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Biomedical subjects

R Thomas

Publications and source records attributed to R Thomas.

At least 325 records · Page 18Linked to original sources

Calcium free hemodialysis: experience in the treatment of 33 patients with severe hypercalcemia.

OBJECTIVE: To assess the efficacy, adverse effects and relevance of calcium-free hemodialysis (CFHD) in the treatment of major hypercalcemia. DESIGN: Retrospective chart review. SETTING: Medical ICU. PATIENTS: All patients admitted over a 9-year period for hypercalcemia requiring urgent treatment and who underwent hemodialysis. INTERVENTIONS: CFHD with an acetate dialysate. MAIN RESULTS: Thirty-three patients with severe hypercalcemia from various etiologies received CFHD. Marked and rapid decrease of serum total calcium was obtained during all sessions (mean decrease: 1.71 +/- 0.54 mmol/l). Calcium rebound within 24 h after CFHD was observed in all evaluable cases (1 +/- 0.45 mmol/l; mean delay 13.7 +/- 5.8 h). Adverse cardiovascular effects occurred in 17 of 48 sessions (35%) and in 13 of 30 evaluable patients (43%). CONCLUSIONS: Adverse effects are frequent during CFHD. After correction of hypovolemia, its use should be restricted to patients with severe clinical symptoms or advanced renal impairment.

Adult↗

Reproducibility of thermodilution cardiac output determination in critically ill patients: comparison between bolus and continuous method.

OBJECTIVE: A semi-continuous thermodilution method (CCO) was recently developed to measure cardiac output with less risk of bacterial contamination, fluid overload, and user-induced errors than the classical bolus technique (BCO). Previous comparison between these two methods showed negligible bias. However, large limits of agreement suggest that the two methods are not interchangeable. We hypothesized that this poor agreement may be due to differences in reproducibility. METHODS: In 23 critically ill patients, 369 paired measurements of CCO and BCO were compared (range of cardiac outputs: 2.8 to 16 L/min). The reproducibility of BCO and CCO methods was evaluated on a sample of 205 and 209 determinations, respectively. RESULTS: The comparison between the CCO and the BCO methods confirmed previous results: i.e., small bias (-0.39 L/min) and large limits of agreement (-2.06 to +1.28 L/min). Reproducibility showed no bias for either the CCO or the BCO method. Limits of reproducibility agreement between repeated determinations were approximately 50% less for CCO than for BCO method: respectively -0.87 to +0.82 L/min for the CCO method and -1.56 to +1.37 L/min for the BCO method. Consequently, the threshold necessary to ascertain that the difference between two measurements was not due to the internal variability of the method (3 x SEM) was 0.39 for the CCO method and 0.75 L/min for the BCO method. CONCLUSION: Differences in reproducibility may explain the poor agreement between the CCO and BCO methods. The better reproducibility of the CCO method allows the detection of smaller variations in cardiac output and suggests the superiority of this new method.

Cardiac Output↗

The application of FISH techniques for physical mapping in the dog (Canis familiaris).

The abundance of CA/GT repeats in the DNA of the dog (Canis familiaris) has established the importance of polymorphic microsatellites in the development of a low density map of the canine genome. The assignment of linkage groups of markers to chromosomes by physical mapping requires reliable cytogenetic techniques for routine production of metaphase cells. The dog has 78 chromosomes, many of which are smaller and more contracted than those of other mammals. Although the molecular study of inherited disease in dogs has important implications for both improved welfare in dogs and the provision of animal models for human diseases, the small size and large number of chromosomes in the canine genome has discouraged the inclusion of cytogenetic analysis in the planning of relevant research protocols. In this report, Fluorescence In Situ Hybridization (FISH) techniques have been optimized for the physical mapping of probes in C. familiaris. A method to obtain a good yield of early and midmetaphases from short-term peripheral blood cultures and the optimal conditions for hybridization and detection of probes is described. Thirteen microsatellite-containing cosmid probes from a canine genomic library in pWE15, a highly repetitive probe (human ribosomal DNA pHr14E3), and a human X Chromosome (Chr) paint have been mapped. Six microsatellites, two ribosomal sites, and the human paint have been assigned to specific chromosomes.

Animals↗

Modelling space-time HIV/AIDS dynamics: applications to disease control.

This paper applies the outputs of a family of HIV/AIDS models to problems in disease control. The epidemic models comprising this suite include single and multiregion representations each adopting either a one or two risk population format. Here, risk is expressed in terms of activity rates and those at low risk are characterized by a reproduction rate of less than unity which defines a simulated epidemic that cannot start. These models are applied to the following problems in prevention and control: first, estimating the impact of national variations in population growth rates on the predicted size of the epidemic, second, constructing control charts to assess the impact of intended interventions, third, evaluating the consequences of targeting preventative action at those at high risk; and last, evaluating the implications for international control of differences between the serological and simulated pandemic pathways. The discussion sets these findings within the context of forming health policy.

Acquired Immunodeficiency Syndrome↗

Sensitivity of testis tumour cells to chemotherapeutic drugs: role of detoxifying pathways.

In contrast to most other types of cancer, metastatic testicular germ cell tumours (TGCT) are cured in most patients using cisplatin-based combination chemotherapy. The biochemical mechanisms underlying this sensitivity have not been defined. Drug detoxification can modulate response to chemotherapy in vivo and in vitro, and therefore we measured levels of glutathione (GSH), glutathione-S-transferase (GST) and both constitutive and cisplatin- and dexamethasone-induced levels of metallothionein (MT) in five human testis tumour cell lines. The levels were compared with those in five human bladder cancer cell lines and two cell lines with cisplatin resistance acquired in vitro. GSH levels were relatively low in the testis tumour cell lines, as might be expected in drug-sensitive cells, and there was a 77-fold increase in GSH levels in the cisplatin-resistant testis tumour cell line. GST levels were similar in the two cell types, while metallothionein levels were relatively high in the testis tumour cell lines. These data indicate that GSH may contribute to the sensitivity of TGCT to chemotherapy, and that GSH expression may be involved in the acquisition of cisplatin resistance in these tumours.

Antineoplastic Agents↗

Gene therapy for donor hearts: ex vivo liposome-mediated transfection.

OBJECTIVE: Liposomes may be an appropriate transfection vehicle for transplanted hearts, avoiding the use of viruses in immunosuppressed hosts and allowing transfection of nondividing cells. To study whether liposome-mediated transfection could be accomplished during transplantation, we used a liposome-reporter gene system in a rabbit model of allograft cardiac transplantation. METHODS: After aortic crossclamping, Stauffland donor hearts were injected with 10 ml Stanford cardioplegic solution; then a 1.3 to 2.0 mg/kg dose of chloramphenicol acetyl transferase in 1:1 deoxyribonucleic acid-liposome complexes was injected proximal to the aortic crossclamp for coronary artery perfusion. The hearts were transplanted into New Zealand White rabbit recipients in the heterotopic cervical position (n = 11 transplants). Recipients were sacrificed at 24 hours. Myocardial specimens (right and left ventricles) and vascular specimens (epicardial coronary artery, aortic root, and coronary sinus) from both the transplanted and native hearts were analyzed for chloramphenicol acetyl transferase protein by means of the enzymatic liquid scintillation assay (counts per minute per milligram of total protein). RESULTS: In the recipient, myocardial chloramphenicol acetyl transferase activity was significantly greater in treated donor hearts (mean 4.6 x 10(5) cpm/mg +/- 1.1 x 10(5) [standard error]) than in native hearts (mean 4.1 x 10(2) cpm/mg +/- 72 [standard error], p < 0.01, Mann-Whitney U test). In treated donor hearts, right and left ventricular specimens, as well as apical and basal myocardial specimens, were transfected equally. Chloramphenicol acetyl transferase activity in vascular specimens also indicated transfection (mean 5.4 x 10(5) cpm/mg +/- 2.5 x 10(5) [standard error]). Chloramphenicol acetyl transferase activity in the coronary sinus was comparable with that in the coronary arteries, which suggests that liposomes can transverse the coronary capillary beds. CONCLUSIONS: These findings demonstrate that ex vivo transfection of donor hearts with a liposome-reporter gene system results in significant in vivo expression of the transfected gene product after cardiac transplantation. Genetic alteration of myocardium and cardiac vasculature has potential clinical applications in the prevention of posttransplantation rejection, ischemia-reperfusion injury, and both transplant and nontransplant coronary artery disease.

Animals↗

An analysis of surveillance for stage I combined teratoma--seminoma of the testis.

We analysed 973 patients with stage I testicular tumours presenting between 1983 and 1994. The median ages at presentation for non-seminomatous germ cell tumour (teratoma) were 27 years, seminoma 36 years and combined tumour 33 years. These differences were statistically significant (Mann-Whitney P < 0.05), suggesting that combined tumours may have a separate natural history. We, therefore, analysed all stage I patients managed with surveillance (530 in total) post orchidectomy. The actuarial 5 year relapse-free survival and anatomical patterns of relapse were identical for non-seminomatous germ cell tumour (NSGCT) and combined tumour and both were statistically distinct from seminoma (P = 0.01, log-rank test, chi-square test P = 0.001). The association of seminoma within a histologically confirmed NSGCT has no influence on the clinical outcome.

Adult↗

The holmium: YAG laser for ureteric stones.

OBJECTIVE: To assess the efficacy of the pulsed holmium: YAG laser for the fragmentation of ureteric stones. PATIENTS AND METHODS: One hundred patients (72 males and 28 females, age range 14 months-85 years) underwent 114 ureteroscopic procedures using either a 7.2 F semi-rigid or 9.5 F flexible ureteroscope. A holmium: YAG laser (Sunrise Technologies. Fremont, Ca, USA) was used for laser lithotripsy at a maximum energy of 1.0 J/pulse at 5 Hz. Most of the stones (46%) were located in the upper third of the ureter. The mean size of the stones was 9 x 8 mm and the mean duration of the procedure was 73 min (including anaesthesia) with a mean hospital stay of 2.7 days. RESULTS: All the stones were accessed successfully using miniaturized endoscopes either retrogradely or antegradely. The holmium laser effectively fragmented all types of stones. Total clearance of all stones fragments was achieved in 87% of cases, with the best results obtained for stones in the lower third of the ureter (96%). The complications attributed directly to the laser included three strictures and three perforations of the ureteric wall. CONCLUSION: The holmium: YAG laser was effective in fragmenting ureteric stones irrespective of their hardness. However, it has the potential to damage the ureteric wall and must be used with caution.

Adolescent↗

Ureteroscopic retrograde endopyelotomy for management of ureteropelvic junction obstruction.

Despite the success of endopyelotomy, many points are still being debated. Ureteroscopic retrograde endopyelotomy was carried out in 49 adult patients with 39 available for long-term follow-up. Prestinting facilitated instrument passage and reduces morbidity. The average operating time was 90.2 minutes. Two patients underwent elective nephrectomy for poorly functioning kidneys that did not improve after treatment, and one patient underwent urgent nephrectomy for bleeding 26 days postoperatively. Improvement in drainage was documented in the successful cases. The authors consider ureteroscopic endopyelotomy the first-line approach for most cases of ureteropelvic junction obstruction.

Adolescent↗

Rationale and design of a multicenter study of selegiline and alpha-tocopherol in the treatment of Alzheimer disease using novel clinical outcomes. Alzheimer's Disease Cooperative Study.

This report describes the rationale and design of a clinical trial using selegiline (10 mg/day) and alpha-tocopherol (2,000 IU/day) to slow the progression of dementia in Alzheimer disease (AD). This study was developed by the Alzheimer's Disease Cooperative Study (ADCS), a consortium of clinical research centers actively involved in AD research. The major goal of the consortium is to design and conduct clinical investigations leading to the development of treatments for AD. This study uses a randomized double-blind, placebo-controlled, 2 x 2 factorial, parallel group design to test two drugs for the treatment of AD. The primary outcome of the study is the time to reach any one of the following four endpoints: death, institutionalization, loss of two of three basic activities of daily living, and progression of Clinical Dementia Rating (CDR) stage from 2 to 3. Patients with moderately severe disease (CDR = 2) were enrolled and evaluated 10 times over a period of 2 years to determine if these agents reduce the time to reach any endpoint. A database from the Consortium to Establish a Registry for Alzheimer's Disease indicated adequate power analyses to observe a treatment effect on this clinically meaningful outcome measure. Recruitment and baseline characteristics of the population are provided. The rationale for the choice of a factorial design, the use of a novel, clinically meaningful endpoint, and the selection of a cohort of patients with AD of moderate severity are discussed.

Aged↗

Primary hepatic leiomyosarcoma.

Hepatomegaly was noted in a 63-year-old man who presented with an exacerbation of chronic pulmonary disease. A diagnosis of hepatic leiomyosarcoma was made by fine needle aspiration biopsy. Intensive investigations failed to reveal a primary source. The patient was treated conservatively.

Biopsy, Needle↗

Complications of urological laparoscopy: a standardized 1 institution experience.

PURPOSE: Urological laparoscopy has a significant and steep learning curve plus its own unique set of complications. Our retrospective study documents the success at 1 institution of maintaining a low number of complications during urological laparoscopy using a standardized approach plus clinicians with significant laparoscopic experience. MATERIALS AND METHODS: We evaluated 282 consecutive adults who underwent urological laparoscopic procedures at our institution. Of the procedures 241 (85%) were performed for pelvic lymph node dissection, and 41 (15%) for renal and other miscellaneous conditions. The common factor in all of these laparoscopic procedures was a single team approach, thus standardization for the entire series of procedures. RESULTS: Of 12 complications (4.2%) 5 were noted intraoperatively and 7 were discovered in the postoperative period. Five patients (1.8%) required open surgical intervention, including 3 intraoperative repairs of vascular (1), ureteral (1) and bladder (1) injuries. Procedures were aborted because of technical difficulties in 7 patients (2.8%) and because of hemorrhage during adrenalectomy in 1. Delayed complications included ureteral injury in 1 patient, seroma at the trocar site in 2, exacerbation of bowel diverticulitis requiring surgical intervention in 1, prolonged endotracheal intubation for hypercapnia in 1 and transient brachial nerve palsy in 2. CONCLUSIONS: Along with appropriate patient selection and adequate instrumentation, the benefit of significant laparoscopic experience and standardization cannot be overemphasized. The success of this combined approach is reflected in the low rate of major (2%) and minor (2.5%) complications experienced at 1 institution.

Adult↗

Three sibs with microcephaly, congenital heart disease, lung segmentation defects and unilateral absent kidney: a new recessive multiple congenital anomaly (MCA) syndrome?

We present three sibs with similar dysmorphic features, including brain, heart and lung malformations that have not been reported previously. Cytogenetic studies have failed to demonstrate a chromosomal abnormality. Although parental consanguinity was not present, we suggest that this may constitute a new recessive syndrome.

Abnormalities, Multiple↗

The flashlight test and van Herick's test are poor predictors for occludable angles.

OBJECTIVE: To determine the reliability and validity of the flashlight test and van Herick's test in detecting occludable anterior chamber angles. METHODS: The flashlight test, van Herick's test and gonioscopy were performed independently by two observers on 96 consecutive new patients in our outpatient clinic. Interobserver agreement was determined using the weighted Kappa statistic. Using the glaucoma specialist's assessment of occludability of the angle (assessed by gonioscopy) as a gold standard, the sensitivities and specificities of the two tests were calculated. RESULTS: All three tests showed good agreement (Kappa more than 0.75). The sensitivity and specificity on the flashlight test were 45.5% and 82.7% respectively. For the van Herick's test they were 61.9% and 89.3%. CONCLUSION: The flashlight test and van Herick's test are of limited use as screening tests for occludable angles.

Adolescent↗

Road humps: accident prevention or hazard?

Two cases of injury to passengers seated on public transport buses occurred after the vehicles had traversed road humps. While the potential dangers to seated bus passengers have been acknowledged in the Department of Transport literature, specific mention in medical reports is lacking. Should the United Kingdom follow the example set by the United States, where the placement of road humps on bus routes is avoided?

Accident Prevention↗