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Biomedical subjects

R Thomas

Publications and source records attributed to R Thomas.

At least 37 records · Page 2Linked to original sources
PubMed2002

The value of risks scores for predicting postoperative nausea and vomiting when used to compare patient group in a randomised controlled trial.

Whilst conducting a randomised controlled trial into the effects of combination anti-emetics, we endeavoured to confirm that our patient groups were matched using the predictive scoring systems for postoperative nausea and vomiting (PONV) and postoperative vomiting (POV) reported in the literature. One hundred and seventy-seven female patients attending for day case gynaecological surgery were studied and their individual risks of PONV and POV were calculated using four predictive models for PONV and two predictive models for POV. The scoring systems were then evaluated to see if agreement existed between them using the method described by Bland and Altman. Bias and 95% limits of agreement were calculated for each combination. Agreement between scoring systems was poor. As the scoring systems gave widely divergent predictions, we concluded that the predictive risk for PONV or POV would be dependent upon the scoring system chosen, thus limiting their usefulness in this role.

Adult↗
PubMed2002

Correlation of ictal EEG and SPECT studies in patients of intractable epilepsy with normal MRI.

Identification of the epileptic focus is the most important requirement for a successful surgical outcome in intractable epilepsy. Patients with normal MRI on high-resolution imaging pose a significant challenge in this regard. We tried to identify the epileptic focus using interictal / ictal SPECT and ictal EEG patterns in 14 patients with normal MRI. Rhythmic ictal onset activity helped to identify a single focus in 10 patients (71.43%). Inter ictal SPECT detected a focus corresponding to ictal EEG in 6 out of 10 patients (60%) in whom the test was performed. Ictal SPECT done in 5 patients correctly identified the focus in all patients (100%). Our data indicate that it is possible to obtain localization in patients with normal MRI using a combination of ictal EEG patterns and an ictal SPECT study.

Adolescent↗
PubMed2001

Radiofrequency ablation in patients with primary breast carcinoma: a pilot study in 26 patients.

BACKGROUND: The authors performed a pilot trial of ultrasound-guided percutaneous radiofrequency ablation (RFA) in patients with T1 and T2 breast tumors 1) to confirm complete coagulative necrosis of tumor tissue and 2) to determine the safety and complications related to this treatment. METHODS: Twenty-six patients with biopsy-proven, invasive breast carcinoma underwent RFA of their breast tumors followed by immediate resection. Treatment was planned to ablate the tumor and a 5 mm margin of surrounding breast tissue. Tumor viability after RFA was assessed by hematoxylin and eosin and nicotinamide adenine dinucleotide vital staining. RESULTS: Twenty patients (77%) had T1 tumors, and six patients (23%) had T2 tumors. The mean greatest dimension of tumors that were treated with RFA was 1.8 cm (range, 0.7-3.0 cm). The mean treatment time for two-phase RFA treatment was 15 minutes and 23 seconds (range, from 6 minutes and 25 seconds to 24 minutes and 54 seconds). Coagulation necrosis of the tumor was complete in 25 of 26 patients (96%): One patient had a microscopic focus of viable tissue adjacent to the needle shaft site. A single patient (1 of 26 patients; 4%) had a complication related to RFA: a full thickness burn of the skin overlying a tumor that was immediately beneath the skin. CONCLUSIONS: This pilot experience with RFA in the treatment of patients with early-stage, primary breast carcinoma revealed that 1) coagulative necrosis of the entire tumor occurred in 96% of the patients, and 2) the treatment was safe, with only a 4% complication rate. The authors have initiated a trial of RFA alone (no resection) for patients with T1 and T2 breast tumors that will include sentinel lymph node mapping and postablation irradiation.

Adult↗
PubMed2001

A biosynthetic classification of fungal and streptomycete fused-ring aromatic polyketides.

Polyketides are one of the largest and most structurally diverse classes of naturally occurring compounds, ranging from simple aromatic metabolites to complex macrocyclic lactones. Fungi and filamentous bacteria, particularly the actinomycetes, are major sources of polycyclic aromatic structures, which include many clinically important antibiotics and other useful metabolites. These fused-ring polyketides are formed by the action of polyketide synthases (PKSs), which catalyse the assembly, folding and cross-linking of poly-beta-ketoacyl intermediates. In view of the taxonomic gulf between the eukaryotic fungi and prokaryotic bacteria, it is not surprising that they are rarely found to produce structurally identical fused-ring metabolites. A review of [(13)C(2)]acetate incorporation data has revealed consistent differences in the reported cyclisation patterns, which require regiospecifically distinct cross-linking of otherwise identical linear polyketide precursors. This observation provides the basis for a structural and biosynthetic classification of microbial fused-ring polyketides, which has a number of useful ramifications.

Anti-Bacterial Agents↗
PubMed2001

Placental bone morphogenetic protein (PLAB) gene expression in normal, pre-malignant and malignant human prostate: relation to tumor development and progression.

The second most common target of prostate-cancer metastasis is bone, and the phenomenon of skeletal metastasis represents the incurable stage of disease. Histologically, skeletal metastasis from prostate cancer is distinctive due to its osteoblastic nature. The osteoblastic bone metastasis shows extensive new bone formation, with possible involvement of the soluble growth factors secreted by tumor cells, such as bone morphogenetic proteins (BMPs). In the present study, we analyzed the gene expression of one of the new members of the BMP family, placental bone morphogenetic protein (PLAB). In situ hybridization studies showed high levels of this gene in normal prostate. However, the gene is down-regulated during the progression of cancer at the primary site. The most significant finding was re-expression of the PLAB gene in osseous metastatic lesions. Our results demonstrate that tumor cells, when released from the primary site and after re-growth elsewhere, are capable of re-expressing specific genes that may play a different role at metastatic sites than at the primary site.

Bone Morphogenetic Proteins↗
PubMed2001

Liposome-mediated gene transfection of endothelial nitric oxide synthase reduces endothelial activation and leukocyte infiltration in transplanted hearts.

BACKGROUND: During cardiac ischemia-reperfusion injury, neutrophilic infiltration of the myocardium is mediated by adhesion molecule expression on activated coronary endothelium. Nitric oxide inhibits neutrophil adhesion to endothelium in vitro by blocking the nuclear factor (NF)-kappaB-dependent transcription of adhesion molecules. We investigated whether intraoperative gene delivery of endothelial nitric oxide synthase (eNOS) into donor hearts before transplantation would have a similar effect on an entire organ. METHODS AND RESULTS: In an allogeneic rabbit heart transplant model, liposomes complexed to the gene encoding eNOS were infused into the donor coronary circulation before transplantation. By 24 hours after transplantation, calcium-dependent nitrite production was significantly higher in eNOS-transfected donor hearts than in the 3 control groups: donor hearts transfected with empty plasmids alone, donor hearts treated with diluent only, and untransplanted native hearts. Intramyocardial neutrophil and T-lymphocyte populations were halved in eNOS-transfected hearts compared with control donor hearts (P<0.05). Moreover, the prevalence of NF-kappaB activation in microvascular endothelial cells and surrounding cardiac myocytes as well as endothelial vascular cell adhesion molecule-1 and intracellular adhesion molecule-1 expression were all significantly reduced in eNOS-transfected hearts compared with control donor hearts (P<0.01). Without immunosuppression, eNOS-transfected hearts survived longer than controls. CONCLUSIONS: Intraoperative liposome-mediated gene delivery of eNOS to donor hearts can result in early gene expression sufficient to reduce ischemia-reperfusion injury by inhibiting NF-kappaB activation, adhesion molecule expression, and the early infiltration of leukocytes, all of which may improve graft survival.

Animals↗
PubMed2001

Genomic organization of the CC chemokine mip-3alpha/CCL20/larc/exodus/SCYA20, showing gene structure, splice variants, and chromosome localization.

We describe the genomic organization of a recently identified CC chemokine, MIP3alpha/CCL20 (HGMW-approved symbol SCYA20). The MIP-3alpha/CCL20 gene was cloned and sequenced, revealing a four exon, three intron structure, and was localized by FISH analysis to 2q35-q36. Two distinct cDNAs were identified, encoding two forms of MIP-3alpha/CCL20, Ala MIP-3alpha/CCL20 and Ser MIP-3alpha/CCL20, that differ by one amino acid at the predicted signal peptide cleavage site. Examination of the sequence around the boundary of intron 1 and exon 2 showed that use of alternative splice acceptor sites could give rise to Ala MIP-3alpha/CCL20 or Ser MIP-3alpha/CCL20. Both forms of MIP-3alpha/CCL20 were chemically synthesized and tested for biological activity. Both flu antigen plus IL-2-activated CD4(+) and CD8(+) T lymphoblasts and cord blood-derived dendritic cells responded to Ser and Ala MIP-3alpha/CCL20. T lymphocytes exposed only to IL-2 responded inconsistently, while no response was detected in naive T lymphocytes, monocytes, or neutrophils. The biological activity of Ser MIP-3alpha/CCL20 and Ala MIP-3alpha/CCL20 and the tissue-specific preference of different splice acceptor sites are not yet known.

Alternative Splicing↗
PubMed2001

The effects of intracellular pH changes on resting cytosolic calcium in voltage-clamped snail neurones.

We have investigated the effects of changing intracellular pH on intracellular free calcium concentration ([Ca2+]i) in voltage-clamped neurones of the snail Helix aspersa. Intracellular pH (pHi) was measured using the fluorescent dye 8-hydroxypyrene-1,3,6-trisulphonic acid (HPTS) and changed using weak acids and weak bases. Changes in [Ca2+]i were recorded using either fura-2 or calcium-sensitive microelectrodes. Acidification of the neurones with 5 mM or 20 mM propionate (approximately 0.2 or 0.3 pH units acidification, respectively) caused a small reduction in resting [Ca2+]i of 5 +/- 2 nM (n = 4) and 7 +/- 16 nM (n = 4), respectively. The removal of the 20 mM propionate after approximately 40 min superfusion resulted in an alkalinization of approximately 0.35 pH units and an accompanying rise in resting [Ca2+]i of 31 +/- 9 nM (n = 4, P < 0.05). The removal of 5 mM propionate did not significantly affect [Ca2+]i. Alkalinizations of approximately 0.2-0.4 pH units of Helix neurones induced by superfusion with 3 mM concentrations of the weak bases trimethylamine (TMA), ammonium chloride (NH4Cl) and procaine were accompanied by significant (P < 0.05) increases in resting [Ca2+]i of 42 +/- 4 nM (n = 26), 30 +/- 7 nM (n = 5) and 36 +/- 4 nM (n = 3), respectively. The effect of TMA (0.5-6 mM) on [Ca2+]i was dose dependent with an increase in [Ca2+]i during pHi increases of less than 0.1 pH units (0.5 mM TMA). Superfusion of neurones with zero calcium (1 mM EGTA) Ringer solution inhibited depolarization-induced calcium increases but not the calcium increase produced by the first exposure to TMA (3 mM). In the prolonged absence of extracellular calcium (approximately 50 min) TMA-induced calcium rises were decreased by 64 +/- 10% compared to those seen in the presence of external calcium (P < 0.05). The calcium rise induced by TMA (3 mM) was reduced by 60 +/- 5% following a 10 min period of superfusion with caffeine (10 mM) to deplete the endoplasmic reticulum (ER) stores of calcium (P < 0.05). Cyclopiazonic acid (10-30 microM CPA), an inhibitor of the ER calcium pump, inhibited the calcium rise produced by TMA (3 mM) and NH4Cl (3 mM) by 61 +/- 4% compared to controls (P < 0.05). These data are consistent with physiological intracellular alkaline shifts stimulating release of calcium, or inhibiting re-uptake of calcium by an intracellular store. The calcium increase was much reduced following application of caffeine, treatment with CPA or prolonged removal of external calcium. Hence the ER was likely to be the source of mobilized calcium.

Ammonium Chloride↗
PubMed2001

Characterization of pica prevalence among patients with sickle cell disease.

OBJECTIVE: To determine the prevalence of pica and its characteristics among children with sickle cell disease. DESIGN: Retrospective, observational study. SETTING: An urban, ambulatory care, interdisciplinary center. PATIENTS: The medical records of all 480 patients who visited the center from March 1, 1998, to June 30, 1999, were reviewed. Patients were excluded for history of stroke, long-term transfusions, pregnancy, acute illness, or age younger than 3 years. MAIN OUTCOME MEASURES: Sex, age, weight, height, Tanner stage, complete blood cell count, sickle cell genotype, pica history, and levels of iron, zinc, lead, and fetal hemoglobin (Hb). RESULTS: Of 395 study patients, 134 (33.9%) reported pica. Ingested items included paper, foam, and powders. There was a significantly higher prevalence of pica among patients homozygous for Hb S (Hb SS, sickle cell anemia) compared with the combined group of double heterozygous patients with Hb SC, Hb SD, and Hb Sbeta thallasemia (Sbeta(+)or Sbeta(0)) (35.6% vs 25.5%; P =.03). Within genotype, mean Hb levels were significantly lower and reticulocyte counts were significantly higher in the patients with pica. Overall, the mean age of patients with pica was significantly lower; however, the prevalence was 23.3% (27/116) among those aged 10.0 to 14.9 years and 14.8% (8/54) among those aged 15.0 to 19.0 years. Within age groups, patients with pica weighed significantly less. CONCLUSIONS: Pica appeared to have an unusually high prevalence in patients with sickle cell disease and a correlation with lower Hb levels. It is unclear whether pica is a specific marker of disease severity, because our review did not show a relationship to increased number and duration of hospitalizations. The association between pica and low body weight suggests a nutritional effect on its prevalence.

Adolescent↗
PubMed2001

Comparison of differentiated dendritic cell infiltration of autoimmune and osteoarthritis synovial tissue.

OBJECTIVE: Infiltration of rheumatoid arthritis (RA) synovial tissue (ST) by differentiated dendritic cells (DC) is a consistent feature in patients with active disease. However, mononuclear cells (MNC), including DC, may be nonspecifically chemoattracted to inflammatory sites regardless of etiology. Therefore, to evaluate the specificity of ST infiltration by differentiated DC, synovial biopsies from patients with RA, spondylarthropathy (SpA), osteoarthritis (OA), and gout were examined. METHODS: Formalin-fixed ST sections were analyzed by double immunohistochemical staining for vascularity and infiltration by differentiated DC, lymphocytes, and macrophages. RESULTS: DC containing nuclear RelB were found in perivascular MNC aggregates from patients with all arthritides studied. Infiltration by differentiated DC was similar in RA and SpA ST, but reduced in OA ST. Differentiated DC were always observed in close association with lymphocytes, and the correlation between these variables suggested that the infiltration of inflammatory sites by DC and lymphocytes was associated. CONCLUSION: Perivascular infiltration by DC, lymphocytes, and macrophages is nonspecifically related to inflammation, but signals present in RA and SpA ST lead to more intense cellular infiltration and accumulation.

Aged↗
PubMed2001

Anthracycline-induced cardiac injury using a cardiac cell line: potential for gene therapy studies.

Anthracyclines are effective antitumor agents whose chief limitation has been cardiotoxicity directly related to free radical production. Therefore, strategies designed to selectively overexpress antioxidant proteins in the heart could protect against drug-induced toxicity and allow higher doses of chemotherapy. However, to date an adequate cardiac model system that is susceptible to anthracycline injury and can express foreign genes in a controlled fashion has been lacking. Developing a cardiac model system would permit examination of the relationship between the expression level of a potentially protective foreign gene and the degree of protection from injury. In this study we have examined the potential of the H9C2 rat cardiac myocyte cell line in this regard. H9C2 cells differentiate in a reproducible fashion, as shown by progressive increases in muscle tropomyosin-expressing cells, the organization of this thin filament protein, and the percentage of muscle cells contained within myotubes. Exposure of this cell line to the anthracycline doxorubicin produces cell injury as indicated by release of the intracellular enzyme lactate dehydrogenase into the culture medium. This injury is preceded by generation of reactive oxygen species, indicated by fluorescence after loading with carboxy-dichlorodihydrofluorescein diacetate. Stable transfection of H9C2 cells with a plasmid producing a tetracycline transactivator protein allows foreign genes to be expressed at a level tightly controlled by the concentration of tetracycline in the culture medium. Since H9C2 cells differentiate, can be injured by anthracycline exposure, and can express foreign genes at controllable levels, this is a suitable system in which to design genetic approaches to prevent this important clinical problem.

Animals↗
PubMed2001

Activation and habituation in olfaction--an fMRI study.

This study investigated human BOLD responses in primary and higher order olfactory cortices following presentation of short- and long-duration odorant stimuli using a 3-T MR scanner. The goal was to identify temporal differences in the course of the response that might underlie habituation. A short-duration stimulus (9 s) consistently activated the primary olfactory cortex (POC). After a long stimulus (60 s), the temporal form of the response differed in different parts of the olfactory network: (1) The POC (piriform, entorhinal cortex, amygdala) and, interestingly, the hippocampus and, to a certain degree, the anterior insula show a short, phasic increase in the signal, followed by a prolonged decrease below baseline. (2) In the orbitofrontal cortex a sustained increase in activation was seen. This increase lasted approximately as long as the duration of odorant presentation ( approximately 60 s). (3) The mediodorsal nucleus of the thalamus and the caudate nucleus responded with an increase in signal which returned to baseline after approximately 15 to 30 s. The correlated biphasic hemodynamic response in the POC, hippocampus, and anterior insula during prolonged olfactory stimulation suggests that these three areas may interact closely with each other in the control of habituation. These results extend recent data which showed habituation of the rat piriform cortex and dissociation between the POC and the orbitofrontal cortex.

Adult↗
PubMed2001

An integrated cytogenetic, radiation-hybrid, and comparative map of dog chromosome 5.

The development of a detailed genome map for the domestic dog (Canis familiaris, CFA) is a prerequisite for the continued use of this species as a model system for the study of inherited traits. We present an integrated cytogenetic, radiation-hybrid, and comparative map of dog Chromosome (Chr) 5 (CFA 5). The map comprises 14 gene markers, selected from loci previously mapped within the corresponding evolutionarily conserved chromosome segments (ECCS) of the human genome. Large-insert clones representing each marker were first isolated and mapped by fluorescence in situ hybridization (FISH) analysis to determine their subchromosomal localization on CFA 5. Thirteen gene markers were subsequently mapped by using a commercially available whole genome radiation hybrid (WG-RH) panel for the dog. Nine anonymous markers were also assigned to CFA 5 by both FISH and WG-RH analysis. The 22 markers formed six RH-linkage groups, spanning each of the four ECCS comprising this 99 megabase chromosome. All cytogenetic, WG-RH, and comparative mapping data were in agreement and were combined to determine both the most likely locus order within each linkage group, and also the gross relative orientation of the corresponding ECCS. This study provides a resource for the transfer of information from the human transcript map to that of the dog, and extends existing data regarding the structural relationships between CFA 5 and its evolutionary counterparts within the human genome.

Animals↗
PubMed2001

Role of frequency doubling perimetry in detecting neuro-ophthalmic visual field defects.

PURPOSE: To report the ability of frequency doubling perimetry to detect "neuro-ophthalmic" field defects, characterize them as hemianopic or quadrantanopic, and differentiate glaucomatous from "other" neuro-ophthalmic field defects. METHODS: Sixty eyes of 30 normal subjects, 50 eyes of 29 patients with glaucomatous defects, and 138 eyes of 103 patients with "typical" neuro-ophthalmic field defects underwent automated perimetry using the Swedish Interactive Threshold Algorithm and frequency doubling perimetry. The sensitivity and specificity for identification of a field defect (frequency doubling perimetry 20-5 and 20-1 screening tests), or to characterize hemianopia/quadrantanopia (full threshold test) were determined. Ability to discriminate glaucomatous defects was determined by comparing frequency doubling perimetry full threshold test in glaucoma to pooled results of normal and neuro-ophthalmic groups. RESULTS: On frequency doubling perimetry, a single point depressed to less than 1% probability had a sensitivity of 97.1% (20-5 test) and 95.7% (20-1 test) for detecting a neuro-ophthalmic visual field defect. The corresponding specificities were 95% using pooled results in normal subjects and patients with glaucoma and "other" neuro-ophthalmic field defects. In 20-5 screening a single abnormal point depressed to less than 2% probability level had a sensitivity of 98.6% (specificity 85%). Two abnormal points in the 20-1 screening depressed to less than 1% probability level had a specificity of 100% (sensitivity 84.8%). In frequency doubling perimetry full threshold, sensitivity and specificity for detection of hemianopia were 86.8% and 83.2%; for quadrantanopia they were 79.2% and 38.6%. The sensitivity and specificity for categorizing a defect as glaucomatous were 86% and 74.7%. CONCLUSIONS: Frequency doubling perimetry is a sensitive and specific test for detecting "neuro-ophthalmic" field defects. The presence of two abnormal points (20-1 screening program) "rules in" the presence of a field defect. A normal 20-5 program (absence of a single abnormal point) almost "rules out" a defect. Frequency doubling perimetry could not accurately categorize hemianopic, quadrantanopic, or glaucomatous defects.

Child↗
PubMed2001

Effect of extracorporeal membrane oxygenation on left ventricular function of swine.

BACKGROUND: Previous clinical and experimental investigations have produced inconsistent data describing the effects of veno-arterial extracorporeal membrane oxygenation (VA ECMO) on intrinsic left ventricular (LV) function. We report an animal model that allows investigation of the effects of VA ECMO on the mechanics of the LV using two load-insensitive indices: end-systolic pressure-minor axis dimension relationship (ESPDR) and preload recruitable dimensional stroke work (PRDSW). METHODS: Eight piglets (5 to 11 kg) were anesthetized, instrumented, and placed on VA ECMO. Throughout the experiment, systemic and left atrial partial pressure of oxygen were maintained between 100 to 200 mm Hg. At ECMO flow rate of 50% of baseline cardiac output, data were collected prior to ECMO, at 4 and 6 hours during ECMO, and after weaning from ECMO. Data measured or calculated for each time point included heart rate, LV pressures and minor axis dimensions at different pre-loads, first derivative of LV pressure with respect to time, velocity of circumferential fiber length shortening (VCF), LV shortening fraction (LVSF), ESPDR, and PRDSW. RESULTS: A significant (p < 0.05) decrease in LVSF and VCF was seen at 4 and 6 hours during ECMO when compared to baseline, but the ESPDR and PRDSW did not change during ECMO. CONCLUSIONS: VA ECMO alone changes some of the load-dependent parameters of contractility, but intrinsic function of the heart is not significantly affected as measured by load-insensitive indices of LV performance.

Animals↗
PubMed2001

Outpatient radical prostatectomy: impact of standard perineal approach on patient outcome.

PURPOSE: As managed care becomes more prevalent, urologists must critically evaluate the economic aspect of and patient satisfaction with urological practice patterns. We have previously reported the advantages of radical perineal prostatectomy, which decreases hospitalization and morbidity, and provides a more rapid return to normal activity, translating into cost savings. We have since evaluated the satisfaction of patients who underwent outpatient radical prostatectomy with and without laparoscopic pelvic lymph node dissection. MATERIALS AND METHODS: We evaluated the charts of 250 consecutive patients who underwent outpatient radical perineal prostatectomy with less than 24 hours of hospitalization from 1992 to 1997. Complications, pain management, blood transfusion, and bowel and urinary dysfunction were assessed. Validated quality of life questionnaires were mailed to 200 patients several months postoperatively and a 62% response rate was achieved. RESULTS: Mean followup in the series was 30 months. In the perioperative period there were rectal perforation in less than 2% of patients, anastomotic stricture in 3%, perineal fistula in 0.4% and blood transfusion in 11%. Some problems with bowel movements immediately after the procedure, such as diarrhea, constipation or soiled underwear, developed in 17% of patients, of whom up to 20% had had some bowel dysfunction before surgery. In the majority bowel problems resolved in an average of 7.3 weeks. Persistent new onset bowel trouble developed in 9 of the 124 patients (7%). The questionnaire demonstrated persistent significant urinary incontinence in 8 cases (7%). Nerve sparing was attempted in 54 patients, including 22 (41%) who achieve erection sufficient for vaginal penetration and are satisfied with sexual function. Of the patients 17% reported problems after hospital discharge that were mostly related to Foley catheter management. Overall 94.8% of patients were satisfied with treatment. Physical and social/family well-being appeared to be excellent according to the questionnaire. Only 12% of patients would have preferred longer hospitalization. The preferred method of pain control was nonsteroidal anti-inflammatory drugs. CONCLUSIONS: Radical perineal prostatectomy is a low morbidity alternative for localized prostate cancer. Outpatient radical perineal prostatectomy may be performed with good patient satisfaction and safety. There appear to be few bowel problems after long-term followup.

Aged↗