Teleophthalmology and Vision 2020 in South Africa.
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Blindness↗
Biomedical subjects
K Johnson
Publications and source records attributed to K Johnson.
Reduced nephron number in adult sheep, hypertensive as a result of prenatal glucocorticoid treatment.
There is some evidence, mainly from rodent studies, that any factor which alters the final total number of nephrons formed, during nephrogenesis, will result in hypertension in adult life. Sheep, programmed to become hypertensive by exposure to synthetic glucocorticoid (dexamethasone, 0.48 mg h-1, for 48 h) early in development (~27 days of gestation), were killed at 7 years of age, and had nephron counting performed by unbiased stereology. Mean arterial pressure was 83 +/- 4 mmHg in the dexamethasone (DEX) group (n = 5), and 73 +/- 5 in the control (CON; n = 7; P < 0.05). The total nephron number, in the right kidney (249 070 +/- 14 331; n = 5) was significantly lower (P < 0.01) than that of controls (402 787 +/- 30 458; n = 7). Mean glomerular volume was larger in the DEX than the CON group (P < 0.01), but there was no significant difference in the sclerosis index between the two groups. Low nephron number was associated with grossly enlarged and dilated proximal tubules and greater accumulation of collagen type I and type III in the tubular interstitium and periadventitia of the renal cortical vessels. These data suggest that the hypertensive programming effect of glucocorticoid treatment, early in kidney development, results, at least in part, from impaired nephrogenesis.
Algorithms↗
Maternal drug use and length of neonatal unit stay.
AIMS: Infants with neonatal abstinence syndrome (NAS) may require a prolonged neonatal unit admission, which has implications for both their families and bed occupancy. The aim of this study was to test the hypothesis that the duration of neonatal unit stay would be influenced by the type of maternal drug use and particularly prolonged for the infants whose mothers had taken methadone with other substances. DESIGN: The medical records of infants born at term who were admitted consecutively to a neonatal unit because of NAS were reviewed. Data were collected regarding antenatal and neonatal factors likely to affect neonatal stay. Comparisons were then made between three groups of infants: those whose mothers took methadone alone, methadone plus other drugs or non-methadone opioids. SETTING: Level three neonatal intensive care unit. PARTICIPANTS: Forty-one infants with a median gestational age of 39 (range 37-42) weeks. FINDINGS: The 41 infants had a median duration of admission of 30 (range 3-68) days. Thirty-six of the infants required treatment for NAS; their median duration of treatment was 29 (range 6-68) days. The duration of stay and requirement for treatment were greater in the infants exposed to methadone and other drugs compared to those exposed to non-methadone opiods only (P = 0.0212, P = 0.0343, respectively). The duration of stay without requirement for treatment was also longest in the methadone plus other drugs group (P = 0.0117). CONCLUSIONS: Prolonged treatment and neonatal unit stay are influenced by the type of maternal drug abused.
Adult↗
Analysis of the consequences of premature termination codons within factor VIII coding sequences.
Inhibitor antibody formation is a complication of factor VIII (FVIII) replacement therapy due to a failure to synthesize sufficient FVIII protein to induce immune tolerance. The incidence of nonsense mutations in inhibitor patients is high, however, this association is variable according to the position of the mutation. We have studied the effect of nonsense mutations on accumulation of FVIII mRNA, protein translation and secretion. Appropriately processed mRNA was detected in cells transfected with wild-type R1966X and R2116X expression constructs and no evidence of nonsense-mediated decay was observed. All constructs directed the translation of detectable intracellular FVIII antigen, however, secreted FVIII was detected only in conditioned media of cells transfected with wild-type cDNA. We have also analyzed ectopic FVIII mRNA transcripts in the lymphocytes of six hemophilia A patients with nonsense mutations (Q139X, R583X, R1941X, R1966X and two unrelated patients with R2116X). FVIII mRNA was detectable in every case. In R1941X and R1966X only normally spliced transcripts were present. In Q139X, R583X and R2116X aberrantly spliced transcripts were observed with two distinct patterns in two individuals with the R2116X mutation. No correlation between mutation, transcript pattern and incidence of inhibitor development was apparent.
Alternative Splicing↗
Programming the cardiovascular system, kidney and the brain--a review.
The concept that 'life before birth' or the 'first environment' is important in determining subsequent risk for the development of cardiovascular/metabolic disease is now gaining acceptance. There are substantial data from animal experiments that complement and enhance the epidemiological data from human studies. We argue that any factor which disrupts nephrogenesis, and lowers nephron number, during the period of active nephrogenesis, will induce malapadaptive changes in the future functioning of that kidney and predispose to the onset of adult hypertension. Such factors include exposure of the mother, to a particular low-protein diet, excess synthetic or natural glucocorticoid at certain critical periods, mild vitamin A deficiency, elevated blood glucose, unilateral nephrectomy during the period of nephrogenesis, as well as the deletion of one allele of a gene (GDNF) involved in normal metanephric development. All of these stresses are associated with a reduction (20-40 per cent) in total nephron number in the adult, and the development of hypertension. In some hypertensive models, (rats) there is evidence of alterations in the components of the hippocampal/hypothalamic/pituitary/adrenal axis, whereas in others (sheep) there are alterations in the expression of angiotensinogen (hypothalamus) and angiotensin II receptor type I (AT(1)) in the medulla oblongata. The surprising finding is that the period when the kidney and brain are most vulnerable is very early in development, when both organs are in an extremely primitive state of development.
Angiotensins↗
Treatment of neonatal abstinence syndrome.
Neonatal abstinence syndrome (NAS) is suffered by infants withdrawing from substances on which they have become physically dependent after in utero exposure. They may require prolonged treatment and spend weeks or even months in hospital. A wide range of drugs have been used to treat NAS. The efficacy of few, however, have been adequately investigated. Evidence suggests that opioids are the most appropriate, at least in infants exposed to diamorphine or methadone. In all "head to head" trials, diazepam has been shown to be ineffective. Morphine and methadone are currently the most commonly prescribed opioids to treat NAS, but randomised trials have not been undertaken to determine which is the more beneficial. Many infants with NAS have been exposed to multiple substances in utero. Further research is required into whether a single opiate or a multiple drug regimen is the best option for such patients.
Clinical Trials as Topic↗
Substance misuse during pregnancy.
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Child Development↗
Survey for coccidia and haemosporidia in the lesser prairie-chicken (Tympanuchus pallidicinctus) from New Mexico with description of a new Eimeria species.
Blood films and fecal samples of the lesser prairie-chicken (Tympanuchus pallidicinctus) were examined for parasites when we surveyed specimens captured during a radio-tracking study conducted in Chaves County, New Mexico (USA). All birds were captured on the Caprock Wildlife Habitat Management Area, administered by the Bureau of Land Management. Samples were collected in late March, April, and early May 1998-2000. Oocysts were detected in five of 64 (8%) birds sampled and, upon sporulation, were determined to be an Eimeria species. This is the first eimerian reported from the lesser prairie-chicken and is described here as a new species. Sporulated oocysts are ellipsoidal, 27.1 x 22.7 (22-32 x 18-26) microns, with micropyle absent, but oocyst residuum and polar granule present. Sporocysts are ovoidal, 11.9 x 7.8 (10-14 x 6-10); a Stieda body, and sporocyst residuum are present, as is a small, indistinct substieda body. Inspection of blood smears revealed four cases of Plasmodium infection of 32 (13%) individuals sampled. The characteristics of this plasmodiid are consistent with the description of Plasmodium (Giovannolaia) pedioecetii, previously found in T. pallidicinctus (Stabler, 1978).
Animals↗
Spinal lipoma misinterpreted as a meningomyelocele on antenatal MRI scan in a baby girl.
INTRODUCTION: Antenatal screening for spina bifida with ultrasound and MR imaging is increasingly used. CASE REPORT: A baby girl's antenatal MRI examination showed features originally interpreted as a lumbar meningomyelocele. Repeat MRI examination soon after birth showed features of a spinal lipoma (lipomeningomyelocele). This was excised surgically and complete spinal cord untethering was achieved. CONCLUSION: As antenatal MR scanning is increasingly used, and fetal surgery is becoming more prominent, the correct interpretation of such images is crucial. We present a rare case of a misleading antenatal radiological diagnosis of spina bifida, which would have had severe implications if termination of the pregnancy or intra-uterine surgical repair had been considered.
Diagnosis, Differential↗
The imaging of paediatric thoracic trauma.
Trauma is a significant cause of morbidity and mortality in children and radiological investigations are almost always used in its management. This article reviews the radiological findings in thoracic trauma, in relation to their effects on lung parenchyma, the airways, the pleura, the great vessels, the diaphragms and the bony skeleton. Particular emphasis is given to plain radiographical and computed tomography findings, since these are the commonest imaging modalities used.
Bronchi↗
The use of melatonin as an alternative to sedation in uncooperative children undergoing an MRI examination.
AIM: Children who are uncooperative, due either to their age or medical condition, usually require sedation or a general anaesthetic (GA) to ensure immobility during magnetic resonance imaging (MRI) examination. These procedures have a risk of respiratory compromise and loss of vital reflexes. Melatonin induces a natural sleep with no known complication or risk of respiratory compromise. We aimed to evaluate the use of melatonin in these uncooperative children. MATERIAL AND METHODS: An unselected group of 40 children, who had been referred for an MRI examination of the brain under sedation or GA, were chosen to receive melatonin instead. They all received 10 mg of melatonin and 17 children additionally underwent some form of sleep deprivation. The number of children who went to sleep and had a successful MRI examination was recorded. RESULTS: Twenty-six children (65%) went to sleep and of these 22 (55%) had a successful MRI examination. In the 17 children who underwent sleep deprivation, 13 (76%) went to sleep and had a successful MRI examination. There was no complication. CONCLUSIONS: Melatonin may provide an alternative to conventional sedation regimes and GA for uncooperative children undergoing an MRI examination. The use of sleep deprivation improves the success rate and there is no risk of respiratory compromise.
Adolescent↗
Benefits of early diagnosis and preemptive treatment of biliary tract complications after major blunt liver trauma in children.
BACKGROUND/PURPOSE: Nonoperative management of blunt liver trauma may delay diagnosis of related biliary complications leading to delayed surgical intervention and related morbidity. The aim of this study was to see whether technetium (tc) 99 trimethylbromo-im-indolacetic acid (TBIDA) nuclear scan would allow noninvasive early diagnosis of bile leak and pre-emptive management. METHODS: Retrospective analysis of the patient records and radiologic investigations of 7 patients admitted between April 1998 and December 2000 with "major" blunt liver trauma (parenchymal fracture of less than 4 cm on computed tomography [CT] scan or involving porta hepatis) and various types of biliary complications. Patients with or without early TBIDA diagnosis were compared. RESULTS: There were 7 patients. The first 2 patients were treated conventionally without TBIDA, and late diagnosis was associated with further related problems (sepsis, life-threatening hemorrhage in both cases) and prolonged hospital stay. The subsequent 5 consecutive patients benefited from early diagnosis (TBIDA scan, 2 to 4 days after trauma), and preemptive management was done (tailored to each case). There was no further or related morbidity. All 7 patients currently are alive and well. CONCLUSIONS: A TBIDA nuclear medicine scan was efficient in providing an early diagnosis of biliary leakage, thus, allowing adequate preemptive management. In turn, this may have helped avoid related added morbidity compared with cases of late diagnosis. Early TBIDA scan should be performed routinely when the initial CT scan confirms liver trauma graded as "major."
Adolescent↗
Hyperphagia, weight gain and neonatal drug withdrawal.
UNLABELLED: Hyperphagia, a classical feature of neonatal drug withdrawal, has been reported not to lead to excessive weight gain, but this is contrary to our clinical experience. The aim of this study was to determine whether infants with neonatal drug withdrawal suffered excessive weight gain because of hyperphagia and, if so, to determine the risk factors. The study population comprised 48 infants consecutively admitted to the neonatal intensive care unit, 11 of whom gained weight by more than 20 g kg(-1) d(-1) for at least 10 d (excessive weight gain). All 11 infants were hyperphagic (>200 ml/kg) for at least part of the excessive weight gain period. During the perinatal period, the 11 infants had a greater fluid intake (p < 0.01) but similar weight gain to gestational-age-matched, neonatal drug-withdrawal infants who did not suffer any excessive weight gain. Compared to the rest of the cohort, the infants with excessive weight gain were more likely to require treatment with morphine/chlorpromzaine (p < 0.05) and had a higher maximum withdrawal score (p < 0.01). CONCLUSION: Hyperphagia can lead to excessive weight gain in infants with neonatal drug withdrawal. Our results suggest that hyperphagia occurs in those who require treatment for severe withdrawal.
Birth Weight↗
Maternal glucocorticoid treatment programs alterations in the renin-angiotensin system of the ovine fetal kidney.
Ovine fetuses exposed to high concentrations of synthetic (dexamethasone, D) or naturally occurring glucocorticoids (cortisol, F) in utero during early gestation develop high blood pressure in adulthood. To investigate potential mechanisms involved, we examined the role of the renal renin-angiotensin system (RAS). Ewes were infused with isotonic saline (S, n = 11), D (n = 12, 0.48 mg/h), or F (n = 5, 5 mg/h) for 48 h between d 26 and 28 of gestation (term = 150 d). Ewes carrying twins (S, n = 5; D, n = 6; F, n = 5) were killed at 130 d of gestation. The mRNA levels for angiotensinogen, the AT(1) receptor and AT(2) receptor, were increased in the fetal kidneys after D treatment. Prenatal infusions of F produced similar effects on the AT(1) receptor. Single fetuses (S, n = 6; D, n = 6) were cannulated and infused with angiotensin II for 3 d beginning at 127 d of gestation. Basal blood pressure was similar in both groups and increased similarly with angiotensin II infusion. However, increases in urine flow and glomerular filtration rate were significantly reduced and kidney weights increased in the D-treated group. These results indicate that treatment with D very early in gestation causes significant alterations in the RAS in the fetal kidney 100 d later with functional consequences. Changes in the RAS in the developing kidney may be an important mechanism in the development of adult disease.
Angiotensin II↗
CRB1 has a cytoplasmic domain that is functionally conserved between human and Drosophila.
Mutations in the human Crumbs homologue 1 (CRB1) gene cause severe retinal dystrophies, ranging from retinitis pigmentosa to Leber congenital amaurosis. The CRB1 gene is expressed specifically in human retina and brain and encodes a protein homologous to the Drosophila Crumbs protein. In crumbs mutant embryos apico-basal polarity of epithelial cells is lost, leading to widespread epidermal cell death. The small cytoplasmic domain of Crumbs organizes an intracellular protein scaffold that defines the assembly of a continuous zonula adherens. The crumbs mutant phenotype can be partially rescued by expression of just the membrane-bound cytoplasmic domain, and overexpression of this domain in a wild-type background results in a multilayered epidermis. A striking difference between CRB1 and Crumbs was that the latter contains a transmembrane region and a 37 amino acid cytoplasmic domain. Here we describe an alternative splice variant of human CRB1 that encodes a cytoplasmic domain 72% similar to that of Drosophila Crumbs. Two intracellular subdomains that are necessary for function in Drosophila are absolutely conserved. Rescuing and overexpression studies in Drosophila show that the cytoplasmic domains are functionally related between these distant species. This suggests that CRB1 organizes an intracellular protein scaffold in the human retina. Human homologues of proteins binding to Crumbs may be part of this complex and represent candidate genes for retinal dystrophies.
Alternative Splicing↗
Oxonium ions from aqua regia: isolation by hydrogen bonding to crown ethers.
The preparation and structures of a variety of oxonium ion tetrachloroaurate(III) salts isolated from aqua regia are reported. The new compounds are [(H(5)O(2))(2)(12-crown-4)(2)][AuCl(4)](2) (1), [(H(7)O(3))(15-crown-5)][AuCl(4)] (2), [(H(5)O(2))(benzo-15-crown-5)(2)][AuCl(4)] (3), [(H(3)O)(18-crown-6)][AuCl(4)] (4), [(H(5)O(2))(dibenzo-24-crown-8)][AuCl(4)] (5), [(H(5)O(2))(4-nitrobenzo-15-crown-5)(2)][AuCl(4)] (6), [(H(3)O)(4-nitrobenzo-18-crown-6)][AuCl(4)] (7), [(H(11)O(5))(tetrachlorodibenzo-18-crown-6)(2)][AuCl(4)] (8), and [(H(7)O(3))(dinitrodibenzo-30-crown-10)][AuCl(4)] (9). A significant correlation between the degree of proton hydration and crown ether size is observed. Aryl crown ethers are nitrated in concentrated aqua regia, but nonnitrated products may be obtained in a dilute solution of aqua regia by reaction with aqueous HAuCl(4).
Journal Article↗
Call to work together on microarray data analysis.
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Algorithms↗
Use of viral fusogenic membrane glycoproteins as novel therapeutic transgenes in gliomas.
Malignant gliomas are the most common primary brain tumors in adults and, with few exceptions, have a dismal prognosis despite the therapeutic use of surgery, radiation therapy, and chemotherapy. Because CNS gliomas rarely metastasize, they represent an attractive target for gene therapy through local gene delivery. Here we report on the use of two different fusogenic membrane glycoproteins (FMGs), the measles virus proteins F and H (MV-F and MV-H) and a mutated form of the retroviral envelope protein of the gibbon ape leukemia virus (GALV.fus), as a novel class of therapeutic transgenes in gliomas. Transfection of U87 and U118 cells with MV-F and MV-H cDNA or GALV.fus cDNA led in 48 hr to massive syncytial formation followed by cell death. FMG-mediated cytotoxicity in the U87 and U118 cell lines was superior to the cytotoxicity caused by transfection with HSV-tk cDNA followed by ganciclovir (GCV) treatment at all time points. At high-density cell seeding, addition of tumor cells transfected with MV-F and H killed at least 1 log more cells than by HSV-tk + GCV treatment, indicating higher bystander effect. Similar results were obtained with GALV.fus. The mechanism of syncytial death in cultured glioma cell lines was predominantly apoptotic. Transfection of U87 cells with F + H or GALV.fus expression constructs completely suppressed their tumorigenicity. Treatment of established U87 xenografts in nude mice with a combination of F and H adenoviruses at 1:1 ratio led to complete tumor regression, significantly higher antitumor effect, and prolongation of survival as compared with control animals treated with a GFP adenovirus. In summary, the viral fusogenic membrane glycoproteins (GALV and the MV-F + MV-H combination) are potent therapeutic transgenes with potential utility in the gene therapy of gliomas.
Animals↗