Intravenous and intracoronary fibrinolytic therapy in acute myocardial infarction: Overview of results on mortality, reinfarction and side-effects from 33 randomized controlled trials

During the past 25 years, 24 randomized trials of intravenous(IV) fibrinolytic treatment have been reported, involving atotal of some 6000 patients in the acute phase of myocardialinfarction. Most tested IV streptokinase (SK), but a few testedIV urokinase (UK). In the past 2 or 3 years numerous small randomizedtrials of intracoronary (IC) SK have been started, 9 of which,involving a total of about 1000 such patients have been reported.Because all of these IV and IC trials were small (the largestincluding only 747 patients), their separate results appearcontradictory and unreliable. But, an overview of the data fromthese trials indicates that IV treatment produces a highly significant(22%±5%, (P<0.001) reduction in the odds of death,an even larger reduction in the odds of reinfarction, and anabsolute frequency of serious adverse effects to set againstthis that is much smaller than the absolute mortality reduction.The apparent size of the mortality reduction in the IV trialswas similar whether anticoagulants were compulsory or optional,whether treatment was in a coronary cure unit or an ordinaryward and, surprisingly, whether treatment began early ( <6h from onset of symptoms) or late (generally 12–24 h).In addition, there was no evidence that UK was more effectivethan the less expensive SK, or that, despite their technicalcomplexity, the new IC regimes were more effective than theold IV regimes. Even the IV schedules that have been studied in randomized trialswere, however, quite complex, and the IC schedules were farmore so. Perhaps partly because of this, none of them is widelyused. If so, then some much simpler, and hence more widely practicable,IV SK regimes should be developed and tested. For example, asimple one hour high-dose IV SK infusion, without anticoagulation,will successfully convert virtually all of the available plasminogeninto plasmin. But, it may be several years before the net effectson mortality of any more widely practicable IV SK regimes canbe agreed unless many of the hospitals that do not wish routinelyto use IC regimes or the complex previous IV regimes will collaboratein multicentre randomized trials that can, if necessary, continuerapid intake until some tens of thousands of patients have beenrandomized, and some thousands of deaths have been observedamong the control and treated patients. The same, of course,may be true for any other fibrinolytic regimes (e.g. infusionof tissue plasminogen activator) if their net effects on mortalityare comparable to those of IV SK.     

HEIGHT, OCCUPATION AND BACK PAIN IN A NATIONAL PROSPECTIVE STUDY

Back pain is an important public health problem but there isa paucity of knowledge about risk factors and causal mechanisms.Previous studies have shown that tall men are more at risk ofback pain, although observations in women have been less consistent.This paper presents findings from a national longitudinal studyof 3262 men and women aged 43 yr. Standing height and sittingheight were related to 18-month reported prevalence of ‘sciatica,lumbago or severe backache’ in both men and women. Thepaper investigates explanations for these findings using previouslycollected data on childhood growth and detailed lifetime occupationalhistories. Neither greater susceptibility of tall men to heavylifting, nor the timing of growth, were able to account forthese relationships. To assess further the association betweenheight and back pain, information is needed on the relationshipbetween stature and characteristics of spinal structure. KEY WORDS: Longitudinal, British, Growth, Adults, Lifting, Spine     

Twins with moyamoya disease

Moyamoya disease is a progressive disease which involves the internal carotid arteries and its branches bilaterally. The disease is reported both in adults and in children. Moyamoya disease is frequently seen in Japanese patients having certain human leucocyte antigen (HLA) haplotypes including HLA-Aw24, Bw46 and Bw54. Twin cases are rarely reported in the literature. We hereby present the first Turkish monozygotic twins with moyamoya disease whose HLA haplotypes are A2, A9, B21, Bw22, Bw4, Bw6, Cw3, and DR2, DR4, DRw52, DRw53, Dq7. The patients with advanced disease were given nifedipine and intravenous immunoglobulin (400mg/kg/d for 5 days). During the 11 months of follow-up, the patients were attack free.     

Histological changes following epidural injection of midazolam in the neonatal rabbit

Midazolam can produce antinociceptive effects when used via intrathecal or epidural routes. Neurotoxicity studies are scanty especially for neonates. The aim of this study was to carry out electron microscopic (EM) examinations in the neonatal rabbit to determine the histological effects of epidural midazolam on spinal cord. Twenty white New Zealand neonatal rabbits were randomly assigned to three groups receiving single dose of 0.9% saline (Group I; Control, n =4), 0.9% saline titrated to pH=3.9 by addition of hydrochloric acid (Group II; n =6), midazolam 250 μg·kg⁻¹ (Group III; n =12) epidurally. Half of each group were sacrificed on the second day and the remainder on the seventh day and spinal cord sections were evaluated by EM. Control group displayed normal histology on grids. Group II and II showed a variable degree of neurotoxic effects such as degeneration of vacuoles, cytoplasm and neurofilaments, disruption of myelin sheaths, lysis of cell membranes, perivascular oedema, pyknosis of nuclei. The toxic effects of acidic saline and midazolam are similar, in view of these results the epidural use of acidic midazolam (commercially available preparations) in neonates should be avoided.     

Significance of a mitral regurgitation systolic murmur complicating a first acute myocardial infarction in the coronary care unit -- assessment by colour Doppler flow imaging

To determine the prevalence and significance of a systolic mitralmurmur heard after a first acute myocardial infarction (MI),we studied 186 consecutive patients in the coronary care unit(CCU) during a one-year period. Fifteen patients had a murmuras a result of mitral regurgitation (MR) (prevalence 8%) documentedby colour Doppler flow imaging. It was heard before the thirdday of hospitalization in 10 (67%) patients, and on the thirdday itself in the remainder. The severity of MR was graded semi-quantitatively:moderate in 12 (80%) patients, and mild, moderate to severeand severe in three respectivety. The direction of the MR jet,determined by colour flow imaging, improved the informationobtained by two-dimensional echocardiography (2D echo) thatcould only diagnose mitral leaflet abnormality in seven (47%)patients. in 10 of 15 (67%) patients, the 2D echo ejection fractionwas 40% and in eight (53%) the wall motion score obtained byanalysing 11 left ventricular (LV) segments was $$$8. Two (13%)patients died in tile CCU, four (27%) had LV failure, one anginaand eight (53%) remained asymptomaric in the hospital. Of 171patients without a systolic murmur, 22 (13%) had LV failure,13 (8%) angina and 25 (15%) died during the in-hospital stay(P-NS for these complications between patients with and withoutMR murmur). During a follow-up of 12–24 months, one MRpatient died, and seven (47%) remained asymptomatic. We conclude that the prevalence of MR systolic murmurs in acuteMI patients is low. The LV function and the prognosis of a majorityof these patients is rather good.     

Fournier's gangrene: Report of thirty-three cases and a review of the literature

Background: Fournier’s gangrene (FG) is an extensive fulminant infection of the genitals, perineum or the abdominal wall. The aim of this study is to share our experience with the management of this difficult infectious disease. Methods: Thirty‐three male patients were admitted to our clinic with the diagnosis of FG between February 1988 and December 2003. The patient’s age, etiology and predisposing factors, microbiological findings, duration of hospital stay, treatment, and outcome were analyzed. The patients were divided into two groups. The first 21 patients (Group I) were treated with broad‐spectrum triple antimicrobial therapy, broad debridement, exhaustive cleaning, and then they underwent split‐thickness skin grafts or delayed closure as needed. The other 12 patients (Group II) were treated with unprocessed honey (20–50 mL daily) and broad‐spectrum triple antimicrobial therapy without debridement. Their wounds were cleaned with saline and then dressed with topical unprocessed honey. The wounds were inspected daily and the honey was reapplied after cleaning with normal saline. Then, the patients’ scrotum and penis were covered with their own new scrotal skin. Results: The mean age of the patients was 53.9 ± 9.56 years (range = 23–71). The source of the gangrene was urinary in 23 patients, cutaneous in seven patients, and perirectal in three patients. The predisposing factors included diabetes mellitus for 11 patients, alcoholism for 10 patients, malnutrition for nine patients, and medical immunosuppression (chemotherapy, steroids, malignancy) for three patients. The mean duration of hospital stay was 41 ± 10.459 (range = 14–54) days. Two patients in Group I died from severe sepsis. The clinical and cosmetic results were better in Group II than Group I. Conclusions: Necrotizing fasciitis of the perineum and genitalia is a severe condition with a high morbidity and mortality. Traditionally, good management is based on aggressive debridement, broad‐spectrum antibiotics, and intensive supportive care but unprocessed honey might revolutionize the treatment of this dreadful disease by reducing its cost, morbidity, and mortality.     

Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non‐valvular atrial fibrillation from the RE‐LY trial

Summary. Background: Dabigatran etexilate (DE) is an orally absorbed prodrug of dabigatran, a thrombin inhibitor that exerts potent anticoagulant and antithrombotic activity. Objectives: To characterize the pharmacokinetics of dabigatran in patients with non‐valvular atrial fibrillation (AF) from the Randomized Evaluation of Long‐term Anticoagulant Therapy (RE‐LY) trial and to quantify the effect of selected factors on pharmacokinetic (PK) model parameters. Patients and methods: A total of 27 706 dabigatran plasma concentrations from 9522 patients who received DE 110 or 150 mg twice daily were analyzed with non‐linear mixed‐effects modeling. Results: The pharmacokinetics of dabigatran were best described by a two‐compartment disposition model with first‐order absorption. The covariates creatinine clearance (CRCL), age, sex, heart failure and the ethnic subgroup ‘South Asian’ exhibited statistically significant effects on apparent clearance of dabigatran. Body weight and hemoglobin significantly influenced the apparent volume of distribution of the central compartment. Concomitant medication with proton‐pump inhibitors, amiodarone and verapamil significantly affected the bioavailability. However, all of the statistically significant factors that were identified, except for renal function status, showed only small to moderate effects (< 26% change in exposure at steady state). On the basis of simulations from the final population PK model, a dose of 75 mg twice daily would result in similar exposure for severely renally impaired patients with CRCL of 15–30 mL min^?1 and patients with normal renal function receiving 150 mg twice daily. Conclusions: The analysis provides a thorough PK characterization of dabigatran in the AF patient population from RE‐LY. None of the covariates investigated, with the exception of renal function, warrants dose adjustment.