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Biomedical subjects

G L Darmstadt

Publications and source records attributed to G L Darmstadt.

At least 19 recordsLinked to original sources
PubMed2001

Zinc supplementation during pregnancy and effects on growth and morbidity in low birthweight infants: a randomised placebo controlled trial.

BACKGROUND: Infant malnutrition and mortality rates are high in less-developed countries especially in low-birthweight infants. Zinc deficiency is also widely prevalent in these circumstances. We aimed to assess the effect of daily zinc supplements given to pregnant mothers on their infants' growth and morbidity. METHODS: We did a double-blind, placebo controlled, randomised trial in 199 and 221 Bangladeshi infants whose mothers took 30 mg daily elemental zinc or placebo, respectively, from 12 to 16 weeks' gestation until delivery. Infants were followed up until 6 months of age. We obtained data for morbidity every week by mothers' recall. Infants' anthropometric measurements were done every month, and their serum zinc was assessed at 1 and 6 months of age. FINDINGS: Infants of mothers who received zinc during pregnancy had at age 6 months reduced risks compared with those in the placebo group for acute diarrhoea (risk ratio 0.84; 95% CI 0.72-0.98), dysentery (0.36; 0.25-0.84), and impetigo (0.53; 0.34-0.82). These reductions were seen in low-birthweight infants but not in those with normal birthweight. There were no differences in infant growth or serum zinc concentrations between treatment groups. INTERPRETATION: Maternal zinc supplementation during pregnancy resulted in a reduction of the health risks in Bangladeshi low-birthweight infants, although this intervention did not improve birthweight. Whether zinc should be added to usual antenatal supplements in regions with high rates of low birthweight should be reviewed.

Anthropometry↗
PubMed2001

Typhoid fever in Bangladesh: implications for vaccination policy.

OBJECTIVE: To describe the age-specific distribution of typhoid fever including the degree of Salmonella typhi bacteremia among patients evaluated at a large private diagnostic center in Bangladesh, a highly endemic area. METHODS: We conducted a prospective-, passive- and laboratory-based study to identify patients with S. typhi bacteremia. Subjects (n = 4,650) from whom blood cultures were obtained during 16-month period were enrolled from private clinics and hospitals throughout Dhaka. Isolation and quantification of S. typhi from blood cultures were performed by the lysis direct plating/ centrifugation method. RESULTS: Bacterial pathogens were recovered from blood of 538 of 4,650 patients (11.6%) evaluated. S. typhi was the single most common pathogen recovered, comprising nearly three-fourths of isolates (72.7%; 391 of 538). Isolation rate of S. typhi was highest in monsoon and summer seasons and lowest in winter months. The majority (54.5%; 213 of 391) of S. typhi isolates were from children who were younger than 5 years, and 27% (105 of 391) were from children in the first 2 years of life. The isolation rate was highest (17.4%, 68 of 486) in the second year of life. The number of bacteria in blood on the basis of colony-forming units per ml of blood by age group was inversely related to age. CONCLUSIONS: Detection of S. typhi bacteremia in young children in Dhaka, Bangladesh, was considerably higher than previously appreciated, with a peak detection rate in children < or =2 years of age, indicating the need to reassess the age-specific burden of typhoid fever in the community on a regional basis. Contrary to current recommendations this study suggests that development of new vaccines should target infants and young children.

Adolescent↗
PubMed2000

Neonatal skin care.

The relative importance of neonatal health and neonatal skin care has been highlighted in recent years as infant mortality rates have decreased while death rates during the neonatal period remain unacceptably high in many areas of the world. During the neonatal period, many newborns develop preventable, clinically apparent skin problems, and many more, especially preterm neonates, experience morbidity caused by compromised skin barrier integrity. Several strategies are available for protecting the integrity and promoting the hygiene of the skin and augmenting its function as a barrier to TEWL and heat loss and the entrance of infectious or toxic agents. Research defining optimal applications of many of these strategies, however, and the development of new approaches in skin care is one of the greatest challenges in pediatric dermatology and holds promise for improving neonatal outcome in the future. The ability to modulate epidermal barrier function and integrity relies largely on the topical use of protective materials and substances and manipulation of the external environment. As understanding of epidermal barrier development advances, perhaps pharmacologic manipulation of barrier development, as now practiced for augmentation of neonatal lung maturity, will become a reality. In the meantime, greater awareness among neonatal health care practitioners of state-of-the-art strategies for optimizing skin integrity in neonates is an important step toward improving neonatal health.

Baths↗
PubMed2000

Role of group A streptococcal virulence factors in adherence to keratinocytes.

To evaluate the role of putative group A streptococcal virulence factors in the initiation of skin infections, we compared the adherence of a wild-type M49-protein skin-associated strain to that of a series of 16 isogenic mutants created by insertional inactivation of virulence genes. None of the mutants, including the M-protein-deficient (emm mutant) strain, displayed reduced adherence to early-passage cultured human keratinocytes, but adherence of the mutant lacking hyaluronic acid capsule expression (has mutant) was increased 13-fold. In contrast, elimination of capsule expression in M2-, M3-, and M18-protein has mutants increased adherence only slightly (1.3- to 2.3-fold) compared to their respective wild-type strains. A mutant with inactivation of both emm and has displayed high-level adherence (34.9 +/- 4.1%) equal to that of the has mutant strain (40.7 + 8.0%), confirming the lack of involvement of M49 protein in attachment. Moreover, adherence of the M49-protein-deficient (emm mutant) and wild-type strains was increased to the same level (57 and 55%, respectively) following enzymatic digestion of their hyaluronic acid capsule. Adherence of mutants lacking oligopeptide permease (Opp) expression was increased 3.8- to 5.5-fold, in association with decreased cell-associated hyaluronic acid capsule. Finally, soluble CD46 failed to inhibit adherence of M49- and M52-serotype skin strains. We conclude that (i) bacterial M protein and keratinocyte CD46 do not mediate adherence of M49 skin-associated Streptococcus pyogenes to epidermal keratinocytes, (ii) hyaluronic acid capsule impedes the interaction of bacterial adhesins with keratinocyte receptors, (iii) modulation of capsule expression may be important in the pathogenesis of skin infections, and (iv) the molecular interactions in attachment of skin strains of S. pyogenes to keratinocytes are unique and remain unidentified.

Antigens, Bacterial↗
PubMed2000

Congenital cutaneous candidiasis: clinical presentation, pathogenesis, and management guidelines.

We describe a term infant with congenital cutaneous candidiasis (CCC), and review all cases in the English literature that reported birth weight and outcome. Presence of an intrauterine foreign body was a predisposing factor for development of CCC and subsequent preterm birth. The most common presentation of CCC in neonates weighing >1000 g was a generalized eruption of erythematous macules, papules, and/or pustules that sometimes evolved to include vesicles and bullae. Extremely low birth weight, premature neonates weighing <1000 g most often presented with a widespread desquamating and/or erosive dermatitis (10 of 15 [67%]), and were at greater risk for systemic infection with Candida spp (10 of 15 [67%]) and death (6 of 15 [40%] than those weighing >1000 g (5 of 48 [10%]; 4 of 48 [8%], respectively). Systemic antifungal therapy is recommended for neonates with burn-like dermatitis attributable to Candida spp, or positive blood, urine, and/or cerebrospinal fluid cultures. Systemic treatment also should be considered for all infants with CCC who have respiratory distress in the immediate neonatal period and/or laboratory signs of sepsis such as an elevated leukocyte count with an increase in immature forms or persistent hyperglycemia and glycosuria.

Candidiasis, Cutaneous↗
PubMed1999

Tumor necrosis factor-alpha and interleukin-1alpha decrease the adherence of Streptococcus pyogenes to cultured keratinocytes.

We hypothesized that the primary epidermal cytokines, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1alpha, which are produced after skin injury, modulate bacterial adherence and the initiation of group A streptococcal skin infections. Streptococcus pyogenes binds preferentially to highly differentiated keratinocytes in vitro, simulating the superficial human skin infection, impetigo, and providing a model system for testing this hypothesis. Exposure of keratinocytes to 10 ng/mL TNF-alpha for 20 h decreased adherence to undifferentiated and differentiated keratinocytes by 33% and 38%, respectively. Treatment with 1 ng/mL IL-1alpha decreased adherence to undifferentiated and differentiated keratinocytes by 23% and 18%, respectively. Exposure to both cytokines simultaneously produced an additive 50% reduction in adherence. These data suggest that TNF-alpha and IL-1alpha may play a role in cutaneous host defense by impeding streptococcal adherence and decreasing its ability to form a nidus of infection in the skin.

Bacterial Adhesion↗
PubMed1999

Role of keratinocyte injury in adherence of Streptococcus pyogenes.

Keratinocytes injured acutely by UVB light or lipopolysaccharide were used to test the hypothesis that keratinocyte injury promotes bacterial adherence and the development of group A streptococcal skin infections. Injury did not affect adherence to undifferentiated and differentiated keratinocytes, but keratinocyte differentiation promoted adherence four- to fivefold.

Bacterial Adhesion↗
PubMed1998

Differentiation of cultured keratinocytes promotes the adherence of Streptococcus pyogenes.

Based on a consideration of the histopathology of nonbullous impetigo that shows localization of Streptococcus pyogenes to highly differentiated, subcorneal keratinocytes, we hypothesized that adherence of an impetigo strain of S. pyogenes would be promoted by terminal differentiation of keratinocytes. An assay was developed in which S. pyogenes adhered via pilus-like projections from the cell wall to the surface of cultured human keratinocytes in a time- and inoculum-dependent manner suggestive of a receptor-mediated process. Terminal differentiation of keratinocytes was induced by increasing the calcium concentration in the growth medium, and was confirmed by morphologic analysis using electron microscopy. Adherence of S. pyogenes was three and fourfold greater to keratinocytes differentiated in 1.0 and 1.5 mM calcium, respectively, compared with undifferentiated keratinocytes in 0.15 mM calcium. The presence of calcium during the adherence assay further enhanced adherence nearly twofold. Adherence occurred preferentially to sites of contact between adjacent keratinocytes, suggesting that the keratinocyte receptor may be a molecule involved in cell-to-cell adhesion. In contrast, nonpathogenic Streptococcus gordonii adhered poorly to keratinocytes regardless of their state of terminal differentiation, and adherence of a pharyngeal strain of S. pyogenes was twofold greater to undifferentiated than differentiated keratinocytes. This is the first report of in vitro adherence of S. pyogenes to keratinocytes in a manner that emulates human impetigo. Adherence of only the impetigo strain, and not the pharyngeal strain of S. pyogenes or the nonpathogenic S. gorgonii isolate, was promoted by keratinocyte differentiation. This result provides a model system for investigating the molecular pathogenesis of streptococcal skin infections.

Bacterial Adhesion↗
PubMed1998

Antibiotics in the management of pediatric skin disease.

An increasingly large number of antibiotics are available for the treatment of uncomplicated skin and skin structure infections in children. Primary factors in the choice among these agents are the antibiotic resistance profile of the target pathogen(s), and the antibiotic's spectrum of activity, pharmacologic properties, potential adverse reactions and interactions and propensity to select for the emergence of resistant organisms. Based on a consideration of these principles, this article provides a practical guide to the use of antibiotics in the management of common cutaneous infections in the pediatric population.

4-Quinolones↗