Improved Cellular Delivery of Antisense Oligonucleotides Using Transferrin Receptor Antibody-Oligonucleotide Conjugates

This work is dedicated to the memory of the late Dr Ian Walker.     

Left internal carotid artery dissection presenting with headache, Collet-Sicard syndrome and sustained hypertension

The baroreflex maintains blood pressure through the glossopharyngeal (IX) cranial nerve. We report a 54-year-old man who developed a left sided headache, hoarseness, dysarthria, dysphagia, and sustained hypertension from a left internal carotid artery dissection. We hypothesise that interruption of the left IX nerve caused hypertension in this patient.     

Shoot First,Draw Later Peroneal Nerve Palsy: A Sonographic Study

A 32–year–old man had an unusual gunshot wound to the leg, causing a peroneal nerve palsy. Sonography provided useful complementary findings to the electrodiagnostic localization of the injury.     

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     

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.     

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.     

Enhanced cis-platinum ototoxicity in children with brain tumours who have received simultaneous or prior cranial irradiation

We report on four children who received cis-platinum simultaneously with, or in one case 10 months after, cranial irradiation and experienced exaggerated ototoxicity affecting all audible frequencies. The hearing loss was severe, affecting the critical areas for speech perception, and necessitated the provision of bilateral hearing aids. The audiograms of these patients are shown and compared to those of four children who had received cis-platinum as part of their treatment for neuroblastoma but without cranial irradiation. The precipitation of the exaggerated hearing loss with the administration of cis-platinum in one patient 10 months after finishing cranial irradiation suggests that care should be taken in the timing of cis-platinum administration in relation to concurrent or previous cranial irradiation.