Microencapsulated enterotoxigenic Escherichia coli and detached fimbriae for peroral vaccination of pigs

The feasibility of peroral immunisation with microencapsulated Escherichia coli and detached fimbriae to prevent enterotoxigenic E. coli infections in pigs was examined. For this E. coli and fimbriae were microencapsulated into poly(lactide-co-glycolide) microspheres by spray-drying. Various microsphere formulations designed to deliver priming and booster doses were fed to new-born and weaned pigs. The pigs were challenged 19 days after the booster dose by peroral administration of an infective dose of the homologous E. coli. Serum IgA antibody titres and excretion of challenge E. coli, as indicators for colonisation, were determined. The data showed that no significant serum antibodies were induced, and E. coli colonisation was not reduced by the peroral administration of the various antigen-loaded microspheres. These results are in contradiction to some of the previously published experiments typically in rats or rabbits, where model antigens or unpractical immunisation procedures have frequently been used.     

Prognostic factors and results after surgical treatment of idiopathic macular holes, stage 2 and 3

PURPOSE: To determine prognostic factors, functional outcome and subjective rating after surgery for macular holes stage 2 and 3. METHODS: We studied 53 eyes of 49 patients undergoing vitreous surgery for macular holes stage 2 (46%) and 3 (54%). Mean follow-op was 114 weeks (32-204, std.dev. +/- 48), mean age 68.9 years (44-89, std.dev. +/- 6.8). 72% were female, 11% were pseudophakic, 19% phakic, 70% had a combined procedure (pars plana vitrectomy, phacoemulsification and IOL). Surgery consisted in a pars plana vitrectomy, peeling of epiretinal membranes and ILM, internal tamponade with SF6 (98%) resp. Si-oil in one case. Patients had to keep face-down position 6 x 20 minutes per day. RESULTS: The hole was completely closed in 90.6%. Anatomical failures included, 86% had an increase of VA, 41% = 5 lines (Final VA median 20/30, max. 20/20). No further increase of the retinal function occurred after 6 months. The visual result did not correlate with the duration of symptoms. 84% were satisfied with the outcome, subjective rating was not correlated with final VA or change of VA. 19% showed postoperative typical peripheral visual field defects. Visual field loss was not correlated with perioperative IOP elevation. CONCLUSION: Macular hole surgery has a high functional success rate. Postoperative visual field defects are an important problem.     

A clinical evaluation of the hearing disability and handicap scale in men with noise induced hearing loss

During the last 30 years several hearing disability and handicap questionnaires have been designed and used for clinical purposes. The present study includes a review of the most frequently used scales. The aim of the present study was to evaluate the reliability and validity of the Hearing Disability and Handicap Scale (HDHS), which is a shortened and modified version of the Hearing Measurement Scale. Correlations between the Hearing Handicap and Support Scale, the Communication Strategy Scale from the Communication Profile of the Hearing Impaired, pure tone audiometry and speech recognition scores in noise were analysed. Data from 168 men with noise induced hearing loss of different degrees was obtained. Also a test-retest was conducted. The disability section of the HDHS seemed accurate but offered no improvement of prediction compared to previous scales. Even though the reliability of the handicap section was sufficient, its validity and clinical use is discussed and suggestions about improvements given. Since standardised scales are necessary if results are to be compared worldwide, guidelines regarding the clinical use and benefit of hearing disability and handicap scales are required.     

Dopamine D3 and D4 receptor antagonists in the treatment of schizophrenia

The findings that dopamine D3 and D4 receptors are highly expressed in limbic and cortical areas (D4 more than D3), and the fact that the atypical drug clozapine has preferential affinity for the D4 receptors have suggested an involvement of these receptors in schizophrenia. Subsequently, many pharmaceutical companies have pursued the approach of developing selective dopamine D3 or D4 antagonists as potential antipsychotics. This review will discuss the current status of selective dopamine D3 and D4 receptor antagonists for the treatment of schizophrenia.     

Living in the paddies: a social science perspective on how inland valley irrigated rice cultivation affects malaria in Northern Côte d'Ivoire

The potential impact of irrigated agriculture on water‐related vector‐borne diseases has been an increasing source of concern for researchers from the bio‐medical sector. While most research on the potential impacts of irrigation on the health of local populations focuses on vector densities, levels of exposures, health services and technologies (prophylaxis, mosquito nets), we argue that it is essential to enlarge the scope of investigation and consider the complex mechanisms by which factors such as agriculture‐generated changes in ecosystems, gender repositioning in the family organization as a result of access to new crops, and production activities combine together in increasing disease risks and producing new scenarios in the management of disease. This paper presents the results of an investigation of how transformations induced on the local society by the intensification of inland valley irrigated rice cultivation influence malaria health care systems and modulate risks to the health of local populations, within well‐defined geographical boundaries in northern Côte d'Ivoire. Our results indicate that socio‐economic transformations and gender repositioning induced, or facilitated, by the intensification of inland valley irrigated rice cultivation lead to a reduction of the capacity of women to manage disease episodes, contributing therefore to increase malaria incidence among farming populations.     

Cost-utility analysis of patient care in children with meningeal signs

OBJECTIVES: We designed a model of diagnostic and therapeutic interventions applied in children with meningeal signs. Using this model, we determined in a cost-utility analysis the consequences for society of different diagnostic strategies in terms of quality-adjusted life-years (QALYs) and costs. METHODS: Data were used from 360 children (0.1-15 years) visiting the pediatric emergency department of the Sophia Children's Hospital Rotterdam, The Netherlands (1988-98) with meningeal signs. Model inputs included probabilities of meningitis and adverse outcome, QALYs for years lived with long-term sequelae, and costs of tests and treatments. Mean outcome measures were costs and effects of diagnostic and therapeutic interventions in children suspected of bacterial meningitis, key determinants of the model outcomes, and evaluation of alternative diagnostic strategies and two vaccination programs in an analysis. RESULTS: The population comprised 99 children with bacterial meningitis (adverse outcome in 10), 36 with serious other bacterial infections, and 225 with self-limiting diseases. Key determinants were the risk of bacterial meningitis or sequelae, costs of treatment, and long-term morbidity. Minimizing lumbar punctures and empirical treatments using a diagnostic decision rule, without missing a single case of meningitis, was a dominant strategy to actual practice. Vaccination strategies of Streptococcus pneumoniae and Neisseria meningitidis resulted in our model in incremental cost-utility ratios of 401,965 Euro dollar ([symbol: see text])/QALY and [symbol: see text]22,635/QALY, respectively. CONCLUSIONS: Costs of long-term morbidity of bacterial meningitis largely outweigh diagnostic and treatment costs. Modeling interventions in children at risk of bacterial meningitis should include long-term consequences in terms of costs and QALYs.     

Coherent infrared emission from myoglobin crystals: an electric field measurement

We introduce coherent infrared emission interferometry as a chi(2) vibrational spectroscopy technique and apply it to studying the initial dynamics upon photoactivation of myoglobin (Mb). By impulsive excitation (using 11-fs pulses) of a Mb crystal, vibrations that couple to the optical excitation are set in motion coherently. Because of the order in the crystal lattice the coherent oscillations of the different proteins in the crystal that are associated with charge motions give rise to a macroscopic burst of directional multi-teraHertz radiation. This radiation can be detected in a phase-sensitive way by heterodyning with a broad-band reference field. In this way both amplitude and phase of the different vibrations can be obtained. We detected radiation in the 1,000-1,500 cm(-1) frequency region, which contains modes sensitive to the structure of the heme macrocycle, as well as peripheral protein modes. Both in carbonmonoxy-Mb and aquomet-Mb we observed emission from six modes, which were assigned to heme vibrations. The phase factors of the modes contributing to the protein electric field show a remarkable consistency, taking on values that indicate that the dipoles are created "emitting" at t = 0, as one would expect for impulsively activated modes. The few deviations from this behavior in Mb-CO we propose are the result of these modes being sensitive to the photodissociation process and severely disrupted by it.     

Glutathathione synthetase of bovine lens: anomalies of the enzyme-catalyzed formation of ophthalmic acid

The activity of glutathione synthetase from bovine lens was examined as a functions of the concentration of L-gamma-glutamyl-L-alpha-aminobutyrate, the dipeptide substrate required in the formation of ophthalmic acid. Several significant anomalies of the glutathione synthetase-catalyzed formation of ophthalmic acid were found. Curvilinearity of double reciprocal plots occurred with this substrate; this curvilinearity shows substrate activation of the reaction which is likely a result of negative cooperativity. Both ATP4- and, to a lesser extent Mg2+ inhibited the reaction, whereas MgATP2- is the substrate; maximum activity occurred with 2 mM Mg2+ in excess of the concentration of added ATP. This investigation shows that it is necessary to establish a defined set of conditions for reporting enzyme activity and that the usual practice of using very large concentrations of Mg2+ relative to ATP, and 5- to 20-fold excess of the dipeptide will give less than optimum activity. The unit of enzyme activity is suggested to be that activity in ml using 2 mM ATP, 4 mM Mg2+, 30 mM glycine and 15 mM L-gamma-glutamyl-alpha-aminobutyrate, which results in the formation of 1 nmole/minute of ADP or P(i). In this study, 5'-AMP was for the first time, shown to be an inhibitor of the reaction with a K(i) of 0.9 mM.