Can increasing the viscosity of formulations be used to reduce the human skin penetration of the sunscreen oxybenzone?

The effect of adding thickening agents on the penetration of a sunscreen benzophenone-3 through epidermal and a high-density polyethylene membrane was studied using both very thick (infinite dose) and thin (in use) applications. Contradictory results were obtained. Thickening agents retard skin penetration, in a manner consistent with a diffusional resistance in the formulation, when applied as an infinite dose. In contrast, when applied as in thin (in use) doses, thickening agents promote penetration, most likely through greater stratum corneum diffusivity arising from an enhanced hydration by the thicker formulations. The two key implications from this work are (i) a recognition of the danger in the potential extrapolation of infinite dosing to in use situations, and (ii) to recognize that thicker formulations may sometimes enhance the penetration of other topical agents when applied "in use".     

Troglitazone improves psoriasis and normalizes models of proliferative skin disease: ligands for peroxisome proliferator-activated receptor-gamma inhibit keratinocyte proliferation

BACKGROUND: Psoriasis is often treated with agents that activate nuclear hormone receptors for glucocorticoids, retinoids, and vitamin D. The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a related nuclear hormone receptor that can be activated by its ligands, including the thiazolidinediones. OBJECTIVE: To assess whether treatment with troglitazone, a currently available thiazolidinedione used to treat diabetes mellitus, has an effect on psoriasis in normoglycemic patients and whether ligands for PPARgamma have an effect on models of psoriasis. DESIGN: Open-label administration of troglitazone in patients with psoriasis and evaluation of drug actions in cellular, organ, and transplant models of psoriasis. SETTING: University and community hospital outpatient departments and university laboratories. PATIENTS: Patients with chronic, stable plaque psoriasis and control subjects. Five patients with psoriasis received troglitazone (none withdrew); 10 different untreated patients and 10 controls provided tissue samples. INTERVENTIONS: Oral troglitazone therapy at various dosages in patients with psoriasis; also, use of troglitazone, ciglitazone, and 15-deoxy-delta-12,14-prostaglandinJ2 in psoriasis models. MAIN OUTCOME MEASURES: Investigator-determined clinical results in patients and cell counts and histological evidence in models. RESULTS: All patients' psoriasis improved substantially during troglitazone therapy. Peroxisome proliferator-activated receptor-gamma was expressed in human keratinocytes; ligands for PPARgamma inhibited the proliferation of normal and psoriatic human keratinocytes in culture. Troglitazone treatment normalized the histological features of psoriatic skin in organ culture and reduced the epidermal hyperplasia of psoriasis in the severe combined immunodeficient mouse and human skin transplant model of psoriasis (P<.05 compared with untreated controls). CONCLUSIONS: Peroxisome proliferator-activated receptor-gamma might be a useful intracellular target for the treatment of psoriasis; further study is needed to assess the clinical value of ligands for PPARgamma, including troglitazone.     

Mature middle and inner ears express Chd7 and exhibit distinctive pathologies in a mouse model of CHARGE syndrome

Heterozygous mutations in the gene encoding chromodomain-DNA-binding-protein 7 (CHD7) cause CHARGE syndrome, a multiple anomaly condition which includes vestibular dysfunction and hearing loss. Mice with heterozygous Chd7 mutations exhibit semicircular canal dysgenesis and abnormal inner ear neurogenesis, and are an excellent model of CHARGE syndrome. Here we characterized Chd7 expression in mature middle and inner ears, analyzed morphological features of mutant ears and tested whether Chd7 mutant mice have altered responses to noise exposure and correlated those responses to inner and middle ear structure. We found that Chd7 is highly expressed in mature inner and outer hair cells, spiral ganglion neurons, vestibular sensory epithelia and middle ear ossicles. There were no obvious defects in individual hair cell morphology by prestin immunostaining or scanning electron microscopy, and cochlear innervation appeared normal in Chd7(Gt)(/+) mice. Hearing thresholds by auditory brainstem response (ABR) testing were elevated at 4 and 16 kHz in Chd7(Gt)(/+) mice, and there were reduced distortion product otoacoustic emissions (DPOAE). Exposure of Chd7(Gt)(/+) mice to broadband noise resulted in variable degrees of hair cell loss which inversely correlated with severity of stapedial defects. The degrees of hair cell loss and threshold shifts after noise exposure were more severe in wild type mice than in mutants. Together, these data indicate that Chd7(Gt)(/+) mice have combined conductive and sensorineural hearing loss, correlating with changes in both middle and inner ears.     

Intention to notify sexual partners about potential HIV exposure among New York city STD clinics' clients

BACKGROUND: Partner notification legislation has recently been implemented in New York State. GOAL: The goal of the study was to assess willingness of individuals seeking HIV testing to (1) give counselors contact information about partners, if infected, and (2) contact partners on their own. STUDY DESIGN: Before implementation of the legislation, 1372 individuals seeking HIV testing at New York City Department of Health STD clinics completed a brief, anonymous survey. RESULTS: More than 90% of heterosexually active individuals and more than 80% of men who have sex with men (MSM) could contact sex partners with whom they had had unprotected vaginal/anal sex. Were they to test HIV-positive, almost all respondents would have been willing to notify sex partners personally; 90% of heterosexually active individuals and 80% of MSM also expressed willingness to provide contact information to providers. Respondents preferred to be notified by a sex partner rather than by a provider. Patient-referred clients reported being more comfortable with the referral than provider-referred clients. CONCLUSIONS: Voluntary partner notification performed by the index case-with notification by the provider should the former fail to occur-is recommended.     

Echocardiographic surveillance for asymptomatic late-onset anthracycline cardiomyopathy in childhood cancer survivors

Background

The optimal frequency of echocardiographic surveillance in asymptomatic childhood cancer survivors exposed to anthracyclines has not been established. We evaluated the effectiveness of performing surveillance echocardiograms according to the Children's Oncology Group's (COG) Long‐Term Follow‐Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers in survivors ≥1 year from concluding therapy.

Methods

We reviewed all children treated at our institution with anthracycline chemotherapy from 1995 to 2003. We assessed the frequency of abnormal echocardiograms according to risk groups defined in the COG guidelines, and evaluated the risk factors for an abnormal echocardiogram using Cox proportional hazards modeling.

Results

At least one echocardiogram was completed by 469/603 (77.8%) eligible survivors. Mean diagnosis age was 7.7 (SD = 4.6) years. Mean cumulative doxorubicin‐equivalent dose was 205 mg/m² (SD = 115). Survivors completed 1,013 echocardiograms (median = 2, range = 1–10) beyond 1 year after concluding therapy. Seventy‐nine (16.8%) survivors had an abnormal echocardiogram at a median of 2.9 years (range 0.01–9.8) from 1 year after concluding therapy. Anthracycline dose >300 mg/m² (hazard ratio [HR] 3.00; 95% CI 1.51–5.98), age 1–4 years at treatment (HR 1.89; 95% CI 1.08–3.31) and radiation to a field involving the heart (HR 1.73; 95% CI 1.08–2.76) predicted an increased risk of an abnormal echocardiogram; however, even survivors in the lower COG risk groups demonstrated abnormalities.

Conclusion

Periodic echocardiographic surveillance in childhood cancer survivors can yield abnormalities that require further evaluation. Abnormalities may become evident as early as 1 year after the conclusion of therapy and can impact even those survivors considered to be at low risk. Pediatr Blood Cancer 2011; 57: 467–472. © 2011 Wiley‐Liss, Inc.     

Cell cycle status of CD34+ cells in human fetal bone marrow

We used flow cytometric analysis to determine the cell cycle characteristics of human CD34+ cells from fetal bone marrow (BM), adult BM, and umbilical cord blood (UCB) samples. Fetal BM had three-fold more cells in the S-phase than did adult BM or UCB.     

Testing the Safe Abortion Care model in Ethiopia to monitor service availability, use, and quality

Objective

To implement the Safe Abortion Care (SAC) model in public health facilities in the Tigray region of Ethiopia and document the availability, utilization, and quality of SAC services over time.

Methods

The project oriented providers in 50 public health facilities in Tigray to the SAC model. Changes in SAC indicators between baseline and endline were assessed using a retrospective review of procedure logbooks at baseline and prospective monitoring of procedure logbooks for facility performance after introduction of the SAC model.

Results

Availability of SAC services increased from 39% to 86% of the recommended number of 5 facilities per 500 000 population, primarily as a result of functional improvements at health centers. Decentralization was accompanied by a 94% increase in the annualized number of women who received services. The proportion of uterine evacuation procedures for induced abortion rose from 7% to 60% (P < 0.01), and the proportion performed with recommended technology increased from 30% to 85% (P < 0.01). The proportion of abortion patients who received modern contraception also increased from 31% to 78% (P < 0.01).

Discussion

While widespread service delivery improvements were recorded using the SAC monitoring approach, the project design was built around existing programmatic activities of the local health authority and reflects some related research limitations. For example, there was no comparison group of facilities, timing did not allow for prospective collection of the baseline data before the intervention, and facilities received different levels of monitoring support.

Conclusion

Using the SAC model, public health facilities tracked progress and made needed adjustments, which improved service delivery. Continued focus on critical safe abortion care elements should increase the availability, quality, and use of life‐saving care to reduce preventable abortion mortality in the region.