Evaluation of eye irritation potential of experimental cosmetic formulations containing glycolic acid, salicylic acid and ethanol using the Bovine Corneal Opacity and Permeability Assay.

OBJECTIVE: Prototype cosmetic formulations containing short-chain acids and alcohols intended to be applied in the proximity of the eyes are sometimes evaluated for ocular irritation potential using the validated Bovine Corneal Opacity and Permeability Assay (OECD TG 437). We evaluated the eye irritation potential of nine experimental cosmetic formulations designed and prepared by Avon Global Reserach and Development to differ only in the concentrations of Ethanol, Glycolic Acid and Salicylic Acid. METHODS: We analysed the data generated using the BCOP assay. The opacity and permeability values obtained following the exposure of bovine corneas to experimental cosmetic formulations were combined into a single In Vitro Irritancy Score used to rank eye irritation potential. Histopathological examination of treated corneas was used to provide additional information about the depth and degree of the injury and to support the prediction of eye irritation potential of each experimental cosmetic formulation. RESULTS: The In Vitro Irritancy Scores and histopathological analysis showed that experimental formulations containing only Ethanol, Glycolic Acid, or Salicylic Acid alone had, at most, a mild ocular irritation potential. The experimental formulations containing both Ethanol and Glycolic Acid had a mild ocular irritation potential, while the experimental formulations containing both Ethanol and Salicylic Acid had a moderate ocular irritation potential. Severe ocular irritation potential was induced by an experimental formulation containing a combination of Glycolic Acid and Salicylic Acid and it was further accentuated by the addition of Ethanol to the formulation. Our data indicate a possible synergistic effect on eye irritation potential of Ethanol, Glycolic Acid and Salicylic Acid in at least some experimental cosmetic formulations. Further, our results provide insight on an apparent concentration-dependent ocular irritation potential effect of combinations of Glycolic Acid, Salicylic Acid and Ethanol in at least one experimental cosmetic formulation. CONCLUSIONS: The results presented herein emphasise the need to consider in vitro testing of prototype cosmetic formulations containing combinations of Ethanol, Glycolic Acid and Salicylic Acid rather than relying on any predicted additive effect on ocular irritation based solely on previously generated results of similar formulations containing Ethanol, Glycolic Acid or Salicylic Acid alone. Further work is required to understand the significance of these observations and to elucidate the mechanisms responsible for the apparent synergistic effects of Glycolic Acid, Salicylic Acid and Ethanol and eye irritation potential suggested by our results.

Molecular hydrogen in minerals as a clue to interpret ∂D variations in the mantle.

Trace amounts of water dissolved in minerals affect density, viscosity and melting behaviour of the Earth's mantle and play an important role in global tectonics, magmatism and volatile cycle. Water concentrations and the ratios of hydrogen isotopes in the mantle give insight into these processes, as well as into the origin of terrestrial water. Here we show the presence of molecular H2 in minerals (omphacites) from eclogites from the Kaapvaal and Siberian cratons. These omphacites contain both high amounts of H2 (70 to 460 wt. ppm) and OH. Furthermore, their ∂D values increase with dehydration, suggesting a positive H isotope fractionation factor between minerals and H2-bearing fluid, contrary to what is expected in case of isotopic exchange between minerals and H2O-fluids. The possibility of incorporation of large quantities of H as H2 in nominally anhydrous minerals implies that the storage capacity of H in the mantle may have been underestimated, and sheds new light on H isotope variations in mantle magmas and minerals.

Qualification of a non-animal vaginal irritation method admitted as nonclinical assessment model (NAM) in the Incubator Phase of the United States Food and Drug Administration (US FDA) Medical Devices Development Tool (MDDT).

The U.S. Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) classifies personal lubricants as Class II medical devices. Because of this status and the nature of body contact common to personal lubricants, CDRH reviewers routinely recommend a standard biocompatibility testing battery that includes: an in vivo rabbit vaginal irritation (RVI) test; an in vivo skin sensitization test, such as the guinea pig maximization test (GPMT); and an in vivo acute systemic toxicity test using mice or rabbits. These tests are conducted using live animals, despite the availability of in vitro and other non-animal test methods that may be suitable replacements. The only test included in the biocompatibility battery currently conducted using in vitro assay(s) is cytotoxicity. FDA's recently launched Predictive Toxicology Roadmap calls for the optimization of non-animal methods for the safety evaluation of drugs, consumer products and medical devices. In line with these goals, a Consortium comprising the Institute for In Vitro Sciences, Inc. (IIVS), industry, the Consumer Healthcare Products Association (CHPA), and the PETA International Science Consortium (PETA-ISC) is qualifying the use of an in vitro testing method as replacement for the RVI test. Participating companies include manufacturers of personal lubricants and those interested in the advancement of non-animal approaches working collaboratively with the FDA CDRH to develop an in vitro testing approach that could be used in place of the RVI in pre-market submissions. Personal lubricants and vaginal moisturizers with diverse chemical and physical properties (e.g., formulation, viscosity, pH, and osmolality) in their final undiluted form will be the focus of the program. In vitro vaginal irritation data generated using commercially available human reconstructed vaginal tissue model(s) will be paired with existing in vivo RVI data and analyzed to develop a Prediction Model for the safety assessment of these products. This research plan has been accepted into the FDA CDRH Medical Device Development Tools (MDDT) program as a potential non-clinical assessment model (NAM). The proposed NAM aligns with the goals of the recently launched FDA Roadmap to integrate predictive toxicology methods into safety and risk assessment with the potential to replace or reduce the use of animal testing.

Confirmation of in vitro and clinical safety assessment of behentrimonium chloride-containing leave-on body lotions using post-marketing adverse event data.

Behentrimonium chloride (BTC) is a straight-chain alkyltrimonium chloride compound commonly used as an antistatic, hair conditioning, emulsifier, or preservative agent in personal care products. Although the European Union recently restricted the use of alkyltrimonium chlorides and bromides as preservatives to ≤0.1%, these compounds have been safely used for many years at ≤5% in hundreds of cosmetic products for other uses than as a preservative. In vitro, clinical, and controlled consumer usage tests in barrier-impaired individuals were conducted to determine if whole body, leave-on skin care products containing 1-5% BTC cause dermal irritation or any other skin reaction with use. BTC-containing formulations were predicted to be non-irritants by the EpiDerm® skin irritation test and the bovine corneal opacity and permeability (BCOP)/chorioallantoic membrane vascular assay (CAMVA) ocular irritation test battery. No evidence of allergic contact dermatitis or cumulative dermal irritation was noted under the exaggerated conditions of human occlusive patch tests. No clinically assessed or self-reported adverse reactions were noted in adults or children with atopic, eczematous, and/or xerotic skin during two-week and four-week monitored home usage studies. These results were confirmed by post-marketing data for five body lotions, which showed only 0.69 undesirable effects (mostly skin irritation) reported per million shipped consumer units during 2006-2011; a value consistent with a non-irritating body lotion. No serious undesirable effects were reported during in-market use of the products. Therefore, if formulated in appropriate conditions at 1-5%, BTC will not cause dermal irritation or delayed contact sensitization when used in a whole-body, leave-on product.

Trends in wound repair: cellular and molecular basis of regenerative therapy using electromagnetic fields.

Chronic ulceration of the leg represents a major, underestimated problem of modern health care, involving physical and cosmetic impairment and social stigma along with high community costs for patients' treatment. The increasing prevalence of chronic ulcers, currently reported to be as much as 0.3% in the general population, should stimulate identification of more efficacious therapeutic approaches to achieve complete healing. The strategies of regenerative medicine based on small molecules, biomimetic scaffolds, gene or cell therapy, and electromagnetic field manipulation represent some of the modern therapeutic alternatives for wound healing. Here we review in an integrated, interdisciplinary approach the modern cellular and molecular mechanistic concepts regarding the involvement of extremely low frequency electromagnetic fields (ELF-EMF) in the complex process of tissue repair, with particular focus on chronic wounds. The data analysis supports three main effects of electromagnetic fields on the wound healing pathways: 1) an antiinflammatory effect, by modulation of cytokine profile that induces the transition of the healing process from a chronic pro-inflammatory to an anti-inflammatory state; 2) a neo-angiogenic effect, by increased endothelial cells proliferation and tubulization and production of fibroblast growth factor (FGF)-2; and 3) a reepithelialization effect, by stimulation of collagen formation. We believe that utilization of ELF-EMF in larger clinical trials designed to optimize these functional parameters would facilitate a better understanding of ELFEMF- induced healing mechanisms and lead to improved therapeutic outcomes for this disabling condition which is often totally resistant to treatment.

Normalization of cortical bone density in children and adolescents with hyperthyroidism treated with antithyroid medication.

UNLABELLED: We assessed bone size and bone density (BD) measurements using computed tomography (CT) in children and adolescents with hyperthyroidism treated with antithyroid medication. We found that cortical BD appeared to improve at 1 year and normalize at 2 years in all tested patients. INTRODUCTION: Our previous study demonstrated that cortical BD in children and adolescents with untreated hyperthyroidism was significantly decreased as compared to age-, sex- and ethnicity-matched healthy controls. The present report evaluated whether attainment of euthyroidism by medical antithyroid treatment was able to improve or normalize cortical BD in these patients. METHODS: Anthropometrics and three-dimensional CT bone measurements including cross-sectional area (CSA), cortical bone area (CBA) and cortical BD at midshaft of the femur (cortical bone), and CSA and BD of L(1) to L(3) vertebrae (cancellous bone) in 15 children and adolescents after 1- and 2-year treatments with antithyroid medication were reviewed and compared to their pretreatment results. RESULTS: All patients were euthyroid at 1 and 2 years after medical antithyroid treatment. After adjusting for age, height, weight and Tanner stage, a significant increase in cortical BD in all patients (15/15) was found after 1 year of treatment (P < 0.001). Normalization of cortical BD was demonstrated in all tested patients (10/15) after 2 years. There were no significant changes in the other cancellous or cortical bone parameters. CONCLUSION: Cortical BD was improved at 1 year and normalized at 2 years in hyperthyroid patients rendered euthyroid with antithyroid medication.

Diagnostic approach of pneumonia in an elderly patient with comorbidities--case report.

Dyspnea is one of the symptoms that has a major impact on patients' health, with a negative influence on the quality of life. The main causes of dyspnea are cardiac, pulmonary and mixed (cardiac or pulmonary). There are several other causes such as metabolic conditions (acidosis), pain, neuromuscular disorders, otorhinolaryngeal disorders, anxiety, panic disorders and hyperventilation. Acute pneumonia in the elderly is a common occurrence and its incidence grows as the elderly population increases. We report the case of a 76 years old patient with a known cardiovascular condition, recently hospitalized for right pulmonary infarction. He presented to our clinic for influenced general state, rest dyspnea, fever, shiver, and productive cough in the last two days. Current medication included oral anticoagulants and triple antihypertensive treatment (responsible for his low blood pressure). Laboratory results showed a nonspecific inflammatory syndrome with leukocytosis and neutrophilia and mild normochromic normocytic anemia; D-dimers were within normal range, fibrin degradation products 1+; myocardial enzyme testing showed no alteration, and BPN (beta natriuretic peptide) was 790 pg/ml. Chest X-ray showed diffuse bilateral reticular shadows (more pronounced on the right side) and left costodiafragmatic opacification. It appears that age-related increase in morbidity and mortality in community-acquired pneumonia is not due to age per se, but to interactions between the immune system, systemic diseases and nutritional factors. Community-acquired pneumonia in the elderly is known to have a high mortality. Although the diagnosis can be easy, the physician must also investigate for less obvious causes of dyspnea such as the presence of comorbidities and fragility of the elderly patient.

Self-neglect in the case of the elderly. Where are we now?

UNLABELLED: Self-neglect in an elderly person is a behavior that threatens his/her own health and safety. It is present when a person refuses to adequately feed, water, shelter, or clothe himself, refuses medication or medical care, and personal safety measures. MATERIAL AND METHOD: This is a multicentric study of self-neglect in three geriatric units from Finland, Greece and Romania The medical, social, psychological and behavioral profile analysis was based on a questionnaire; this questionnaire relied on existing studies and social, economic and medical facts in the three countries. The cognitive function, nutritional status, and the presence or absence of depression have also been assessed. RESULTS AND DISCUSSIONS: The data obtained until now support the importance of self-neglect among the elderly. The social-medical network should not only identify, diagnose, prevent, and treat the elderly affected by the phenomenon of self-neglect, but also educate the society to help them and, moreover, to prevent their marginalization.

Bone size and density measurements in prepubertal children with Turner syndrome prior to growth hormone therapy.

UNLABELLED: Using computed tomography (CT), we found the decreases in bone size of vertebrae and femur, cortical bone area (CBA) of femur and bone density (BD) of vertebrae in prepubertal female with Turner syndrome (TS) compared to those of controls. INTRODUCTION: Bone mineral density results from previous studies utilizing single-photon absorptiometry (SPA) or dual-energy X-ray absorptiometry (DXA) in children with TS are controversial. The present study used CT to assess the differences in cancellous and cortical bone size and BD between prepubertal TS patients prior to growth hormone therapy and historical age and ethnicity-matched female controls. METHODS: Anthropometrics and CT bone measurements including cross-sectional area (CSA) and BD of lumbar vertebrae and femur and CBA of femur in prepubertal TS females were reviewed and compared with those in controls. RESULTS: Twenty-two prepubertal TS patients had delayed bone age, were shorter and lighter than controls (Ps < 0.001). After adjusting for weight, height and skeletal age, vertebral BD and CBA of the femur were lower in patients than in controls (P < 0.001 and P = 0.021, respectively). However, after additional adjusting for puberty, results were not different from controls. While a positive correlation between vertebral BD and age was noted in controls (r = 0.367, P = 0.092), a significant negative correlation was noted in patients (r = -0.615, P = 0.002). CONCLUSIONS: While the decrease in vertebrae and femur sizes of patients with TS appeared to be secondary to their small body size, the decreased BD of vertebrae and CBA of femur were likely secondary to estrogen deficiency.

Cellular and molecular mechanisms involved in the action of vitamin D analogs targeting vitiligo depigmentation.

The active metabolite of vitamin D3 - 1,25-(OH)2D3 - exerts most of its physiological and pharmacological actions through its nuclear receptor (VDR), regulating the transcriptional machinery of a variety of cell types. Basic research motivated by the detection of VDR in numerous target cells, has indicated potential therapeutic applications of VDR ligands in osteoporosis, cancer, secondary hyperparathyroidism and autoimmune diseases such as psoriasis, systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes and multiple sclerosis. In recent years vitamin D analogs, particularly calcipotriol and tacalcitol, have been used as topical therapeutic agents in vitiligo, an autoimmune pigmentary disorder characterized by aberrant loss of functional melanocytes from involved epidermis. The presence of cytotoxic T cells targeting melanocyte antigens and imbalance of the cytokine network were described as characteristics of the disease, eventually leading to melanocyte damage and death. Vitamin D ligands are designed to target the local immune response in vitiligo, acting on specific T cell activation, mainly by inhibiting the transition of T cells from early to late G1 phase and by inhibiting the expression of several pro-inflammatory cytokines genes, such as those encoding tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma). Vitamin D(3) compounds are known to influence melanocyte maturation and differentiation and also to up-regulate melanogenesis through pathways activated by specific ligand receptors, such as endothelin receptor and c-kit. In this review we summarize the complex pathogenetic rationale of vitamin D analogs in vitiligo depigmentation. Understanding the cellular and molecular mechanisms through which vitamin D targets the epidermal melanin unit is of great interest for identification of new effective therapeutic combination(s) that might induce repigmentation in vitiligo.

Autoantibodies and human leucocyte antigen class II in first-degree family members of Mexican-American type 1 diabetic patients.

As part of a genetic study of type 1 diabetes in Mexican-Americans, 360 first-degree relatives of 108 type 1 diabetic probands were studied. Islet cell antibody (ICA), insulin autoantibody, glutamic acid decarboxylase (GAD(65)), and protein tyrosine phosphatase autoantibodies were measured and human leucocyte antigen (HLA) class II alleles DRB1 and DQB1 genotyping was performed. ICA was positive in 37% of the probands and 5.8% of the relatives. A subgroup of 26 probands (12 ICA+, 14 ICA-) was tested for GAD(65) and was found positive. 4/14 ICA+ first-degree relatives were GAD(65) positive. Four relatives, positive for two antibodies, subsequently developed type 1 diabetes. Life-Table analysis of first-degree relatives with autoantibodies indicated an 80% disease-free survival at 3.5 yr. HLA-DRB1 was found to be associated with the presence of ICA in both probands and relatives, whereas HLA-DPB1 was associated with autoantibody in relatives of type 1 diabetic probands. These results suggest that autoimmunity occurs in type 1 diabetes families of Mexican descent in similar frequencies to that of non-Hispanic, Caucasian families. The presence of autoantibodies appears to be regulated in part by HLA class II genes, even in the absence of overt diabetes.

Investigation of the intracellular transport of tyrosinase and tyrosinase related protein (TRP)-1. The effect of endoplasmic reticulum (ER)-glucosidases inhibition.

Melanin biosynthesis is completely inhibited in the B16 melanoma cells following their incubation with inhibitors of the two ER glucosidases. This is primarily due to the inactivation of tyrosinase. Under the same conditions, the DOPA-oxidase activity of TRP-1 was only partially affected. In this report we investigate the effects of the perturbation of N-glycan processing in ER on the transport and activation of tyrosinase and TRP-1. We have localized the DOPA-oxidase activity in normal and inhibited cells and suggest that the first DOPA-reactive compartment of the secretory pathway (trans Golgi network) is also the site of tyrosinase activation. The inhibition of N-glycan processing does not affect the intracellular trafficking of the two melanogenic enzymes that are correctly transported to melanosomes. Immunoprecipitation experiments followed by analysis in SDS-PAGE under non-reducing conditions suggest that in inhibited cells, both tyrosinase and TRP-1 are synthesized in a modified conformation as compared to the normal proteins. These data suggest that the inhibition of melanin synthesis is not due to a defective transport but rather to conformational changes induced in the structure of tyrosinase and TRP-1 during their transit through the ER.

Differential effect of gender on the sizes of the bones in the axial and appendicular skeletons.

Recent observations suggest that throughout life the size of the vertebral bodies in females is smaller than that in males even after accounting for differences in body size. To confirm these reports and to determine whether similar differences exist in the appendicular skeleton, detailed measurements of the sizes of the vertebrae and the femur were obtained using computed tomography in 30 pairs of prepubertal boys and girls matched for age, height, and weight. Anthropometric parameters as well as gender influenced the cross-sectional area of the vertebrae. Heavier children had greater vertebral cross-sectional area than slender children regardless of gender, and the vertebral bodies were found to be significantly smaller in girls than in matched boys (approximately 11%), both using Student's t test (P < 0.0001) and its multivariate analog, the Hotelling's T2 test (P < 0.0001). In contrast to these findings in the axial skeleton, gender status did not influence the size of the bones in the appendicular skeleton, and neither the cross-sectional area (3.28 +/- 0.84 vs. 3.10 +/- 0.56 cm2) nor the cortical bone area (1.80 +/- 0.37 vs. 1.85 +/- 0.36 cm2) at the midshaft of the femur differed between boys and girls. These values, however, correlated strongly with all anthropometric indexes, and multiple regression analyses indicated that both measurements were primarily related to weight. The results suggest that although increases in mechanical loading associated with growth are the main determinant of the cross-sectional properties of the appendicular skeleton in children, factors other than body mass and related to gender have a significant role in the regulation of the sizes of the bones in the axial skeleton.

Brain infarction in children with diabetic ketoacidosis.

During the last 10 years, five children were treated at Childrens Hospital Los Angeles for acute, persistent neurologic loss during diabetic ketoacidosis (DKA). Four were transferred from local hospitals after the neurologic crisis. Computed tomography (CT) studies showed one or more areas of brain infarction in each patient, and none had evidence of diffuse cerebral edema. As three of the five patients had been treated for cerebral edema before their CT, brain edema may have been present initially. Our findings emphasize the importance of brain infarction as a cause of persistent neurologic loss in children with DKA.

Perioperative management with prolonged intravenous insulin infusion versus subcutaneous insulin in children with type I diabetes mellitus.

Our objective was to retrospectively evaluate glycemic excursion and insulin dosage in the perioperative period in children and adolescents with type I diabetes mellitus receiving prolonged intravenous insulin infusion for 2-3 days compared to conventional subcutaneous insulin treatment. A retrospective review of surgical admissions at the Children's Hospital of Los Angeles in patients with type I diabetes mellitus was conducted for the 3-year period from July 1989 to June 1992, to evaluate two treatment protocols used during that period. For the nine admissions in group 1, patients received 0.06-0.1 units regular insulin/kg/h beginning 2 h prior to surgery and lasting for 2-3 days postoperatively; while, for the ten admissions in group 2 subjects were given subcutaneous regular and intermediate-acting insulin as 2-4 injections daily, with the regular insulin dose prior to surgery decreased to 66-75% of usual. Blood glucose levels were determined at the bedside at hourly intervals and insulin dose adjustment done with the aim of achieving blood glucose levels between 5.5 and 8.3 mmol/L (100-150 mg/dL). The mean bedside blood glucose levels for group 2 were significantly higher 1 h prior to surgery and during the intraoperative period (p < 0.05). In the postoperative period, group 2 blood glucose levels were significantly higher at multiple times for up to 3 days with multiple levels greater than 11.1 mmol/L (200 mg/dL), which was not seen in group 1. The mean insulin dosage (units/kg) prior to admission was not different for the two groups. On the day of surgery and during postoperative days 1 and 2, patients in group 1 received a greater insulin dosage than group 2 subjects (p < 0.025). In group 1, insulin dosage was increased 23% and 15% over baseline for postoperative days 1 and 2, respectively, then, by day 3, was decreased back toward the baseline. In group 2 subjects, a 13.8% increase occurred on the day of surgery due to extra insulin given immediately following the procedures, followed by a 5.4, 44.2, and 66.6% increase over baseline for postoperative days 1 through 3, respectively. In conclusion, meticulous glycemic control was readily achieved in the perioperative period with a constant intravenous insulin infusion for up to 3 days in children and adolescents with type I diabetes. To achieve glycemic control, insulin dosage needs to be increased on the day of surgery and for approximately 2 postoperative days.

Growth hormone effects on wound healing in malnourished animals: a histological study.

Systemic growth hormone (GH) markedly improves celiotomy wound strength in protein malnourished (PM) animals. This study was undertaken to analyze the effect of GH as a basis for anatomically understanding. Adult female Spraque-Dawley rats were divided into normally nourished controls, PM and GH-treated PM groups. Protein malnutrition was achieved by feeding 5.5% protein restricted chow every other day for eight weeks before surgery. Controls were fed 23.4% protein chow. All animals were fed 23.4% protein chow postoperatively. Rat-GH was injected subcutaneously twice daily (1.0 mg/day) for three days prior to and five days after 5 cm midline celiotomy. Bursting strength of the wound was measured at 3, 6 and 14 days postoperatively. Histologic wound specimens (hematoxylin and eosin) were obtained from each group. Wound strength of malnourished rats was significantly less than that of normal controls at six days after operation (p < 0.001). With administration of growth hormone, the wound strength was significantly improved. Histologically, there was no difference between groups on day 3. On day 6 the normal control group showed a decrease in the early inflammatory cell infiltrate with concurrent development of granulation tissue and a dense proliferation of fibroblasts. The PM wound showed fatty infiltration, a very narrow band of poorly formed granulation tissue and a sparse fibroblastic proliferation. The GH-treated PM group showed a combination of histologic findings. Fatty infiltration, similar to that in malnourished non-treated animals, was still evident but there was also a dense proliferation of capillary channels and fibroblasts comparable to normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous subcutaneous insulin infusion (CSII) in children and adolescents with chronic poorly controlled type 1 diabetes mellitus.

This study was undertaken to determine if continuous subcutaneous insulin infusion (CSII) could improve control, diminish episodes of diabetic ketoacidosis (DKA), decrease number of hospitalizations and save health care expenditure in children and adolescents with long-standing poorly controlled diabetes mellitus. A retrospective analysis was done of six patients with type 1 diabetes for 1-8 years, of whom 4 were non-adherent to the diabetic regimen (ages 12-16.5 years) and 2 of whom had brittle diabetes (ages 8.5 and 10 years). These patients were non-randomly placed on the MiniMed (Sylmar, CA) CSII system. The year prior to CSII was compared with the year during pump use. Glycoslyated hemoglobin (HbA1c), spot urinary microalbumin, total cholesterol, insulin dose, growth velocity, number of convulsions and hypoglycemic events, number of episodes of DKA, number of hospitalizations and total inpatient costs were compared for the 2 years. The year prior to CSII, mean HbA1c was 9.02% (S.D. = 0.86%), mean number of hospitalizations was 5.2/patient (S.D. = 4.6), mean number of hospital days was 20.8/patient (S.D. = 14.7) and mean cost was $29330/patient (S.D. = $22804). During 1 year of CSII, mean number of hospital days decreased to 5 days/patient (S.D. = 0.8, P = 0.016), mean number of hospitalizations (including DKA and pump initiation) decreased to 1.7/patient (S.D. = 0.7, P = 0.31), mean inpatient costs decreased to $12762/patient (S.D. = $5.950, P = 0.047). HbA1c, urinary microalbumin, cholesterol, insulin dose and growth velocity did not change in a statistically significant manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of HLA-DQA1 and -DQB1 genes in Mexican Americans with insulin-dependent diabetes mellitus.

Mexican American patients (n = 35) with insulin-dependent diabetes mellitus (IDDM) and control subjects (n = 39) were HLA-DQA and DQB typed by the polymerase chain reaction technique combined with allele-specific oligonucleotide probes. Either DQB1*0302 or DQB1*0201 was present among 91% (32/35) of the patients compared to 67% (26/39) of controls. Either DQA1*0501 or DQA1*0301 was present in all patients (100% or 35/35) compared to 29/39 (74%) (OR 12.06 Pc < 0.05) of controls. All four of these genes, in cis or trans, were present in 15/35 (43%) of the patients compared to 3/39 (8%) of controls (OR 9.0; Pc < 0.01). The presence of one or more non-susceptibility alleles showed a dose-related decrease in relative risk. Presence of aspartic acid (Asp) at position 57 of the DQ beta chain did not confer protection and non-Asp homozygosity did not confer susceptibility to IDDM in this ethnic group. In conclusion, susceptibility to IDDM in Mexican Americans is associated with particular DQA and DQB combinations, illustrates dose-dependent parameters and contradicts the critical residue hypothesis.

HLA class II alleles and susceptibility and resistance to insulin dependent diabetes mellitus in Mexican-American families.

The role of HLA class II alleles in genetic predisposition to insulin dependent diabetes mellitus (IDDM) was examined by PCR/oligonucleotide probe typing of 42 Mexican-American IDDM families derived from Hispanic Caucasians and Native Americans. All high risk haplotypes (HLA-DR3 and DR4) were of European origin while the most strongly protective haplotype (DRB1*1402) was Native American. Of the 16 DR-DQ DR4 haplotypes identified, only those bearing DQB1*0302 conferred risk; the DRB1 allele, however, also markedly influenced IDDM risk. The general pattern of neutral and protective haplotypes indicates that the presence of Asp-57 in the HLA-DQ beta chain does not confer IDDM protection per se and indicates that both DRB1 and DQB1 influence IDDM susceptibility as well as protection.

Subcutaneous growth hormone-releasing hormone therapy in growth hormone-deficient children: first year of therapy.

The purpose of this study was to determine the efficacy and safety of GH-releasing Hormone [GHRH-(1-44)] therapy in GH-deficient children. Twenty previously untreated prepubertal children with GHRH deficiency were treated for 1 yr in a multicenter, open label, company-sponsored study with at least 20 micrograms/kg GHRH-(1-44), sc, half at bedtime and half upon awakening. The main effects were enhancement of linear growth, advancement in bone age, and alteration in general blood chemistries and hormonal values. The mean velocity of the entire group increased from 3.6 +/- 1.1 to 8.1 +/- 1.5 cm/yr (P < 10(-4)) at 1 yr of therapy. After 6 months of therapy, 16 were growing at a mean of 9.4 +/- 2.0 cm/yr and were continued on this dose. In 4 patients who were growing at a rate of 5.5 +/- 1.7 cm/yr, the dose was increased to 40 micrograms/kg daily for the second 6 months. The high dose group increased their mean linear growth velocity for the second 6 months while on the higher dose to 7.6 +/- 0.4 cm/yr (P < 10(-2)). This was equal to the mean velocity for the second 6 months of therapy of the 16 subjects who remained on the 20 micrograms/kg daily therapy (7.6 +/- 1.2 cm/yr). Mean advancement of bone age was 1.3 +/- 0.6 yr during the first year of therapy. No adverse changes in general biochemical, hormonal, or pituitary radiographic analyses were noted. No change in fasting glucose or insulin concentrations, or excessive generation of insulin-like growth factor-I concentrations occurred. We conclude that GHRH in a daily dose of 20-40 micrograms/kg for 1 yr was effective in increasing growth velocity in most GHRH-responsive GH-deficient patients. It was well tolerated without side-effects. Glucose intolerance was not noted.