A pilot methodology study for the photographic assessment of post‐inflammatory hyperpigmentation in patients treated with tretinoin

Background Post‐inflammatory hyperpigmentation (PIH) is a common occurrence in patients with acne vulgaris, particularly in those with skin of colour. Aims A previous study has demonstrated the benefit of tretinoin (retinoic acid) in the treatment of PIH; however, there is currently no standard protocol to evaluate change in PIH following treatment. Based on these findings, we performed a pilot, exploratory, blinded, intraindividual‐controlled methodology study that consisted of a photographic assessment protocol with facial mapping. Materials and methods The study was based on a secondary analysis of a phase 4, community‐based trial of 544 acne patients who were treated with tretinoin gel microsphere 0.04% or 0.1%. Only patients with Fitzpatrick types III–V (skin of colour) were included in the study; subjects with Fitzpatrick skin type VI were excluded because the photographic assessment did not allow for proper evaluation. Results Despite the small number of subjects evaluated (n = 25), the results revealed consistent assessment of improvement in PIH between two independent graders (weighted κ = 0.84). Conclusion Further study with a larger population is recommended to validate the accuracy of this method.     

Prostate cancer risk in relation to anthropometry and physical activity: the National Health and Nutrition Examination Survey I Epidemiological Follow-Up Study.

We studied the relationship of prostate cancer to anthropometry and self-reported physical activity among 5377 African-American and Caucasian participants in the National Health and Nutrition Examination Survey I cohort. The cohort was first examined between 1971 and 1975 and then followed prospectively through the Epidemiologic Follow-up Study in 1982-1984, 1986, 1987, and 1992. Men who reported low levels of nonrecreational physical activity had increased risk of prostate cancer compared with very active men. These findings were unchanged after adjustment for potential confounders and were stronger for African-Americans (relative risk, 3.7; 95% confidence interval, 1.7-8.4) than for Caucasians (relative risk, 1.7; confidence interval, 0.8-2.3). Lower levels of recreational activity were weakly associated with increased prostate cancer risk among African-Americans but not among Caucasians. Prostate cancer risk was unrelated to a variety of anthropometric variables. These results suggest that inactive men are at increased risk of prostate cancer.     

Remission following an elemental diet or prednisolone in Crohn's disease

The short- and long-term effects of an elemental diet in children with acute Crohn's disease were compared with those of prednisolone in historical controls. Clinical remission was induced in 25 of 30 and in 18 of 28 episodes treated for six weeks with an elemental diet and prednisolone. Patients with proximal disease had longer remission after treatment with an elemental diet (p < 0.05) than did patients with colonic disease after treatment with prednisolone (p < 0.01). Disease activity index score improved in both groups compared with the pretreatment scores (p < 0.05). However, the improvement in the elemental diet group was significantly better than in the prednisolone group (p < 0.001). Changes in linear growth were better after treatment with an elemental diet compared with steroids (p < 0.001). Serum albumin and haematocrit concentrations all improved significantly in the children treated with an elemental diet (p < 0.001) but not in those treated with steroids. Thus an elemental diet was better than prednisolone in proximal disease and confirmed improved growth and nutritional status.     

Pelvic ultrasound findings in different forms of sexual precocity

Recently produced reference curves for various ultrasound dimensions were used to retrospectively assess 67 pelvic ultrasound scans carried out at the initial presentation in girls with sexual precocity. At presentation the group with precocious puberty had significantly increased uterine lengths and ovarian volumes compared with the normal population, and a significantly increased fundal–cervical ratio. Ovarian volume was also significantly increased in thelarche and thelarche variant. The fundal–cervical ratio was significantly increased in thelarche variant. There was considerable overlap between individuals with sexual precocity and normal subjects. The ultrasound findings that best discriminated early or precocious puberty from other forms of sexual precocity were the presence of a midline endometrial echo, and a uterine length above the 97th centile for age. An entirely normal pelvic ultrasound at presentation did not rule out the possibility of precocious puberty.     

Immediate food hypersensitivity reactions on the first known exposure to the food

We report 8 infants with immediate hypersensitivity reactions to foods (milk, egg, or peanut), occurring at the first-known exposure. Each developed symptoms within the first hour, but these generally settled within 2 hours. Sensitisation to the food concerned was demonstrated by positive immediate allergen skin prick tests in every case. Symptoms experienced included irritability, erythematous rash, urticaria, angio-oedema, vomiting, rhinorrhoea, and cough. Five infants were being followed prospectively and 4 were clinically tolerant of the food by age 16 months. The most likely route of sensitisation was via breast milk. None of the infants experienced similar reactions while being breast fed, suggesting that the reaction was dose dependent. As 5 out of a group of 80 infants being followed prospectively developed an immediate reaction at their first known exposure to a food, this appeared to be a not uncommon presentation of food hypersensitivity in infancy.     

Race, epithelial ovarian cancer survival, and membership in a large health maintenance organization

BACKGROUND: African-American ovarian cancer patients present with more advanced disease and have poorer survival than do white patients. METHODS: To determine whether these differences occur among African-American and white patients who have equal access to medical care, we analyzed ovarian cancer patient characteristics separately for 1,587 members of the Kaiser Permanente Medical Plan of Northern California and 5,757 non-members. RESULTS: The distributions of disease stage at diagnosis were similar among African-American and white patients, both in the Kaiser plan and elsewhere. However, ovarian cancer death rates, adjusted for disease stage and age at diagnosis and for histology, were higher for African-American patients compared with white patients, regardless of Kaiser membership status. The death rate ratios for African-Americans compared with whites were 1.32 (95% CI = 1.02-1.70) for Kaiser members and 1.20 (95% CI = 1.04-1.40) for Kaiser non-members. CONCLUSION: Further research within an equal-access care system is needed to evaluate other important factors such as specialty of surgeon, extent of residual tumor after surgery, chemotherapy treatment, and postoperative management to determine whether these factors are contributing to the differences in survival between African-American and white ovarian cancer patients.     

Stem cell repair of central nervous system injury

Neural stem cells (NSCs) have great potential as a therapeutic tool for the repair of a number of CNS disorders. NSCs can either be isolated from embryonic and adult brain tissue or be induced from both mouse and human ES cells. These cells proliferate in vitro through many passages without losing their multipotentiality. Following engraftment into the adult CNS, NSCs differentiate mainly into glia, except in neurogenic areas. After engraftment into the injured and diseased CNS, their differentiation is further retarded. In vitro manipulation of NSC fate prior to transplantation and/or modification of the host environment may be necessary to control the terminal lineage of the transplanted cells to obtain functionally significant numbers of neurons. NSCs and a few types of glial precursors have shown the capability to differentiate into oligodendrocytes and to remyeliate the demyelinated axons in the CNS, but the functional extent of remyelination achieved by these transplants is limited. Manipulation of endogenous neural precursors may be an alternative therapy or a complimentary therapy to stem cell transplantation for neurodegenerative disease and CNS injury. However, this at present is challenging and so far has been unsuccessful. Understanding mechanisms of NSC differentiation in the context of the injured CNS will be critical to achieving these therapeutic strategies.     

Differential lineage restriction of rat retinal progenitor cells in vitro and in vivo

To identify and characterize the lineage potential of rat neural retina progenitor cells (NRPCs) in vitro and engrafted into rats with retinal degeneration, NRPCs were isolated from neural retinas of embryonic day 17 Long Evans rats and cultured in serum-free or serum-containing media with fibroblast growth factor 2 and neurotrophin 3. After expansion, cellular differentiation was initiated by the withdrawal of these growth factors. Despite forming primary neurospheres, NRPCs cultured in serum-free medium survived poorly after passage. In contrast, NRPCs cultured in serum-containing medium could be expanded for up to 12 passages and differentiated into glial fibrillary acidic protein-positive glial cells and retina-specific neurons expressing rhodopsin, S-antigen, calbindin, recoverin, and calretinin. For in vivo analysis, passage 1 (P1) undifferentiated NRPCs were labeled with bromodeoxyuridine (BrdU), implanted into the subretinal space of Royal College of Surgeons (RCS) rats, and analyzed immunohistochemically 4 weeks postgrafting. The grafted NRPCs showed extensive glial differentiation, irrespective of their topographic localization. A few BrdU-labeled grafted NRPCs expressed protein kinase C, a marker for bipolar and amacrine interneuron-specific differentiation. Other retina-specific or oligodendrocytic differentiation was not detected in the grafted cells. Although NRPCs are capable of self-renewal and multilineage differentiation in vitro, they developed mostly into glial cells following engraftment into the adult retina. These data suggest that the adult retina retains epigenetic signals that are either restrictive for neuronal differentiation or instructive for glial differentiation. Induction of lineage-specific cell differentiation of engrafted NRPCs to facilitate retinal repair will likely require initiation of specific differentiation in vitro prior to grafting and/or modification of the host environment concomitantly with NRPC grafting.     

Segregation analysis of prostate cancer in 1,719 white,African-American and Asian-American families in the United States and Canada

Some data suggest that brothers of prostate cancer patients have higher disease risk than their fathers, supporting an X-linked or recessive mode of inheritance. However, higher observed frequencies in brothers than fathers may merely reflect the strong temporal changes in US incidence rates. Objectives: (a) to evaluate the fit of X-linked, recessive, and dominant modes of inheritance to prostate cancer incidence, specific for calendar year, age, and race, in population-based samples of US and Canadian families; and (b) to evaluate a simple multifactorial model for familial aggregation of prostate cancer due to shared low-penetrance variants of many genes or shared lifestyle factors. Methods: The data consist of reported prostate cancer incidence in first-degree relatives of 1719 white, African-American, and Asian-American men with and without prostate cancer at ages < 70 years. Model parameters were estimated by maximizing a pseudo-likelihood function of the data, and goodness of model fit was assessed by evaluating discrepancies between observed and expected numbers of pairs of relatives with prostate cancer. Results: After adjusting for temporal trends in prostate cancer incidence rates we found that the X-linked model fit poorly, underpredicting the observed number of affected father–son pairs. This also was true of the recessive model, although the evidence for poor fit did not achieve statistical significance. In contrast, the dominant model provided adequate fit to the data. In this model the race-specific penetrance estimates for carriers of deleterious genotypes were similar among African-Americans and whites, but lower among Asian-Americans: risk by age 80 years for carriers born in 1900 was estimated as 75.3% for African-Americans and whites, and 44.4% for Asian-Americans. None of the Mendelian models fit the data better than did the simple multifactorial model. Conclusions: The good fit of the multifactorial model suggests that multiple genes, each having low penetrance, may be responsible for most inherited prostate cancer susceptibility, and that the contribution of rare highly penetrant mutations is small.