Respiratory insufficiency in neuronopathic and neuropathic disorders

Twenty-nine patients with a neuronopathic or neuropathic disorder were referred for assessment of respiratory insufficiency between 1978 and 1994. Diagnoses included spinal muscular atrophy (6), chronic idiopathic demyelinating neuropathy (4), Vialetto-van Laere syndrome (3), hereditary motor and sensory neuropathy (3) and a miscellaneous group (5). We also describe seven patients with Guillain-Barre syndrome (GBS) who required long-term ventilatory support for over 6 months to 7 years after the initial illness. Respiratory insufficiency occurred as a consequence of respiratory muscle weakness, impaired bulbar function and restrictive lung defects. In some groups presentation was with progressive nocturnal hypoventilation culminating in acute respiratory failure. Five patients with GBS or chronic idiopathic demyelinating neuropathy were weaned from ventilatory support up to 18 months after the initial illness. The remaining 24 patients required continuous or nocturnal ventilatory support using intermittent positive-pressure ventilation (13), negative pressure ventilation (4), nasal-mask-delivered intermittent positive-pressure ventilation (4), nasal-mask-delivered continuous positive-pressure ventilation (3), mouthpiece-assisted ventilation by day (2) and rocking bed (1). None have been weaned from support after a period of ventilation ranging from one month to 10 years. Eight patients have subsequently died.      

Glycerol-3-phosphate dehydrogenase activity in the red cells of patients with thalassemia

L-alpha-Glycerol-3-phosphate dehydrogenase (EC 1.1.1.8) has been reported to be absent in the erythrocytes of normal adults, but can be found in those of cord blood and of thalassemia major. The aid of this study was to investigate whether there is any relation between GDH and gamma-chain synthesis. Erythrocyte GDH activity was determined on 118 different blood samples. It was undetectable in normal adult erythrocytes and definitely high in cord blood cells (23.6 UI/10(11) RBC). Considerable GDH activity was also noted in patients with thalassemia major (11.0 IU10(11) RBC) as well as in cases with pronounced reticulocytosis (11.4 IU/10(11) RBC). Red cells from beta- thalassemia heterozygotes exhibited moderate but distinct GDH activity (5.2 IU/10(11) RBC). After fractionation into young and old erythrocyte populations, clearly higher GDH activity was found in the younger cells; however, there was no significant correlation with the reticulocyte count. Presence of reticulocytes alone appears insufficient to explain the values obtained in cord blood and the thalassemias, especially heterozygous. Furthermore, no direct correlation between GDH and fetal hemoglobin (HbF) was obtained in cord and thalassemic erythrocytes.     

Visual acuity in an Australian Aboriginal population

Background: Australia is a developed country, However; Aboriginal Australians have rates of blindness comparable to Third World countries. There have been well-funded eye health programs for 15 years in Central Australia. This paper examines if there has been an improvement in visual disability of one traditional group of Aboriginal Australians. Methods: Results from an eye health survey of the Anangu Pitjantjatjara of South Australia in 1990 are presented. These data are compared with results for ‘blindness’ and ‘poor vision’ from a national survey undertaken in 1976. The two surveys were comparable in design, both were cross-sectional population-based prevalence surveys. Prevalence rates were adjusted for the size of the source population. Results: Young rural Aboriginal Australians have good visual acuity. Low vision and blindness (WHO definitions) occur in 19.6% and 10.4% of 60+ year olds, respectively. Women were more likely than men to be blind or have low vision (OR= 1.93; 1.06-3.58). There was a decline in ‘poor vision’ between surveys (OR=2.86; 1.86-4.75) but not in ‘blindness’. Conclusion: Although there has been a reduction in the prevalence of visual disability in rural Aboriginal Australians, improvements in the provision of eye care for the elderly need to occur.     

Long-term renal allograft function under maintenance immunosuppression with cyclosporin A or azathioprine: A single center, five-year follow-up study

Abstract. In order to evaluate long-term renal graft function, 149 cyclosporin A and prednisolone (CyA/P)-treated renal transplant recipients were compared with 119 azathioprine and prednisolone (Aza/P)-treated patients. Only patients who had a functioning graft for at least 1 year and who were maintained on their initial immunosuppressive protocol were included. The minimum follow-up period was 4 years. Renal graft function was estimated by yearly determinations of serum creatinine and creatinine clearance. The CyA/P-treated patients had a significantly higher serum creatinine and a significantly lower creatinine clearance at every point in time post-transplantation than Aza/P-treated patients ( P < 0.001). The evolution of renal graft function, as reflected in the line of regression for serum creatinine and creatinine clearance versus time, was estimated for each individual patient. There was an almost stable renal function, as assessed by the median of the slopes of the regression line for serum creatinine versus time in both groups. The median increase in serum creatinine was only 1.4 μmol/l per year for Aza/P-treated patients and 2.4 μmol/l per year for CyA/P-treated patients (difference NS). The median decline in creatinine clearance was 2.18 ml/min per 1.73 m²/year in the Aza/P group and 1.07 ml/min per 1.73 m²/year in the CyA/P group ( P = 0.05). In patients with a functioning graft for at least 5 years, creatinine clearance remained unchanged in both groups during the study period. In conclusion, renal graft function, as assessed by measurements of serum creatinine and creatinine clearance, remained essentially unchanged for at least 5 years after transplantation, regardless of the immunosuppressive protocol used. Thus, these data do not indicate a progression with time of the nephrotoxicity observed in CyA-treated patients.     

Induction of CD4(+) T cell-dependent antitumor immunity by TAT-mediated tumor antigen delivery into dendritic cells

Dendritic cell-based (DC-based) immunotherapy represents a promising approach to the prevention and treatment of many diseases, including cancer, but current strategies have met with only limited success in clinical and preclinical studies. Previous studies have demonstrated that a TAT peptide derived from the HIV TAT protein has the ability to transduce peptides or proteins into various cells. Here, we describe the use of TAT-mediated delivery of T cell peptides into DCs to prolong antigen presentation and enhance T cell responses. While immunization of mice with DCs pulsed with an antigenic peptide derived from the human TRP2 protein generated partial protective immunity against B16 tumor, immunization with DCs loaded with a TAT-TRP2 peptide resulted in complete protective immunity, as well as significant inhibition of lung metastases in a 3-day tumor model. Although both DC/TRP2 and DC/TAT-TRP2 immunization increased the number of TRP2-specific CD8(+) T cells detected by K(b)/TRP2 tetramers, T cell activity elicited by DC/TAT-TRP2 was three- to tenfold higher than that induced by DC/TRP2. Furthermore, both CD4(+) and CD8(+) T cells were required for antitumor immunity demonstrated by experiments with antibody depletion of subsets of T cells, as well as with various knockout mice. These results suggest that a TAT-mediated antigen delivery system may have important clinical applications for cancer therapy.