Pharmacokinetics and haemodynamic effects of ISDN following different dosage forms and routes of administration

The pharmacokinetics and haemodynamic effects of isosorbide dinitrate (ISDN) have been investigated following administration of single doses as a sublingual (SL) spray (2.5 mg), sublingual tablet (5 mg) and peroral tablet (10 mg) in a randomised, placebo-controlled double-blind cross-over trial in 16 healthy volunteers.After the sublingual spray C_max was higher (39.0 ng·ml^-1) and t_max was shorter (3.9 min) than after the sublingual (22.8 ng·ml^-1 and 13.8 min) and peroral (16.9 ng·ml^-1 and 25.6 min) tablets. The AUC of ISDN did not differ following any of the three formulations (1031; 879; 997 ng·ml^-1·min, for the spray, SL tablet and PO-tablet, respectively). Mononitrate metabolites of ISDN (IS-2-MN and IS-5-MN) and total nitrates in plasma increased in proportion to the administered dose. This indicates that the fraction of the dose absorbed was the same for all the formulations but that the extent of first-pass metabolism increased in the order sublingual spray < sublingual tablet < peroral tablet. Thus, compared to the spray, the relative bioavailability of ISDN was 48% and 28% from the sublingual and peroral tablets, respectively.The haemodynamic effects were quantified using the a/b ratio of the finger pulse wave and the systolic blood pressure and heart rate under orthostatic conditions. For the a/b ratio of the finger pulse, the maximal effect was higher (e_max=130%) and the time to e_max (t_emax) shorter (16.6 min) after the spray than the sublingual tablet (84.4% and 25.5 min) or peroral tablet (90.2 and 31.3 min). The onset of effect was within 3, 5 and 7.5 min after the spray, sublingual and peroral tablets, respectively. A larger change in the orthostatically-induced decrease in systolic blood pressure and increase in heart rate was obtained following peroral than sublingual administration despite the similar plasma concentrations of ISDN. This probably reflects the larger amount of pharmacodynamically active mononitrate metabolites formed after oral dosing. The integrated effect following administration of 2.5 mg ISDN as spray was similar to that of a sublingual tablet of 5 mg.     

Peritoneal morphology in children treated by continuous ambulatory peritoneal dialysis

Fifty peritoneal biopsies (PB) from 35 patients with end-stage renal disease, treated by continuous ambulatory peritoneal dialysis (CAPD) and aged 2 months to 18 years, were examined by light microscopy (n=50) and/or scanning electron microscopy. PB were performed during surgical procedures immediately before the start of, during, or after the cessation of CAPD treatment. PB from 15 children without renal disease undergoing laparatomy were examined similarly. Before the start of CAPD, a scarcity and shortening of the mesothelial microvilli was observed by scanning electron microscopy. During and after CAPD, variable alterations of mesothelium, interstitium and capillaries were found. The mesothelial layer was absent in all 5 PB obtained during episodes of active peritonitis. In patients treated by CAPD for longer than 6 months, mesothelial denudation was observed more frequently (6/11) than in children treated for shorter periods (1/7) (P<0.08). Fibrosis of the peritoneal membrane was present in about 50% of patients during or after the cessation of CAPD without impairment of peritoneal function. No correlation was found between the presence of fibrosis and the frequency of peritonitis or the duration of CAPD treatment.     

Utilisation des implants biodégradables dans le traitement chirurgical des fractures et au cours des ostéotomies

Résumé L'utilisation de matériaux d'ostéosynthèse biodégradables a l'avantage d'éviter la réintervention pour extraire le matériel. Les biomatériaux de polymères polyglycolides ont été expérimentés sur plus de 3 600 animaux de laboratoire avant leur introduction en pratique clinique. Depuis 1984 nous les avons utilisés comme matériau d'ostéosynthèse dans près de 1 700 cas parmi lesquels 880 cas de fracture malléolaire, 226 cas d'ostéotomie en chevron pour hallux valgus, 65 cas de fracture de la tête radiale et 54 cas de fracture de l'olécrane. Parmi les 800 premiers cas traités par broches biodégradables nous avons obtenu des résultats favorables et sans incidents dans 91 pour cent des cas. Il y eut 7 cas de fixation défaillante nécessitant une réintervention. Il y a eu 7 cas d'infection superficielle et 3 cas d'infection profonde. Nous avons observé la formation d'une collection séreuse sous-cutanée sans influence sur le résultat radiologique ou clinique dans 52 cas (6,5 %). Au vue de ces résultats et compte tenu des avantages économiques et psychologiques des matériaux biodégradables (pas de réintervention), on peut penser que l'usage de biomatériaux rivalise favorablement avec l'usage de matériaux conventionnels dans certains types d'ostéosynthèse.

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Utilization of biodegradable implants in the surgical treatment of fractures and osteotomies

Summary The utilization of biodegradable implants instead of metals in orthopaedic surgery abolishes the need to remove the fixation material. For this study biodegradable rods and screws of self-reinforced polyglycolide, polylactide and lactide-glycolide copolymer were developed and manufactured. The clinical introduction of these implants was preceded by thorough experimental studies with 3 600 animals. From November 1984 the developed biodegradable method of osteofixation was used in 1 700 operations. These included 880 displaced malleolar fractures, 226 chevron-osteotomy for hallux valgus, 65 displaced fracture of the radial head, 54 displaced frature of the olecranon and other fresh fractures or orthopaedic operations. In the first 800 cases operated on using self-reinforced polyglycolide rods the postoperative course was uneventful (91%). Because of failure in the fixation reoperation was needed in 7 cases. A superficial wound infection was observed in 7 cases, deep infection in 3 and transient fluid accumulation in 52 cases (6,5%). Fluid accumulation did not influence the radiological or clinical end-result. The advantages of biodegradable fixation are many-sided. There is a costbenefit and clinical capacity is free for other use, and psychological advantages must be emphasised because removal of implants is not needed. The over all results of this study were considered favourable.

     

Nationales Reanimationsregister

Within the scope of the symposium “Rescue Medicine in Germany” (held at the Reisensburg near Ulm in 2002), the need for a standardized data acquisition set for prehospital cardiac arrest patients was identified. Therefore, the working group “Emergency Medicine” of the German Society of Anesthesiology and Intensive Care Medicine (DGAI) created a nationwide data acquisition system for primary medical care in prehospital cardiac arrest patients treated with cardiopulmonary resuscitation procedures. The system is in full accordance with the “Utstein style.” Integration of this data acquisition system, for example into the “Dortmund protocol,” is providing a standardized data web base of all acquired prehospital data analyze and to compare processing and structural quality. As additional modules for this nationwide data web base system, an inhospital module “further clinical treatment” and a “long-term follow-up” module are currently in the developmental process.     

Die Bedeutung von Assessments in der Ausbildung diplomierter Rettungssanitäter

Learning and exams are closely interconnected. Test elements should accompany the learning process and not only serve to complete the training period. Examinations should be oriented toward the ideas learned and the forms of instruction used. However, the significance of examinations during the training period for emergency medical technicians is hardly ever addressed in the literature. All of the procedures that serve to evaluate the students’ performance are subsumed under the term “assessments.” This contribution presents the tasks of assessments and their requirements for occupational training of certified emergency medical technicians. It also offers a suggestion to develop a modern testing concept.     

PLACENTAL CALCIUM PUMP: CLINICAL-BASED EVIDENCE

Placenta can be considered as a pump of calcium necessary for the normal development of the fetus. We believe that the location of this pump is in the placental basement membrane. The calcification of this membrane has been described only in cases of in utero fetal death. In this study we describe for the first time a case of placental calcification in a living fetus. The fetus of a normal 21-year-old pregnant woman showed heart abnormalities but the genetic analysis showed a normal male karyotype. The histology of the placenta demonstrated multiple intravillous linear and granular calcific incrustations The hemtoxylin/eosin stain of the sections revealed basement membrane calcific incrustations and intravillous calcium deposits. We postulate that the fetal circulation in the villi was impaired and the calcium that reached the villi from the mother was deposited at this level.