A performance evaluation of commercial fibrinogen reference preparations and assays for Clauss and PT-derived fibrinogen

The wide availability of fibrinogen estimations based on the prothrombin time (PT-Fg) has caused concern about the variability and clinical utility of fibrinogen assays. In a multi-centre study, we investigated fibrinogen assays using various reagents and analysers. Clauss assays generally gave good agreement, although one reagent gave 15-30% higher values in DIC and thrombolysis. Two commercial reference preparations had much lower potencies than the manufacturers declared, and plasma turbidity influenced parallelism in some Clauss assays. PT-Fg assays gave higher values than Clauss and showed calibrant dependent effects, the degree of disparity correlating with calibrant and test sample turbidity. Analyser and thromboplastin dependent differences were noted. The relationship between Clauss and PT-Fg assays was sigmoid, and the plateau of maximal PT-Fg differed by about 2 g/l between reagents. ELISA and immunonephelometric assays correlated well, but with a high degree of scatter. Antigen levels were higher than Clauss, but slightly lower than PT-Fg assays, which appeared to be influenced by degraded fibrinogen. Clauss assays are generally reproducible between centres, analysers and reagents, but PT-Fg assays are not reliable in clinical settings.     

Diagnosis of hemochromatosis

Hereditary hemochromatosis is an inherited disorder of iron metabolism affecting approximately 1 in 200 to 300 individuals of Northern European descent. Over time, the continued deposition of iron in parenchymal cells of many organs can eventually lead to diabetes mellitus, cardiomyopathy, and hepatic cirrhosis, the last of which is frequently followed by hepatocellular carcinoma. Although the complications of hereditary hemochromatosis can be devastating, its clinical management is simple and effective if the disease is identified early in its progression. In affected individuals, it is important to confirm or exclude the presence of cirrhosis and begin therapy as early as possible. The insidious onset and high prevalence of nonspecific symptoms in the early stages of the disease requires the clinician to have a high index of clinical suspicion for this disease. This is particularly important because treatment before there is permanent organ damage can reverse the iron toxicity and restore life expectancy to normal. Because of its familial occurrence all first-degree relatives of patients with hereditary hemochromatosis should be tested for the disease.     

Using a harm reduction approach with clients who have alcohol/drug dependencies in a spinal cord rehabilitation program

BACKGROUND: Dissatisfied with the frequently adversarial nature of relationships with clients who use alcohol or drugs while rehabilitation inpatients, and the often less than optimal outcomes for these individuals, the Spinal Cord Program at the G.F. Strong Rehabilitation Center in Vancouver, BC, decided to pilot a new approach. OBJECTIVE: The goal of the pilot project is to promote successful rehabilitation, including less conflict in rehabilitation, a completed rehabilitation program, and continued connection after discharge if needed. METHOD: A dedicated team was formed and trained to work with these clients using harm reduction principles. PARTICIPANTS: From its inception in December 2000, through May 2001, the team worked with 6 inpatients, 12% of admissions to the Spinal Cord Program during that period. RESULTS: Outcomes based on the above goals have been positive. There have been no discharges against a client's will or instances of significant conflict with the team. Several clients have returned to the center for assistance or to visit post-discharge. Only 1 client left rehabilitation prematurely.     

Pilot randomised controlled trial of community pharmacy administration of buprenorphine versus methadone

Objectives The established regime for opiate substitute prescribing for drug misusers is daily methadone administered under supervision in community pharmacies. Buprenorphine has recently been introduced as an alternative. However there is a lack of evidence of the effectiveness of buprenorphine maintenance therapy (BMT) in the UK treatment setting. This study aimed to assess methods for a randomised controlled trial (RCT) and the feasibility of pharmacy‐based supervised self‐administration (SSA) of buprenorphine compared to methadone. Setting Specialist substance misuse service, general practices and community pharmacies in Aberdeen, Scotland. Method The design was a pilot RCT. Opiate‐dependent drug misusers, newly referred for maintenance treatment were randomised to receive BMT or methadone maintenance therapy (MMT). Clients and pharmacists were interviewed at baseline and at the end of a 12‐week intervention period. Clients completed the quality of life measure EQ‐5D. Pharmacy activities were timed. Key findings Twenty‐one opiate‐dependent clients were recruited (BMT = 11, MMT = 10). Recruitment levels improved as the trial progressed. Clients' treatment preferences were evident. Withdrawals occurred early with BMT. Clients found SSA of buprenorphine acceptable, but found daily administration more manageable than three times weekly. Pharmacists found the dispensing of buprenorphine to be an acceptable role, but felt less certain of ensuring against diversion with buprenorphine than they were with methadone. Pharmacy activities associated with buprenorphine took longer than those associated with methadone (mean = 7 min 25 s versus mean = 3 min 27 s, respectively). Conclusion Recruitment to a trial comparing MMT to BMT for opiate‐dependent clients within a UK treatment setting is feasible. Clients and pharmacists found buprenorphine acceptable.     

1H NMR as a non-invasive probe of amniotic fluid in insulin dependent diabetes mellitus

Ten amniotic fluid samples obtained from third trimester pregnant women suffering from insulin dependant diabetes mellitus were analysed by 1H-NMR and compared to ten samples from a group of normal volunteers. A subset of the metabolites identified; valine, lactate, alanine, acetate, citrate and glucose were quantitated using standard addition methods. Apart from valine and citrate, a general diminution in the concentration of each of these species was found, especially glucose, in the diabetic group. The abnormally low glucose levels in the diabetic group are suggestive of infection in the patient group. However, the depressed lactate levels in the diabetic group suggest that in these cases the fetus was not subjected to stress.     

Elephantiasis nostras verrucosa: beneficial effect of oral etretinate therapy

Elephantiasis nostras verrucosa is characterized by chronic secondary, non-filarial lymphoedema due to recurrent lymphangitis, dermal fibrosis, and epidermal changes consisting of hyperkeratotic, verrucous and papillomatous lesions. Histologically, there is pseudoepitheliomatous hyperplasia. Therapeutic efforts should aim to reduce lymph stasis, which will also lead to improvement of the cutaneous changes. In this study, rapid disappearance of the hyperkeratotic and verrucous lesions, remarkable flattening of the papillomatous nodules and improvement of lymphoedema occurred in three obese patients treated with etretinate in an initial dose of 0.6-0.75 mg/kg/day for 4-6 weeks. Monitoring of plasma concentrations of etretinate, acitretin and 13-cis-acitretin by HPLC revealed sufficient short-time absorption (4 h) and bioavailability of the drug (30 days; two out of three patients). Long-term maintenance therapy in one patient produced a remarkable improvement in the lymphoedema; another patient relapsed after discontinuation of the etretinate and responded again after this was reintroduced. In the third patient treatment was withdrawn because of an increase in triglycerides, but improvement persisted 6 months later. The clinical side-effects of oral retinoid therapy were moderate and well tolerated.     

Right mini-thoracotomy: an adjunct to left subcostal automatic implantable cardioverter defibrillator implantation

High defibrillation thresholds are encountered in some patients during implantation of the automatic implantable cardioverter defibrillator (AICD). In a consecutive series of 52 patients with AICD implants, 46 had allepicardial implants by left subcostal thoracotomy, and 8 of these patients had thresholds greater than 30 J. Placement of an apicolateral large left ventricular patch and an extrapericardial large right atrial patch electrode through a limited right thoracotomy produced substantial reduction in their thresholds. Especially in patients who have had previous intrapericardial operations, this technique provides a simple solution to the problem of high thresholds.