A cross-sectional study of peripartum blood transfusion in the Eastern Cape, South Africa.

BACKGROUND: Obstetric haemorrhage (OH) remains a major contributor to maternal morbidity and mortality. Blood transfusion is critical in OH management; yet, data on peripartum transfusion are lacking. A pilot study reported high rates of peripartum transfusion in a sample of South African (SA) hospitals, which was independently associated with HIV status. OBJECTIVES: To assess the incidence of peripartum transfusion in a sample of Eastern Cape, SA hospitals to evaluate generalisability of preceding study findings. METHODS: Hospital chart reviews were conducted of all deliveries at three large regional hospitals from February to June 2013. Additional clinical data were collected for patients who sustained OH and/or were transfused. RESULTS: A total of 7 234 women were enrolled in the study; 1 988 (27.5%) were HIV-positive. Of the 767 HIV-positive women with a CD4 count <350 cells/µL, 86.0% were on full antiretroviral therapy and 9.9% received drugs for prevention of mother-to-child transmission. The overall transfusion rate was 3.2%, with significant variability by hospital: Frere Hospital (1.5%), Dora Nginza Hospital (3.8%) and Cecilia Makiwane Hospital (4.6%). The number of red blood cell units per transfused patient and per delivery varied significantly by hospital. Bivariate analysis showed significant association between transfusion and HIV status. In a multivariate analysis, controlling for OH, age, mode of delivery, gestational age, parity and birthweight, this association (odds ratio 1.45; 95% confidence interval 0.78 - 2.71) was no longer significant. CONCLUSION: These findings confirm high rates of peripartum transfusion in SA. While this can be possibly ascribed to variability in practice and patient profile, variation in care and improvement in HIV treatment should be considered.

Abnormal retinotopic organization of the dorsal lateral geniculate nucleus of the tyrosinase-negative albino cat.

Visual defects associated with hypopigmentation have been studied extensively in Siamese and albino cats. Previous research on tyrosinase-negative albino cats has shown that (1) approximately 95% of all nasal and temporal retinal fibers cross at the optic chiasm, and (2) ocular dominance columns normally found in cortex are replaced with hemiretinal domains. In this study, we compared the retinotopic organization of the dorsal lateral geniculate nucleus (LGNd) and visual cortex in albino cats. Extracellular recordings were conducted in the LGNd, area 17, and area 18 of six albino cats. Receptive fields (RFs) were plotted for all sites. We find that, as in albino visual cortex, the albino LGNd contains (1) normal cells with RFs in the visual hemifield contralateral to the recording site (RFc), (2) abnormal cells with RFs in the ipsilateral hemifield (RFi), (3) abnormal cells with dual, mirror-symmetric RFs, one in each hemifield (RFd), and (4) abnormal cells with broad RFs that span the vertical meridian (RFb). Our data indicate that lamina A and lamina A1 consist predominantly of normal RFc and abnormal RFi cells, respectively. The C laminae contain a mixture of RFc, RFi, RFd, and RFb cells. The interlaminar zones contained RFd cells, RFb cells, or both. Thus, the albino LGNd is arranged into hemiretinal and not ocular dominance laminae. Finally, the percentage of normal cells is significantly larger in area 17 (84%) and area 18 (70%) than in the LGNd (46%), suggesting a suppression of abnormal activity in albino cat cortex, which could underlie the existing competence of visual function in albinos.

Selective loss of the electroretinogram B-wave in a patient with Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) is a neurodegenerative disease characterized by movement abnormalities and dementia that inevitably progress to death. Familial, infectious, and sporadic forms of the disease are recognized. The worldwide incidence of CJD is estimated at 1:1,000,000 per year, and it affects middle-aged men and women in roughly equal proportions. The disease is caused by a unique infectious vector, the prion, which is a mutant form of a normally occurring cell surface protein found predominantly in the central nervous system. A significant proportion of patients with CJD will have visual disturbances at some point in their illness and may therefore consult a neuro-ophthalmologist. The case of a woman in whom the diagnosis of CJD was not known until autopsy is reported. Early in the course of her disease, she sought ophthalmic consultation because of vision problems.

Previously apparently undescribed autosomal recessive MCA/MR syndrome with light fixation, retinal cone dystrophy, and seizures: the M syndrome.

We report on two sisters from healthy families with a syndrome of severe developmental delay, ataxia, impaired social interaction, a seizure disorder with early onset but without epileptiform electroencephalogram changes, and a striking light-fixating behavior which was associated with retinal cone dystrophy. Additionally, they have minor anomalies including peripheral iris hypoplasia, bluish sclerae, mild anteversion of nostrils, micrognathia, ear anomalies, broad halluces and thumbs, hypoplastic toenails, short perineal body, "Mongolian spots," mild hirsutism, hypoplastic ridges in the hypothenar area, and distal axial triradii. Growth and general health are normal in both, but one also had tetralogy of Fallot and vesicoureteral reflux. Because this condition appears to be previously undescribed we postulate a new autosomal recessive disorder with light-fixating behavior and retinal cone dystrophy as leading symptom.

Retinal toxicity associated with occupational exposure to the fish anesthetic MS-222.

PURPOSE: To report a case of retinopathy associated with chronic occupational exposure to ethyl-m-aminobenzoic acid methanesulfonate (MS-222), a retinotoxic fish anesthetic. METHOD: Case report with electroretinograms to document changes in visual electrophysiology. RESULTS: An ichthyologist with a long history of skin exposure to MS-222 was initially examined for decreased vision, photophobia, and photopsia. His electroretinogram abnormalities were similar to those seen in animal models of acute MS-222 toxicity. After terminating MS-222 contact for 7 months, his vision returned to normal, and his electroretinogram improved. CONCLUSION: Individuals with occupational exposure to MS-222 should exercise caution to avoid systemic absorption of this retinotoxic compound.

Hyperopic shift induced by high altitude after radial keratotomy.

BACKGROUND: The collagen fibrils embedded in the ground substance of the stromal lamellae provide the structural support for the cornea. When the stromal lamellae are cut in a radial keratotomy surgical procedure, the remaining uncut lamellae carry the tensile forces. METHODS: We studied two expert climbers who had bilateral radial keratotomy before participating in six climbs of extreme altitude, including Mount McKinley and above 7500 m (24,606 ft) on Mount Everest. RESULTS: Whenever either climber was exposed to altitudes greater than approximately 5000 m (16,405 ft) for more than a day, their refraction would become +3.00 D or more hyperopic and remain so al long as they were at or above this altitude. Visual acuity slowly returned to normal after descent. CONCLUSION: It appears that in the presence of significantly reduced atmospheric pressure and/or oxygen there is a greater effect of radial keratotomy in some patients, making the cornea more vulnerable to changes in shape. The cornea appears to respond by further flattening, exacerbating the intended surgical effect and producing a refractive shift toward hyperopia.

Children and adolescents with neurofibromatosis 1: a behavioral phenotype.

Twenty 6- to 17-year-old children with neurofibromatosis 1. (NF1) were compared to 20 age- and sex-matched siblings on a wide range of neuropsychological and behavioral dimensions. In familial cases, diagnostic status was confirmed by gene linkage with greater than 98% accuracy. Visual examinations that included assessments of visual evoked responses (VER) were performed on subjects with NF1. Forty-two percent of NF1 subjects had abnormal VER and underwent magnetic resonance imagery or computed tomography scans of the brain. On a variety of skills, subjects with NF1 performed more poorly than unaffected siblings. Children with NF1 were found to be less competent on measures of cognitive, language, and motor development, visual-spatial judgment, visual-motor integration, and academic achievement. Learning disabilities were common in children with NF1. Parents and teachers reported that NF1 subjects had internalizing problems and difficulty interacting with peers. A behavioral phenotype for NF1 and recommendations for preventative interventions are proposed.

Differential effects of gentamicin on the distribution of cochlear function in albino and pigmented guinea pigs.

It has been suggested that the high affinity of melanin pigment for aminoglycoside antibiotics may cause these drugs to bind preferentially to the pigmented inner ear, producing greater ototoxicity than in the amelanotic albino cochlea. However, evidence of greater ototoxicity in albinos has led to the hypothesis that melanin inhibits the toxicity of these drugs in the pigmented inner ear. On the other hand, ototoxicity in the pigmented animals may simply be delayed relative to the albinos, only to become equal or even more severe with time. The present study was conducted to determine whether a relatively low dose of gentamicin (68.5 mg/kg) would produce differential ototoxicity between albino and pigmented guinea pigs which would persist long after drug exposure had stopped. Nine pigmented and eight albino guinea pigs were given gentamicin sulfate for 14 consecutive days, and were then allowed a two-month recovery period before cochlear analysis; 11 pairs of saline-injected or untreated albino and pigmented guinea pigs served as controls. The results showed that the gentamicin-treated albinos had significantly elevated thresholds for the compound action potential from the auditory nerve (CAP), and significantly lower endocochlear potentials (EP) and cochlear microphonic (CM) input-output voltage functions when compared to their respective controls, or to either group of pigmented guinea pigs. The CAP in drug-treated pigmented animals did not differ significantly from controls, and the differences in EP and CM were marginally significant. The results indicate that the pigmented cochlea is less susceptible to gentamicin than the albino cochlea, and support the hypothesis that melanin may inhibit aminoglycoside ototoxicity in the pigmented inner ear.

Abnormal ipsilateral visual field representation in areas 17 and 18 of hypopigmented cats.

We compared the central projections of retinal ganglion cells in temporal retina and the cortical representation of visual fields in areas 17 and 18 in cats with various hypopigmentation phenotypes (albino, heterozygous albino, Siamese, and heterozygous Siamese). In all cats studied, we found that the extent of abnormal ipsilateral visual field representation varied widely, and more of the ipsilateral visual field was represented in area 18 than in area 17. The greatest degree of ipsilateral visual field representation was found in albino cats, followed by Siamese, heterozygous albino and heterozygote Siamese cats, respectively. Additionally, in the different groups there was wide variation in the numbers of contralaterally projecting alpha and beta ganglion cells in temporal retina. In all cases, however, contralaterally projecting alpha cells were found to extend further into temporal retina than beta cells. We found that in each cat studied, the maximum extent of the abnormal ipsilateral visual field representation in areas 18 and 17 corresponded to the location of the 50% decussation line (i.e., the point where 50% of the ganglion cells in temporal retina project to the contralateral hemisphere) for alpha and beta cells, respectively, for that cat. Our results suggest that the extent of the abnormal visual field representations in visual cortex of hypopigmented cats reflects the extent of contralaterally projecting retinal ganglion cells in temporal retina.

Pattern dystrophy and retinitis pigmentosa caused by a peripherin/RDS mutation.

PURPOSE: To describe the clinical and molecular genetic findings in members of a family with features of autosomal dominant retinitis pigmentosa (RP) and pattern dystrophy. METHODS: Members of a four-generation family underwent ophthalmoscopic examination, electrophysiologic testing, and screening of blood samples for rhodopsin and peripherin/RDS mutations. RESULTS: Three members of the family had clinical evidence of both RP and pattern dystrophy, and another family member had symptoms suggestive of RP. In one case of pattern dystrophy, pigment deposition in an unusual ring-like configuration was seen. All affected family members were found to have a Pro216Ser mutation in the peripherin/RDS gene on chromosome 6p, a mutation not found in unrelated (normal) spouses or in a normal control population. CONCLUSION: In members of this family, both autosomal dominant RP and pattern dystrophy were associated with a Pro216Ser mutation in the peripherin/RDS gene.

Auditory brainstem responses in cats with Chediak-Higashi syndrome.

Auditory brainstem responses ABRs were recorded in cats with Chediak-Higashi syndrome using monaural stimulation. The components appearing between 1 and 3 ms after stimulus onset were greatly attenuated in the ABRs recorded using a reference contralateral to the stimulated ear. These data suggest that abnormalities exist in the brainstem auditory pathway in the region of the superior olivary complex in cats with Chediak-Higashi syndrome.

Pattern reversal evoked potentials: gender differences and age-related changes in amplitude and latency.

This report is intended to complement the current body of literature by describing pattern reversal evoked potential (PREP) component amplitudes and latencies in a larger sample than has been previously studied and providing comparisons of males and females across the lifespan. Binocular PREPs were measured from 406 normal subjects, 6-80 years of age. In general, latencies were found to decrease during maturation, stabilize across early adulthood, then begin to increase sometime after the late 20s. There were minimal gender differences in latencies during development but males tended to have longer latencies than females during adulthood. Across the lifespan, amplitudes were larger for females. Results of regression analyses using the entire data set were compared to results of separate regression analyses for developmental years (6-20) and adulthood (21-80). Separate analyses appear to provide more useful descriptions of PREP latency and amplitude changes across the lifespan. It is clear that predicted normal values can vary depending on age range and relative proportion of males and females comprising a reference sample. Appropriate clinical values should be based on age- and sex-matched normal subjects and should be specific with regard to technical and methodological variables.

Pigment-dependent differences in the stria vascularis of albino and pigmented guinea pigs and rats.

Functional models of the stria vascularis (SV) have ascribed roles for the marginal and basal cells, but not for the intermediate cells, which remain poorly understood. Intermediate cells have been identified as melanocytes, which produce melanin in most pigmented animals including humans. The relationship of melanin to intermediate cell function may be addressed through comparisons with the albino inner ear. Albinos have a normal distribution of melanocytes that are unable to synthesize melanin pigment. In the present study, the SV was compared between albino and pigmented littermates in both the guinea pig and the rat. Photomicrographic montages of the SV were analyzed from each of 7 cochlear regions in the guinea pig and 5 regions in the rat. Stereological procedures were used to determine the volume density (Vv) for each of the three main cell types in the stria, the surface density (Sv) of the marginal cells, and to derive estimates of absolute cell volume and surface area. In the guinea pig, comparisons between pigment groups showed that marginal cell Vv was larger across cochlear turns in the albinos, while intermediate cell Vv was smaller. Intermediate cell cytoplasmic and total cell volumes were smaller in the albino guinea pigs; however, marginal cell Sv and absolute area were larger. In the rat, intermediate cell Vv was alos smaller across cochlear turns in the albinos. Similarly, intermediate cell cytoplasmic and total cell volumes were smaller in the albinos, while marginal cell total surface area per radial cross-section of the SV was larger. These results demonstrate that amelanotic melanocytes occupy significantly less volume than do pigmented melanocytes, and suggest that melanin may influence the structure and function of the SV.

Magnetic resonance imaging of the visual pathways in human albinos.

Neuroanatomical and electrophysiological studies of albino visual pathways have demonstrated that retinogeniculate axons arising from the temporal retina decussate abnormally in the optic chiasm to synapse in the contralateral lateral geniculate nucleus (LGN). Anomalies in the LGN secondarily disrupt normal geniculo-cortical and interhemispheric cortico-cortical (callosal) visual connections. It is not known whether retinogeniculate misrouting affects the size or configuration of the afferent visual pathways in human albinos. We used T1-weighted coronal and sagittal magnetic resonance imaging (MRI) to examine the prechiasmatic intracranial optic nerves, optic chiasm, and corpus callosum in 10 human albinos. In all subjects, these structures were normal in size and configuration. Despite the complex cascade of aberrant central neuronal connections, the human albino visual pathways and their interhemispheric connections appear normal in size and configuration when viewed with MRI.

Auditory brain-stem responses in blepharospasm.

The auditory brain-stem response (ABR) has been reported to detect abnormalities in both the auditory pathways and in adjacent structures. Ten of 35 consecutive patients with blepharospasm were found to have abnormal ABRs involving poor form and delayed peak latency of positive components III or V. Abnormal ABRs in approximately 30% of patients with essential blepharospasm suggest pathology in the brain-stem of a substantial proportion of patients with this form of cranial-cervical dystonia.

Variable expression of vision in sibs with albinism.

Oculocutaneous albinism is defined by the presence of cutaneous and ocular hypopigmentation, the latter associated with nystagmus, iris transillumination, reduced retinal pigment, foveal hypoplasia, and misrouting of the optic fibers at the chiasm. The visual acuity is variable but almost always reduced. We report on two brothers with oculocutaneous albinism and markedly different visual acuity. One brother has a visual acuity of 20/100, while the second has similar cutaneous pigmentation and visual acuity of 20/20 and had not previously been recognized as having oculocutaneous albinism. Both brothers have foveal hypoplasia and misrouting of the optic fibers at the chiasm. Biochemical analysis suggests that this is a tyrosinase-related type of oculocutaneous albinism. This study demonstrates that careful observation of foveal development in relatives with normal vision is necessary to detect all individuals with albinism in a family. A suspected diagnosis of albinism may be confirmed when the visual-evoked potentials show excessive decussation of the optic fibers at the chiasm.

Turn-specific and pigment-dependent differences in the stria vascularis of normal and gentamicin-treated albino and pigmented guinea pigs.

The aims of the present study were to determine which structures in the stria vascularis (SV) may depend upon the presence of pigmented melanocytes both for normal morphology and for the expression of gentamicin ototoxicity in the inner ear. These pigment-dependent influences were inferred through comparisons of the SV in pigmented guinea pigs and in albinos containing nonpigmented melanocytes. Results were obtained from 6 albino and 8 pigmented guinea pigs given gentamicin, and from 3 albino and 3 pigmented control animals not receiving the drug. One-month old animals received gentamicin daily (100 mg/kg) for 14 days and recovered for an additional 14 days before being prepared for electron microscopy. The SV from each of the 4 cochlear turns was analyzed using stereological point counting procedures. In control animals, differences were found in the higher cochlear turns, where volume density for the marginal cells in albinos was abnormally large (turns 3 and 4), while the volume density for intermediate cells (melanocytes) was abnormally small (turn 3). Cell volume estimates for the intermediate cells were significantly smaller in the albino than pigmented control animals in the higher cochlear turns, indicating that functional abnormalities may be found in the albino cochlea. In animals exposed to gentamicin, marginal cell volume density was reduced significantly in turn 4 of albinos, but not in any region of the pigmented inner ears. Radial area of SV and estimates of the absolute volumes for marginal cells in albinos given gentamicin also were significantly reduced in turn 1 compared to their controls; such differences were not observed in the pigmented animals. The results indicate that marginal cell size is significantly reduced in albino but not pigmented animals 14 days after gentamicin exposure, and further suggest a role of pigmented melanocytes in ameliorating gentamicin-induced cochlear damage.

Visual anomalies associated with albinism.

All mammals with hypopigmentation of the retinal pigment epithelium have abnormal visual systems. Albino mammals have been found to have: (1) reduced numbers of uncrossed optic fibers projecting to all visual centers, (2) disorganization of the pattern (lamination) of the dorsal lateral geniculate nuclei, and (3) disorganization of projections from the dorsal lateral geniculate nuclei to the visual cortex. The disorganization of central visual centers has catastrophic effects on stereovision and optokinetic nystagmus. Variable expression in oculocutaneous albinism suggests that affected individuals cannot always be identified by hypopigmentation, reduced visual acuity and nystagmus. Careful observation of foveal development in individuals even with normal vision is necessary to detect all persons with albinism. The scalp-recorded visually evoked potential designed to detect optic misrouting is the most reliable concomitant for determining albinism.

Differential susceptibility to gentamicin ototoxicity between albino and pigmented guinea pigs.

The known chemical affinity of melanin pigment for aminoglycoside antibiotics has led to the suggestion that higher concentrations of these drugs will bind to the pigmented inner ear and produce greater ototoxicity compared to the nonpigmented albino cochlea. Although this has provided a compelling hypothesis, results from the few investigations to address this question have been equivocal. In the present study, cochlear microphonic (CM) thresholds were recorded from albino and pigmented guinea pigs both before and two weeks after exposure for 14 consecutive days to 100 mg/Kg gentamicin. Cochleae were dissected and half-turn segments prepared for surface examination of the organ of Corti. After gentamicin exposure, threshold shifts averaged a statistically reliable 33 dB in albinos and 19 dB for the pigmented animals. Anatomical studies revealed a significant 44% mean outer hair cell loss in albinos compared to a 21% loss in the pigmented inner ears. The results showed that albinos display greater ototoxicity from gentamicin than do pigmented guinea pigs. Aminoglycosides are known to exert toxicity through interaction with polyphosphoinositides found in high concentrations in the inner ear. Cochleae in both albino and pigmented animals appear to possess significant phospholipid concentrations and bind toxic levels of these drugs independent of inner ear pigment content. However, evidence showing that melanin can inhibit aminoglycoside activity in vitro suggests that, once these drugs bind to pigmented tissue, they may undergo inactivation in a manner unavailable to the nonpigmented albino cochlea. The present results are consistent with the possibility that cochlear melanin may inhibit gentamicin activity in vivo and decrease the severity of aminoglycoside ototoxicity in the pigmented inner ear.