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Biomedical subjects

W Taylor

Publications and source records attributed to W Taylor.

At least 73 records · Page 4Linked to original sources

Inhibitors of serine/threonine phosphoprotein phosphatases alter circadian properties in Gonyaulax polyedra.

Protein serine/threonine phosphatases were implicated in the regulation of circadian rhythmicity in the marine dinoflagellate Gonyaulax polyedra based on the effects of three inhibitors specific for protein phosphatases 1 and 2A (okadaic acid, calyculin A, and cantharidin). Chronic exposure to okadaic acid resulted in a significant period lengthening, as measured by the bioluminescent glow rhythm, whereas cantharidin and calyculin A caused large phase delays but no persistent effect on period. Short pulses of the phosphatase inhibitors resulted in phase delays that were greatest near subjective dawn. Unlike 6-dimethylaminopurine, a protein kinase inhibitor, okadaic acid, calyculin A, and cantharidin did not block light-induced phase shifts. The inhibitors tested also increased radiolabeled phosphate incorporation into Gonyaulax proteins in vivo and blocked protein phosphatase 1 and 2A activities in Gonyaulax extracts. This study indicates that protein dephosphorylation catalyzed by protein serine/threonine phosphatases is necessary for proper functioning of the circadian system.

Animals↗

A preliminary investigation of chlorinated hydrocarbons and chronic fatigue syndrome.

OBJECTIVE: To determine whether serum levels of chlorinated hydrocarbons are elevated in patients with chronic fatigue syndrome. METHODS: Chlorinated hydrocarbon levels were measured in 22 patients with chronic fatigue syndrome (CFS) (as defined by the Centers for Disease Control [CDC]); in 17 patients with CFS symptoms whose history of exposure to toxic chemicals excluded them from the research definition of CFS; and in 34 non-CFS control subjects matched for age and sex. RESULTS: DDE (1,1-dichloro-2,2-bis (p-chlorophenyl) ethene) was detected in all serum samples at levels over 0.4 ppb. The incidence of hexachlorobenzene (HCB) contamination (> 2.0 ppb) was 45% in the CFS group, compared with 21% in the non-CFS control group (P < 0.05). The CFS group had a significantly higher total organochlorine level (15.9 ppb; SEM, 4.4) than the control group (6.3 ppb; SEM, 1.1; P < 0.05). The toxic exposure group also had a higher mean organochlorine level (13.6 ppb; SEM, 6.2) than the control group, but the difference was not statistically significant. DDE and HCB comprised more than 90% of the total organochlorines measured in each of the groups. CONCLUSION: The results suggest that recalcitrant organochlorines may have an aetiological role in CFS. There were no significant differences in serum organochlorine concentrations between CFS patients and chronic fatigue patients with a history of toxic chemical exposure. Therefore, exclusion of patients from the CDC research definition of CFS on the basis of a reported history of known exposure to toxic chemicals is not valid. The role of low-level organochlorine bioaccumulation in the development of CFS symptoms requires further investigation.

Adolescent↗

Pial arteriovenous fistula in children as presenting manifestation of Rendu-Osler-Weber disease.

We present four cases of pial arteriovenous fistula (AVF) in children as the presenting manifestation of Rendu-Osler-Weber disease (ROW). The common clinical manifestations of ROW in adults, such as skin telangiectasia and mucosal haemorrhagic complications, seldom occur in children, since telangiectases develop with age. Pial AVF in ROW also conform to the usual age incidence and are therefore present in childhood. Of the four children in this series, three had multiple AVF. Two presented with central nervous system haemorrhage, one with seizures and the other with progressive neurological deficit. There were no clinical or angioarchitectural differences between the AVF associated with ROW and sporadic AVF. The diagnosis was based in all cases on the family history. Transarterial embolisation to obliterate the AVF was carried out in all patients. One patient had early rebleeding after partial embolisation of the AVF, with a fatal outcome. Three patients were cured and one asymptomatic in long-term follow up. No exhaustive search was conducted for multiorgan telangiectases, since there is no indication for treatment of asymptomatic telangiectasia in ROW. No pulmonary fistulae were found. ROW should be suspected in children with multiple pial AVF; they may be the only manifestation of the disease, since epistaxis and telangiectasia are unusual in early life.

Adolescent↗

Assessment of the safety and efficacy of iobitridol, an iodinated contrast medium (30% iodine), in cranial CT.

In a single-centre comparative randomised double-blind trial, 40 patients undergoing head CT were examined using iobitridol and compared with 40 examined using iohexol. The contrast media were assessed for clinical safety and diagnostic efficacy. No significant difference was observed between the two groups and there were no significant reactions. It is concluded that iobitridol is a safe and effective contrast medium.

Adult↗

Juvenile xanthogranuloma of nerve root origin.

A case of juvenile xanthogranuloma arising from the first sacral nerve root is reported together with a review of the literature. The patient presented with symptoms of low back pain and sciatica, and with S1 nerve root tensions signs. Computed tomography and magnetic resonance imaging revealed a mass arising from the right S1 nerve root. The tumour was resected, and the morphological and immunocytochemical appearances of the lesion confirmed the diagnosis of juvenile xanthogranuloma. Soft tissue juvenile xanthogranulomas have been described but are extremely rare. However, we believe this is the first reported case of such a tumour affecting a spinal nerve root.

Adolescent↗

The genetic and functional basis of purine nucleotide feedback-resistant phosphoribosylpyrophosphate synthetase superactivity.

The genetic and functional basis of phosphoribosylpyrophosphate synthetase (PRS) superactivity associated with purine nucleotide inhibitor-resistance was studied in six families with this X chromosome-linked purine metabolic and neurodevelopmental disorder. Cloning and sequencing of PRS1 and PRS2 cDNAs, derived from fibroblast total RNA of affected male patients by reverse transcription and PCR amplification, demonstrated that each PRS1 cDNA contained a distinctive single base substitution predicting a corresponding amino acid substitution in the PRS1 isoform. Overall, the array of substitutions encompassed a substantial portion of the translated sequence of PRS1 cDNA. Plasmid-mediated expression of variant PRS1 cDNAs in Escherichia coli BL21 (DE3/pLysS) yielded recombinant mutant PRS1s, which, in each case, displayed a pattern and magnitude of purine nucleoside diphosphate inhibitor-resistance comparable to that found in cells of the respective patient. Kinetic analysis of recombinant mutant PRS1s showed that widely dispersed point mutations in the X chromosome-linked PRPS1 gene encoding the PRS1 isoform result in alteration of the allosteric mechanisms regulating both enzyme inhibition by purine nucleotides and activation by inorganic phosphate. The functional consequences of these mutations provide a tenable basis for the enhanced production of phosphoribosylpyrophosphate, purine nucleotides, and uric acid that are the biochemical hallmarks of PRS superactivity.

Base Sequence↗

A prospective trial comparing the efficacy and complications of the modified Dornier HM3 and MFL 5000 lithotriptors for solitary renal calculi.

A prospective randomized study of 198 patients was conducted to compare the efficacy of the modified Dornier HM3 lithotriptor to the MFL 5000 lithotriptor. Entrance criteria included solitary stones at any location within the upper collecting system that had not previously been treated with lithotripsy. Following lithotripsy the patients were evaluated by a blinded radiologist with a plain abdominal film, tomograms and renal ultrasound at 1, 4 and 12 weeks. Patients were classified at 12 weeks after lithotripsy as failing treatment if any stone fragments were imaged. Of the patients 170 were available for complete 3-month followup. No statistical or clinical difference in stone-free rates was apparent for calculi in the ureter or renal pelvis in either group. Of patients with lower caliceal stones 80% had no residual fragments visualized at 12 weeks when treated with the modified HM3 device versus 56% with the MFL 5000 lithotriptor (p = 0.05). Treatment time on the MFL 5000 unit was significantly prolonged compared with the modified HM3 device (0.7 hours versus 0.4 hours, respectively) resulting in fewer patients being treated in a given day (p < 0.001). No statistical difference in complication rates could be found between the 2 machines. Steinstrasse were noted in 10% of the patients treated with the modified HM3 device and 6% of the MFL 5000 group. Subcapsular hematomas were noted in 4% of the MFL 5000 treatment arm compared to 1% in the modified HM3 group. Overall, the MFL 5000 lithotriptor was believed to offer no significant clinical advantage over the modified HM3 device in terms of lithotripsy efficacy, although the multifunctional table did offer more versatility for stone treatment. For a busy lithotripsy center, the modified HM3 lithotriptor is still the most efficacious.

Adult↗

Can bruits distinguish high-grade from moderate symptomatic carotid stenosis? The North American Symptomatic Carotid Endarterectomy Trial.

OBJECTIVE: To determine whether cervical bruits, alone or combined with other clinical characteristics, can distinguish high-grade (70% to 99%) carotid artery stenoses from less severe stenoses in patients with symptoms of cerebrovascular disease. DESIGN: Cross-sectional comparison of clinical observations with contemporaneous angiography. SETTING: The North American Symptomatic Carotid Endarterectomy Trial (NASCET), a multicenter randomized controlled trial of carotid endarterectomy. PATIENTS: All patients enrolled in the NASCET from its inception in 1988 to November 1991. RESULTS: A focal ipsilateral carotid bruit had a sensitivity of 63% and a specificity of 61% for high-grade stenosis and, when absent, only lowered the probability for high-grade stenosis from a pretest value of 52% to a post-test probability of 40%. When combined with four other clinical characteristics (an infarction on computed tomography of the head, a carotid ultrasound scan suggesting more than 90% stenosis, a transient ischemic attack rather than a minor stroke as a qualifying event, and a retinal rather than a hemispheric qualifying event), the predicted probabilities of high-grade stenosis ranged from a low of 18% (when none of the features was present) to a high of 94% (when all the features were present. CONCLUSIONS: Cervical bruits alone were not sufficiently predictive of high-grade symptomatic carotid stenosis to be useful in selecting patients for angiography; they were absent in over one third of patients with high-grade stenosis. When combined with other clinical variables, patients with high or low probabilities of 70% to 99% stenoses could be identified, but this prediction model still missed many individuals with high-grade stenosis, even in this training set of selected patients.

Angiography↗

Carpal tunnel syndrome and hand-arm vibration syndrome. A diagnostic enigma.

OBJECTIVE: This article serves to draw attention to the risk to workers from repetitive strain and hand-arm vibration in the workplace and to the diagnostic difficulty in distinguishing carpal tunnel syndrome from the sensorineural component of hand-arm vibration syndrome. DATA SOURCES: Journal publications, textbooks on hand-arm vibration, guidelines of the International Standards Organisation, and European Economic Community directives. STUDY SELECTION: Recent reports and current standards. CONCLUSION: Carpal tunnel syndrome can be distinguished from hand-arm vibration syndrome if all factors--anatomical, associated physiological and medical conditions, work exposure history, and ulnar nerve involvement--are evaluated. In some circumstances, the conditions may be present together. A correct diagnosis is crucial because surgical intervention is not usually beneficial if hand-arm vibration exposure has been a contributing factor. The further reduction in grip strength may constitute a serious additional handicap for a worker.

Carpal Tunnel Syndrome↗

Absence of paramyxovirus RNA in cultures of pagetic bone cells and in pagetic bone.

It has been proposed that Paget's disease of bone is caused by the infection of bone cells with one or several paramyxoviruses. In this study we used the polymerase chain reaction (PCR), which allows the detection of very low levels of a target nucleic acid sequence, to study cultures of pagetic bone cells and samples of pagetic bone. Oligonucleotide primers were designed to flank a sequence of the nucleocapsid genome of measles virus and canine distemper virus (CDV). Within this fragment there were contrasting restriction endonuclease sites specific to measles or CDV that allowed identification of the original template. We were unable to detect paramyxovirus RNA in four strains of human bone cells outgrown from pagetic bone and one strain derived from an uninvolved site of a patient with Paget's disease. Furthermore, paramyxovirus sequences were not detected in cDNA prepared from six samples of pagetic bone biopsies. The work presented here further questions the role of measles and CDV in the abnormal remodeling observed in Paget's disease.

Aged↗

Borrelia burgdorferi decreases hyaluronan synthesis but increases IL-6 production by fibroblasts.

Despite the prevalence of clinical data on human Lyme disease, little is known about the immunopathologic effects of the causative organism on the host. We studied the effect of Borrelia burgdorferi on hyaluronan (hyaluronic acid, HYA) production and the effect on interleukin-6 (IL-6) synthesis by cultured fibroblasts. The cell line employed in this study produced an average of 1406 ng of hyaluronan/ml within 48 h. Using both a morphological staining protocol and a quantitative radiometric assay, we noted that in the presence of a low dose of Borrelia (9.4 x 10(5) cells/ml) the hyaluronan production decreased to an average of 1008 ng/ml, a significant difference (p < 0.05) from the amount of hyaluronan produced by the cells alone. The reduction was even more significant (p < 0.01) when a higher dose of Borrelia (9.4 x 10(6) cells/ml) was used giving an average hyaluronan concentration of 682 ng/ml. In contrast, we found that Borrelia stimulated the cells to produce IL-6 from a baseline of 293 pg/ml to a maximal value of 842 pg/ml (p < 0.01). The spirochetes had no significant effect on cell viability, nor were we able to demonstrate invasion of the cells by the bacteria. Both a decrease in hyaluronan and an increase in IL-6 may correlate with the pathogenicity of Lyme disease in man.

Borrelia burgdorferi Group↗

Reversible tonsillar prolapse in vein of Galen aneurysmal malformations: report of eight cases and pathophysiological hypothesis.

We report eight cases of vein of Galen aneurysmal malformation (VGAM) associated with a "Chiari type I malformation." In four cases magnetic resonance imaging (MRI) or computed tomography performed in the neonatal period did not demonstrate the posterior fossa anomaly, which appeared on later scans. In the other cases the MRI was performed in infancy and the anomaly was already present. We compared the venous phases of the posterior fossa angiograms and the MRI in these patients. In all eight cases, the angiograms showed a reflux in the cerebellar veins, via the petrous vein, associated with a uni- or bilateral stenosis or thrombosis of the distal posterior dural sinuses. Furthermore, in two cases the posterior fossa returned to normal on MRI following endovascular treatment, while in three cases the herniation of the cerebellar tonsils decreased after the embolization. Tonsillar prolapse becomes irreversible when the venous outlet is incapable of taking the flow even when the VGAM has been treated adequately. In eight additional cases of VGAM for which MRI and angiogram studies were available and in which stenosis or thrombosis of posterior dural sinuses was present without tonsillar prolapse, no reflux into the cerebellar veins was shown. We suggest that the posterior fossa hydrovenous congestion is a result of inadequate venous drainage and that the tonsillar descent is reversible if adequate venous drainage is reconstituted following therapeutic embolization of the fistula. Tonsillar prolapse is not a consequence of mass or raised intraventricular pressure. Our observation suggests that in some other conditions, the "Chiari I malformations" may be secondary to early hydrovenous dysfunction of the posterior fossa.

Arteriovenous Shunt, Surgical↗

Haemorrhage associated with silastic dural substitute.

Three cases of haemorrhage after the use of a silastic dural substitute are presented. In all cases the implant was removed and further haemorrhage has not occurred. Published work is reviewed and the implications for the continued use of silastic are discussed.

Adult↗

Sensorineural objective tests in the assessment of hand-arm vibration syndrome.

Assessment (staging) of workers exposed to vibration, based solely on a subjective history, has been shown to be unsatisfactory. The internationally agreed use of a sensorineural component in the Stockholm classification requires the use of sensory objective tests. Four hundred and twenty two subjects were assessed by a subjective history supplemented by multiple objective tests. These tests covered the vascular, sensorineural, musculoskeletal and dexterity aspects of hand-arm vibration syndrome. Tests to help with the differential diagnosis were also performed. Sensorineural tests are reported as are the associations between the subject's final Stockholm sensorineural staging and the subject's aesthesiometry, temperature threshold results, and grip strength. Scoring systems for these tests were evolved. Data showed that multiple sensory tests increased the accuracy of staging. Aesthesiometry, the temperature neutral zone tests, and grip strength were appropriate for the assessment of the sensory component, especially in separating sensorineural stages 0 and 1 from sensorineural stages 2 and 3. This is an important separation for an occupational physician monitoring subjects exposed to vibration. Analyses of the sensory tests clearly indicated that they need to be done on all digits. In this survey the sensorineural damage was greatest in the forefinger (second) and the little (fifth) fingers. No association was found between smoking and the final staging, aesthesiometry, temperature neutral zone thresholds, or grip strength.

Adult↗

Hyperoxia induces interstitial (type I) and increases type IV collagenase mRNA expression and increases type I and IV collagenolytic activity in newborn rat lung.

Oxygen toxicity is attributed to the reaction of oxygen metabolites with cellular components leading to cell destruction. Activation of latent human neutrophil interstitial collagenase by reactive oxygen species has been demonstrated. The potential role of collagenases in hyperoxic lung injury has not been investigated. We studied the effect of hyperoxia on newborn rat lung water content, morphology and ultrastructure, interstitial (type I) and type IV collagenase gene expression and type I and IV collagenolytic activity. We observed that hyperoxia causes pulmonary edema, alters newborn rat lung morphology in a sequential manner and produces ultrastructural alterations, induces type I and increases type IV collagenase mRNA expression, and increases type I and IV collagenolytic activity. A role for type I and IV collagenase in hyperoxic newborn lung injury or in the recovery following the injury is proposed.

Animals↗