Determinants and Policy Implications of Male Circumcision in the United States

Objective. We sought to determine whether lack of state Medicaid coverage for infant male circumcision correlates with lower circumcision rates.Methods. We used data from the Nationwide Inpatient Sample on 417 282 male newborns to calculate hospital-level circumcision rates. We used weighted multiple regression to correlate hospital circumcision rates with hospital-level predictors and state Medicaid coverage of circumcision.Results. The mean neonatal male circumcision rate was 55.9%. When we controlled for other factors, hospitals in states in which Medicaid covers routine male circumcision had circumcision rates that were 24 percentage points higher than did hospitals in states without such coverage (P < .001). Hospitals serving greater proportions of Hispanic patients had lower circumcision rates; this was not true of hospitals serving more African Americans. Medicaid coverage had a smaller effect on circumcision rates when a hospital had a greater percentage of Hispanic births.Conclusions. Lack of Medicaid coverage for neonatal male circumcision correlated with lower rates of circumcision. Because uncircumcised males face greater risk of HIV and other sexually transmitted infections, lack of Medicaid coverage for circumcision may translate into future health disparities for children born to poor families covered by Medicaid.Three recent randomized clinical trials in South Africa, Kenya, and Uganda found that male circumcision reduces a man''s risk of becoming infected with HIV through contact with a female partner by 55% to 76%.^1–3 These results are consistent with meta-analyses based on observational studies in Africa^4,5 and the United States.^6,7The recent randomized clinical trial findings prompted the American Academy of Pediatrics (AAP) to form a committee in June 2007 to review its position on male circumcision.⁸ In 1999 the AAP had adopted a neutral stance, stating that the medical benefits were not compelling enough to recommend routine neonatal circumcision. In the wake of the AAP statement, several states withdrew Medicaid coverage for routine, nontherapeutic circumcision. Currently, 16 state Medicaid plans do not cover the procedure. In 2006, legislators in Hawaii and Vermont introduced resolutions challenging the need for state funding of routine male circumcision.⁹In view of the striking results from the African clinical trials, it is timely to examine the impact of US hospital- and state-level policies on domestic rates of male circumcision. In particular, we hypothesized that male circumcision rates would be higher in states in which the Medicaid program pays for routine circumcision.     

Similarity of insulin detemir pharmacokinetics, safety, and tolerability profiles in healthy caucasian and Japanese american subjects

The objective of this study was to compare the pharmacokinetics of insulin detemir in three ascending doses in healthy Japanese and Caucasian subjects. This was an open-label, single-center, parallel-group design evaluating 30 subjects (15 Japanese and 15 Caucasians). Subjects received a total of three subcutaneous injections (one injection per visit) of insulin detemir (0.19, 0.38, 0.75 U/kg [1 U = 24 nmol]) in ascending order. Following drug administration, subjects received intravenous glucose in 0.5-mg/kg/min increments every 30 minutes, followed by a constant rate of 2.0 mg/kg/min for up to 12 hours. For pharmacokinetic evaluations, serial blood sampling was performed over a period of 30 hours after dosing. Of the subjects, 36 were enrolled, and 30 completed the study. There was a linear dose-response relationship between the three ascending insulin detemir doses and serum insulin detemir AUC values for both the Japanese and Caucasian subjects. The two dose-response regression lines had equivalent slopes but slightly different intercepts (although not statistically significant). This difference may be due to variation in AUC, body weight differences, or chance. Six subjects discontinued the study, 2 as a result of adverse events (blood draw-related ecchymosis and hypoglycemia). The most frequent treatment-emergent adverse events (TEAE) were headache, dizziness, and reactions related to blood draws/infusion sites. All TEAEs were mild to moderate in severity. The results show that an increase in insulin detemir dose will result in a similar increase in insulin detemir concentration in the two ethnic groups. Therefore, therapeutic dosing of insulin detemir is expected to be similar in both ethnic groups, with no special dose adjustment or algorithm based on race. Insulin detemir at 0.19, 0.38, and 0.75 U/kg was generally well tolerated in both Japanese and Caucasian subjects.     

Presenile dementia in Israel

A nationwide epidemiologic study of presenile dementia of the Alzheimer type (PDAT) with onset through age 60 years was carried out in Israel. The Israeli National Neurologic Disease Register and clinical records of all patients discharged from hospitals between 1974 and 1983 with a neurologic or psychiatric diagnosis suggestive of dementia were reviewed. A total of 71 Jewish patients with onset of PDAT between 1974 and 1978 was ascertained. The age at onset in these patients ranged from 43 to 60 years. The median survival was 8.1 years, with slightly longer survival if onset occurred before age 55 years, even after correction for expected mortality according to age and sex. The average annual incidence rate per 100,000 population at risk was 2.4 in the population aged 40 through 60 years. Although the incidence rates were slightly greater for women, the difference between the rates by sex was not statistically significant. The age- and sex-adjusted incidence of PDAT per 100,000 population was significantly higher in those born in Europe or America (2.9) than in those born in Africa or Asia (1.4). No significant difference in survival was found between these two groups. The curve of the incidence rates by age for PDAT in Israel is continuous with that for senile dementia of the Alzheimer type collected by similar methods elsewhere, which suggests that one disease process may account for both conditions.     

Ultrastructural changes in the posterior layers of the cornea in Schnyder's crystalline dystrophy

A case of central crystalline dystrophy of Schnyder is presented in which ultrastructural studies were performed on the corneal specimen after penetrating keratoplasty. Electron microscopic changes were documented not only in the anterior but in the posterior stroma and in the corneal endothelium. In the posterior stroma and at the interface between the stroma and Descemet's membrane, numerous ovoid, electron-lucent spaces were present that most likely represented foci of lipid deposition. In addition, rare, focal areas of endothelial cell degeneration were observed that produced minute discontinuities in the endothelial cell covering of Descemet's membrane. Changes in the posterior layers of the cornea in Schnyder's crystalline dystrophy may contribute to the comparatively poorer surgical results obtained with lamellar rather than full-thickness grafts in these cases.     

Mapping of breakpoints, and relationship to BCR-ABL RNA expression, in Philadelphia-chromosome-positive chronic myeloid leukaemia patients with a breakpoint around exon 14 (b3) of the BCR gene

The BCR gene, on chromosome 22, is involved in the Philadelphia (Ph1) chromosome which is a characteristic cytogenetic marker of chronic myeloid leukaemia (CML). Breakpoints in CML occur within the M-bcr region (5.8 kb) which encompasses exons 12-15 (b1-b4), and the M-bcr can be conveniently divided into five zones by restriction mapping. One of these zones (3) contains exon b3 which can be either present or absent from the hybrid mRNA, even if it is present in the chimaeric gene. We have mapped the breakpoints around BCR exon b3 and related this to the type of RNA splice site expressed, in CML patients at diagnosis. Breakpoints within zone 3 were restriction mapped to one of six sub-zones and the site related to the type of RNA splice site. Two clusters of breakpoints within zone 3 were observed. One cluster was located around exon b3 and often resulted in deletion of exon b3 from the chimaeric gene. The majority of this cluster expressed b2-a2 spliced RNA, usually as a consequence of a deletion removing exon b3. The second cluster occurred within two sub-zones that spanned an Alu sequence, and 90% of this cluster exhibited b3-a2 spliced RNA. Furthermore, a greater number of patients had entered blast crisis if the RNA contained BCR exon b3 (8 of 10 patients), compared to those with b2-a2 spliced RNA (3 of 12 patients). The high degree of heterogeneity in the site of the breakpoint within zone 3 of the M-bcr, combined with the type of BCR-ABL hybrid mRNA expressed, further implicates BCR exon b3 in the pathogenesis of CML.     

THE IN VITRO PRODUCTION OF ANTIBODY BY DELAYED PHASE CORNEAL LIMBAL LYMPHOID FOCI

The intracorneal inoculation of a sufficient quantity of a soluble protein antigen into the eye of a rabbit produces a biphasic allergic reaction in that cornea. The earlier stage, characterized by a diffuse corneal clouding, is a manifestation of delayed hypersensitivity and is accompanied by a limbal infiltrate composed predominantly of lymphocytic-mononuclear elements. The later response, known as the Wessely Phenomenon, is a ring of opacification in the cornea which is visible in the gross. This reaction is dependent upon the presence of specific circulating antibodies and is therefore classified among the immediate types of hypersensitivity. It is accompanied by a dense limbal infiltration of plasma cells. Intervening between the two reactions is a period of several days during which the eye appears relatively normal. Explants containing large numbers of infiltrating lymphocytic-mononuclear elements were removed from the corneal-scleral junction of experimental eyes during the height of the delayed type hypersensitivity reaction and maintained in vitro in tissue culture. At a later date the overlay fluid in which the explants were maintained was shown to contain specific humoral antibodies, demonstrating the capability of cells present at a delayed reaction for the later production of antibodies. The possible linkage of the two modes of immune phenomena is discussed.