Changes with malnutrition in the concentration of plasma vitamin D binding protein in growing rats

The work presented here examines the possible effects of nutritional deficiencies on the characteristics of the plasma transport protein for vitamin D and its metabolites (vitamin D binding protein, DBP) in the growing rat. Deficiencies in both dietary protein intake and dietary energy intake may decrease the concentration of DBP in the circulation, although plasma DBP was not affected by dietary Ca deficiency. None of the dietary factors examined appears to influence the affinity of DBP for its major ligand, 25-hydroxycholecalciferol (25(OH)D(3)). Protein-deficient rats seemed to have difficulty in maintaining adequate concentrations of 1,25-dihydroxycholecalciferol (1,25(OH)(2)D(3)) in the circulation. The sensitivity of DBP to dietary protein and energy intake may constitute a novel mechanism that may help to explain the observed associations between malnutrition and the development of metabolic bone disease, through alterations to the cellular availability of vitamin D ligands to DBP.     

Simultaneous GeneGun immunisation with plasmids encoding antigen and GM-CSF: significant enhancement of murine antivenom IgG1 titres

GeneGun DNA immunisation is a potent means of inducing antibody-dominant immune responses that we are exploiting to generate venom toxin-specific antibodies to improve the therapy of systemic envenoming by snakes. Here, we report that mice immunised with DNA encoding the carboxyl domain (JD9) of a haemorrhagic Zn metalloprotease (Jararhagin) in venom of the South American pit viper, Bothrops jararaca, and a plasmid expressing murine cytokine granulocyte/macrophage-colony stimulating factor (GM-CSF) raised significantly higher antigen-specific IgG1 titres than mice immunised with JD9 DNA alone. Serological responses to GeneGun JD9 DNA immunisation were shown to be dominated by IgG1, an IgG subclass associated with T lymphocyte helper 2 (Th2) immune responses. Further significant enhancement of JD9-specific IgG1 titres was achieved by increasing the number of immunisations. This report illustrates that DNA immunisation protocols to achieve high-titre, venom toxin-specific antibody production are well advanced and encourage the development of a DNA-based approach to antivenom production.     

Mutations of the slow muscle alpha-tropomyosin gene,TPM3, are a rare cause of nemaline myopathy

The alpha-tropomyosin-3 (TPM3) gene was screened in 40 unrelated patients with nemaline myopathy (NM). A single compound heterozygous patient was identified carrying one mutation that converts the stop codon to a serine and a second splicing mutation that is predicted to prevent inclusion of skeletal muscle exon IX. TPM3 mutations are a rare cause of NM, probably accounting for less than 3% of cases. The severity of cases with TPM3 mutations may vary from severe infantile to late childhood onset, slowly progressive forms.     

A quantitative study of fungiform papillae and taste pore density in adults and children

Male children (8-9 years) are reported to have a higher sensitivity than male adults to the sweet tastant sucrose when small regions of the anterior tongue are stimulated. The present study investigated the hypothesis that the higher sensitivity was due to a greater density of fungiform papillae and taste pores (buds), since it has been reported in adults that increased densities of these two structures correlates with increased taste suprathreshold sensitivity [Physiol. Behav. 47 (1990) 1213]. Quantitative measures of the number and size of papillae and pores in two areas of the tongue that had been shown to have a higher sensitivity for sucrose were achieved in 20 male children 8-9 years of age and 20 adults 18-30 years of age, using videomicroscopy and NIH Image software. Customized templates and a red food dye were used to define the equivalent tongue locations across the 40 subjects and taste pores were stained with methylene blue. Children were found to have substantially smaller papillae than adults but significantly higher papilla densities in both areas. Similar numbers of taste pores per papilla were found for both groups, resulting in children having much higher taste pore densities in each area than adults. Other differences included smaller taste pore diameters in children compared to adults, and the papillae tended to be rounder in children. Overall, the results support the hypothesis that the higher densities of fungiform papillae and taste pores in children underlie their greater sensitivity for sucrose in the two areas. In addition, the anatomical differences between adults and children indicate the sense of taste is in a state of development during mid-childhood.     

Screening measurements for sleep apnea: is a single measurement enough?

In patients with sleep apnea syndrome a high night by night variability of the respiratory breathing disturbance was reported in some studies. In the following study the variability of the apnoe-/hypopnoeindex (AHI) was prospectively determined with an ambulant monitoring system. Outpatients were instructed to perform three measurement at home independently. The influence of the variability was determined with respect to a first night effect (FNE), body position, severity of SAS, age and sex of the patients. 19 patients (12 men and 7 women, mean age 51.6 +/- 12.4 years) were investigated. The measurements were done with the ambulatory device Jaeger pro (ViaSys Comp., Wuerzburg). No statistically significant differences of the AHI and the cardiorespiratory parameters between the 3 nights were found (AHI 9.8 +/- 11.7/h, 10.1 +/- 9.6/h vs. 8.5 +/- 9.0/h). However the individual AHI difference was 5,6 +/- 5,0/h. In 15 % of the patients the AHI varied even by more than 10 per h. The variability of the AHI was associated with the severity. No FNE, dependency of body position, sex or age was found. Due to the individual variability of the AHI severity in patients with sleep apnoe syndrome, the severity is underestimated in a considerable number of patients. Repetitive measurements improve the diagnostic power.     

A Spanner in the works: the use of a new temporary urethral stent to relieve bladder outflow obstruction after prostate brachytherapy

PURPOSE: Assessment of the Spanner, a new temporary urethral stent to relieve bladder outflow obstruction and urinary symptoms after brachytherapy. METHODS AND MATERIALS: Five patients with unusually severe urinary morbidity after (125)I brachytherapy were recruited. The mean time after implant was 40 days (range 25-90). Spanner intraprostatic stents were introduced using topical anesthetic without complication. RESULTS: All patients were able to void spontaneously with no post-void residual volume of urine. The flow rates increased in all cases (p=0.03) and the International Prostate Symptom Scores were significantly improved after stent insertion in all patients (p=0.03). All patients experienced some degree of pain or dysuria during stent use. CONCLUSIONS: Bladder outflow obstruction was effectively treated with the Spanner intraprostatic stent, however pain limited the use of the device in the early post-brachytherapy patient group. Pharmacotherapy, stent design modification, or smaller stent diameter may increase the utility of stents after brachytherapy.     

Malignant hyperthermia associated with exercise-induced rhabdomyolysis or congenital abnormalities and a novel RYR1 mutation in New Zealand and Australian pedigrees

Malignant hyperthermia (MH) is rarely associated with specificmyopathies or musculoskeletal abnormalities. Three clinicalinvestigations of MH associated with either non-specific myopathiesor congenital disorders in three separate families are presented.Two of these cases also show evidence of exercise-induced rhabdomyolysis.In each case MH susceptibility was confirmed by in vitro contracturetesting of quadriceps muscle. DNA sequence analysis of eachkindred revealed the presence of a common novel mutation thatresults in an arginine401–cysteine substitution in theskeletal muscle ryanodine receptor gene (RYR1). Haplotype analysisusing chromosome 19q markers indicated that the three familiesare likely to be unrelated, providing confirmation that theMH/central core disease region 1 of RYR1 is a mutation hot spot. Br J Anaesth 2002; 88: 508–15