Gene/Protein Disease Symptom Drug Enzyme Compound
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A retrospective review was performed of 448 consecutive patients undergoing primary, unilateral, bicondylar, and cemented total knee arthroplasty under epidural anesthesia by three surgeons to determine factors contributing to deep vein thrombosis rate. All had venography on the fourth or fifth postoperative day and received aspirin and elastic stockings as their only thromboprophylaxis. The overall deep vein thrombosis rate was 41% (2% had proximal clots). The rate of deep vein thrombosis was not related to obesity, history of heart disease, hypertension, prior malignancy, smoking, diagnosis of osteoarthritis, duration of surgery, type of local anesthetic used, or the use of postoperative epidural analgesia. The rate of deep vein thrombosis varied significantly between surgeons: one surgeon had an overall deep vein thrombosis rate of 58% (proximal thrombi, 4%) whereas the other two surgeons had a deep vein thrombosis rate of 35% (proximal clot thrombi, 1%). A number of possible mechanisms to explain the variation in deep vein thrombosis rates between surgeons are provided.
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PMID:Factors affecting deep vein thrombosis rate following total knee arthroplasty under epidural anesthesia. 847 30

The objectives for the provision of a safe anaesthetic include rendering the patient analgesic for the procedure (amnesic if appropriate), with control of adverse haemodynamic perturbations, and muscle relaxation to facilitate surgery as necessary. This must be done with an understanding of the patient's pre-existing pathophysiology and drug therapy. This article focuses on the management of medications in the perioperative period from the practitioner's perspective. Areas of drug therapy examined include drugs affecting the cardiovascular, central nervous, haemostatic and endocrine systems. Review of the limited data available suggests that the safest course of action for the preoperative management of the vast majority of drug therapy is to continue such therapy until the time of surgery, particularly agents in which a withdrawal syndrome has been described, e.g. beta-adrenoceptor blocking agents, alpha 2-adrenoceptor agonists. Exceptions to this generalisation might include discontinuing ACE inhibitors prior to surgery as these agents may be associated with adverse haemodynamic changes during surgery. The management of drug therapy for patients receiving monoamine oxidase inhibitors (MAOIs) continues to be challenging due to the potential for drug interactions, e.g. severe hypertension with use of indirect-acting vasopressors and excitatory/depressive reactions with administration of pethidine (meperidine) or dextromethorphan. However, recent clinical experience has demonstrated the relative safety of continuing MAOIs prior to surgery by use of specific 'MAOI safe' anaesthetic techniques and/or substitution of short-acting MAOIs which do not irreversibly inhibit the enzyme. For drugs affecting the coagulation system, such as heparin and warfarin, prudence dictates discontinuing these agents whenever possible prior to surgery where it can be anticipated that haemorrhage will occur, e.g. vascular surgery, or where the consequences of even minor bleeding could be catastrophic, e.g. eye surgery. Controversy exists as to the management of patients receiving prophylactic low dose heparin for deep vein thrombosis prophylaxis or in whom intraoperative or postoperative anticoagulation is planned, e.g. aortic surgery, and in whom a regional anaesthetic technique is planned as part of the anaesthetic management. The data available suggest that, where prophylactic use of heparin is concerned, and provided the administration of the last dose of heparin and the institution of a regional anaesthetic nerve block does not occur at the same time, use of regional anaesthesia is not contraindicated in such circumstances. Where therapeutic anticoagulation is planned as part of the surgical management, there is a very small risk of the development of epidural or spinal haematoma when major central conduction nerve block is employed for anaesthesia, with resultant spinal cord compression and paralysis. These precautions do not apply to patients receiving aspirin or other nonsteroidal anti-inflammatory agents as there is a large clinical and published experience of the safety of regional anaesthesia in this group of patients. Patients treated with fibrinolytic agents are at increased risk for bleeding should surgery be required. For these patients, pre- and intraoperative use of agents with antifibrinolytic activity, e.g. aprotinin, has been demonstrated in case reports to be beneficial. Finally, recommendations for the management of patients who have received or are receiving glucocorticoids are given. Throughout the review, areas of uncertainty where further research is required are identified.
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PMID:Perioperative management of drug therapy, clinical considerations. 880 66

In the UK, the Committee for Safety of Medicines (CSM) issued a warning in October 1995 about the possible increased risk of nonfatal deep venous thrombosis (DVT) among users of oral contraceptives (OCs) containing the third generation progestogens, desogestrel and gestodene. Subsequent media coverage increased the number of consultations and enquiries about these OCs. CSM had concluded that, overall, the third generation OCs are safe. CSM recommended their continued use. Nevertheless, many women stopped using them and induced abortions increased by 11%. In April 1996, the Committee for Proprietary Medicinal Products issued a more cautious statement about the OCs and called for further evaluation. Chance, confounding, and bias may account for the increased risk observed in the studies in question. Yet, it is possible that these OCs may increase the risk of DVT. The increased risk may be offset by a reduced risk of acute myocardial infarction. Physicians need to conduct careful and thorough counseling and to allow the patient to be involved and to take responsibility in making a decision about OC use. They should document all counseling with a note that the patient understands and accepts the increased risk of DVT. They should not prescribe the third generation OCs to women with any of the absolute contraindications to OC use (ischemic heart disease, hypertension, atherogenic lipid disorders, focal or crescendo migraine, cigarette smoking, transient ischemic attacks, past cerebral/subarachnoid hemorrhage, history of vascular thrombosis, prothrombotic abnormalities [e.g., Factor V Leiden], conditions predisposing to thrombosis [e.g., systemic lupus erythematosus], and obesity. Women who are intolerant of second generation OCs may prefer third generation OCs. Physicians should selectively screen women with a family history of a first-degree relative younger than 45 with thromboembolism for Factor V Leiden. They should also screen for protein C, protein S, and antithrombin III deficiency and for acquired antiphospholipid antibodies.
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PMID:Oral contraceptives and the risk of DVT. 898 64

In spite of efforts to reduce complications associated with inguinal-femoral lymphadenectomy (IFL), morbidity continues to be substantial. We sought to assess the efficacy of sartorius transposition (ST) in reducing groin wound complications following IFL, in patients with vulvar malignancy. The records of 101 patients with vulvar cancer undergoing IFL through separate incisions between March 1975 and December 1994 were examined. Sixty-two patients undergoing ST (group 1) were compared to 38 who did not (group 2). The groups were similar with respect to age, weight, tobacco/alcohol use, prior abdominal/vulvar surgery, prevalence of diabetes, hypertension, or peripheral vascular disease, and previous exposure to irradiation or chemotherapy. Additionally, there was no significant difference with respect to extent of disease, incidence of macro-/microscopic groin metastases, use of groin drains, and use of perioperative antibiotics or deep venous thrombosis prophylaxis. Groin wound complications were less frequent in patients undergoing ST (group 1). The incidence of groin cellulitis was 30% in group 1 compared with an incidence of 58% in group 2 (P = 0.011). Significant groin wound morbidity, defined as either wound breakdown or cellulitis, was seen less frequently in group 1 (41% vs 66%; P = 0.029). Employing a multivariate analysis, only patient weight < 150 lbs and performance of ST were established as independently associated with a reduction in groin morbidity following IFL (P = 0.0281 and P = 0.0075, respectively). In conclusion, despite waning enthusiasm for its performance, ST appeared to significantly reduce the incidence of wound morbidity after IFL. Our data confirmed that separate incisions, and improved perioperative antibiotics, have not eliminated the value inherent in this surgical modification. We suggest a prospective trial to further establish the benefit of sartorius transposition during IFL.
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PMID:The effect of sartorius transposition on wound morbidity following inguinal-femoral lymphadenectomy. 903 69

Duplex ultrasonography was used to measure the diameters of the common femoral, superficial femoral and popliteal vein segments in 123 patients following DVT. A cross sectional analysis was done based on the most recent visit to determine chronic venous diameter changes following DVT. Venous diameters in recanalized segments were smaller at all levels compared to those never occluded (p = 0.06 for CFV and p < 0.05 for SFV and PV). After accounting for a previous history of occlusion, the diameters of the segments with and without reflux were not significantly different. There was also no evidence of venodilation in segments caudal to cephalad reflux or thrombus. Recanalized veins are smaller in diameter than those which were never thrombosed. Cephalad thrombus or reflux is not associated with venodilatation of caudal segments. Reflux following DVT is probably secondary to valvular damage rather than hypertension, since there was no diameter difference between refluxing and non-refluxing segments.
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PMID:The relationship of venous diameter to reflux, cephalad thrombus and cephalad reflux following deep venous thrombosis. 906 94

The presence of lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) are associated with recurring pregnancy loss. Of 387 consecutive patients investigated at a Recurring Miscarriage Clinic over a three year period, 63 (16%) were positive for LA and ACA or both. Fifty-nine patients by definition were classified as having antiphospholipid syndrome and four also had systemic lupus erythematosus (SLE). Fifty-three subsequent pregnancies occurred in 63 patients and of these 37 ended in a live birth giving an overall livebirth rate of 70%. Treatment included low dose aspirin alone in 37 pregnancies and low dose aspirin and low molecular weight heparin (LMWH) in 16 pregnancies. The decision for treatment was made empirically on past obstetric history and level of LA and ACA, and past history of venous thromboembolic disease. Obstetric outcome was worst in the group who were positive for both LA and ACA, with a success rate of 53%, compared to 72 or 81% in the single parameter groups. Complications in the 37 successful pregnancies included eight Caesarean sections, four cases of intra-uterine growth restriction, one case of pregnancy induced proteinuric hypertension, one deep vein thrombosis and one pulmonary embolism. Patients with antiphospholipid syndrome are at high risk of pregnancy loss as well as maternal morbidity, especially thrombo-embolic disease. A randomised prospective controlled trial is necessary to determine the optimum therapy for pregnancy conservation and thrombprophylaxis.
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PMID:Obstetric outcome in antiphospholipid syndrome. 925 8

Proponents for the free TRAM flap have advocated enhanced tissue vascularity, easier inset, and limited abdominal dissection. Equal aesthetic results without increased morbidity and without the risks of microvascular surgery have been suggested by surgeons using the pedicled technique. The free TRAM flap has been criticized for its considerably higher costs. The purpose of this study was to provide a cost comparison and outcome analysis of the free versus the pedicled TRAM flap. All patients who had had a TRAM flap performed in the authors' teaching institutions between March of 1990 and April of 1995 were evaluated. Outpatient and hospital records, and hospital and surgeon billing records, were reviewed for patient demographics, TRAM technique, delayed versus immediate, operating room time, length of stay, hospital and surgeon reimbursement, and surgical complications and their costs. All patients were sent a questionnaire asking about time back to work, abdominal strength, fitness, symmetry, and satisfaction. During the 5-year period, 125 TRAM flaps were performed. Of these flaps, 72 were free flaps and 53 were pedicled. Seventy percent were immediate reconstructions regardless of the technique used. Four percent of the free and 17 percent of the pedicled TRAM flaps were bilateral. There were no significant differences between the two techniques with regard to patient age, weight, or percentage of smokers, diabetes, hypertension, or preoperative chemotherapy or radiotherapy. Average operating room time was 7 hours with both techniques either delayed or immediate. Average length of stay was 7 days with the free (immediate and delayed) and 8 days with the pedicled (immediate and delayed) technique, although the difference was not significant. Average hospital reimbursement was $5300 for both the free and pedicled TRAM patients. Average surgeon reimbursement was significantly different, with $5000 for the free and $3500 for the pedicled TRAM flap. There were no differences in the occurrence of hematoma, partial/total flap loss, wound infection, hernia/bulge, fat necrosis, deep vein thrombosis, and pulmonary embolus with regard to the technique used. The cost of the treatment of the complications was not significantly different between the two techniques. There was a significant difference in the complication rate for the free TRAM patients compared with those treated by a routine reconstructive microsurgeon versus a more occasional microsurgeon. Ninety percent of both the free and pedicled patients responded to the questionnaire. There were no statistical differences between the free flap and pedicled flap survey results. The free flap patients returned to work 9 weeks after surgery; the pedicled flap patients returned at 10 weeks. Abdominal strength and overall fitness ranged from 74 to 79 percent for both groups. Symmetry and overall satisfaction averaged 3.4 of 4 for all. Average follow-up for the survey respondents was 20 months. This study did not demonstrate any significant differences in outcome or complications between the free and pedicled TRAM flaps. A modest cost difference of $1500 occurred for the free TRAM patients. An experienced microsurgeon had significantly fewer complications with the free TRAM patients. The authors recommend that surgeons use the technique with which they are comfortable and obtain predictable results.
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PMID:Free versus the pedicled TRAM flap: a cost comparison and outcome analysis. 938 52

Venous valves are more frequent in distal veins and venulae, providing a protecting action against blood skin reflux. Structurally simple, collagen and endothelium, they allow a cavity to be formed by distension, when occlusion occurs. Venous angioscopy can distinguish bicuspid floating valves, reinforced, reinforcing valves with free edges and seat valves as well as the presence of apertures of small collateral vessels in the sinus, of which they play a role in the filling up. Valves are inefficient in supine and in standing among 20% of the adult population. Sinuses allow vortices to be created, low recirculating zones, where blood flow move slowly in niches, at a low shear rate, independently from the main stream. A deep vortex is located in sinus, usually empty, but likely to receive red cell aggregates and leukocytes in the condition of stasis and hyperviscosity. Such a vortex is hypoxic, cause of endothelial activation. In such areas fibrin-leucocytic nidus are created, histologically recognized, of which sub-endothelium has become thick and thrombogenic. Two stages characterized its progression: stage I: a few alteration in the valves, little thrombin generation, taken over by the coagulation inhibitors: AT III, APC and TFPI. Stage II: damaged valves, local consumption of the inhibitors and extended generation of thrombin over the platelets, through factor IXa. Hereditary inhibitor deficits increase the risk (frequent factor Leyden V). When the coagulation cascade is considered, VIIa-tissue factor complex appears to be the thrombotic pathway, leading first to wall linked thrombin, uneasily reached by AT III and facteur IXa non inhibited by TFPI, therefore explaining the platelet extension. Monocytes, which can bear tissue factor, may be "lodged" inside the niches. Besides this important role in deep venous thrombosis, incompetent venous valves are responsible for the skin venous hypertension, a subsequent ground for ulcers. Their role in chronic venous insufficiency is uncertain. In the near future, venous angioscopy will bring about new findings about the pathophysiology of venous valves.
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PMID:[Venous valves in the legs: hemodynamic and biological problems and relationship to physiopathology]. 948 Mar 31

Calcium channel blockers are becoming increasingly popular in veterinary medicine for the treatment of systemic hypertension, cardiac arrhythmias, and hypertrophic cardiomyopathy. Calcium is vital to many cellular functions and thus stringent regulation of intracellular calcium concentrations is required. Pharmacologic manipulation of the regulatory mechanisms has the potential to alter cellular function in all body systems. In human medicine, calcium channel blockers are being evaluated for, among other things, use in treating glaucoma, deep vein thrombosis, and pulmonary hypertension, in renal transplantation, and for prevention of reperfusion injury. The potentially beneficial effects of these drugs have often been overshadowed by adverse effects including hypotension, inappetence, bradycardia, conduction abnormalities, and decreased cardiac output. With the introduction of sustained-release formulations (diltiazem) and 2nd generation calcium channel blockers (amlodipine) many of these effects have been attenuated or eliminated. This paper will review the functions of calcium and the calcium channels as well as discussing the classes and current and potential uses of the various calcium channel blockers.
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PMID:Calcium channel blockers in veterinary medicine. 959 72

To assess the influence of oral contraceptives (OC) on the risk for venous thromboembolism (VTE) in young women, a 5-year case-control study including all women 15-44 years old suffering a first deep venous thrombosis or a first pulmonary embolism from all Danish hospitals, along with 1200 control subjects during the period 1994-1995, was conducted. Of 586 patient and 1200 control subject questionnaires sent out, 523 patient (89.2%) and 1074 control (89.5%) questionnaires were returned with an agreement to participate. After exclusion of women with nonvalid diagnoses, women who were pregnant, and women with previous VTE or acute myocardial infarction (AMI), 375 patients and 1041 control subjects were available for analysis. Potential tested confounders included: body mass index, length of OC use, family history of VTE, AMI, or stroke, smoking habits, coagulopathies, diabetes, years of schooling, certainty of diagnosis, previous births, and treated hypertension during any pregnancy. A multivariate analysis was performed. Estrogen dose had no influence on the risk for VTE. The risk for VTE among current users of OC was primarily influenced by duration of use, with significantly decreasing odds ratios (OR) over time: < 1 year; 5.1 (3.1-8.5); 1-5 years; 2.5 (1.6-4.1); and > 5 years; 2.1 (1.5-3.1), all compared with those for nonusers of OC. This trend was still significant after adjustment for progestin types. Without adjustment for duration of use, current users of OC with second generation (levonorgestrel or norgestimate) and third generation (desogestrel or gestodene) progestins had OR of 1.8 (1.1-2.9) and 3.2 (2.3-4.4), respectively. After correction for duration of use, however, no significant differences were found between users of OC with different types of progestins. In conclusion, OC increase the risk for VTE significantly. The risk among current users of OC is primarily influenced by duration of use. No difference in risk was found according to estrogen dose, and the difference in risk between different types of progestins was not statistically significant after adjustment for duration of use.
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PMID:Oral contraceptives and venous thromboembolism. A case-control study. 967 36


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