7q11.23 microduplication syndrome: neurophysiological and neuroradiological insights into a rare chromosomal disorder.

BACKGROUND: The phenotypical consequence of the heterozygous chromosome 7q11.23 interstitial microdeletion is the Williams-Beuren syndrome, a very well-known genetic multi-systemic disorder. Much less is known about the reverse condition, the heterozygous interstitial microduplication of 7q11.23 region. The first molecular cytogenetic description was published in 2005, and only after several years were the reported patients numerous enough to attempt a description of a common phenotype. METHOD: By using a broad multidisciplinary approach, we investigated 12 patients with this rare genetic anomaly. Ten of them harboured the duplication of the classical Williams-Beuren syndrome region and two a slightly larger duplication. Upon a detailed description of the clinical and psychological features, we used electroencephalography and magnetic resonance imaging to explore neurophysiological function and brain structures. RESULTS: We analysed the clinical, psychological, neuroradiological and neurophysiological features of 12 yet-unpublished individuals affected by this rare genetic anomaly, focusing specifically on the last two aspects. Several structural abnormalities of the central nervous system were detected, like ventriculomegaly, hypotrophic cerebellum, hypotrophic corpus callosum and hypoplastic temporal lobes. Although only one of 12 individuals suffered from seizures during childhood, three others had abnormal electroencephalography findings prominent in the anterior brain regions, without any visible seizures to date. CONCLUSION: Taken together, we enlarged the yet-underrepresented cohort in the literature of patients affected by 7q11.23 microduplication syndrome and shed further light on neuroradiological and neurophysiological aspects of this rare genetic syndrome.

LC-MS/MS-based quantification of cholesterol and related metabolites in dried blood for the screening of inborn errors of sterol metabolism.

Smith-Lemli-Opitz syndrome (SLOS) is an inherited metabolic disease in the cholesterol biosynthesis pathway which is characterised by accumulation of 7- and 8-dehydrocholesterol and by reduced cholesterol concentrations in all tissues and body fluids. With this study, we developed a new, rapid, robust and high-throughput tandem mass spectrometric method as routine application for the selective SLOS screening and therapy monitoring in serum and dried blood. After protein precipitation of 10 µL serum or 4.7 mm dried blood spot, the sum of 7- and 8-dehydrocholesterol (DHC) was analysed by rapid chromatography combined with tandem mass spectrometry. Method comparison with GC-MS was performed for 46 serum samples. A comparison between serum and corresponding dried blood spots for DHC and cholesterol was performed with 40 samples from SLOS patients. Concentrations of DHC and cholesterol were analysed in 2 dried blood samples from newborns with SLOS and 100 unaffected newborns. Intra- and inter-assay variabilities ranged between 3.7 and 17.7% for serum and dried blood spots. Significant correlations between the new LC-MS/MS method and GC-MS were determined for DHC (r = 0.937, p < 0.001) and for cholesterol (r = 0.946, p < 0.001). Significant coefficients of correlation between serum and dried blood spot samples above 0.8 were calculated for both analytes. A cut-off value of 5.95 for the ratio of DHC/cholesterol (multiplied by 1000) was found to distinguish newborns diagnosed with SLOS from normal newborns in a retrospective analysis after 5 years. The developed method enables a rapid quantification of the sum parameter 7- and 8-DHC in newborns and SLOS patients under therapy in serum as well as dried blood spot samples.

Evaluation of early hearing damage in personal listening device users using extended high-frequency audiometry and otoacoustic emissions.

Although sound exposure from personal listening devices (PLDs) could potentially lead to noise-induced hearing loss (NIHL), the actual hearing risk associated with the use of these devices is still unclear. In this study, early hearing effects related to PLD usage were evaluated in 35 young adult PLD users (listening for >1 h/day, at >50% of the maximum volume setting of their devices) and their age- and sex-matched controls using a combination of conventional and extended high-frequency audiometry as well as transient-evoked otoacoustic emission (TEOAE) and distortion product of otoacoustic emission (DPOAE) measurements. The mean listening duration of the PLD users was 2.7 ± 1.0 h/day while their estimated average listening volume was 81.3 ± 9.0 dBA (free-field corrected). Typical signs of NIHL were not detected in the audiogram of PLD users and their audiometric thresholds at most of the conventional test frequencies (0.25-8 kHz) were comparable with those obtained from controls. However, compared with the controls, mean hearing thresholds of PLD users at many of the extended high-frequencies (9-16 kHz) were significantly higher. In addition, TEOAE and DPOAE amplitudes in users were reduced compared with controls. The deterioration of extended high-frequency thresholds and the decrease in DPOAE amplitudes were more evident in the users' right ears. These results indicate the presence of an early stage of hearing damage in the PLD user group. Preventive steps should be taken as the initial hearing damage in these users could eventually progress into permanent NIHL after many years of PLD use.

Hearing risk associated with the usage of personal listening devices among urban high school students in Malaysia.

OBJECTIVES: To investigate listening habits and hearing risks associated with the use of personal listening devices among urban high school students in Malaysia. STUDY DESIGN: Cross-sectional, descriptive study. METHODS: In total, 177 personal listening device users (13-16 years old) were interviewed to elicit their listening habits (e.g. listening duration, volume setting) and symptoms of hearing loss. Their listening levels were also determined by asking them to set their usual listening volume on an Apple iPod TM playing a pre-selected song. The iPod's sound output was measured with an artificial ear connected to a sound level meter. Subjects also underwent pure tone audiometry to ascertain their hearing thresholds at standard frequencies (0.5-8 kHz) and extended high frequencies (9-16 kHz). RESULTS: The mean measured listening level and listening duration for all subjects were 72.2 dBA and 1.2 h/day, respectively. Their self-reported listening levels were highly correlated with the measured levels (P < 0.001). Subjects who listened at higher volumes also tend to listen for longer durations (P = 0.012). Male subjects listened at a significantly higher volume than female subjects (P = 0.008). When sound exposure levels were compared with the recommended occupational noise exposure limit, 4.5% of subjects were found to be listening at levels which require mandatory hearing protection in the occupational setting. Hearing loss (≥25 dB hearing level at one or more standard test frequencies) was detected in 7.3% of subjects. Subjects' sound exposure levels from the devices were positively correlated with their hearing thresholds at two of the extended high frequencies (11.2 and 14 kHz), which could indicate an early stage of noise-induced hearing loss. CONCLUSIONS: Although the average high school student listened at safe levels, a small percentage of listeners were exposed to harmful sound levels. Preventive measures are needed to avoid permanent hearing damage in high-risk listeners.

Prevalence of human papilloma virus with risk of cervical cancer among south Indian women: A genotypic study with meta-analysis and molecular dynamics of HPV E6 oncoprotein.

Cervical cancer (CC) is a major fatal health problem in women with high mortality worldwide. Human Papilloma Virus (HPV) is considered as one of the causative factors for CC. The HPV prevalence and their genotype distribution among women population are essential to evaluate the deteriorating impact of HPV. A cross-sectional study was performed involving 212 participants to identify the prevalence of high-risk HPV genotypes in south India using PCR and DNA Sequencing. The results obtained from cross-sectional study were used to conduct a meta-analysis of the previous published studies on HPV prevalence and genotype distribution across six geographical regions (North, Northeast, East, Central, West, and South) of India. Additionally, molecular simulation was performed using GROMACS software to determine the structural differences of E6 oncoprotein in HPV-16 and 18 genotypes, characterized from Indian subjects. Among the study participants, the HPV prevalence was found to be 81.70% in CC, 71.42% in HSIL and 61.30% in LSIL. The meta-analysis showed a high prevalence of HPV-16 in CC across the entire six regions. Of which, South and North India were found to have high HPV prevalence among Indian regions. Further, simulation of E6 oncoprotein revealed structural differences between HPV-16 and 18 which may be associated with their oncogenic nature. The HPV-16 and 18 were noticed to be highly prevalent in Indian women. Health awareness and vaccination programs are regularly needed to protect Indian women community.

Efficient nonviral transfection of dendritic cells and their use for in vivo immunization.

Immunization with dendritic cells (DCs) transfected with genes encoding tumor-associated antigens (TAAs) is a highly promising approach to cancer immunotherapy. We have developed a system, using complexes of plasmid DNA expression constructs with the cationic peptide CL22, that transfects human monocyte-derived DCs much more efficiently than alternative nonviral agents. After CL22 transfection, DCs expressing antigens stimulated autologous T cells in vitro and elicited primary immune responses in syngeneic mice, in an antigen-specific manner. Injection of CL22-transfected DCs expressing a TAA, but not DCs pulsed with a TAA-derived peptide, protected mice from lethal challenge with tumor cells in an aggressive model of melanoma. The CL22 system is a fast and efficient alternative to viral vectors for engineering DCs for use in immunotherapy and research.

Genetic predisposition of IL-10 promoter polymorphisms with risk of multiple sclerosis: A meta-analysis.

Interleukin-10 (IL-10) is a anti-inflammatory cytokine, which controls inflammation by inhibiting the synthesis of several cytokines produced by Th1 cells and macrophages. The association between Interleukin-10 promoter polymorphisms with the risk of multiple sclerosis (MS) remains inconclusive. In this study, a meta-analysis has been performed to assess the relationship between IL-10 gene polymorphisms rs1800896, rs1800871 and rs1800872 with the risk of MS. Nine case-control studies were selected involving 2755 participants. The association between the polymorphisms and MS was examined by the pooled odds ratios (ORs) with 95% confidence intervals (CIs) in allelic, homozygote, heterozygote, dominant and recessive genetic models. Of analyzed genetic models, the pooled ORs and CIs of each SNPs calculated based on random (I2>50) or fixed effects (I2<50) methods, which showed no significant association (p-value>0.05) of genetic predisposition with MS susceptibility across Asian and Caucasian populations. In addition, assessment based on funnel plot and Egger's linear regression test suggests no publication bias in all analyzed genetic models. Overall, our results demonstrated that rs1800896, rs1800871 and rs1800872 polymorphisms may not be the risk factor for the development of MS in both the populations.

PSEN1 gene polymorphisms in Caucasian Alzheimer's disease: A meta-analysis.

BACKGROUND: A meta-analysis was performed to assess PSEN1 gene polymorphisms (rs1800839 and rs17125721) in Alzheimer's disease (AD) risk. METHODS: A systematic electronic search was performed across databases to retrieve studies published before 31 January 2017. The association between the selected PSEN1 polymorphisms and AD was based on five genetic models using DerSimonian and Laird's method or Mantel-Haenszel's method. RESULTS: A total of 14 case-controlled studies were included. Results showed that rs1800839 polymorphism was significantly associated with AD in allelic OR=0.85 (95% CI [0.72-1.00]) and dominant OR=0.82 (95% CI [0.69-0.98]) genetic models, respectively. However, an insignificant association was found for rs17125721 polymorphism in all genetic models. CONCLUSIONS: Meta-analysis of PSEN1 gene suggests that the rs1800839 polymorphism has potential influence on AD among Caucasians.

Association Between NOS1 Gene Polymorphisms and Schizophrenia in Asian and Caucasian Populations: A Meta-Analysis.

Schizophrenia is a complex psychiatric disorder characterized by memory impairments with delusions and hallucinations. Several investigations have focused on determining the association between NOS1 (nitric oxide synthase-1) polymorphisms and risk of schizophrenia (SZ). However, the association of rs2682826, rs3782206, rs499776, rs3782219, rs41279104, rs3782221, rs1879417, rs4767540, rs561712, and rs6490121 polymorphisms with schizophrenia remains inconclusive. We performed a systematic meta-analysis for each polymorphism to determine its association with SZ by calculating their pooled odds ratio and 95% confidence intervals. The heterogeneity between studies was evaluated using Cochran's Q test to adopt random effects or fixed effects model. Based on our analysis, the rs3782206 polymorphism showed a strongest association with schizophrenia in allelic OR 1.15 (95% CI [1.05-1.25]), homozygote OR 1.35 (95% CI [1.09-1.66]), dominant OR 1.16 (95% CI [1.04-1.29]), and recessive OR 1.29 (95% CI [1.05-1.58]) models in Asian population. Similarly, in Caucasian population, the rs499776 polymorphism attributes risk association in homozygote OR 0.70 (95% CI [0.50-0.98]), dominant OR 3.57 (95% CI [2.34-5.27]), and recessive models OR 0.68 (95% CI [0.50-0.93]) with schizophrenia. Further, the sensitivity analysis was carried out based on leave-one-out method to confirm the reliability of the analysis. Overall, our meta-analysis demonstrates the significance of NOS1 genetic variants that are functionally associated with cognitive and neuropsychiatric symptoms of schizophrenia.

Visual acuity after acute primary angle closure and considerations for primary lens extraction.

BACKGROUND/AIM: Primary lens extraction has been advocated for acute primary angle closure (APAC), but it is not known if this is warranted in all cases. The aim of this study was to investigate the visual acuity (VA) of APAC eyes shortly after resolution of the acute episode in order to assess the appropriateness of performing such surgery in this condition. METHODS: This was a prospective observational case series. As part of a randomised controlled trial comparing phacoemulsification and laser iridotomy, 135 consecutive APAC subjects over a 2 year period underwent subjective refraction and measurement of Snellen VA once the acute episode had resolved with reduction of intraocular pressure (IOP) and improved corneal clarity. RESULTS: Subjects were predominantly Chinese (95.6%) and female (79.3%), with a mean age of 63.6 (SD 9.6) years. When assessed 1.7 (2.7) days after presentation, the majority of APAC cases (50.4%) had good VA (6/12 or better), with more than a quarter of cases having VA of 6/7.5 or better. Poor VA was associated with duration of symptoms (p = 0.04, OR = 4.1, 95% CI 1.1 to 15.7) and time taken to resolution of APAC (p = 0.04, OR = 2.2, 95% CI 1.02 to 4.6), but not with sex (p = 0.31), age (p = 0.26), duration from presentation to measurement of visual acuity (p = 0.53), or presenting IOP (p = 0.73). CONCLUSION: Within days after APAC, more than half of APAC affected eyes had good VA (6/12 or better). The role of lens extraction in the management of APAC warrants further debate, especially for eyes with good VA.

Association between MDR1 gene polymorphisms and Parkinson's disease in Asian and Caucasian populations: a meta-analysis.

Parkinson's disease (PD) is a complex neurodegenerative disease, its etiology is largely unknown. Studies demonstrate the association of genetic and environment factors in causing neuronal degeneration. Reports suggest that the multi-drug resistance gene (MDR1) plays a vital role in preventing the toxic substance in entering the brain, which is associated with PD. However, the association between the MDR1 polymorphisms (C1236T and C3435T) and its susceptibility to PD is inconclusive. Meta analysis was carried by retrieving literatures from databases to search the case-control studies on the associations between the MRD1 polymorphisms and PD. The pooled odds ratios (ORs) and its 95% confidence intervals (CIs) were calculated using fixed and random model to determine the association between the polymorphisms and PD susceptibility. Significant association was noticed for C1236T polymorphism and PD risk in the recessive model OR=0.80, 95% CI=0.66-0.97. Further, ethnicity based analysis showed significant association for C1236T in allelic model of Asian population and also in the recessive models of both Asian and Caucasian populations. However, insignificant associations were noticed for C3435T in all the four models. Overall, the analysis suggested that MDR1 C1236T polymorphism substantially contribute to Parkinson's disease in the recessive genetic model.

Choroidal expansion as a mechanism for acute primary angle closure: an investigation into the change of biometric parameters in the first 2 weeks.

BACKGROUND/AIM: Choroidal expansion with anterior movement of the lens was recently proposed as a mechanism for acute primary angle closure (APAC). The aim of this study was to compare the biometric parameters, central anterior chamber depth, limbal chamber depth, lens thickness, and lens position, within 24 hours of presentation and 2 weeks later in eyes with APAC. METHODS: This was a prospective observational case series of 41 subjects with APAC. Subjects who presented with APAC were treated with medical therapy followed by laser iridotomy (LI) in both eyes once the acute attack was broken. Ocular biometry was performed in affected and fellow eyes before LI (baseline) and then 2 weeks later. Optical pachymetry was used to measure central anterior chamber depth (ACD) and the limbal chamber depth (LCD) was graded at the slit lamp. A-scan ultrasound was used to measure lens thickness (LT) and axial length (AL). Lens position (LP) was defined as ACD +(1/2)LT. RESULTS: The majority of subjects were Chinese (83%) and female (61%), and the mean age was 60.4 (SD 10.3) years. In affected eyes, the ACD was 1.81 (0.29) mm before and 1.80 (0.28) mm 2 weeks after LI (p = 0.63), while in fellow eyes, the ACD was 1.83 (0.29) mm and 1.81 (0.38) mm, respectively (p = 0.21). There was no significant change in lens position, relative lens position, or axial length in both affected and fellow eyes over the 2 weeks. CONCLUSIONS: There was no change observed in central anterior chamber depth, lens thickness, or lens position at the time of the acute attack compared to 2 weeks later in both APAC affected and fellow eyes. The findings do not support the hypothesis of lens movement due to choroidal expansion in APAC.

Global Variation of Human Papillomavirus Genotypes and Selected Genes Involved in Cervical Malignancies.

BACKGROUND: Carcinoma of the cervix is ranked second among the top 5 cancers affecting women globally. Parallel to other cancers, it is also a complex disease involving numerous factors such as human papillomavirus (HPV) infection followed by the activity of oncogenes and environmental factors. The incidence rate of the disease remains high in developing countries due to lack of awareness, followed by mass screening programs, various socioeconomic issues, and low usage of preventive vaccines. Over the past 3 decades, extensive research has taken place in cervical malignancy to elucidate the role of host genes in the pathogenesis of the disease, yet it remains one of the most prevalent diseases. It is imperative that recent genome-wide techniques be used to determine whether carcinogenesis of oncogenes is associated with cervical cancer at the molecular level and to translate that knowledge into developing diagnostic and therapeutic tools. OBJECTIVE: The aim of this study was to discuss HPV predominance with their genotype distribution worldwide, and in India, as well as to discuss the newly identified oncogenes related to cervical cancer in current scenario. FINDINGS: Using data from various databases and robust technologies, oncogenes associated with cervical malignancies were identified and are explained in concise manner. CONCLUSION: Due to the advent of recent technologies, new candidate genes are explored and can be used as precise biomarkers for screening and developing drug targets.

Restoration of trimethyltin induced hippocampal degeneration by single and multiple transplantation.

Trimethyltin produces a selective loss of pyramidal neurons in the hippocampus resulting in functional deficits. The present study was aimed to assess the comparative restoration of behavioural and neurochemical deficits in trimethyltin chloride (7.5 mg/Kg body weight, i.p) treated rats following single or multiple site fetal hippocampal transplants. Exposure to trimethyltin caused a decrease in learning ability (51 %), an increase in locomotor activity (92 %) and decrease in acetylcholinesterase activity (36%) and muscarinic receptor binding (31%). Trimethyltin treated rats receiving multiple transplants of fetal hippocampal cell suspension (0.25 µl at 8 stereotaxic coordinates) showed significant restoration of the functional deficits 4 weeks post transplantation. This restoration by multiple site transplants persisted upto 16 weeks post transplantation. Restoration of the above deficits by single site transplants (2 µl at a single coordinate), 4 weeks post transplantation was less marked in comparison to multiple transplants and was evident only in learning ability and muscarinic receptor binding after 16 weeks of transplantation. The results suggest that multiple site transplants provide better restoration , on long term basis, in chemical induced neurodegeneration.

Neurobehavioral, neurochemical and electrophysiological studies in 6-hydroxydopamine lesioned and neural transplanted rats.

Unilateral injection of 6-hydroxydopamine (6-OHDA) into the caudate nucleus of rat caused degeneration of dopaminergic terminals, evidenced by significant (P < 0.05) elevation of spontaneous and drug-induced motor behaviour, enhanced DA receptor binding and significant increase in the neuronal firing rate of caudate neurons, suggesting supersensitivity of dopaminergic receptors. Eight weeks following the transplantation of embryonic cell suspensions from caudate at the lesioned site, a significant restoration of the enhanced 3H spiperone binding and neuronal activity of caudate neurons was observed in comparison with lesioned rats. These results clearly demonstrate that transplanted embryonic neuronal tissue at the lesioned site is capable of restoring the neuronal deficits caused by 6-OHDA as evidenced by significant amelioration in neurochemical, behavioral and electrophysiological alterations.

Cholinergic and serotonergic alterations in the rat hippocampus following trimethyltin exposure and fetal neural transplantation.

Trimethyltin (TMT) apart from causing cholinergic denervation of the hippocampus, damages the serotonergic inputs into the hippocampus as well. In the present study, fetal cholinergic and serotonergic rich neuronal populations from septal and raphe regions, respectively, were transplanted alone or in combination (as co-grafts) in the hippocampus of TMT exposed rats. Neurotransmitter receptor binding and neurotransmitter levels were assayed 6 months post-transplantation. Fetal septal transplants (rich in cholinergic neurons) significantly restored the deficits in cholinergic (muscarinic) receptor binding and acetylcholinesterase activity caused by TMT exposure. Raphe transplants (rich in serotonergic neurons) restored the deficit in serotonergic receptor binding and serotonin levels caused by TMT. Co-grafts of fetal raphe and septal neurons restored both the cholinergic (muscarinic) and serotonergic receptor functions. The results suggest that co-grafting technique could provide a better restoration of functional deficits when more than one type of neuronal population is damaged.

Microbiological diagnosis of suppurative keratitis in Bangladesh.

Experience in setting up an inexpensive microbiology laboratory in the Bangladesh National Society for the Blind Eye Hospital and Training Complex at Chittagong is presented, together with the results of a pilot study to identify organisms responsible in 33 consecutive cases of suppurative keratitis in the Chittagong area of Bangladesh. Of the 33 cases 21 were positively identified by means of Gram stain and/or culture. Two-thirds of the responsible organisms were bacteria, and one-third were fungi. The bacterial causes included Streptococcus pneumoniae and Pseudomonas aeruginosa. The fungi isolated were Aspergillus fumigatus, Aspergillus ochraceus, and Fusarium solani. Among the causes of failure to diagnose the organism was chronicity of infection and previous treatment. The value of the study in the planning of future treatment regimens, and the implications of setting up similar relatively cheap microbiology laboratory facilities in developing countries, are discussed.

Causes of low vision and blindness in rural Indonesia.

AIM: To determine the prevalence rates and major contributing causes of low vision and blindness in adults in a rural setting in Indonesia METHODS: A population based prevalence survey of adults 21 years or older (n=989) was conducted in five rural villages and one provincial town in Sumatra, Indonesia. One stage household cluster sampling procedure was employed where 100 households were randomly selected from each village or town. Bilateral low vision was defined as habitual VA (measured using tumbling "E" logMAR charts) in the better eye worse than 6/18 and 3/60 or better, based on the WHO criteria. Bilateral blindness was defined as habitual VA worse than 3/60 in the better eye. The anterior segment and lens of subjects with low vision or blindness (both unilateral and bilateral) (n=66) were examined using a portable slit lamp and fundus examination was performed using indirect ophthalmoscopy. RESULTS: The overall age adjusted (adjusted to the 1990 Indonesia census population) prevalence rate of bilateral low vision was 5.8% (95% confidence interval (CI) 4.2 to 7.4) and bilateral blindness was 2.2% (95% CI 1.1 to 3.2). The rates of low vision and blindness increased with age. The major contributing causes for bilateral low vision were cataract (61.3%), uncorrected refractive error (12.9%), and amblyopia (12.9%), and the major cause of bilateral blindness was cataract (62.5%). The major causes of unilateral low vision were cataract (48.0%) and uncorrected refractive error (12.0%), and major causes of unilateral blindness were amblyopia (50.0%) and trauma (50.0%). CONCLUSIONS: The rates of habitual low vision and blindness in provincial Sumatra, Indonesia, are similar to other developing rural countries in Asia. Blindness is largely preventable, as the major contributing causes (cataract and uncorrected refractive error) are amenable to treatment.

Randomised trial of 0.2% chlorhexidine gluconate and 2.5% natamycin for fungal keratitis in Bangladesh.

AIM: The management of suppurative keratitis due to filamentous fungi presents severe problems in tropical countries. The aim was to demonstrate the efficacy of chlorhexidine 0.2% drops as an inexpensive antimicrobial agent, which could be widely distributed for fungal keratitis. METHODS: Successive patients presenting to the Chittagong Eye Institute and Training Complex with corneal ulcers were admitted to the trial when fungal hyphae had been seen on microscopy. They were randomised to drop treatment with chlorhexidine gluconate 0.2% or the standard local treatment natamycin 2.5%. The diameters, depths, and other features of the ulcers were measured and photographed at regular intervals. The outcome measures were healing at 21 days and presence or absence of toxicity. If there was not a favourable response at 5 days, "treatment failure" was recorded and the treatment was changed to one or more of three options, which included econazole 1% in the latter part of the trial. RESULTS: 71 patients were recruited to the trial, of which 35 were randomised to chlorhexidine and 36 to natamycin. One allocated to natamycin grew bacteria and therefore was excluded from the analysis. None of the severe ulcers was fully healed at 21 days of treatment, but three of those allocated to chlorhexidine eventually healed in times up to 60 days. Of the nonsevere ulcers, 66.7% were healed at 21 days with chlorhexidine and 36.0% with natamycin, a relative efficacy (RE) of 1.85 (CL 1.01-3.39, p = 0.04). If those ulcers were excluded where fungi were seen in the scraping but did not grow on culture, the estimated efficacy ratio does not change but becomes less precise because of smaller numbers. Equal numbers of Aspergillus (22) and Fusarium (22) were grown. The Aspergillus were the most resistant to either primary treatment. CONCLUSIONS: Chlorhexidine may have potential as an inexpensive topical agent for fungal keratitis and warrants further assessment as a first line treatment in situations where microbiological facilities and a range of antifungal agents are not available.

Low protein diet modifies acrylamide neurotoxicity.

The present study deals with the role of protein deficiency in the neurobehavioural effects of acrylamide in rat pups exposed during pregnancy and early infancy. The data indicated that acrylamide could be more toxic in protein-deficient hosts as it significantly decreased the dopamine and benzodiazepine receptor binding and delayed the development of reflexes and land marks in these pups.