A human immunodeficiency syndrome caused by mutations in CARMIL2.

Human T-cell function is dependent on T-cell antigen receptor (TCR) and co-signalling as evidenced by immunodeficiencies affecting TCR-dependent signalling pathways. Here, we show four human patients with EBV+ disseminated smooth muscle tumours that carry two homozygous loss-of-function mutations in the CARMIL2 (RLTPR) gene encoding the capping protein regulator and myosin 1 linker 2. These patients lack regulatory T cells without evidence of organ-specific autoimmunity, and have defective CD28 co-signalling associated with impaired T-cell activation, differentiation and function, as well as perturbed cytoskeletal organization associated with T-cell polarity and migration disorders. Human CARMIL2-deficiency is therefore an autosomal recessive primary immunodeficiency disorder associated with defective CD28-mediated TCR co-signalling and impaired cytoskeletal dynamics.

[Tumor-associated macrophages: Function and differentiation]. / Tumorassoziierte Makrophagen : Funktion und Differenzierung.

Macrophages are important factors in the pathogenesis and prognosis of malignant tumors and represent a possible target for therapeutic intervention. Depending on the tumor entity and the prevalent polarization status, macrophages can be associated with a favorable or unfavorable clinical outcome. It is becoming clear, however, that the conventional definitions of M1 polarized tumor inhibitory and M2 polarized tumor promoting macrophages do not adequately reflect the heterogeneity and plasticity of macrophages. Macrophages can support tumor growth through direct interactions with the neoplastic cells, by promoting tissue remodeling and angiogenesis and by inhibiting local immune reactions. To achieve comparability of clinical studies, it will be necessary to reach a consensus nomenclature of macrophage polarization. Furthermore, methods for the quantitative characterization of macrophage populations in malignant tumors will have to be standardized. It is unlikely that single marker immunohistochemistry will be adequate in this context. In any case it is necessary to provide unequivocal information regarding the markers or marker combinations used.

Chilblain lupus erythematosus--a review of literature.

Chilblain lupus erythematosus (CHLE) is a rare, chronic form of cutaneous lupus erythematosus. Sporadic cases and two families with autosomal dominant-inherited CHLE have been reported. In familial CHLE, two missense mutations in TREX1 encoding the 3'-5' repair exonuclease 1 were described in affected individuals. The pathogenesis of sporadic CHLE remains unknown. Up to 20% of patients develop systemic lupus erythematosus (SLE). An association with anorexia is discussed. In many cases, there is good response to symptomatic therapy. SLE therapeutics have good effects on SLE-typical symptoms but not on chilblains themselves. This article reviews the clinical presentation, pathogenesis, diagnosis and treatment of CHLE. As an index patient with unique features, we report a 13-year-old boy developing CHLE after anorexia nervosa. Sequencing of TREX1 was normal. With psychotherapeutic support for anorexia and after antibiotic therapy, topical steroids, physical warming and calcium channel blockers, the patient experienced significant relief. Improvement of phalangeal perfusion was demonstrated by angio-MRI.

Laryngeal basement membrane thickening is not a reliable postmortem marker for SIDS: results from the Chicago Infant Mortality Study.

It has been suggested that laryngeal basement membrane (LBM) thickening is a pathognomonic postmortem marker for sudden infant death syndrome (SIDS) and is not seen in other causes of explained sudden infant death. To test this hypothesis, we evaluated longitudinal sections of the right hemilarynx taken through the midpoint of the true vocal cord from 129 SIDS cases and 77 postneonatal sudden infant death controls. Using a five-point semi-quantitative scale, maximum LBM thickness (LBMT) for SIDS cases and controls was not statistically different (mean, 2.39 + 0.69 and 2.40 + 0.77, respectively). Likewise, scores based on the average thickness along the entire basement membrane (i.e., "average" score), were not found to be different between SIDS cases and controls. Average and maximum LBMT increased with age in both SIDS cases and controls and were not different between SIDS cases and controls within each age interval. Similar trends in the distribution of maximum and average LBMTs were found between black and Hispanic SIDS and controls; the number of white/non-Hispanic infants was too low for meaningful comparisons. Maximum and average LBMTs were not different in SIDS cases and controls exposed to environmental tobacco compared with unexposed infants. The LBMTs also increased significantly with body weight and length in both SIDS cases and controls. Finally, there were no differences in LBMT in infants intubated prior to death compared with those who were not intubated. From these data, we conclude that LBMT is not pathognomonic of SIDS, is present or absent with equal frequency in SIDS and controls, increases with postnatal age, and does not correlate with passive smoke exposure. Therefore, LBMT should not be used to diagnose SIDS.

Sudden infant death syndrome rates subsequent to the American Academy of Pediatrics supine sleep position.

OBJECTIVES: In April 1992, the American Academy of Pediatrics (AAP) recommended that healthy infants be positioned for sleep on their side or back to reduce the risk of Sudden Infant Death Syndrome (SIDS). The authors hypothesized three different forms of the intervention to examine the impact of the recommendation according to theory such as technology diffusion. Seasonality was included in the models to control its effect when testing. METHODS: Box and Tiao time-series intervention methodology was used to examine the effect of the AAP recommendation on SIDS rates. Sudden Infant Death Syndrome mortality data from Philadelphia and Chicago were examined separately for white and nonwhite populations over 32 quarters. RESULTS: Overall SIDS rates dropped significantly according to an abrupt effect from the intervention. However, the effect appeared to be gradually declining in Philadelphia but permanent in Chicago. In Philadelphia, a decline of 62.3% was estimated in whites in the first quarter after the intervention but decreased to only 5% in the last quarter of 1994. A decline of 35.8% was estimated in nonwhites in the first quarter after the intervention but decreased to only 9.4% in the last quarter of 1994. An abrupt and permanent decrease of 26.7% and 16.5% was found in Chicago for whites and nonwhites, respectively. CONCLUSIONS: Evidence of an abrupt adoption of the recommendation can be explained by the authority innovation decision made by the AAP. Some evidence was found that the effect is temporary, perhaps because physicians are reversing earlier decisions. The demonstrated methodology provides a powerful way to test naturally occurring interventions from quasiexperimental designs to test the impact of policy guidelines.

Inaccuracy of self-reported weights and heights among American Indian adolescents.

To determine the accuracy of self-reported weights and heights and of relative weight status in a sample of American Indian adolescents, a survey was conducted in middle and high schools on or near three Indian reservations-Navajo, Choctaw, and Blackfeet. Self-reported weights and heights were compared with measured weights and heights. Participants were 12 through 19 years old. (N = 806, 47.4% male). Overall, both boys and girls underreported weight (mean difference = self-reported - measured mean values)(-3.4 +/- 13.1 and -4.6 +/- 13.0 lb, respectively) and overreported height (0.6 +/- 2.1 and 0.2 +/- 2.6 in, respectively) However, underweight boys and girls overreported weight (normal: -1.6 +/- 7.9 and -1.4 +/- 6.3; overweight: -7.5 +/- 17.9 and -11.6 +/- 19.0 lb, respectively). Although correlations between measured and reported weight, height, and body mass index (BMI) were high, the sensitivity of relative weight categories based on BMI using self-reported weight and height compared with measured weight and height was poor: 66.7% for underweight (BMI < 15th percentile, based on a national reference population), 88.9% for normal weight, and 73.6% for overweight (> 85th percentile). These results call into question the accuracy of self-reported weight and height measurements among American Indian youth and are similar to findings among non-American Indian adolescents. Therefore, their use in prevalence studies should be avoided, and they should be used cautiously in other types of epidemiologic studies.

Weight perceptions and weight control practices in American Indian and Alaska Native adolescents. A national survey.

OBJECTIVE: To assess weight perceptions and weight control practices among American Indian-Alaska Native adolescents. DESIGN: Survey. SETTING: Nonurban schools from eight Indian Health Service areas. PARTICIPANTS: A total of 13,454 seventh- through 12th-grade American Indian-Alaska Native youths. MAIN OUTCOME MEASURES: A revised version of the Adolescent Health Survey, a comprehensive, anonymous self-report questionnaire with eating- and body image-related questions. RESULTS: Forty-one percent of the adolescent girls reported feeling overweight, 50% were dissatisfied with their weight, and 44% worried about being overweight. Almost half (48%) had been on a weight-loss diet in the past year, with 27% reporting that they had self-induced vomiting at some time to try to lose weight. Eleven percent reported using diet pills. Girls who reported feeling overweight were more likely to engage in unhealthy weight control practices than were those who felt they were of normal weight or underweight. A larger proportion of boys were satisfied with their weight (68%), with 22% worrying about being overweight. However, compared with rural Minnesota youth, both American Indian girls and boys had greater dissatisfaction with body weight. CONCLUSIONS: Our study shows that American Indian youth, particularly girls, are dissatisfied with their weight and are worried about being overweight, and that unhealthy weight control practices are common. More attention needs to be placed on developing culturally appropriate weight management programs for Indian youths.

Trends in anthropometric measurements among Mescalero Apache Indian preschool children. 1968 through 1988.

OBJECTIVE: To determine if there were trends in underweight, short stature, and obesity among 1- through 5-year-old Mescalero (NM) Apache Indian children from 1968 through 1988. DESIGN: Cross-sectional review of hospital clinic charts for five cohorts. SETTING: General pediatric outpatient clinic at the Mescalero Indian Health Service Hospital. PARTICIPANTS: Sixty-nine patients aged 1 through 5 years in 1968, 1973, 1978, 1983, or 1988 for whom weight and height were recorded during a well-child visit that occurred in the respective year. SELECTION PROCEDURES: Approximately half the charts were screened for eligibility through systematic sampling for all years except 1988; for 1988 all available charts were screened for eligibility for the study. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: We found trends of decreasing prevalence of both underweight (defined as weight-for-height below the fifth percentile) and short stature (defined as height-for-age below the fifth percentile) based on the Centers for Disease Control/World Health Organization growth reference. We found no secular trends in obesity (weight-for-height above the 95th percentile), although the prevalences throughout the 21-year period were as much as two to four times higher than expected when compared with the Centers for Disease Control/World Health Organization reference. There has been an upward shift in both weight-for-height and height-for-age distributions since 1968, indicating that Mescalero children today are, on average, heavier and taller. CONCLUSIONS: Underweight and short stature decreased among Mescalero preschool children from 1968 through 1988, suggesting nutritional improvements. However, given the current high prevalence of obesity, it is recommended that surveillance of nutritional status be continued and appropriate interventions be developed to treat and prevent obesity in this population.

Primary health care in Senegal: lessons learned.

PIP: USAID began funding the Rural Health Delivery Services Project (RHDS) in Sine Saloum region (later divided into 2 regions--Kaolack and Fatick) of Senegal in 1977. Its aim was to improve the health of rural inhabitants and to set up a model health care delivery system. It specifically set out to increase agricultural output by reducing illness-related absence from work. USAID funds and local taxes paid for the construction of almost 400 village health huts, each staffed by a 1st aid worker and a traditional birth attendant. In 1982, 90% of villagers sought preventive and curative services from the health huts. In 1984, USAID extended funding to a 2nd phase of the RHDS II/Child Survival (CS) project which aimed to expand preventive health efforts and to introduce new preventive services targeting pregnant women and children. These services were immunizations, malaria control, oral rehydration therapy, and growth monitoring. Other objectives were to integrate these services and to institute program sustainability. Other agencies also were involved, such as UNICEF. RHDS II/CS successfully integrated several interventions at health hut and health post levels. An evaluation team found that the spirit of village-based primary health care made the RHDS system work. No follow-up survey to a 1982-83 baseline survey occurred, making it difficult for the team to determine whether RHDS II/CS achieved child survival goals. It recommended that teams have both expatriate and native representatives who are flexible and adaptable to local conditions and constraints and that agencies be pragmatic in their objectives and expectations about what evaluation teams can accomplish and provide advance documents to team members to allow them more of their often limited time in the country to do field work. The team called for donor agencies to cooperate on reporting requirements. It also suggested that new programs should be added to existing health systems and structures instead of forsaking previous successes.^ieng

Obesity among Mescalero preschool children. Association with maternal obesity and birth weight.

The prevalence of obesity among native American children ranks with the highest in the United States. However, little is known about associated risk factors for obesity among these children. We conducted a medical record review of 261 preschool children enrolled in the Mescalero Apache tribe to determine the prevalence of obesity and associated risk factors. The prevalence of obesity (weight for height greater than 95th percentile) in this population was 19.5%. The prevalence of obesity (body mass index greater than 95th percentile) in their mothers was 23%. Children with obese mothers were more than twice as likely to be obese than children of nonobese mothers. Children with a high birth weight were three times as likely to be obese as children of low or normal birth weight. The high prevalence of obesity may be due to both life-style and dietary patterns on the reservation. Family-based interventions are needed to prevent obesity and its long-term consequences in this population.

Prevalence of obesity in American Indians and Alaska Natives.

Obesity is an important risk factor for cardiovascular diseases and non-insulin-dependent diabetes, which are chronic diseases that afflict American Indians and Alaska Natives today. Because American Indians are not represented in most national health and nutrition surveys, there is a paucity of data on actual prevalence of obesity in American Indians. We estimated prevalence of overweight and obesity for American Indian adults, school-age children, and preschool children from existing data. The prevalence of obesity in adults was estimated from self-reported weights and heights obtained from a special survey of American Indians performed as part of the 1987 National Medical Expenditure Survey. Prevalence of obesity in American Indians was 13.7% for men and 16.5% for women, which was higher than the US rates of 9.1% and 8.2%, respectively. Obesity rates in American Indian adolescents and preschool children were higher than the respective rates for US all-races combined.

Patient perceptions of humanism in physicians: effects on positive health behaviors.

Although humanism has emerged as an important issue in medical education and practice, there is no standardized definition of humanism or an instrument that measures patients' perceptions of their physician's level of humanism. This study addressed these three issues: 1) A definition of physician humanism was developed based on the current literature; 2) an instrument was designed that measured patients' perceptions of humanism in their family physicians; and 3) health outcome variables were measured relative to these perceptions. The design was a cross-sectional survey of 185 randomly selected patients from two family practice sites. The questionnaire consisted of a humanism scale, in addition to items to assess patient satisfaction and patients' adherence to medical advice regarding exercise, diet, and smoking cessation. A positive association was found between perceived physician humanism and patient satisfaction. Greater success in patients' attempts to quit smoking was associated with higher physician humanism. The implications of these findings for evaluation and training of health care providers and patients' use of health care services are discussed.

Treating childhood respiratory illness in developing countries: mist therapy without electricity.

We have developed an effective and well-accepted method of providing mist for children with acute respiratory distress. This method can be especially useful in areas of the world where resources are limited.