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Biomedical subjects

F Warren

Publications and source records attributed to F Warren.

At least 19 recordsLinked to original sources
PubMed2006

Meta-analysis of mortality and cancer incidence among workers in the synthetic rubber-producing industry.

Production of synthetic rubber involves exposure to several potentially harmful chemicals. The authors carried out a systematic review and meta-analysis of cohort studies of workers in the rubber-producing industry. Data were obtained from computerized literature searches of several databases from their inception through December 2003. The reference lists of identified articles were inspected for further relevant articles. The authors conducted random-effects meta-analyses of log standardized mortality ratios (SMRs)/standardized incidence ratios. Heterogeneity between study results was explored through subgroup analyses and meta-regression on cohort demographic factors and study quality indicators. The authors identified 36 published articles reporting information on 31 different cohort groups. The meta-SMR was 0.86 (95% confidence interval (CI): 0.82, 0.91) for all-cause mortality (28 cohorts) and 0.94 (95% CI: 0.89, 1.01) for all malignant neoplasms (27 cohorts). Heterogeneity was observed for these endpoints and for the majority of disease-specific outcomes. Statistically significant excesses were observed for diabetes (meta-SMR=1.36, 95% CI: 1.17, 1.59) (five cohorts) and leukemia (meta-SMR=1.21, 95% CI: 1.03, 1.43) (16 cohorts), the latter particularly for persons working exclusively in nontire manufacturing (meta-SMR=1.70, 95% CI: 1.14, 2.54) (four cohorts). Excesses highlighted in previous narrative reviews were not substantiated. Interpretation of these results is complicated by substantial unexplainable heterogeneity; small excesses in specific mortality outcomes may have been disguised by the healthy worker effect.

Diabetes Mellitus↗
PubMed2001

The possible effects on health, comfort and safety of aircraft cabin environments.

A consultation was undertaken to investigate the views and concerns of stakeholders in the aircraft industry about the possible harmful effects on personal health, comfort and safety of aircraft cabin environments. Stakeholders were identified from a variety of sources including Government agencies, the Internet, House of Lords inquiry, and suggestions of interviewees. They represented: aircraft crews, aircraft constructors and engineers, government departments and authorities, holiday/flight companies, insurance companies, non-governmental organisations, occupational health physicians, passenger representatives, and independent researchers and consultants. Eighty-seven were contacted of which 57 were interviewed over the telephone using a semi-structured questionnaire. Their concerns were transcribed into a standard format and analysed qualitatively. Key stakeholders, along with Government officials, were invited to a workshop to discuss and prioritize the issues raised during the interviews. The main concerns expressed by the participants fell into five main areas: deep vein thrombosis, air quality, infection, cosmic radiation, and jet lag and work patterns. In addition, a number of safety concerns were raised as well as comments on the provision of appropriate advice to passengers. It was generally felt that further research was required on each of these subjects, as well as an improvement in the quality, quantity and availability of information provided for passengers prior to boarding a flight.

Air Pollution, Indoor↗
PubMed1997

Change in borderline symptoms one year after therapeutic community treatment for severe personality disorder.

BACKGROUND: The view that severe personality disorder (SPD) is untreatable derives from poor-quality studies of treatment outcome which use indirect measures of SPD pathology. This study evaluates the impact of psychotherapeutic in-patient treatment on core personality disorder symptoms. METHOD: 137 SPD patients completed the Borderline Syndrome Index (BSI) on referral and one year post-treatment ('admitted', n = 70) or one year post-referral ('non-admitted', n = 67); 22 of the non-admitted group were refused extra-contractual referral funding for their treatment. RESULTS: There was a significantly greater reduction in BSI scores in the treated than in the non-admitted group. Changes in BSI scores were significantly positively correlated with length of treatment. Assessment of the reliability and clinical significance of changes in individual subjects showed that the magnitude of this change was reliable and clinically significant in 42.9% of the admitted sample, compared with only 17.9% of the non-admitted sample (18.2% of the unfunded group). CONCLUSIONS: Specialist in-patient treatment is effective in reducing core SPD psychopathology.

Borderline Personality Disorder↗
PubMed1996

Beneficial effects of corticosteroids on ocular myasthenia gravis.

OBJECTIVE: To determine if moderate-or low-dose corticosteroid therapy can reduce the diplopia and frequency of deterioration to generalized disease in ocular myasthenia gravis. DESIGN: Retrospective record review. SETTING: Two university-based neuro-ophthalmology services. PATIENTS: All 32 patients with ocular myasthenia gravis, treated with prednisone, followed up for a minimum of 2 years were included. Patients were treated with 1 or more courses of daily prednisone (highest initial dose, 40-80 mg) gradually withdrawn over 4 to 6 weeks. Subsequently, in 6 patients, 2.5 to 20 mg of prednisone was given on alternate day. OUTCOME MEASURES: Diplopia in the primary position or downgaze diplopia and generalized myasthenia gravis after 2 years of follow-up. RESULTS: Diplopia, which was initially found in the primary position in 29 patients and in the downgaze position in 26 patients, was absent in 21 patients at 2 years. Generalized myasthenia gravis occurred in 3 patients at 2 years. Elevated serum acetylcholine receptor antibody levels and abnormal electromyography findings were not predictive of worsening. No patient experienced a major steroid complication. CONCLUSIONS: Moderate-dose daily prednisone for 4 to 6 weeks, followed by low-dose alternate-day therapy as needed, can control the diplopia in patients with ocular myasthenia gravis. The frequency of deterioration to generalized myasthenia gravis at 2 years may be reduced; 9.4% in this study compared with more than 40% previously reported frequency. Corticosteroids may be useful even when ocular motor dysfunction is not normalized.

Adrenal Cortex Hormones↗
PubMed1996

Venous obstruction as the cause of retinal/choroidal dysfunction associated with arteriovenous shunts in the cavernous sinus.

OBJECTIVE: To determine the hemodynamic abnormalities that result in visual acuity loss because of retinal or choroidal dysfunction associated with arteriovenous shunts (AVS) that involve the cavernous sinus. METHODS: Retrospective study of the records of 250 patients with either a carotid cavernous fistula or dural arteriovenous malformation revealed a total of 10 patients with vision loss secondary to retinopathy (group I) or choroidal effusion (group II). The cerebral angiograms of these 10 patients and 10 additional patients with visual dysfunction due to elevated intraocular pressure (group III) were evaluated to determine whether the three groups could be distinguished by a specific vasculopathic pattern. Particular attention was given to the extent of thrombosis in the ophthalmic venous system and cavernous sinus. RESULTS: There were angiographic signs of severe thrombosis in the ophthalmic vein in nine patients and in the cavernous sinus in seven patients ipsilateral to the retinal or choroidal lesion. In contrast, in group III, severe thrombosis in the ipsilateral ophthalmic vein and in the cavernous sinus occurred in one and two patients, respectively. Closure of the AVS improved the visual acuity in 1 of 4 patients in group I and in 4 of 5 patients in group II, and normalized the intraocular pressure in all patients. CONCLUSIONS: Ophthalmic vein thrombosis, rather than arterialization of the venous system or an arterial "steal, " is the principal cause of retinal or choroidal dysfunction associated with AVS to the cavernous sinus. Following AVS closure, visual recovery is more frequent with choroidal effusion or detachment rather than with retinopathy.

Adult↗
PubMed1993

Medical applications of single-chain antibodies.

A single-chain antibody or single-chain Fv (sFv) incorporates the complete antibody binding site in a single polypeptide chain of minimal size, with an approximate molecular weight of 26,000. In antibodies, the antigen combining site is part of the Fv region, which is composed of the VH and VL variable domains on separate heavy and light chains. Efforts over nearly two decades have indicated that Fv fragments can only rarely be prepared from IgG and IgA antibodies by proteolytic dissection. Beginning in 1988, single-chain analogues of Fv fragments and their fusion proteins have been reliably generated by antibody engineering methods. The first step involves obtaining the genes encoding VH and VL domains with desired binding properties; these V genes may be isolated from a specific hybridoma cell line, selected from a combinatorial V-gene library, or made by V gene synthesis. The single-chain Fv is formed by connecting the component V genes with an oligonucleotide that encodes an appropriately designed linker peptide, such as (Gly4-Ser)3. The linker bridges the C-terminus of the first V region and N-terminus of the second, ordered as either VH-linker-VL or VL-linker-VH. In principle, the sFv binding site can faithfully replicate both the affinity and specificity of its parent antibody combining site, as demonstrated in our model studies with the 26-10 anti-digoxin sFv. Furthermore, the sFv remains stable at low concentrations that promote VH and VL dissociation from the Fv heterodimer, resulting in loss of Fv binding. Intravenously administered sFv proteins exhibit accelerated biodistribution and exceptionally fast clearance compared to IgG or Fab. These pharmacokinetic properties allow rapid imaging by sFv, which therefore may be labeled with a short-lived isotope such as Tc-99m. Expression of a single gene product from fused sFv and effector genes facilitates immunotargeting of the effector protein, as shown for single-chain Fv toxin fusion proteins.

Amino Acid Sequence↗
PubMed1992

Maculopathy caused by intra-arterially administered cisplatin and intravenously administered carmustine.

Eight patients with malignant gliomas were monitored with clinical examinations to study the effects of the combination of intravenous administration of carmustine and infraophthalmic intra-arterial administration of cisplatin on retinal and optic nerve function. Three patients developed a severe macular retinal pigment abnormality in the eye ipsilateral to the intra-arterial infusion. Electrophysiologic studies disclosed no evidence of a generalized disturbance in the photoreceptors, middle retinal layers, or retinal pigment epithelium. In contrast to previous studies involving patients whose visual loss was caused by vaso-occlusive lesions in the retina and optic nerve, our study involved patients with clinically significant maculopathy, that was not vascular in origin and that developed after treatment with carmustine and cisplatin. We suggest that the deficit may result from a localized retinal pigment disturbance in the macula.

Adult↗
PubMed1992

Evolution of oculomotor nerve palsies.

The management of patients with isolated oculomotor nerve palsies (OMPs) who have normal pupils and no other signs of neurological disease is a controversial issue. A more precise delineation of the clinical course of isolated OMPs may help to determine whether neuroradiologic evaluation is indicated in these cases. We studied 41 patients with isolated third cranial nerve palsies, emphasizing the times of progression and resolution of the oculomotor nerve dysfunction. The average interval from onset to development of maximal ophthalmoplegia failed to differentiate between a microvascular etiology (3.3 days) or posterior communicating artery aneurysm (3 days). Of the 28 patients with diabetic or idiopathic palsies, regardless of pupillary involvement, 68% had improvement of the oculomotor paresis within 4 weeks, 96% within 8 weeks, and 100% within 12 weeks of the onset of symptoms. Our study suggests that patients with pupil-sparing OMPs should be considered for extensive neuroradiologic evaluation only if there is deterioration or failure to improve within 4 to 8 weeks.

Adult↗
PubMed1989

Increasing gene expression in yeast by fusion to ubiquitin.

Heterologous gene expression in yeast can be increased up to several hundred-fold by expressing a foreign gene as a fusion to the ubiquitin gene. An endogenous yeast endoprotease (Ub-Xase) removes the ubiquitin from the fusion product to produce the authentic protein. The utility of this technique has been demonstrated by expression of three different proteins in yeast as both unfused and ubiquitin-fused forms: 1) the alpha subunit of the mammalian stimulating G-protein of the adenylate cyclase complex (Gs alpha); 2) a soluble fragment of the T cell receptor protein (sCD4); and 3) the protease domain of human urokinase (UKP). The sequence specificity of the Ub-Xase was demonstrated by mutagenesis of the carboxyl-terminal glycine of ubiquitin to an alanine, which inhibited ubiquitin removal in vivo. Processing of the ubiquitin-Gs alpha fusion protein (ub-Gs alpha) in vivo resulted in Gs alpha which could be reconstituted in mammalian membrane preparations and had the same specific activity as the authentic Gs alpha expressed in yeast. The yeast Ub-Xase has also been shown to work in vitro by the processing of a ub-sCD4 fusion protein synthesized in Escherichia coli. This technology should greatly enhance the utility of yeast for heterologous protein production.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Management of nontraumatic vascular shunts involving the cavernous sinus.

The authors managed 38 consecutive cases of nontraumatic vascular shunts involving the cavernous sinus. Selective angiography demonstrated 12 carotid cavernous fistulas (CCFs) and 26 dural arteriovenous shunts (DAVSs). Visual disability occurred from glaucoma, venous retinopathy, optic neuropathy, or diplopia. Ten patients with slow-flow shunts and minimal dysfunction were treated medically to lower intraocular pressure (IOP) and/or instructed in manual compression of the internal carotid artery, ipsilateral to the lesion, using the contralateral hand. Percutaneous intraarterial embolization using detachable balloons, isobutylcyanoacrylate, or polyvinyl alcohol particles was successful in 16/18 DAVSs and 9/10 CCFs. The neuro-ophthalmic signs resolved in these 25 cases. Complications occurred in five patients. These included a transient hemiparesis, twelfth nerve palsy, unilateral nasal field loss, a pseudoaneurysm causing a third-nerve paresis, and temporary cavernous sinus thrombosis. Conservative therapy in mild cases and embolization in cases with visual disability or progressive signs are warranted.

Arteriovenous Fistula↗
PubMed1987

Regulation of NAD metabolism in Salmonella typhimurium: genetic analysis and cloning of the nadR repressor locus.

The nadR locus (99 min) controls the transcription of several genes involved with either the biosynthesis (nadAB) or recycling (pncB) of NAD in Salmonella typhimurium. Point mutations in this locus were found to cause defects either in the transport of nicotinamide mononucleotide (PnuA-), the regulation of nadAB (NadR-) or both transport and regulation (PnuA-NadR-). Deletions or insertions into nadR always resulted in the PnuA- NadR- phenotypes. Merodiploids constructed with various combinations of PnuA-, NadR- or PnuA- NadR- strains indicate a single complementation group. The results suggest the NadR product is a bifunctional regulatory protein. Operon fusions to lacZ (nadR :: Mud1-8) were used to show that nadR is not autoregulated and is transcribed in a clockwise direction. The gene was also cloned and located within a 2 kb EcoR1-Bg/II fragment.

Biological Transport↗
PubMed1986

Oxygen-regulated stimulons of Salmonella typhimurium identified by Mu d(Ap lac) operon fusions.

Using the technique of Mu d1(Ap lac)-directed lacZ operon fusions, several oxygen-regulated genetic loci were identified in Salmonella typhimurium. Thirteen anaerobically inducible and six aerobically inducible operon fusions were identified. Based on control by the oxrA and oxrB regulatory loci, the anti-lacZ fusions were grouped into three classes: class I loci were regulated by both oxr loci, class II genes were regulated by oxrA only, and class III loci were not affected by either regulatory locus. Several of the anti-lacZ fusions required growth in complex medium before they exhibited the inducible phenotype. While the expression of some of these loci was repressed when organisms were grown in nitrate, others were stimulated by nitrate. Fusions into the hyd and phs loci were identified among the isolated anti-lacZ fusions. Six oxygen-inducible (oxi) operon fusions were also identified. Two of the oxi loci mapped near oxygen-regulatory loci: oxiC near oxrA and oxiE near oxyR. However, neither fusion appeared to occur within the regulatory locus. The data presented serve to further define the aerobic and anaerobic stimulons of S. typhimurium but indicate additional regulatory circuits above those already defined.

Aerobiosis↗
PubMed1984

Formation of termination-resistant transcription complex at phage lambda nut locus: effects of altered translation and a ribosomal mutation.

Transcription antitermination by lambda N gene product is affected in a mutant Escherichia coli with altered ribosomal protein S10, caused by the nusE71 mutation. To study the role of translation in antitermination, we have fused the phage nutR locus, the site of action of N, with the lac regulatory region. We have monitored N action by measuring galactokinase, whose synthesis depends on suppression of terminators located between nutR and the galK cistron. We show that a deletion removing potential ribosome binding signals and AUG codons from the upstream region of nut site does not affect N action. Moreover, the lack of translation upstream of nutR does not overcome the antitermination defect caused by nusE mutation. When the upstream region is translated, however, N action is impaired if translation terminates 19 base pairs upstream of nutR . Termination of translation at further upstream sites, such as 23 or 97 base pairs upstream, does not interfere with N action. Our results suggest that the S10 ribosomal protein is required for N action without involving translation. These results also suggest that the nut site RNA itself plays an important role in the formation of a termination-resistant transcription complex.

Bacteriophage lambda↗