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Biomedical subjects

M Thomas

Publications and source records attributed to M Thomas.

At least 19 recordsLinked to original sources

Female liver transplant recipients with the same GFR as male recipients have lower MELD scores--a systematic bias.

Women have lower glomerular filtration (GFR) than men for the same serum creatinine (Cr) value, not accounted for in model for end-stage liver disease (MELD). We compare male/female Cr, GFR (using MDRD formula) and respective MELD scores in 403 Cr measurements using standard (sCr), O'Leary modified (mCr) and Compensated (cCr) Jaffe and Enzymatic (eCr) in 158 liver disease patients, mCr in 208 liver transplantation (LT) candidates, and EDTA-Cr(51)-GFR in 38 other candidates for LT; considering each female as male, a 'corrected' Cr was derived. MELD scores were calculated for measured and "corrected" Cr in females. Median Cr and GFR in females were lower than males (p < 0.05). Both MDRD and EDTA-Cr(51) GFR were lower in females than males, despite lower Cr values. In females, each MELD score was lower than the corresponding MELD-corrected Cr (p < 0.001) with > or =three-point difference in liver disease patients: 25%[sCr]; 23%[mCr]; 11%[eCr]; and 14%[cCr]. In 65% of female LT candidates, two- or three-point difference was found. Females with liver disease have lower GFR than males for the same Cr value; correcting Cr increases MELD score by two or three points in 65% of female LT candidates. MELD score adjustment in females would ensure equal LT priority by gender.

Adult↗

OEIS complex: prenatal ultrasound and autopsy findings.

OBJECTIVE: To describe prenatal ultrasound and autopsy findings in fetuses with OEIS (omphalocele, bladder exstrophy, imperforate anus, spina bifida) complex. METHODS: This was a retrospective study of the nine cases with OEIS complex diagnosed at our center using detailed fetal ultrasound during the last 10 years. We summarized the fetal ultrasound findings that led to the diagnosis and compared them with the autopsy results. RESULTS: All affected fetuses were diagnosed using detailed fetal ultrasound after 16 weeks' gestation. The main prenatal findings were omphalocele, skin-covered lumbosacral neural tube defect, non-visualized bladder and limb defects. Prenatal sonography failed to detect the abnormal genitalia, bladder exstrophy and anal atresia. All cases had abnormalities in a 'diaper distribution', which helped in making the prenatal diagnosis. Eight of the nine couples chose to terminate the pregnancies following multidisciplinary counseling. The pregnancy that was continued was a case with dizygotic twins discordant for OEIS, and the affected fetus died in utero. CONCLUSIONS: The combination of the following ultrasound findings: ventral wall defect, spinal defect and a non-visualized bladder with or without limb defects, are characteristic of OEIS complex. Diagnosis can be made with confidence as early as 16 weeks' gestation, although earlier diagnosis may be possible.

Abnormalities, Multiple↗

Controlled drug delivery to the lung: Influence of hyaluronic acid solution conformation on its adsorption to hydrophobic drug particles.

This work reports investigations into the interaction and adsorption of the hydrophilic polymer hyaluronic acid (HA) onto the surface of the hydrophobic corticosteroid drug fluticasone propionate (FP). The eventual aim is to formulate a bioadhesive pulmonary drug delivery system with prolonged action that avoids rapid clearance from the lungs by the mucociliary escalator. Adsorption isotherms detailing the adsorption of HA from aqueous HA solution concentrations ranging from 0.14 to 0.0008% (w/v) to a fixed FP particle concentration of 0.1% (w/v) were investigated. The method of preparing FP particles with HA molecules adsorbed on their surfaces (FP/HA particles) involved suspension of the FP either in hydrated HA solution or in water followed by addition of solid HA, centrifugation of the solids to form a pellet, washing the pellet several times with water until no HA was found in the supernatant and then freeze drying the suspension obtained by dispersing the final pellet. The freeze dried powder was then analysed for adsorbed HA using a Stains-all assay. The influence of order of addition of HA to FP, time for the adsorption process, and temperature of preparation on the adsorption isotherms was investigated. The non-equilibrium adsorption isotherms produced generally followed the same trend, in that as the HA solution concentration increased, the amount of HA adsorbed increased to a maximum at a solution concentration of approximately 0.1% (w/v) and then decreased. The maxima in the adsorption isotherms were close to the change from secondary to tertiary conformation in the HA solutions. Below the maxima, adsorption occurred via interaction of FP with the hydrophobic patches along the HA chains in the secondary structures. Above the maxima, secondary HA molecules aggregate in solution to form tertiary network structures. Adsorption from tertiary structure was reduced because strong interactions between the HA molecules limited the availability of hydrophobic patches for adsorption of HA onto FP. The influence of preparation variables on adsorption was also related to the availability of hydrophobic patches for adsorption.

Adsorption↗

A rare case of nasal cysticercosis mimicking a nasal dermoid.

Cysticercosis, caused by infestation with the pork tapeworm Taenia solium, is known to commonly involve the brain, muscles and subcutaneous tissue. Diagnosing cysticercosis can be difficult as its clinical presentation is usually non-specific. When involving subcutaneous tissue, it can present as firm, non-tender, solitary or multiple nodules. We report a case of subcutaneous cysticercosis at the nasion mimicking a nasal dermoid.

Child↗

Clinical relevance of laboratory-reported antibiotic resistance in acute uncomplicated urinary tract infection in primary care.

OBJECTIVES: To determine whether patients with an uncomplicated community-acquired urinary tract infection (UTI) and an isolate resistant to trimethoprim had worse clinical outcomes following empirical treatment with trimethoprim 200 mg twice daily for 3 days than did those with a susceptible isolate. PATIENTS AND METHODS: This was a prospective cohort study of clinical outcome. We enrolled 497 women (>or=18-70 years) presenting to general practitioner surgeries in Norwich and Gloucester with at least two symptoms of acute (<7 days) uncomplicated UTI. Significant bacteriuria was defined as >or=10(4) cfu/mL from a mid-stream urine (MSU). RESULTS: Of enrolled patients 75% (334/448) had significant bacteriuria, and trimethoprim resistance was present in 13.9% (44/317) of isolates. Patients with resistant isolates had a longer median time to symptom resolution (7 versus 4 days, P=0.0002), greater reconsultation to the practice (39% versus 6% in first week, P<0.0001), more subsequent antibiotics (36% versus 4% in first week, P<0.0001) and higher rates of significant bacteriuria at 1 month (42% versus 20% with susceptible isolate, P=0.04). Half of patients reconsulting in the first week had a resistant organism. CONCLUSIONS: Patients with uncomplicated UTI caused by trimethoprim-resistant organisms had significantly worse clinical outcomes than those with trimethoprim-susceptible organisms. Nevertheless, trimethoprim resistance was rarer than predicted from routine laboratory submissions and we calculate that 23 women require microbiological investigation to prevent one reconsultation arising from resistance-based treatment failure. We therefore suggest empirical antibiotic treatment in acute, uncomplicated UTIs. If patients reconsult in the first week, we suggest a change of antibiotic treatment with urine culture and susceptibility testing then done. More generally, laboratory resources should concentrate on resistance surveillance to inform empirical antibiotic choice.

Acute Disease↗

Factors contributing to deletion within Mungbean yellow mosaic virus partial dimers in binary vectors used for agroinoculation.

Mungbean yellow mosaic virus-Vigna (MYMV) sequences cloned as partial dimers within the T-DNA of a binary vector were deleted at a high frequency upon conjugal mobilization from Escherichia coli into Agrobacterium tumefaciens. This deletion involving the genome-length viral DNA did not occur when the binary plasmid was inside E. coli and when the binary plasmid was introduced into Agrobacterium by electroporation. Deletions occurred in both DNA A and DNA B partial dimers. A minimum of 500-nt continuity on either side of the nonanucleotide in the duplicated common region is required for deletion. A. tumefaciens cells in which deletion was complete, grew as larger colonies reflecting a growth advantage. The small, slow-growing colonies eventually lost the genome-length viral sequences after a few more cycles of growth. Partial dimers in binary plasmids pGA472 and pBin19 with RK2 replicon underwent deletion while those in pPZP with pVS1 replicon did not undergo deletion. Deletion was observed in A. tumefaciens strains C58, A136, A348 and A281 with C58 chromosome background, but not in Ach5 and T37. Interestingly, deletion did not occur in A. tumefaciens strain AGL1 with a recA mutation in C58 chromosome, implying a clear role for recombination in deletion. These observations suggest the choice of Agrobacterium strains and binary vectors for agroinoculation of geminiviruses.

Agrobacterium tumefaciens↗

Treatment of non-small cell lung cancer with intensity-modulated radiation therapy in combination with cetuximab: the NEAR protocol (NCT00115518).

BACKGROUND: Even today, treatment of Stage III NSCLC still poses a serious challenge. So far, surgical resection is the treatment of choice. Patients whose tumour is not resectable or who are unfit to undergo surgery are usually referred to a combined radio-chemotherapy. However, combined radio-chemotherapeutic treatment is also associated with sometimes marked side effects but has been shown to be more efficient than radiation therapy alone. Nevertheless, there is a significant subset of patients whose overall condition does not permit administration of chemotherapy in a combined-modality treatment. It could be demonstrated though, that NSCLCs often exhibit over-expression of EGF-receptors hence providing an excellent target for the monoclonal EGFR-antagonist cetuximab (Erbitux) which has already been shown to be effective in colorectal as well as head-and-neck tumours with comparatively mild side-effects. METHODS/DESIGN: The NEAR trial is a prospective phase II feasibility study combining a monoclonal EGF-receptor antibody with loco-regional irradiation in patients with stage III NSCLC. This trial aims at testing the combination's efficacy and rate of development of distant metastases with an accrual of 30 patients. Patients receive weekly infusions of cetuximab (Erbitux) plus loco-regional radiation therapy as intensity-modulated radiation therapy. After conclusion of radiation treatment patients continue to receive weekly cetuximab for 13 more cycles. DISCUSSION: The primary objective of the NEAR trial is to evaluate toxicities and feasibility of the combined treatment with cetuximab (Erbitux) and IMRT loco-regional irradiation. Secondary objectives are remission rates, 3-year-survival and local/systemic progression-free survival.

Adult↗

Revalidation of general dental practitioners in Scotland: the results of a pilot study. Part 2 - acceptability to practitioners.

AIM: To investigate the acceptablility of a pilot scheme of revalidation to general dental practitioners. METHOD: Ten general dental practitioners completed portfolios of evidence of being up to date and fit to practise. This portfolio was assessed by a panel of three experts, using an assessment tool developed specifically for that purpose. An action research methodology was used to evaluate participants' perceptions, consisting of a focus group and semi-structured interviews. The views of the assessors on the portfolio and its assessment were collected using a questionnaire. RESULTS: The views of the participants on revalidation, the pilot scheme portfolio and its use, who should assess it and how its use could be supported were collected. Also areas of difficulty in using the portfolio were identified, along with suggestions for improving it and alternative ways of evidencing competence. Assessors noted that the quality of evidence was adequate, but also made suggestions for improvement of the portfolio. CONCLUSIONS: The pilot scheme appears to have been acceptable to the dentists in this scheme, given some caveats. The assessors felt that appraisal would significantly enhance any substantive scheme.

Attitude of Health Personnel↗

Revalidation of general dental practitioners in Scotland: the results of a pilot study. Part 1--feasibility of operation.

AIM: To devise and operate a pilot scheme of revalidation for general dental practitioners. METHOD: A representative group of dental practitioners was convened to advise on an approach to piloting revalidation. Ten general dental practitioners volunteered and completed portfolios of evidence of fitness to practise. The portfolios were assessed by a panel of three calibrated experts, using a specially developed assessment tool. A single decision "evidence presented allowed revalidation to be recommended" was made. A timesheet was used to record the time spent producing the portfolio. RESULTS: Eight portfolios were assessed as sufficient for revalidation purposes. Two dentists were required to make supplementary submissions of evidence before they were found to be acceptable. An average of eight hours of dentist time and six hours of delegated time was spent producing the portfolios. CONCLUSIONS: The small number of dentists in this pilot were able to use the portfolio satisfactorily. The dentists were all volunteers and so may not necessarily be fully representative of the profession. The time spent completing the portfolio was not considered excessive. The assessors were adequately prepared and calibrated for their work.

Clinical Competence↗

Cross-reinnervation changes the expression patterns of the monocarboxylate transporters 1 and 4: An experimental study in slow and fast rat skeletal muscle.

The monocarboxylate transporters 1 and 4 are expressed in brain as well as in skeletal muscle and play important roles in the energy metabolism of both tissues. In brain, monocarboxylate transporter 1 occurs in astrocytes, ependymocytes, and endothelial cells while monocarboxylate transporter 4 appears to be restricted to astrocytes. In muscle, monocarboxylate transporter 1 is enriched in oxidative muscle fibers whereas monocarboxylate transporter 4 is expressed in all fibers, with the lowest levels in oxidative fiber types. The mechanisms regulating monocarboxylate transporter 1 and monocarboxylate transporter 4 expression are not known. We hypothesized that the expression of these transporters would be sensitive to long term changes in metabolic activity level. This hypothesis can be tested in rat skeletal muscle, where permanent changes in activity level can be induced by cross-reinnervation. We transplanted motor axons originally innervating the fast-twitch extensor digitorum longus muscle to the slow-twitch soleus muscle and vice versa. Four months later, microscopic analysis revealed transformation of muscle fiber types in the cross-reinnervated muscles. Western blot analysis showed that monocarboxylate transporter 1 was increased by 140% in extensor digitorum longus muscle and decreased by 30% in soleus muscle after cross-reinnervation. In contrast, cross-reinnervation induced a 62% decrease of monocarboxylate transporter 4 in extensor digitorum longus muscle and a 1300% increase in soleus muscle. Our findings show that cross-reinnervation causes pronounced changes in the expression levels of monocarboxylate transporter 1 and monocarboxylate transporter 4, probably as a direct consequence of the new pattern of nerve impulses. The data indicate that the mode of innervation dictates the expression of monocarboxylate transporter proteins in the target cells and that the change in monocarboxylate transporter isoform profile is an integral part of the muscle fiber transformation that occurs after cross-reinnervation. Our findings support the hypothesis that the expression of monocarboxylate transporter 1 and monocarboxylate transporter 4 in excitable tissues is regulated by activity.

Animals↗

Spinal anaesthesia in a patient with hereditary spastic paraplegia: case report and literature review.

We report the use of spinal anaesthesia in a patient with hereditary spastic paraplegia who presented for manual removal of placenta following a normal vaginal delivery. This 18-year-old primigravida had been diagnosed with hereditary spastic paraplegia at 8 years of age when neurological examination revealed mild bilateral lower limb spasticity. A 25-gauge Whitacre spinal anaesthetic needle was inserted at the L3-4 intervertebral space and 0.5% plain bupivacaine 2 mL plus fentanyl 25 microg administered. The procedure was uneventful. At 24 hours postoperatively, there was full neurological recovery to pre-anaesthetic levels. The hereditary spastic paraplegias are a group of neurological disorders characterised by a slowly progressing spastic paraparesis. The neurological disorder and its anaesthetic implications are reviewed.

Adolescent↗

Analysis of hospitalizations comparing rifaximin versus lactulose in the management of hepatic encephalopathy.

INTRODUCTION: Patients with end-stage liver disease often develop hepatic encephalopathy. The loss in cognitive abilities results in marked economic loss to the patient and health care community. We report hospital admission rates and economic impact of patients with end-stage liver disease suffering from hepatic encephalopathy. METHODS: The medical records were reviewed involving liver transplant patients started on lactulose or rifaximin therapy after presenting with stage 2 hepatic encephalopathy from January 2004 to November 2005. Information collected included demographics, hospitalizations required for hepatic encephalopathy, economic data, and Model for End-stage Liver Disease (MELD) score. RESULTS: Thirty-nine patients met study criteria: 24 patients treated with lactulose (group one) and 15 with rifaximin (group two). Group one included 18 men and six women of mean age 48 (range 39 to 58), average MELD 14 (range 10 to 19). Group two included 10 men and five women of mean age 47 (range 42 to 58), average MELD 15 (range 10 to 19). Group one patients required 19 hospitalizations overall: three patients with three hospitalizations, four patients with two hospitalizations, and two patients required one hospitalization. Total drug cost per month was 50 dollars(group one) and 620 dollars(group two). The average annual cost of hospitalization, emergency room visit, and drug per patient treated was 13,284.96 dollars for a total of 318,839 dollars (range 5005 dollars to 26,255 dollars, including drug cost and hospital care). Group two required three hospitalizations, all three with one visit. The average annual cost of hospitalization, emergency room visit, and drug per patient treated was 7958.13 dollars for a total of 119,372 dollars (range 6005 dollars to 19,255 dollars, including drug cost and hospital care). The total cost of therapy per patient per year was 13,285 dollars (group one) versus 7958 dollars (group two). The average length of stay was shorter in group two [3.5 days (range 3 to 4)] versus group 1 [5.0 days (range 3 to 10); P < .0001]. CONCLUSION: These pilot data demonstrate the marked difference in economic costs for the treatment of hepatic encephalopathy. The results also show that in comparative groups, the economic gains are quickly lost when using lactulose.

Adult↗

[CT-based software-supported prediction of the postoperative lung function after partial resection of the lung].

PURPOSE: The predicted postoperative forced exspiratory volume in one second (FEV (1)) is an important functional factor for predicting the operability of patients with bronchial carcinoma. A software tool that uses a preoperative chest MSCT and pulmonary function test (PFT) for largely automated prediction of the FEV (1) was evaluated. MATERIALS AND METHODS: Fifteen patients with surgically treated lung cancer were examined with a preoperative chest MSCT (1.25 mm slice thickness, 0.8 mm reconstruction increment) and PFT before and after surgery. CT scans were analyzed by the prototype software MeVisPulmo (MeVis gGmbH, Bremen) that predicted the postoperative FEV (1) as a percentage of the preoperative values measured by PFT. The automated segmentation and volumetry of lung lobes were performed either without or with minimal user interaction. Patients underwent lobectomy in twelve cases (6 upper lobes, 1 middle lobe, 5 lower lobes) and pneumectomy in three cases. The predicted FEV (1) values were compared to the observed postoperative values as a standard of reference. The additional functional parameters "total lung capacity" (TLC) and "forced vital capacity" (FVC) were compared to the FEV (1) results. RESULTS: Automated calculation of predicted postoperative lung function was successful in all cases. Due to an implausible PFT, two of the 15 patients were excluded from the collective. A mean postoperative FEV (1) value of 75 % (SD +/- 12 %) of the preoperative FEV (1) was calculated and 74 % (SD +/- 12 %) was actually measured. The deviations of the predicted value from the measured postoperative FEV (1) ranged between - 289 ml (-12 % of the measured postoperative FEV (1)) and + 294 ml (+ 15 % of the postoperative FEV (1)). The mean deviation (absolute value) was 137 +/- 77 ml/s. This corresponds to 7 +/- 3 % of the measured postoperative FEV (1). Bland-Altman-Statistics showed the 95 % "limits of agreement" for the predicted FEV (1) values to be between - 341 ml and + 301 ml, corresponding to - 17.5 % and + 15.8 of the measured postoperative FEV (1) value. Analysis of the TLC and FVC yielded similar results. CONCLUSION: In the present pilot study the software-assisted prediction of the postoperative FEV (1) using a preoperative MSCT and pulmonary function test corresponded satisfactorily with the observed postoperative values. The introduced approach may make it possible to obtain additional information for the prediction of functional operability prior to performing lung cancer surgery.

Adenocarcinoma↗

Atopic optic neuritis.

PURPOSE: To report a case of optic neuritis associated with atopic dermatitis, which may represent an optic nerve counterpart of atopic myelitis. METHODS: Clinical examination, MRI, blood investigations. RESULTS: A 34-year-old man with severe atopic dermatitis developed a steroid-responsive bilateral optic neuritis. Serum IgE was highly elevated, with high titers of mite-specific IgE. Clinical ophthalmological fluctuations paralleled those of atopic dermatitis. CONCLUSIONS: The clinical features and parallel fluctuations strongly suggest that the patient's optic neuritis was related to atopic dermatitis. This atopic optic neuritis may represent the optic nerve equivalent of atopic myelitis.

Adult↗

Isolation of viral haemorrhagic septicaemia virus from muskellunge, Esox masquinongy (Mitchill), in Lake St Clair, Michigan, USA reveals a new sublineage of the North American genotype.

Viral haemorrhagic septicaemia virus (VHSV) was isolated from muskellunge, Esox masquinongy (Mitchill), caught from the NW portion of Lake St Clair, Michigan, USA in 2003. Affected fish exhibited congestion of internal organs; the inner wall of the swim bladder was thickened and contained numerous budding, fluid-filled vesicles. A virus was isolated using fish cell lines inoculated with a homogenate of kidney and spleen tissues from affected fish. Focal areas of cell rounding and granulation appeared as early as 24 h post-inoculation and expanded rapidly to destroy the entire cell sheet by 96 h. Electron microscopy revealed virions that were 170-180 nm in length by 60-70 nm in width having a bullet-shaped morphology typical of rhabdoviruses. The virus was confirmed as VHSV by reverse transcriptase-polymerase chain reaction. Sequence analysis of the entire nucleoprotein and glycoprotein genes revealed the virus was a member of the North American genotype of VHSV; however, the isolate was sufficiently distinct to be considered a separate sublineage, suggesting its origin may have been from marine species inhabiting the eastern coastal areas of the USA or Canada.

Air Sacs↗

Use of tissue-fluid correlations to estimate gentamicin residues in kidney tissue of Holstein steers.

Gentamicin continues to be one of the most effective antibiotics for the treatment of gram-negative infections. Greater than 90% of the drug is rapidly eliminated from the body in <2 days, however, a small residue remains bound to the kidney cortex tissue for many months. In beef steers, the gentamicin residue is unacceptable and its presence is monitored by the FAST (Fast Antimicrobial Screen Test) applied to the kidney at the time of slaughter. The sensitivity of the FAST to gentamicin in the kidney cortex is reported to be 100 ng/g, therefore, this level of gentamicin defines the acceptable limit of gentamicin drug residue in the bovine kidney. In the present study, three doses of 4 mg/kg gentamicin was administered intramuscularly to eight steers. Gentamicin was allowed to deplete from the kidneys for a range of times from 7 to 10 months. At slaughter the level of gentamicin in the kidney cortex varied from 91 to 193 ng/g, but a total of 160 FAST tests performed on the kidneys were negative. Blood and urine samples were collected at varying times following the last dose of gentamicin. Kidney tissue samples were collected by laparoscopic surgery in the live steers as well as the final sample obtained at slaughter. Plasma levels of gentamicin declined rapidly to nondetectable within 3 days, while measurable urine persisted for 75 days before the concentration of gentamicin declined to levels too low to quantitate by the available liquid chromatography tandem mass spectrometry (LC/MS/MS) technique. An estimated correlation between an extrapolation of urine gentamicin concentration to the corresponding kidney tissue sample suggests a urine to kidney tissue relationship of 1:100. A test system sufficiently sensitive to a urine gentamicin concentration of 1 ng/mL will correlate with the estimated 100 ng/g gentamicin limit of the FAST applied to the fresh kidney of the recently slaughtered bovine.

Animals↗

Molecular screening of the neutrophil elastase gene in congenital neutropenia.

Congenital neutropenia is a rare hematopoietic disease, which occurs sporadically or as an auto-somal dominant inherited disorder. Pathogenesis of congenital neutropenia can now be attributed to mutations of the ELA2 gene encoding neutrophil elastase. A child with severe congenital neutropenia with a heterozygous mutation G1887A in exon 2 of ELA2 gene is reported.

DNA Mutational Analysis↗