Chromosomes in patients treated with Azathioprine

Summary Chromosomes from leukocyte cultures and direct bone marrow preparations from patients under Azathioprine treatment were examined and compared with those from uremic patients and normal controls not taking Azathioprine. The results indicate a toxic effect of the drug, as well as an effect of uremia on the chromosome complement. The significance of these findings is discussed, especially in relation to several reports concerning malignant processes arising during or after Azathioprine intake. According to our findings, a relation between immunosuppression and malignancy seems more likely than a direct cancerogenicity of Azathioprine.

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Zusammenfassung Chromosomen aus peripherem Blut und direkten Knochenmarkspräparaten von Patienten unter Azathioprin-Therapie wurden verglichen mit solchen von gesunden Kontrollpersonen und urämischen Patienten ohne Azathioprin-Einnahme. Die Ergebnisse sprechen für eine toxische Chromosomenschädigung sowohl durch Azathioprin als auch die urämische Stoffwechsellage. Die Bedeutung dieser Befunde, insbesondere im Zusammenhang mit mehrfach berichteten malignen Prozessen nach Azathioprin-Einnahme, wird diskutiert. Unsere Ergebnisse lassen eher einen Zusammenhang zwischen Immunosuppression und malignem Geschehen vermuten als eine direkte cancerogen Wirkung von Azathioprin.

     

Brace treatment for patients with Scheuermann's disease - a review of the literature and first experiences with a new brace design

Background

In healthy adolescents normal back shape asymmetry, here termed truncal asymmetry (TA), is evaluated by higher and lower subsets of BMI. The study was initiated after research on girls with adolescent idiopathic scoliosis (AIS) showed that higher and lower BMI subsets discriminated patterns of skeletal maturation and asymmetry unexplained by existing theories of pathogenesis leading to a new interpretation which has therapeutic implications (double neuro-osseous theory).

Methods

5953 adolescents age 11–17 years (boys 2939, girls 3014) were examined in a school screening program in two standard positions, standing forward bending (FB) and sitting FB. The sitting FB position is thought to reveal intrinsic TA free from back humps induced by any leg-length inequality. TA was measured in both positions using a Pruijs scoliometer as angle of trunk inclinations (ATIs) across the back at each of three spinal regions, thoracic, thoracolumbar and lumbar. Abnormality of ATIs was defined as being outside 2 standard deviations for each age group, gender, position and spinal region, and termed severe TA.

Results

In the sitting FB position after correcting for age, relatively lower BMIs are statistically associated with a greater number of severe TAs than with relatively higher BMIs in both girls (thoracolumbar region) and boys (thoracolumbar and lumbar regions). The relative frequency of severe TAs is significantly higher in girls than boys for each of the right thoracic (56.76%) and thoracolumbar (58.82%) regions (p = 0.006, 0.006, respectively). After correcting for age, smaller BMIs are associated with more severe TAs in boys and girls.

Discussion

BMI is a surrogate measure for body fat and circulating leptin levels. The finding that girls with relatively lower BMI have significantly later menarche, and a significant excess of TAs, suggests a relation to energy homeostasis through the hypothalamus. The hypothesis we suggest for the pathogenesis of severe TA in girls and boys has the same mechanism as that proposed recently for AIS girls, namely: severe TAs are initiated by a genetically-determined selectively increased hypothalamic sensitivity (up-regulation, i.e. increased sensitivity) to leptin with asymmetry as an adverse response to stress (hormesis), mediated bilaterally mainly to the growing trunk via the sympathetic nervous system (leptin-hypothalamic-sympathetic nervous system (LHS) concept). The putative autonomic dysfunction is thought to be increased by any lower circulating leptin levels associated with relatively lower BMIs. Sympathetic nervous system activation with asymmetry leads to asymmetries in ribs and/or vertebrae producing severe TA when beyond the capacity of postural mechanisms of the somatic nervous system to control the shape distortion of the trunk. A test of this hypothesis testing skin sympathetic responses, as in the Rett syndrome, is suggested.     

Influence of a valgus knee brace on muscle activation and co-contraction in patients with medial knee osteoarthritis

The purpose of this study was to analyse the effect of a valgus knee orthosis designed for patients with knee osteoarthritis on the electromyographic activity (EMG) of seven muscles of the lower limb during gait. Twelve patients with medial knee osteoarthritis walked on a treadmill in three different conditions: without orthosis, with a knee orthosis in 4° valgus adjustment and with an orthosis in a neutral flexible adjustment. Root-mean-square (RMS) was analysed in each condition during a 150 ms pre-activation phase and during the stance phase of gait, which was divided in four sub-phases. In addition, co-contraction ratios (CCRs) were calculated between extensor/flexor, medial/lateral muscles and between agonist and antagonist muscle pairs. Significant decreases in muscle activity and CCRs were observed with the use of the knee orthosis in both adjustments compared to the condition without orthosis. Using the valgus brace, medial/lateral CCR decreased significantly during the late stance and the flexor/extensor CCR decreased significantly during the loading phase and late stance. Decreases of muscle pairs CCRs were observed with the neutral flexible adjustment. The results support the theory of a possible beneficial effect of knee braces in reducing knee loading by decreasing muscle activation and co-contraction levels, which could contribute to decelerate disease progression in patients with knee osteoarthritis.     

Bacterial fora of patients treated with bleomycin]

Microflora of the pharynx, nose, sputum and excrements was investigated. It was found that bleomycin therapy may induce or aggravate the shifts in microbiocenosis of the pharynx and sputum in the direction of pathogenization (increase in the number of Staph. aureus, hemolytic streptococci, enterobacteria). A tendency to elimination of bifidobacteria and appearance of Proteus in the excrements was observed. Complications associated with the treatment are rarely of infectious origin.     

Cytogenetic studies in patients treated with penicillamine.

Cytogenetic studies were performed on bone-marrow cells from 11 patients with rheumatoid arthritis treated with penicillamine. One of the patients was studied while developing a granulocytopenia and thrombocytopenia. The findings show that penicillamine had no chromosome-damaging effect as estimated by the micronucleus test and by the number of structural chromosomal aberrations.     

Urine surface tension in patients with urolithiasis treated with pharmalite

It was shown that pharmalite is an effective drug in the therapy of urolithiasis. The efficiency of pharmalite was determined from the surface tension of urine.