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The presence or absence of chlorpropamide-alcohol flushing (CPAF) was not correlated with the classification of diabetes. Five out of twelve patients with juvenile-onset diabetes (JOD) flushed and three out of four patients with maturity-onset diabetes in young people (MODY) did not flush. Consequently, CPAF cannot be used for individual genetic counseling in diabetes mellitus.
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PMID:Chlorpropamide-alcohol flushing is not useful for individual genetic counseling of diabetic patients. 743 99

Genetic heterogeneity, the concept that diabetes can have many different causes, was first suggested by the existence of rare genetic syndromes with diabetes, ethnic differences in clinical features and genetic heterogeneity of animal models. Genetic heterogeneity is now considered to be firmly established by family, twin, metabolic, immunologic and HLA disease association studies that separate idiopathic diabetes into insulin-dependent types (juvenile-onset type) and noninsulin-dependent types (maturity-onset type). Further heterogeneity is being demonstrated within each of these broad groups of disorders--within insulin-dependent diabetes using the HLA antigens and immunologic studies, and within noninsulin-dependent diabetes using such criteria as obesity, insulin response, age of onset and chlorpropamide-primed alcohol-induced flushing. This heterogeneity has major implications for the research and care of our diabetic patients since the precise etiology, risk of complications and genetic counseling are likely to vary among these different disorders that result in diabetes.
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PMID:The genetics of the glucose intolerance disorders. 745 85

Octreotide is a synthetic octapeptide somatostatin analogue which has higher potency and longer duration of action than the natural hormone. It is effective after subcutaneous administration and no rebound hypersecretion has been observed. Pharmacological effects of octreotide include inhibition of numerous hormones (growth hormone, TSH, insulin, glucagon and all gut hormones), of exocrine secretion (gastric acid, pancreatic enzyme), and of small-bowel absorption. This review deals with clinical application of octreotide in endocrine disorder. In patients with acromegaly octreotide treatment results in decrease of growth hormone (GH) and IGF-I together with tumour shrinkage and clinical improvement. Although variability in response to treatment is obvious for majority of patients the most effective dose is 100 mcg three times daily subcutaneously. Normalization of GH levels could be achieved in more than 50% of treated patients. It has also been shown that octreotide could be effective in TSH secreting pituitary adenoma, ACTH secreting adenoma as well as in non-secretory pituitary tumours. A marked biochemical and clinical responses together with longer survival have been reported in most of the patients with gastroenteropancreatic (GEP) tumours. Patients who benefit the most from octreotide therapy are those with carcionid syndrome (successful control of diarrhoea, flushing episodes and wheezing) and VIPomas (control of diarrhoea). In patients with insulin-dependent diabetes mellitus (IDDM) octreotide suppresses GH levels, postprandial blood glucose increases with resultant decrease in daily insulin requirements. In women with polycystic ovary syndrome (PCOS) octreotide has inhibitory effect on serum LH and ovarian androgens. This could have beneficial effect on ovulatory performance in women with PCOS.
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PMID:[Clinical use of octreotide (Sandostatin) in endocrinology]. 799 11

The oral ethanol loading test (0.5 g/kg body mass given as 40% solution) was carried out in 5 groups, each of 10 out-patients with non-insulin-dependent (type 2) diabetes before and after 10 days of treatment with one of the following sulphonylurea derivatives: tolbutamide (CAS 64-77-7) 0.5 t.i.d., chlorpropamide (CAS 94-20-2) 0.5 once daily morning, glibornuride (CAS 26944-48-9) 0.025 t.i.d., glibenclamide (CAS 10238-21-8) 0.005 t.i.d. and glipizide (CAS 29094-61-9) 0.005 t.i.d. The response to alcohol (facial flush, heart rate, blood pressure) were compared, and blood concentrations of ethanol, acetaldehyde, pyruvate, lactate, hydrocarbonates as well as blood pH, pO2 and pCO2 were determined in fasting state and during 6 hours after alcohol ingestion. In all patients the family history of diabetes and the presence and degree of vascular complications were registered. Evident flushing phenomenon was observed in 6 patients treated with chlorpropamide, in 3 treated with tolbutamide, in 2 treated with glibenclamide, in one receiving glibornuride and in none treated with glipizide. All drugs caused a greater rise of blood ethanol and acetaldehyde levels in relation to the control tests, but the difference reached statistical significance only in the group receiving chlorpropamide. Moreover, patients (pooled) with positive thermographic response had also significantly higher blood levels of ethanol and acetaldehyde during the second test. The ratio of acetaldehyde to ethanol concentration in blood (mumol:mmol) was not significantly changed in any group indicating parallel impairment of both steps of ethanol metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alcohol tolerance in patients with non-insulin-dependent (type 2) diabetes treated with sulphonylurea derivatives. 805 71

The failure of patients to adhere adequately to prescribed medication and behavioral regimens is an important medical problem. Poor adherence is most common when the treatment regimen is preventive rather than curative, when patients are asymptomatic, and when the duration of treatment is long. For these reasons, adherence with dietary therapy for hypercholesterolemia is well recognized to be a significant clinical and research challenge. Medication adherence has been acknowledged to be a problem for those treatments with significant side effects, such as flushing and pruritus or the low palatability of bile acid sequestering agents. The availability of drugs that lack these effects has long been viewed as an important contribution to improving overall patient compliance. However, the literature on patient adherence with life-long treatment regimens that are simple and palatable (e.g., antihypertensives) suggests that while these improved treatments can enhance adherence, the overall rates of patient compliance still average only 50%. The fact that patients with heterozygous familial hypercholesterolemia are at high risk for early coronary artery disease and death if they fail to adhere to therapy is not sufficient to assure high rates of appropriate therapy over long periods of time, as demonstrated by the poor or erratic adherence commonly reported to treatments for other life-threatening diseases, such as advanced renal disease, hemophilia, and type I diabetes. The measurement of patient adherence to hypercholesterolemia therapy is often neglected in clinical practice and inadequate in hypercholesterolemia research.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Measuring adherence with therapy for chronic diseases: implications for the treatment of heterozygous familial hypercholesterolemia. 821 1

Data from studies in diabetic rodents and evidence from clinical situations of severe resistance to insulin suggest that insulin-like growth factor I (IGF-I) is able to at least partly overcome insulin resistance. To assess the efficacy of recombinant human IGF-I in subjects with the most common form of insulin resistance, e.g., obese, type II diabetic patients, we administered recombinant human IGF-I (rhIGF) in doses of 120 and 160 micrograms/kg twice daily for 4-52 days to seven such individuals who had been treated previously with high doses of insulin (> 0.7 U.kg-1 x day-1). Four patients exhibited comparable or enhanced, whereas three had diminished, blood glucose control on rhIGF-I relative to that while on twice daily NPH insulin during the six-week control period. The occurrence of adverse effects in all patients compelled us to discontinue rhIGF-I administration before completing the 8-week treatment period. These adverse effects included edema primarily on the face and hands, mild weight gain, occasional dyspnea, bilateral jaw tenderness, arthralgias and myalgias, fatigue, tachycardia, flushing, orthostatic hypotension, and local burning at the injection site. We conclude that the frequency and severity of side effects associated with administering high-dose subcutaneous rhIGF-I to obese insulin-resistant diabetic patients make it an unacceptable therapeutic agent for these patients despite its ability to produce reasonable blood glucose control in approximately 50% of them.
Diabetes 1994 Mar
PMID:Adverse effects of recombinant human insulin-like growth factor I in obese insulin-resistant type II diabetic patients. 831 9

In a prospective, randomized, blinded study, 826 patients undergoing clean neurosurgical procedures received single intravenous doses of ceftizoxime (2 g) (n = 422) or a combination of vancomycin (1 g) and gentamicin (80 mg) (n = 404) 1 hour before an incision was made. Patients with infected or contaminated wounds and those receiving shunts or other implants were excluded. Primary wound infections occurred within 30 days in five patients in each group and were most common after spinal surgery and procedures through previous incisions. Secondary infections (pneumonias, urinary tract infections, and intravenous line-related bacteremia) occurred in 24 patients in the ceftizoxime group and 25 in the vancomycin/gentamicin group. The infection rates after transsphenoidal procedures (n = 129) were remarkably low in both groups. Ceftizoxime caused no adverse drug reactions, but six patients in the vancomycin/gentamicin group had clinically significant infusion-related hypotension or flushing. Placement of a temporary external drain, use of an operating microscope, preoperative steroids, and diabetes were not associated with increased infection rates. Analysis of routinely encountered ventricular cerebrospinal fluid and simultaneously obtained peripheral blood showed low but detectable levels of all three antibiotics within 2 hours; only ceftizoxime, however, achieved cerebrospinal fluid levels sufficient to inhibit the staphylococcus and Gram-negative bacilli most often associated with postneurosurgical infections. We conclude that ceftizoxime is as effective as vancomycin and gentamicin in neurosurgical prophylaxis but is less toxic and penetrates cerebrospinal fluid better.
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PMID:Ceftizoxime versus vancomycin and gentamicin in neurosurgical prophylaxis: a randomized, prospective, blinded clinical study. 841 95

The oral ethanol loading test (0.5 g per kg b.m. given as 40% solution) was carried out in 5 groups, each of 10 patients with non-insulin-dependent (type 2) diabetes before and after 10 days of treatment with one of the following sulphonylurea derivatives: tolbutamide 0.5 t.i.d., chlorpropamide 0.5 once daily morning, glibornuride 0.025 t.i.d, glibenclamide 0.005 t.i.d. and glipizide 0.005 t.i.d. The response to alcohol (facial flush, heart rate, blood pressure) were compared, and blood concentration of ethanol, acetaldehyde, pyruvate, lactate, carbonates as well as blood pH, pO2 and pCO2 were determined in fasting state and during 6 hours after alcohol ingestion. In all patients the family history of diabetes and the presence and degree of vascular complications were registered. Evident flushing phenomenon was observed in 6 patients treated with chlorpropamide, in 3 treated with tolbutamide, in 2 treated with glibenclamide, in one receiving glibornuride and in none treated with glipizide. All drugs caused a greater rise of blood ethanol and acetaldehyde levels in relation to the control tests, but the difference reached statistical significance only in the group receiving chlorpropamide. Moreover, patients (pooled) with positive thermographic response had also significantly higher blood levels of ethanol and acetaldehyde during the second test. The ratio of acetaldehyde to ethanol concentration in blood (mumol:mmol) was not significantly changed in any group indicating parallel impairment of both steps of ethanol metabolism. All studied drugs intensified to a similar degree the alcohol-induced hypoglycaemia, but had no significant effect on the decrease of blood pyruvate level neither on the increase of blood lactate level. They didn't change the post-alcohol decrease of blood bicarbonate and pH, and didn't modify the behaviour of partial gas pressure. There was also no difference between pooled groups of patients with positive and negative thermographic reaction with respect to family history of diabetes and frequency and intensity of vascular complications. It is concluded that in patients with non-insulin-dependent (type 2) diabetes the second generation sulphonylurea derivatives are associated with lower risk of alcohol intolerance in case of its incidental ingestion in small amounts. The hypothesis of association of positive thermographic reaction to alcohol during treatment with sulphonylurea derivatives with more frequent occurrence of diabetes in family members and lower tendency to vascular complications was not confirmed.
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PMID:[Alcohol tolerance in patients with non-insulin-dependent diabetes (type 2) treated orally with drugs--derivatives of sulphonylurea]. 841 9

A simple system for the continuos withdrawal of blood and the serial collection of blood samples in human subjects and experimental animals is described. It consists of heparin-coated tubing, a connector attached to an indwelling cannula that allows flushing of the i.v. catheter, a peristaltic pump and a fraction collector and an alarm system which is activated when blood flow through the system is interrupted. It can be assembled from parts available in every laboratory or hospital.
Exp Clin Endocrinol Diabetes 1995
PMID:A simple device for serial blood collection in human subjects and animals. 878 14

Niacin has been used for many years to treat hyperlipidemia. It has been shown to reduce coronary death and non-fatal myocardial infarction and, in a separate analysis of long-term (15-year) follow-up, all cause mortality. It reduces total cholesterol, low density lipoprotein cholesterol (LDL-C) and triglycerides and increases high density lipoprotein cholesterol (HDL-C). Sustained-release niacin may be associated with more dramatic changes in LDL-C and triglyceride, whereas the short acting preparation causes greater increases in HDL-C. The increase of HDL-C occurs at a lower dose (1500 mg/day) than the reduction of LDL-C (> 1500 mg/day). Niacin also favorably influences other lipid parameters including lipoprotein(a) [Lp(a)], alimentary lipemia, familial defective apolipoprotein B-100 and small dense LDL. Combination of niacin with a bile acid sequestrant or a reductase inhibitor represents a powerful lipid-altering regimen. Whereas the reductase inhibitors and bile acid binding resins primarily affect LDL-C, the combined therapy has a synergistic effect to reduce LDL-C and, in addition, the niacin reduces triglycerides and increases HDL-C. The major drawback in the use of niacin is associated side effects (flushing and palpitations) and toxicity (worsening of diabetes control, exacerbation of peptic ulcer disease, gout, hepatitis). Niacin has a long history of use as a lipid lowering agent and has several attractive features. Unfortunately, the side effect profile of this agent warrants its use only in patients with marked dyslipidemia in whom side effects and potential toxicity are closely monitored.
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PMID:New developments in the use of niacin for treatment of hyperlipidemia: new considerations in the use of an old drug. 885 85


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