Effect of partial hepatectomy on the expression of seven rat sulphotransferase mRNAs.

1. The effect of partial hepatectomy on the expression of sulphotransferase (SULT) mRNA was studied. SULTs fall into two distinct classes based on substrate preference: phenol SULT1 family (SULT1A1, SULT1B1, SULT1C1 and SULT1E2) and hydroxysteroid SULT2 family (SULT20/21, SULT40/41 and SULT60). 2. Hepatic expression of SULT mRNA was analysed in the sham-hepatectomised rat (sham) and in the partially hepatectomised (PH) rat at various times after PH. Northern-blot analysis with [alpha-32P]dATP-labelled oligonucleotide probes specific for individual SULT mRNAs was used to monitor hepatic SULT mRNA expression. In general, SULT mRNAs underwent a decrease in expression after PH and the magnitude of decrease was dependent on the SULT isoform. 3. The decrease in SULT mRNA expression was resolved and even induced (SULT40/41 in the female rat) by 10-30 days after PH. Of the phenol SULT isoforms, both SULT1C1 and SULT1E2 mRNAs were significantly decreased by 18-24 h after PH in the male rat. The other phenol SULTs (SULT1A1 and SULT1B1) tended to decrease in the male rat after PH, but the decreases were not statistically significant. Expression of SULT20/21 mRNA was decreased in the female rat (80% at 24 h) and fully recovered by 10 days. SULT40/41 mRNA tended to decrease after PH; however, the decrease was not statistically significant. SULT 60 mRNA was decreased from 24 to 96 h after PH. 4. Thus, during the period of rapid liver growth that occurs after partial hepatectomy, SULT mRNA expression is decreased. The phenomenon of decreased SULT mRNA expression is similar to other states of rapid liver growth (e.g. cancer tissue and young animals) in which expression of SULT enzymes is characteristically low.     

Enoxaparin. A pharmacoeconomic appraisal of its use in thromboembolic prophylaxis after total hip arthroplasty

Total hip arthroplasty (THA) is a major orthopaedic procedure with a high risk of postoperative thromboembolism. Increasing demand for this type of surgery, together with its high cost, has led to examination of means by which the cost of THA may be minimised. Current clinical opinion favours the use of suitable pharmacological thromboprophylaxis in patients undergoing THA; such prophylaxis may be provided with subcutaneous standard unfractionated heparin (UFH), oral warfarin or subcutaneous low molecular weight heparin (LMWH). Traditionally, LMWHs have been perceived as being more expensive to use than UFH or warfarin because of their relatively high acquisition cost. However, recent pharmacoeconomic data have shown that cost savings are possible when LMWHs are used. This is attributed mainly to reduced frequency of administration, reductions in costs associated with diagnosis and treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and the lack of need for laboratory monitoring of blood coagulation parameters. LMWHs have proportionally less anti-factor IIa (antithrombin) activity relative to anti-factor Xa activity than UFH. Enoxaparin, a LMWH with a mean molecular weight of 4 to 5kD, is reported to have approximately 5 times less activity against thrombin than UFH, for equivalent anti-factor Xa activity. Randomised clinical trials in patients undergoing THA have shown enoxaparin to be at least as effective as UFH in the prevention of DVT and PE, with consistent trends towards a lower incidence of DVT with enoxaparin than with UFH. Similar rates of haemorrhagic complications were reported for enoxaparin and UFH in most trials, although a significantly higher total transfusion requirement was reported for UFH than for enoxaparin in a double-blind study. A significantly higher incidence of bleeding was observed with UFH than with enoxaparin in another study, with similar transfusion requirements for both treatment groups. Cost comparisons in which costs were assigned retrospectively to clinical data have shown cost advantages for LMWHs in general over UFH when costs of administration, hospital bed occupancy and laboratory/radiology procedures are calculated. Cost savings with LMWHs were attributed mainly to reductions in the cost of managing thromboembolic complications in patients receiving these drugs. One meta-analysis showed a saving of $US50 000 (1993 figures) for LMWH over UFH (both subcutaneously twice daily) for every 1000 patients. Subcutaneous enoxaparin at a dosage of 30mg twice daily was shown to be more cost effective than oral warfarin in the prophylaxis of DVT and PE in 2 North American studies in which costs were related to outcomes. One study comprised the application of a decision analysis to a hypothetical group of 10 000 patients; an incremental cost effectiveness of $US12 288 (1993 figures) per death averted was reported for enoxaparin. Enoxaparin was also associated with an overall incremental cost effectiveness of $Can29 140 (1992 figures) per year of life saved (YLS) in the other study, in which costs were applied to clinical data obtained retrospectively from 10 randomised trials. Although no cost-effectiveness analyses have been carried out to compare enoxaparin with UFH, a UK cost comparison reported an overall cost saving of pounds 20 per patient (figures from 1989 to 1990) with enoxaparin 40mg once daily subcutaneously over subcutaneous UFH 5000IU 3 times daily. It has also been suggested that the use of once- or twice-daily enoxaparin in preference to UFH may reduce the overall length of hospital stay; a significant difference emerged in 1 analysis (9.9 or 9.5 vs 11.3 days). Pharmacoeconomic data therefore support the use of enoxaparin as an effective thromboprophylactic treatment with potential cost advantages over warfarin and UFH. Cost-effecti     

Breast implant materials: sense and safety.

Cosmetic breast augmentation, and post-mastectomy breast reconstruction surgery using synthetic implants, have become established in surgical practice over more than 20 years. The operative technique for implant placement have changed somewhat during this time, as many different implant presentations have become available, but the same basic materials have remained in use. We have reviewed the present state of knowledge about breast implant materials with particular reference to the possible connection between polydimethylsiloxane and polyurethane to the so-called "Human Adjuvant Disease", and to carcinogenesis. Problems related to capsular contracture and mammography are also discussed.     

Mechanisms of graft versus host disease produced by small bowel transplantation

Mechanisms of graft versus host disease have been studied in Lew x BN animals transplanted with a Lew small bowel. Grafted mesenteric lymph nodes but not host mesenteric lymph nodes or host spleen, in small bowel transplanted rats undergoing lethal GVHD, provide a source of CTL with specific anti-recipient cytotoxic activity. Host MLN and host spleen display anti-recipient CTL activity only when GVHD is provoked by intraperitoneal lymphocyte injection. These data demonstrate that lethal GVHD after SBTx may occur in the absence of detectable cytotoxic activity in host lymphoid tissues, suggesting that other mechanisms are involved in the pathogenesis of GVHD after SBTx. GVHD after SBTx or lymphocyte transfer is associated with the appearance of TNF in the serum. The intensity and reversibility of this phenomenon correlate with both the clinical severity and the lethality of GVHD. Taken together these data highly suggest that TNF is directly involved in the pathogenesis of GVHD after SBTx.     

Prosthetic arteriovenous fistula for vascular access in hemodialysis.

Vascular access through subcutaneous prosthetic arteriovenous fistulas was studied in eighteen dogs. Dacron velour and woven Dacron grafts (6 mm diameter) were constructed across the lower abdomen between the common femoral artery and the opposite common femoral vein. In heparinized animals 197 percutaneous punctures were made with a "14 guage hemodialysis cannula at weekly intervals. Over a period of one and a half years there was no instance of infection. One of the fourteen Dacron velous and all four woven Dacron fistulas thrombosed. These data suggested the feasibility of achieving repetitive blood access through Dacron velour vascular prostheses. Nineteen Dacron velour fistula bypasses between the brachial artery and median basilic vein were performed in fifteen selected patients for a total dialysis period of ninety-six months. Failed standard subcutaneous fistulas or absence of suitable vessels in the upper extremity were indications for the primary procedure. Of three looped forearm fistulas, two thrombosed at twenty-two and two months. Complications among sixteen straight bypasses in the arm included two graft infections and one cannula tract infection. There were no instances of thrombosis in this group. The advantages of single needle dialysis in these high risk patients have been emphasized. Eleven grafts are presently functioning two to nine months postoperatively. Our preliminary results suggest that a Dacron velour fistula merits consideration as an alternative for vascular access in maintenance hemodialysis.     

Insulin, macronutrient intake, and physical activity: are potential indicators of insulin resistance associated with mortality from breast cancer?

High levels of insulin have been associated with increased risk of breast cancer, and poorer survival after diagnosis. Data and sera were collected from 603 breast cancer patients, including information on diet and physical activity, medical history, family history, demographic, and reproductive risk factors. These data were analyzed to test the hypothesis that excess insulin and related factors are directly related to mortality after a diagnosis of breast cancer. The cohort was recruited from breast cancer patients treated at the British Columbia Cancer Agency between July 1991 and December 1992. Questionnaire and medical record data were collected at enrollment and outcomes were ascertained by linkage to the BC Cancer Registry after 10 years of follow-up. The primary outcome of interest was breast cancer-specific mortality (n = 112). Lifestyle data were analyzed using Cox proportional hazards regression models to relate risk factors to outcomes, controlling for potential confounders, such as age and stage at diagnosis. Data for biological variables were analyzed as a nested case-control study due to limited serum volumes, with at least one survivor from the same cohort as a control for each breast cancer death, matched on stage and length of follow-up. High levels of insulin were associated with poorer survival for postmenopausal women [odds ratio, 1.9; 95% confidence interval (CI), 0.7-6.6, comparing highest to lowest tertile, P trend = 0.10], while high dietary fat intake was associated with poorer survival for premenopausal women (relative risk, 4.8; 95% CI, 1.3-18.1, comparing highest to lowest quartile). Higher dietary protein intake was associated with better survival for all women (relative risk, 0.4; 95% CI, 0.2-0.8, comparing highest to lowest quartile).     

Head injury in the severely injured: long-term follow-up in 157 patients

Ninety-two patients with head injury in the context of multiple injury were followed up 5 years after injury. Severe disability in this group of patients was nearly always due to brain/spinal cord injury, rather than musculoskeletal injury. A substantial number of patients with mild or moderate head injuries had significant persisting disability 5 years after injury.