Suppression by Trypanosoma brucei rhodesiense of the capacities of human T lymphocytes to express interleukin-2 receptors and proliferate after mitogenic stimulation.

We studied the suppressive effects induced in phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC) by purified blood forms of Trypanosoma brucei rhodesiense. The parasite was found to markedly impair lymphocyte proliferation (measured in terms of [3H]thymidine incorporation). The extent of this effect increased with parasite concentration and was not due to mitogen absorption, depletion of medium nutrients, or PBMC killing by the parasite. Significant reductions in interleukin-2 receptor (IL-2R) expression, determined by flow cytometric analysis, were also observed in PHA-stimulated PBMC cultured in the presence of T. b. rhodesiense as evidenced by marked decreases in the surface density of the receptor. Concomitant decreases in the percentage of IL-2R+ cells were recorded in approximately half of the experiments. A discrete, dimly stained subpopulation of IL-2R+ cells were consistently demonstrable whether or not a reduction in the percentage of IL-2R+ cells occurred. Living, but not glutaraldehyde-fixed, parasites suppressed IL-2R expression. In kinetic studies, a low but reproducible level of suppression of IL-2R was demonstrable as early as 6 h after PHA stimulation; the extent of this effect became considerably more pronounced as additional culture time elapsed. Levels of IL-2 biological activity in cocultures of T. b. rhodesiense with PHA-stimulated PBMC were comparable with or higher than those present in control cultures lacking the parasite. Therefore, insufficient levels of this cytokine would be an unlikely explanation for the noted suppression of IL-2R expression and lymphoproliferation. These effects of T. b. rhodesiense could represent an important component of the mechanism by which immunosuppression develops in African sleeping sickness.     

The MMPI and premenstrual syndrome: profile fluctuations between best and worst times during the menstrual cycle

The MMPI was administered during the patient-perceived best time of the menstrual cycle and during the patient-perceived worst time of the cycle in order to examine the stability of MMPI profile configurations. Subjects were 214 women who were referred to two metropolitan outpatient premenstrual syndrome (PMS) clinics for moderate to severe premenstrual complaints. This sample was selected from 1,849 intake files after screening by strict selection criteria for PMS. The results indicate that there are wide fluctuations in profile patterns between the best and worst times of the menstrual cycle for a large number of patients. Caution in using the MMPI is strongly advised.     

Facial reanimation after acoustic neuroma excision: the patient's perspective

Facial reanimation after acoustic neuroma excision is currently accomplished using a variety of surgical techniques. A multi-institutional survey of patient perceptions of facial reanimation success was accomplished by mailing a questionnaire to 809 randomly selected members of the Acoustic Neuroma Association. Four hundred sixty patients who underwent 296 reanimation procedures responded. Facial to hypoglossal nerve anastomosis, tarsorrhaphy, and upper eyelid implants were most frequently performed. The patient's estimations of initial deficit, spontaneous recovery, and overall satisfaction with the reanimation procedures are discussed.     

Acute multilocular osteomyelitis in infancy and childhood

38 cases of acute multilocular osteomyelitis out of a total of 165 osteomyelitis patients were treated between 1974 and 1986 at the Department of Paediatric Surgery and Paediatric Diseases at the University of Mainz. Osteomyelitis in infants was separated from juvenile osteomyelitis because of the different problems inherent to this disease depending upon the age; likewise, multilocular remote involvement was separated from regional multiple involvement. It was found that distant involvement is of special importance in infancy. 6 of the 8 cases in this group presented with symmetrical involvement. This interesting phenomenon is described in this article for the first time in acute multilocular osteomyelitis; so far, it was known to occur only in chronic recurrent multifocal osteomyelitis (CRMO). The infants in this group were predominantly newborn who were particularly severely handicapped by predisposing factors such as necessary intensive-care measures or surgical interventions. Our findings showed that in this age group most of the problems occurred, namely: 3 deaths and 2 healing defects in 8 children. For this reason it is imperative to effect particularly close monitoring of multilocular acute osteomyelitis in infancy. This must be considered as a paediatric and paediatric-surgical emergency requiring not only accurate diagnostic measures but also early internistic and surgical treatment to improve the prognosis of this specific disease pattern.     

Fetal growth in hypertensive women]

The Authors examine the correlation between hypertensive disorders of pregnancy and fetal growth. The results of a study of 342 pregnancies, confirm a significant correlation between hypertension and fetal growth retardation. These findings, so evident in moderate and severe hypertension, have also been confirmed in cases of mild hypertension. The medical treatment also in the pregnancies with mild hypertension, and a larger utilisation of operative deliveries, determined a decrease in perinatal mortality and morbidity.     

Effect of norethisterone acetate on serum lipid and lipoprotein parameters as well as on blood coagulation in female monkeys (M. fascicularis)

The effects of daily oral administration of a high dose of 10 mg norethisterone acetate (NET-Ac.)/kg/day over 14 weeks on serum lipid and lipoprotein parameters as well as on blood coagulation were investigated in female monkeys (M. fascicularis). Measurements of lipids and lipoprotein cholesterol were performed in weeks —5 and — 1 before treatment and in weeks 4, 8 and 12 after treatment. In addition, various blood coagulation and fibrinolytic parameters were determined in weeks 11–14 after treatment with NET-Ac. Furthermore, the serum levels of norethisterone (NET) were determined in order to monitor the real systemic compound exposure and revealed that C_max and AUC (0–3 h) values reached for norethisterone in this experiment in monkeys were about 25 times higher than those obtained after an oral contraceptive dose of NET-Ac. in women.

The results of lipid and lipoprotein cholesterol determinations showed decreases in serum total lipids, phospholipids, triglycerides and total cholesterol associated with similar decreases in HDL-, LDL- and VLDL-cholesterol fractions after NET-Ac.-treatment in monkeys. These effects were observed from week 4 onwards and maintained their magnitude up to week 12 after treatment. Since both HDL- and LDL-cholesterol fractions decreased, the HDL/LDL-ratio remained almost unchanged. Thus, the results obtained in this study after high-dose treatment with NET-Ac. in monkeys did not indicate any changes of lipid and lipoprotein parameters which in humans are supposed to be associated with an increased risk of cardiovascular lesions, namely a decrease in HDL- and increase in LDL-cholesterol fractions.

The results of blood coagulation and fibrinolytic parameters showed increased antithrombin-III and plasminogen levels besides minor changes in other parameters, thus indicating that NET-Ac. -treatment does not contribute to an increased risk of cardiovascular thrombotic events in the cynomolgus monkey.     

Monocyte chemotactic protein expression during schistosome egg granuloma formation. Sequence of production, localization, contribution, and regulation.

The present study explored the role of murine monocyte chemotactic protein (MCP) in the T cell-mediated hypersensitive granulomatous response to Schistosoma mansoni eggs. The study examined the time course of local production, contribution to cellular infiltration, and the role of T cells in endogenous regulation. Synchronized pulmonary granulomas were induced under conditions of primary and secondary states of immunity. Primer-directed polymerase chain reaction analysis showed increased MCP mRNA expression in granulomatous lungs, mainly in the secondary response. Levels of MCP were measured by enzyme-linked immunosorbent assay in cultures of intact granulomas. Spontaneous MCP production was modest in primary granuloma cultures, reaching a maximum of 5.7 +/- 0.9 ng/ml by 16 days. In contrast, the secondary response showed augmented and accelerated production, achieving 13 +/- 2.0 ng/ml by 2 days. Immunohistochemical staining revealed the strongest MCP expression within microvascular adventitial cells or pericytes as well as in scattered mononuclear cells associated with granulomas. Staining was not detected in normal lungs. Passive immunization with anti-MCP-1 antibodies caused a 40% reduction in the secondary granuloma area but did not significantly affect the primary response. With adoptive cell transfer and T cell subset depletion, it was shown that Thy-1+ and CD5+ cells augmented, whereas CD8+ cells appeared to impair, MCP production. This provides direct evidence that MCP is involved in secondary Th2-mediated response to schistosome eggs and is subject to regulation by T cells.