Dermatoepidemiology

Dermatoepidemiology is an important emerging discipline in dermatology. This article reviews clinical and analytic epidemiology pertinent to reading, interpreting, and critically examining the literature, and presents an overview of evidence-based dermatology as a starting point for further study.     

Disinfection with 10% povidone-iodine versus 0.5% chlorhexidine gluconate in 70% isopropanol in the neonatal intensive care unit

AIM: The finding that 10% povidone-iodine skin disinfectant may compromise thyroid function in premature infants prompted its replacement with 0.5% chlorhexidine gluconate solution in 70% isopropanol. The objective of this study was to compare the incidence rates of true infection and contamination associated with the use of these two disinfectants in the neonatal intensive care unit. METHODS: The study population comprised two cohorts of infants admitted to our neonatal intensive care unit: 1) in 1992-1993 when only 10% povidone-iodine was used as a skin disinfectant, and 2) in 1995-1996 when only 0.5% chlorhexidine gluconate solution in 70% isopropanol was used. A retrospective chart review was conducted to determine whether all documented positive blood, CSF and suprapubic aspirate cultures indicated true infection or contamination. True infection was defined as clinical symptoms and/or laboratory abnormalities suggestive of sepsis, with positive blood, CSF or suprapubic aspirate cultures. RESULTS: 1146 infants were admitted during the study periods, 507 during the first period and 639 during the second. In the early group, 17.6% of infants had major malformations, 72.0% were premature and 25.2% had weights of < 1500 g. Corresponding percentages for the latter group were 16.0%, 80.6% and 32.9%, respectively. No statistically significant differences were found between the two research periods in rate of infants with positive blood cultures, true infections, or contamination. CONCLUSION: The use of 0.5% chlorhexidine gluconate solution in 70% isopropanol as a skin disinfectant is justified in neonatal intensive care units because it is not associated with an increased incidence of infections as opposed to 10% povidone-iodine and is devoid of detrimental effects.     

Hepatic insulin resistance precedes the development of diabetes in a model of intrauterine growth retardation

Intrauterine growth retardation (IUGR) has been linked to the development of type 2 diabetes in adulthood. We developed an IUGR model in rats whereby at age 3-6 months the animals develop a diabetes that is associated with insulin resistance. Hyperinsulinemic-euglycemic clamp studies were performed at age 8 weeks, before the onset of obesity and diabetes. Basal hepatic glucose production (HGP) was significantly higher in IUGR than in control rats (14.6 +/- 0.4 vs. 12.3 +/- 0.3 mg. kg(-1). min(-1); P < 0.05). Insulin suppression of HGP was blunted in IUGR versus control rats (10.4 +/- 0.6 vs. 6.5 +/- 1.0 mg. kg(-1). min(-1); P < 0.01); however, rates of glucose uptake and glycogenolysis were similar between the two groups. Insulin-stimulated insulin receptor substrate 2 and Akt-2 phosphorylation were significantly blunted in IUGR rats. PEPCK and glucose-6-phosphatase mRNA levels were increased at least threefold in liver of IUGR compared with control rats. These studies suggest that an aberrant intrauterine milieu permanently impairs insulin signaling in the liver so that gluconeogenesis is augmented in the IUGR rat. These processes occur early in life, before the onset of hyperglycemia, and indicate that uteroplacental insufficiency causes a primary defect in gene expression and hepatic metabolism that leads to the eventual development of overt hyperglycemia.     

Geographic and patient variation in receipt of surveillance procedures after local excision of cutaneous melanoma

Little is known about variation in surveillance practices following the diagnosis of invasive melanoma. The objective of this study was to characterize geographic, patient, and tumor variation in the use of follow-up surveillance testing in patients with local or regional stage melanoma. A cohort of Medicare beneficiaries > or =65 y diagnosed with invasive melanoma during 1992 to 1996 living in a Surveillance, Epidemiology, and End Results registry area was studied. Outpatient and inpatient Medicare claims 3 mo following diagnosis were examined for up to 2 y for surveillance procedures of interest. Use of chest X-ray, chest computed tomography scan, abdominal and/or pelvic computed tomography scan, abdominal ultrasound, head computed tomography scan, head magnetic resonance imaging, laboratory testing, and skin examinations were compared between patient groups and geographic regions. A total of 3389 patients were identified for the analysis. Surveillance testing was relatively common, ranging from 13% for abdominal ultrasound to 80% for laboratory testing. Follow-up skin examinations were performed in 70% to 90% of patients. The use of most surveillance procedures was associated (p<0.01) with younger age, male gender, regional stage tumors, and geographical area, with up to 2-fold differences observed. In contrast, there was much less variability in the receipt of skin examinations. Further studies are needed to determine the etiology and impact of such disparities, and the influence of surveillance procedures on morbidity and mortality.     

Amelioration of sulfur mustard skin injury following a topical treatment with a mixture of a steroid and a NSAID

The ability to ameliorate sulfur mustard (HD)-induced oedema by treatment with anti-inflammatory drugs was reported previously after screening four steroids and four non-steroidal anti-inflammatory drugs (NSAIDs) using the mouse ear vesicant model. Following the screening study, one steroid and one NSAID (Adexone and Voltaren) were selected as the most effective, and a mixture of the two was chosen for the present more extensive research. The effect of the combined treatment on clinical, biochemical and histopathological parameters following HD insult was studied. Mice ears were exposed to 0.2 micro l of HD for 10 min to produce a moderate skin injury. Oedema development peaked ca. 48 h following exposure, as determined by weighing ear biopsies. Histological observations at that time exhibited damage to the epidermis and dermis. An increase in prostaglandin E (PGE) was measured in skin homogenates, starting 8 h following exposure and lasting at least up to 48 h post-exposure. A topical treatment using the above anti-inflammatory mixture significantly reduced inflammatory parameters when applied up to 4 h following exposure. These parameters included extent of oedema, levels of PGE, area of clinical damage and extent of cytotoxic injury (vesications and damaged epithelial cells). Thus, a combination of a steroid and NSAID was found to be effective in reducing the intensity of HD skin injury and possibly shortening the time to full recovery. The treatment, however, did not prevent completely the ensuing cytotoxic processes in the epithelial layer.     

The 1100delAT BRCA1 and the 8765delAG BRCA2 Mutations: Occurrence in High-Risk Non-Ashkenazi Jews and Haplotype Comparison of Jewish and Non-Jewish Carriers

Few mutations have been described in BRCA1 and BRCA2 in high-risk non-Ashkenazi Jews. In a Libyan family the 1100delAT BRCA1 mutation was detected and the 8765delAG BRCA2 mutation was previously described in two Jewish-Yemenite-families. In this study, the rate of these mutations in high-risk Jews of North African and Yemenite origin was assessed, and the BRCA1 -linked haplotype of Jewish and non-Jewish 1100delAT mutation carriers were compared. Genotyping included 64 high-risk Yemenite women (tested only for the BRCA 2 mutation) and 147 high-risk North African women, tested for both mutations. PCR amplification was followed by either restriction enzyme digestion or DGGE or dHPLC analyses and direct sequencing. For haplotyping, 5 BRCA1 -linked markers were used. Neither the 1100delAT BRCA1 nor the 8765delAG BRCA2 mutations were detected in any non-Ashkenazi individual. The haplotype of the non-Jewish 1100delAG mutation carrier differed from that of the Jewish-Libyan mutation carriers. We conclude that both1100delAT BRCA1 and 8765delAG BRCA2 mutations occur rarely in high-risk non-Ashkenazi Jews, and while the latter seems to be a founder mutation in some populations, the former occurs on a different background in ethnically diverse families.     

Mediterranean spotted fever during pregnancy: case presentation and literature review

Mediterranean spotted fever (MSF) is caused by Rickettsia conorii, an obligate intracellular parasite of eukaryotic cells. Although, usually this disease has a benign course, a rapidly fatal outcome can occur even in young healthy adults. We describe a case of a 40-year-old Bedouin woman gravida 11, para 10, who was admitted at 36 weeks gestation with this rickettsial disease. During pregnancy, the treatment of choice for Mediterranean spotted fever is chloramphenicol, but it seems that Azithromycin could be another possible option.     

Mechanisms of matrix metalloproteinase-9 and matrix metalloproteinase-2 inhibition by N-acetylcysteine in the human term decidua and fetal membranes

OBJECTIVE: The purpose of this study was to evaluate the effect of N-acetylcysteine on the activity and secretion of the matrix metalloproteinases in the decidua, amnion, and chorion and the secretion of the tissue inhibitor of matrix metalloproteinase-1. STUDY DESIGN: Samples from eight nonlaboring women were taken at elective cesarean section and incubated in an in vitro organ culture in the absence or presence of N-acetylcysteine. Matrix metalloproteinase-2 and matrix metalloproteinase-9 activity was measured with the use of gel zymography. Western blot analysis was used to measure matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase-1 secretion. Data were analyzed with the paired Student t test. RESULTS: N-acetylcysteine had a direct inhibitory effect on matrix metalloproteinase-2 and matrix metalloproteinase-9 activity, regardless of tissue origin, starting at 1.0 mmol/L. In cultured media, 20 mmol/L N-acetylcysteine inhibited matrix metalloproteinase-2 and matrix metalloproteinase-9 activity in all three tissues. A differential response was demonstrated for matrix metalloproteinase-2 secretion, depending on the tissue that was studied. Its secretion was decreased in decidua at 10 mmol/L and 20 mmol/L; in amnion, the secretion was inhibited at 0.1 mmol/L and not affected at all in chorion. Matrix metalloproteinase-9 secretion was not affected in a statistically significant manner in any tissue. In the chorion, matrix metalloproteinase-9 showed a trend toward increased secretion. Tissue inhibitor of matrix metalloproteinase-1 secretion significantly decreased in the decidua at 20 mmol/L. CONCLUSION: N-acetylcysteine, at higher concentrations, has an inhibitory effect on matrix metalloproteinase-2 and matrix metalloproteinase-9 activity, regardless of the tissue origin and the differential effect on secretion depending on the tissue and N-acetylcysteine concentration.