Immunology

A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in immunology.     

Stability of parenteral midazolam in an oral formulation.

Midazolam is increasingly being used for oral sedation in pediatric dentistry. Unfortunately, it is available only as a parenteral formulation in Canada and the United States. Preparation of the parenteral solution for oral use is not uniform and leads the clinician to question the stability of this drug when used in conjunction with these vehicles. Therefore, the purpose of this study was to investigate the chemical stability of parenteral midazolam as an oral formulation to determine its expiry date. This was evaluated using a validated stability-indicating liquid chromatographic method. Midazolam was diluted in orange-flavored syrup to yield concentrations of 0.35, 0.64, and 1.03 mg/ml and then stored at room temperature. Samples were drawn on each of 9 study days (0, 1, 2, 6, 7, 9, 13, 21, and 102) and chromatographed. On each study day, solutions were inspected visually for changes in color, clarity, and appearance of particulate matter. Midazolam concentrations were considered within acceptable limits if they were not less than 90% of the initial concentration. Over the 102-day study period, there was no significant change in concentration in any of the solutions. On day 102, the remaining midazolam was within 7% of the day zero concentration. Therefore, these formulations of midazolam are stable at room temperature for a period of 102 days and would be suitable for clinical use.     

Cardiomyopathy: a late complication of hemolytic uremic syndrome

This report describes a child who presented with classic hemolytic uremic syndrome (HUS) and 4 months later developed a life-threatening but reversible cardiomyopathy with global cardiac dysfunction and a left ventricular ejection fraction of 14%. There was no evidence of electrolyte abnormalities, anemia, hypertension, severe fluid overload, or viral infection. Endomyocardial biopsies were consistent with a dilated cardiomyopathy. This paper highlights the importance of considering the diagnosis of associated cardiomyopathy when presenting with late-onset edema following HUS. Received February 12, 1996; received in revised form and accepted August 22, 1996     

MOBILITY AIDS FOR CHILDREN WITH HIGH-LEVEL MYELOMENINGOCELE: PARAPODIUM VERSUS WHEELCHAIR

The optimal method for providing mobility for children with myelomeningocele remains controversial. 39 children using a parapodium were compared with 29 children in wheelchairs. There were no significant differences between the two groups for medical complications, use of health-care services or activities of daily living, although there were differences in the patterns of complications. Children using the parapodium were more likely to develop lesions of the lower extremities, to have dislocated hips, to be more obese and to watch more television; children using wheelchairs were more likely to develop lesions of the gluteal region, to have knee-flexion contractures and to have fewer fecal accidents. The parapodium was judged by families to be less effective as a mobility aid; however, the upright posture it allows was considered extremely advantageous. A combined approach allowing upright posture and wheeled mobility would appear to be optimal.     

Marchiafava-Bignami Disease

Marchiafava-Bignami disease is a rare demyelinating disease involving the corpus callosum and other central white matter tracts. In the patient described here, the disease produced extensive demyelination of the corpus callosum and deep cerebral white matter. This widespread demyelination, confirmed pathologically, was associated with a fulminant fatal course. The magnetic resonance imaging appearance is quite suggestive of Marchiafava-Bignami disease and plays an important role in the premortem diagnosis.     

Developing a VATS lobectomy programme--can VATS lobectomy be taught?

OBJECTIVE: Although VATS lobectomy has been demonstrated to be safe and effective, the technique is not widely practiced. This may, in part, reflect difficulty in acquiring appropriate skills. We have evaluated the effect of experience and training on surgical outcomes during the development and establishment of a VATS lobectomy programme. METHODS: Data were collected prospectively on 276 consecutive VATS lobectomies under the care of a single consultant as either the primary surgeon or supervising four trainees. The series was divided into cohorts of 46 patients. These comprised one trainee cohort and five sequential consultant cohorts. Statistical analysis utilised standard tests of significance. RESULTS: Increasing experience with the VATS lobectomy programme was associated with a significant reduction in operating time but intraoperative blood loss and postoperative stay were not influenced by increasing consultant surgical experience. Training was associated with a mean increase of 22 min operative time (p=0.0005) but no increase in intraoperative blood loss, morbidity, mortality or postoperative stay. The 46 trainee operative times were similar to the first 46 consultant cases. CONCLUSIONS: VATS lobectomy can be safely taught to trainee thoracic surgeons. However, in view of the limited number of centres undertaking VATS lobectomy, training should be coordinated at a national level to concentrate experience and improve uptake of this technique.     

Spiral laminar flow in the abdominal aorta: a predictor of renal impairment deterioration in patients with renal artery stenosis?

BACKGROUND: Spiral or helical arterial blood flow patterns have been widely observed in both animals and humans. The absence of spiral flow has been associated with carotid arterial disease. The aim of this study was to detect the presence of aortic spiral flow using magnetic resonance imaging (MRI) and to evaluate the relationship of the presence of spiral aortic flow with renal arterial disease and renal function in the follow-up of patients with suspected renal atheromatous disease. METHODS: Prospective study of 100 patients with suspected renal arterial disease and 44 patient controls. Using a 1.5 T MRI unit (Siemens Symphony), phase contrast flow quantification and three-dimensional contrast enhanced MR angiography of the abdominal aorta were performed. Renal arterial stenoses (RAS) were classified minimal, moderate or severe. Renal function was followed at 3 months before and 6 months after MRI. RESULTS: Non-spiral flow was more prevalent in patients with more severe RAS. Renal impairment progressed significantly in severe RAS without spiral flow (P = 0.0065), but did not progress significantly in severe RAS with spiral flow (P = 0.12). In minimal or moderate RAS with or without spiral flow there was no significant progression (P = 0.16, 0.13, 0.47, 0.092, respectively). CONCLUSIONS: Aortic spiral blood flow can be assessed with MRI. Lack of aortic spiral blood flow in patients with severe RAS is associated with significant short-term renal function deterioration. Determination of blood flow patterns may be a useful indicator of renal impairment progression in patients with suspected renal artery stenosis.     

Direct expression of Bordetella pertussis filamentous hemagglutinin in Escherichia coli and Salmonella typhimurium aroA.

Nonfused (i.e., nonhybrid) filamentous hemagglutinin (FHA) of Bordetella pertussis was efficiently expressed in Escherichia coli K-12 and Salmonella typhimurium aroA at levels higher than those found in wild-type B. pertussis when the upstream signals of the gene were replaced and the translation initiation region was engineered to optimize translational efficiency. Inclusion of part of the C-terminal FHA open reading frame, whose translation product does not appear to be part of the major secreted species of FHA, was shown to be important in achieving protein expression in both E. coli and S. typhimurium aroA; removal of the downstream gene sequence abolished recombinant FHA production. The levels of expression observed varied widely according to the construct and host bacterium used.