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Biomedical subjects

J Thomas

Publications and source records attributed to J Thomas.

At least 343 records · Page 19Linked to original sources

An EORTC pilot study of filgrastim (recombinant human granulocyte colony stimulating factor) as support to a high dose-intensive epiadriamycin-cyclophosphamide regimen in chemotherapy-naive patients with locally advanced or metastatic breast cancer.

BACKGROUND: In an attempt to increase chemotherapy dose intensity by step-wise reduction of the time interval between treatment cycles, filgrastim was administered to breast cancer patients receiving a three-month combination chemotherapy with epirubicin (E) and cyclophosphamide (C). PATIENTS AND METHODS: Chemotherapy-naïve patients with locally advanced or metastatic breast cancer received fixed doses of E (120 mg/m2) and C 9830 mg/m2) by 15-min i.v. infusion on day 1 of each cycle and filgrastim at a dose of 4 micrograms/kg once daily by SC injection starting 24 hours after chemotherapy. Cohorts of patients were treated in successive schedules, each schedule corresponding to a specified time interval between chemotherapy cycles. The toxicity observed in each schedule was evaluated before patients were accrued to the next schedule, which corresponded to a shorter time interval between chemotherapy cycles. RESULTS: The maximum tolerated schedule was E (120 mg/m2) plus C 9830 mg/m2) given every 14 days with filgrastim support from day 2 until day 13. On this schedule, 5 of 12 patients experienced dose-intensity-limiting toxicities (DLT) during the 3-month study period. Non-hematological DLT occurred in 2/12 patients (mucositis, skin toxicity) while /312 experienced febrile neutropenia requiring i.v. antibiotics. All patients achieved recovery of ANC to >1.5 x 10(9)/l by the time of scheduled retreatment. The combination of filgrastim with this regimen did not seem to add major toxicities. The efficacy was high, with 87% of patients achieving an objective response and a median response duration of 18 months (range: 4-52 months). CONCLUSIONS: Filgrastim permits at 33% increase in 'EC' dose intensification over that of the conventional every-3-week administration. Randomized studies should now be initiated to evaluate the merit, if any, of 'accelerated' chemotherapy in advanced breast cancer.

Adult↗

Surgical management of malignant melanoma.

Wide and mutilating surgical excision is contraindicated for primary malignant melanoma. Tumours less than 1 mm thick require only 1 cm excision margins while those 1-4 mm thick need only 2 cm margins. Primary closure without skin grafting should always be attempted. Axillary and inguinal block dissection remain standard treatment for established lymphatic metastases but elective block dissection is still controversial and should only be performed in the context of a clinical trial. Selective lymphadenectomy based on intraoperative lymphatic mapping is being evaluated. Isolated limb perfusion plays an important role in palliation, and perfusion with a combination of cytotoxic agents and cytokines is an exciting therapeutic advance. Laser vapourization under local or general anaesthesia is an alternative way of treating multiple small cutaneous and subcutaneous lesions and is much better tolerated.

Humans↗

Interrater reliability of auscultation of breath sounds among physical therapists.

BACKGROUND AND PURPOSE: Although auscultation is routinely used in the assessment of respiratory status, the ability of the rater to accurately and consistently identify lung sounds has been questioned. The literature on this issue is sparse and has focused on reliability of auscultation of tape-recorded rather than in vivo lung sounds. The purposes of this study were to determine the interrater reliability of physical therapists in the direct auscultation of lung sounds based on their clinical experience in chest physical therapy and to determine whether the adoption of standardized nomenclature and education on proper technique and interpretation affects reliability. SUBJECTS AND METHODS: A group of 57 registered physical therapists were stratified by clinical experience into four groups. Sixteen therapists (ie, 4 in each stratum) were randomly chosen using a random number table. The following criteria were developed to delineate clinical experience. Group 1 subjects were senior chest physical therapists with at least 5 years of experience in this area of practice. Group 2 subjects were experienced therapists who had a minimum of 2 years of experience in chest physical therapy and were currently practicing in this area. Group 3 subjects were experienced physical therapists in other areas who were also practicing in chest physical therapy on occasional weekend service. Group 4 subjects were new graduates. Ten patients were evaluated by each group of 4 physical therapists using a teaching stethoscope with one diaphragm/bell and four pairs of earpieces. The education session consisted of discussion of the adoption of standardized nomenclature and education on proper technique and interpretation of auscultation. Interrater reliability was assessed before and after the education session using kappa (kappa) values. Comparisons were made between kappa values before and after the education session to determine the effect of education and between groups to determine the effect of clinical experience. RESULTS: The kappa values before the education session were low, indicating poor reliability in detecting specific abnormal sounds (kappa = -.02-.59). Group 1 (seniors in respiratory therapy) and group 4 (new graduates) demonstrated the greatest reliability levels. The lowest kappa values were observed for detecting and categorizing the quality of breath sounds (normal, absent, bronchial, or decreased) (kappa = -.02-.25). Following the education session, there was a general improvement in reliability (kappa = -.30-.77), especially for group 3 (specialists in other areas). The most improvement was noted for the detection of the quality of breath sounds (kappa = .08-.50). CONCLUSION AND DISCUSSION: Reliability of auscultation was poor to fair, in general, before the education session. There was a definite improvement in reliability after the education session. There was no clear effect of clinical experience on reliability, and the agreement among observers appeared to depend on the abnormal lung sound present. Limitations of this study and recommendations for future research are discussed. [Brooks D, Thomas J. Interrater reliability of auscultation of breath sounds among physical therapists.

Auscultation↗

Clinico-pathological predictors of recurrence for acinic cell carcinoma.

The biological behaviour of acinic cell carcinomas, even if well differentiated, is unpredictable. We studied 45 patients with acinic cell carcinoma followed-up from 10 to 379 months (5 year recurrence-free and survival rate of 69% and 81% respectively), and compared clinico-pathological parameters with outcome. The presence of a predominately solid architecture was strongly associated with a poor outcome (P < 0.01) and this was the only independent prognostic variable when log rank testing was performed. Tumour size (> 2.75 cm) was a significant predictor of recurrent deep parotid lobe involvement, the presence of cervical nodal disease and lymphocytic infiltration, although not significant, factors showed a tendency towards recurrence. For acinic cell carcinoma, the predominant solid architecture would appear to be a strong predictor of recurrence.

Adolescent↗

Mantle cell lymphoma: a clinicopathological study of 55 cases.

A recently described unifying proposal for mantle cell lymphoma has led to the formulation of strict diagnostic criteria based on morphology, immunology and molecular data to define this specific entity. Previous studies were often based on broader definitions such as centrocytic lymphoma, intermediately differentiated lymphoma or mantle zone lymphoma and, therefore, included a variety of entities with some, but not all, features ascribed to the mantle cell lymphoma. Since the publication of the unifying proposal no comprehensive studies have been published to confirm and support it. We selected 55 cases of mantle cell lymphoma collected in our institution in order to evaluate the validity of the proposal and, by using strict criteria, we analysed the morphological features, their variations and the changes occurring in the course of the disease as well as its clinical behaviour. The analysis of this material demonstrates that mantle cell lymphoma affects predominantly elderly males presenting with an advanced stage of disease. Twenty-four out of 55 patients died with, or of, the disease with a median survival of 32 months, even though most of them received aggressive chemotherapy. In all cases the histological features were strikingly uniform and most cases had a diffuse growth pattern. The neoplastic cells corresponded to small cleaved cells with a minimal variation in shape and size from one case to the other. The phenotype of the neoplastic cells was remarkably constant with expression of several pan-B cell markers, IgM, IgD and CD5, and lack of CD10 and CD23.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Evaluation of capnography in nonintubated emergency department patients with respiratory distress.

OBJECTIVE: To evaluate the ability of noninvasive capnographic measurement of end-tidal CO2 tension (PetCO2) to predict arterial CO2 tension (PaCO2) in nonintubated ED patients with respiratory distress. METHODS: A prospective, nonblind study was performed in a level I trauma center/community teaching hospital ED. Participants included all nonintubated adult patients with respiratory distress requiring measurement of arterial blood gases (ABGs); 29 patients were enrolled. PetCO2 was measured with a capnography monitor, using both baseline tidal volumes and forced expiratory volumes. The bias between PetCO2 values and simultaneous measurements of PaCO2 by ABG was assessed. RESULTS: PetCO2, measured with forced expiration, and PaCO2 agreed well, with bias (i.e., average difference) = 0.44 +/- 0.52 kPa (3.3 +/- 3.9 torr). PetCO2 measured with the tidal volume breath produced an unacceptably high bias of 0.82 +/- 0.70 kPa (6.1 +/- 5.2 torr). Levels of agreement between PaCO2 were similar for smokers and nonsmokers and for men and women. The arterial-end-tidal CO2 tension (Pa-etCO2) difference was not related to PaCO2. Pa-etCO2 correlated with age (r = 0.473; p = 0.01), and was significantly higher in patients with pulmonary disease (1.32 +/- 0.56 kPa; 9.9 +/- 4.2 torr) than it was in those without pulmonary disease (0.46 +/- 0.55 kPa; 3.5 +/- 4.1 torr; p < 0.001). CONCLUSIONS: Noninvasive PetCO2 monitoring may adequately predict PaCO2 in nonintubated ED patients with respiratory distress who are able to produce a forced expiration. PetCO2 is less accurate for PaCO2 with tidal volume breathing and in patients with pulmonary disease.

Adult↗

Reliability of single and double probing attachment level measurements.

Clarification of the reliability associated with probing attachment level measurements and with diagnostic rules derived from them is necessary to examine the potential of these measurements as reliable markers of the disease process and as an outcome measure in clinical treatment studies. The purpose of the present study was to describe and compare the longitudinal reliability of single and double probing attachment level measurable by estimating false positive and false negative rates. In 20 systemically healthy adults with untreated advanced adult periodontitis, probing attachment levels and probing depth were measured at 6 sites in all teeth at the start of the study, and every 30 days thereafter for 11 months. Attachment levels were double measured, using acrylic onlays providing reference points and an electronic pressure sensitive probe. Attachment loss from baseline of 2.5 mm or more was used to accept dynamic attachment loss. The statistical methods for the cross-sectional analysis included mean absolute differences between double measurements and cross-correlations. Longitudinal analyses, expressing estimates of diagnostic error rates were made using maximum likelihood methods. 5 measurement protocols were compared. The results showed that the mean absolute difference between replicate measurements was 0.095 mm in bicuspids and 0.107 mm in molars. The mean absolute differences decreased over time from 0. 128 mm in visit 3 to 0.08 mm in visit 7. Correlation coefficients for replicate measurements were higher than 0.98. In general, false positive rates were markedly lower (< or = 0.02) than false negative rates (< or = 0.31). The relative sample size required to obtain comparable statistical power, was minimized in premolars when using the first of 2 measurements or the mean of 2 measurements, and in molars when using the first of 2 measurements. The methodology used in the present study provides guidelines for designing clinical studies which maintain statistical power by balancing off examiner reliability and sample size.

Acrylic Resins↗

Cotranscriptional splicing of a group I intron is facilitated by the Cbp2 protein.

The nuclear CBP2 gene encodes a protein essential for the splicing of a mitochondrial group I intron in Saccharomyces cerevisiae. This intron (bI5) is spliced autocatalytically in the presence of high concentrations of magnesium and monovalent salt but requires the Cbp2 protein for splicing under physiological conditions. Addition of Cbp2 during RNA synthesis permitted cotranscriptional splicing. Splicing did not occur in the transcription buffer in the absence of synthesis. The Cbp2 protein appeared to modify the folding of the intron during RNA synthesis: pause sites for RNA polymerase were altered in the presence of the protein, and some mutant transcripts that did not splice after transcription did so during transcription in the presence of Cbp2. Cotranscriptional splicing also reduced hydrolysis at the 3' splice junction. These results suggest that Cbp2 modulates the sequential folding of the ribozyme during its synthesis. In addition, splicing during transcription led to an increase in RNA synthesis with both T7 RNA polymerase and mitochondrial RNA polymerase, implying a functional coupling between transcription and splicing.

Base Sequence↗

Blood lactate levels of decathletes during competition.

There are many detailed physiological profiles of athletes who participate in a wide variety of sporting activities but few data have been obtained on decathletes. This study defines some physiological characteristics of these athletes and measures capillary lactate concentrations [La(b)] during a laboratory test of progressive maximal exhaustion and the different events during competition. The treadmill test is similar to the 100 m, 400 m and 1500 m in terms of [La(b)] accumulation but only similar to the 1500 m in terms of velocity. The 400 m is the most demanding event with the greatest blood lactate accumulation (mean(s.d.) 16.38(2.36) mmol l-1). The [La(b)] at the end of the 110 m hurdles is significantly lower than in any other racing events (mean(s.d.) 6.96(1.32) mmol l-1) compared with mean(s.d.) 12.14(2.87) and mean(s.d.) 11.44(2.16) for the 100 m and 1500 m respectively. The [La(b)] after the long jump, the high jump and the pole vault are not significantly different (mean(s.d.) 5.30(2.23), 4.64(1.39) and 5.36(1.34) mmol l-1) respectively).

Adolescent↗

Intrarectal pressures and balloon expulsion related to evacuation proctography.

Seventy four patients with constipation were examined by standard evacuation proctography and then attempted to expel a small, non-deformable rectal balloon, connected to a pressure transducer to measure intrarectal pressure. Simultaneous imaging related the intrarectal position of the balloon to rectal deformity. Inability to expel the balloon was associated proctographically with prolonged evacuation, incomplete evacuation, reduced anal canal diameter, and acute anorectal angulation during evacuation. The presence and size of rectocoele or intussusception was unrelated to voiding of paste or balloon. An independent linear combination of pelvic floor descent and evacuation time on proctography correctly predicted maximum intrarectal pressure in 74% of cases. No patient with both prolonged evacuation and reduced pelvic floor descent on proctography could void the balloon, as maximum intrarectal pressure was reduced in this group. A prolonged evacuation time on proctography, in combination with reduced pelvic floor descent, suggests defecatory disorder may be caused by inability to raise intrarectal pressure. A diagnosis of anismus should not be made on proctography solely on the basis of incomplete/prolonged evacuation, as this may simply reflect inadequate straining.

Catheterization↗

Chest physical therapy management of patients with cystic fibrosis. A meta-analysis.

The purpose of this overview is to quantitatively assess the conflicting body of literature concerning the efficacy of physical therapy modalities for clearing bronchial secretions in the treatment of patients with cystic fibrosis (CF). The modalities examined included positive expiratory pressure (PEP) mask, forced expiratory technique (FET), exercise (EX), autogenic drainage (AD), and standard physical therapy (STD), consisting of postural drainage, percussion, and vibration. Computerized searches of the MEDLINE and Cumulative Index for Nursing and Allied Health databases were performed for the years from 1966 to 1993. The authors of relevant papers were contacted for unpublished information. Studies were considered relevant if they met the following criteria: randomized trials in patients with a definite diagnosis of CF; an intervention of any combination of PEP, FET, STD, AD, or EX; and an outcome of FEV1, sputum weight, or sputum clearance. A review of 456 citations yielded 65 potentially relevant trials and 8 review articles; of these, 35 met the inclusion criteria and were incorporated into the overview. These studies evaluated different combinations of physical therapy modalities; therefore, we performed seven separate meta-analyses comparing the independent techniques using the pooled effect size technique. Standard physical therapy resulted in a significantly greater sputum expectoration than no treatment (effect size of 0.61 SD units, p < 0.0001). The combination of standard therapy with EX with associated with a statistically significant increase in FEV1 over STD alone (effect size of 0.48 SD units, p = 0.04). No other differences between physical therapy modalities were found.

Cystic Fibrosis↗

Action of metformin on glucose transport and glucose transporter GLUT1 and GLUT4 in heart muscle cells from healthy and diabetic rats.

The effects of the antidiabetic drug metformin on glucose transport were investigated in freshly isolated heart muscle cells from healthy and streptozotocin-diabetic rats. In vivo treatment of diabetic rats with metformin failed to affect the basal and insulin-stimulated rate of glucose transport measured in isolated cells. In vitro exposure to therapeutic concentrations (< or = 10(-4) M) of metformin did not influence glucose transport, even upon incubation times up to 5 h or in the presence of high glucose (20 nM). In contrast, higher metformin concentrations produced an 8- to 12-fold increase in glucose uptake (with a lag of 90 min, and a maximum at 180 min and approximately 5 mM). In the presence of submaximal insulin concentrations (< or = 3.10(-10) M), the effects of metformin (5 mM) and of insulin were more than additive, whereas, at saturating insulin concentrations (10(-8) M), partial additivity was observed. Like insulin, metformin caused an approximately 1.6-fold increase in the content of both glucose transporter isoforms GLUT1 and GLUT4 in the plasma membrane of cardiac myocytes, with a corresponding decrease in an intracellular membrane fraction. cAMP-elevating treatments depressed the metformin-, but not the insulin-dependent glucose uptake, by 20-30%. In myocytes from diabetic rats, the rate of metformin-activated glucose transport was similar to that of cells from control animals, whereas basal and insulin-stimulated transport were substantially diminished. Finally, metformin (5 mM) induced a slight depression of oxygen consumption and energy metabolism of myocytes (as determined by measuring their level of energy-rich phosphates) comparable to the effects of hypoxia in rat hearts. In conclusion, these data do not provide evidence in favor of the hypothesis that glucose uptake by muscle tissue represents the site of metformin's therapeutic action in vivo. On the other hand, the large, insulin-independent effect of metformin at high concentrations (approximately mM) in vitro may be related to the action of hypoxia and occurs through a redistribution of glucose carriers from an intracellular locus to the plasma membrane. The mechanism (or signal) involved in metformin's action is likely to differ from that triggered by insulin and is not impaired in the diabetic state.

Animals↗

[Uro-oxalic renal lithiasis. Certain characteristics].

In a paper published in 1974, it was reported that uro-oxalic stones are found more often in subjects with group O than with group A blood types although the proportions of these two blood types are approximately equivalent in the French population. The present work confirms these data, the ratio of group O to group A renal lithiasis being approximately 3 to 1. In a paper published in 1987, uro-oxalic stones were found to occur preferentially on the left side: 84 on the left and 39 on the right. The present work confirms this notion since in 57 cases, stones were bilateral in 2 cases, on the left in 39 and on the right in 16. Extra corporeal shock wave lithotripsy was performed in 40 of the 57 cases and showed that uro-oxalic stones are most resistant to shock-waves than the other types of stones. They are about as hard as calcium oxalate monohydrate stones or harder in certain cases: A mean of 3,865 shock-waves were required in the 40 cases of the uro-oxalic lithiasis treated with the HM3 Dornier device, while the mean number of shock-waves required for all types of stones in general varies from 2,000 to 2,500. In 4 cases, 5,000 or 6,000 high power shock-waves (7,000 in one session and 9,500 in two sessions) had to be used to obtain a satisfactory result. The calcium oxalate part of these stones is almost always composed of calcium oxalate monohydrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Group Antigens↗