Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
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Patients with severe gastrointestinal motility disorders are often found to have intravenous access clots or deep venous thrombosis. It has previously been reported that many patients who have intravenous access thrombosis have concomitant thrombotic risk factors. In this study, the goal was to determine the underlying prevalence of hypercoagulable risk in a series of patients with documented gastroparesis. Investigators studied 62 consecutive patients (52 female; mean age, 42 y) who had symptoms of gastroparesis. All patients were evaluated for placement of a gastric neural stimulation device, or they had had one placed previously. Patients underwent a hematologic interview and standardized coagulation measures of thrombotic risk. Laboratory studies measured acquired elevations of Factor VII, Factor VIII, fibrinogen, lupus anticoagulant panel, antiphospholipid antibody panel, homocysteine (in the setting of kidney disease), and activated protein resistance. Investigators also measured congenital factors: Factor VIII (with C-reactive protein levels), antithrombin III, protein C, protein S (total and free), Factor II mutation, Factor V Leiden, methylenetetrahydrofolate reductase, and homocysteine. Fifty-five patients (89%) were found to have detectable hypercoagulable risk factors. Twenty-five of the 62 patients (40%) had a documented history of abnormal clotting, including deep venous thrombosis, intravenous access thrombosis, and pulmonary embolism. All patients with a previous history of thrombosis had detectable clotting abnormalities. Of 56 patients, 40 (71%) had hypercoagulability and did not have diabetes (P=.036), and 20 (36%) had hypercoagulability and no known history of infection. However, this value was not statistically significant when infection and hypercoagulability were compared (P=.408). A high prevalence of acquired and congenital hypercoagulable defects has been observed in patients with gastroparesis, which may predispose them to arterial and venous clots. This unique finding warrants consideration of coagulation evaluation in patients with severe gastroparesis, especially when these patients are placed in high-risk thrombophilic situations, such as hospitalization, prolonged intravenous access, and surgery.
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PMID:Assessing thrombosis risk in patients with idiopathic, diabetic, and postsurgical gastroparesis. 1714 10

We present a case of deep venous thrombosis (DVT) during pegylated interferon (peg-IFN)-alpha2b plus ribavirin treatment of chronic hepatitis C (CHC). A 67-year-old man, who had been under treatment for hypertension and diabetes mellitus, was admitted to our hospital for peg-IFN-alpha2b plus ribavirin treatment for CHC. His serum hepatitis C virus (HCV) RNA level became undetectable 1 week after the initiation of peg-IFN-alpha2b plus ribavirin treatment. He suffered from severe pain, flare, and edema in both of his lower legs 6 weeks after the initiation of peg-IFN-alpha2b plus ribavirin treatment. He was diagnosed as having DVT because of the presence of a thrombus in the right soleus vein by ultrasonography. Peg-IFN-alpha2b plus ribavirin treatment was discontinued because a causal relationship between DVT and peg-IFN-alpha2b plus ribavirin treatment was suspected. DVT was not observed and the symptoms in both of his legs were improved after the administration of warfarin potassium. Subsequently, DVT has not recurred, and he has remained HCV-RNA negative.
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PMID:A case of deep venous thrombosis associated with pegylated interferon alpha2b plus ribavirin treatment of chronic hepatitis C. 1728 4

Seasonal variation in the occurrence of cardiovascular and cerebrovascular events, including pulmonary embolism (PE), has been reported; however, recent large-scale, population-based studies conducted in the United States did not confirm such seasonality. The aim of this large-scale population study was to determine whether a temporal pattern in the occurrence of PE exists. The analysis considered all consecutive cases of PE in the database of all hospital admissions of the Emilia Romagna region in Italy at the Center for Health Statistics between January 1998 and December 2005. PE cases were first grouped according to season of occurrence, and the data were analyzed by the chi(2) test for goodness of fit. Then, inferential chronobiologic (cosinor and partial Fourier) analysis was applied to monthly data, and the best-fitting curve for the annual variation was derived. The total sample consisted of 19,245 patients (8,143 male, mean age 71.6+/-14.1 yrs; 11,102 female, mean age 76.1+/-13.7 yrs). Of these, 2,484 were <65 yrs, 5,443 were between 65 and 74, and 11,318 were > or = 75 yrs. There were 4,486 (23.3%) fatal-case outcomes. PE occurred least frequently in spring (n=4,442 or 23.1%) and most frequent in winter (n=5,236 or 27.2%, goodness of fit chi(2)=75.75, p<0.001). Similar results were obtained for subgroups formed by gender, age, fatal/non-fatal outcome, presence/absence of major underlying co-morbid conditions, and specific risk factors. Inferential chronobiological analysis identified a significant annual pattern in PE, with the peak between November and December for the total sample of cases (p<0.001), males (p<0.001), females (p=0.002), fatal and non-fatal cases (p<0.001 for both), and subgroups formed by age (<65 yrs, p=0.012; 65-74 yrs, p<0.001; > or = 75 yrs, p=0.012). This pattern was independent of the presence/absence of hypertension (p=0.003 and p<0.001, respectively), pulmonary disease (p<0.001 and p<0.001, respectively), stroke (p<0.001 and p=0.004, respectively), neoplasms (p=0.005 and p=0.001, respectively), heart failure (p=0.022 and p<0.001, respectively), and deep vein thrombosis (p=0.002 and p<0.001, respectively). However, only a non-statistically significant trend was found for subgroups formed by cases of diabetes mellitus, infections, renal failure, and trauma.
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PMID:Seasonal variation in occurrence of pulmonary embolism: analysis of the database of the Emilia-Romagna region, Italy. 1736 85

The use of fibrates in the management of lipoprotein disorders has a history dating back to the mid-1960s. This group of drugs has now been tested in several large long-term trials with cardiovascular end points. Overall, there is good evidence for the reduction of cardiovascular disease in primary prevention studies and in those of subjects with manifest disease. More recent trials have suffered from high interference due to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) introduction, particularly in their placebo control groups. However, there is very good evidence for overall safety from a combined study of >20,000 patients in these controlled clinical trials lasting approximately 5 years. Abdominal pain has been observed more frequently in the statin vs placebo group. Myopathy, liver enzyme elevations, and cholecystitis have been potential adverse reactions of interest. However, these have occurred at a very low rate and are rarely found to be statistically more frequent in the active-treatment group compared with the subjects taking placebo. The recent Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study found a slightly higher incidence of pancreatitis, deep venous thrombosis, and pulmonary embolism. Small creatinine and homocysteine elevations are observed in many patients taking fibrates, and the effect of this on long-term outcomes is under study. The FIELD study also described a significant reduction in the rates of progression of proteinuria and vascular retinopathy with fibrate therapy. To date, there has been no study exclusive to patients with elevated triglycerides, raising the question of the potential benefit of these drugs in patients with the lipid abnormalities most effectively treated with fibrates.
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PMID:Expert commentary: the safety of fibrates in lipid-lowering therapy. 1736 73

Incidence of type 1 diabetes mellitus is continuing to rise in children. The presentation of diabetic ketoacidosis (DKA) in children with newly diagnosed diabetes is significantly higher in those less than 5 years old. Critically ill patients admitted to Paediatric Intensive Care Units (PICU), would have a central venous line (CVL) inserted as part of their ongoing management. There are associations linking with the development of deep venous thrombosis (DVT) in DKA/CVL patients. An 18-month-old boy presented with a short history of polydypsia, polyuria and weight loss. The initial blood sugar was 27.0 mmol/L and a venous blood gas showed severe metabolic acidosis. He was diagnosed and treated for DKA. He was transferred to the regional PICU for further management. There, a central venous line (CVL) was inserted in his left femoral vein. This was removed on Day 4. Subsequently, he developed a swelling on his left leg, with significant discrepancy in leg circumference. Doppler ultrasound confirmed a deep venous thrombosis. Conclusion Diabetes has a propensity for hypercoagulability and DKA promotes a prothrombotic state. Retrospective studies have shown younger patients with DKA and a femoral CVL are at higher risk of developing DVT. A central femoral line should avoided in such patients. DVT prophylaxis and Doppler follow up should also be considered.
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PMID:DKA, CVL and DVT. Increased risk of deep venous thrombosis in children with diabetic ketoacidosis and femoral central venous lines. 1738 Sep 29

Background. Total hip arthroplasty (THA) is today one of the most frequently performed major surgical operations in orthopedics. Although it is the standard method of treatment for advanced degenerative changes in the joint, the operation is accompanied by a high risk of thromboembolic complications. Material and methods. The present study is a retrospective analysis of two groups of THA patients. Group I consisted of 80 patients (average age 62) operated 1980-1983, for whom no prophylaxis was applied. In Group II, low molecular weight heparin (LMWH) was applied pre- and postoperatively. This group consisted of 94 patients (average age 63.5) operated in the year 1998. Thromboembolic complications were diagnosed on the basis of reported symptoms, physical examinations and additional tests (chest x-ray, EKG, gasometry). Results. In Group I there were 11 complications (13.75%), including 10 cases (91%) of deep venous thromboembolic disease of the lower extremities (DVT) and 1 case (9%) of pulmonary embolism (PE), while in Group II there were only 2 complications (2.1%), 1 DVT and 1 PE. The difference between groups was statistically significant. The risk factors for venous thromboembolic disease were analyzed. In both study groups, the predominant risk factors were prolonged duration of surgery and diabetes accompanied by venous insufficiency. Conclusions. The results of our analysis showed that the use of DVT prophylaxis with low-molecular heparin in the preoperative and postoperative period reduced the occurrence of thromboembolic complications.
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PMID:Thromboembolic complications after total hip arthroplasty and prevention of thrombosis: own experience. 1767 66

Polymorphic variants of genes encoding blood coagulation proteins have been extensively studied as risk factors for venous or arterial thrombosis A variation in the 3' untranslated region (UTR) involved in the post-transcriptional regulation of factor VII (FVII) gene has been recently identified, a two adenine insertion/deletion at nucleotide 11293. In this study, we investigated its effect on the risk of thrombosis in the frame of two case-control studies, including patients suffering from peripheral arterial disease (PAD) or venous thromboembolic (VTE) disease. The 3'UTR FVII gene polymorphism was investigated i) in 181 patients who had symptomatic atherosclerotic disease of the lower limbs, ii) in 178 patients who had had at least one episode of objectively diagnosed deep venous thrombosis and iii) in controls matched for age and sex. Plasma FVII antigen (FVII: Ag) levels were lower in the presence of the 3'UTR 2A insertion (68.4 +/- 12.3%, 81.3 +/- 14.5% and 89.5 +/- 13.7% in 2A/2A, 2A/0 and 0/0 subjects respectively, p < 0.0001). No significant relationship was found with VTE disease. In the contrary we observed a lower risk of PAD for the 2A/2A compared to the 0/0 genotype after adjustment for traditional risk factors (hypercholesterolemia, smoking status, diabetes and hypertension), with an OR of 0.24 [95% CI 0.06-0.99]. In conclusion, the 2 adenine insertion in the 3'UTR of FVII gene, related to lower plasma FVII levels, is a genetic variation that may contribute to reduce the risk of PAD.
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PMID:A two adenine insertion polymorphism in the 3' untranslated region of factor VII gene is associated with peripheral arterial disease but not with venous thrombosis. Results of case-control studies. 1793 95

A case of intravenous precipitation of erythromycin is reported along with the patient history, pathologic findings, and a description of the analytical methods and results. The patient was a 75-year-old woman with a history of myocardial infarction, deep venous thrombosis, and diabetes mellitus who underwent aortic valve replacement. She developed endocarditis and recurrent episodes of urosepsis, with multiple organ failure including severe gastric retention, for which she was treated with erythromycin intravenously. She died because of refractory septic shock. Autopsy revealed aortic valve endocarditis, thrombi in the right femoral vein, arterial (nonfungal) thromboemboli in the celiac trunk, and coarse material in the right femoral vein where the tip of the central venous catheter had been located. Microscopical examination of the coarse material showed that it was birefringent crystalline material. Part of the postmortem material was analyzed in the laboratory of the department of clinical pharmacy and revealed the presence of erythromycin. Erythromycin was detected using Fourier transform infrared spectroscopy. An additional specific color test and thin-layer chromatography confirmed this finding. On the basis of the postmortem findings, patient history, and analytical-toxicologic results, we conclude that erythromycin precipitation can occur in vivo after intravenous administration in patients with impaired blood flow.
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PMID:Erythromycin precipitation in vena femoralis: investigation of crystals found in postmortem material of an intensive care unit patient. 1822 76

As arterial and venous thrombosis share common risk factors, a link between arterial and venous thrombosis has been suggested recently. Therefore, we aimed to investigate the impact of established cardiovascular risk factors on the risk of recurrent venous thromboembolism (VTE). With a cross-sectional study design, we analyzed the data of 1006 patients (582 F, 424 M) consecutively treated in our outpatient department for VTE (i.e. lower extremity deep vein thrombosis and/or pulmonary embolism) and registered in the MAISTHRO (MAin-ISar-THROmbosis) database. Of the total cohort, 324 (32.2%) patients suffered a recurrent VTE. Compared with the patients with a single thromboembolic event, patients with recurrent VTE were more frequently male (39.4 vs. 27.0%, P < 0.001). In univariate analysis, the relative risk of recurrent VTE was 1.9 [95% confidence interval (CI) 1.53-2.39] for male sex and 1.6 (1.25-1.95) for age over 50 years (PAOD). After adjustments for age, sex, thrombophilia and other common VTE risk factors, male sex [hazard ratio (HR) = 1.7 (1.38-21.9)] and arterial hypertension [HR = 1.4 (1.05-1.78)] were independent risk factors of recurrent VTE. The higher risk in men than in women persisted even after the exclusion of women with transient hormonal risk factors [HR = 1.57 (1.19-2.07)]. In contrast, no association between the presence of diabetes, obesity, hypercholesterolemia or smoking and the risk of VTE recurrence was observed. Male sex and arterial hypertension are independently associated with an increased risk of recurrent VTE after termination of anticoagulant therapy for the first VTE event.
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PMID:Impact of sex and traditional cardiovascular risk factors on the risk of recurrent venous thromboembolism: results from the German MAISTHRO Registry. 1827 38

Fertility is improved within months and conception is achieved within one to six years after kidney transplantation. Pregnancy is safe and has little effect on long-term graft survival, but has increased maternal and fetal risks. Pregnancy is contraindicated in the first two years post-kidney transplantation due to increased risk of acute rejections and higher doses of immunosuppressive drugs. Poor renal function, uncontrolled diabetes mellitus and hypertension are other contraindications. Family planning and counseling, and consideration of a suitable contraceptive method are essential before transplantation. Tubal ligation and vasectomy are permanent contraceptives with the least failure results. Combined pills are highly effective and are among the lowest failure rate contraceptives, but they interact with cyclosporine, and are contraindicated in patients with thromboembolism and deep vein thrombosis. Progesterone-only minipill has the advantage of avoiding the risks associated with estrogen, but has a higher failure rate than the combined pills. The barrier methods (condom and diaphragm) are effective and safe contraceptives and can prevent sexually transmitted diseases, but require motivated couples. Intra uterine devices are convenient contraceptives, but have higher failure rate and are associated with increased incidence of pelvic infection. Pregnancy in renal transplant recipients should be managed by a multidisciplinary approach in a tertiary centre.
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PMID:Pregnancy and contraceptive issues in renal transplant recipients. 1831 Aug 62


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