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It is known that, among human patients with sepsis, acute renal failure (ARF) dramatically increases mortality rates to 50 to 80%. However, the pathogenesis of septic ARF is not fully understood. An increase in endotoxin-induced mortality rates for leptin-deficient ob/ob mice was recently demonstrated. In comparison with ob/ob mice, db/db mice, which are deficient in the long isoforms of leptin receptors (Ob/Rb), demonstrate lower mortality rates after exposure to the endotoxin LPS. In db/db mice, mRNA for the short isoforms of leptin receptors is constitutively expressed in the kidney, lung, liver, and macrophages. It is known that plasma leptin levels increase in rodents after exposure to LPS, and this was demonstrated for db/db mice. Because ob/ob and db/db mice are both obese, factors other than obesity must be involved in the increased mortality rates for ob/ob mice. In this study, the hypothesis that the short forms of leptin receptors might offer protection against endotoxin-induced lethality at least in part by providing protection against ARF was examined. Serum leptin levels were significantly increased with LPS treatment in wild-type and db/db mice but not ob/ob mice. GFR decreased significantly 16 h after the homozygous ob/ob mice received intraperitoneal injections of 0.3 mg/kg LPS (0.37 +/- 0.04 ml/min per g kidney versus 0.83 +/- 0.06 ml/min per g kidney, n = 6, P < 0.01); the mean arterial pressure (MAP) remained unchanged. For ob/ob littermates (+/?ob), there was no significant change in either MAP or GFR when the mice were challenged with the same time interval (16 h) and dose of LPS. In contrast to ob/ob mice, there was no significant change in GFR or MAP when homozygous db/db mice or their littermates received injections of an even higher dose of LPS (0.4 mg/kg). Mouse recombinant leptin had no effect on GFR when ob/ob mice received 0.3 mg/kg LPS injections. However, renal function (serum creatinine levels, 0.4 +/- 0.1 mg/dl versus 0.9 +/- 0.1 mg/dl, P < 0.01) and MAP (68 +/- 4 mmHg versus 51 +/- 2 mmHg, n = 6, P < 0.01) were significantly improved with leptin replacement when the ob/ob mice developed hypotensive ARF with a higher dose of LPS (0.5 mg/kg). In summary, the previously reported increased susceptibility to LPS of ob/ob mice, compared with db/db mice, may be attributable at least in part to increased susceptibility to ARF.
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PMID:Role of leptin deficiency in early acute renal failure during endotoxemia in ob/ob mice. 1497 66

Patients with diabetes mellitus are at increased risk for repeat interventions and mortality after coronary angioplasty and stenting. The efficacy of sirolimus-eluting stents (SESs) to improve the outcomes of these patients is a focus of interest. In the first 1,407 patients treated with SESs at our institution, 492 were diabetic (insulin dependent diabetes mellitus [IDDM], n = 160 and non-insulin-dependent DM [NIDDM], n = 332). The in-hospital and 1- and 6-month clinical outcomes were compared with those of 915 patients without DM (non-DM). The baseline characteristics were similar, except for more women, obesity, previous myocardial infarction, coronary artery bypass grafting, and renal insufficiency in the DM group (p <0.001). Compared with non-DM patients, DM patients had higher in-hospital (p <0.05) and 1-month mortality (p = 0.02). IDDM patients had more in-hospital renal failure (p = 0.04) and Q-wave myocardial infarctions (1.6% vs 0%, p = 0.04) compared with NIDDM patients, and higher mortality (3.1% vs 0.8%, p = 0.04) and subacute stent thromboses (2.3% vs 0.5%, p = 0.07) than non-DM patients at 30 days. At 6 months, DM patients had a higher incidence of Q-wave myocardial infarction, target lesion revascularization-major adverse cardiac events, and composite of death and Q-wave myocardial infarction than non-DM patients (6.0% vs 2.7%, p = 0.01). Late outcomes between the IDDM and NIDDM groups were similar. Multivariate analysis showed diabetes and acute renal failure as independent predictors of target lesion revascularization-major adverse cardiac events. In conclusion, our data showed that, despite a reduction in repeat revascularization, coronary intervention with SESs in diabetic patients is limited by higher mortality at 1 month and a higher incidence of Q-wave myocardial infarction and target lesion revascularization-major adverse cardiac events at 6 months compared with non-DM patients. Careful surveillance is required in IDDM patients undergoing SES implantation.
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PMID:Impact of treatment of coronary artery disease with sirolimus-eluting stents on outcomes of diabetic and nondiabetic patients. 1621 45

Nutrition support in the critically ill patient is challenging but is even more difficult in a morbidly obese patient. This case report chronicles the care of a 6-foot-tall, 256-kg male (body mass index 76.5 kg/m(2)) who spent over a month in the intensive care unit for respiratory failure, sepsis, and acute renal failure. Parenteral nutrition was provided throughout his critical care course. One of the major difficulties encountered was determining his nutritional needs. A hypocaloric nutritional regimen was used, along with moderate protein provisions. Numerous electrolyte imbalances occurred, including hypercalcemia that did not resolve by eliminating calcium from the parenteral nutrition solution. Enteral nutrition was desired but was not used initially because of a need for vasopressors, a diagnosis of pancreatitis, difficulty in documenting feeding tube placement because of diagnostic limitations secondary to the patient's large size, and concern about managing stools. Eventually, oral intake and supplemental enteral feeding were initiated. Nutrition support team members worked closely with the interdisciplinary care team to develop strategies to manage the nutritional problems related to his obesity. A discussion of the various nutritional issues encountered in the care of this patient is provided. Reasonable nutritional status was achieved, but this case reflects some of the challenges encountered in caring for the nutritional needs of select patient populations in clinical practice and the need for increased research and guidelines in this area.
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PMID:Nutrition support in the morbidly obese, critically ill patient. 1621 17

Atheromatous embolization is a multisystem disease complicating advanced atherosclerosis. It occurs most often as a complication of angiography, an endovascular procedure or cardiovascular surgery. Atheromatous embolization can present in a subtle manner where it is often under-recognized, or with catastrophic results including myocardial infarction, strake or acute renal failure. It may mimic other disease processes and often goes underdiagnosed and undertreated. A high clinical suspicion is the key to diagnosis. Atheromatous embolization results in significant morbidity and mortality; therefore, early recognition followed by aggressive management may help to prevent end-organ damage and improve overall clinical outcomes. Management strategies should include risk factor modification, prevention of further insults by discontinuing or avoiding predisposing factors, supportive treatment and interventional or surgical approaches to remove the atheroembolic source. Atheromatous embolization is expected to increase as our population ages and the epidemics of diabetes mellitus and obesity increase.
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PMID:Atheromatous embolization. 1644 59

The medical records of 54 dogs presented to the Hebrew University Veterinary Teaching Hospital and diagnosed with heat stroke were retrospectively reviewed. Data abstracted included history, clinical and clinicopathological signs at admission, treatment, disease progression, and outcome. Exertional and environmental heat stroke were present in 63% (34 of 54) and 37% (20 of 54) of the dogs, respectively, and 78% (42 of 54) were examined between June and August. The mean temperature and heat discomfort index in the particular days of heat stroke were significantly increased (P < .001, P < .001, respectively) compared with their corresponding average daily values. In 27 dogs the body temperature was > or = 41 degrees C (105.8 degrees F). Belgian Malinois (15%, odds ratio [OR] = 24, 95% confidence interval [CI95%] 8.2-64.5), Golden and Labrador Retrievers (21%, OR = 2.08, CI95% 0.95-4.2), and brachycephalic breeds (25%, OR = 1.7, CI95%], 0.81-3.21) were overrepresented, whereas small breeds (<8 kg) were underrepresented (2%, OR = 0.08, CI95%, 0.002-0.48). Thrombocytopenia (45 of 54 dogs) and prolongation of the prothrombin (PT) and activated thromboplastin (aPTT) times (27 of 47 dogs) were recorded during hospitalization. Disseminated intravascular coagulation (P = .013) and acute renal failure (P = .008), diagnosed in 28 of 54 and 18 of 54 of the cases, respectively, were risk factors for death. The overall mortality rate was 50%. Hypoglycemia (<47 mg/dL, P = .003), prolonged PT (>18 seconds, P = .05), and aPTT (>30 sec, P < .001) at admission were associated with death. Serum creatinine >1.5 mg/dL (P = .003) after 24 hours, delayed admission (>90 minutes, P = .032), seizures (P = .02), and obesity (P = .04) were also risk factors for death. Heat stroke in dogs results in serious complications and high fatality rate despite appropriate treatment.
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PMID:Heat stroke in dogs: A retrospective study of 54 cases (1999-2004) and analysis of risk factors for death. 1649 21

In most Western countries, diabetic nephropathy (DN) has become the single most common condition found in patients with end-stage renal disease (ESRD). This is to some extent due to better survival of diabetic patients with renal failure, but mostly due to the dramatic increase in the prevalence of type 2 diabetes. The majority of type 2 diabetic patients with renal failure suffer from nodular glomerulosclerosis (Kimmelstiel-Wilson); but ischemic nephropathy, irreversible acute renal failure (mostly acute on chronic) and diabetes co-existing with primary renal diseases are common as well. Classical DN evolves in a sequence of stages. After a period of glomerular hyperfiltration, increased urinary albumin excretion [microalbuminuria (MA)] i.e. 30-300 mg/day or 20 - 200 microg/minute indicates the onset of overt DN. Risk factors for development of DN are positive family history, hyperglycemia in the mother during pregnancy, high blood pressure, obesity and insulin resistance. Poor glycemic control (HbAlc) and elevated systolic blood pressure (> 135 mm Hg) interact in enhancing the risk of DN. Proteinuria and smoking are major promoters of progression. The risk of onset of microalbuminuria can be reduced by lowering of blood pressure and specifically by blockade of the renin angiotensin system (RAS). In patients with established DN, the target systolic blood pressure should be <130 mm Hg and RAS blockade is obligatory. Treating all cardiovascular risk factors is a high priority. Antihypertensive management is rendered difficult by extreme volume sensitivity, pronounced activation of the RAS and autonomic neuropathy. Cardiac events are excessively frequent, glycemic control becomes difficult and autonomic diabetic neuropathy with gastroparesis and diabetic foot are additional problems. Hemodialysis or continuous ambulatory peritoneal dialysis should be started relatively early. In the absence of contraindications, transplantation (renal transplantation, combined kidney/pancreas transplantation or pancreas after kidney transplantation) is the treatment of choice.
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PMID:Diabetic nephropathy. 1718 81

Several autoimmune diseases are thought to be mediated in part by interleukin (IL)-18. Many are those with associated increased interferon-gamma (IFNgamma) levels such as systemic lupus erythematosus, macrophage activation syndrome, rheumatoid arthritis, Crohn's disease, psoriasis, and graft-versus-host disease. In addition, ischemia, including acute renal failure in human beings, appears to involve IL-18. Animal studies also support the concept that IL-18 is a key player in models of lupus erythematosus, atherosclerosis, graft-versus-host disease, and hepatitis. Unexpectedly, IL-18 plays a role in appetite control and the development of obesity. IL-18 is a member of the IL-1 family; IL-1beta and IL-18 are related closely, and both require the intracellular cysteine protease caspase-1 for biological activity. The IL-18 binding protein, a naturally occurring and specific inhibitor of IL-18, neutralizes IL-18 activities and has been shown to be safe in patients. Other options for reducing IL-18 activities are inhibitors of caspase-1, human monoclonal antibodies to IL-18, soluble IL-18 receptors, and anti-IL-18 receptor monoclonal antibodies.
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PMID:Interleukin-18 and the pathogenesis of inflammatory diseases. 1733 92

Companion animals represent an under-utilised resource. The present paper is designed to encourage collaborative studies. Dogs and cats are out-bred animals that are willing to consume a consistent diet for long periods, so are ideal candidates for prospective studies of naturally-occurring disease. In some studies the effect of diet on survival has been substantial. Food restriction, for example, slows the development of osteoarthritis and increases the lifespan of Labrador retrievers by 2 years, protein and P restriction more than doubles the median survival time of dogs and cats with chronic kidney disease and adding n-3 fats and arginine to the diet of dogs with stage 3 lymphoma improves median survival time by one-quarter. Obesity is also very common in both dogs and cats and is also associated with disease as in human subjects. When interpreting these results, however, it is essential to take into account pathophysiological differences among species. Dogs and cats do not display all the characteristics of metabolic disease in human subjects, they metabolise fat well and atherosclerosis and cardiac infarction are uncommon. Such differences should not, however, preclude further study because differences among species often clarify knowledge. Monitoring of disease in companion animals may also provide a surveillance system for the safety of the food supply, as illustrated by recent outbreaks of acute renal failure and liver failure in cats and dogs in the USA caused respectively by melamine and mycotoxin contamination of pet foods.
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PMID:Conference on "Multidisciplinary approaches to nutritional problems". Symposium on "Nutrition and health". Nutritional therapies to improve health: lessons from companion animals. 1904 Jul 82

We report an unusual complication of orlistat, a gastrointestinal and pancreatic lipase inhibitor used in the treatment of obesity. A 66-year-old man with history of Type 2 diabetes and obesity presented to our hospital with recurrent episodes of hypoglycemia over 2 weeks. His medications included twice daily biphasic insulin and 3 months previously he was prescribed orlistat as treatment for his obesity. On admission he was in acute renal failure with a creatinine concentration of 405 micromol/l. His renal function 4 months previously was normal. Urinalysis revealed neither blood nor protein, but microscopy of his urine revealed moderate amounts of crystals. A renal biopsy revealed normal glomeruli, but there were features of acute tubular necrosis associated with oxalate crystal deposition. Over the next few days his renal function declined and needed hemodialysis. 3 weeks after his admission he continued to require hemodialysis and he unexpectedly had a cardiac arrest and died. Our patient had acute tubular necrosis secondary to orlistat-induced acute oxalate nephropathy. The identification of high risk patients treated with orlistat and regular monitoring of their renal function might reduce the risk of renal failure due to acute oxalate nephropathy.
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PMID:An unusual complication of treatment with orlistat. 1935 76

There is increasing evidence that obesity, independently from other comorbidities such as diabetes and hypertension, can cause renal dysfunction. While this indolent dysfunction may be asymptomatic, it can render patients more susceptible to renal insufficiency when the kidneys are further injured by other pathological processes. Here, we present a morbidly obese patient whose type-A aortic dissection was complicated by acute renal failure that subsequently progressed into end-stage renal disease. However, his renal function improved dramatically following substantial weight reduction after gastric bypass surgery obviating the need for dialysis and transplantation. The potential mechanisms by which a patient's obesity may lead to renal dysfunction are discussed. This case and other similar reports suggest that obese patients with renal failure can safely undergo bariatric surgery and that bariatric surgery may have a role in treating chronic kidney disease in select morbidly obese patients.
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PMID:Recovery of renal function in a dialysis-dependent patient following gastric bypass surgery. 1969 39


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