Effects of pre- and postnatal cysteamine exposure on renal function in the rat

The safety of cysteamine after renal transplantation and during pregnancy is an important issue, since girls with cystinosis are in better health on cysteamine therapy and thus more likely to become pregnant. In the first study, cysteamine was given to pregnant rats on days 6.5–18.5 post conception in oral doses of 0, 37.5, 75, 100, and 150 mg/kg per day. The dams were sacrificed on day 20.5, the fetal kidneys removed and prepared for histological examination. In the second study, cysteamine was given to dams on days 6.5–19.5 post conception in oral doses of 0, 37.5, 50, and 75 mg/kg per day. Dams were allowed to give birth naturally and pups were given cysteamine on days 4–21 to yield the same oral doses of cysteamine given to the dam. Renal function was evaluated on day 35. Histological examination of fetal kidneys revealed no changes even in kidneys from fetuses with growth retardation and malformations. Furthermore, there were no alterations in renal function in offspring on day 35. These findings demonstrate that cysteamine therapy does not affect renal development in the rat. Further investigations will be required to prove whether cysteamine therapy has the potential to affect renal development in the human. Received: 25 September 1998 / Revised: 17 November 1998 / Accepted: 13 December 1998     

Complications Following Swedish Adjustable Gastric Banding: A Long-Term Follow-up

Background: The Swedish adjustable gastric band (SAGB) has been in use since 1985. The aim of this study was to analyze short and long-term complications linked to the SAGB. Materials and Methods: Between August 1990 and December 1996, we operated on a series of 326 patients (78 men and 248 women) at the Huddinge University Hospital and the Norra ?lvsborg County Hospital. The mean age of patients at surgery was 40 years (range 19-62). The mean preoperative weight was 125 kg (range 81-181). The mean excess weight was 80%. Results: The mean time of follow-up was 28 months (range 6-76). Complications requiring reoperation included two (0.6%) band dislocations, six (1.8%) band leakages, and 16 (4.6%) band migrations-erosions. The most common reason for abdominal reoperation, band migration, was attributed to overfilling of the band system. In the patients in whom migration occurred, the bands had been filled with a mean volume of 12.6 ml fluid. In the remaining patients, the mean volume was 8.7 ml. The most common complication not requiring reoperation was reflux disease (4.7%). In cases with a small pouch, this complication did not seem to be a serious problem. The mean excess weight loss in the 296 patients without complications was 68%. Conclusion: The overall long-term complication rate following SAGB is reasonable. With improved operating technique and closer follow-up, it should be possible to reduce the complication rate further. Reoperation because of band migration appears to be related to overfilling of the system and should therefore be avoidable in most cases.     

An Early Onset Rehabilitation Program for Children and Adolescents after Traumatic Brain Injury (TBI): Methods and First Results

Survived traumatic brain injuries (TBI) are one of the most serious challenges to the patient's future life. Recent literature increasingly questions the long believed protective effects of functional cerebral plasticity in children. Although TBI in children and adolescents is frequent, they are less frequently admitted to rehabilitation centers as in-patients than adults. This emphasizes the role of out-patient treatment. The progressing study described here aims to achieve a contribution to a comprehensive approach in TBI-rehabilitation for youngsters. A two-stage multimethodal program, starting with stimulation in coma while the patient is on the intensive care unit, and neuropsychological therapy after regaining consciousness is to be evaluated in a controlled, prospective and randomized study. After including nearly 50 % of the planned sample (100 persons), some preliminary results can be mentioned with all applicable caution. The effectiveness of the applied therapy can be stated here with respect to the posttraumatic development of intellectual abilities in the 6- and 12 months follow ups. Moreover, in the control group development of psychopathological alterations was found to a considerable degree and also lower ratings in a quality of life questionnaire, compared to the experimental group. It is expected to prove these differences statistically, after the total sample has been included, and thus equal distributions have been achieved in all predictive variables.     

Autism and Congenital Blindness

The nature of autism in congenitally blind children has long been a source of interest and perplexity. A group of nine congenitally blind children with an autism-like syndrome were closely matched on chronological age and verbal mental age with nine sighted autistic children, and were compared on the Childhood Autism Rating Scale (Schopler, Reichler, & Renner, 1986) and the Behavior Checklist for Disordered Preschoolers, together with the Play Items for Disordered Preschoolers (Sherman, Shapiro, & Glassman, 1983). A checklist of clinical features characteristic of autism (derived from DSM-III-R) was also completed through an interview with teachers. There was substantial similarity between the groups, but also suggestive evidence of possible group differences, specifically in the domain of social-emotional responsiveness. Research on the psychological development of congenitally blind children promises to yield insights into the nature of autism itself.     

Initial manifestation of a manic syndrome in advanced age in subcortical arteriosclerotic encephalopathy (Binswanger disease)

We describe the case of a 65-year old man who presented with a first episode of mania lacking a history of previous affective illness. Clinical, neuropsychological and NMR-findings pointed to a subcortical arteriosclerotic encephalopathy (Morbus Binswanger) as an underlying organic condition. According Kleman's concept of "secondary mania" this case illustrates the necessity a thorough search for organic conditions in late manifesting affective illness which may also involve therapeutic considerations.     

Oxidative stress and atherosclerosis: its relationship to growth factors, thrombus formation and therapeutic approaches

The initiating event of atherogenesis is thought to be an injury to the vessel wall resulting in endothelial dysfunction. This is followed by key features of atherosclerotic plaque formation such as inflammatory responses, cell proliferation and remodeling of the vasculature, finally leading to vascular lesion formation, plaque rupture, thrombosis and tissue infarction. A causative relationship exists between these events and oxidative stress in the vessel wall. Besides leukocytes, vascular cells are a potent source of oxygen-derived free radicals. Oxidants exert mitogenic effects that are partially mediated through generation of growth factors. Mitogens, on the other hand, are potent stimulators of oxidant generation, indicating a putative self-perpetuating mechanism of atherogenesis. Oxidants influence the balance of the coagulation system towards platelet aggregation and thrombus formation. Therapeutic approaches by means of antioxidants are promising in both experimental and clinical designs. However, additional clinical trials are necessary to assess the role of antioxidants in cardiovascular disease.     

New therapeutic strategies to avoid intra- and extraperitoneal metastases during laparoscopy: results of a tumor model in the rat

BACKGROUND: Therapeutic strategies to prevent port site recurrences in laparoscopy surgery of malignancies have not been investigated until now. METHODS: The effects of taurolidine, heparin, and povidone iodine on the growth of rat and human colon adenocarcinoma as well as gallbladder carcinoma were investigated in vitro. Furthermore, cytokine release of growth-stimulating IL-1beta by peritoneal macrophages was measured after incubation with carbon dioxide and additional incubation with the different agents. In the third experiment, prevention of intra- and extraperitoneal metastases by intraperitoneal instillation of the different agents during laparoscopy was investigated in a colon carcinoma model in the rat. Tumor cells were administered intraperitoneally in 100 rats, and pneumoperitoneum (8 mm Hg) was established over 30 min with carbon dioxide. Rats received either tumor cells, cells + heparin, cells + povidone iodine, cells + taurolidine, or cells + taurolidine + heparin. RESULTS: In vitro, tumor cell growth decreased after incubation with taurolidine, taurolidine/heparin, and povidone iodine. Cytokine release was stimulated by incubation with carbon dioxide and could only be suppressed by incubation with taurolidine in vitro. In vivo, intraperitoneal tumor weight was lower in rats receiving heparin (251 +/- 153 mg) and povidone iodine (134 +/- 117 mg) compared to the control group (541 +/- 291 mg), but even less when taurolidine (79 +/- 82 mg) or taurolidine/heparin (18.3 +/- 30 mg) were instilled. CONCLUSION: Heparin slightly inhibits intraperitoneal tumor growth in vivo, while povidone iodine and taurolidine cause a significant decrease in tumor cell growth in vitro as well as intraperitoneal tumor growth in vivo. Cytokine release of peritoneal macrophages is only suppressed by taurolidine. Total tumor take and trocar metastases are only suppressed by taurolidine and taurolidine/heparin. Copyright Copyright 1999 S. Karger AG, Basel     

Human phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvant

Two phase I vaccine trials were conducted to test the immunogenicity and safety of a vaccine containing three recombinant malaria antigens from the asexual stage of Plasmodium falciparum. The three antigens are a fragment of MSP1 (190LCS.T3); MSP2 and a portion of RESA and were formulated in Montanide ISA720 adjuvant. These trials investigated the dose response of each antigen for eliciting both antibody and T-cell responses and the immunogenicity of a mixture of the antigens compared with the antigens injected separately. All three antigens elicited both antibody and T-cell responses. Strong T-cell responses were observed with 190LCS.T3 and RESA with stimulation indices exceeding 100 for peripheral blood leucocytes in some individuals. The antibody responses were generally weak. The human antibody responses observed with MSP2 in Montanide ISA720 were not significantly different from those obtained in an earlier trial which used MSP2 with alum as the adjuvant. No antigenic competition was observed: volunteers receiving a mixture of antigens had similar responses to those receiving the three antigens at separate sites. Tenderness and pain at the injection site were common over the first few days following immunization. In some volunteers, especially those receiving the highest doses tested, there was a delayed reaction at the injection site with pain and swelling occurring approximately 10 days after injection.     

Quality of life of stroke survivors

Adaptation to stroke requires complex, long-term change in stroke survivors' lives. This study aimed at identifying those factors that influence quality of life (QOL) of geriatric stroke survivors 1–3 years post-discharge. The objectives were: to describe the overall quality of life of stroke survivors; to examine the relationships between sociodemographic variables, neurological variables, functional status, social support, perceived health status, depression, and overall QOL; and to determine the best predictors of QOL. Data were collected on 50 stroke survivors using a cross-sectional design and standardized questionnaires, including the Quality of Life Index, the Functional Independence Measure, the Social Support Inventory for Stroke Survivors and the Centre for Epidemiologic Studies Depression Scale. The overall quality of life of the study participants was low. The most important predictors of QOL were depression, marital status, quality of social support, and functional status. Depression was the strongest predictor of QOL. By employing a multi-dimensional perspective, this study confirmed that adaptation to stroke involves much more than physical function. Thus, rehabilitation programs for this group would be more effective if they are based upon a holistic approach.