Pharmaceutics: Comparative Measurement of the Molecular Weight of an Antineoplastic Glucan from BCG Vaccine

Bacillus Calmette-Guérin (BCG) vaccine, developed originally for the prophylaxis of tuberculosis, is a potent immunostimulant used to treat superficial bladder carcinoma in man. The aim of this study was to compare the molecular weight and self-association properties of an antineoplastic glucan (PS1A1) extracted from BCG vaccine as determined by different techniques including diffusion, light-scattering and chromatographic methods. In the diffusion experiments, a semi-empirical relationship was derived between the effective diffusion coefficients, D_p, and the weight-average molecular weights, M_w, of several dextrans used as standards, according to the equation D_p = 2.233 times 10^?6 x M_w^?0.66. On the basis of this relationship, the molecular weight of PS1A1 was found to be 57.4 kDa, although, unexpectedly, membrane association was high, most probably because of molecular branching. In the light-scattering experiment it was observed that, unlike dextran, PS1A1 undergoes concentration-dependent multimerization in water. However, the molecular weight of PS1A1 in 0.1 M sodium chloride ranged from 60 to 68 kDa, with a mean of 65 kDa, over the same concentration range. This value was in agreement with the molecular weight determined for PS1A1 by gel-filtration chromatography in previous studies, suggesting that 65 kDa represents the approximate monomeric size of the unassociated molecule. Thus, it was evident that the aggregation was suppressed by electrolyte. Elemental analysis by X-ray fluorescence showed that PS1A1 contained carbon, oxygen, hydrogen and phosphorus, indicating that hitherto unobserved ionized phosphate groups might promote electrostatic interactions.     

Nephnologists’ and Internal Medicine Physicians’ Expectations of Renal Dietitians and General Dlinical Dietitians

Objective To document and compare nephrologists’ and internal medicine physicians’ expectations of renal dietitians and general clinical dietitians.

Design Subjects completed a mailed survey. Respondents provided demographic information and used a 5-point Likert scale to note whether each of 14 job functions was appropriate for general clinical dietitians, renal dietitians, or both.

Subjects Five hundred forty-one physicians registered with the Ohio State Medical Board (OSMB) were surveyed. Within this group were 283 nephrologists (the population of nephrologists registered with the OSMB) and 258 internal medicine physicians (selected randomly by the OSMB). A total of 133 physicians (25%) returned the survey; 119 surveys were usable: 70 from nephrologists and 49 from internists.

Statistical analyses performed A composite variable was created by coding and summing physicians’ responses regarding dietitian job functions. This variable was averaged for both physician categories. A t test was conducted to compare composite variable results between the two physician groups.

Results At least 50% of nephrologists and internists agreed that both types of dietitians should conduct nutrition assessments, determine patients’ energy needs, evaluate medication-nutrient interactions, recommend diet and tube-feeding orders, instruct patients about physician-ordered diets, and teach nutrition concepts to hospital interns. Few physicians agreed that either type of dietitian should order diets, tube feedings, or diet instructions.

Applications/conclusions Clinical dietitians can educate physicians about dietitians’ roles informally in their institutions and formally by supporting programs like The American Dietetic Association Physician Nutrition Education Program. In addition, dietetics educators can hone their students’ communication and problem-solving skills to promote positive physician-dietitian interaction. J Am Diet Assoc. 1997;97:1389-1393.     

Pyruvate dehydrogenase complex deficiency: four neurological phenotypes with differing pathogenesis

Aim To describe the phenotype and genotype of pyruvate dehydrogenase complex (PDHc) deficiency. Method Twenty‐two participants with enzymologically and genetically confirmed PDHc deficiency were analysed for clinical and imaging features over a 15‐year period. Results Four groups were identified: (1) those with neonatal encephalopathy with lactic acidosis (one male, four females; diagnosis at birth); (2) those with non‐progressive infantile encephalopathy (three males, three females; age at diagnosis 2–9mo); (3) those with Leigh syndrome (eight males; age at diagnosis 1–13mo); and (4) those with relapsing ataxia (three males; 18–30mo). Seventeen mutations involved PDHA1 (a hotspot was identified in exons 6, 7, and 8 in seven males with Leigh syndrome or recurrent ataxia). Mutations in the PDHX gene (five cases) were correlated with non‐progressive encephalopathy and long‐term survival in four cases. Interpretation Two types of neurological involvement were identified. Abnormal prenatal brain development resulted in severe non‐progressive encephalopathy with callosal agenesis, gyration anomalies, microcephaly with intrauterine growth retardation, or dysmorphia in both males and females (12 cases). Acute energy failure in infant life produced basal ganglia lesions with paroxysmal dystonia, neuropathic ataxia due to axonal transport dysfunction, or epilepsy only in males (11 cases). The ketogenic diet improved only paroxysmal dysfunction, providing an additional argument in favour of paroxysmal energy failure.     

Accuracy and Limitations of Published Algorithms Using the Twelve-Lead Electrocardiogram to Localize Overt Atrioventricular Accessory Pathways

INTRODUCTION: The purpose of this study was to evaluate the accuracy and limitations of published algorithms using the 12-lead ECG to localize AV accessory pathways (APs). METHODS AND RESULTS: The 11 relevant algorithms found in the literature (MEDLINE database and major scientific sessions) were tested on a series of 266 consecutive patients who successfully underwent radiofrequency catheter ablation of a single overt AV AP. The positive predictive values (PPV) of the algorithms in applicable patients were significantly lower for algorithms with > 6 accessory location sites (40.6% +/- 10.9% vs 61.2% +/- 8.0%; P < 0.03) and show a tendency for algorithms not relying on delta wave polarity but on QRS polarity only (36.6% +/- 11.2% vs 52.3% +/- 13.1%; P = 0.09). The PPV in applicable patients is related to the AP location (P < 0.001) and ranked from the highest to the lowest as follows: left lateral (mean PPV = 86.3%), posteroseptal (mean PPV = 65.2%), right anteroseptal (mean PPV = 45.2%), and right posterolateral (mean PPV = 23.4%). CONCLUSION: Our study suggests that the accuracy of algorithms relying on the 12-lead ECG depends on AP locations as defined in the algorithms and on the number of AP sites. The accuracy tends to be lower when delta wave polarity is not included in the algorithm's architecture. This should be considered when using these algorithms or when building new ones.     

Characterization of T-cell immune responses of Echinococcus multilocularis-infected C57BL/6J mice

Specific and non-specific parasite-induced changes in lymphocyte responses were analysed in C57BL/6J mice after intrahepatic infection with Echinococcus multilocularis. Spleen cells harvested at selected times after infection were in vitro stimulated with mitogens or a crude soluble parasitic extract (EmAg) at an optimized dose. Cell proliferative responses to Con-A were not modified by the infection over the first 22 weeks. In contrast, LPS-induced responses were decreased from the 13th week. A strong CD4 ⁺ proliferative T-cell response to the parasitic extract of infected mouse spleen cells was observed at the early stage of infection. This response then progressively decreased but remained significantly higher than that of control mice until the 19th week of infection. Cytokine production was investigated after in vitro EmAg stimulation of spleen cells. IFN-γ, IL-2. IL-5 were produced within the first weeks after infection whereas the detection of IL-10 was slightly delayed. Thus, the promotion of the disease does not appear associated with the expansion of one rather than another T-cell subset in C57BL/6J mice. A general immunosuppression affecting both mitogenic and parasite-specific T-cell responses was observed at the end of the infection.     

Visual screening in a school for hearing-impaired children

Hearing-impaired children use vision to compensate for impaired auditory information. This fact, and the relatively high incidence of visual defect among the deaf population, render regular visual screening essential. The Royal School for Deaf Children, Margate, caters for children with a wide range of needs; screening involving a single-assessment structure for all pupils is felt to be inappropriate. This paper describes the implementation of a 'tiered' screening system, and the factors affecting allotment of pupils to particular 'tiers'. The screening structure is illustrated by a case study, and generalization of the system to other educational settings is discussed.     

Leukaemic non-Hodgkin's lymphomas with hyperdiploid cells and t(ll;14)(ql3;q32): a subtype of mantle cell lymphoma?

The present study describes five patients with leukaemic non-Hodgkin's lymphoma (NHL) detected on the basis of particular morphology and cytogenetic findings. With respect to histological, immunological and cytogenetic features these NHL are closely related to mantle cell Iymphoma/intermediate differentiated lymphocytic lymphoma. However, the presence of unusual large cells associated with the t(ll;14)(ql3;q32) translocation and numerical chromosome changes, in the near triploid or near tetraploid range, could delineate a particular subtype of mantle cell lymphoma.     

Therapeutic bronchoalveolar lavage for pulmonary alveolar proteinosis in an infant

A 2-year-old male infant suffering from pulmonary alveolar proteinosis was treated by four unilateral bronchoalveolar lavages (BAL) in a 12-month period. The lavages were performed under general anaesthesia and controlled ventilation by introducing a fibrescope (3.6 mm external diameter) though either a tracheal tube (4.5 mm internal diameter) or a rigid bronchoscope. Each lobe of the lung was successively catheterized and the segments were washed separately with prewarmed saline solution injected through the side channel of the fibrescope. The described technique allows to perform BAL in safe conditions (i.e., controlled airways) in infants weighing more than 9 kg.