Fenfluramine treatment of twenty children with autism

The effects of fenfluramine were examined on 20 children with autism over a 48-week period utilizing a double-blind placebo-controlled crossover design. Blood and urine samples and psychological tests (Griffith's Developmental Scales and Real Life Rating Scale) were obtained at each crossover period. The only significant improvement was a decrease in abnormal motor behavior. We did not find any significant improvement in intellectual functioning or any correlation between good clinical response and low baseline serotonin levels or high baseline IQ. Serotonin decreased 53% after fenfluramine treatment and rebounded to a level 35% higher than baseline following a placebo period. Fenfluramine and the active metabolite norfenfluramine were determined in plasma samples.The authors thank Eva Mattsson-Mårn and Elisabeth Lilie for assistance in psychological testing, Suzanne Steffenburg for help with data collection, Ulla Themnér for assistance in obtaining laboratory samples, Per Karlsson for assistance in statistical analysis, and Margareta Säker and Ingegerd Blomkvist for assistance in laboratory analysis. This work was supported by the St. Göran's Fund, Alfred Benzon AB, the Emil and Maria Palm's Foundation, the Sven Jerring Fund, the Bror Gadelius Foundation, the Karolinska Institute, the Fund for Neurobiological Research, the Swedish Medical Research Council, and the Nyström Memorial Foundation.     

Tranexamic acid derivatives with enhanced absorption

Derivatives of the antifibrinolytic drug tranexamic acid [trans-4-(aminomethyl)cyclohexanecarboxylic acid] containing one or two tranexamic acid moieties were synthesized. Most of the derivatives have good stability in acidic and neutral solutions but are easily hydrolyzed in plasma. By measuring the amount of tranexamic acid excreted in the urine after an oral dose, relative absorptions of a number of derivatives in the rat were estimated. Most of the derivatives showed greater absorption than tranexamic acid itself. 1-[(Ethoxycarbonyl)oxy]ethyl trans-4-(amino-methyl)cyclohexanecarboxylate hydrochloride was chosen for studies in man.     

Digital subtraction angiography with bandpass filtration during by-pass operation

Experience is reported on a simple, inexpensive video processor for angiographic control during operation. In 6 patients with graft complications instant operative corrections could be performed.     

A factor analytic study of the Autism Behavior Checklist

The factor structure of the Autism Behavior Checklist (ABC) (Krug, Arick, & Almond, 1980a, 1980b), a 57-item screening instrument for autism, was examined on a sample of 383 individuals with autism spectrum disorders (i.e., autistic disorder, Asperger syndrome, and other autism-like conditions) aged 5-22 years. A five-factor model accounted for 80% of the total variance in the checklist. Thirty-nine of the 57 items had factor loadings of 0.4 or more, with 13 items loading on Factor 1, 11 items on Factor 2, 6 items on Factor 3, 5 items on Factor 4, and 4 items on Factor 5. No support was found for classifying the 57 items into the five subscales proposed by Krug et al. (1980a, 1980b) or for the three-factor solution suggested by Wadden, Bryson, and Rodger (1991).     

Severe lactic acidosis due to thiamine deficiency in a patient with B-cell leukemia/lymphoma on total parenteral nutrition during high-dose methotrexate therapy

An 11-month-old girl with B-cell leukemia/lymphoma developed profound lethargy due to severe lactic acidosis during chemotherapy and total parenteral nutrition (TPN). Initial treatment with NaHCO3 was ineffective. Treatment with a vitamin cocktail (OH-cobalamin, pyridoxine, thiamine, riboflavine, biotin, carnitine) at pharmacologic doses rapidly improved the child's clinical and laboratory status. Lactic acidosis was caused by an impairment of pyruvate dehydrogenase complex, which was due to lack of its necessary cofactor thiamine in the TPN. This case report indicates that lactic acidosis may be a front-line diagnosis in patients on TPN with lethargy and outlines the need for monitoring thiamine supply in TPN.     

Renal functional recovery 47 days after renal artery occlusion

A patient with a single kidney and oliguric renal failure for 47 days experienced dramatic restoration of glomerular filtration and renal function following graft bypass of an occluded renal artery. There was very little evidence of acute tubular necrosis. The case emphasizes the importance of the renal collateral circulation in the maintenance of tissue viability, even when the hydrostatic pressure of collateral flow is inadequate for glomerular ultrafiltrate formation. The differentiation of oliguric renal failure due to renal arterial occlusion from that due to acute tubular necrosis following arterial injection of radiocontrast material is imperative because of the dramatic response to reconstructive vascular surgery.     

TNF-alpha and IFN-gamma are overexpressed in the bone marrow of Fanconi anemia patients and TNF-alpha suppresses erythropoiesis in vitro

In Fanconi anemia (FA) C mice tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) have key roles in the pathogenesis of bone marrow failure. In FA subjects TNF-alpha was found to be increased in the serum and overproduced by patient-derived B-cell lines. In acquired aplastic anemia, a disease in which, similarly to FA, marrow failure occurs, TNF-alpha and IFN-gamma act as late mediators of the stem cell damage and are overexpressed in patient marrow lymphocytes. This study evaluated in marrow mononuclear cells (MNCs) of patients with FA, the expression of negative modulators of the hematopoiesis, such as TNF-alpha, IFN-gamma, macrophage inflammatory protein 1alpha (MIP-1alpha), and surface Fas ligand, and the role of TNF-alpha on FA erythropoiesis in vitro. TNF-alpha and IFN-gamma were significantly overexpressed in stimulated marrow MNCs of FA patients as compared to healthy controls. MIP-1alpha and Fas ligand were undetectable in patients and controls. In bone marrow cultures, the addition of anti-TNF-alpha increased the size and significantly increased the number of erythroid colony-forming units and erythroid burst-forming units grown from FA patients but not from healthy controls. This indicates that FA subjects have a marrow TNF-alpha activity that inhibits erythropoiesis in vitro. TNF-alpha has a relevant role in the pathogenesis of erythroid failure in FA patients.     

Changes in health complaints after removal of amalgam fillings

The aim of the present study was to investigate whether removal of all amalgam fillings was associated with long-term changes in health complaints in a group of patients who attributed subjective health complaints to amalgam fillings. Patients previously examined at the Norwegian Dental Biomaterials Adverse Reaction Unit were included in the study and assigned to a treatment group (n = 20) and a reference group (n = 20). Participants in the treatment group had all amalgam fillings replaced with other restorative materials. Follow-ups took place 3 months, 1 and 3 years after removal of all amalgam fillings. There was no intervention in the reference group. Subjective health complaints were measured by numeric rating scales in both groups. Analysis of covariance was used to compare changes in health complaints over time in the two groups. In the treatment group, there were significant reductions in intra-oral and general health complaints from inclusion into study to the 3-year follow-up. In the reference group, changes in the same period were not significant. Comparisons between the groups showed that reductions in intra-oral and general health complaints in the treatment group were significantly different from the changes in the reference group. The mechanisms behind this remain to be identified. Reduced exposure to dental amalgam, patient-centred treatment and follow-ups, and elimination of worry are factors that may have influenced the results.