Biomedical subjects
Publications and source records attributed to J Osborne.
We describe in this case report a new technique for treatment of hypopharyngeal haemangioma, using the surgical diathermy snare. The snare was easily introduced through the direct laryngoscope, without any difficulties. The procedure was simple, rapid and involved minimal bleeding. We also discuss the histological types of haemangioma, clinical picture, radiological findings and other modalities of treatment.
OBJECTIVE: To determine the frequency of mutations in CDKL5 in both male and female patients with infantile spasms or early onset epilepsy of unknown cause, and to consider whether the breadth of the reported phenotype would be extended by studying a different patient group. METHODS: Two groups of patients were investigated for CDKL5 mutations. Group 1 comprised 73 patients (57 female, 16 male) referred to Cardiff for CDKL5 analysis, of whom 49 (42 female, 7 male) had epileptic seizure onset in the first six months of life. Group 2 comprised 26 patients (11 female, 15 male) with infantile spasms previously recruited to a clinical trial, the UK Infantile Spasms Study. Where a likely pathogenic mutation was identified, further clinical data were reviewed. RESULTS: Seven likely pathogenic mutations were found among female patients from group 1 with epileptic seizure onset in the first six months of life, accounting for seven of the 42 in this group (17%). No mutations other than the already published mutation were found in female patients from group 2, or in any male patient from either study group. All patients with mutations had early signs of developmental delay and most had made little developmental progress. Further clinical information was available for six patients: autistic features and tactile hypersensitivity were common but only one had suggestive Rett-like features. All had a severe epileptic seizure disorder, all but one of whom had myoclonic jerks. The EEG showed focal or generalised changes and in those with infantile spasms, hypsarrhythmia. Slow frequencies were seen frequently with a frontal or fronto-temporal predominance and high amplitudes. CONCLUSIONS: The spectrum of the epileptic seizure disorder, and associated EEG changes, in those with CDKL5 mutations is broader than previously reported. CDKL5 mutations are a significant cause of infantile spasms and early epileptic seizures in female patients, and of a later intractable seizure disorder, irrespective of whether they have suspected Rett syndrome. Analysis should be considered in these patients in the clinical setting.
Adult users of unilateral Nucleus CI24 cochlear implants with the SPEAK processing strategy were randomised either to receive a second identical implant in the contralateral ear immediately, or to wait 12 months while they acted as controls for late-emerging benefits of the first implant. Twenty four subjects, twelve from each group, completed the study. Receipt of a second implant led to improvements in self-reported abilities in spatial hearing, quality of hearing, and hearing for speech, but to generally non-significant changes in measures of quality of life. Multivariate analyses showed that positive changes in quality of life were associated with improvements in hearing, but were offset by negative changes associated with worsening tinnitus. Even in a best-case scenario, in which no worsening of tinnitus was assumed to occur, the gain in quality of life was too small to achieve an acceptable cost-effectiveness ratio. The most promising strategies for improving the cost-effectiveness of bilateral implantation are to increase effectiveness through enhanced signal processing in binaural processors, and to reduce the cost of implant hardware.
Two experiments were conducted to investigate egg weight, fertility, hatchability, and embryonic mortality in relation to time of oviposition of young and old broiler breeder flocks. In experiment 1, eggs were collected from 2 flocks (34 and 59 wk) for 2 d at hourly intervals between 0700 and 1900 h. Most eggs were laid between 0700 and 1300 h, but eggs were laid later in the day by the old flock. Weights of early laid (C1) eggs were significantly greater than middle laid (Cs) and the late laid (Ct) eggs in the young flock, whereas late laid eggs (Ct) were significantly smaller than early laid (C1) and middle laid (Cs) eggs in the old flock. In experiment 2, eggs from experiment 1 were categorized as early laid first-in-sequence (C1) eggs (0700 to 0800 h), the mid-sequence (Cs) eggs (0900 to 1200 h), and the late laid terminal-in-sequence (Ct) eggs (1300 to 1700 h). These eggs were incubated to determine fertility, hatchability, and stage of embryonic mortality relative to oviposition time and flock age. Fertility declined with flock age, but there were no differences due to time of oviposition. There were no differences in hatchability of fertile eggs or embryonic mortality relative to time of oviposition (sequence position) or flock age. These results suggested that although there were differences in egg weight among eggs at different times of the day (different sequence positions), there were no differences in fertility, fertile hatchability, or embryonic mortality in naturally mated broiler breeders.
OBJECTIVE: To compare neurodevelopmental outcome of survivors of the multicentre trial of etamsylate (the iRNN for ethamsylate) for prevention of periventricular haemorrhage in very low birthweight infants. DESIGN: Double blind, single observer, prospective follow up of placebo controlled study. SETTING: Six neonatal intensive care units in the United Kingdom. Neurodevelopmental outcome was assessed in health premises or children's homes. SUBJECTS: 268 of 276 survivors of the original study were seen between 3.5 and 4.2 years of age. All were inborn and weighed 1500 g or less at birth. INTERVENTION: Etamsylate 12.5 mg/kg or placebo six hourly from within one hour of delivery for four days. MAIN OUTCOME MEASURES: McCarthy scales of children's abilities, standardised neurological examination, full physical examination, functional assessment, seven letter Stycar vision test, and audiometry. RESULTS: There was no difference between the groups in neuromotor outcome (cerebral palsy) or in the general cognitive index (GCI) of the McCarthy scales (mean GCI was 93.3 for the etamsylate group (n = 133) and 89.7 for the placebo group (n = 131); p = 0.10). There were more children with GCI < 70 (9 v 19; p = 0.047) or </= 50 (3 v 11; p = 0.03) in the placebo group. Fewer children in the etamsylate group had squints (17 v 30; p = 0.042) or required surgery for patent ductus arteriosus (1 v 8; p = 0.036). CONCLUSIONS: Etamsylate was not associated with a reduction in cerebral palsy. Severe cognitive impairment was reduced, but more children died and the improvement may be because fewer survived with low GCI.
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AIM: This study aimed to chart the time course and durability of the effects of rosiglitazone, a potent thiazolidinedione-based peroxisome proliferator-activated receptor gamma agonist, on hepatic steatosis and intramyocellular lipid in an animal model of obesity, the Zucker Fatty (ZF) rat. METHODS AND RESULTS: Rosiglitazone (3 mg/kg/day p.o.) significantly reduced both liver fat content (by 59%; p < 0.05) and size (11.5%; p < 0.05) in male ZF rats that received between 3 days and 1 week of treatment, and these reductions were maintained for at least 12 weeks. Liver fat content measured by magnetic resonance spectroscopy (MRS) correlated closely and positively with plasma insulin levels (reduced by 89% within a week, r = 0.8) and with postmortem histological fat fractional volume (r = 0.89). Similarly, liver volume measured by magnetic resonance imaging (MRI) correlated closely with postmortem wet weight (r = 0.99). MRS also showed, and numbers of lipid vacuoles counted in transmission electron micrographs confirmed, that rosiglitazone significantly reduced the elevated intramyocellular lipid seen in ZF rat skeletal muscle by at least 40% (p < 0.05). CONCLUSIONS: Localized MRS and MRI showed that rosiglitazone reversed the hepatic steatosis, hepatomegaly and intramyocellular lipid, characteristic of the ZF rat, an animal model of obesity.
BACKGROUND: Infantile spasms (West's Syndrome) is a syndrome which includes a peculiar type of epileptic seizure, usually hypsarrhythmia and in the majority of patients, psychomotor retardation. It remains poorly understood and despite modern imaging techniques an underlying cause is often not found. Little is known about their pathophysiological basis and treatment remains problematic. OBJECTIVES: To compare the effects of single drugs used to treat infantile spasms upon long-term psychomotor development, subsequent epilepsy, control of the spasms and side effects. SEARCH STRATEGY: Our search included the Cochrane Epilepsy Group trials register, MEDLINE (1960 to 2001), EMBASE (1981 to 2001), contacting pharmaceutical companies and appeals at international conferences. SELECTION CRITERIA: Randomized controlled trials (RCTs) of the administration of drugs to people with infantile spasms. DATA COLLECTION AND ANALYSIS: Three reviewers independently selected trials for inclusion and extracted data. Study quality and potential sources of heterogeneity were assessed. Outcomes included cessation of spasms, time to cessation of spasms, participants with cessation of spasms remaining spasm free, reduction in spasms, resolution of hypsarrhythmia, subsequent epilepsy rates and side effects. MAIN RESULTS: Ten small RCTs were included. In total these studies recruited just 335 participants and tested eight different drugs. Overall, studies were of poor methodological quality. No study assessed long-term psychomotor development or the development of other seizure types. One small study found vigabatrin to be more efficacious than hydrocortisone in stopping infantile spasms in a group of people with tuberous sclerosis. One underpowered study showed a trend for vigabatrin to be more efficacious than placebo in stopping infantile spasms, two small studies when combined showed ACTH to be more efficacious than low-dose prednisone (2mg/kg). It was not possible to compare reduction in the number of spasms between the different treatments because of differences in methods of analysis. Overall, only nine participants were reported to have been withdrawn from the trial treatments due to side effects and two deaths were reported. REVIEWER'S CONCLUSIONS: We found no reliable evidence that any of the treatments assessed were more efficacious than any other. Few studies considered psychomotor development or subsequent seizure rates as outcomes and none had long term follow-up. Further trials with larger numbers of participants, and longer follow-up are required.
Tuberous sclerosis (TSC) is an inherited disorder best known for its association with severe learning difficulties, epilepsy, behavioural problems, skin and renal pathology Lymphangioleiomyomatosis (LAM), characterized by alveolar smooth muscle proliferation and cystic destruction of parenchyma, occurs as an infrequent symptomatic pulmonary complication in TSC and as a very rare sporadic disease in those without signs of TSC. Considered a generalized and progressive cystic lung disease that is difficult to treat with a poor prognosis, it has been reported almost exclusively in women, most commonly presenting with dyspnoea and pneumothorax in those of childbearing age. We investigated the clinical features and prognosis of LAM in patients with TSC including the effects of treatment, stratified by the method of diagnosis of LAM (i.e. histological or radiological). We found histological proof of diagnosis in 10 of 21 patients with TSC and symptomatic lung disease, onset in childhood in four, three males with LAM, individuals with apparently focal disease, great variation in clinical course and no clear treatment benefit. In those with TSC, symptomatic LAM is infrequent but causes a significant morbidity and mortality It was not possible to detect predisposing factors, other than being female. Males with apparent LAM should be rigorously investigated.
Lymphangioleiomyomatosis (LAM), characterized by alveolar smooth muscle proliferation and cystic destruction of lung parenchyma, can occur as a rare sporadic disease or as a complication of tuberous sclerosis (TSC). It is a cystic lung disease, usually generalized and progressive, may be extremely difficult to treat and has been considered to have a poor prognosis. It has almost exclusively been reported to present in women of childbearing age, most commonly with dyspnoea and pneumothorax. We reviewed the English literature from 1939 to 1997 for cases of LAM both with and without TSC, in order to document the prevalence, clinical features, investigations, treatment and outcome within and between these two groups. No study has yet determined the prevalence of LAM symptomatically within the general population, but it probably affects 1-3% of the TSC population. Patients with TSC often present with an insidious onset of dyspnoea whilst non-TSC patients present more commonly with acute breathlessness secondary to pneumothorax. Patients with TSC are also less likely to suffer from chylothorax. The age of onset of symptoms and of diagnosis are similar. LAM is rare in children and even less common in males in both groups. The natural course of LAM remains unclear and effect of treatment variable. Although symptomatic LAM is uncommon it causes a significant amount of morbidity and mortality both in the TSC and general population, but asymptomatic LAM is not uncommon in TSC. Further research is required to determine the natural history of this condition and to evaluate current treatment regimes.
BACKGROUND: This study was undertaken to assess whether the use of clomiphene citrate in conjunction with albumin-separated sperm would alter the sex ratio (expressed as the proportion of males) towards females and, if so, whether this skewing was due solely to the induction of ovulation. METHODS: The sex ratios of 184 single and 42 twin births at five assisted reproduction biology clinics were determined. The normal approximation to the binomial distribution was used to determine significant differences between these sex ratios and the established sex ratios for single, twin and combined (single and twin) non- and ovulation-induced births. RESULTS: The non-ovulation-induced sex ratios for singletons (51.4%) and twins (50.2%) were greater than the treatment singleton (27.7%; P < 0.001) and twin (33.3%; P < 0.01) sex ratios respectively. Correspondingly, the non-induced sex ratio for combined births (51.4%) was greater than the treatment sex ratio (28.8%; P < 0.001). The previously established induced singleton and twin sex ratios (48.1%) were lower than the non-induced sex ratio (51.4%), but higher than the treatment singleton (27.7%; P < 0.001) or twin (33.3%; P < 0.03) sex ratios. The ovulation-induced combined ratio (48.1%) was less than the non-induced combined (51.4%) sex ratio, although greater than the treatment combined sex ratio (28.8%; P < 0.001). CONCLUSION: Clomiphene citrate in conjunction with albumin-separated sperm decreased the sex ratio; a reduction that was not exclusively due to induction of ovulation.
AIM: To determine the diagnostic efficiency of assays routinely used in the investigation of hereditary angio-oedema. METHODS: Over a four year period, 1144 samples were received for analysis from 907 patients suspected of C1 inhibitor deficiency. Analyses were performed for C4 and C1 inhibitor (functional and immunochemical). Notes were reviewed retrospectively on patients with low serological indicators to determine diagnosis. RESULTS: These are the first data to indicate the sensitivity, specificity, and predictive values of the assays most frequently used to screen for C1 inhibitor deficiency. A combination of low C4 and low C1 inhibitor function has 98% specificity for C1 inhibitor deficiency in this population and a 96% negative predictive value, and is thus a very effective screen. All patients with untreated C1 inhibitor deficiency had a low C4 value. CONCLUSIONS: All patients considered for a diagnosis of C1 inhibitor deficiency should have serum examined to measure both C4 and functional C1 inhibitor. If either is normal at presentation this essentially excludes a diagnosis of C1 inhibitor deficiency. These tests can be performed sequentially. If C4 is normal it is not necessary to proceed to C1 inhibitor analysis. If C1 inhibitor function and C4 are both low then a repeat sample should be obtained to confirm the findings.
We present the first case of a middle cerebral artery aneurysm presenting as isolated hyperacusis. The patient had a Guglielmi detachable coil (GDC) embolization of his aneurysm with complete resolution of his symptoms. The pathophysiological mechanism is discussed. We suggest further radiological investigation in young patients presenting with this symptom.
BACKGROUND: Dental amalgamators may become contaminated internally with metallic mercury. This contamination may result from mercury leakage from capsules during trituration or from the long-term accrual from microscopic exterior contaminants that result from the industrial assembly process. The potential health risk to dental personnel from this contamination is unknown. METHODS: The authors assessed used amalgamators from the federal service inventory for the amounts of mercury vapor levels, as well as the visual presence of mercury contamination. They evaluated these amalgamators for potential mercury vapor health risk, using established National Institute for Occupational Safety and Health methods and American Conference of Governmental Industrial Hygienists standards. RESULTS: Ten of the 11 amalgamators assessed had measurable mercury vapor levels. Four amalgamators were found to have internal static mercury vapor levels above Occupational Safety and Health Administration ceiling limit thresholds. During a simulated worst-case clinical use protocol, the authors found that no amalgamators produced mercury vapor in the breathing space of dental personnel that exceeded established time-weighted federal mercury vapor limits. CONCLUSIONS: Amalgamators may be contaminated internally with metallic mercury. Although the authors detected mercury vapor from these units during aggressive, simulated clinical use, dilution factors combined with room air exchange were found to keep health risks below established federal safety thresholds. CLINICAL IMPLICATIONS: Dental personnel should be aware that amalgamators may be contaminated with mercury and produce minute amounts of mercury vapor. These contaminated amalgamators may require disposal as environmentally hazardous waste.
In the olfactory sensory system, neurons expressing a given odorant receptor project with precision to two of 1800 spatially invariant glomeruli creating a topographic map within the olfactory bulb. Olfactory sensory neurons have a half-life of about 90 days and are continually renewing. This poses the problem of how this precise spatial map is maintained throughout the life of the organism. We have developed a genetic approach to effect the synchronous ablation of subpopulations of neurons expressing a given receptor. The axons of newly generated neurons can then be followed as they enter the brain and converge on glomerular targets during adult life. The observation that following neuronal cell killing, the spatial map is faithfully restored, demonstrates that the information necessary for the establishment of the sensory map persists throughout the life of the organism.
In this review, we focus on the role of the L3 (third-stage larva) of lymphatic filarial nematodes in immunomodulation and in the development of protective immunity. Studies in the mouse models of Brugia have been fundamental to our understanding of the mechanisms by which infection with L3 results in Th2 responses and the active suppression of Th1 responses. The relevance of these phenomena to the human infection is discussed.
High school and junior high school students with neuromuscular weakness and other disorders of the arms evaluated a recently commercialized robotic workstation, the Arlyn Arm, to carry out art projects and science experiments. These tasks were designed for independent execution with the workstation using standard or custom-designed tools. Each task was divided into subtasks, and the execution time of each subtask was determined as a measure of efficiency. Special attention was given to the causes of required experimenter intervention. While subjects easily accomplished some subtasks, others required considerable intervention. Most of these interventions could be avoided by further customizing accessories. It is concluded that the Arlyn Arm workstation could be of considerable benefit in a classroom setting to persons with severe neuromuscular disorders.
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