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 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HIV-associated lipodystrophy often includes excess accumulation of visceral fat. Recombinant human growth hormone (rhGH) is a potential treatment for the excess visceral fat. Prospective, open-label trials of 24 weeks of rhGH 6 mg/d and 24 weeks of 4 mg every other day were conducted with an intervening washout period of 12 weeks. Thirty HIV-positive participants (26 men and 4 women) with visceral adiposity were enrolled. The main outcome measure was change in visceral adipose tissue (VAT) on whole-body magnetic resonance imaging scan. Changes in whole-body subcutaneous adipose tissue and skeletal muscle, glucose metabolism, serum lipids, and quality of life were also assessed. Despite stable body weight, VAT decreased in evaluable subjects an average of 42% with rhGH 6 mg/d (n = 24; p <.001) and 15% with 4 mg every other day (n = 10; p <.01) after 12 weeks, with trends toward further decreases after an additional 12 weeks at each dose. Subcutaneous adipose tissue also decreased, but proportionately less and not significantly on the lower dose. Skeletal muscle increased. Body composition rebounded to or near baseline after the washout period. Effects on lipids were inconsistent. Total cholesterol levels fell on the higher dose only, whereas high-density lipoprotein cholesterol levels increased on the lower dose only, and there was no effect on triglyceride levels. Joint pain was the most common adverse event, and was reflected in subjective quality of life measurements as an increase in bodily pain. Insulin sensitivity fell, and 4 participants developed diabetes. Other adverse events included cancer of unknown relationship to treatment in 3 participants. Levels of distress decreased after 24 weeks on the higher dose. In conclusion, rhGH effectively reduces the excess visceral adipose tissue often associated with HIV fat redistribution/lipodystrophy. However, frequent adverse effects warrant controlled studies and careful patient monitoring, especially regarding glucose tolerance.
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PMID:Effect of recombinant human growth hormone in the treatment of visceral fat accumulation in HIV infection. 1213 44

Locomotor disability, as defined by difficulties in activities of daily living related to lower limb function, can be the consequence of diseases and impairments of the cardiovascular, pulmonary, nervous, sensory and musculoskeletal system. We estimated the associations between specific diseases and impairments and locomotor disability, and the proportion of disability attributable to each condition, controlling for age and comorbidity. The Rotterdam Study is a prospective follow-up study among people aged 55 years and over in the general population. Locomotor disability in 1219 men and 1856 women was assessed with the Stanford Health Assessment Questionnaire. Diseases and impairments were radiological osteoarthritis, pain of the hips and knees, morning stiffness, fractures, hypertension, vascular disease, ischemic heart disease, stroke, heart failure, chronic obstructive pulmonary disease (COPD), depression, Parkinson's disease, osteoporosis, diabetes mellitus, overweight, and low vision. Adjusted odds ratios, etiologic and attributable fractions were calculated for locomotor disability. The occurrence of locomotor disability can partly be ascribed to joint pain, COPD, morning stiffness, diabetes and heart failure in both men and women. In addition in women osteoarthritis, osteoporosis, low vision, fractures, stroke and Parkinson's disease are significant etiologic fractions. In men with morning stiffness, joint pain, heart failure, diabetes mellitus, and COPD a significant proportion of their disability is attributable to this impairment. In women this was the case for Parkinson's disease, morning stiffness, low vision, heart failure, joint pain, diabetes, radiological osteoarthritis, stroke, COPD, osteoporosis, and fractures of the lower limbs, in that order. We conclude that locomotor complaints, heart failure, COPD and diabetes mellitus contribute considerably to locomotor disability in non-institutionalized elderly people.
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PMID:Determinants of locomotor disability in people aged 55 years and over: the Rotterdam Study. 1238 Jul 18

Iron overload in body tissues can cause complications such as cirrhosis, cardiomyopathy, diabetes, hypogonadism and arthritis. In populations of northern European descent, most iron overload is due to hereditary haemochromatosis (HHC), a genetic condition that causes increased iron absorption. HHC can be treated or prevented by regular phlebotomy treatments. Some experts have called for population screening for HHC, so that early phlebotomy treatment can be initiated. Two screening tests are available: measurement of the serum iron transferrin saturation (Tf%) and genetic testing for HFE mutations. However, both methods have low positive predictive values. Current data suggest that most people at risk are unlikely to develop clinical symptoms and that the population prevalence of clinical complications of HHC is low, arguing against population screening. Two other prevention strategies are available. (1) Health provider education, to heighten awareness of HHC as an explanation for symptoms and signs seen in early iron overload including unexplained fatigue, joint pain, palpitations, abdominal pain, elevated liver function tests, hepatomegaly and elevated serum ferritin. (2) Family-based testing after a diagnosis of HHC, to ensure that relatives are evaluated for evidence of iron overload. More research is also needed to identify the factors that increase risk for disease in persons with excess iron uptake, to determine whether moderate iron overload is a health risk and to evaluate the causes of iron overload other than HHC.
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PMID:Hereditary haemochromatosis: a realistic approach to prevention of iron overload disease in the population. 1240 10

The presence of steatosis and inflammatory infiltrate in liver biopsies is essential for the diagnosis of non-alcoholic steatohepatitis (NASH). These findings are similar to those with alcoholic liver disease. However, in the NASH-situation alcohol doesn't play an important role. Risk factors for the development of NASH are obesity and diabetes. Most of the patients are clinically asymptomatic. This means, that a diagnosis of NASH is a diagnosis of exclusion: Viral induced, autoimmune, metabolic and toxic liver disease have to be excluded. The disease has a benign clinical course. The risk of cirrhosis is low. So far, there is no established treatment. Preliminary reports suggest a positive effect of weight-loss and ursodeoxycholic acid. Wilson's disease, a copper storage disorder, in which biliary copper excretion is reduced, is inherited as an autosomal recessive trait. Most patients with Wilson disease become symptomatic between the ages of 6 and 15. In about 90% of patients serum ceruloplasmin levels and serum copper concentrations are reduced. Copper excreation is increased. Histologic examination of liver biopsy specimens reveals fatty infiltration, Mallory bodies and ballooned glycogen nuclei, abnormalities which are also found in alcoholic liver disease. The definitive diagnostic parameter is the quantitative determination of liver copper content (> 250 micrograms/g dryweight). Untreated Wilson disease is always fatal. Lifelong treatment with anti-copper drugs are essential, D-penicillamine being the firstline therapy. Hereditary hemochromatosis (HH) is an iron overload disease inherited as an autosomal recessive trait. The frequency of the disease is high. The first symptoms usually can be found at the age of 20-50 years. Arthralgia develops in up to 50% of the patients. Many organs are involved, most often the liver. The organ is usually enlarged, transaminases are always moderately elevated. Laboratory findings disclose a marked elevation in serum ferritin and transferrin saturation. More than 80% of HH-patients are homozygous for the C282Y-mutation in the HFE-gene. The firstline treatment of HH is phlebotomy. Treatment is lifelong. When serum ferritin drops below 50 micrograms/l, the frequency of phlebotomy should be reduced (4-12 per year). If the patient already has cirrhosis, the risk of HCC is very high.
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PMID:[Rare, but important chronic liver diseases]. 1250 71

A 56-year-old woman with diabetic triopathy, rheumatoid arthritis and chronic renal failure was admitted for severe hypoglycemic coma. Arthralgia had been deteriorating for 6 months. Therefore, 5 mg of prednisolone was administered. Postprandial blood glucose (PPG), however, elevated from 260 to 290 mg/dl, although fasting blood glucose (FBG) levels ranged from 80 to 110 mg/dl. Three months after, 270 mg of nateglinide was given in addition to acarbose. After 2 days, hypoglycemia occurred at 02:00 h. Nateglinide was then decreased to 180 mg (before breakfast and lunch). After 5 days, hypoglycemia re-occurred at 01:00 h. Nateglinide was subsequently decreased to 90 mg before breakfast. The PPG levels ranged from 130 to 150 mg/dl. Hypoglycemia did not occur during the next 2 months. On admission, FBG; 59 mg/dl, fasting immunoreactive insulin; 34 microU/ml, indicated hyperinsulinemic hypoglycemia. We administered 20 g of glucose intravenously, however, hypoglycemia recurred 4 times and 20 g of glucose was then administered. Although the plasma nateglinide level decreased, the nateglinide metabolite, N-[trans-4-(1-hydroxy-1methylethyl)-cyclohexanecarbonyl]-D-phenylalanine levels still had not decreased 29 h after nateglinide administration. Therefore, chronic renal failure appeared to alter the pharmacokinetic parameters of the nateglinide metabolite, which had accumulated by chronic renal failure. The nateglinide metabolite caused severe hypoglycemia in this case.
Diabetes Res Clin Pract 2003 Mar
PMID:Hypoglycemia due to nateglinide administration in diabetic patient with chronic renal failure. 1259 15

Acromegaly is a chronic disorder invariably caused by a growth hormone (GH)-secreting pituitary tumour and is characterised by disabling symptoms (sweating, arthralgia, headache, paraesthesiae, fatigue), significant comorbidities (diabetes mellitus, hypertension, sleep apnoea), and premature mortality. Symptomatic control can be achieved by lowering insulin-like growth factor-I (IGF-I) concentrations to within the age-adjusted normal range, and survival can be improved to match that of the general population. However, even with optimal surgery and current medical therapies (dopamine agonists, somatostatin analogues), 30% to 50% of patients do not achieve target concentrations of IGF-I and GH. Pegvisomant is a new GH-receptor antagonist that blocks GH activity by inhibiting functional dimerisation of GH-receptors. Given as subcutaneous injections at dosages of 10 mg, 15 mg, or 20 mg/day for 3 Months, pegvisomant normalised serum IGF-I concentrations in, respectively, 54%, 81%, and 89% of acromegalic patients. Moreover, long-term pegvisomant therapy normalised IGF-I concentrations in 97% of patients treated for 12 Months or longer, with no evidence of tachyphylaxis. Pegvisomant is the most effective medical therapy, reported to date, in terms of normalisation of circulating IGF-I concentrations. In addition, pegvisomant appears to be safe and well tolerated. Although additional long-term studies are required to further assess safety, the introduction of this innovative treatment should allow for optimal disease control in patients with acromegaly.
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PMID:Pegvisomant: an advance in clinical efficacy in acromegaly. 1267 Feb 98

EPIDEMIOLOGY ADN PHYSIOPATHOLOGY: Hereditary haemochromatosis is the most common genetic disease in France. Its frequency is on average 1 out of 300 French individuals. It is due to excessive dietary iron absorption, leading to accumulation of iron in the body. Mutations of the HFE1 gene are responsible for the majority of the case of haemochromatosis. FROM A CLINICAL POINT OF VIEW: The first clinical manifestations (weakness, sexual dysfunction, arthralgia, cardiac symptoms, dyspnoea on effort) can occur after the age of 30 years in men and 35 years in women (protected for longer by menstruation, pregnancy and delivery). In the absence of diagnosis, severe complications can develop during the 5th decade: nervous breakdown, arthropathy, heart failure, diabetes mellitus, cirrhosis with risk of progression towards carcinoma, responsible for handicaps and premature death. DIAGNOSTIC ELEMENTS: The diagnosis is evoked in the case of an increase in transferrine saturation (>45%), associated or not with excessive ferritin plasma levels. It is confirmed by the genetic test, showing homozygotes for the C282Y mutation or compound heterozygotes for the C282Y and H63D mutations on the HFE1 gene. RMI quantifies hepatic iron loading and generally avoids the need for a liver biopsy. The differential diagnosis must exclude secondary iron overload due to chronic transfusions in congenital or acquired blood diseases, a polymetabolic syndrome, chronic viral or alcoholic hepatic diseases and porphyria cutanea tarda. EFFICIENT TREATMENT: Today, haemochromatosis is still treated by phlebotomy. This consists in withdrawing 400 to 500ml of blood every week at the initial depletion stage and subsequently a maintenance therapy in order to maintain ferritin levels below 50 ng/ml. Paradoxically and through ignorance, hereditary haemochromatosis remains a serious disease, although its diagnosis is easy and the treatment simple and effective.
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PMID:[Hereditary haemochromatosis]. 1579 37

Normal ageing is associated with a decline in spontaneous growth hormone (GH) secretion, and although elderly hypopituitary adults demonstrate an increase in total and central fat compared with age-matched controls and are distinguishable from control subjects in terms of GH responsiveness on dynamic testing, there are few data available on the response to GH replacement in older subjects. We have studied the baseline characteristics of 295 patients (173 males and 122 females) aged >65 years of age who began GH replacement therapy at the time of entry into the KIMS program (Pfizer International Metabolic Database) and the effects of GH replacement in 125 patients who completed at least 12 months of GH replacement therapy. Data were compared with those of 2469 (1249 males and 1220 females) patients aged <65 years with adult-onset GH deficiency (GHD). The patients were selected using strict criteria in accordance with the recommendations from the Growth Hormone Research Society. There was a higher proportion of pituitary adenoma relative to craniopharyngioma in the older age group (P<0.001), but there was no difference between groups in the degree of hypopituitarism (number of additional hormone deficiencies). Blood pressure, cholesterol and low-density lipoprotein (LDL) cholesterol levels were positively correlated with age, and older patients had a predictably higher prevalence of diabetes mellitus, coronary heart disease, stroke and history of hypertension. Quality of life (Assessment of Growth Hormone Deficiency in Adults (AGHDA) score) was impaired in both groups before the start of GH therapy. GH replacement doses were lower in older patients with GHD as compared with patients <65 years old. After 12 months of GH replacement, significant improvements were evident in waist circumference, waist/hip ratio, lean body mass, diastolic blood pressure, total and LDL cholesterol levels and AGHDA scores in patients aged <65 years. Similar significant reductions were evidenced in patients >65 years old compared with those observed in younger patients. The total number of adverse events was similar in younger and older patients with GHD. However, younger patients had more fluid retention-related adverse events such as headache, oedema and arthralgia; whereas, older patients with GHD had more adverse events related to glucose metabolism, cardiovascular events and neoplasms. These data indicate a positive benefit from GH replacement in older patients with hypopituitarism - particularly in relation to quality of life - using a lower dose of GH for replacement and with appropriate age-related safety controls.
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PMID:Aspects of growth hormone deficiency and replacement in elderly hypopituitary adults. 1513 78

Insulin-like growth factor-1 (IGF-1) and its receptors share considerable homology with insulin and insulin receptors, and their respective signaling pathways interact at the post receptor level. While the growth hormone (GH)-IGF-1 axis principally regulates tissue growth and differentiation, insulin exerts it primary effects on fuel metabolism. However, these two endocrine systems interact at multiple levels and in diabetes mellitus the GH-IGF-1 axis is grossly disturbed, with increased secretion of GH, reduced plasma levels of IGF-1, and complex tissue-specific changes in IGF binding proteins (IGFBPs). These observations have given rise to the view that GH-IGF-1 axis dysfunction, particularly low plasma levels of circulating IGF-1, probably play a significant role in several aspects of the pathophysiology of diabetes mellitus, including insulin resistance and poor glycemic control, and may also influence the development of microvascular complications. The availability of recombinant human IGF-1 (rhIGF-1; mecasermin), used either alone or in combination with insulin, has led to experimental studies and clinical trials in humans testing these hypotheses. These studies have examined the impact of subcutaneous rhIGF-1 injections on sensitivity and metabolic parameters. In patients with type 1 and 2 diabetes mellitus, insulin sensitivity is significantly improved, insulin requirements are reduced, and glycemic control of dyslipidemia is generally improved in short-term studies. rhIGF-1 is a particularly attractive possibility in patients with type 2 diabetes mellitus, where insulin resistance is the fundamental problem. Some patients with genetic syndromes of severe insulin resistance also benefit from treatment with rhIGF-1, which can bypass blocks in the insulin signaling pathway. The common adverse effects reported for rhIGF-1 are dose-related and include edema, jaw pain, arthralgia, myalgia, hypotension, injection site pain, and less commonly, Bell's palsy and raised intracranial pressure. Although disturbance of the GH-IGF-1 axis participates in the development of diabetic complications, the functional consequences of the complex changes in IGFBP expression at the tissue level are uncertain, and it is not known whether systemic IGF-1 therapy or other manipulations of the GH-IGF-1 axis would be helpful or harmful. Experimentally, IGF-1 has a protective effect on neuropathy, and could find an application in the healing of neuropathic ulcers. The potential benefits of IGF-1 therapy in diabetes mellitus have yet to be realised.
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PMID:Therapeutic potential of insulin-like growth factor-1 in patients with diabetes mellitus. 1583 92

The prevalence, severity, and clinical significance of physical and emotional symptoms in patients who are on maintenance hemodialysis remain incompletely characterized. This study sought to assess symptoms and their relationship to quality of life and depression. The recently developed Dialysis Symptom Index was used to assess the presence and the severity of 30 symptoms. The Illness Effects Questionnaire and Beck Depression Inventory were used to evaluate quality of life and depression, respectively. Correlations among symptom burden, symptom severity, quality of life, and depression were assessed using Spearman correlation coefficient. A total of 162 patients from three dialysis units were enrolled. Mean age was 62 y, 48% were black, 62% were men, and 48% had diabetes. The median number of symptoms was 9.0 (interquartile range 6 to 13). Dry skin, fatigue, itching, and bone/joint pain each were reported by > or =50% of patients. Seven additional symptoms were reported by >33% of patients. Sixteen individual symptoms were described as being more than "somewhat bothersome." Overall symptom burden and severity each were correlated directly with impaired quality of life and depression. In multivariable analyses adjusting for demographic and clinical variables including depression, associations between symptoms and quality of life remained robust. Physical and emotional symptoms are prevalent, can be severe, and are correlated directly with impaired quality of life and depression in maintenance hemodialysis patients. Incorporating a standard assessment of symptoms into the care provided to maintenance hemodialysis patients may provide a means to improve quality of life in this patient population.
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PMID:Prevalence, severity, and importance of physical and emotional symptoms in chronic hemodialysis patients. 1597 96


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