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Biomedical subjects

W Wall

Publications and source records attributed to W Wall.

At least 19 recordsLinked to original sources

A pragmatic protocol for I-131 rhTSH-stimulated ablation therapy in patients with renal failure.

PURPOSE: Ablation of thyroid remnants in patients with differentiated thyroid carcinoma and renal failure can be challenging because of the altered and variable clearance rates of iodine from the blood secondary to variations in dialysis protocols, which complicate the selection of the appropriate I-131 dose. The advent of recombinant human TSH allows a simpler approach to dosimetry and ablation without rendering the patient hypothyroid. Avoidance of hypothyroidism may be an important consideration for patients who are experiencing various morbidities from conditions associated with renal failure. METHOD: Three patients on dialysis, who had undergone total thyroidectomy and were euthyroid on L-thyroxine replacement, were given diagnostic doses of I-131 followed by blood and whole-body retention measurements through serial dialyses to determine individual blood clearance rates. After administration of rhTSH, each patient received an ablative dose of I-131 calculated to keep total body dose below 1 Gy. RESULTS: The treatments were administered without complications, and in follow-up imaging of 2 available patients, the ablations were demonstrated to be complete. CONCLUSION: Dosimetry performed on euthyroid dialysis patients permits I-131 dose selection and avoids the additional morbidity of hypothyroidism.

Adult↗

Use of recombinant factor VIIa in pediatric patients with liver failure and severe coagulopathy.

BACKGROUND: Several reports have suggested a benefit for recombinant Factor VIIa (rFVIIa) in nonhematological conditions, including liver disease and transplantation. However, there are few reports of its use in children with liver failure. Recently, we used rFVIIa in four patients with liver failure and severe coagulopathy with bleeding who demonstrated significant laboratory and clinical improvement following its use with no side effects. PATIENTS AND METHODS: All four patients were hospitalized with liver failure, coagulopathy, and bleeding that was controlled with fresh frozen plasma, platelets, and other therapies, as indicated. Their international normalization ratios (INR) ranged from 1.7 to 5.8 (normal 0.9-1.1). All four patients received rFVIIa for bleeding episodes that were not responding to their usual therapy, for procedures with a high risk of bleeding, or both. The dose of rFVIIa ranged from 0.067 to 0.3 mg/kg. The INR improved to normal or near normal in all four patients. In all cases, bleeding stopped within 10 minutes of receiving the rFVIIa, and there were no complications observed. CONCLUSIONS: rFVIIa provided significant benefit in these children with liver failure and severe coagulopathy, in terms of clinical and laboratory improvement in their bleeding and coagulation profiles. There were no obvious side effects from the rFVIIa. This drug may be an important tool in the treatment of children with liver failure and more study is needed to define the optimal dosing for children.

Blood Coagulation Disorders↗

Liver transplantation for primary sclerosing cholangitis.

UNLABELLED: Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease that progresses to end-stage liver disease. This report is a retrospective analysis of a Canadian centre experience with liver transplantation (LT) for PSC. Of 1107 LTs performed between 1984 and 2002, 132 were performed on 111 patients with PSC. Patient survival at 1, 3, 5, and 10 years was 84.5%, 84.5%, 83.4%, and 68.9%, respectively. Graft survival at 1, 3, 5, and 10 years was 80.8%, 79.8%, 72.7%, and 55.3%. These were not significantly different from overall patient survival (P =.91) or graft survival (P =.28) in non-PSC patients transplanted over the same time period. Early mortality was predominantly related to primary nonfunction and multi-organ failure; late mortality was predominantly related to malignancy. No patient with known cholangiocarcinoma (CCA) underwent LT, but three patients had an incidental CCA noted on explant pathology. All three died of widespread metastatic disease (10.8, 38.0, and 39.8 months after LT). Nineteen patients lost their primary grafts requiring retransplantation, and two of these patients required a third transplant. Recurrent PSC was detected in six patients and suspected in another six. Four patients have been retransplanted for recurrent PSC. Chronic rejection was detected in nine patients. Eight have required retransplantation. The incidence of biliary complications was 16.2%. CONCLUSIONS: LT is effective therapy for PSC. Patient and graft survival is comparable to that seen in patients transplanted for indications other than PSC, but long-term graft survival may be lower. Recurrent PSC and chronic rejection are the major determinants of graft loss.

Actuarial Analysis↗

Electrically driven microseparation methods for pesticides and metabolites: V. Micellar electrokinetic capillary chromatography of aniline pesticidic metabolites derivatized with fluorescein isothiocyanate and their detection in real water at low levels by laser-induced fluorescence.

Anilines are important pollutants occurring in the environment as industrial discharges as well as the transformation products (i.e., metabolites) of a wide variety of commonly used pesticides. In this report, we describe the precolumn derivatization of anilines with fluorescein isothiocyanate (FITC) and their subsequent separation and detection by capillary electrophoresis-laser induced fluorescence (CE-LIF) detection. The FITC-aniline derivatives were readily detected at the 10(-10) M level. This limit of detection (LOD) was achieved in the presence of glycosidic surfactants complexed with borate at alkaline pH yielding the so-called in situ charged micelles. The glycosidic surfactants evaluated were n-octyl- and n-nonylglucopyranoside. Furthermore, and under optimum conditions, the FITC precolumn derivatization of the anilines was performed in real water (e.g., tap and lake water) spiked with anilines at the LOD level. The water matrices showed marginal effects on the extent of derivatization at the LOD level, and the possible interferents in the water samples did not affect the FITC-solute signal due to the selectivity of the derivatization and detection schemes. Besides filtration from microparticles, the real water samples did not necessitate extensive sample cleanup prior to derivatization.

Aniline Compounds↗

Electrically driven microseparation methods for pesticides and metabolites: VI. Surfactant-mediated electrokinetic capillary chromatography of aniline pesticidic metabolites derivatized with 9-fluoroenylmethyl chloroformate and their detection by laser-induced fluorescence.

In this report, we describe a surfactant-mediated electrokinetic capillary chromatography (SM-EKC) system for the separation of 9-fluoroenylmethyl chloroformate (FMOC)-derivatized anilines by capillary electrophoresis (CE). The SM-EKC system consisted of dioctyl sulfosuccinate (DOSS)/acetonitrile mixtures and was suited for the CE separation of the relatively hydrophobic FMOC-aniline analytes and other neutral compounds, e.g. alkylphenyl ketones. While the organic modifier acetonitrile (ACN) allowed the solubilization of the hydrophobic solutes and maintained the DOSS surfactant in its monomeric form by inhibiting micellization, the DOSS surfactant associated with the FMOC anilines to a varying degree thus leading to their differential migration and separation. Under these conditions, the FMOC-anilines were readily detected at the 10(-6) M level by UV at 214 nm and at the 10(-8) M level by laser-induced fluorescence (LIF) using a solid-state UV laser operating at 266 nm line as the excitation wavelength. The FMOC precolumn derivatization was also readily performed in lake water spiked with anilines at near the limit of detection (LOD) level. The lake water matrix showed no significant effects on the extent of derivatization at the LOD level as well as on the detection of the analytes due to the selectivity of the FMOC derivatization. The derivatization and detection of spiked lake water necessitated only the removal of microparticles by microfiltration prior to derivatization and detection.

Aniline Compounds↗

Immortality in a name.

Have you ever wondered where flora and fauna found their names? Many are named for people--rich and poor, large and small. Even tabletop football is not immune.

Animals↗

Arteritis and increased intracellular calcium as a possible mechanism for tacrolimus-related cardiac toxicity in a pediatric transplant recipient.

We recently reported partially to wholly reversible hypertrophic cardiomyopathy, including severe hypertrophic obstructive cardiomyopathy, as a side effect in pediatric transplant recipients receiving tacrolimus immunosuppression. This seemed to be dose related. We describe a pediatric patient receiving tacrolimus who died 3 weeks after liver/bowel transplantation. Postmortem findings revealed arteritis of cardiac arteries and extensive calcification of cardiac tissue suggesting a possible mechanism of tacrolimus cardiac toxicity. This is consistent with recent reports of tacrolimus increasing calcium release into the sarcoplasmic reticulum of cardiac and striated muscle.

Arteritis↗

An analysis of late deaths after liver transplantation.

Late deaths (after more than 1 year) after liver transplantation were analyzed in a series of 464 consecutive patients who received liver grafts between 1982 and 1993. Recipients who survived the first posttransplant year (n = 365) had actuarial 5- and 10-year survival rates of 92% and 84%, respectively. Thirty-five patients died between 1.1 and 7.6 years after transplantation (mean, 3.2 +/- 1.9 years). The most common causes of death were related to immunosuppression (40%), namely, chronic rejection, opportunistic infection, and lymphoma. The second most common causes of death were related to the primary disease for which liver transplantation was performed (34.3%), mainly recurrence of hepatobiliary malignancy and hepatitis B. Eight patients (22.9%) died of unrelated and unpredicted causes, most commonly of cardiovascular disease. Although the survival of liver recipients who live beyond the first posttransplant year is excellent, control of rejection and the consequences of chronic immunosuppression are continual threats. Modification of immunosuppression may help in decreasing the mortality of long-term survivors. In addition, better selection of recipients and effective adjuvant therapies (antiviral and antineoplastic) are needed in patients in whom the primary liver disease is notorious for recurrence.

Adolescent↗

Small bowel transplantation. A life-saving option for selected patients with intestinal failure.

Thirty-seven patients were listed for small bowel transplantation; 16 were transplanted and 15 died while waiting for a donor. Cyclosporine (N = 6) or tacrolimus (N = 10) were used for immune suppression. Graft rejection rates were lower in the combined liver/small bowel grafts than the isolated intestinal transplants (1/7 vs 5/7; P < 0.01) All of the cyclosporine group have died; the median survival was 25.7 months with two patients living more than five years. The tacrolimus group had fewer infections and a shorter hospital stay. All but two are alive with a median survival of 13 months. Seven of eight long-term survivors are off intravenous feedings. We conclude that small bowel transplantation is a life-saving option for patients with intestinal failure who cannot be maintained on total parenteral nutrition.

Adolescent↗

Hypertrophic cardiomyopathy associated with tacrolimus in paediatric transplant patients.

Reported side-effects of tacrolimus, a potent immunosuppressive agent, have not included cardiotoxicity. We describe 5 consecutive paediatric transplant recipients (3 small bowel with or without liver and 2 liver) who received tacrolimus. 2 developed congestive heart failure and hypertrophic obstructive cardiomyopathy which resolved after changing to cyclosporin. In the other 3 patients the cardiomyopathy regressed or improved with a lower dose of tacrolimus or after stopping the drug.

Blood Pressure↗

The OKT3 Antibody Response Study: a multicentre study of human anti-mouse antibody (HAMA) production following OKT3 use in solid organ transplantation.

Human anti-murine antibody titres following patient exposure to the monoclonal antibody Orthoclone OKT3 (muromonab-CD3) are determined by laboratories using diverse analytical methods which are not standardized and whose concordance is not established. A multicentre study group therefore compared testing for IgG anti-OKT3 antibody among seven laboratories. A set of 270 sera was obtained from 30 heart, 30 kidney and 30 liver transplant recipients with no previous exposure to OKT3 who were receiving OKT3 for induction immunosuppression. Sera were collected from each patient prior to and at 24 +/- 2 days and 31 +/- 2 days following initial OKT3 exposure. Identical aliquots of all 270 sera were tested for IgG anti-OKT3 antibody by each laboratory. In addition, the limit of detection of each laboratory's method was estimated by titration of an affinity-purified IgG anti-OKT3 reference material of known concentration. Anti-OKT3 antibody formation differed greatly among the three organ groups. Cardiac patients demonstrated the least sensitization and almost exclusively lower titres, while kidney recipients had more frequent and higher titre antibody formation. Liver recipients yielded the highest sensitization rate and the most frequent high titre sera. Importantly, the seven laboratories differed widely in the number of pretreatment sera reported as positive (ranging from 0% to 41% among laboratories), the number of post-OKT3 sera reported as positive (17-63%), the number of post-OKT3 samples with titre > or = 1000 (2-31%), and the number of patients sensitized 19-69%). Concordance among laboratories was highly variable, with interlaboratory agreement ranging from 38% to 83% on the sample titres assigned to 180 post-OKT3 sera. Many of the discordant results were consistent with differences in the limit of detection of the analytical methods, which ranged from 0.19 microgram/ml to > or = 15 micrograms/ml, a nearly 100-fold difference among laboratories. This study demonstrated the presence of both good concordance and significant discordance among laboratories in determining human anti-mouse antibody titres, and demonstrated that common titre categories (100, 1000, 10,000) were not equivalent among laboratories. The level of concordance among methods should be considered when comparing anti-OKT3 antibody results from different centres and their correlation with clinical events. Universal comparative testing, patterned after proficiency testing programmes, is needed to assess differences among laboratories and to bring uniformity and a sound interpretative basis to this field of testing.

Adult↗