive the next greatest benefit: around $450 per case studied. In contrast patients having valve replacement have an overall cost of around $150 per case studied. Patients having surgery for coronary artery disease also derive an overall benefit: around $100-$300 per case studied, depending upon assumptions regarding TEE's role in prevention of intraoperative strokes. This analysis indicates that the financial benefits of TEE are substantial and frequently outweigh costs in patients requiring cardiac surgery.     

Effect of 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) enantiomers,major metabolites of phenytoin,on the occurrence of chronic-gingival hyperplasia: in vivo and in vitro study

The purpose of this study was to assess the possible role of the (R)- and (S)- enantiomers of the phenytoin metabolite p-HPPH in the pathogenesis of gingival hyperplasia (GH). About 98% of circulating p-HPPH is in the (S)-form. There were significant differences between patients with and without GH in (R)-p-HPPH level (0.055 vs 0.042 g·ml^–1), both enantiomer/racemate level ratios, and R/S enantiomeric ratio (0.0313 vs 0.0232); an increase in serum (R)-p-HPPH level was observed in patients with GH. In separate experiments, the effect of p-HPPH enantiomers on the proliferation of the normal human dermal fibroblast was studied. The in vitro study showed that (R)-p-HPPH selectively stimulated fibroblast growth. The results suggest that the least abundant metabolite, (R)-p-HPPH, is the most toxic with respect to gingival hyperplasia.