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D Ellis

Publications and source records attributed to D Ellis.

At least 37 records · Page 2Linked to original sources

A case of Pelizaeus-Merzbacher disease showing increased dosage of the proteolipid protein gene.

Clinical, neuropathological and molecular genetic studies in a 9 month old boy with Pelizaeus-Merzbacher disease are described. The principal clinical features were developmental delay, nystagmus, stridor and seizures. Both brain and spinal cord showed almost complete absence of stainable central myelin, while cranial and spinal root myelin was preserved. Probes for cDNA in the boy and his asymptomatic mother indicated an increase in the dosage of proteolipid protein gene (of at least twofold) compared with controls.

DNA Probes

Atypical hyperlipidemia and nephropathy associated with apolipoprotein E homozygosity.

Hyperlipidemia has been implicated in the pathogenesis of experimental progressive glomerulosclerosis, but its role in human renal injury is controversial. This report describes a 12-yr-old boy presenting with massive proteinuria, hepatomegaly, anemia, severe mixed hyperlipidemia, and progressive renal failure. The initial renal biopsy disclosed large numbers of foam cells that were shown to be monocytes. Evidence is presented suggesting that apoprotein-E2 homozygosity in our patient, together with an 88% reduction in plasma lipoprotein lipase activity associated with severe nephrotic syndrome, is responsible for the atypical clinical features, lipoprotein phenotype III with chylomicronemia, and renal lipidosis. A regimen of dietary lipid restriction, gemfibrozil, and niacin resulted in significant but partial improvement of the dyslipidemia and resolution of the hepatomegaly and ascites. This report stresses the importance of characterizing unique lipid disorders in patients with nephrotic syndrome in order to prescribe effective lipid-lowering strategies. Moreover, the striking resemblance of the clinical and nephrohistologic features of this patient to those occurring in experimental models of coexisting glomerular injury and hyperlipidemia led to the speculation that, in this setting, the hyperlipidemia may contribute to the development of progressive glomerulosclerosis.

Apolipoproteins E

The influence of pregnancy on IDDM complications.

OBJECTIVE: Although pregnancy has been associated with an increased progression of certain insulin-dependent diabetes mellitus (IDDM) complications, particularly retinopathy, both the short- and long-term relationships between pregnancy and both neuropathy and macrovascular disease are poorly documented. This study was conducted to comprehensively examine the influence of pregnancy on the development and progression of IDDM complications. RESEARCH DESIGN AND METHODS: Using the Pittsburgh Epidemiology of Diabetes Complications Study population (childhood-onset IDDM), two nested, pair-matched case-control studies were conducted. Women who had completed at least one successful pregnancy (n = 80) were matched to women with no history of pregnancy by age, duration of IDDM, race, and marital history. The first nested study (study 1) compared the prevalences of five IDDM complications between case and control groups. The second nested study (study 2) compared the incidences of the same five complications over an approximate 2-year interval during which the case subjects (n = 30) completed a successful pregnancy. RESULTS: There were no significant differences in the prevalence rates of coronary heart disease, neuropathy, proliferative retinopathy, lower extremity arterial disease, and overt nephropathy by case-control status, while parity did not predict any complication in multiple logistic analysis (study 1). In study 2, there were small but nonsignificant differences in incidence rates of overt nephropathy and lower extremity arterial disease between the groups, whereas case subjects had almost 3 times the incidence rate of proliferative retinopathy (P = 0.58) and 10 times the incidence rate of neuropathy (P < 0.001) as did other matched control subjects. In multivariate analysis, parity predicted neuropathy incidence but did not predict the incidence of any other complication, including proliferative retinopathy. CONCLUSIONS: Women with IDDM who experience a pregnancy may not be at an increased risk of diabetes complications later in life. However, in the short term, pregnancy may accelerate the development of some complications, such as neuropathy.

Adult

Benefits realised from a blood transfusion policy for elective joint arthroplasty.

Transfusion practice and blood ordering policy for major joint replacement was studied during 1989-93. Existing practice requiring automatic preoperative cross-match was prospectively audited. A blood ordering policy rationalising transfusion practice, using the group and screen technique, was then introduced. This resulted in a decrease in the total number of units cross-matched and increased the transfusion fraction significantly. The percentage of blood returned to the blood bank decreased by 46% for knees and 41% for hip arthroplasty. After the introduction of low molecular weight heparin (LMWH) as routine deep vein thrombosis (DVT) prophylaxis for all major total joint arthroplasties, the total transfusion requirement did not increase. In fact, the average number of units transfused per case after its introduction was marginally less at 1.3 units per hip, and 0.9 units per knee.

Arthroplasty

The superiority of tacrolimus in renal transplant recipients -- the Pittsburgh experience.

Tacrolimus is a superior immunosuppressive agent in patients undergoing renal transplantation. In adults, the 1- and 3-year actuarial patient survivals were 95% and 92%, and the 1- and 3-year actuarial graft survivals were 89% and 80%. For first cadaver kidneys, the 1- and 3-year actuarial graft survivals were 91% and 82%, with a projected half-life of 11.9 years. Sixty-nine percent of successfully transplanted patients were weaned off steroids. In pediatric patients, the 1- and 4-year actuarial patient survivals were 100% and 96%, and the 1- and 4-year actuarial graft survivals were 99% and 85%. Seventy-three percent of successfully transplanted children were weaned off steroids. Tacrolimus was also useful as a rescue agent, with an initial success rate of 74%. Tacrolimus has been used successfully in kidney/ pancreas transplantation, with 100% patient, 95% kidney, and 79% pancreas graft survival. Tacrolimus should be considered the immunosuppressive agent of choice in renal transplantation.

Adolescent

Measurement of intracellular ionized magnesium concentration in myocytes isolated from the septomarginal band of sheep hearts.

The preparation by collagenase dispersion is described of isolated, calcium-tolerant myocytes from the septomarginal (moderator) band dissected from the sheep heart. Cells obtained were small rods (85 x 9 microns), with pronounced striations characteristic of cardiac myocytes. Isolated cells were loaded with the fluorescent ion-sensitive probes Mag-fura-2 or fura-2, for use in microspectrofluorimetry experiments to measure cytosolic free magnesium ([Mg2+]i) and calcium ([Ca2+]i) respectively; cells remained usable for up to 8 h after isolation. Glycolysis and electron transport were inhibited by a short exposure (4 min) to deoxyglucose (15 mM) and cyanide (2 mM), added simultaneously. This appeared to produce a small, but not statistically significant (P = 0.056) rise in [Mg2+]i, presumably resulting from Mg2+ liberated following consumption of MgATP. Inhibition of the Na pump by strophanthidin (20 microM), followed by removal of external Na in the presence of strophanthidin, caused an increase in both [Mg2+]i and [Ca2+]i. The time course of changes in the two ions were dissimilar, so it seems unlikely that the observed rise in the [Mg2+]i was due solely to a direct effect of [Ca2+]i on Mag-fura-2 or due to the displacement of [Mg2+]i by Ca from binding sites. Evidence is presented that suggests sodium-magnesium exchange plays a role in the regulation of myocyte [Mg2+]i.

Animals

Hypoxia-induced intracellular acidification in isolated sheep heart Purkinje fibres and the effects of temperature.

The changes of intracellular pH (pHi) produced by hypoxia in sheep heart Purkinje fibres were studied using liquid ion exchanger-filled microelectrodes. A decrease of temperature from 35 degrees C to 22 degrees C caused an alkalinization of 0.3 pH units. Hypoxia (partial pressure of oxygen < 10 mm Hg) for 20 min induced an acidification of 0.26 +/- 0.18 units (n = 14) at 35 degrees C. The hypoxia-induced acidification at 22 degrees C was smaller than that at 35 degrees C by approximately 65%. Increasing the buffering capacity of the cells decreased the hypoxic acidification. This could be achieved either by use of high extracellular HEPES concentrations (40 mM) or by the use of bicarbonate buffers. Sodium cinnamate (5 mM) increased the hypoxic acidification and slowed the pHi recovery on reintroduction of oxygen, implying an importance role for lactate flux in pH regulation during hypoxia.

Animals

Comparison of FK-506 and cyclosporine regimens in pediatric renal transplantation.

Clinical aspects of FK-506 or cyclosporine immunosuppression regimens were evaluated in 48 consecutive pediatric renal transplant recipients. Tapering and discontinuation of prednisone was employed only in children receiving FK-506 who experienced minor or no rejection episodes during the 1st posttransplant month. At 1 year follow-up, 17 of 22 (77%) of all children with functioning allografts were receiving no prednisone (n = 13) or a mean dosage of 0.07 mg/kg per day (n = 4). During the 1st month, acute cellular rejection was more common in the FK-506 group (0.58 vs. 0.21 rejections per patient, P < 0.05) but allograft survival (92%) and renal function at 1 year posttransplant were identical in both groups. Compared with the cyclosporine regimen, FK-506 immunosuppression may be associated with a higher incidence of cytomegalovirus or reversible Epstein-Barr virus-induced lymphoproliferative disease. However, the FK-506 group had less hirsutism and gingival hypertrophy and required fewer antihypertensive medications independent of steroid use. Height standard deviation scores and weight-for-height index improved only in pre-adolescents receiving FK-506 but no prednisone (P < 0.02 and P < 0.05, respectively), but did not differ between children on FK-506 plus prednisone and those in the cyclosporine group. We conclude that the major advantages of FK-506 over cyclosporine immunosuppression are a reduced severity of hypertension and an improved cosmetic appearance which may improve long-term medical compliance. When used as monotherapy, FK-506 also shows promise in relieving the growth retardation associated with cyclosporine regimens that include prednisone.

Adolescent

The association of waist/hip ratio with diabetes complications in an adult IDDM population.

Cross-sectional data from the Epidemiology of Diabetes Complications Study were used to examine the relationships between waist to hip circumference ratio (WHR) and the presence of diabetes complications in IDDM adults ages 18-45 years (N = 586). Significantly higher WHRs were observed among both genders with proliferative retinopathy or peripheral vascular disease and only among males with either neuropathy or nephropathy compared to those free of these complications. Logistic regression to determine the strength of association between WHR and each complication demonstrated that although WHR was significantly related to each complication (except nephropathy among females), WHR was only independently related to neuropathy in males and PVD in females in the final model when hypertension, LDL- and HDL-cholesterol and fibrinogen were included. These findings suggest that WHR acts as a marker of risk for diabetes complications mainly through an influence on other complication risk factors.

Adolescent

Histopathological changes in human prostatic adenoma following neodymium:YAG laser ablation therapy.

Transurethral laser ablation of the prostate is a procedure currently under evaluation as an alternative to transurethral resection of the prostate in the management of benign prostatic hyperplasia. Removal of prostatic tissue by endoscopic resection or open surgical techniques from 7 patients in whom prostatic laser ablation was previously attempted offered an opportunity to evaluate the sequential effects of such energy upon the human prostate at varying intervals after treatment. A progressive inflammatory and necrotic response, initially akin to that demonstrated after a thermal burn, together with evolving vascular changes within the residual viable prostatic tissue were demonstrated. Our study demonstrates the changes in the human prostate whereby neodymium:YAG laser energy causes a deep coagulative necrosis and arterial thrombosis in the prostatic adenoma. These changes differ significantly from those noted in canine studies. A slower cavitation effect is observed in the human compared with the canine, and this finding mirrors the continuing clinical improvement in voiding parameters with time.

Aged

A controlled comparison of HIV and general medical referrals to a liaison psychiatry service.

A retrospective case-control study was performed to compare the patterns of psychiatric illness and treatment in 70 patients referred to the psychiatric liaison service from the HIV/AIDS team in a London teaching hospital with 70 age- and sex-matched controls referred for psychiatric assessment from general medical and surgical wards or out-patient clinics. Organic, mood, adjustment and personality disorders were the most common primary diagnoses. The rate of referral in the HIV group was five times that in the control group. The prevalence of each group of diagnoses was not significantly different between the HIV and control groups, except in the case of alcohol dependence (15/70 (control) v. 3/70 (HIV), p = 0.005). Forty-four per cent of the HIV group and 30% of the control group fulfilled DSM-III-R criteria for a secondary diagnosis of non-alcohol psychoactive substance abuse. A diagnosis of borderline personality disorder was made more often in the HIV group. The high frequency of psychoactive substance abuse in both the HIV and control groups has important implications for the provision of psychiatric services.

Adult

Improving results of pediatric renal transplantation.

BACKGROUND: Outcome after renal transplantation in children has been variable. We undertook a retrospective study of our experience over the past five years. STUDY DESIGN: From January 1, 1988, to October 15, 1992, 60 renal transplantations were performed upon 59 children at the Children's Hospital of Pittsburgh. Twenty-eight (47 percent) of the kidneys were from cadaveric donors, and 32 (53 percent) were from living donors. The recipients ranged in age from 0.8 to 17.4 years, with a mean of 9.8 +/- 4.8 years. Forty-six (77 percent) recipients were undergoing a first transplant, while 14 (23 percent) received a second or third transplant. Eight (13 percent) of the patients were sensitized, with a panel reactive antibody of more than 40 percent. Eleven of the 14 patients undergoing retransplantation and seven of the eight patients who were sensitized received kidneys from cadaveric donors. Thirty-three (55 percent) patients received cyclosporine-based immunosuppression, and 27 (45 percent) received FK506 as the primary immunosuppressive agent. RESULTS: The median follow-up period was 36 months, with a range of six to 63 months. The one- and four-year actuarial patient survival rate was 100 and 98 percent. The one- and four-year actuarial graft survival rate was 98 and 83 percent. For living donor recipients, the one- and four-year actuarial patient survival rate was 100 and 100 percent; for cadaveric recipients, it was 100 and 96 percent. Corresponding one- and four-year actuarial graft survival rates were 100 and 95 percent for the living donor recipients and 96 and 69 percent for the cadaveric recipients. Patients on cyclosporine had a one- and four-year patient survival rate of 100 and 97 percent, and patients on FK506 had a one- and three-year patient survival rate of 100 and 100 percent. Corresponding one- and four-year actuarial graft survival rates were 100 and 85 percent in the cyclosporine group, while one- and three-year actuarial graft survival rates were 96 and 84 percent in the FK506 group. The mean serum creatinine level was 1.24 +/- 0.64 mg per dL; the blood urea nitrogen level was 26 +/- 13 mg per dL. The incidence of rejection was 47 percent; 75 percent of the rejections were steroid-responsive. The incidence of cytomegalovirus was 10 percent. The incidence of post-transplant lymphoproliferative disorder was 8 percent. None of the patients on cyclosporine were able to be taken off prednisone; 56 percent of the patients receiving FK506 were taken off prednisone successfully. Early growth and development data suggest that the patients receiving FK506 off prednisone had significant gains in growth. CONCLUSIONS: These results support the idea that renal transplantation is a successful therapy for end-stage renal disease in children. They also illustrate the potential benefits of a new immunosuppressive agent, FK506.

Adolescent

Parasexual crosses and hybrid selection with a near haploid variant of the epithelioma papulosum cyprini, cell line EPC: a tissue culture model for the analyses of dominance, recessiveness, and complementation of mutant phenotypes.

We describe techniques for insertional mutagenesis of tissue-cultured piscine cells in which we use transfection with G418 and hygromycin B resistance-conferring plasmids, cell matings by electrofusion, and positive selections of fusion hybrids by dual challenge with the antibiotics G418 and hygromycin B. These techniques are designed to facilitate genetic and molecular analyses of tissue-cultured cells. The experiments were conducted with EPC-1, a new variant of the carp epithelioma cyprini cell line. EPC, with a near haploid number of chromosomes, EPC-1 retains cell morphology and growth characteristics of EPC, including anchorage independence, but shows a higher degree of contact inhibition. The number of metaphase chromosomes of EPC-1 is 53, as opposed to 96 reported for EPC.

Animals

Cervicography.

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Cervix Uteri