Changes in maternal and newborn lymphocyte reactivity in reciprocal mixed lymphocyte cultures during the postpartum period

Reciprocal one-way mixed mother-newborn lymphocyte cultures (MMNLC) containing alternatively maternal or newborn responding (R) or stimulating (S) cells were investigated in both directions in primiparae at three different times: a few hours after delivery, and at 4 and at 16 weeks. Cultures were grown in the presence of maternal and pooled control serum prepared from the blood of five to eight unrelated healthy donors. Four weeks after delivery in maternal and in control serum a significant increase in MMNLC reactivity could be observed, which disappeared at 16 weeks when a pronounced decline in MMNLC values in both directions was found. The suppressive effect of maternal serum was more pronounced at delivery, still evident 4 weeks later, and insignificant after 16 weeks. The results of this study suggest that 4 weeks after delivery, maternal sensitization to fetal histocompatibility antigens can be detected in primiparae with MMNLC; and that 16 weeks later, this was no longer detectable with the same test.     

Behavioral treatment of essential hypertension: a comparison between cognitive therapy and biofeedback of heart rate

The efficacy and the mechanisms of action of two behavioral treatments for essential hypertension were compared: cognitive group therapy for anger control and biofeedback for heart rate control. The cognitive therapy aimed at lowering the "general anger" level and helping overt expression of "anger out;" heart rate biofeedback aimed at slowing heart rate in stress situations. Ninety-seven essential hypertensive patients were randomly assigned to three groups; after 20 dropouts, 77 patients fully participated in the study: cognitive treatment (N = 30), biofeedback (N = 27), and control (no treatment, N = 20). The treatments were held in 17 weekly sessions; during treatment, blood pressure was measured once a month, and during follow-up after 1 and 6 months. The anger level and heart rate control were assessed at the beginning and the end of treatment. The main results were: 1) a significant decrease of blood pressure for both treatments as compared with control, 2) a significant decrease of blood pressure with heart rate biofeedback as compared with cognitive therapy, and 3) a better control in anger achieved with cognitive therapy and a lesser control in heart rate as compared with biofeedback.     

Monoclonal antibody purified beta 2-microglobulin: heterogeneity revealed by radioimmunoassay

A monoclonal antibody, CMRF1, to human beta 2-microglobulin (beta 2m) was used to purify antigen to develop an in-house beta 2m radioimmunoassay. This immunoadsorption purified material was used to prepare a rabbit anti-beta 2m serum and was radiolabelled for the radioimmunoassay. The assay compared favourably with a widely used commercial radioimmunoassay but the immunological potency of the in-house standard was lower than that of the commercial reagent. This potency difference was not accounted for by antigenic denaturation. Subsequent two-dimensional gel electrophoresis revealed a second 12,000 dalton protein with a higher isoelectric point than beta 2m in the immunoadsorption purified material, which was also present, although in lesser amounts, in the commercial product. The different relative content of the additional 12,000 dalton protein appeared to explain the immunological potency difference between the in-house and the commercial standard. These results strengthen suggestions that there may be some heterogeneity or polymorphism in human beta 2m.     

Effects of tibolone on lipoprotein(a) and HDL subfractions

Objective: To determine the effects of tibolone, a synthetic steroid used to alleviate climacteric symptoms and prevent osteoporosis, on lipoprotein metabolism, with particular reference to lipoprotein(a) levels and HDL subfraction profiles.Design: Thirty nine postmenopausal women were treated with tibolone (Livial) 2.5 mg/day for 6 months and fasting serum lipoprotein levels were estimated at 0, 2, 4 and 6 months. Results: Lipoprotein(a) levels were reduced significantly over the 6 months from a median level of 245 (range <60–780) mg/I to 152 (range <60–530) mg/l, a reduction of 39% in the median level. A decrease was observed in approximately two thirds of the women. Reductions were noted in all 6 subjects whose pretreatment levels were high, although concentrations remained at a level associated with increased risk in all but one. There were significant decreases in triglycerides and VLDL cholesterol and no significant change in LDL cholesterol. There was a significant reduction of 18% in HDL cholesterol and a 26% reduction in the HDL₂:HDL₃ ratio. Conclusion: The reduction in lipoprotein(a) levels may have a beneficial effect on cardiovascular risk, which could go some way towards balancing the potentially adverse effect on the cardiovascular system caused by the reduction in HDL cholesterol.     

Follow-up of solitary autonomous thyroid nodules treated with 131I

We studied the long-term effects of 131I therapy for solitary autonomous thyroid nodules on the size of the nodule and on thyroid function. Twenty-three patients with autonomous thyroid adenomas that had been treated with 131I from 4 to 16.5 years earlier (mean, 8.5) were examined, and their thyroid function was tested. In 12 patients (54 per cent), the nodules were still palpable, and in 2 they had increased in size. Eight patients (36 per cent) had become hypothyroid. The incidence of hypothyroidism was not related to nodule size or the level of thyroid function before therapy with 131I or to the total dose of 131I that had been given. We conclude that 131I therapy for autonomous thyroid adenoma often causes hypothyroidism and in many cases does not eradicate the offending nodule.     

The clinical pharmacokinetics of the novel antifolate N10-propargyl-5,8-dideazafolic acid (CB 3717)

Summary The pharmacokinetics of the new antifolate CB 3717 were studied in 20 patients during its phase-I clinical evaluation. The drug was administered at doses of 100–550 mg/m² in 1-h and 12-h infusions, resulting in peak plasma concentrations of CB 3717 of 40–200 M. There was a linear relationship between the dose and both CB 3717 AUC and peak plasma levels. Following a 1-h infusion, drug levels in the plasma decayed biphasically (t_1/2=49±9 min, t_1/2=739±209 min). 27%±2% of the dose was excreted in urine in the 24-h period after treatment, suggesting that the major route of elimination was via the bile. Furthermore, the parent compound CB 3717 and its desglutamyl metabolite, CB 3751, were found in a faecal collection although the metabolite was not detected in plasma or urine samples. Plasma protein binding of CB 3717 was extensive (97.6%±0.1%). Significant quantities of CB 3717 penetrated into ascitic fluid but not into cerebrospinal fluid.Residual drug was detected in postmortem kidney tissue from a patient who died of progressive disease 8 days after treatment with 330 mg/m² CB 3717. Thus, dose-limiting renal toxicity (maximum tolerated dose 600 mg/m²) may be due to drug precipitation in the renal tubules. Elevation of liver enzymes, in particular transaminases, occurred frequently as a toxic manifestation of CB 3717 therapy. In 11 patients studied after their first treatment there was a positive correlation between the rise in serum alanine transaminase and peak drug levels (r=0.69, P=0.02)These pharmacokinetic studies have shown that, by analogy with experimental systems, cytotoxic plasma levels of CB 3717 are archieved in man. In addition, they have been valuable in interpreting toxicities observed during phase-I clinical studies.This work was supported by grants from the Medical Research Council and Cancer Research Campaign, U. K.     

Changing aspects of radiation enteropathy

Fifty-two patients with radiation enteropathy secondary to radiation for abdominal or pelvic malignant neoplasms are described. This series (1977 to 1984) is compared with a series of 50 patients from the same institution over an earlier period (1961 to 1977). Intestinal obstruction was the principal complication in both series; 96% of the patients underwent either intestinal resection or anastomotic bypass of the affected segment. Changes that have occurred since the last report are as follows: changes in source of radiation energy (linear accelerator); less evidence of mucosal damage; increased serosal reaction ("serosal peel"); and increased use of elemental diets, parenteral nutrition, and long intestinal tubes in surgical management. Since postoperative radiation injury occurs most frequently in the pelvis, new developments for the exclusion of small bowel from the pelvis during radiation are reviewed. Changes in fractionation of radiation dosage should also be considered in patients with enteric symptoms during radiation therapy.     

Spoilage of hydrogel contact lenses by lipid deposits. Tear-film potassium depression, fat, protein, and alcohol consumption

"Jelly-bump" deposits, which are composed mainly of lipids, on high water content, extended-wear hydrogel lenses, are a clinically significant problem of unknown etiology. The authors explored the effect of nutrition on the frequency of deposition of these jelly bumps. Forty-three patients were included in this masked case-control study from five contact lens practices in North America. Thirty patients were lipid-depositor cases and 13 were controls. Tear specimens were drawn and analyzed for potassium by atomic-absorption spectrophotometry. Detailed dietary histories were conducted and diet nutrient composition was computed. Patients with diminished tear-potassium concentrations have an increased risk of jelly-bump deposition. Elevated intake of protein, alcohol, and cholesterol also appeared to be correlated significantly with increased jelly-bump deposition. The authors found that diabetics and the use of diuretics, anticholinergics, sympathomimetics, were associated with tear-film potassium depletion and lipid deposit formation.     

Northern infant syndrome: a deficiency state?

A syndrome is described that affected 16 Indian and Inuit infants roughly 3 months old, most of whom were born in settlements in the Canadian Arctic. The infants presented with a clinical picture that included hepatitis, hemolytic anemia, rickets and respiratory distress, a combination that resembled a syndrome first described in malnourished infants at the turn of the century by von Jaksch and Luzet. The clinical course was self-limited, and all the infants survived without sequelae. The cause of the syndrome was not determined; no infectious agents were discovered. However, low levels of vitamins A, C, D and E were found in a few infants in whom assays were done. The implications of these findings and their relation to the possible cause of this "northern infant syndrome" are discussed.     

Enhancing Behavior Change Skills in Health Extension Workers in Ethiopia: Evaluation of an Intervention to Improve Maternal and Infant Nutrition

Maternal and infant nutrition are problematic in areas of Ethiopia. Health extension workers (HEWs) work in Ethiopia’s primary health care system, increasing potential health service coverage, particularly for women and children, providing an opportunity for health improvement. Their roles include improving maternal and infant nutrition, disease prevention, and health education. Supporting HEWs’ practice with ‘non-clinical’ skills in behavior change and health communication can improve effectiveness. This intervention study adapted and delivered a UK-developed training intervention for Health Extension Workers (HEWs) working with the United Nations World Food Programme in Ethiopia. The intervention included communication and behavioral training adapted with local contextual information. Mixed methods evaluation focused on participants’ reaction to training, knowledge, behavior change, and skills use. Overall, 98 HEWs were trained. The intervention was positively received by HEWs. Pre-post evaluations of communication and behavior change skills found a positive impact on HEW skills, knowledge, and motivation to use skills (all p < 0.001) to change women’s nutritional behavior, also demonstrated in role-play scenarios. The study offered substantial learning about intervention delivery. Appropriate cultural adaptation and careful consideration of assessment of psychological constructs are crucial for future delivery.