Effect of nedocromil on bronchospasm induced by inhalation of substance P in asthmatic subjects

Several studies have demonstrated that neuropeptides are present in peptidergic fibres of bronchial tissue. The aim of the present study was to evaluate in vivo the effect of nedocromil sodium (2 x 2 mg) on bronchospasm induced by inhalation of substance P. Six moderate asthmatic patients, mean age 25.17 years, were studied. Airway response was measured as FEV1 and the dose of substance P (using a dose range of 23-736 nmol) producing a 20% decrease in FEV1 (PD20) was calculated from the individual semilogarithmic dose-response curves. Patients were studied on 3 separate days in a randomized, double-blind manner. On the first day a baseline PD20 value was determined. On subsequent days substance P challenge was performed after pretreatment (20 min before challenge) with either placebo or nedocromil sodium. Student's paired t-test and Wilcoxon's test were used for statistical analysis. The results of this study demonstrated that inhalation of substance P causes a dose-dependent bronchoconstriction and that the bronchoconstriction induced by substance P can be prevented by pre-treatment with nedocromil sodium.     

Human interleukin 4 regulates the phenotype of lymphocytes generated during mixed lymphocyte culture and inhibits the IL-2-induced development of LAK function in normal and leukaemic cells

This study examined the immunoregulatory role of recombinant interleukin 4 (IL-4), also known as B-cell stimulating factor 1, on the generation of cytotoxic effector cells from normal and leukaemic human blood mononuclear cells. When tested on cells from normal individuals, the addition of IL-4 to mixed lymphocyte cultures led to a dose-dependent proliferation of T-helper cells (CD3, 4 positive) with a concomitant decrease in phenotypic and functional cytotoxic T cells and natural killer (NK) cells. IL-4 also inhibited the interleukin-2 (IL-2)-induced generation of lymphokine-activated killer (LAK) activity when added at the beginning of mixed lymphocyte culture. When tested on mature leukaemic NK cells, IL-4 also inhibited the ability of IL-2 to induce LAK function using a short-term culture system. These results show that IL-4 acts on both normal and leukaemic cells and suggests that it acts at more than one level during the development of LAK function.     

Anti-thyroid drugs decrease mucosal damage in a rat model of experimental colitis

Background : Methimazole, an anti-thyroid drug, was recently found to be useful in the treatment of systemic lupus erythematosus and other autoimmune diseases. Moreover, decreased thyroid hormone production is associated with a variety of immunological manifestations, such as reduced activation of CD4⁺ cells, increased CD8⁺ cell activity and reduced soluble IL-2 receptors. In the present study we examined the effects of methimazole and propylthiouracil on a rat model of experimental colitis.
Methods : Colitis was induced by intracolonic administration of 30 mg trinitrobenzene sulphonic acid (TNB). Two weeks prior to induction of colitis, rats were treated by either methimaziole (0.04%) or propylthiouracil (0.01%) in drinking water after a week of free access to water. Rats were sacrificed 48 h or 7 days after induction of colitis. The colon was isolated, rinsed with ice-cold water and weighed. Damage was assessed both macroscopically and microscopically and myeloperoxidase (MPO) activity determined.
Results : All treated rats were hypothyroid as manifested by a significant elevation of thyroid stimulating hormone (TSH), by comparison with the control groups (mean -1.82±0.40 versus 0.11±0.02 mmol/L, respectively). The inflammatory response elicited by TNB resulted in severe mucosal damage 48 h after damage induction, which persisted for 7 days. Pre-treatment with either methimazole 0.04% or propylthiouracil 0.01% significantly decreased mucosal damage macroscopically (lesion area, lesion score and segmental weight) microscopically and also significantly decreased MPO level at both time points ( P <0.01).
Conclusions : Methimazole and propylthiouracil significantly reduce mucosal damage and colonic weight in a rat model of colitis. The mode by which they do so remains to be studied.     

Effects of acute administration of d-amphetamine and haloperidol on procedural learning in man

The effects of an indirect dopamine-agonist, d-amphetamine, and a non-selective dopamine receptor antagonist, haloperidol, were investigated in normal male volunteers using a between-subjects double-blind design in a procedural learning task, thought mainly to involve unconscious/automatic learning. The results showed: (1) d-amphetamine facilitated response speed, whereas haloperidol inhibited it, in comparison to placebo; (2) the linear increase in procedural learning corresponded with pharmacological manipulation of degree of dopaminergic activity, i.e. subjects given haloperidol showed the least, and subjects given d-amphetamine the greatest, procedural learning. The implications of these findings are discussed in relation to investigation of abnormalities of procedural learning processes in schizophrenia. Received: 28 June 1996/Final version: 2 October 1996     

Reactive oxygen species and human spermatozoa: physiology and pathology

The role of reactive oxygen species (ROS) in the pathophysiology of human sperm function has been emphasized in recent years. ROS production in semen has been associated with loss of sperm motility, decreased capacity for sperm–oocyte fusion and loss of fertility. There is a current presumption that the most prolific source of ROS in sperm suspensions is an NADPH oxidase located in leukocytes or in spermatozoa which produces superoxide which is further converted to peroxide by the action of superoxide dismutase. Hydrogen peroxide has been recognized as the most toxic oxidizing species for human spermatozoa, which are very sensitive to lipid peroxidation owing to the high content of polyunsaturated fatty acids in their plasma membrane, though this is not the sole mechanism by which sperm function might be impaired by ROS. Although the excessive production of ROS is detrimental to human spermatozoa, there is a growing body of evidence which suggests that ROS are also involved in the physiological control of some sperm functions. This review focuses on the nature and source of the ROS generated by human spermataozoa as well as their operational mechanisms and their effects, which may be detrimental or beneficial.     

Location and geometric description of carpal bones in CT images

The carpal regions of ten cadaver extremities were imaged by CT. The images were combined into a 3-dimensional model of the carpus using a technique based on a dynamic programming algorithm to find an optimal estimate of the location of the bone boundaries in the CT images. The resulting set of surface points on each bone was used to compute volumes and principal and antipodal axes for the bones. A spatial coordinate system was established based on the positions of the centroids of three bones in the distal carpal row. The angular orientations of all carpal bones were determined with respect to this system. The principal axes for the same bone among ten wrist specimens proved to be more widely dispersed than the antipodal axes for the same bones. The antipodal axes also correspond more closely to an intuitive notion of the “longest axis” of the bones. We conclude that the antipodal axis is a more reliable and useful measure of bone orientation than the principal axis.     

The in vitro fertilisation programme at Tygerberg Hospital and the University of Stellenbosch. Five years' experience, April 1983-January 1988

The results of the in vitro fertilisation programme at Tygerberg Hospital for the period April 1983 to January 1988 are presented. Of the 1117 laparoscopies performed, 825 patients reached the transfer stage. A live-birth rate of 9.3% was achieved. The pregnancy rate after transfer of 4 embryos was 25.9% compared with 15.4% after 2 embryos and 10.8% after 3 embryos (P = less than 0.0001). The multiple pregnancy rate was 2.8% in the group receiving 2 embryos and 11.7% and 10.4% in those receiving 3 and 4 embryos, respectively. Of the 77 successful pregnancies (90 babies), 1 baby died at 34 weeks' gestation as the result of abruptio placentae due to preeclampsia and 1 cot death occurred. The only congenital abnormality encountered was a cleft palate.     

A reassessment of the peritoneal lavage leukocyte count in blunt abdominal trauma

Nine hundred and three patients undergoing diagnostic peritoneal lavage (DPL) over a 6-year period were retrospectively reviewed to evaluate the utility of the white blood cell (WBC) count in the lavage fluid. Eleven patients (1.2%) had dialysate WBC counts greater than 500/mm3, with erythrocyte counts less than 10(5)/mm3. Nine of these patients who were lavaged within 4 hours of injury had no intra-abdominal pathology. Two patients, lavaged after 4 hours, demonstrated intra-abdominal injury. Two hundred twenty-three patients (24.7%) had grossly clear dialysate which was not sent for laboratory analysis. None of these patients required laparotomy. We conclude that the WBC count in DPL fluid is of no diagnostic value in victims of blunt abdominal trauma who are lavaged within 4 hours of injury. In addition, laboratory analysis of clear dialysate is not required in these patients.