(+)-CYANIDANOL-3 FOR ALCOHOLIC LIVER DISEASE: RESULTS OF A SIX-MONTH CLINCIAL TRIAL

A prospective randomized double-blind trial of (+)-cyanidanol-3at a dose of 2 g daily (500 mg qds) for six months versus placebohas failed to demonstrate statistically significant clinical,biochemical or histological benefit in patients with biopsy-provenalcoholic liver disease although certain trends were identified.The group receiving the active drug tended to drink more bothbefore and during the trial and had mean serum aspartate aminotransferase(AsT) and gamma-glutamyltranspeptidase (-GT) levels which werehigher on admission to the trial. After the fourth week of treatment,the mean serum levels of these enzymes remained consistentlylower in the group receiving the active drug. In order to reproduce the beneficial effects of the drug observedin the rat, it is suggested that further trials be conductedwith the dosage so far used in man (ca. 20–40 mg/kg daily)increased toward that successfully employed in animal experiments(200 mg/kg daily).     

Evolution of coronary stenoses is related to baseline severity--a prospective quantitative angiographic analysis in patients with moderate coronary disease

A correlation of the angiographic evolution of coronary stenoses(stenosis diameter 20%) with morphological stenosis parametersat baseline could help to identify the risk of progressive stenoses.Therefore, the data of the prospective INTACT study (InternationalNifedipine Trial on Antiatherosclerotic Therapy) were reviewed.In 348 patients with moderate coronary artery disease, standardizedcoronary angiograms were taken 3 years apart and were quantitativelyanalysed. Changes in the minimal diameter of the 1063 preexistingcoronary stenoses compared between both angiograms were setin relation to a number of conventional stenosis parametersat baseline. Regression analysis demonstrated a significantcorrelation of the changes in minimal diameter with baseline% diameter stenosis (r=0.30; P<0.001), minimal diameter (r=—0.28;P<0.001) and reference diameter of stenoses (r=–0.14;P<0.001). The changes were not correlated with stenosis lengthand plaque area. The baseline parameters of 22 preexisting stenosesprogressing to occlusions differed from those remaining patentonly with regard to the % diameter stenosis (43 ± 9%vs 39 ± 11%; P<0.05). Additional progression of coronarydisease became manifest through development of 228 stenosesand 19 occlusions at arterial sites free from definitive stenosesin the baseline angiograms. Thus, progression of atherosclerosis predominantly occurredin mild preexisting coronary stenoses and developed at previouslyangiographically normal sites. Since the conventional angiographicparameters analysed in this study failed to identify individualarterial sites with an increased risk for progression, definitionof new angiographic parameters or application of new techniquesseem mandatory to this end.     

Delays to Care in Pediatric Lupus Patients: Data From the Childhood Arthritis and Rheumatology Research Alliance Legacy Registry

Objective

Prompt treatment for lupus is important to prevent morbidity. A potential barrier to early treatment of pediatric lupus is delayed presentation to a pediatric rheumatologist. To better understand factors contributing to delayed presentation among pediatric lupus patients, we examined differences in demographic and clinical characteristics of lupus patients within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry with regard to time between symptom onset and presentation to a pediatric rheumatologist.

Methods

We analyzed data from 598 CARRA Legacy Registry participants for differences between those who presented early (within <1 month of symptom onset), between 1–3 months (typical presentation), with moderate delays (3–12 months), and with severe delays (≥1 year). Factors associated with early presentation, moderate delay, and severe delay were determined by multinomial logistic regression.

Results

Forty‐four percent of patients presented early, while 23% had moderate delays and 9% had severe delays. Family history of lupus, absence of discoid rash, and location in a state with a higher density of pediatric rheumatologists were associated with earlier presentation. Younger age, low household income (<$25,000 per year), and a family history of lupus were associated with severe delay.

Conclusion

Delays to care ≥1 year exist in a notable minority of pediatric lupus patients from the CARRA Legacy Registry. In this large and diverse sample of patients, access to care and family resources played an important role in predicting time to presentation to a pediatric rheumatologist.

     

BROMOCRIPTINE-INDUCED PREGNANCIES IN WOMEN WITH LARGE PROLACTINOMAS

Fourteen women with large prolactinomas experienced a total of nineteen bromocriptine-induced term pregnancies. None of the women had received prior pituitary tumour therapy. Post-partum sellar X-ray examinations showed signs of tumour enlargement in two women. Only one of them had clinical symptoms of tumour expansion with visual field defects during the pregnancy. The visual impairment improved when bromocriptine treatment was reinstituted and the pregnancy continued to term. The other twelve women had a total of seventeen uneventful pregnancies without symptoms or signs of pituitary tumour expansion. Thus, medical therapy with dopamine receptor agonists is the primary treatment for most infertile women with prolactinomas. The risk of serious pregnancy-induced tumour expansion is very small in properly investigated and carefully supervised patients with large PRL-secreting pituitary adenomas.     

Recombinant activated factor VII in treatment of bleeding complications following hematopoietic stem cell transplantation

BACKGROUND: Bleeding is a common complication following hematopoietic stem cell transplantation (HSCT) and standard hemostatic treatment is often ineffective. We conducted a multicentre, randomized trial of the efficacy and safety of activated recombinant factor VII (rFVIIa, NovoSeven) in the treatment of bleeding following HSCT. METHODS: 100 patients with moderate or severe bleeding (52 gastrointestinal; 26 hemorrhagic cystitis; seven pulmonary; one cerebral; 14 other) were included from days +2 to +180 post-transplant (97 allogeneic; three autologous) to receive seven doses of rFVIIa (40, 80 or 160 microg kg(-1)) or placebo every 6 h. The primary efficacy endpoint was the change in bleeding score between the first administration and 38 h. RESULTS: No significant effect of increasing rFVIIa dose was observed on the primary endpoint. A post hoc analysis comparing each rFVIIa dose with placebo showed that 80 microg kg(-1) rFVIIa improved the bleeding score at the 38 h time point (81% vs. 57%, P = 0.021). This effect was not seen at 160 microg kg(-1). There were no differences in transfusion requirements across dose groups. There was no trend in the type or number of severe adverse events observed. Six thromboembolic events were observed in the active treatment groups: three during, and three following the 96-h observation period. CONCLUSIONS: Despite no overall effect of rFVIIa treatment on primary endpoint, post hoc analysis showed an improvement in the control of bleeding for 80 microg kg(-1) rFVIIa vs. standard hemostatic treatment. The heterogeneity of the population may have contributed to the lack of an increasing effect with increased dose. Further trials should focus upon identifying the patient populations that may benefit from treatment with rFVIIa.     

Improved Short-Term Outcomes of Primary Coronary Stenting Compared to Primary Balloon Angioplasty in Acute Myocardial Infarction at Experienced Centers: The PAMI Study Group Experience

To study the additive benefits of routine stent implantation in patients undergoing primary percutaneous transluminal coronary angioplasty (PTCA) at experienced centers, we compared the outcomes of the 982 patients undergoing PTCA for acute myocardial infarction (AMI) in the Primary Angioplasty in Myocardial Infarction-2 (PAMI-2) trial (only 1% of whom were stented) to the 312 patients in the PAMI Stent Pilot Trial (236 [76%] of whom were stented). The inclusion and exclusion criteria, PTCA methodology, and definitions used were prespecified to be identical between the two trials. Compared to the primary PTCA approach in PAMI-2, the strategy of stenting all eligible lesions in the PAMI Stent Pilot Trial was associated with reduced rates of in-hospital death (0.6% vs 2.7%, P = 0.03), reinfarction (1.3% vs 4.6%, P = 0.008), recurrent ischemia (3.5% vs 11.6%, P < 0.0001), target vessel revascularization (7.3% vs 11.4%, P = 0.04), and a shorter hospital stay (6.4 ± 4.4 vs 7.1 ± 6.2 days, P = 0.01). By multiple logistic regression analysis in 1,294 patients, stent implantation versus PTCA only was the strongest predictor of freedom from the composite in-hospital end point of death, reinfarction, or target vessel revascularization (TVR) (8.3% vs 15.0%, multivariate odds ratio = 0.4, P < 0.0001). These data strongly suggest that despite the excellent results achieved when primary PTCA is performed by experienced operators, the short-term outcomes of mechanical reperfusion can be further improved by a primary stent strategy.