HA1 (Hemagglutinin) quantitation for influenza A H1N1 and H3N2 high yield reassortant vaccine candidate seed viruses by RP-UPLC

The only effective measure to decrease morbidity and mortality caused by the influenza virus in the human population is worldwide vaccination. Vaccination produces neutralizing antibodies that target the HA1 subunit of the HA (hemagglutinin) protein and are strain specific. The effectiveness of new influenza vaccines are linked to two factors, the correct prediction of the circulating strains in the population in a particular season and the concentration of the HA1 protein in the vaccine formulation. With the advent of the licensing of quadrivalent vaccines, pharmaceutical manufacturers are under considerable pressure due to time constraints and dedicated resources to deliver 194–198 million doses (2020–2021 U.S. market) of vaccine. Considering the valuable resources needed to produce the influenza vaccine in a timely manner, the efficient quantitation of the HA1 protein (the main component in the influenza vaccine) is required. Currently the only method approved by regulatory agencies for quantitation of the HA antigen in vaccines is the single radial immunodiffusion assay (SRID), an antibody dependent assay that is not time efficient. Time efficient methods that are antibody independent e.g. reverse phase-high performance liquid chromatography (RP-HPLC) or size exclusion-HPLC (SE-HPLC) are available. An improved method implementing reverse phase-ultra performance liquid chromatography (RP-UPLC) has been developed to quantitate the HA1 protein antigen present in the high yield reassortant vaccine seed viruses from influenza A H1N1 and H3N2 subtypes harvested from inoculated embryonated chicken eggs. This method differentiates between high yield and lower yielding reassortants in order to select the best vaccine candidate seed virus with the highest growth ‘in ovo’. This direct capability to monitor the HA1 concentration of potential reassortant seed viruses and to choose the best yielding HA influenza reassortant when faced with multiple viral seed candidates provides a major advantage on the industrial scale to the influenza vaccine process.     

Electroconvulsive therapy in octogenarians

Medical records of 81 older patients (65 years of age and over) who underwent electroconvulsive therapy (ECT) at a university-affiliated private geriatric hospital were reviewed to evaluate the safety and efficacy of this treatment for depression in the "young-old" (65 to 80 years) compared with the "old-old" age group (over 80 years), a group that has not yet been adequately studied. Information was obtained regarding demographics, medical and psychiatric diagnosis, medications, indications for ECT, number and laterality of treatments, outcome, and complications. Thirty-nine patients 80+ years of age (mean age, 85 +/- 3.2) were compared with 42 patients 65 to 80 years of age (mean age, 74 +/- 5.2). Statistical analysis was performed using confidence intervals of the difference in proportions of patients in each group. There were no significant differences in the demographics, number and laterality of ECT treatments, indications for ECT treatment, medical diagnosis, medications, or prior history of falls, but psychiatric diagnoses differed slightly. Patients over 80 years had significantly more cardiovascular complications and falls (95% confidence interval) and tended to have a worse ASA (American Society of Anesthesiologists) scale rating and a somewhat less successful outcome. This study confirms the role of ECT as a relatively safe and effective treatment, which may be lifesaving in selected depressed older patients. Prospective studies are needed to understand better the long-term outcome and to prevent the morbidity and mortality associated with ECT in this frail, high-risk older group.     

Parental perceptions of children's communicative development at stuttering onset.

There has been clinical speculation that parents of young stuttering children have expectations of their children's communication abilities that are not well-matched to the children's actual skills. We appraised the language abilities of 15 children close to the onset of stuttering symptoms and 15 age-, sex-, and SES-matched fluent children using an array of standardized tests and spontaneous language sample measures. Parents concurrently completed two parent-report measures of the children's communicative development. Results indicated generally depressed performance on all child speech and language measures by the children who stutter. Parent report was closely attuned to child performance for the stuttering children; parents of nonstuttering children were less accurate in their predictions of children's communicative performance. Implications for clinical advisement to parents of stuttering children are discussed.     

Recognition and management of Kawasaki disease

Kawasaki disease is the leading cause of acquired heart disease in children in the developed world, with coronary artery aneurysms occurring in up to 25% of untreated cases. The mean annual incidence of Kawasaki disease across Canada is about 13 per 100,000 children less than 5 years of age, based on hospital discharge data from 1990 to 1995. The cause remains unknown, and the diagnosis is based on the same clinical criteria used to describe the disease over 30 years ago. However, nonspecific clinical features, evolving presentations and atypical or incomplete presentations make early diagnosis and timely treatment difficult. Delays in diagnosis and treatment, which occur more frequently in older children, are associated with an increased risk of coronary artery aneurysms. Hence, high diagnostic suspicion and prompt referral are required to reduce the rate of cardiac complications.     

Localized scleroderma: Imaging features

Localized scleroderma is distinct from the diffuse form of scleroderma and does not show Raynaud's phenomenon and visceral involvement. The imaging features in 23 patients ranging from 2 to 17 years of age (mean 11.1 years) were reviewed. Leg length discrepancy and muscle atrophy were the most common findings (five patients), with two patients also showing modelling deformity of the fibula. One patient with lower extremity involvement showed abnormal bone marrow signals on MR. Disabling joint contracture requiring orthopedic intervention was noted in one patient. In two patients with en coup de sabre facial deformity, CT and MR scans revealed intracranial calcifications and white matter abnormality in the ipsilateral frontal lobes, with one also showing migrational abnormality. In a third patient, CT revealed white matter abnormality in the ipsilateral parietal lobe. In one patient with progressive facial hemiatrophy, CT and MR scans showed the underlying hypoplastic left maxillary antrum and cheek. Imaging studies of areas of clinical concern revealed positive findings in half our patients.     

Acute hyperthermia following stereotactic radiosurgery for pituitary adenoma

A 71-year-old male presented with a large pituitary adenoma with superior extension into the optic chiasm and suprasellar cistern. He was treated with stereotactic radiosurgery to a dose of 16 Gy. Approximately 1 h after radiosurgery he developed fever; his temperature peaked at 105.1 degrees F and normalized about 20 h later. This case demonstrates that acute hyperthermia is a potential complication following high dose stereotactic radiosurgery for large pituitary tumours.     

Intravitreal gas injection diminishes hyaluronic acid

OBJECTIVES: To determine if compression of the vitreous by an intraocular gas bubble diminishes the concentration of hyaluronic acid (NaHA). MATERIALS AND METHODS: Eighteen albino rabbits had air, xenon or perfluoroethane (C2F6) injected into the vitreous to displace 12.5% to 90% of the vitreous volume. After the gas was absorbed, the vitreous was analyzed for NaHA by the Carbazole method (1, 13). RESULTS: A 90% displacement diminished the NaHA concentration by 18.6%. Lesser displacements caused a lesser loss, but the differences are not significant. CONCLUSION: Intraocular gas injections, both large and small, reduce the concentration of NaHA and destabilize the vitreous structure.     

Inhibition and substrate activity of conformationally rigid vigabatrin analogues with gamma-aminobutyric acid aminotransferase

Several cyclopentene GABA analogues were synthesized as conformationally rigid analogues of the epilepsy drug vigabatrin and tested as inhibitors and substrates of gamma-aminobutyric acid aminotransferase (GABA-AT). None of these compounds produced time-dependent inhibition. (1R, 4S)-(+)-4-Amino-2-cyclopentene-1-carboxylic acid ((+)-3), (4R)-(-)-4-amino-1-cyclopentene-1-carboxylic acid ((-)-4), and d, l-3-amino-1-cyclopentene-1-carboxylic acid (6) are good substrates. The K(m) and k(cat) values for the latter two compounds are very similar to those of GABA, suggesting that they bind in an orientation similar to that of GABA. The K(m) value for (+)-3 is 24 times lower than that for GABA, although its k(cat) value is only one-fourth that for GABA; nonetheless, it is a better substrate for GABA-AT than is GABA. All of these compounds, as well as the enantiomers of 3 and 4 and d, l-trans-4-amino-2-cyclopentene-1-carboxylic acid (5), are competitive inhibitors of GABA-AT. These results demonstrate the effects of the carboxylate group orientation and the stereochemistry of the amino and carboxylate groups on the substrate activity and inhibitor activity, and this should be important to the future design of inhibitors of GABA-AT.     

Cancer in the elderly patient. Unique aspects of presentation, management and screening.

The high incidence of cancer in the rapidly expanding geriatric population presents a major challenge to the health care field. Since most cancers present and behave similarly in both older and younger persons, similar approaches to management must be considered in both. The elderly, however, are a heterogeneous group with individuals demonstrating varying degrees of comorbidity and physiologic change. Decisions, therefore, should be based on a sound knowledge of geriatric assessment and the factors important for "successful" aging rather than on chronological age alone.