Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten patients with heterozygous familial hypercholesterolaemia (Fredrickson type II) were treated by the operation of partial ileal bypass. Postoperatively, serum cholesterol levels fell by an average of 34% (P less than 0.005), and the decrease was satisfactorily sustained over a period of 12-30 months. Angina and xanthomas also improved in some patients. Postoperatively all patients experienced considerable diarrhoea, which lessened with time. Other complications of surgery included abdominal distension and cramps, colonic dilatation, sepsis and intestinal obstruction. It is concluded that partial ileal bypass significantly lowers serum cholesterol levels, but that in view of the complications the operation should be offered only to carefully selected patients who are intolerant of or unresponsive to conservative measures.
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PMID:Treatment of familial hypercholesterolaemia by partial ileal bypass. 44 62

Between January 1989 and June 1993, a total of 470 liver transplantations were performed at King's College Hospital. Thirty-seven transplantations were performed in 34 patients with liver-based metabolic disease. There were 16 females and 18 males with a median age of 19 years (range 1 month to 62 years). There were 14 patients under 16 years of age. The indications for liver transplantation were Wilson's disease (n = 16), alpha 1-antitrypsin deficiency (n = 10), tyrosinaemia (n = 2), primary hyperoxaluria type 1 (PH1; n = 2), congenital haemochromatosis (n = 1), familial amyloidotic polyneuropathy (FAP; n = 1, familial hypercholesterolaemia) (n = 1) and Crigler-Najjar syndrome type I (CNS1; n = 1). These included two patients who received combined heart-liver grafts for familial hypercholesterolaemia and FAP, respectively. Two patients received combined liver-kidney transplants for PH1. There were four deaths: from sepsis (n = 2), acute hepatic vein obstruction in a left lateral segment graft (n = 1) and portal vein thrombosis with liver necrosis (n = 1). Three patients were retransplanted, one for chronic rejection and two for hepatic artery thrombosis, giving an overall graft survival of 81% and patient survival of 88% (30/34), at a mean follow-up of 34 months (range 10-64 months).
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PMID:Orthotopic liver transplantation for hepatic-based metabolic disorders. 788 50

A 37-yr-old woman with RF-positive RA developed cholestatic hepatitis after 10 days of D-penicillamine therapy. This was discontinued immediately. The cholestasis persisted for the remaining 14 months of her life. Severe hypercholesterolemia developed with xanthelasmata and eventually pancytopenia, which was caused by a massive infiltration of the bone marrow by lipid-containing foam cells. The patient died of sepsis. Review of the literature shows intrahepatic cholestasis to be a rare and idiosyncratic complication of D-penicillamine therapy. To our knowledge, ours is the first documented case of persistent cholestatic icterus.
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PMID:Fatal cholestatic hepatitis caused by D-penicillamine. 805 7

After the discovery by Furchgott and colleagues in 1980 that the endothelium plays an obligatory role in acetylcholine-induced vasodilation many investigators have elucidated the role of the endothelium in the regulation of vascular tone. While the sympathetic nervous system serves the organism as a whole, the endothelium appears to act as a local regulator adapting blood flow to local metabolic needs. A variety of endothelium-derived relaxing and contracting factors such as nitric oxide, prostacyclin, endothelium-derived hyperpolarizing factor, endothelin and thromboxane A2 play a role in the endothelium-dependent control of vascular tone. Furthermore, nitric oxide inhibits thrombocyte aggregation and adhesion. Many diseases have been reported to be associated with an impaired endothelium-dependent vasodilation which may contribute to an increased susceptibility to vasospasm, decreased inhibition of thrombus formation and an impaired ability to reduce vascular resistance in ischaemic conditions. In hypertension, hypercholesterolaemia and diabetes mellitus this impairment may be interpreted as an early marker of a process that ultimately will lead to atherosclerosis. The impaired endothelium-dependent vasodilation probably contributes to the increased peripheral vascular resistance in hypertension and heart failure. The role of the endothelium does not seem to be restricted to cardiovascular diseases. Several mediators of inflammation stimulate the endothelium to release nitric oxide, suggesting an important role of the endothelium in the haemodynamic sequelae of sepsis.
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PMID:Endothelium and the regulation of vascular tone with emphasis on the role of nitric oxide. Physiology, pathophysiology and clinical implications. 820 3

Hyperlipidemia commonly occurs following renal transplantation. As hyperlipidemia has been postulated to contribute to renal dysfunction in animal models, the effect of early hyperlipidemia was studied in a cohort of 43 cyclosporine-treated renal transplant recipients over a 4-year follow-up period. Hypercholesterolemia occurred in 25 patients, with 18 patients remaining normolipidemic during the initial 3 months following transplantation. Prospective follow-up over a 4-year period was available for 16 of the 18 normolipidemic patients and 25 patients who developed hyperlipidemia, as well as 11 other hyperlipidemic patients who were not included in the initial analysis. Graft function was maintained in 11 (69%) of the patients with early normolipidemia and there has been one patient death (7%). Of the hypercholesterolemic group, two patients were lost to follow-up and 23 of the remaining 34 (68%) had persistent graft function. There have been two patient deaths (6%). No deaths from cardiovascular deaths have occurred in either group, all deaths resulting from infection/sepsis. Mean cholesterol values at 4-year follow-up were 202.0 +/- 11.2 mg/dL for the patients with early normolipidemia 282.9 +/- 14.3 mg/dL for the patients with early hyperlipidemia (p < 0.00001). The most recent cholesterol value was not associated with pretransplant cholesterol value, creatinine, or cyclosporine dose, but was associated with cholesterol value at 3 months both by regression analysis (P < 0.0001) and by Pearson R (r = 0.71, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of early hyperlipidemia on graft and patient survival in cyclosporine-treated renal transplant patients. 832 88

Liposomes have been used therapeutically to deliver drugs to certain anatomical sites. The use of liposomes to deliver antigens, although not a new concept, has received less attention. At least two vaccines of nearly identical liposome base composition to our vaccines have been tested in humans. A malaria vaccine study showed that the liposomal preparation is quite safe: reaction profiles of volunteers receiving the vaccine demonstrated little reactivity and virtually no pyrogenicity (14). The concentration of MPLA in the vaccine was substantially higher (nearly 50,000 times) than the pyrogenic dose of free lipid A. The same vaccine, but different antigen (gp120, an HIV protein), was tested in volunteers and had the same lack of toxicity (27). In both studies, antibodies and cytotoxic cells specific for the respective antigens were produced. We have several subunit vaccines under development for infectious diseases (gram negative sepsis, fungal infections, protozoan infections), metabolic disorders (hypercholesterolemia, diabetic retinopathy, macular degeneration), and neoplastic diseases (multi-drug resistant cancer, primary and metastatic tumors, and angiogenic hyperproliferative disorders). In each case, one or more antigens were identified that might be useful in immunologic control of biologic proliferation (i.e., pathogen or tumor growth, rise in serum cholesterol, growth of blood vessels). We anticipate that at least one of these vaccines will be ready for testing in humans in the next calendar year.
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PMID:Liposomal vaccines. 864 17

Heparin induced extracorporeal lipoprotein fibrinogen precipitation (HELP) is an established procedure for removal of low-density lipoprotein (LDL) cholesterol, lipoprotein (a), and fibrinogen in patients with severe hypercholesterolemia. In vitro studies revealed that HELP also removes endotoxin, tumor necrosis factor alpha (TNF-alpha) and C-reactive protein (CRP). With the intention to treat, we applied this procedure to 4 patients with severe gram-negative sepsis with highly elevated endotoxin blood levels. Nine treatments were performed, 6 using the standard HELP precipitating buffer and 3 without addition of heparin to the precipitating buffer. Heparin was omitted from the precipitating buffer to avoid fibrinogen depletion in patients at risk (low fibrinogen, postoperative). The average processed plasma volume was 3,386 ml in the standard and 2,963 ml in the modified treatment. Mean reductions (%) in plasma solute concentrations were (standard/ modified procedure) as follows: endotoxin, 50/57; TNF-alpha, 25/5; CRP, 49/55; fibrinogen, 49/6; total cholesterol, 38/5; and apolipoprotein B (Apo B), 41/2. Both treatment modalities were equally effective in removing endotoxin and CRP. With the modified precipitation buffer, fibrinogen was not removed. To further simplify the extracorporeal treatment, we have designed a closed-loop circuit with 2 adsorbers in series, one for removal of TNF-alpha (dextran sulfate modified cellulose) and the other for removal of endotoxin (DEAE-cellulose). In vitro evaluation confirmed very efficient endotoxin and TNF-alpha removal from plasma. This system is very simple, operates at physiological pH, and uses adsorbers already in clinical use for other purposes.
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PMID:HELP apheresis in the treatment of sepsis. 945 25

Nitric oxide (NO) is synthesized by at least three distinct isoforms of NO synthase (NOS). Their substrate and cofactor requirements are very similar. All three isoforms have some implications, physiological or pathophysiological, in the cardiovascular system. The endothelial NOS III is physiologically important for vascular homeostasis, keeping the vasculature dilated, protecting the intima from platelet aggregates and leukocyte adhesion, and preventing smooth muscle proliferation. Central and peripheral neuronal NOS I may also contribute to blood pressure regulation. Vascular disease associated with hypercholesterolaemia, diabetes, and hypertension is characterized by endothelial dysfunction and reduced endothelium-mediated vasodilation. Oxidative stress and the inactivation of NO by superoxide anions play an important role in these disease states. Supplementation of the NOS substrate L-arginine can improve endothelial dysfunction in animals and man. Also, the addition of the NOS cofactor (6R)-5,6,7, 8-tetrahydrobiopterin improves endothelium-mediated vasodilation in certain disease states. In cerebrovascular stroke, neuronal NOS I and cytokine-inducible NOS II play a key role in neurodegeneration, whereas endothelial NOS III is important for maintaining cerebral blood flow and preventing neuronal injury. In sepsis, NOS II is induced in the vascular wall by bacterial endotoxin and/or cytokines. NOS II produces large amounts of NO, which is an important mediator of endotoxin-induced arteriolar vasodilatation, hypotension, and shock.
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PMID:Nitric oxide in the pathogenesis of vascular disease. 1068 59

Besides cyclooxygenase and NO-synthase, another distinct endothelial pathway, endothelium-dependent hyperpolarization (EDHF), is involved in the relaxation of the vascular smooth muscle cells. EDHF has been demonstrated unequivocally in various blood vessels from different species, including human, and is likely to play an important role in cardiovascular physiology. This alternative pathway involves the activation of two populations of endothelial potassium channels, the small conductance and intermediate conductance calcium-activated potassium channels (SK(Ca) and IK(Ca), respectively). EDHF-mediated responses are clearly altered in various pathological conditions (ageing, hypertension, atherosclerosis, hypercholesterolemia, heart failure, ischemia-reperfusion, angioplasty, eclampsia, diabetes, sepsis). Therapeutic or adjutant interventions (angiotensin converting enzyme inhibitors, antagonist of the angiotensin receptor, estrogen, omega-3 polyunsaturated fatty acids, polyphenol derivatives, potassium and/or calcium intake) can restore these responses, suggesting that the improvement of the EDHF pathway contributes to the observed beneficial effect of these various substances. However, the improvement or restoration of EDHF responses has not been, yet, the direct purpose of any pharmaceutical effort. Activating endothelial IK(Ca) and/or SK(Ca) or increasing their expression as well as improving myo-endothelial communication, for instance by increasing the expression of connexin(s), could become interesting therapeutic targets.
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PMID:EDHF: new therapeutic targets? 1502 34

We analyzed survival rates of 144 prevalent patients on maintenance hemodialysis from 1998 to 2003 at the Department of Nephrology and Dialysis, Rijeka University Hospital, Rijeka, Croatia, and evaluated risk factors predicting their survival. Included were only end-stage renal disease (ESRD) patients on maintenance hemodialysis treatment dialysed more than 6 months before entering the study and who were clinically stable. The patients were randomised in two groups according to the presence or absence of diabetic nephropathy as the cause of ESRD and followed-up. The patient's death as outcome measure was recorded. The survival rates were estimated by the Kaplan-Meier method. The major causes of death were cardiovascular disease in 40 (60.6%) patients. An acute myocardial infarction in 15 (22.7%) patients was the major single cause of death. We found a significantly lower survival of diabetic patients than non-diabetic patients (P=0.0013). The most important predictors of death among diabetic patients on maintenance hemodialysis were hyperglycaemia (P<0.001), ischemic heart disease (P=0.004), hypercholesterolemia (P=0.013), and low delivered dialysis dose (P=0.013). The survival of diabetic patients undergoing hemodialysis was much worse than survival of non-diabetic patients. The cardiovascular disease remained the major cause of death in both groups. Early detection of pre-existing cardiovascular risk factors and diseases, and treatment of infections leading to sepsis, are of great importance, as they may influence the survival rates. Intensive management of diabetic patients is essential.
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PMID:Comparison of survival between diabetic and non-diabetic patients on maintenance hemodialysis: a single-centre experience. 1682 39


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