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.     

Sirolimus oral absorption in rats is increased by ketoconazole but is not affected by D-alpha-tocopheryl poly(ethylene glycol 1000) succinate

The contributions of cytochrome P450 3A (CYP3A) and P-glycoprotein to sirolimus oral bioavailability in rats were evaluated by coadministration of sirolimus (Rapamune) with the CYP3A inhibitor ketoconazole or the P-glycoprotein inhibitor D-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS). Groups of six male Sprague-Dawley rats (250-300 g) were administered Rapamune (1 mg/kg) by oral gavage, alone and with ketoconazole (30 mg/kg) or TPGS (50 mg/kg). Sirolimus levels were measured in whole blood over a 6-h time course. Sirolimus C(max) (6.6 +/- 1.6 versus 26 +/- 7 ng/ml) and area under the concentration versus time curve from 0 to 6 h (AUC(0-6)) (22 +/- 7 versus 105 +/- 27 ng. h/ml) were increased 3- to 5-fold by ketoconazole. Median T(max) (1.5-2 h) was unchanged. TPGS had no effect on sirolimus absorption. The interaction of sirolimus with P-glycoprotein was also evaluated in vitro using HCT-8 and Caco-2 cell monolayers. Consistent with published reports, sirolimus was a good inhibitor of P-glycoprotein, inhibiting polarized basolateral-to-apical flux of rhodamine 123 with an IC(50) of 0.625 to 1.25 microM (cyclosporine caused >80% inhibition at 5 microM). Sirolimus did not demonstrate significant polarized flux in either direction using the same monolayers (basolateral-to-apical flux was <2 times the apical-to-basolateral). Moreover, sirolimus flux was not impacted by cyclosporine, suggesting that it does not undergo P-glycoprotein-mediated transport in this system. The lack of significant sirolimus transport by P-glycoprotein may, in part, explain the lack of a TPGS effect on sirolimus absorption in rats.     

Acute lymphocytic leukemia after fulminant varicella associated with severe neutropenia

Acute lymphocytic leukemia developed within 3 weeks after a fulminant case of varicella complicated by pneumococcal sepsis and severe bone marrow suppression in a child treated with filgrastim (human granulocyte colony-stimulating factor).     

Diabetes mellitus in a subgroup of older Mexicans: prevalence,association with cardiovascular risk factors,functional and cognitive impairment,and mortality

OBJECTIVES: To examine the prevalence and effects of diabetes mellitus in a subgroup of older Mexicans to allow comparisons to older persons of Mexican origin living in the United States. DESIGN: Longitudinal study. SETTING: High-rise retirement housing in Mexico City. PARTICIPANTS: Seven hundred eighty-five public servants and their family members aged 65 and older. MEASUREMENTS: Geriatric survey of function; mental status and depression; a physical examination; and blood samples for glucose and cholesterol. RESULTS: The prevalence of diabetes mellitus in this population was 15.1%, substantially lower than the prevalence reported in people of Mexican origin living in the United States. Nondiabetics were more obese than diabetics. Diabetes mellitus was more common in men than women. The mortality rate was greater in diabetics than nondiabetics (relative risk=1.73, P <.05). Diabetics had more coronary artery disease and were more likely to die from myocardial infarction and neoplasms than nondiabetics. Diabetics were more likely to be functionally impaired (P <.0001) but no more likely to fall or to have fractures. Diabetics did not differ from nondiabetics in cognitive impairment or level of dysphoria. CONCLUSION: These studies highlight some important similarities and differences in comparing a middle class subgroup of older diabetics in Mexico City with diabetics of Mexican origin living in the United States.     

Treatment of lupus erythematosus with pulsed dye laser

BACKGROUND AND OBJECTIVES: The treatment of cutaneous lupus erythematosus (CLE) with dye and argon laser has been evaluated in a number of articles in recent years. The improvement of telangiectasias and chronic erythema of the cutaneous lesions was based on the selective photothermolysis ablation of the dilated capillaries and venules. STUDY DESIGN/MATERIALS AND METHODS: We describe the results of the treatment of cutaneous lesions of 14 patients; eight with discoid lupus erythematosus (DLE) and six with systemic lupus erythematosus (SLE). Three patients received a treatment with flashlamp pulsed dye laser (FPDL) (585 nm, 450 microseconds) with fluences in the range from 5 to 7.75 J/cm(2); the other 11 patients were treated with long pulsed dye laser (LPDL) (595 nm, 1.5-10 milliseconds) with fluences in the range from 6 to 13 J/cm(2) depending on the pulse duration. RESULTS: During a median follow-up of 10 months, we observed an average improvement in over 60% of the lesions. A few side effects were observed in all patients: four had transient hyperpigmentation and one patient had light scarring. Three patients had a relapse after more than 1 year; they were then offered conventional treatment. CONCLUSIONS: We confirm that pulsed dye laser is a good alternative treatment for the erythema in active cutaneous lesions of lupus erythematosus (LE).     

Antagonism of VIP-stimulated cyclic AMP formation in chick brain

Of eight peptides tested (0.01-5 microM), only two, that is, pituitary adenylate cyclase-activating polypeptide (PACAP27) and chicken vasoactive intestinal peptide (cVIP), potently stimulated cyclic AMP (cAMP) production in cerebral cortical slices of the chick. Mammalian VIP (mVIP) showed some activity only at the highest dose tested, whereas truncated forms of PACAP or VIP, that is, PACAP6-27, cVIP6-28, and mVIP6-28, or hybrid compounds, that is, neurotensin6-11-cVIP7-28 (NT-cVIP) and neurotensin6-11-mVIP7-28 (NT-mVIP), were inactive. Thirty-minute preincubation of chick cortical slices with 5 microM PACAP6-27, NT-cVIP, or NT-mVIP competitively antagonized the cAMP effects of cVIP (0.03-1 microM), with the truncated form of PACAP being the best antagonist. Preincubation of slices with 5 microM mVIP6-28 also produced a significant inhibition of the cVIP (0.1-1 microM)-induced increase in cAMP production; however its action was independent of the concentration of cVIP. In contrast to mVIP6-28, cVIP6-28 showed no antagonistic activity against the full-length peptide. In parallel experiments, 30-min pretreatment of cortical slices with 5 microM PACAP6-27 significantly antagonized the PACAP38-evoked increase in cAMP formation, whereas mVIP6-28 or the NT-mVIP hybrid was ineffective. It has been concluded that in the chick brain, PACAP and cVIP stimulate cAMP biosynthesis via PAC1 and VPAC-type receptors, respectively, and PACAP6-27 seems to be the most potent, yet PACAP/VIP receptor-nonselective antagonist. Unlike truncated PACAP, the NT-VIP hybrid peptides tested may represent VPACtype receptor-selective blocking activity.     

Apigenin inhibits TGF-β1 induced fibroblast-to-myofibroblast transition in human lung fibroblast populations

BackgroundFlavonoids are dietary plant compounds suspected to reduce the incidence of chronic diseases in several regions of the world. Due to anti-allergic and anti-inflammatory activities, apigenin (4’,5,7,-trihydroxyflavone) is thought to interfere with crucial events in the pathomechanism of asthma. However, the effect of apigenin on TGF-β-induced fibroblast-to-myofibroblast transition (FMT) in human lung fibroblast populations, a key event in asthma progression, has not yet been addressed.MethodsPrimary human bronchial fibroblasts (HBFs) propagated from ex vivo bronchial biopsies derived from patients with diagnosed asthma and human embryonic lung IMR-90 fibroblasts were cultured in vitro and treated with TGF-β₁ and apigenin. The myofibroblast fraction in fibroblast populations was evaluated by immunocytochemistry. Expression of α-smooth muscle actin (α-SMA) and tenascin C were assessed at the mRNA and protein level by real-time RT-PCR and immunoblotting, respectively. Additionally, proliferation and viability tests and time lapse-monitoring ofmovement of individual HBFs and IMR-90 cellswere evaluated.ResultsWe show that apigenin attenuates TGF-β₁-induced FMT in cultures of HBFs, and the magnitude of this attenuation was found to be similar to that observed in the established cell line of lung IMR-90 fibroblasts. Notably, FMT inhibition was observed at low (~10 μM), non-cytotoxic and non-cytostatic apigenin concentrations and could be correlated with the inhibition of α-SMA and tenascin C expression in HBFs at the mRNA level.ConclusionsOur data are the first to demonstrate that apigenin inhibits the TGF-β₁-induced expansion of hyper-contractile, α-smooth muscle actin – positive myofibroblasts within populations of HBFs derived from asthmatic patients. They also indicate the possible interference of apigenin with bronchial wall remodeling during the asthmatic process in vivo.     

Male Involvement in PMTCT Services in Mbeya Region,Tanzania

Throughout all stages of programmes for the prevention of mother-to-child-transmission of HIV (PMTCT), high dropout rates are common. Increased male involvement and couples’ joint HIV counselling/testing during antenatal care (ANC) seem crucial for improving PMTCT outcomes. Our study assessed male attitudes regarding partner involvement into ANC/PMTCT services in Mbeya Region, Tanzania, conducting 124 individual interviews and six focus group discussions. Almost all respondents generally supported PMTCT interventions. Mentioned barriers to ANC/PMTCT attendance included lacking information/knowledge, no time, neglected importance, the services representing a female responsibility, or fear of HIV-test results. Only few perceived couple HIV counselling/testing as disadvantageous. Among fathers who had refused previous ANC/PMTCT attendance, most had done so even though they were not perceiving a disadvantage about couple counselling/testing. The contradiction between men’s beneficial attitudes towards their involvement and low participation rates suggests that external barriers play a large role in this decision-making process and that partner’s needs should be more specifically addressed in ANC/PMTCT services.     

Capillary electrophoresis with indirect UV detection for the determination of stabilizers and citrates present in human albumin solutions

Sodium caprylate and N-acetyltryptophan are the most frequently used stabilizers that protect the albumin from aggregation or heat induced denaturation. In turn citrates – excipients remaining after fractionation process – can be treated as by-product favoring leaching aluminum out of glass containers whilst albumin solution is stored. With ionic nature these substances have all the markings of a subject for capillary electrophoresis analysis. Thus CE methods were proposed as new approach for quality control of human albumin solution in terms of determination of stabilizers and citrates residue.