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Biomedical subjects

M J Cassidy

Publications and source records attributed to M J Cassidy.

At least 19 recordsLinked to original sources

Hidden Markov based autoregressive analysis of stationary and non-stationary electrophysiological signals for functional coupling studies.

In this paper, we apply multivariate autoregressive (MAR) models to problems of spectral estimation for stationary and non-stationary electrophysiological data. We describe how to estimate spectral matrices and approximate confidence limits from MAR coefficients, and for stationary data spectral results obtained from the MAR approach are compared with fast Fourier transform (FFT) estimates. The hidden Markov MAR (HMMAR) model is derived for spectral estimation of non-stationary data, and traditional model order selection problems such as the number of states to include in the hidden Markov model or the choice of MAR model order are addressed through the use of a Bayesian formalism.

Algorithms↗

fas-fas-ligand antigen expression and its relationship to increased apoptosis in acute renal transplant rejection.

BACKGROUND: To examine the role of fas-fas-ligand interaction and apoptosis in acute transplant rejection. METHODS: Pre- and posttransplant renal allograft biopsies were stained by in situ 3-end labeling of DNA for detection of apoptotic cells (TUNEL) and immunohistochemistry techniques were used for demonstration of fas and fas-ligand antigen expression. RESULTS: Posttransplantation apoptosis was significantly increased in acute rejection and acute tubular necrosis (P<0.0001) compared to preimplantation biopsies and biopsies taken from grafts showing dysfunction not attributed to rejection. Fas and fas-ligand expression was demonstrated predominantly in the tubular epithelium. In preimplant biopsies fas was expressed in 11% (4/37) of cases; posttransplantation expression increased to: 44% (8/18) acute rejection, 63% (5/8) acute tubular necrosis, and 38% (5/13) dysfunction without evidence of rejection. Fas-ligand was expressed by 30% (11/37) of preimplant biopsies, posttransplantation expression was reduced in all groups: 17% (3/18) acute rejection, 13% (1/8) acute tubular necrosis, delayed xenograft rejection and 15% (2/13) dysfunction without evidence of rejection. A correlation with fas-1 expression preimplantation and a subsequent absence of acute rejection post transplant was noted (P<0.001). CONCLUSIONS: Apoptosis is a feature of acute rejection and acute tubular necrosis. Fas expression is uncommon preimplantation and increases non-specifically post transplant. Fas-1 was expressed by a third of preimplantation biopsies and expression was lost non-specifically post transplant. The expression of fas-ligand preimplantation correlated with an absence of acute rejection episodes posttransplant, suggesting some degree of immune privilege. These data suggest that the fas-fas-1 mediated pathway does not play a specific role in apoptosis during acute rejection. We were unable to find any evidence that the fas-fas-1-mediated pathway has a role in the increased apoptosis seen during acute rejection.

Adult↗

Diagnosis and monitoring of renal osteodystrophy.

A variety of biochemical investigations and radiological techniques are available to assist in the diagnosis and monitoring of renal osteodystrophy. Measurement of serum parathyroid hormone remains the single most useful biochemical test in predicting bone histology in an individual patient. Newer biochemical markers of bone turnover are unlikely to supplant this in everyday practice, but may provide useful supplementary information in the future. The present review discusses the role of radiological investigation, including bone densitometry and quantitative ultrasound. Bone biopsy remains the 'gold standard' investigation. Its invasive nature and the need for specialized processing and interpretation limits its use in clinical practice, although it still has a role particularly in the investigation of low turnover states. Also, as molecular biological techniques are increasingly being used, the evaluation of biopsy specimens will in the future provide new insights into the disordered bone cell function that occurs in renal osteodystrophy.

Absorptiometry, Photon↗

Usefulness of quantitative heel ultrasound compared with dual-energy X-ray absorptiometry in determining bone mineral density in chronic haemodialysis patients.

BACKGROUND: Reduced bone mineral density (BMD) is associated with renal osteodystrophy and osteoporosis in end-stage renal failure patients. Dual-energy X-ray absorptiometry (DXA) is the standard non-invasive method to assess BMD, but is not always widely available. Quantitative heel ultrasound (QUS) is a mobile, relatively inexpensive, easy to perform and radiation-free method which can predict fractures to the same extent as DXA. This study assessed the usefulness of QUS vs DXA in determining BMD in chronic haemodialysis patients. METHODS: Patients had their BMD at the hip and spine measured by DXA (Lunar Expert). QUS of the left heel (McCue CubaClinical II machine) measured broadband ultrasound attenuation (BUA) and velocity of sound (VOS). Correlations between DXA and QUS parameters were calculated. Receiver operator characteristic (ROC) curves were plotted for BUA and VOS and used to define cut-off points for calculating sensitivities and specificities for BUA and VOS. Femoral neck BMD was applied as the standard for diagnosing osteoporosis (T< or =-2.5) and osteopaenia (T>-2.5 and < or =-1) by WHO criteria. RESULTS: Eighty eight patients (45.5% women), mean age 58+/-17 years, were studied. A total of 19% and 49% had femoral neck BMDs in the 'osteoporosis' and 'osteopaenia' ranges, respectively. There were good correlations between hip BMD and QUS parameters (r=0.68-0.79, P<0.001). Areas under the ROC curves for BUA and VOS in diagnosing 'osteoporosis' were 0.86 and 0.80, respectively. BUA and VOS had sensitivities of 76 and 71% and specificities of 80 and 69%, respectively, for diagnosing 'osteoporosis'. The positive predictive values for BUA and VOS were 48 and 35%, respectively, and the negative predictive values were 93 and 91% respectively. CONCLUSIONS: DXA and QUS parameters were significantly correlated. However, sensitivities and specificities of QUS parameters were not sufficiently high for QUS to be used simply as an alternative to DXA. The relatively high negative predictive values suggest that QUS may reliably screen out patients unlikely to have a BMD in the osteoporotic range. The relatively low positive predictive values, however, mean that subjects classified as osteoporotic using QUS require further investigations such as DXA to confirm the diagnosis.

Absorptiometry, Photon↗

Risk factors for reduced bone density in haemodialysis patients.

BACKGROUND: Renal osteodystrophy may result in considerable morbidity for patients with end-stage renal disease. Secondary hyperparathyroidism, adynamic bone disease and osteomalacia, the main bony problems in chronic renal failure, may all be responsible for a reduction in bone mineral density (BMD). This can result in an increased fracture risk. By virtue of their age, post-menopausal status (in women), sedentary life-style and treatment (including previous corticosteroids), haemodialysis patients may be expected also to be at risk for developing osteoporosis, but little is known about the relative importance of these factors. METHODS: We report a prospective study examining the prevalence of reduced bone mineral density (BMD) and its association with a wide range of factors, in a heterogenous group of 88 chronic haemodialysis patients. Femoral neck and lumbar BMD were measured by dual-energy X-ray absorptiometry (DXA). Stepwise multiple linear regression analysis was used to identify risk factors associated with low bone mass. RESULTS: Forty three patients (48.9%) had reduced BMD, and in 17 (19.3%) BMD was below the fracture threshold as defined on DXA measurements by the World Health Organization (WHO). The BMD had significant negative associations with age, serum parathyroid hormone (PTH) levels, current gastric acid suppression therapy, female gender, age at menarche and history of previous fracture. Positive associations were found with weight, haemoglobin concentration, average serum phosphate, weekly heparin dose, oral calcium supplementation and history of parathyroidectomy. CONCLUSIONS: We have confirmed the importance of PTH-related bone disease in affecting BMD in haemodialysis patients, but have found that some other factors, which are known to be risk factors for osteoporosis, are also important.

Absorptiometry, Photon↗

High-resolution endoluminal sonography is a sensitive modality for the identification of Barrett's metaplasia.

BACKGROUND: The "gold standard" and only accurate method for diagnosing Barrett's esophagus is by esophagogastroduodenoscopy with biopsy. We evaluated the ability of high-resolution endoluminal sonography (HRES) to detect the mucosal changes in Barrett's esophagus. METHODS: Seventeen patients with documented Barrett's and 12 normal controls underwent endoscopy with HRES examination using a 20 MHz ultrasound transducer to evaluate for mucosal changes. HRES examinations were videotaped then reviewed by an unblinded investigator to identify criteria possibly diagnostic of Barrett's and then by a blinded investigator to test the validity of these criteria. Barrett's was diagnosed by HRES if the second hypoechoic layer appeared thicker than the first hyperechoic layer of the mucosa. Normal mucosa was defined as having a pencil-thin second hypoechoic layer on HRES. Measurements of the second hypoechoic layer were made using a computer and compared in patients with Barrett's and patients with normal esophagus. RESULTS: All 17 patients with Barrett's were correctly identified by HRES (sensitivity 100%). Ten of 12 controls were correctly identified as normal (specificity 86%). There was good correlation between HRES and pathologic diagnoses (r 0.86). The second hypoechoic layer was significantly thicker in Barrett's patients than in normal controls (p < .001). CONCLUSIONS: HRES is a sensitive new method for identifying Barrett's esophagus. However, dysplasia could not be identified by HRES in this study.

Barrett Esophagus↗

Sequential mixed lymphocyte culture after kidney transplantation: induction of tolerance or sensitization.

Serial mixed lymphocyte culture (MLC) was used to monitor the evolution of donor-specific responsiveness over the first 2 years after cadaveric renal transplantation. Lymphocytes obtained from 37 patients at 0, 1, 3, 6, 12, 18 and 24 months following transplantation were assayed in a one-way MLC using donor lymphocytes as stimulator cells. Donor-specific hyporesponsiveness developed in 66% of the patients with functioning grafts. Donor-specific sensitization was noted in 2 patients with functioning grafts and the MLC reactivity remained unchanged compared to the pretransplant value in 8 patients. The patients with donor-specific hyporeactivity tended to remain either free of rejection episodes or experienced early rejection episodes only. Thus, using serial MLC we were able to identify patients who developed hyporeactivity or tolerance to donor antigens. These patients may require less immunosuppression.

Adult↗

Treatment of symptomatic nonachalasia esophageal motor disorders with botulinum toxin injection at the lower esophageal sphincter.

The purpose of this study was to determine if botulinum toxin injection at the lower esophageal sphincter improves symptoms in patients with nonachalasia spastic esophageal motility disorders. Fifteen patients with nonachalasia spastic esophageal motility disorders (diffuse esophageal spasm, nonspecific esophageal motility disorders, and lower esophageal sphincter dysfunction) unresponsive to medical therapy underwent endoscopic injection of botulinum toxin at the level of the gastroesophageal junction. Symptoms were scored (0 = no symptoms, 1 = mild, 2 = moderate, 3 = severe and 4 = very severe) before treatment, at seven days and every 30 days after treatment. There was significant improvement in chest pain, dysphagia, and regurgitation at 7,30,60 and 90 days after treatment. At one month after treatment, 11 of 15 (73%) patients had a good or excellent response to treatment. At the last patient interview (mean follow-up of 10.6 months), five (33%) patients continued to have a good to excellent response, whereas 10 (67%) underwent subsequent treatment with repeat botulinum toxin, pneumatic dilation, or bougienage. We conclude that botulinum toxin injection at the gastroesophageal junction leads to significant symptom improvement in patients with nonachalasia esophageal motility disorders. These results suggest that botulinum toxin may be an effective treatment option in some of these patients not responsive to conventional medical therapy.

Adolescent↗

Use of high-resolution endoluminal sonography to measure the radius and wall thickness of esophageal varices.

BACKGROUND: Measurement of variceal wall tension theoretically provides the most accurate method of predicting future variceal bleeding. Using high-resolution endoluminal sonography in 45 patients with known portal hypertension, we measured and correlated the two previously unmeasured variables involved in the calculation of variceal wall tension (radius and wall thickness) by the Laplace equation. METHODS: A 20 MHz 6.2F ultrasound transducer was used to image esophageal varices during standard esophagoscopy. All images were captured on videotape and later reviewed by two blinded investigators. Outer and inner variceal wall circumferences were measured at a cross section of each varix. The radius of each varix and the variceal wall thickness were calculated. The radius of each varix was then correlated with its wall thickness. The interobserver and intraobserver variabilities were measured. RESULTS: The mean variceal radius was .86 +/- .34 cm for the inner radius and 1.48 +/- .41 cm for the outer radius; mean variceal wall thickness was .099 +/- 0.037 cm. Intraobserver and interobserver correlation for the radius was r = .98 and r = .97, respectively. The intraobserver and interobserver correlations for the wall thickness were r = .92 and r = .91, respectively. Variceal radius did not correlate with the wall thickness of the varix. CONCLUSIONS: High-resolution endoluminal sonography provides a method for the accurate measurement of esophageal variceal radius and wall thickness. Variceal radius does not correlate with variceal wall thickness, implying that variceal wall tension cannot be accurately estimated by measurement of variceal size alone. Combining these data with measurements of variceal pressure should allow for the direct determination of wall tension and, subsequently, identification of patients at risk for variceal bleeding.

Adult↗

The effect of recombinant human erythropoietin on haematopoiesis in patients undergoing haemodialysis.

OBJECTIVE: To define the effect of intravenous recombinant human erythropoietin (rHuEPO) in patients with anaemia caused by chronic renal failure. Data collection included bone marrow response, ferrokinetics, red cell survival as well as the influence on red cell mass and plasma volume. DESIGN: A convenience sample of stable individuals on haemodialysis, with haemoglobin (Hb) levels of less than 80 g/l, was surveyed over a 12-week period while they were receiving the hormone. Blood counts and iron studies were monitored serially, while 51Cr-labelled red cells and 59Fe (III) citrate were used in the radionuclide investigations carried out before and after the course of replacement therapy was completed (pre and post injection). Bone marrow aspiration and trephine biopsy were performed at each of these times. RESULTS: The actual mean trial period was 14 weeks. Eight patients were enrolled but 1 was withdrawn after developing tuberculosis at the start of the study. Haemoglobin levels rose from 59 g/l (SD 8.8) to 96 g/l (SD 13.9) (P < 0.0001); mean red cell mass rose from 675 ml to 954 ml (P < 0.01). Concurrently, the serial studies in 6 patients showed prominent erythroid hyperplasia. Plasma iron turnover increased insignificantly from 42.5 to 118.9 mumol/l/day; erythron turnover increased from 42.5 to 87.3 mumol/l/day (P < 0.01). There was a marked shortening of the marrow transit time from 4.4 to 3.3 days (P < 0.03). Efficacy of erythropoiesis decreased from 1.17 to 0.65 (P < 0.05). Red cell survival was not altered. CONCLUSIONS: The patient with end-stage renal failure remains fully responsive to erythropoietin therapy. This is reflected in improved ferrokinetics, red cell hyperplasia in the marrow and rise in haemoglobin level without alteration in mean erythrocyte lifespan. Simple hormonal replacement is therefore a rational approach to management.

Anemia↗

The prevalence of antibodies to hepatitis C virus at two haemodialysis units in South Africa.

The prevalence of antibodies against hepatitis C virus (HCV) was determined in 103 haemodialysis patients who attended two dialysis units in South Africa. With the use of a second-generation enzyme-linked immunosorbent assay (UBI HCV EIA, Organon Teknika, The Netherlands) and a 4-recombinant immunoblot assay (Chiron Corporation, USA), antibodies to HCV were found in 22 patients (21%). Statistically significant associations with anti-HCV carrier status were duration of dialysis (P = 0.0005) and number of blood transfusions received (P = 0.008). With stepwise logistic regression analysis it was not possible to separate the effects of HCV status associated with these two variables. A transient elevation in alanine aminotransferase (ALT) occurred in 8 of the 22 anti-HCV-positive patients, compared with 14 of the 81 anti-HCV-negative patients (P = 0.054). As yet, no patients have clinical evidence of ongoing liver disease or persistently elevated ALT levels. Of the 45 dialysis staff members tested, none was positive for anti-HCV.

Adolescent↗

Omentopexy for the difficult perigraft lymphocele after renal transplantation.

Between January 1977 and October 1992, 6 patients who had undergone renal transplantation presented with a symptomatic lymphocele that failed to resolve after conventional therapy and eventually required surgical intervention. This complication developed between 7 and 36 months postoperatively. Patients presented with local discomfort combined with deteriorating graft function caused by ureteric obstruction. The lymphoceles recurred after aspiration or external drainage and resolved after omentopexy. We conclude that omentopexy is a satisfactory procedure for the treatment of lymphoceles which fail to resolve after aspiration or external drainage.

Adult↗