Evaluation of Enoxaparin Given before and after Operation to Prevent Venous Thromboembolism during Digestive Surgery: Play-the-Winner Designed Study

A total of 316 patients were included in a play-the-winner (PTW) designed study comparing the safety of enoxaprain started preoperatively versus postoperatively as prophylaxis against venous thromboembolism for digestive surgery. In a PTW-designed study the treatment of any next patient depends on the outcome of the previous patient. If successful, the next patient receives the same treatment, if not, the comparative regimen is given. Excessive bleeding according to specified criteria, severe adverse reactions, clinically detected deep venous thrombosis (DVT), or pulmonary embolism (PE) were criteria for classification as “loser.” The PTW design allocates most patients to the superior treatment. The main variable in PTW studies is the number of consecutive patients receiving the same treatment. In this study 163 patients were allocated to postoperatively started and 153 to preoperatively started prophylaxis with enoxaparin. The frequency of “winners” was found to be 82.8% and 78.4% in the post- and preoperatively treated groups, respectively. No significant differences were found between the groups with regard to frequency of “winners” or the number of consecutive patients before change of treatment. The percentile of survival distribution did not detect superiority of any group. Prophylaxis against postoperative venous thromboembolism for digestive surgery using enoxaparin can safely be started preoperatively.     

Lipoprotein particle abnormalities and the impaired lipolysis in renal insufficiency.

BACKGROUND: Increased concentrations of very low- (VLDL) and intermediate-density (IDL) lipoproteins in chronic renal failure (CRF) are thought to result from a defect(s) in degradation of plasma triglyceride (TG)-rich lipoproteins. The purpose of this study was to identify lipoprotein abnormalities associated with the reduced lipolytic rate constant, k1, of combined VLDL and IDL substrate from renal patients and asymptomatic controls. METHODS: The VLDL + IDL were isolated from 18 predialytic patients (CRF-I), 8 patients on hemodialysis (CRF-II) and 10 asymptomatic controls. The lipolytic rate constant (k1) of VLDL + IDL was measured by an assay using bovine milk lipoprotein lipase and determination of TG before and after incubation by gas chromatography (GC). Neutral lipids were measured by GC and apolipoproteins by electroimmunoassays; the apolipoprotein-defined TG-rich lipoproteins including Lp-B:C, Lp-B:C:E and Lp-A-II:B:C:D:E were determined by immunoaffinity chromatography. RESULTS: The k1 values of VLDL + IDL were significantly (P < 0.001) lower in CRF-I and CRF-II patients (0.0341 and 0.0352 min-1, respectively) than controls (0.0515 min-1). The levels of apolipoproteins B, C-III and E, and TG-rich Lp-B:C, Lp-B:C:E and Lp-A-II:B:C:D:E particles normalized to 100 mg TG per VLDL + IDL were significantly higher in both groups of CRF patients than in controls. All three TG-rich lipoproteins were characterized by significantly increased percent contents of free (FC) and esterified (CE) cholesterol and a decreased percentage of TG. The k1 values of the combined CRF-I and CRF-II patient groups showed significant negative correlations (P < 0.001) with FC (r=-0.81) and CE (r=-0.63) and a positive correlation with TG (r=0.72). Among lipoprotein particles, only Lp-A-II:B:C:D:E levels showed a significant negative correlation with k1 values (r=-0.47, P < 0.03). CONCLUSIONS: This study shows that the abnormal neutral lipid composition of all three TG-rich lipoprotein particles and increased concentrations of Lp-A-II:B:C:D:E particles represent the main factors affecting the in vitro lipolytic rates of VLDL + IDL substrate in both the CRF patients before dialysis and patients on hemodialysis.     

Homozygosity for the transthyretin-Met30-gene in seven individuals with familial amyloidosis with polyneuropathy detected by restriction enzyme analysis of amplified genomic DNA sequences

Familial amyloidotic polyneuropathy (FAP) with a mutation in position 30 of transthyretin (TTR) (previously called prealbumin) is an autosomal dominant inherited disorder characterized by varying degrees of peripheral neuropathy, nephropathy, gastrointestinal problems, and vitreous amyloid. We have earlier diagnosed homozygosity for the TTR-Met30-gene using Southern analysis in four Swedish individuals. We have found it possible to detect homozygosity for the Met-30 mutation by amplifying discrete regions of the TTR-gene using polymerase chain reaction (PCR), and the amplification products restricted with NsiI analysed by gel electrophoresis. Clinical data on seven homozygous individuals, including three new cases, are presented.