The effect of wet granulation on the erosion behaviour of an HPMC-lactose tablet, used as a rate-controlling component in a pulsatile drug delivery capsule formulation.

The purpose of this study was to investigate the variability in the performance of a pulsatile capsule delivery system induced by wet granulation of an erodible HPMC tablet, used to seal the contents within an insoluble capsule body. Erodible tablets containing HPMC and lactose were prepared by direct compression (DC) and wet granulation (WG) techniques and used to seal the model drug propranolol inside an insoluble capsule body. Dissolution testing of capsules was performed. Physical characterisation of the tablets and powder blends used to form the tablets was undertaken using a range of experimental techniques. The wet granulations were also examined using the novel technique of microwave dielectric analysis (MDA). WG tablets eroded slower and produced longer lag-times than those prepared by DC, the greatest difference was observed with low concentrations of HPMC. No anomalous physical characteristics were detected with either the tablets or powder blends. MDA indicated water-dipole relaxation times of 2.9, 5.4 and 7.7x10(-8)ms for 15, 24 and 30% HPMC concentrations, respectively, confirming that less free water was available for chain disentanglement at high concentrations. In conclusion, at low HPMC concentrations water mobility is at its greatest during the granulation process, such formulations are therefore more sensitive to processing techniques. Microwave dielectric analysis can be used to predict the degree of polymer spreading in an aqueous system, by determination of the water-dipole relaxation time.     

Ocular complications of paediatric patients with nephrotic syndrome

Purpose : To investigate ocular complications arising from nephrotic syndrome and/or its treatments in children. Methods : A cross‐sectional study was conducted in a teaching hospital. A total of 31 paediatric patients with nephrotic syndrome were studied. Comprehensive ophthalmic assessments on best‐corrected visual acuity, intraocular pressure, slit‐lamp and fundus examination were taken. Information regarding histological diagnosis of nephrotic syndrome and its treatment regimen in each patient was reviewed and analysed. Results : Bilateral posterior subcapsular cataracts were detected in three of 29 patients (10.3%) who received steroid therapy. Two had normal vision while one had visual acuity reduced to 6/15 in both eyes. The age of onset of the nephrotic syndrome in these three patients was 2 years, which was significantly younger than those without cataract (5.4 ± 3.2 years, P < 0.001). Three patients (9.7%) had isolated asymptomatic fundal findings of tortuous and dilated retinal vessels. Hypertensive retinopathy was found in one patient (3.2%). No steroid‐induced glaucoma, uveitis, ocular infection, or other eye complications related to the use of steroids or other immunosuppressive agents were noted. Conclusions : Children who have nephrotic syndrome often require prolonged, intermittent high dose of systemic corticosteroid therapy. Paediatricians should be aware of the potential risk of developing steroid‐related complications, especially posterior subcapsular cataract. It appears to have a higher risk when steroid therapy is used in very young patients. Early detection would help to prevent amblyopia development, particularly in the group of immature eyes.     

Posttransplant Bronchiolitis Obliterans Syndrome Is Associated with Bronchial Epithelial to Mesenchymal Transition

Bronchiolitis obliterans syndrome (BOS) compromises lung transplant outcomes and is characterised by airway epithelial damage and fibrosis. The process whereby the normal epithelial configuration is replaced by fibroblastic scar tissue is poorly understood, but recent studies have implicated epithelial mesenchymal transition (EMT). The primary aim of this study was to assess the utility of flow cytometry in detecting and quantifying EMT in bronchial epithelial cells.
Large airway brushings were obtained at 33 bronchoscopies in 16 BOS-free and 6 BOS grade 1–3 patients at 2–120 months posttransplant. Flow cytometry was used to assess expression of the mesenchymal markers αSMA, S100A4 and ED-A FN and HLA-DR. TGF β1 and HGF were measured in Bronchoalveolar lavage (BAL). Expression of all three mesenchymal markers was increased in BOS, as was HLA-DR. BAL HGF, but not TGF β1 was increased in BOS. Longitudinal investigation of one patient revealed a 100% increase in EMT markers concurrent with a 6-fold increase in BAL TGF β1 and the diagnosis of BOS at 17 months posttransplant.
Flow cytometric evaluation of bronchial epithelium may provide a novel and rapid means to assess lung allografts at risk of BOS.     

Common bile duct calculi: updated experience with dissolution with methyl tertiary butyl ether

The authors describe their experience with methyl tertiary butyl ether (MTBE) in a larger series of patients than previously reported in order to acquaint physicians with both its effectiveness for dissolution of common bile duct calculi and the limitations of its use. Ten patients with 13 biliary calculi underwent percutaneous stone dissolution treatment with the experimental cholesterol solvent, MTBE. Three stones completely dissolved within 30 minutes, seven were reduced in size, and three were visibly unaffected. All stones not completely dissolved were easily extracted by means of a stone basket except for one in a patient taken to surgery. Although MTBE perfusion is an effective technique for management of biliary calculi, practitioners should be aware that its use is quite time consuming and its odor difficult to control.     

P REHOSPITAL U SE OF A NALGESIA FOR S USPECTED E XTREMITY F RACTURES

Introduction. Pain and its control have been studied extensively in the emergency department. Numerous studies indicate that inadequate treatment of pain is common, despite the availability of myriad analgesics. It has been suggested that oligoanesthesia is also a common practice in the prehospital setting. Objective. To assess the use of prehospital analgesia in patients with suspected extremity fracture. Methods. Emergency medical services (EMS) call reports were reviewed for all patients with suspected extremity fractures treated from June 1997 to July 1998 in a midwestern community with a population base of 223,000. Data collected included demographic information, mechanism of injury, medications given, and field treatment. Standing orders for administration of analgesia were available and permitted paramedics to give either morphine sulfate or nitrous oxide per protocol. Results. The EMS call reports were analyzed for 1,073 patients with suspected extremity fractures. The mean patient age was 47 years. Accidental injuries comprised 86.5% of those reviewed. Suspected leg fractures were most common (20%), followed by hips (18%), arms (11%), knees (10%), ankles (9%), shoulders (7.2%), hands (5.5%), and wrists (5.3%). Multiple trauma and assorted broken digits accounted for the remaining 14%. The most common mechanisms of injury were: fall (43%), motor vehicle collision (21%), and human assault (10%). Intravenous lines were placed in 9.4% of patients; 17% received ice packs; 16% received bandage/dressings; 25% received air splints; and 19% were fully immobilized. Analgesia was administered to 18 patients (1.8%): 16 patients received nitrous oxide and two received morphine. Conclusion. Administration of analgesics to prehospital patients with suspected fractures was rare. Prehospital identification and treatment of pain for patients with musculoskeletal trauma could be improved.