Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
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Noninvasive assessment of vascular dysfunction in the pediatric population has taken advantage of the development of high-resolution ultrasound techniques. The most frequently used methods are the quantification of flow-mediated endothelium-dependent dilation of the brachial artery and measurement of the intima-media thickening of the carotid artery. Both reduced flow-mediated dilation and increased intima-media thickness have been proven to correlate with late cardiovascular events and/or mortality in adults. As these noninvasive methods can easily be applied in children, there have been recent investigations in high-risk pediatric patients harboring classical cardiovascular risk factors. Endothelial dysfunction and increased thickness of the intima media are currently observed in children with familial hypercholesterolemia, obesity, and type 1 diabetes mellitus. The association of early vascular dysfunction with a known risk factor is an important issue as these anomalies precede the formation of atherosclerotic plaques. Therefore, they may help in stratification of the risk for cardiovascular event and to better tailor therapeutic interventions in at risk children. Finally, these methods have been applied in specific pediatric populations, such as children with end-stage renal disease, chronic parenteral nutrition, HIV infection, and coarctation of the aorta. In these conditions, endothelial dysfunction and vascular remodeling are also present early in life and these data raise new possibilities in the understanding of the pathogenesis of atherosclerosis in these populations.
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PMID:Noninvasive assessment of arterial stiffness and risk of atherosclerotic events in children. 1605 29

There is a paucity of data describing the incidence of pre-existing diseases or risk factors and their effects in trauma patients. We conducted a prospective study to determine the incidence of such factors in critically ill trauma patients and to evaluate their impact on outcome. The study, performed over a 2-year period, examined the hospital course of all trauma patients admitted to the ICU. Multiple risk factors were evaluated and analyzed via multivariate regression analysis. Outcome was evaluated by infection rate, hospital length of stay, ventilator days, and mortality matched for age and Injury Severity Score (ISS). A total of 1172 patients (73% blunt injury) were enrolled over the study period. Of these, 873 (74.5%) were male. The mean age was 42.5 years with an ISS of 19.8. Tobacco use (24%) was the most common risk factor identified, followed by hypertension (HTN, 17%), coronary artery disease (9%), chronic obstructive pulmonary disease (COPD)/reactive airway disease (4%), non-insulin-dependent diabetes (NIDDM) (4%), insulin-dependent diabetes (IDDM) (3.2%), cancer (3%), liver disease (2%), and HIV/AIDS (1.4%). Of these risk factors, IDDM was found to be an independent risk factor for infection (0.004) and ventilator days (0.047), increasing age was found to be an independent risk factor for hospital length of stay (0.023) and mortality (<0.001), and HTN was found to be an independent risk factor for increased ventilator days (0.04). In addition, COPD/reactive airway disease was found to be an independent predictor of ventilator days, infection, and ICU days (P < 0.05). Thus, increased age, IDDM, COPD, and HTN are most predictive of outcome in critically ill trauma patients. With our aging population it is becoming increasingly important to identify pre-existing risk factors on admission in order to minimize their effects on outcome.
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PMID:Incidence and impact of risk factors in critically ill trauma patients. 1636 14

Endemic histoplasmosis occurs uncommonly in Australia and has not previously been reported in the tropical Northern Territory, nor in Aboriginal Australian patients. We report one suspected and one confirmed case of severe disseminated histoplasmosis in Aboriginal Australians from the Northern Territory. Underlying illness included chronic cardiac disease and Type 1 diabetes mellitus, respectively, and neither patient was infected with HIV. The clinical presentations resembled malignancy. Diagnosis of histoplasmosis was made on the basis of bowel histology in Case 1, demonstrating characteristic yeasts, and lymph node histology and culture in Case 2. Histoplasmosis should be considered in relevant clinical situations, even in HIV-negative patients who have not left Australia.
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PMID:Histoplasmosis in two aboriginal patients from Australia's tropical Northern Territory. 1648 24

The chemokine receptor CCR5 came into worldwide prominence a decade ago when it was identified as one of the major coreceptors for HIV infectivity. However, subsequent studies suggested an important modulatory role for CCR5 in the inflammatory response. Specifically, CCR5 has been reported to directly regulate T cell function in autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and type 1 diabetes. Moreover, T cell-mediated immune responses are proposed to be critical in the pathogenesis of autoimmune and viral liver diseases, and recent clinical and experimental studies have also implicated CCR5 in the pathogenesis of autoimmune and viral liver diseases. Therefore, in this brief review, we highlight the evidence that supports an important role of CCR5 in the pathophysiology of T cell-mediated liver diseases with specific emphasis on autoimmune and viral liver diseases.
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PMID:CCR5 in T cell-mediated liver diseases: what's going on? 1688 60

The course of HIV-infection has changed dramatically since the beginning of the epidemic. Opportunistic infections and AIDS-defining tumors are diagnosed less frequently since the introduction of antiretroviral therapy and the time of survival has increased. According to German-Austrian therapy guidelines highly active antiretroviral therapy (HAART) should be started on the onset of HIV-related symptoms and/or when the CD4 cell count is lower than 350/microl. Patients should be treated in specialized centres because of the complexity of HIV-infection and its therapy. For monitoring CD4 cell counts and viral load are determined. Reasons for therapeutic failure can be drug interactions, resistance or compliance problems. Although HIV-infection is often compared to insulin dependent diabetes mellitus psychological and social impact on HIV patients is still high. Increasing viral multi-drug resistance, long-term toxicity like lipodystrophy, osteoporosis and cardiovascular disease are only some problems HIV-infected patients are facing in the next years. In Germany 600 to 700 patients still die because of AIDS every year.
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PMID:[HIV-related symptoms]. 1711 97

Niacin (nicotinic acid and nicotinamide) is a vitamin used as a source of the NAD+ and NADP+ coenzymes required for many metabolic processes. Its low dietary levels induce the development of pellagra. Niacin has been used for decades in the treatment of patients with disturbed lipid and lipoprotein metabolism, this being the main cause of atherosclerotic changes in cardiovascular diseases. It is still the most efficacious drug in terms of its ability to increase HDL cholesterol content accompanied by a decrease in all atherogenic lipoproteins (VLDL, LDL, and L(a)) as well as fatty acids and triglycerides. Niacin also increases adiponectin level, which might result in additional atheroprotection. There are studies confirming the beneficial action of niacin against migraine and hyperphosphatemia associated with renal failure, ethanol-induced neurodegeneration, and loss of beta-cell function in type 1 diabetes. Moreover, it augments plasma tryptophan concentrations in HIV-infected patients and thyroid radiosensitivity to 131I. Inhibition of the invasion of hepatoma cells has also been proven. However, it is necessary to point out that the currently applied niacin preparations might exhibit such side effects as cutaneous flushing, gastrointestinal disturbances, and hepatotoxicity, particularly during treatment with sustained-release niacin preparations. The recent discovery of the G-protein-coupled receptor GPR109A, which mediates the antilipolytic effects induced by nicotinic acid in adipocytes as well as cutaneous vasodilation, allows the development of new agents interacting with this receptor. In view of these observations, niacin therapy must be accompanied by control of the choice of niacin preparation and its dose in order to eliminate or at least limit its side effects.
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PMID:[Niacin in therapy]. 1755 32

Exenatide is an incretin mimetic indicated for the treatment of type 2 diabetes mellitus in combination with a sulfonylurea, a thiazolidinedione, metformin, or metformin plus a sulfonylurea or thiazolidinedione. Exenatide lowers postprandial blood glucose levels by stimulating glucose-dependent insulin secretion, inhibiting glucagon secretion, slowing gastric emptying, and increasing satiety. Therapy with exenatide often results in weight loss, which further assists in decreasing insulin resistance. This feature makes the drug an attractive therapeutic option for obese patients. We report the successful off-label use of exenatide in an obese, 40-year-old man with type 1 diabetes and human immunodeficiency virus (HIV) infection who had gastrointestinal intolerance to pramlintide. The patient had experienced a dramatic weight gain secondary to his antiretroviral drugs. This weight gain led to insulin resistance and the development of type 2 diabetes; thus he had characteristics of both types 1 and 2 diabetes, or double diabetes. Before the start of exenatide therapy, he weighed 123 kg, had a body mass index of 42.3 kg/m(2), and had a suboptimal hemoglobin A(1c) value of 8.7%. After 11 months of therapy, the patient lost 24 kg (19.5% of his body weight) and achieved a hemoglobin A(1c) value of 7.3%. His basal insulin requirement was reduced by 25%, and his use of short-acting insulin before breakfast and before dinner was discontinued. In addition, the patient's quality of life substantially improved, as he was able to return to work and exercise after being nearly incapacitated by his weight. To our knowledge, this is the first published case report of the use of exenatide in a patient with type 1 diabetes mellitus or human immunodeficiency virus infection. Given this experience, exenatide may prove to be a useful alternative in selected patients with type 1 diabetes.
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PMID:Off-label use of exenatide for the management of insulin-resistant type 1 diabetes mellitus in an obese patient with human immunodeficiency virus infection. 1789

We report an 8 year-old girl with well-controlled perinatally acquired HIV infection who developed autoimmune type 1 diabetes mellitus (DM1A) confirmed by the presence of diabetes-related auto-antibodies. Although non-autoimmune insulin dependent diabetes mellitus (DM1B) and more frequently type 2 DM has been reported in patients affected with HIV, this is the first report of DM1A diagnosed in an HIV positive patient.
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PMID:Autoimmune type I diabetes mellitus in a perinatally HIV infected patient with a well-preserved immune system. 1955 12

Vitamin D has historically been considered to play a role solely in bone and calcium metabolism. Human disease associations and basic physiological studies suggest that vitamin D deficiency is plausibly implicated in adverse health outcomes including mortality, malignancy, cardiovascular disease, immune functioning and glucose metabolism. There is considerable evidence that low maternal levels of 25 hydroxyvitamin D are associated with adverse outcomes for both mother and fetus in pregnancy as well as the neonate and child. Vitamin D deficiency during pregnancy has been linked with a number of maternal problems including infertility, preeclampsia, gestational diabetes and an increased rate of caesarean section. Likewise, for the child, there is an association with small size, impaired growth and skeletal problems in infancy, neonatal hypocalcaemia and seizures, and an increased risk of HIV transmission. Other childhood disease associations include type 1 diabetes and effects on immune tolerance. The optimal concentration of 25 hydroxyvitamin D is unknown and compounded by difficulties in defining the normal range. Whilst there is suggestive physiological evidence to support a causal role for many of the associations, whether vitamin D deficiency is a marker of poor health or the underlying aetiological problem is unclear. Randomised controlled trials of vitamin D supplementation with an appropriate assessment of a variety of health outcomes are required.
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PMID:Vitamin D and pregnancy: An old problem revisited. 2083 34

Since children with chronic diseases represent a primary target for immunization strategies, it is important that their immunization coverage and timeliness of vaccines is optimal. We performed a study to measure immunization coverage and timeliness of vaccines in children with type 1 diabetes, HIV infection, Down syndrome, cystic fibrosis, and neurological diseases. A total of 275 children aged 6 months-18 years were included in the study. Coverage for diphtheria-tetanus-pertussis (DTP), polio (Pol), and hepatitis B (HBV) vaccines approximated 85% at 24 months, while measles-mumps-rubella (MMR) coverage was 62%. Immunization coverage for seasonal influenza was 59%. The analysis of timeliness revealed that there was heterogeneity among children with different chronic diseases. A proportional hazard model showed that children with HIV infection had the longest time to complete three doses of DTP, Pol, and HBV, and those with neurological diseases received the first dose of MMR later than the other categories. Causes of missing or delayed vaccination mostly included a concurrent acute disease. Children with chronic diseases should be strictly monitored for routine and recommended vaccinations, and health care providers and families should be properly informed to avoid false contraindications.
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PMID:Immunization coverage and timeliness of vaccination in Italian children with chronic diseases. 2141 80


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