Determinants of linear growth and predictors of severe stunting during infancy in rural Malawi

Stunting is common among children under 5 y of age in sub-Saharan Africa. Several risk factors have been associated with poor growth but few studies have prospectively addressed the development of linear growth faltering and stunting during the first year of life. The present study was designed to analyse typical growth among rural Malawian infants, focusing particularly on the impact of birth size, adherence to feeding guidelines and morbidity in the development of severe stunting during infancy. A community-based cohort of 613 singleton newborns was prospectively followed by monthly home visits. Data were collected on the children's socioeconomic background, maternal size and weight gain during pregnancy, birth events, morbidity, breastfeeding and complementary feeding, growth and mortality. Univariate and multivariate analyses were used to determine associations between predictor variables and poor linear growth. The proportions of stunted infants (Height-for-age Z-score 3 32) at 3, 6 and 9 mo of age were 27%, 51%, and 63%, respectively. At 1 y of age, over two-thirds (71%) of the infants were at least moderately (HAZ 3 32) and 31% severely stunted (HAZ 3 33). Conclusion: The strongest predictor of severe stunting at 12 mo of age was small birth size. Other variables independently associated with this outcome included inappropriate complementary feeding, high morbidity, maternal short stature, male gender, and home delivery. Faltering of linear growth started soon after birth and continued throughout infancy. Interventions increasing birth size could have a significant role in the prevention of early childhood stunting. The ideal strategy should also emphasize the importance of appropriate infant feeding and decreasing the number of illness episodes amongst the infants.     

Exposure-response relations among laboratory animal workers exposed to rats

Aim: To explore exposure-response relations in a cohort of laboratory animal workers.     

Occupational distribution and geographic clustering of deaths certified to be cryptogenic fibrosing alveolitis in england and wales

STUDY OBJECTIVES: The etiology of cryptogenic fibrosing alveolitis (CFA) remains largely obscure, although a 1996 report suggested an increased risk from occupational exposure to metal and wood dusts. Using data from death certificates in England and Wales, we sought evidence of any relationship between occupation and CFA and of the extent of any temporospatial clustering of place of birth and place of death as possible evidence of a geographically related environmental factor. DESIGN AND SETTING: Data on occupation and address (postal code) were obtained from certificates of men and women dying as a result of CFA between 1981 and 1990 and were compared with national mortality statistics. Place of birth data were extracted from certificates for deaths between 1993 and 1995, the only available years, and were compared with national birth statistics. MEASUREMENTS AND RESULTS: Standardized mortality ratios (SMRs) were raised (p<0.05) in the following four occupational groups: members of the armed forces (SMR, 217.8); miners and quarrymen (SMR, 142.0); service, sports, and recreation workers (SMR, 118.6); and electrical and electronic workers (SMR, 146.6). Of these four groups, the latter group might be worth testing in a future study. There was statistical evidence of geographic clustering in postal code sectors for the recorded place of death, but the high-rate areas were different in men and women. Deaths were increased for those subjects born in urban areas, although these did not follow a clear geographic pattern. CONCLUSIONS: Overall, these analyses provide little evidence of any important contribution from environmental factors to the etiology of CFA and suggest that more consideration be given to alternative concepts of causation.     

The distal pole complex: a novel membrane domain distal to the immunological synapse

Summary: While much interest has focused on the finding that T cell–antigen presenting cell (APC) interaction induces the recruitment of proteins to the immunological synapse (IS), we have recently discovered that APC binding induces the formation of a novel protein complex distal to the site of T‐cell receptor ligation. This ‘distal pole complex’ (DPC) is important for appropriate T‐cell activation, functioning either to remove proteins from the synapse or as a signaling complex in its own right. The first component of the DPC to be identified was CD43, a cell‐surface mucin that has been proposed to function as a negative regulator of T‐cell signaling. CD43 movement was found to depend on ezrin and moesin, members of the ERM family, which serve to link CD43 and other cargo molecules to the actin cytoskeleton. ERM proteins interact with several other important surface receptors and cytoplasmic signaling molecules, some of which we have identified as additional components of the DPC. Disruption of the DPC leaves early T‐cell activation events intact but affects cytokine expression. Here, we review what is currently known about the formation and function of the DPC and speculate on how this novel protein complex serves to facilitate T‐cell activation.     

Periodontal disease and systemic illness: will the evidence ever be enough?

The concept of focal infection or systemic disease arising from infection of the teeth was generally accepted until the mid‐20th century when it was dismissed because of lack of evidence. Subsequently, a largely silo approach was taken by the dental and medical professions. Over the past 20 years, however, a plethora of epidemiological, mechanistic and treatment studies have highlighted that this silo approach to oral and systemic diseases can no longer be sustained. While a number of systemic diseases have been linked to oral diseases, the weight of evidence from numerous studies conducted over this period, together with several systematic reviews and meta‐analyses, supports an association between periodontitis and cardiovascular disease, and between periodontitis and diabetes. The association has also been supported by a number of biologically plausible mechanisms, including direct infection, systemic inflammation and molecular mimicry. Treatment studies have shown that periodontal treatment may have a small, but significant, systemic effect both on endothelial function and on glycemic control. Despite this, however, there is no direct evidence that periodontal treatment affects either cardiovascular or diabetic events. Nevertheless, over the past 20 years we have learnt that the mouth is an integral part of the body and that the medical and dental professions need to work more closely together in the provision of overall health care for all patients.     

Methods for the prediction of low-molecular-weight occupational respiratory sensitizers.

PURPOSE OF REVIEW: There is recognition that respiratory sensitization is an occupational hazard of high concern. Despite international regulatory requirements there is no established protocol for the efficient prospective identification of chemical respiratory sensitizers. We review the predictive behaviour of available methods and suggest a possible high-throughput protocol. RECENT FINDINGS: Animal or in-vitro tests specific to respiratory exposure and resulting in direct asthma-related outcomes have not been developed, although the use of a local lymph node assay originally designed for skin sensitization has been advocated in a respiratory context. Various methods have been used to develop quantitative structure-activity relationship models for prediction of low-molecular-weight organic chemical respiratory sensitizers. The estimated negative predictive value for all of the published models is 1, but their differences in positive predictive value can be exploited. SUMMARY: The most pragmatic as well as valid approach for screening large numbers of industrial chemicals for respiratory sensitization hazard is likely to consist of an algorithm starting with quantitative structure-activity relationship models. Further corroboration from animal or human data, however, may be required for chemicals with a positive result by quantitative structure-activity relationship.     

Allergen exposure, atopy and smoking as determinants of allergy to rats in a cohort of laboratory employees.

This study aimed to examine the relationship between exposure to rat urinary allergens, atopic status, smoking and the development of allergic symptoms and specific sensitization. It is a case-referent analysis of a cohort of 342 newly employed laboratory animal workers. Cases comprised persons developing symptoms of laboratory animal allergy or a positive skin prick test to rat urinary allergens; each was matched with up to two asymptomatic referents. Subjects were assigned to categories of exposure based on measurements of airborne rat urinary allergens. Of the cases, 80% reported that their symptoms started within 2 yrs of employment. The odds ratio (OR) for development of each symptom type (respiratory, eye or nose and skin) and of an immediate skin test reaction was increased in those with direct contact with rats. A gradient of increasing OR for the development of any such symptom across exposure categories was found; for respiratory symptoms and skin test reactions the OR for subjects in the highest exposure category were lower than those in intermediate categories, a pattern attenuated when the analysis was confined to outcomes developing within 2 yrs of first exposure. Atopy increased the OR of most outcomes as did cigarette smoking, although there was no evidence of a relationship between smoking and the development of a specific skin test reaction. In conclusion, allergen exposure was confirmed as the most important determinant of laboratory animal allergy; by implication, measures to reduce exposure may be the most effective means to reduce its incidence.     

Ineffectiveness of tamoxifen in advanced endometrial carcinoma after failure of progestin treatment

Between May 1980 and November 1983, 46 eligible patients with advanced, objectively evaluable endometrial carcinoma were treated with tamoxifen, 10 mg twice daily. Twenty-two of the patients had previously received progestational agents. None of the progestin-refractory patients experienced tumor regression on tamoxifen treatment, while five of the 24 previously untreated with progestins did experience tamoxifen-induced tumor regression. Of the five patients previously treated with cytotoxic drugs, only one experienced objective tumor regression on tamoxifen. Although 28 of these 46 patients were completely ambulatory at the beginning of tamoxifen treatment, only 26% were alive 1 year later; median survival for the entire group was only 120 days. Tamoxifen in this dose cannot be recommended routinely as effective secondary treatment for patients with progestin-refractory advanced endometrial carcinoma.     

Depression characteristics among mildly handicapped students

The present study was conducted to determine the prevalence of depressive characteristics among learning disabled, mentally retarded, and behaviorally disordered students. The influence of sex and age on the prevalence within each handicapping condition was also considered. A “depression subscale” of the Behavior Problem Checklistwas administered to 2078 learning disabled students, 705 behaviorally disordered students, and 1184 nonhandicapped students. The scores were examined via analysis of variance, as well as an extreme-scores analysis using the 95th percentile of nonhandicapped students as a criterion for extremely depressive functioning. The results indicated that (a) behaviorally disordered students, particularly older males, appear more depressed than learning disabled, mentally retarded, and nonhandicapped students; (b) mentally retarded students, particularly younger girls, appear more depressed than the nonhandicapped; (c) learning disabled students are not seen as significantly more depressed than nonhandicapped students. The extreme-scores analysis also revealed interesting interactions of student age and sex. The results are discussed with reference to the need for effective methods for differentially diagnosing handicapping conditions and depressive disorders. Emphasis is also placed on the need for effective strategies for treating depression in behaviorally disordered and mentally retarded students.