Insulin pump therapy in pediatrics: a therapeutic alternative to safely lower HbA1c levels across all age groups

Abstract: Objective: To examine the efficacy and safety of using continuous subcutaneous insulin infusion (CSII) therapy in a large group of patients 18 months to 18 yr from a single pediatric diabetes program. Research design and methods: All patients ≤ 18 yr of age starting on CSII from 1 January 1997 to 31 March 2000 at the Yale Children's Diabetes Program were included. Clinical data were collected prospectively before and during pump treatment. HbA1c was the primary efficacy outcome and rates of diabetes‐related adverse events were the primary safety measures. Results: One hundred and sixty‐one children ranging in age from 18 months to 18 yr received CSII for an average of 32 ± 9 months when data collection was closed on 31 October 2001, including 26 preschoolers (< 7 yr), 76 school‐agers (7–11 yr) and 59 adolescents (12–18 yr). Mean HbA1c levels were 7.1% in the preschoolers, 7.8% in the school‐agers and 8.1% in the adolescents prior to the start of CSII. There was a significant and consistent reduction in mean HbA1c levels after 12 months of CSII (to 6.5% in preschoolers, 7.3% in school‐agers and 7.4% in adolescents, p < 0.02 vs. prepump) that was maintained at the most recent visit. Improved diabetes control was achieved with CSII without increasing daily insulin doses and in association with a decrease in the frequency of severe hypoglycemic events (p < 0.05 vs. prepump, all three age groups combined). Conclusions: CSII is an effective alternative to injection therapy in a large pediatric diabetes clinic setting. Even very young patients can utilize CSII to safely lower HbA1c levels.     

Cylindrocarcinoma in a patient with Brooke-Spiegler syndrome

BACKGROUND: Cutaneous cylindromas are benign adnexal tumors that may occur as a solitary lesion or in a multiple familiar pattern. Malignant change is rare. The association of multiple trichoepitheliomas and cylindromas, the so called Brooke-Spiegler Syndrome, is supposed to be inherited in an autosomal dominant manner. PATIENTS: A 55 year old woman presented with multiple skin tumors on the scalp, as well as the nasolabial and periauricular area since the age of 20 years. Her daughter and her nephew were also affected. Tumors were surgically removed for cosmetic reasons and showed histological signs of benign cylindromas and trichoepitheliomas. 35 years after diagnosis patient presented with a large exulceration on the right occipital area with intracranial invasion. Staging revealed multiple metastases in both lungs. Patient died 1 month later. RESULTS: Histological examination showed beside zones of massive necrosis multiple mitosis. The jigsaw puzzle pattern and the thick PAS positive basal layer, the striking characteristics of benign cylindromas, were lost. These histological findings and the clinical presentation led to the diagnosis of cylindrocarcinoma. CONCLUSIONS: Cylindrocarcinoma is an aggressive tumor with tendency to a local destructive growth and metastases. As malignant transformation of a benign cylindroma occurs more often in the multiple form a close follow-up of patients with multiple cylindromas is necessary. A family study is indicated.     

Distribution of protein nitrotyrosine in synovial tissues of patients with rheumatoid arthritis and osteoarthritis

OBJECTIVE: Because nitric oxide related species have been found in the inflamed joints of patients with arthritis, we investigated whether protein nitrotyrosine (a marker of tissue exposure to peroxynitrite) is present in their synovial tissues. METHODS: Protein nitrotyrosine was detected immunohistochemically and by Western blot analysis. Synovial tissues removed surgically from 12 patients with rheumatoid arthritis (RA) (mean age 63.7 yrs) and 20 with osteoarthritis (OA) (mean age 66.6 yrs) were studied. RESULTS: Nitrated proteins were detected immunohistochemically in all of 18 tissues examined. Diffuse staining of the stroma was seen in all patients, with more extensive staining in RA than OA (p = 0.008). Intense staining was detected in some lymphocytes, but not in others, even within a single lymphoid aggregate. Neutrophils did not stain for nitrotyrosine. Vascular endothelial cells stained for nitrotyrosine but adjoining smooth muscle cells did not. Both cytoplasmic and nuclear staining was seen in macrophages, endothelial cells, and lymphocytes. Numerous bands of nitrated proteins were detected by Western blot analysis of 15 synovial tissue extracts. Inducible nitric oxide synthase (iNOS) was detected immunohistochemically in endothelial cells, macrophages, vascular smooth muscle cells, and synoviocytes. CONCLUSION: Nitrotyrosine-containing proteins were found in essentially all synovia from RA and OA patients. The most prominent site of nitration in all cases was the stroma. iNOS, the likely source of the nitrating species, was found in a variety of cell types.     

Community-based care and risk of nursing home placement

OBJECTIVE: To test the substitution hypothesis, that community-based care reduces the probability of institutional placement for at-risk elderly. RESEARCH DESIGN: The closure of the Social Health Maintenance Organization (Social HMO) at HealthPartners (HP) in Minnesota in 1994 and the continuation of the Social HMO at Kaiser Permanente Northwest (KPNW) in Oregon/Washington comprised a "natural experiment." Using multinomial logistic regression analyses, we followed cohorts of Social HMO enrollees for up to 5 years, 1995 to 1999. To adjust for site effects and secular trends, we also followed age- and gender-matched Medicare-Tax Equity and Fiscal Responsibility Act (TEFRA) cohorts, enrolled in the same HMOs but not in the Social HMOs. SUBJECTS: All enrollees in the Social HMO for at least 4 months in 1993 and an age-gender matched sample of Medicare-TEFRA enrollees. To be included, individuals had to be alive and have a period out of an institution after January 1, 1995 (total n = 18,143). MEASURES: The primary data sources were the electronic databases at HP and KPNW. The main outcomes were long-term nursing home placement (90+ days) or mortality. Covariates were age, gender, a comorbidity index, and geographic site effect. RESULTS: Adjusting for variations in the 2 sites, we found no difference in probability of mortality between the 2 cohorts, but approximately a 40% increase in long-term institutional placement associated with the termination of the Social HMO at HealthPartners (odds ratio, 1.43; 95% confidence interval, 1.15-1.79). CONCLUSIONS: The Social HMO appears to help at-risk elderly postpone long-term nursing home placement.     

Detection of Epstein-Barr virus genomes in peripheral blood B cells from solid-organ transplant recipients by fluorescence in situ hybridization

Resolution of Epstein-Barr Virus (EBV) infection in pediatric solid-organ transplant recipients often leads to an asymptomatic carrier state characterized by a persistently elevated circulating EBV load that is 2 to 4 orders of magnitude greater than the load typical of healthy latently infected individuals. Elevated EBV loads in immunosuppressed individuals are associated with an increased risk for development of posttransplant lymphoproliferative disease. We have performed fluorescence in situ hybridization (FISH) studies with peripheral blood B cells from carriers of persistent EBV loads in order to directly quantitate the number of EBV genomes per infected cell. Patients were assigned to two groups on the basis of the level of the persistent load (low-load carriers, 8 to 200 genomes/10(5) peripheral blood lymphocytes; high-load carriers, >200 genomes/10(5) peripheral blood lymphocytes). FISH analysis revealed that the low-load carriers predominantly had circulating virus-infected cells harboring one or two genome copies/cell. High-load carriers also had cells harboring one or two genome copies/cell; in addition, however, they carried a distinct population of cells with high numbers of viral genome copies. The increased viral loads correlated with an increase in the frequency of cells containing high numbers of viral genomes. We conclude that low-load carriers possess EBV-infected cells that are in a state similar to normal latency, whereas high-load carriers possess two populations of virus-positive B cells, one of which carries an increased number of viral genomes per cell and is not typical of normal latency.     

Referrals for bereavement counselling in primary care: a qualitative study

The growth in the provision of counselling services in British primary care offers an opportunity for general practitioners (GPs) to refer patients to counsellors following bereavement. This study explores the factors that influence GPs referral decisions. Qualitative interviews were conducted with 50 GPs from two cities in southern UK. The study found that GPs draw on notions of abnormal bereavement in making referral decisions. Indicators of bereavement problems related to: the nature of the death; level of social support; and reaction to the death. GPs views about the types of patients likely to benefit from counselling were further criteria employed in referral decisions. The study indicated that consideration of these factors may discriminate against certain types of patients being referred. Further education in the range of psychological theories of bereavement may assist GPs in understanding their bereaved patients' experiences and in developing their skills in recognising abnormal reactions and making appropriate referrals.