Undernutrition and childhood infections: a prospective study of childhood infections in relation to growth in the Sudan

The relationships between both diarrhoea and respiratory infections and linear and ponderal growth were prospectively examined among 28 753 Sudanese pre-school children. Childhood infections were significantly and inversely associated with attained height and attained weight and gain in height and weight over a 6-mo period. They were significantly and positively associated also with stunting after adjusting for age, gender, socio-economic status, dietary variables and previous morbidity. Attained height was on average 17 mm lower (95% CI [-19 -15]) for children with diarrhoea and 11 mm lower (95% CI [-3 -9]) for children with complicated cough than for those without these symptoms. The association between morbidity and attained weight was significant for diarrhoea and complicated cough, but the differences between children with and without symptoms were negligible. The risk of being stunted 6 mo later was 1.38 times (95% CI [1.20 1.59]), 1.29 times (95% CI [0.97 1.72]) and 1.32 times (95% CI [1.13 1.54]) greater among normally-nourished children with diarrhoea, febrile diarrhoea and fever, respectively, than among children without these symptoms. The difference in attained height between children with diarrhoea or complicated cough and those without symptoms increased with age, and was larger among the non-breastfed children compared with breastfed children. CONCLUSION: The results underline the need to reduce child morbidity to prevent the impairment of growth and development.     

A randomized trial of vitamin A supplements in relation to mortality among human immunodeficiency virus-infected and uninfected children in Tanzania

OBJECTIVES: To determine whether vitamin A supplements result in reduced mortality among HIV-infected and uninfected children. DESIGN: Randomized, double blind, placebo-controlled trial. METHODS: Starting in April, 1993, we randomized 687 children age 6 months to 5 years who were admitted to the hospital with pneumonia. Children who were severely malnourished or had clinical signs of vitamin A deficiency were excluded. At baseline children received placebo or 400 000 IU (or half that for infants) of vitamin A, in addition to standard treatment for pneumonia. They received further doses of the same regimen 4 and 8 months after hospital discharge. Sera from children were tested for HIV antibodies by enzyme-linked immunosorbent assay and Western blot tests. For positive children <15 months of age, HIV infection was confirmed by amplified heat-denatured HIV-p24 antigen assays with confirmatory neutralization assays. HIV status was ascertained for 648 of 687 enrolled children. The mean duration of follow-up was 24.4 months (SD = 12.1). RESULTS: Of 648 children 58 (9%) were HIV-infected. Compared with uninfected children, all-cause mortality was higher among HIV-infected children, as was mortality caused by pneumonia or diarrhea (P < 0.001 for each). Overall vitamin A supplements resulted in a 49% reduction in mortality [relative risk (RR), 0.51; 95% confidence interval (CI), 0.29 to 0.90, P = 0.02]. Vitamin A supplements reduced all-cause mortality by 63% among HIV-infected children (RR 0.37; CI 0.14 to 0.95, P = 0.04) and by 42% among uninfected children (RR 0.58, CI 0.28 to 1.19, P = 0.14). Vitamin A supplements were also associated with a 68% reduction in AIDS-related deaths (P = 0.05) and a 92% reduction in diarrhea-related deaths (P = 0.01). CONCLUSION: Vitamin A deficiency, which is common among children in many developing countries, is particularly severe among HIV-infected children. Our findings indicate that vitamin A supplements, a low cost intervention, reduce mortality of HIV-infected children.     

Smooth muscle cell expression of a constitutive active form of human Rac 1 accelerates cutaneous wound repair

BACKGROUND: Hyperoxia has been shown to improve wound healing; however, the mechanism for such therapeutic effects of oxygen remains hypothetical. Rac 1 regulates a wide variety of cellular activities, including cell proliferation and migration, and also is a key regulator for the activity of the nicotinamide dinucleotide phosphate oxidase the enzyme complex responsible for the production of a large fraction of cellular superoxide. METHODS: We generated transgenic mice that express either the cDNA of a constitutively active mutant of human Rac 1 (V12 mutant or Rac CA) or the dominant negative isoform (V12 and N17 mutant or Rac DN) in the blood vessels using mouse vascular smooth muscle promoter for alpha-actin. We placed 2 wounds of 6 mm in diameter at the middorsal region of each mouse and allowed about 3 weeks for the wounds to heal. RESULTS: The size of the wounds in Rac CA transgenic mice was reduced relative to wild type mice; healing of Rac DN mice was slower than wild type and Rac CA ( P < .05). Blood vessel formation appeared faster in Rac CA mice, a finding associated with enhanced expression of some angiogenic growth factors. CONCLUSION: The current studies suggest that Rac 1 activation accelerates the wound healing process and is associated with more efficient angiogenesis at the wound site.     

Vitamin supplementation of HIV-infected women improves postnatal child growth

BACKGROUND: Linear growth retardation and wasting are common in children born to HIV-infected women. Inexpensive interventions that could improve the postnatal growth pattern of such children are needed. OBJECTIVE: The objective was to examine the effect of supplementing HIV-infected women with multivitamins or vitamin A and beta-carotene, during and after pregnancy, on the growth of their children during the first 2 y of life. DESIGN: We conducted a randomized placebo-controlled trial in 886 mother-infant pairs in Tanzania. At the first prenatal visit, HIV-infected women were randomly assigned to 1 of 4 daily oral regimens in a 2 x 2 factorial fashion: multivitamins (MV: thiamine, riboflavin, vitamin B-6, niacin, vitamin B-12, vitamin C, vitamin E, and folic acid), preformed vitamin A + beta-carotene (VA/BC), MV including VA/BC, or placebo. Supplementation continued during the first 2 y postpartum and thereafter. Children were weighed and measured monthly, and all received vitamin A supplements after 6 mo of age per the standard of care. RESULTS: Multivitamins had a significant positive effect on attained weight (459 g; 95% CI: 35, 882; P = 0.03) and on weight-for-age (0.42; 95% CI: 0.07, 0.77; P = 0.02) and weight-for-length (0.38; 95% CI: 0.07, 0.68; P = 0.01) z scores at 24 mo. VA/BC seemed to reduce the benefits of MV on these outcomes. No significant effects were observed on length, midupper arm circumference, or head circumference. CONCLUSION: Supplementation of HIV-infected women with multivitamins (vitamin B complex, vitamin C, and vitamin E) during pregnancy and lactation is an effective intervention for improving ponderal growth in children.     

Trial of zinc supplements in relation to pregnancy outcomes, hematologic indicators, and T cell counts among HIV-1-infected women in Tanzania

BACKGROUND: In observational studies, the zinc status of HIV-infected persons has been associated with both positive and adverse clinical outcomes. Such endpoints may affect the risk of adverse birth outcomes among HIV-infected women. OBJECTIVE: We examined the effects of zinc supplements on birth outcomes, hematologic indicators, and counts of T lymphocyte subsets among 400 HIV-infected pregnant women. DESIGN: Eligible women between 12 and 27 wk of gestation were randomly assigned to daily oral supplementation with either 25 mg Zn or placebo between recruitment and 6 wk after delivery. All women received iron, folic acid, and multivitamin supplements irrespective of the experimental assignment. RESULTS: We observed no significant differences in birth weight, duration of gestation, or fetal and neonatal mortality between women in the zinc and placebo groups. Hemoglobin concentrations increased between baseline and 6 wk postpartum in both groups. However, the rise in hemoglobin over this period was significantly lower (P = 0.03) in the zinc group (x +/- SD: 11.5 +/- 17.9 g/L) than in the placebo group (15.2 +/- 18.6 g/L). Similarly, the changes in red blood cell count and in packed cell volume over the same period were significantly lower in the zinc group (P < 0.01 and P = 0.01, respectively). Zinc had no effect on CD4(+), CD8(+), or CD3(+) cell counts during the follow-up period. CONCLUSION: Because of the lack of beneficial effects of zinc on adverse pregnancy outcomes and the likelihood of negative effects on hemoglobin concentrations, no compelling evidence exists to support the addition of zinc to prenatal supplements intended for pregnant HIV-infected women.     

Plasma zinc concentrations are depressed during the acute phase response in children with falciparum malaria

Plasma concentrations of some micronutrients are altered in the setting of acute infectious or inflammatory stress. Previous studies have provided conflicting evidence concerning the extent and direction of changes in plasma zinc concentrations during the acute phase response. We carried out an observational cohort study in 689 children enrolled in a randomized trial of zinc supplementation during acute falciparum malaria in order to evaluate the relation between plasma zinc concentration and the acute phase response. Plasma zinc was measured by atomic absorption spectrophotometry. On admission, 70% of all subjects had low plasma zinc (<9.2 micromol/L). Multivariate analysis of predictors of admission plasma zinc showed that admission C-reactive protein (CRP), parasite density, and study site were the most important predictors. Predictors of changes in plasma zinc from admission to 72 h included baseline CRP, change in CRP, treatment group, study site, and baseline zinc concentration. In children with acute malaria infection, baseline plasma zinc concentrations were very low and were inversely correlated with CRP (r = -0.24, P < 0.0001) and the degree of parasitemia (r = -0.19, P < 0.0001). Even when CRP and time were taken into account, zinc supplementation increased plasma zinc concentration from admission to 72 h. When available, plasma zinc concentrations should be interpreted with concurrent measures of the acute phase response such as CRP. In children whose age, diet, and/or nutritional status place them at risk of zinc deficiency, those with low plasma zinc levels should be supplemented with oral zinc and followed for clinical and/or biochemical response.     

Chronic perforation of the sigmoid colon by foreign body

Colorectal foreign bodies (FBs) may be ingested or introduced transanally and then migrate proximally. Without a reliable history, it may be impossible to determine which way a certain colorectal FB gained access. We present a case of a nonverbal mentally retarded boy with a flat piece of plastic impacted in the sigmoid colon, the colonoscopic extraction of which failed. He underwent laparotomy more than a year later to remove the FB, where chronic perforation of the sigmoid colon was discovered. The perforation was sealed with extensive adhesions to the pelvic wall, and histologically, the colon showed a chronic granulomatous reaction. We discuss the types, presentations, and diagnosis of intestinal perforation with FBs. Chronic perforation may present with radiologic and pathologic features that suggest inflammatory bowel disease.     

Experience with incompatible maternal donors for bone marrow transplantation

Summary Marrow transplantation in aplastic anemia and leukemia has generally been limited to siblings who have been histocompatible at both the serological (A and B) and lymphocyte determined (D or MLC) loci of the HLA system. We studied three male patients, two with aplastic anemia and one with acute myelogenous leukemia, who received transplants from their histoincompatible mothers. MLC studies between donors and recipients showed varying degrees of stimulation. Definite engraftment occurred in one patient and transient engraftment in another. Engraftment in the third patient could not be evaluated. In the patient with sustained engraftment, there was clinical evidence of severe graft versus host disease (GVHD) however, this was not substantiated by histologic findings. This preliminary study suggests that MLC incompatibility may be more of an indicator of the risk of GVHD than of bone marrow rejection. If more effective control of GVHD can be accomplished, marrow transplantation between MLC-reactive individuals may become feasible.This work was presented, in part, at the Fourth Congress of the International Society for Experimental Hematology, Trogir, Yugoslavia, September 24, 1975.     

Blood supply and oxidative metabolism in muscle biopsies of female cleaners with and without myalgia

OBJECTIVES: Pathomechanisms of work-related myalgia are poorly understood. Myalgia is thought to be caused by excitation of nociceptors present in the muscular tissue but not in the muscle fiber itself. Muscle contraction in combination with hypoxia is known to excite nociceptors. Morphologic analysis can contribute to the knowledge of the excitation of nociceptors. This study thoroughly examines the morphology of the trapezius muscle's capillary supply and signs of disturbed oxidative metabolism to understand their role in work-related myalgia. METHODS: Surgical trapezius muscle biopsies were obtained from 25 female cleaners with long-standing work-related myalgia, 25 female cleaners without trapezius myalgia, and 21 healthy teachers. Enzyme and immunohistochemical stainings were performed to highlight fibers with aberrant intermyofibrillar patterns, indicating a disturbed oxidative metabolism (also known as moth-eaten fibers) and a disturbed capillary supply of different fibers. RESULTS: A significantly lower number of capillaries per fiber area in cleaners suffering from myalgia compared with cleaners without trapezius myalgia was found. Moth-eaten fibers were found in the 3 groups, but these fibers were significantly more prevalent in the groups of cleaners than in the healthy teacher group. CONCLUSION: This work indicates that the capillary supply of trapezius is affected in work-related trapezius myalgia. More studies are needed to understand possible mechanisms that would explain the occurrence of moth-eaten fibers.