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Query: UMLS:C0028754 (obesity)
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From 120 patients attending a referral gout clinic, 12 patients were found to have primary renal disease at the time of, or prior to, their first attack of acute gouty arthritis. This number excluded those with chronic lead nephropathy, polycystic kidneys or who were receiving diuretics. The nature of the renal disease was usually of the tubulointerstitial variety rather than of glomerular origin. The renal clearance of urate per unit of glomerular filtration rate, which usually increases with renal disease, was generally reduced, suggesting impairment of renal excretion of urate. Nine of the patients were female (four premenopausal) and only three were males. The degree of renal impairment was only mild to moderate. Other common associations with gout, such as obesity, hypertension and regular alcohol consumption, were not prominent. The intrinsic renal disease in these patients was considered to be the major contributor to their development of hyperuricaemia and gout.
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PMID:Gout due to renal disease. 173 Jan 9

Between December 15, 1988 and November 30, 1990, the application of Rome and New York criteria enabled the diagnosis of 60 cases of gout among patients with arthritis or hyperuricemia seen as out-patients or hospitalised in the Department of Rheumatology of the Brazzavile T.H.G. There were 57 men and 3 women, with a mean age of 51. Gout is the primary form of inflammatory arthropathy in adults in the Congo. Affecting all socio-professional groups, it is diversely associated with obesity, alcoholism, hypertension and diabetes. Initial involvement affects the big toe. Oligo and polyarticular forms predominate because of the absence or delay in specific treatment. This series included 30 per cent of cases of chronic gout. Evidence of renal impairment was found in one third of patients. However, urate lithiasis was absent. Tophi were found preferentially over the elbows. Sickle cell disease was responsible for one case of tophaceous gout. In contrast with the results of studies undertaken before the 1980s, gout is seen to be a common condition in equatorial Africa.
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PMID:[Epidemiological and clinical aspects of gout in equatorial Africa. Apropos of 60 cases followed in the Department of Rheumatology of the Teaching Hospital Center in Brazzaville]. 178 Jun 67

The overfed rat served as the animal model for examining the influence of obesity on the hepatotoxic and nephrotoxic potential of metabolically activated drugs, and acetaminophen served as the prototype drug. Weanling Sprague-Dawley rats were given a standard pellet diet or semisynthetic, energy-dense diet designed to produce obesity. After 24 weeks, when overfed rats outweighed controls by more than 50%, animals received 710 mg/kg of acetaminophen i.p., based on total body weight. Toxicity evaluation included biochemical signs of organ injury over the first 24 hr and histopathologic changes in tissue morphology at 48 hr. Both enzyme release (alanine aminotransferase into plasma, alkaline phosphatase into urine) and frank cellular necrosis in liver and kidney of obese rats greatly exceeded that in pellet-fed controls. Contributing to the potentiation of injury were higher peak plasma concentrations of acetaminophen in obese animals resulting from total body weight dosing. However, liver and kidney injury and mortality remained elevated when peak plasma concentrations were matched by fat-free mass dosing, indicating that increased toxicity also was related to obesity. Incomplete recovery of acetaminophen and metabolites from obese animals (45 vs. 71% in control rats) caused by a functional renal impairment made it impossible to determine the metabolic fate of acetaminophen in overfed animals from the analysis of urine collections. Drug products measured in urine were summed with amounts remaining in carcass at sacrifice, computed as terminal plasma concentrations times respective distribution volumes. These results showed obese rats to form more glucuronide and less sulfate conjugate than did pellet-fed controls, coinciding with clinical evidence for enhanced glucuronidation in obese humans.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Obesity as a risk factor in drug-induced organ injury: increased liver and kidney damage by acetaminophen in the obese overfed rat. 359 8

We measured the blood pressure of 1226 patients with newly diagnosed maturity-onset diabetes, age 25 to 65 years (mean 52 years), mean fasting plasma glucose 11.4 mmol/L. Forty percent of males and 53% of females had hypertension by the World Health Organization criteria of either having blood pressure more than 160/95 mm Hg or receiving hypotensive therapy. Male patients were less obese than female patients (21% and 40% over ideal weight respectively) and a mean 1.3 years younger. Blood pressure was higher in women than men, but it was not significantly greater if age and obesity were taken into account. Twenty-three percent of men and 42% of women had already been informed they were hypertensive, and 12% of men and 26% of women were already receiving hypotensive therapy. The prevalence of hypertension in diabetic white patients was greater than that reported in a sex- and age-matched healthy population. The blood pressure of those taking diuretics was not significantly greater than that of untreated patients, but the 8% of men and 13% of women receiving other hypotensive drugs still had significantly higher blood pressure than the untreated patients. Both patients treated by diuretics and those treated by other hypotensive agents had significantly higher mean plasma urea and creatinine concentrations than untreated patients. This may have been induced by therapy, but one cannot exclude the possibility that treated patients already had renal impairment from diabetic, hypertensive, or other pathology.
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PMID:United Kingdom Prospective Diabetes Study. III. Prevalence of hypertension and hypotensive therapy in patients with newly diagnosed diabetes. A multicenter study. 407 42

We developed two multidisciplinary tutorial programs (TOBRA-DIDACT and VANCO-DIDACT) for teaching the basic principles of antibiotic drug monitoring by simulation of repeated administrations to fictitious patients whose physio-pathologic characteristics were pre-defined in the programs. To illustrate the two types of bactericidal kinetics, we have chosen one time-dependent (vancomycin) and one concentration-dependent (tobramycin) antibiotic. These computer-assisted programs operate on an interactive mode. In each of them, three main steps are connected: (1) Various types of clinical cases are submitted to the student: for each of them, case report includes clinical characteristics, location of infection, bacterial strain and minimal bactericidal concentration. These data must be taken into account during the following steps. (2) The student has to establish the treatment schedule: route of administration, dose for each injection, intervals between injections and duration of infusion. (3) The result of the dosage scheme proposed by the student is represented by a simulation of plotting antibiotic plasma concentrations vs. time during the first 4 days of treatment. These curves are obtained by a monoexponential (TOBRA-DIDACT) or biexponential (VANCO-DIDACT) pharmacokinetic model. Peak and trough concentrations are calculated at steady-state. An expert system provides a commentary with each result to evaluate the efficacy of the treatment and to assist the student in improving his prescription. TOBRA-DIDACT and VANCO-DIDACT illustrate the influence of age, obesity, renal impairment, location of infection and bacterial strain on antibiotic therapy. They also show the role of route of administration, dosing and intervals between injections on therapeutic response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Teaching individualized antibiotic dosage regimens by means of two computer-assisted learning programs. 792 49

Fluoxetine is well absorbed after oral intake, is highly protein bound, and has a large volume of distribution. The elimination half-life of fluoxetine is about 1 to 4 days, while that of its metabolite norfluoxetine ranges from 7 to 15 days. Fluoxetine has a nonlinear pharmacokinetic profile. Therefore, the drug should be used with caution in patients with a reduced metabolic capability (i.e. hepatic dysfunction). In contrast with its effect on the pharmacokinetics of other antidepressants, age does not affect fluoxetine pharmacokinetics. This finding together with the better tolerability profile of fluoxetine (compared with tricyclic antidepressants) makes this drug particularly suitable for use in elderly patients with depression. Furthermore, the pharmacokinetics of fluoxetine are not affected by either obesity or renal impairment. On the basis of results of plasma concentration-clinical response relationship studies, there appears to be a therapeutic window for fluoxetine. Concentrations of fluoxetine plus norfluoxetine above 500 micrograms/L appear to be associated with a poorer clinical response than lower concentrations. Fluoxetine interacts with some other drugs. Concomitant administration of fluoxetine increased the blood concentrations of antipsychotics or antidepressants. The interactions between fluoxetine and lithium, tryptophan and monoamine oxidase inhibitors, in particular, are potentially serious, and can lead to the 'serotonergic syndrome'. This is because of synergistic pharmacodynamic effects and the influence of fluoxetine on the bioavailability of these compounds.
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PMID:Clinical pharmacokinetics of fluoxetine. 819 83

Bardet-Biedl syndrome is a rare autosomal recessive disease characterized by dysphormic extremities, retinal dystrophy, obesity, hypogenitalism in males, and renal structural abnormalities. Because the clinical outcome of these patients is not well known, 21 families with Bardet-Biedl syndrome (BBS) were studied to determine the natural history of the disease. In a prospective cohort study, 38 patients with the syndrome and 58 unaffected siblings were identified. Patients were studied in 1987 and again in 1993. Age of onset of blindness, hypertension, diabetes, renal impairment, and death was determined. The prevalence of obesity, gonadal dysfunction, and renal structural abnormalities was assessed. All but 5 BBS patients (86%) were legally blind, 26% being blind by the age of 13 years and 50% by 18 years. Eighty-eight percent were above the 90th percentile for height and weight. Twenty-five (66%) patients had hypertension, 25% of BBS patients by age 26 years, and 50% by age 34 years, whereas in the unaffected group, 25% had hypertension by age 49 years (P < 0.0001). Twelve (32%) BBS patients developed diabetes mellitus, compared with none of the unaffected group. Only 2 patients were insulin dependent. Twenty-five percent of BBS patients had diabetes by the age of 35 years. In 12 women of reproductive age, 1 (8%) had primary gonadal failure. In 10 men, 4 had primary testicular failure. Nine (25%) patients developed renal impairment, with 25% of the BBS group affected by the age of 48 years. Imaging procedures of the kidney were performed in 25 patients with normal renal function. Whereas fetal lobulation and calyceal cysts/diverticula/clubbing were characteristic, occurring in 96% of patients, 20% (n = 5) had diffuse and 4% (n = 1) focal cortical loss. Eight patients with BBS died, 3 with end-stage renal failure and 3 with chronic renal failure. On life-table analysis, 25% of BBS patients had died by 44 years, whereas at that age 98% of unaffected siblings were still alive (P < 0.0001). Bardet-Biedl syndrome has an adverse prognosis, with early onset of blindness, obesity, hypertension, and diabetes mellitus. Renal impairment is frequent and an important cause of death. Survival is substantially reduced.
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PMID:The importance of renal impairment in the natural history of Bardet-Biedl syndrome. 865 Dec 40

To evaluate the effect of insulin and/or triglycerides on the pathogenesis of glomerulosclerosis, acarbose (BAYg5421), an inhibitor of intestinal alpha-glucosidases, was administered as a dietary admix (40 mg/100 g chow) to Zucker obese rats (ZOA), from 1.5 months until sacrifice at 1.5, 5, 8, 10 and 15 months. Obese (ZO) and lean (ZL) rats served as controls. Despite a similar food intake, ZOA weighed less than ZO at all ages. Acarbose reduced serum triglycerides at all ages, and insulin until 10 months. Glycemia remained normal in all groups. Proteinuria developed with age and to a greater degree in ZO than in ZOA rats. In ZL, a faint proteinuria appeared only in the oldest animals. Glomerulosclerosis, tubular and interstitial lesions rapidly affected ZO kidneys. These lesions were reduced in ZOA until 10 months. Acarbose did not modify the hypertrophy of the glomeruli that developed after three months, but slowed down the expansion of the mesangial domain seen in ZO. Thus, by reducing the amount of ingested glucose, acarbose yielded a normal glycemia with a lesser production of insulin and reduced renal impairment. Therefore, insulin could be a key factor involved in the pathogenesis of glomerulosclerosis, either directly or through a control of triglyceride concentrations.
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PMID:Reduction of insulin and triglycerides delays glomerulosclerosis in obese Zucker rats. 940 98

A case of familial Bardet-Biedl syndrome (BBS) in a 64-year-old woman is presented; it is characterized by abdominal obesity (BMI: 38.28; WHR: 0.98), slight mental retardation, polydactyly, pigmentary retinopathy and moderate renal failure, with insulin-resistant diabetes mellitus and severe inflammation of the left limb with necrosis of the last toe (the sixth) of the left foot. Four brothers and sisters of the patient presented the same syndrome. The patient had had healthy offsprings. The review of current literature indicates that BBS is a genetic autosomal recessive disease, formerly grouped with Laurence-Moon-Biedl syndrome but today considered as a separate entity. It is characterized by obesity, mental retardation, dysphormic extremities (syndactyly, brachydactyly or polydactyly), retinal dystrophy or pigmentary retinopathy, hypogonadism in males, and renal structural abnormalities or functional impairment. Extra- and intrafamilial variability of expressivity and severity of the various clinical manifestations was reported, among affected families and also in the same family. BBS is a rare but important syndrome, that should be known by the endocrinologist and the specialist in internal medicine, because it has an adverse prognosis, with early onset of blindness, insulin-resistant diabetes mellitus and severe renal impairment. Renal failure is a frequent cause of death early in life, even in the infant-juvenile years.
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PMID:[A case of familial Bardet-Biedl syndrome (obesity, slight mental retardation, polydactyly, retinitis pigmentosum and renal failure) with insulin-resistant diabetes mellitus]. 1006 26

The selective serotonin reuptake inhibitors (SSRIs) antidepressants are at present time the most useful for the treatment of depression. SSRIs exhibit differences in potency of inhibiting serotonin reuptake, although the differences do not correlate with clinical efficacy. There are substantial pharmacokinetic differences among the five SSRIs, fluvoxamine, fluoxetine, paroxetine, sertraline and citalopram. Optimum use of these drugs requires a working knowledge of these differences. Among these pharmacokinetic parameters, half-life and metabolism pathways are the most relevant. There are substantial differences in term of their half-life between fluoxetine and others SSRIs. The half-life of fluoxetine and its active metabolite norfluoxetine is respectively 2 to 4 days and 7 to 15 days, more extended than other SSRIs (approximately 1 day). The extended half-life of fluoxetine and its active metabolite may be an advantage in the poorly compliant patient and may offer a potential safety advantage over shorter-acting SSRIs, with respect to abrupt discontinuation of therapy. Conversely, this long half-life needs a long period of wash-out (5 weeks) before introducing other drugs (MAOIs, sumatriptan) which can interact with serotonin function and can lead to the serotoninergic syndrome. SSRIs are potent inhibitors of the hepatic isoenzyme P450-2D6 and would be expected to have effects on the clearance of drugs metabolized by this enzyme. Paroxetine is the most potent inhibitor, followed by fluoxetine, sertraline, citalopram and fluvoxamine. The metabolite elimination of citalopram, paroxetine and fluvoxamine is delayed by renal disease and dosages should be lowered in elderly patients. Conversely the pharmacokinetic of fluoxetine and sertraline are not affected by either age or renal impairment and, for fluoxetine, by obesity.
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PMID:[Pharmacokinetics of SSRI antidepressants: half-life and clinical applicability]. 1059 11


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