Evidence for fetal involvement in the pathologic process of clinical chorioamnionitis

OBJECTIVE: Clinical and histologic chorioamnionitis have recently been identified as risk factors for cerebral palsy. Proinflammatory cytokines have been implicated in the mechanisms that are responsible for brain injury in cases of intrauterine infection. The purpose of this study was to determine whether clinical chorioamnionitis, which is a maternal syndrome, is associated with an elevation in the fetal plasma interleukin-6 (IL-6) that is indicative of fetal inflammation. STUDY DESIGN: A cross-sectional study was designed to determine plasma concentrations of IL-6 in umbilical venous blood from patients with clinical chorioamnionitis (n = 26) and a control group (n = 111). Umbilical cord blood was obtained at the time of delivery. Plasma concentrations of IL-6 were measured with a sensitive and specific immunoassay. Nonparametric statistics were used for analysis. RESULTS: Plasma concentrations of IL-6 were detectable in all samples of umbilical venous plasma. The median concentration of plasma IL-6 was higher in neonates born to mothers with clinical chorioamnionitis than in neonates born to mothers in the control group (clinical chorioamnionitis: median, 27.46 pg/mL; range, 1.3-5550.0 pg/mL; vs control: median, 2.13 pg/mL; range, 0.6-812.3 pg/mL; P <.001). Sixty-two percent of neonates (16/26) who were born to women with clinical chorioamnionitis had fetal plasma concentrations of IL-6 >11 pg/mL and 54% (14/26) had fetal plasma concentrations of IL-6 >18 pg/mL (these cutoff points have been used previously to define the fetal inflammatory response syndrome). CONCLUSION: Umbilical vein plasma concentrations of interleukin-6 are elevated in the neonates who were born to mothers with clinical chorioamnionitis, which suggests that the inflammatory process that is responsible for the maternal syndrome of clinical chorioamnionitis frequently involves the human fetus.     

Craniofacial hyperhidrosis successfully treated with topical glycopyrrolate

Treatment of craniofacial hyperhidrosis currently consists of thoracic sympathectomy, which is not widely available. Oral anticholinergic agents and beta-blockers may be effective but also carry significant side effects. We describe a healthy, active 27-year-old male resident physician who had excessive facial sweating with minimal exertion or stress. The sweating was especially pronounced on the forehead, nose, and upper lip. Daily topical application of a 0.5% glycopyrrolate solution to the face and forehead was offered. After the first treatment, facial sweating was significantly reduced and was well controlled under stressful situations, without any discomfort to the skin. No loss of efficacy was seen after multiple face washings. Facial hyperhidrosis recurred after withdrawal of the glycopyrrolate for 2 days, confirming its therapeutic effect. Two years later, he continues to use glycopyrrolate as needed. We conclude that topical glycopyrrolate is effective in treating craniofacial hyperhidrosis and is associated with few adverse effects.     

Community-based participatory research: implications for public health funding

Community-based participatory research (CBPR) increasingly is being recognized by health scholars and funders as a potent approach to collaboratively studying and acting to address health disparities. Emphasizing action as a critical part of the research process, CBPR is particularly consistent with the goals of "results oriented philanthropy" and of government funders who have become discouraged by the often modest to disappointing results of more traditional research and intervention efforts in many low income communities of color. Supporters of CBPR face challenging issues in the areas of partnership capacity and readiness, time requirements, funding flexibility, and evaluation. The authors suggest strategies for addressing such issues and make a case for increasing support of CBPR as an important tool for action-oriented and community-driven public health research.     

A one-year experience with a capitated health care plan for infertility

OBJECTIVE: To report on a one-year experience participating in a capitated healthcare plan for infertility. DESIGN: Prospective study. SETTING: University population. PATIENT(S): Reproductive-age women 15 to 50 years. INTERVENTION(S): The first-generation Lewin infertility algorithm and CATHI software were used to negotiate infertility services under a capitated arrangement for $0.50 per member per month. The following reports our experience for the fiscal year 1997. MAIN OUTCOME MEASURE(S): Infertility services rendered, pregnancy rate, cost of services, collection rates. RESULT(S): Five thousand forty-six women representing 39,689 member months generated 39 new and 198 return visits. Thirty-two percent of the patients required three visits or less; six patients generated 22% of the visits. Fifty-one percent listed infertility as one of their chief complaints; 31% had mixed diagnoses. Eight (7.6%) patients required surgery, 11 (10.5%) patients underwent either IVF or GIFT cycles. Total charges submitted were $176,636; the amount assigned to specialty care was $135,277, and to IVF/GIFT, $33,433. Total capitated payments, including copayments, was $126,256 under the reproductive medicine agreement and $32,891 under the infertility rider. This resulted in a 71% gross collections rate. CONCLUSION(S): This study indicates that entering into a capitated health care plan to provide an infertility benefit can produce a successful result.     

Effects of intra-amniotic meconium exposure on the fetal rat: development of a pathogenic model

OBJECTIVE: To develop an in vivo animal model for the study of the effects of intrauterine meconium exposure on the fetus. METHODS: Timed pregnant Long-Evans rats were purchased on gestational day (GD) 12 and allowed to acclimate for at least 48 h prior to surgery. Laparotomy was performed and both uterine horns were exteriorized through the abdominal incision. A 26-gauge needle was used to inject either 0.1-cm(3) sterile normal saline or a 20% meconium suspension into each individual gestational sac. The uterus was returned to the abdomen and the incision was closed. On GD 21 (term = 21 days) a cesarean section was completed and the number and viability of fetuses in each horn were recorded. RESULTS: A total of 14 animals were involved in this pilot study. One rat underwent sham surgery with only intra-amniotic saline injection and 13/15 fetuses survived to term. Two animals that underwent surgery on day 18 expired < 24 h postinjection. Eleven maternal animals were injected on GD 20 and underwent cesarean delivery at term; survival rates for saline-injected animals were 71.2% compared to 66.2% for meconium-exposed fetuses. CONCLUSION: We have established an in vivo animal model that allows for the examination of the effects of prolonged intrauterine meconium exposure on the fetus.     

Cutaneous larva migrans: clinical features and management of 44 cases presenting in the returning traveller

BACKGROUND: Cutaneous larva migrans (CLM) is the result of a nematode infection, and shows a characteristic creeping eruption. As travel to the tropics increases, many British citizens may be returning with this infection, which is often misdiagnosed or treated incorrectly. OBJECTIVES: To perform a retrospective survey of 44 cases of CLM presenting to the Hospital for Tropical Diseases in London over the last 2 years. METHODS: Cases were reviewed with regard to patient characteristics, source of infection, source of referral, clinical features and therapy. RESULTS: Most infections were acquired in Africa (32%), the Caribbean (30%) and South-east Asia (25%), but also in Central and South America. There was a history of exposure to a beach in 95% of patients and the median duration of symptoms was 8 weeks (range 1-104). Lesions mainly affected the feet (39%), buttocks (18%) and abdomen (16%), but the lower leg, arm and face were also affected. Multiple lesions were seen in seven of 44 cases (16%). Laboratory abnormalities were absent in all patients. Of 44 patients seen, four needed no treatment, 28 were cured by a single course of treatment, 11 required a second course of therapy and one patient was treated three times. Thirty-one patients received oral albendazole 400 mg daily for 3-5 days and 24 were cured (77%). Five patients received 10% thiabendazole cream topically for 10 days and four were cured (80%). Four patients received oral thiabendazole 1.5 g daily for 3 days and all required further therapy. CONCLUSIONS: In view of the range of treatment regimens recorded, a randomized controlled trial comparing topical and systemic therapies is warranted.     

The role of hyperplasia in multiple parathyroid adenomas

BACKGROUND: Parathyroid adenoma is the most common cause of primary hyperparathyroidism (pHPT). Adenomas usually involve only a single gland, and the remaining glands are normal or suppressed. Multiple parathyroid adenomas have been reported to occur in as high as 11% of patients with pHPT. The significant incidence of multiple adenomas with histologic similarities to hyperplasia has raised the possibility that adenoma is a continuation of the hyperplasia state. To test this theory, we used molecular genetics to compare clonality and proliferative activity of parathyroid adenoma with its corresponding normal glandular tissue. Furthermore, we devised a scheme to definitively distinguish between the different parathyroid states on a molecular level, because histologic distinction is unreliable. METHODS: The study included three patients with a diagnosis of singular parathyroid adenoma and three with double parathyroid adenomas. Paraffin-embedded surgical specimens of both adenomas and normal glands were retrieved from each patient. Clonal analysis of the phosphoglycerolkinase (PGK) gene has suggested that parathyroid adenomas are monoclonal. Clonality of parathyroid adenomas and normal parathyroid glands was studied by polymerase chain reaction-based restriction fragment length polymorphic analysis for the PGK gene. Proliferative activity of the specimens was also analyzed using the immunohistochemical markers PCNA and Ki-67. RESULTS: All adenomas were monoclonal and all normal parathyroid glands were polyclonal for the PGK gene in both the single and double adenoma specimens. All adenomas stained positive for proliferative activity. In the three patients with singular adenoma, proliferative activity was not detected in the normal parathyroid tissue. However, in the double adenoma group, two of the three patients showed hyperproliferative activity in the normal glands. CONCLUSION: Proliferative activity consistent with hyperplasia was present in some normal glands of multiple adenoma patients. Our observation supports the theory that multiple adenomas may be a continuation of the hyperplasia state.     

Genetic epidemiology of visceral leishmaniasis in northeastern Brazil

Familial clustering of disease, racial differences in asymptomatic:disease ratios, and studies of mice all point to a genetic component for disease susceptibility in visceral leishmaniasis. Analysis of 87 multi-case pedigrees (824 individuals; 138 nuclear families) from a region of northeastern Brazil endemic for Leishmania chagasi demonstrates a high relative risk ratio (lambda(2S) = 34) to further siblings of affected sibling pairs. Complex segregation analysis using POINTER and COMDS show that all single locus models, as well as polygenic and multifactorial models, provide a significantly (P < 0.001) better fit to the data than a sporadic model. Of the genetic models, the general single locus model was not significantly different from additive or dominant single locus models, all of which gave a gene frequency for the putative disease susceptibility allele of approximately 0.002. The general single locus model was strongly favored (P < 0.001) over a recessive single gene model. Using POINTER, polygenic and multifactorial models were clearly rejected (P < 0.001 in all cases) in favor of the general single locus model. Using COMDS, the analysis was extended to consider two locus models. Results under a general two-locus model did not differ significantly from the dominant, additive, or general single locus models. Under this model, one locus was estimated at a gene frequency of 0.0017, i.e., in the same range as the disease susceptibility locus for the most favored single gene models, with the second locus at a much lower frequency of 0.0002. Hence, the data support the hypothesis that a single major gene may be important in determining disease susceptibility in this population. To identify the gene(s) involved, a genome scan with replication using two subsets of these larger pedigrees with power to detect linkage is in progress.