A path-analytical approach to differentiate between direct and indirect drug effects on negative symptoms in schizophrenic patients

The hypothesis that differences in drug effects of risperidone and haloperidol on negative symptoms in schizophrenia are secondary to effects on positive, extrapyramidal, and depressive symptoms was investigated by means of an analysis of the data from the USA-Canada risperidone double-blind randomized clinical trial of 523 chronic schizophrenic patients. Regression analyses in the total sample and within treatment groups confirmed a strong relationship between changes in negative symptoms and the other variables studied (R²=0.50–0.51,p<0.001). Only depressive symptoms did not contribute significantly to these results (p>0.10). Path analysis showed that the greater mean change (p<0.05) of negative symptoms with risperidone compared to haloperidol could not be fully explained by correlations with favourable effects on positive and extrapyramidal symptoms. The relationship between shift in extrapyramidal symptoms and shift in negative symptoms failed to reach statistical significance; however, there was a clear tendency in the expected direction in both treatment groups.     

Renal sensitivity to angiotensin II in type 1 diabetes

The role of the renin angiotensin system for the regulation of kidney function in diabetes mellitus is uncertain. Results from studies in diabetic animals suggest that a reduced activity in this system contributes to the renal hyperperfusion and hyperfiltration in diabetes. The renal sensitivity to angiotensin II in diabetic patients is also unknown. Changes in renal hemodynamics were measured after infusion of two low doses of angiotensin II in ten young type 1 diabetic patients without complications and in ten healthy controls. The renin and angiotensin II levels were found to be the same in both groups. The baseline glomerular filtration rate was higher in the diabetics. During the highest angiotensin II dose, the 51Cr-EDTA and PAH clearance decreased 14 +/- 15 and 157 +/- 118 ml/min in the diabetics and 14 +/- 15 and 146 +/- 109 in the controls respectively. The changes in blood pressure and renal vascular resistance or sodium excretion did not differ between the groups. A malfunction of the renin angiotensin system is thus unlikely as a cause of the glomerular hyperfiltration in type 1 diabetes.     

A rat model of monitoring liver allograft rejection

Rat models are often used to study liver allograft rejection. We have established a model for rat liver allograft rejection, monitored by fine needle aspiration biopsy (FNAB), in the strain combination PVG-to-BN with a mean survival time of 37 ± 20 days. In this model, we observed acute rejection with an intense peak of lymphoid blasts and lymphocyte-dominated inflammation in the FNAB [9.1 ± 3.0 corrected increment units (CIU)], and an eventual increase in macrophages (up to 4.2 ± 4.4 CIU), together with fibrosis and parenchymal necrosis in the graft. Markers of immune activation, such as an increase in IL-2-receptor (from 1 % ± 2 % to 21 % ± 13 %) and class II (from 20 % ± 9 % to 43 % ± 13 %) expressing lymphoid cells and induction of ICAM-1 in the graft, were consistent with the overall cellular response. The FNAB correlated well with parallel graft histology. In this rat model, the atraumatic monitoring makes a close follow-up possible without having to sacrifice the experimental animals. This saves work, animals, and costs in the study of liver rejection. Received: 2 July 1996 Accepted: 28 October 1996     

Is obesity still a risk factor in renal transplantation?

At our center, since 1982, a body mass index (BMI) of less than 30 has been a prerequisite for placing a patient on the waiting list for renal transplantation. This decision was made because obese transplant recipients seemed to have a less than favorable post-transplant outcome. The aim of this study was to evaluate whether this requirement is still justified. Forty-six patients with a BMI above 30 underwent primary cadaveric renal transplantation between 1972 and 1993. For each of these obese patients, five consecutive non-obese (BMI 20–25) control patients were selected. Patient and graft survival, causes of graft loss, and acute rejection rate were evaluated for the two patient groups before and after the year 1982. Within the first 30 post-transplant days, one patient (2 %) and 11 grafts (24 %) were lost in the group of obese patients whereas seven patients (3 %) and 36 grafts (16 %) were lost in the control group. Among the obese patients, renal circulatory complications were a major cause of graft loss. In the period 1973–1981, the 1-year patient survival rate was 65 % among obese patients versus 75 % among controls from 1982 to 1993, this was 90 % versus 93 %. From 1973 to 1981, the 1-year graft survival rate was 25 % among obese patients versus 53 % among controls (P < 0.05); from 1982 to 1993, it was 68 % versus 84 % (P = NS). Multivariate analysis showed that the immunosuppressive regimen, age of the patient, BMI, and cold ischemia time of the graft had a significant influence on graft survival. The acute rejection rate within the first 30 days was 28 % among obese patients and 35 % among controls (P = NS). We conclude that a BMI below or equal to 30 is still justified as a prerequisite for placement on the waiting list for renal transplantation, for despite an overall improvement, the outcome of renal transplantation in obese patients remains worse than that in non-obese patients. Received: 3 February 1997 Received after revision: 4 April 1997 Accepted: 8 April 1997     

Effects of enteral feedback inhibition on motility,luminal flow,and absorption of nutrients in proximal gut of minipigs

We wanted to clarify whether the postprandial intestinal feedback control activated by nutrients in the distal gut exerts different effects on motility, transit of digesta, and absorption of nutrients in the proximal gut. Additionally, interrelationships among motility, transit, and absorption were to be elucidated because these relationships have only been investigated in the fasted state. In five minipigs, a 150-cm segment of the proximal jejunum was isolated by two cannulas. Motility of the jejunal segment was recorded by multiple strain gauges and analyzed by computerized methods. Markers (Cr- and Cu-EDTA) were used for the measurement of the flow rate, transit time, and absorption of nutrients. After a meal, the test segment was perfused with 2 kcal/min of an elemental diet over a period of 90 min. A feedback inhibition was activated by infusion of nutrients into the midgut at rates of 1–4 kcal/min. Saline was infused as control. With increasing energy loads infused into the midgut, the motility index and the length of contraction waves decreased, whereas the incidence of stationary contractions increased, ie, the motility changed from a propulsive to a segmenting pattern. These modulations of motility were associated with a linear decrease in the flow rate and a linear increase in transit time. Flow and transit were linearly correlated with each other. Additionally, the reduction in flow rate and the delay in luminal transit were associated with a linear increase in the absorption of nutrients. However, the increase in absorption induced by the feedback mechanism was small (7.3–13.4%) compared to the marked inhibition of the motility parameters (54–64%), the flow rate (59%), and the delay of transit (5.8-fold). Feedback control primarily modulated motor patterns and luminal flow, whereas the small increase in absorption was only a side effect due to the longer contact time of the nutrients with the mucosa.The study was supported by the Deutsche Forschungsgemeinschaft, grant Eh 64/6-3.     

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.

     

Computergestützte Charakterisierung von sonographischen Plazentastrukturen

Schlu?folgerungen Aus der Me?wert-Verteilung der Grauwerte im Sonogramm lassen sich Kennwerte berechnen, die eine computergestützte sonographische Reifebeurteilung der Plazenta erm?glichen. Allerdings sind die Verteilungsparameter (Median, Varianz, Schiefe, Exze?) abh?ngig von den Ger?teparametern. Zuverl?ssiger ist die Berechnung von Kennwerten, die sich auf die strukturellen Eigenschaften des Sonogramms beziehen. Bei den hier dargestellten Untersuchungen k?nnen Kennwerte für den Kontrast bzw. für die Ansammlung gleichartiger Grauwerte um einen bestimmten Punkt die sonographische Beurteilung der Plazenta optimieren. Damit erweitern sich die M?glichkeiten für die Zustandsdiagnostik der intrauterinen Lebensbedingungen.     

A novel technique of ab interno glaucoma surgery: follow-up results after 24 months

Purpose It was the aim of this study to investigate the efficacy, longevity, and safety of a new ab interno intervention for the treatment of primary open-angle glaucoma (POAG). Methods The previously described method of radiofrequency-mediated “sclerothalamotomy ab interno” was applied in 53 eyes of consecutive patients with POAG between April 2002 and July 2002. Average preoperative intraocular pressure (IOP) was 25.6±2.3 mmHg (range 18–48 mmHg). Sclerothalamotomies were carried out with a custom-made high-frequency dissection 19 G probe (tip 0.3×1 mm) applying bipolar current with a frequency of 500 kHz (tip temperature 130°C). Results After a follow-up period of 24 months, the average IOP was 15.0±1.6 mmHg (range 11–20 mmHg) (p<0.005). The average number of topical agents was 2.6±1.0 (range 1–5) preoperatively. Twenty-four months after surgery such agents were used in only five (9.6%) eyes and the average was 0.21±0.53 (range 0–2). Transient IOP elevation was observed in 12 of 53 eyes (22.6%) postoperatively. In all cases elevated IOP could efficiently be controlled with topical medication. In general, IOP dropped continuously over the course of the 6 months following surgery and then remained constant. Conclusions This study indicates that sclerothalamotomy ab interno is a safe and efficient surgical method for the treatment of POAG. Long-term results clearly demonstrate the longevity of IOP reduction.