Causes of blindness in children attending four schools for the blind in Thailand and the Philippines

Using WHO definitions of visual loss and a standardised methodology, 256 children were examined in schools for the blind in Thailand (1 school) and the Philippines (3 schools). 244 (95%) were blind (BL) or severely visually impaired (SVI). Causes of SVI and blindness were classified anatomically and aetiologically, and avoidable causes identified. Causes of visual loss in Khon Kaen, Thailand (n = 65) and Manila, Philippines, (n = 113) were similar, with conditions of the whole globe accounting for 27.7 and 27.4% of SVI/BL; retinal disease 29.2 and 23.0%; cataract 16.9 and 16.8%; corneal disease 12.3 and 13.4%; and optic nerve disease and glaucoma 6.2 and 8.8%. Perinatal factors accounted for 20.0 and 23.0% of SVI/BL; hereditary disease 13.8 and 17.7%; and 12.3 and 15.0% was due to events occurring during childhood. The underlying aetiology could not be determined in 50.8 and 41.6% of cases, respectively. In the two schools together twenty six children (15%) were blind from retinopathy of prematurity (ROP) and 16 (9%) from corneal scarring attributed to Vitamin A deficiency. 103 of 178 (58%) children had avoidable causes of visual loss. In the Filipino towns of Baguio and Davao (n = 66), the causes of visual loss were different from those in Khon Kaen and Manila, with 54.8 and 42.9% of SVI/BL being due to corneal disease, and only 3.2 and 8.5% to retinal disease. Childhood factors were more important (61.3 and 57.1%) than hereditary (9.7 and 17.1%) or perinatal factors (0 and 2.9%). Thirty one children (47%) had SVI/BL attributed to Vitamin A deficiency. No child was blind from ROP. 42 of 66 (64%) of children had avoidable causes of blindness. Overall 60% of children with SVI/BL had avoidable causes of visual loss in these 4 schools. Approximately half could have been prevented by primary health and eye care services and half could have been managed by surgical ophthalmological procedures. The causes of blindness identified in this blind school study suggest that the major causes are different for schools serving rural populations compared to those serving urban communities. Different control strategies are required for the different situations.     

Extracorporeal membrane oxygenation (ECMO) as lung or heart assist

Extracorporeal membrane oxygenation (ECMO) may serve as extracorporeal lung assist (ECLA) in patients with acute respiratory failure (ARF) or as extracorporeal heart assist (ECHA) in patients with low output syndrome (LOS) after open heart surgery. From 1988 to 1992 seven patients underwent ECMO in our hospital; four suffered from ARF and three from LOS. Various bypass techniques were employed. Two ARF patients, aged 58 and 18 years, had veno-venous bypass; in the latter, ECMO was reinstituted as a veno-arterial bypass one week after weaning. In a three-year-old boy, the ECMO outflow tubing was primarily connected to the pulmonary artery, and shortly afterwards relocated to the common carotid artery. In a 31-year-old man with ARF, and three LOS patients, a 56-year-old woman, and two men aged 68 and 70 years, ECMO was veno-arterial with direct access to the ascending aorta. A heparin-coated system was used, and all but one patient, who was treated with warfarin, received a daily low dose of heparin, which was withdrawn after from one to nine days.
Six patients were weaned off ECMO after 4.5 to 21 days. Three ARF patients recovered completely; the child died. In one LOS patient, ECMO was withdrawn due to a poor general condition. Two others were weaned off ECMO and the intra-aortic balloon pump, and the inotropic support was significantly reduced, but both died of multiple system organ failure. Although no firm conclusions can be drawn from these few case reports, the heparin-coated system used as ECLA appears promising, whereas ECHA seems to imply a poor prognosis in patients who are not candidates for cardiac transplantation.     

A complementarity-determining region peptide of an anti-desmosome autoantibody may interact with the desmosomal plaque through molecular mimicry with a cytoplasmic desmoglein 1 sequence

The sera of patients with pemphigus, a group of autoimmune blistering skin diseases, contain autoantibodies directed against components of adhering junctions termed desmosomes. F12, a human monoclonal antibody derived from a pemphigus patient, recognizes an unknown polypeptide of the desmosomal and hemidesmosomal plaques. The third complementarity-determining region of the F12 heavy chain (VH-CDR3) was shown to share a four-amino-acid sequence (GSSG) with the intracellular domains of desmoglein 1 and bullous pemphigoid antigen 2 which interact with components of, respectively, the desmosomal and hemidesmosomal plaques. Computer modeling of F12 showed that the GSSG sequence protudes inside the antigen-combining site and thus might be involved in antigen interactions. The GSSG sequence is essential to F12 function, since a peptide containing the VH-CDR3 inhibited its binding to target antigens while VH-CDR3 peptides with specific modifications of the GSSG sequence did not. These data allow us to hypothesize that certain autoantibodies produced during the course of an autoimmune disease can behave as adhesion molecules, through the molecular mimicry of the motif involved in protein/protein adhesion, and to propose a new self-antigen binding mechanism for some autoantibodies.     

Increased risk of pneumococcal infections in cardiac transplant recipients

We observed 5 episodes of pneumococcal infection among 129 cardiac transplant patients between March 1985 and December 1987, giving an estimated incidence of 36 cases per 1000 patient-years. Infections occurred a mean of 58 days after transplantation and included bacteremia with empyema, bacteremia alone, and pneumonia. All patients recovered from their infections. There was no correlation between infection and age, sex, immunosuppression, or rejection episodes. We also measured antibody levels to 12 pneumococcal antigens in 6 unvaccinated, uninfected patients before and after cardiac transplantation, to see if baseline antibody levels decreased. Protective levels of antibody were defined as greater than or equal to 300 ng of anticapsular antibody nitrogen per milliliter serum. Before transplantation patients had protective antibody levels to a mean of 8.7 +/- 1.2 pneumococcal serotypes; after transplantation, the number of presumably protective antibody levels decreased to 6.5 +/- 1.4 (P = 0.021). One of these patients subsequently developed pneumococcal pneumonia. Cardiac transplant patients are at increased risk of pneumococcal infections. Vaccinating transplant candidates prior to transplantation may provide protection after transplantation.     

Identification and characterization of insulin receptors in basolateral membranes of dog intestinal mucosa

Little is known about hormonal regulation of substrate transport and metabolism in the mucosal lining of the small intestine. Because insulin regulates these functions in other tissues by binding to its receptor, we have investigated the presence of insulin receptors in canine small intestinal mucosa with basolateral membranes (BLM) and brush border membranes (BBM) prepared by sorbitol density centrifugation. A14-[125I]iodoinsulin was used to study binding and structural characteristics of specific insulin receptors in BLM. Analysis of receptors in BLM identified binding sites with high affinity (Kd 88 pM) and low capacity (0.4 pmol/mg protein) as well as with low affinity (Kd 36 nM) and high capacity (4.7 pmol/mg protein). Binding was time, temperature, and pH dependent, and 125I-labeled insulin dissociation was enhanced in the presence of unlabeled insulin. Cross-reactivity of these receptors to proinsulin, IGF-II, and IGF-I was 4, 1.8, and less than 1%, respectively. Covalent cross-linking of labeled insulin to BLM insulin receptors with disuccinimidyl suberate revealed a single 135,000-Mr band that was completely inhibited by unlabeled insulin. There was a 16-fold greater specific binding of insulin to BLM (39.0 +/- 2.4%) than to BBM (2.5 +/- 0.6%). These results demonstrate the presence of a highly specific receptor for insulin on the vascular, but not the luminal, surface of the small intestinal mucosa in dogs, and suggest that insulin may play an important role in the regulation of gastrointestinal physiology.     

The effect of apical foramen patency on condensation stresses

Abstract Mathematical models and computer-based engineering tools were used to evaluate the effect of a patent or closed apical foramen on stresses that are produced within gutta-percha during condensation. We examined a mathematical model of a tapered canal with a definite constriction and compared the results when the apical foramen was closed or open. When the canal was closed an almost constant stress was seen throughout the gutta-percha. When the foramen was open a sharp increase in lateral stress was observed in the apical portions of the canal. The constriction near the foramen caused the gutta-percha to be squeezed together and the stress was increased. This increases the likelihood that the gutta-percha is well adapted to the apical constriction. However, the stresses are also transferred to the surrounding dentin, resulting in a stress concentration near the apical foramen where the bulk of dentin is minimal.     

Pyrethroids and enhanced inhibition in the hippocampus of the rat

The pyrethroid insecticides have been divided into two classes on the basis of their biochemical actions and behavioral indices of toxicity. Both types of pyrethroids have effects on sodium conductance, and Type II pyrethroids have been reported to antagonize gamma-aminobutyric acid (GABA) by interacting with the t-butyl-bicyclophosphorothionate (TBPS)/picrotoxinin binding site. The dentate gyrus of the hippocampus is equipped with GABAergic recurrent inhibitory circuits. The present experiment was designed to demonstrate dissociation in the biochemistry of pyrethroids by activating the perforant path with pairs of stimulus pulses and monitoring the recurrent inhibition in this circuit. Antagonism of GABA leads to a reduction in inhibition, measured as an increase in the size of the population spike in response to the second pulse of the pair. The GABAergic properties of the pyrethroids were assessed by examining paired pulse inhibition before and after oral treatment with 20 mg/kg of cismethrin (Type I), 20 mg/kg of fenvalerate, or 10 mg/kg of deltamethrin (Type IIs). Input/output (I/O) functions revealed a reduction in excitatory postsynaptic potential (EPSP) following cismethrin and deltamethrin. Population spike height was unaffected. Fenvalerate had no effect on I/O functions. In contrast to the prediction of reduced inhibition following treatment with Type II pyrethroids, deltamethrin and fenvalerate increased inhibition up to 500 and 150 ms interpulse intervals, respectively. Cismethrin was without effect on paired pulse inhibition. These findings fail to provide evidence of GABA antagonistic properties of Type II pyrethroids and may be best explained by a differential effect of these three pyrethroids on sodium channel kinetics.     

Stereoselective disposition of (+/-)-sotalol at steady-state conditions.

The objective of this study was to assess, under steady-state conditions, the stereoselective disposition of (+/-)-sotalol in man. In all patients studied (n = 7) values of oral clearance (137 +/- 51 ml min-1), renal clearance (96 +/- 42 ml min-1) and nonrenal clearance (41 +/- 25 ml min-1) of (-)-sotalol were greater than those for (+)-sotalol (123 +/- 45 ml min-1, 89 +/- 39 ml min-1 and 34 +/- 23 ml min-1, respectively; P < 0.05, Student's paired t-test). Binding to plasma proteins was greater for (+)-sotalol (38 +/- 9% vs 35 +/- 9% for the (-)-enantiomer; P < 0.05) such that unbound oral clearance (+)/(-) ratio (0.95 +/- 0.06) and unbound renal clearance (+)/(-) ratio (0.97 +/- 0.06) were not stereoselective. In contrast, estimated unbound nonrenal clearance, which represents approximately 25% of the total unbound clearance of the drug, was greater for the (-)-enantiomer (64 +/- 42 ml min-1) compared with (+)-sotalol (57 +/- 42 ml min-1; P < 0.05). The difference in the pharmacokinetics of sotalol enantiomers is mainly related to stereoselectivity in plasma protein binding.