Residual coronary stenosis after thrombolysis with rt-PA or streptokinase: acute results and 3 weeks follow-up

Ninety-one patients with acute myocardial infarction were assignedto intravenous treatment with streptokinase or rt-PA as partof the randomized trial carried out by the European Study Groupfor Recombinant Tissue-Type Plasminogen Activator (rt-PA). Apatent coronary artery was found in 37 of 45 (82%) patientstreated with rt-PA and in 27 of 46 (59%) patients treated withstreptokinase 75–90 minutes after start of infusion. Patientswere subsequently anticoagulated with heparin or dicoumarolup to a repeat angiography 3 weeks after the infarction.Of the64 patients with successful reperfusion, 3 died and 3 sufferedreocclusion of the vessel. Quantitative analysis of the coronarystenosis both immediately after thrombolvsis and at 3 weeksfollow-up was possible in 33 cases. Residual stenosis (percentagenarrowing of diameter) decreased from 74± 14% to 56±17% P<0.05). No difference was observed between the groupsof patients treated with streptokinase (74±9% to 57±12%,N = 17) and with rt-PA (74±17% to 56±21%, N =16). Despite the significant regression, a coronary stenosisof more than 50% of the diameter persisted in 82% of the patientsthree weeks after the infarction.     

Current use of by-passing agents in Europe in the management of acute bleeds in patients with haemophilia and inhibitors

The ultimate goal of treatment for patients with inhibitory antibodies should be to permanently eradicate the inhibitor by immune tolerance induction therapy (ITI). However, ITI procedures fail in a substantial number of patients and in many countries ITI is not even offered owing to its high cost. How patients with inhibitors are managed in different European countries is evaluated with a special focus on the use of by-passing agents, i.e. recombinant FVIIa (rFVIIa) and activated prothrombin complex concentrates (aPCC), as well as the type of monitoring performed. Investigators from 22 large haemophilia centres participating within the network of the European Haemophilia Therapy Standardisation Board (EHTSB) were asked to complete a questionnaire. rFVIIa was routinely used in all centres for both children and adults at dosages ranging from 90 to 250 mug kg(-1) at an interval of 2-4 h. aPCC was used in 85% of the centres in adults and in 25% of the centres in children with haemophilia A at dosages of 50-100 IU kg(-1) every 6-12 h. The corresponding figures for children and adults with haemophilia B were 40% and 15% of the centres, respectively. Higher dosages of both agents were considered in the case of life-threatening bleeds. General recommendations were developed, based on the information provided by the survey. The results clearly indicate the need for well-designed comparative studies to optimize the use of by-passing agents.     

Should prophylaxis be used in adolescent and adult patients with severe haemophilia? An European survey of practice and outcome data

A survey of 21 haemophilia doctors, throughout Europe, who care for a total of approximately 5000 patients with bleeding disorders addressing practice and opinions regarding prophylaxis in patients aged 16-24 years and adults aged over 50 years, is presented. The outcome of adolescent patients who reduced or stopped prophylaxis was recorded. Eighteen of 19 respondents would consider modification of established prophylaxis in the adolescent age group, principal considerations being avoidance of risks of further concentrate exposure, predicted poor compliance and treatment costs. The preferred age for modification was 16-20 years, but there was very little consensus on the particular prophylactic regime recommended. Approximately, half of a cohort of 218 patients with severe haemophilia successfully reduced or stopped prophylaxis when they reached adolescence. Only 26 of 92 (28%) of the patient cohort who stopped prophylaxis, required reintroduction of a prophylactic regime and 12 of 59 (20%) of those who reduced the intensity of prophylaxis had to reintroduce a more intensive regime. A majority of respondents would consider starting prophylaxis in those over 50 years. There was no consensus as to indications for this practice or the nature of the prophylaxis protocol. We conclude that there is an absence of consensus on the management of patients with severe haemophilia, as they pass through adolescence and young adulthood, and reach the age of 50. Aggregate outcome data suggest a significant proportion of patients in the 18-22 years age range may be able to reduce or stop prophylaxis. A substantial number of older patients are on prophylaxis.     

Clinical trial: the treatment of gastro-oesophageal reflux disease in primary care – prospective randomized comparison of rabeprazole 20 mg with esomeprazole 20 and 40 mg

Background  A trial of empirical PPI therapy is usual practice for most patients with symptoms of gastro-oesophageal reflux disease (GERD) in primary care.
Aim  To determine if the 4-week efficacy of rabeprazole 20 mg for resolving heartburn and regurgitation symptoms is non-inferior to esomeprazole 40 mg or 20 mg.
Methods  In all, 1392 patients were randomized to rabeprazole 20 mg, esomeprazole 20 mg or 40 mg once daily. Patients, doctors and assessors were blinded. Symptom resolution data were collected on days 0–7 and day-28 using the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index with a shortened version used on days 8–27.
Results  Rabeprazole 20 mg was non-inferior to esomeprazole 40 mg for complete resolution of regurgitation and satisfactory resolution of heartburn and regurgitation. For complete heartburn resolution, the efficacy of rabeprazole 20 mg and esomeprazole 40 mg was statistically indistinguishable, although the non-inferiority test was inconclusive. Rabeprazole 20 mg was non-inferior to esomeprazole 20 mg for all outcomes.
Conclusions  In uninvestigated GERD patients, rabeprazole 20 mg was non-inferior to esomeprazole 40 mg for complete and satisfactory relief of regurgitation and satisfactory relief of heartburn, and not different for complete resolution of heartburn.     

Antenatal determinants of oro-facial clefts in Southern Nigeria

Objectives

Cleft lip with or without cleft palate, is the most common serious congenital anomaly that affects the orofacial regions. The management and care of the cleft patient constitutes a substantial proportion of the workload of the Nigerian maxillofacial surgeon and allied specialties. Yet, there are no specific programmes targeted at this group. We believe that the findings of this study is capable of identifying useful interventions for designing programs that will lead to a reduction in the burden of orofacial cleft in Nigeria.

Methods

It was a transverse cross-sectional study that was undertaken at the Maxillofacial Units of the University of Benin Teaching Hospital and the Central Hospital, Benin City respectively. The prevalence and antenatal determinants of cleft lip and palate were determined.

Results

Cleft lip and palate were often encountered in clinical practice in Benin City with a prevalence of 1.35%. The results showed that orofacial clefts were commoner in females and that the combined unilateral cleft lip and palate was the commonest entity encountered amongst the cases. The following risk factors were associated with the risk of development of cleft lip and palate: Paternal age >40 years, maternal age >35 years, genetic/family history, low socio-economic status, alcohol consumption and indulgence in the intake of herbal medications in pregnancy.

Conclusion

Public health education programmes and advocacy activities geared towards raising awareness of the identified risk factors for the development of cleft lip and or cleft palate would go a long way to obviate the occurrence and reduce the burden.Key Words: Prevalence, Antenatal determinants, orofacial clefts, Southern Nigeria     

Lupus anticoagulant testing using plasma spiked with monoclonal antibodies: performance in the UK NEQAS proficiency testing programme

We report here results from a United Kingdom National Quality Assessment Scheme (UK NEQAS) exercise in which both plasma spiked with monoclonal antibodies and plasma from a patient known to have lupus anticoagulant (LA) were distributed to 245 hemostasis laboratories with a request for them to test for possible LA using their routine screening procedure. In general, good agreement was seen in the diagnosis of samples spiked with monoclonal antibodies against beta2-glycoprotein 1 (beta2GP1) and prothrombin, the LA-positive patient sample, and a normal pooled plasma; over 87% of centers correctly identified each sample. However, methods employing platelet neutralizing procedures were associated with a higher proportion of false-negative responses with the antiprothrombin-spiked sample, and it is important to recognize that sensitivity and responsiveness of different methods may vary between artificial plasmas and different LA-positive patient plasmas.     

The value of dipyridamole echocardiography in risk stratification before vascular surgery: A multicenter study

PURPOSE: Patients undergoing major vascular surgery are at relativelyhigh risk of cardiac events, and pharmacological stress echocardiographyis increasingly used for peri-operative risk strattfication. PATIENTS AND METHODS: One hundred and twenty-one patients undergoing vascular surgery(age 65±7 years) were studied by dipyridamole echocardiographytesting in six different centres. Of the total 136 patients,15 were subsequently excluded because surgery was either cancelled(n=8) or postponed pending cardiac revascularization (n=7) becauseof the presence of a ‘high-risk’ stress echo response(identified ‘a priori’ as a positive dipynidamoleecho cardiography testing with a dipyridamole-time <5 minand/or a peak wall motion score index>2, upon scoring eachsegment from 1=normal to 4=dyskinetic in an 11-segment model) RESULTS: No major complications occurred during dipyridamole echocardiographytesting. Technically adequate images were obtained in all patients;however, in one patient only the low dipyridamole dose (56 Prig.kg^–1 over 4 min) was given to limit side effects. Of the121 patients undergoing surgery 28 (23%) had a positive test.Pen-operative events occurred in nine patients (8%) two deaths,two myocardial infarctions, five cases of unstable angina. Sensitivityand speccificity of dipyridamole echocardiography testing forpredicting cardiac events were 78% and 81%, respectively, witha positive predictive value of 25% and a negative predictivevalue of 98% Dipyridamole echocardiography testing effectivelysingled out patients with, from those without, events, but neitherclinical parameters, such as Detsky score, nor baseline echoparameters, such as resting wall motion score index or ejectionfraction were able to distinguish between such patients. CONCLUSION: In conclusion, dipyridamole echocardiography testing is safeand well tolerated in patients undergoing major vascular surgery,and provides an effective pre-operative screening test for riskstrat fi cation of these patients mainly due to the extremelyhigh negative predictive value. Stress echocardiography is abetter discriminator than clinical and rest echocardiographicvariables.     

Myeloid Karyotype and the Malignant Phase of Chronic Granulocytic Leukaemia

During the course of a 30 month study period, 26 patients with typical chronic granulocytic leukaemia (CGL) developed karyotype abnormalities in addition to the Philadelphia (Ph1) chromosome. All cases had received at least 14 months continuous low dose busulphan, and the chromosome changes were found before clinical transformation in six patients and at the time this occurred in 20. Survival following the discovery of these additional abnormalities was short, with a median of 11 weeks for the whole group. Trisomy 8 was the commonest additional chromosome abnormality, but no one karyotype change was clearly associated with shorter survival than another. 23 of the 26 have died as a direct result of their disease, forming part of a total of 40 deaths from typical CGL encountered during the study period where karyotype analyses were performed during the terminal stages of disease. Of these 40, only two (5%) patients showed no chromosome abnormalities extra to the Ph1 prior to death. (The 17 non-study patients who died were similar in all respects to the 23 from the study group, but had no prior chromosome studies performed during the chronic phase of the disease.) It is suggested that an expanding aneuploid or pseudodiploid clone arising from the leukaemic cells during the benign phase of CGL can be used to mark the sometimes ill-defined onset of the malignant phase in all but a small proportion of cases.