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Biomedical subjects

D Ellis

Publications and source records attributed to D Ellis.

At least 37 records · Page 2Linked to original sources
PubMed2000

Epidemiology and host- and variety-dependent characteristics of infection due to Cryptococcus neoformans in Australia and New Zealand. Australasian Cryptococcal Study Group.

A prospective population-based study was conducted in Australia and New Zealand during 1994-1997 to elucidate the epidemiology of cryptococcosis due to Cryptococcus neoformans var. neoformans (CNVN) and C. neoformans var. gattii (CNVG) and to relate clinical manifestations to host immune status and cryptococcal variety. The mean annual incidence per 10(6) population was 6.6 in Australia and 2.2 in New Zealand. Of 312 episodes, CNVN caused 265 (85%; 98% of the episodes in immunocompromised hosts) and CNVG caused 47 (15%; 44% of the episodes in immunocompetent hosts). The incidence of AIDS-associated cases in Australia declined annually (P<.001). Aborigines in rural or semirural locations (P<.001) and immunocompetent males (P<.001) were at increased risk of CNVG infection. Cryptococcomas in lung or brain were more common in immunocompetent hosts (P< or =.03) in whom there was an association only between lung cryptococcomas and CNVG. An AIDS-associated genetic profile of CNVN serotype A was confirmed by random amplification of polymorphic DNA analysis. Resistance to antifungal drugs was uncommon. The epidemiology of CNVN infection has changed substantially. Clinical manifestations of disease are influenced more strongly by host immune status than by cryptococcal variety.

AIDS-Related Opportunistic Infections↗
PubMed2000

The social context of insight in schizophrenia.

BACKGROUND: Psychiatrists place great weight on impaired insight in schizophrenia, generally attributing it to pathological mental processes. However, denial of illness may be based on attitudes common in patients' social and cultural groups. Moreover, even where denial of illness has a pathological element, it may be affected by the social context. In this paper, we predicted that denial of illness would be associated with social distance between clinician and patient, and reduced by access to 'normalizing' social interaction. METHOD: One hundred and fifty patients with schizophrenia in the London arm of the European Schizophrenia cohort were assessed using the 'Awareness of Illness' (AI) subscale of David's Assessment of Insight. Clinical and social attributes were related to AI. RESULTS: There was little evidence for our social distance hypotheses: there was little variation in AI by social class, ethnicity, membership of a drug taking culture or the presence of strongly held religious beliefs. However, there were strong relations between AI and the size of primary group, consistent with our normalizing hypothesis. CONCLUSIONS: The normalizing function of social support is in line with modern psychological models of delusion formation. Longitudinal data will eventually be available from the current study that will assist in establishing the causal direction of this association.

Adult↗
PubMed2000

Growth and renal function after steroid-free tacrolimus-based immunosuppression in children with renal transplants.

Steroid withdrawal after renal transplantation and cyclosporine-based immunosuppression enhances growth in children, but this practice is not widely employed because of a 50%-60% rate of rejection, graft dysfunction, or graft loss. The current study evaluates growth and renal function after withdrawal and discontinuation of steroids within 1 year of transplantation in 52 children receiving tacrolimus (FK-506)-based immunosuppression. Height Z-score, weight-for-height index (WHI), and body mass index (BMI), as well as graft loss and calculated creatinine clearance as a measure of glomerular filtration rate (GFR), were assessed. Children were divided into three groups according to age at transplantation: group I, 16 children aged 0-5 years; group II, 17 children aged 6-12 years; group III, 19 children aged 13-16 years. Significant and sustained improvement in height occurred in groups I and III, with Z-scores increasing by 1.51 and 1.57 standard deviations at 3 years after transplantation compared with the Z-score at transplantation (P<0.02). Mean WHI values remained near 100% in groups I and III, and significantly increased above 100% only in group II at 2 years after transplantation. Although actual BMI scores improved significantly in groups II and III at both 2 and 3 years post transplantation (P<0.05), when BMI scores were adjusted for height age, none of these groups had values >95% denoting obesity. Failure of steroid withdrawal, defined as reinstitution of steroids, graft dysfunction, or graft loss, occurred in 9 of 68 (13%) children who underwent steroid withdrawal at any time after transplantation, and resulted in graft dysfunction or graft loss in 5 (7%). Over a 3-year period, rates of renal dysfunction, as manifested by >50% rise in the serum creatinine level above baseline, or graft loss were lower in these 68 children compared with 8 children who never had steroid withdrawal (P<0.05). Mean GFR at 3 years after transplantation ranged from 96 to 102 ml/min per 1.73 m2 in all three steroid withdrawal groups, and remained stable during the 3 years of follow-up. These data indicate that steroid withdrawal enables normalization of growth without obesity, and without imposing an excessive risk for graft dysfunction or graft loss.

Adolescent↗
PubMed2000

A global evaluation of the susceptibility of Candida species to fluconazole by disk diffusion. Global Antifungal Surveillance Group.

An improved fluconazole 25-mg disk diffusion method was used to test the susceptibility of 20,900 consecutively isolated clinical strains of Candida species from 40 hospital laboratories in 26 countries. The procedure is similar to the National Committee for Clinical Laboratory Standards (NCCLS) M2-A6 method for testing bacteria, except Mueller-Hinton agar is supplemented with 2% glucose and 0.5 mcg/mL methylene blue. Plates were incubated at 35 degrees C and read after 18 to 24h. Tentative zone interpretive criteria were based on the correlation by regression analysis with the NCCLS M27-A Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts: > =19mm Susceptible, < = 12mm Resistant, and 13-18 mm Susceptible-Dose Dependent. Of 14,368 isolates of Candida albicans, 2,073 C. glabrata, 869 C. tropicalis, 752 C. parapsilosis, and 351 C. krusei, 99%, 67%, 90%, 94%, and 26%, respectively, were susceptible in vitro to fluconazole. All study sites used the BIOMIC System to electronically read zones on plates, interpret, record test results and verify quality control data. This is the largest study to date that evaluated a broad range of sequentially collected yeasts from various infections and different types of hospitals. The modified disk testing procedure is facile and economical to perform and offers a reproducible and accurate means to assess the in vitro susceptibility of Candida species to fluconazole.

Antifungal Agents↗
PubMed2000

Familial nephrotic syndrome: clinical spectrum and linkage to chromosome 19q13.

BACKGROUND: Familial nephrotic syndrome (NS) has both autosomal dominant and recessive forms of inheritance. Recent studies in families with an autosomal dominant form of focal segmental glomerulosclerosis (FSGS) have been at odds concerning linkage to chromosome 19q13 (Mathis et al, Kidney Int 53:282-286, 1998; Winn et al, Kidney Int 55:1241-1246, 1999), suggesting genetic heterogeneity. This study examines the clinical features and confirms linkage to chromosome 19q13 in a family with autosomal dominant NS. METHODS: DNA samples were obtained from 16 of 17 family members. Genomic DNA was isolated, and polymerase chain reaction was performed for five markers spanning the area of interest on chromosome 19q13. Data were evaluated using two- and six-point linkage analysis. RESULTS: Clinical features included presentation of NS in childhood, steroid unresponsiveness, and slow progression to renal failure. Renal biopsy in affected family members showed lesions ranging from minimal change to mesangial proliferative glomerulonephritis to FSGS. Linkage was confirmed between the disease state and chromosome 19q13, with a maximum logarithm of odds (LOD) score of 2.41. Linkage was observed for a 7 cM region on chromosome 19q13, defined by markers D19S425 and D19S220. CONCLUSIONS: This study confirms the Mathis et al report of linkage to chromosome 19q13 in a family with autosomal dominant NS. However, there were notable differences in the presenting clinical and histopathologic features of our affected family members compared with those of Mathis et al. This suggests that the gene on chromosome 19q13 may be responsible for considerable phenotypic heterogeneity and variable expression in both clinical presentation and renal histopathology.

Adolescent↗
PubMed2000

7,8-Diphenyl-9-dimethylsulfido-10,11-mu-hydro-7, 8-dicarba-nido-undecaborane(9).

In the title compound, C(16)H(25)B(9)S, there are two crystallographically independent molecules, and the conformations of the phenyl and SMe(2) substituents indicate some intramolecular steric crowding. The bridging H atom is asymmetrically disposed. The title compound is a precursor to a crowded vertex-labelled nido carborane ligand important in establishing the mechanism of isomerization of icosahedral heteroboranes.

Journal Article↗
PubMed2000

Fenoldopam, a dopamine agonist, for hypertensive emergency: a multicenter randomized trial. Fenoldopam Study Group.

UNLABELLED: Despite successful therapies for chronic hypertension, hospital admissions for hypertensive emergency more than tripled between 1983 and 1992. OBJECTIVE: To examine the safety and efficacy of fenoldopam, the first antihypertensive with selective and specific action on vascular dopamine (DA1) receptors, in a clinical trial involving emergency department patients with true hypertensive emergencies. METHODS: Patients with a sustained diastolic blood pressure (DBP) of > or =120 mm Hg and evidence of target organ compromise were randomized in a double-blinded manner to one of four fixed doses of intravenous fenoldopam (0.01, 0.03, 0.1, or 0.3 microg/kg/min) for 24 hours. The primary endpoint was the magnitude of DBP reduction in each of the three higher-dose groups after four hours of fenoldopam treatment compared with the lowest-dose group. RESULTS: One hundred seven participants from 21 centers were enrolled, and 94 patients received fenoldopam. Evidence of acute target-organ damage included new renal dysfunction or hematuria (50%), acute congestive heart failure or myocardial ischemia (48%), and papilledema or grade III-IV hypertensive retinopathy (34%). The DBP decreased in a dose-dependent fashion, with significant differences between the 0.1- and 0.3-microg/kg/min groups compared with the lowest-dose group. Treatment was well tolerated, and there were no deaths or serious adverse events during follow-up, up to 48 hours. All patients were successfully transitioned to oral or transdermal antihypertensives with maintenance of blood pressure control. CONCLUSIONS: Fenoldopam safely and effectively lowers blood pressure in a dose-dependent manner in patients with hypertensive emergencies. Observations supporting potential risk factors for hypertensive emergency are discussed.

Adult↗
PubMed2000

Human immunodeficiency virus type 1 mutations selected in patients failing efavirenz combination therapy.

Efavirenz is a potent and selective nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Nucleotide sequence analyses of the protease and RT genes (coding region for amino acids 1 to 229) of multiple cloned HIV-1 genomes from virus found in the plasma of patients in phase II clinical studies of efavirenz combination therapy were undertaken in order to identify the spectrum of mutations in plasma-borne HIV-1 associated with virological treatment failure. A K103N substitution was the HIV-1 RT gene mutation most frequently observed among plasma samples from patients for whom combination therapy including efavirenz failed, occurring in at least 90% of cases of efavirenz-indinavir or efavirenz-zidovudine (ZDV)-lamivudine (3TC) treatment failure. V108I and P225H mutations were observed frequently, predominantly in viral genomes that also contained other nonnucleoside RT inhibitor (NNRTI) resistance mutations. L100I, K101E, K101Q, Y188H, Y188L, G190S, G190A, and G190E mutations were also observed. V106A, Y181C, and Y188C mutations, which have been associated with high levels of resistance to other NNRTIs, were rare in the patient samples in this study, both before and after exposure to efavirenz. The spectrum of mutations observed in cases of virological treatment failure was similar for patients initially dosed with efavirenz at 200, 400, or 600 mg once a day and for patients treated with efavirenz in combination with indinavir, stavudine, or ZDV-3TC. The proportion of patients carrying NNRTI resistance mutations, usually K103N, increased dramatically at the time of initial viral load rebound in cases of treatment failure after exposure to efavirenz. Viruses with multiple, linked NNRTI mutations, especially K103N-V108I and K103N-P225H double mutants, accumulated more slowly following the emergence of K103N mutant viruses.

Alkynes↗
PubMed2000

Epidemiology: surveillance of fungal infections.

Surveillance for fungal diseases is essential to improve our understanding of their epidemiology and to enable research and prevention efforts to be prioritized. In order to conduct better surveillance for fungal diseases, it is important to develop more accurate and timely diagnostic tests, to follow rigorous epidemiological methods and to have adequate support from public health agencies and the pharmaceutical industry. Investigations of nosocomial and community outbreaks of fungal infection have also resulted in a better understanding of the sources and routes of transmission of these diseases, and of the risk factors for infection. This has led to more effective prevention and control strategies. In addition, outbreak investigations have offered excellent opportunities to develop new molecular sub-typing methods, and to evaluate and validate older ones. For example, results obtained from a global epidemiological study of the genomic structure of Cryptococcus neoformans have led to a better understanding of the epidemiology of cryptococcosis. Similarly, a study of variations in the genotype of Trichophyton rubrum has found that patients may become infected with multiple strains, which has important implications for study design when looking at the epidemiology of dermatophyte infections.

Arthrodermataceae↗
PubMed1999

Posttransplant lymphoproliferative disorders in adult and pediatric renal transplant patients receiving tacrolimus-based immunosuppression.

Between March 27, 1989 and December 31, 1997, 1316 kidney transplantations alone were performed under tacrolimus-based immunosuppression at our center. Posttransplant lymphoproliferative disorders (PTLD) developed in 25 (1.9%) cases; the incidence in adults was 1.2% (15/1217), whereas in pediatric patients it was 10.1% (10/99; P<.0001). PTLD was diagnosed 21.0+/-22.5 months after transplantation, 25.0+/-24.7 months in adults and 14.4+/-18.2 months in pediatric patients. Of the 4 adult cases in whom both the donor and recipient Epstein Barr virus (EBV) serologies were known, 2 (50%) were seropositive donor --> seronegative recipient. Of 7 pediatric cases in whom both the donor and recipient EBV serologies were known, 6 (86%) were EBV seropositive donor --> seronegative recipient. Acute rejection was observed before the diagnosis of PTLD in 8 (53%) of 15 adults and 3 (30%) of 10 pediatric patients. Initial treatment of PTLD included a marked decrease or cessation of immunosuppression with concomitant ganciclovir therapy; two adults and two pediatric patients required chemotherapy. With a mean follow-up of 24.9+/-30.1 months after transplantation, the 1- and 5-year actuarial patient and graft survival rates in adults were 93% and 86%, and 80% and 60%, respectively. Two adults died, 3.7 and 46.2 months after transplantation, of complications related to PTLD, and 10 (including the 2 deaths) lost their allograft 3.7-84.7 months after transplantation. In children, the 1- and 5-year actuarial patient and graft survival rates were 100% and 100%, and 100% and 89%, respectively. No child died; one child lost his allograft 41.3 months after transplantation. One child had presumed recurrent PTLD that responded to discontinuation of tacrolimus and reinitiation of antiviral therapy. The mean serum creatinine level in adults was 2.5+/-1.2 mg/dl, and in children, it was 1.3+/-0.6 mg/ dl. Under tacrolimus-based immunosuppression, PTLD is less common after renal transplantation in adults than in children, but PTLD in children is associated with more favorable outcomes than in adults.

Adolescent↗
PubMed1999

Epstein-Barr virus-related disorders in children undergoing renal transplantation with tacrolimus-based immunosuppression.

In children undergoing renal transplantation, Epstein-Barr virus- (EBV) related disorders, including posttransplant lymphoproliferative disorder, constitute a major complication associated with tacrolimus-based immunosuppression. In this study, we reviewed the EBV complications in 81 children, all of whom had EBV serological studies before renal transplantation. We also highlight the data in a subgroup of 30 children transplanted more recently who were monitored sequentially for EBV symptoms and signs and with immunological studies, and in whom the donor EBV serology was also determined. During a mean follow-up time of 3.9+/-2.3 years, 19 children developed symptomatic Epstein-Barr virus (EBV*) infection. This consisted of the clinical syndrome of infectious mononucleosis in 7 children; in addition, 10 children developed posttransplant lymphoproliferative disorder (PTLD), which was histologically confirmed in 8, and 2 others developed malignant lymphoma. Recipient seronegativity (EBV-) and donor EBV seropositivity (EBV+) predicted a high probability for seroconversion (P=0.0072) and for developing PTLD or malignancy (P<0.01). In the subgroup of 30 children studied prospectively, seroconversion occurred in 15 of 19 seronegative recipients of EBV seropositive grafts at 6.6+/-2.6 months (mean+/-SD) after transplantation. Seven children developed symptomatic EBV infection (including three with PTLD) in association with seroconversion and a rise in EBV viral load in the peripheral blood, demonstrated by an EBV-specific polymerase chain reaction (EBV-PCR). Of 15 seroconverters, 7 who developed symptomatic infection had received EBV+ grafts; 8 others with EBV+ grafts seroconverted but did not become symptomatic. These two subgroups did not differ in age, rejection rate, antiviral prophylaxis, or level of immunosuppression. In the overall group of 81 children, only the two with malignant lymphoma who were managed with chemotherapy had substantial morbidity. The 10 individuals with PTLD received a regimen combining i.v. ganciclovir and CytoGam, and stopping or reducing the tacrolimus. Four children with associated marked tonsilar growth underwent tonsillectomy. All 19 individuals with EBV disorders resolved their symptoms and signs, and all have maintained good allograft function during a follow-up time of 3.0+/-2.5 years (mean+/-SD) after the development of symptomatic EBV infection, PTLD, or malignancy. We conclude that seronegative recipients of EBV+ grafts are at high risk for developing EBV-related disorders after renal transplantation under tacrolimus-based immunosuppression, although the ultimate clinical outcomes have been remarkably good. These data form the basis for formulating strategies for early identification of children at risk for EBV complications, and for instituting preventive and treatment strategies that permit these children to realize the substantial benefits offered by tacrolimus-based immunosuppression.

Adolescent↗
PubMed1999

Pediatric renal transplantation under tacrolimus-based immunosuppression.

BACKGROUND: Tacrolimus has been used as a primary immunosuppressive agent in adult and pediatric renal transplant recipients, with reasonable outcomes. Methods. Between December 14, 1989 and December 31, 1996, 82 pediatric renal transplantations alone were performed under tacrolimus-based immunosuppression without induction anti-lymphocyte antibody therapy. Patients undergoing concomitant or prior liver and/or intestinal transplantation were not included in the analysis. The mean recipient age was 10.6+/-5.2 years (range: 0.7-17.9). Eighteen (22%) cases were repeat transplantations, and 6 (7%) were in patients with panel-reactive antibody levels over 40%. Thirty-four (41%) cases were with living donors, and 48 (59%) were with cadaveric donors. The mean donor age was 27.3+/-14.6 years (range: 0.7-50), and the mean cold ischemia time in the cadaveric cases was 26.5+/-8.8 hr. The mean number of HLA matches and mismatches was 2.8+/-1.2 and 2.9+/-1.3; there were five (6%) O-Ag mismatches. The mean follow-up was 4.0+/-0.2 years. RESULTS: The 1- and 4-year actuarial patient survival was 99% and 94%. The 1- and 4-year actuarial graft survival was 98% and 84%. The mean serum creatinine was 1.1+/-0.5 mg/dl, and the corresponding calculated creatinine clearance was 88+/-25 ml/min/1.73 m2. A total of 66% of successfully transplanted patients were withdrawn from prednisone. In children who were withdrawn from steroids, the mean standard deviation height scores (Z-score) at the time of transplantation and at 1 and 4 years were -2.3+/-2.0, -1.7+/-1.0, and +0.36+/-1.5. Eighty-six percent of successfully transplanted patients were not taking anti-hypertensive medications. The incidence of acute rejection was 44%; between December 1989 and December 1993, it was 63%, and between January 1994 and December 1996, it was 23% (P=0.0003). The incidence of steroid-resistant rejection was 5%. The incidence of delayed graft function was 5%, and 2% of patients required dialysis within 1 week of transplantation. The incidence of cytomegalovirus was 13%; between December 1989 and December 1992, it was 17%, and between January 1993 and December 1996, it was 12%. The incidence of early Epstein-Barr virus-related posttransplant lymphoproliferative disorder (PTLD) was 9%; between December 1989 and December 1992, it was 17%, and between January 1993 and December 1996, it was 4%. All of the early PTLD cases were treated successfully with temporary cessation of immunosuppression and institution of antiviral therapy, without patient or graft loss. CONCLUSIONS: These data demonstrate the short- and medium-term efficacy of tacrolimus-based immunosuppression in pediatric renal transplant recipients, with reasonable patient and graft survival, routine achievement of steroid and anti-hypertensive medication withdrawal, gratifying increases in growth, and, with further experience, a decreasing incidence of both rejection and PTLD.

Actuarial Analysis↗
PubMed1999

Lithium induced changes in intracellular free magnesium concentration in isolated rat ventricular myocytes.

We have examined the effect of exposing isolated rat ventricular myocytes to lithium while measuring cytosolic free magnesium ([Mg2+]i) and calcium ([Ca2+]i) levels with the fluorescent, ion sensitive probes mag-fura-2 and fura-2. There was a significant rise in [Mg2+]i after a 5 min exposure to a solution in which 50% of the sodium had been replaced by Li+, but not when the sodium had been replaced by bis-dimethylammonium (BDA). However, there were significant increases in [Ca2+]i when either Na+ substitute was used. The possibility that Li+, which enters the cells, interferes with the signal from mag-fura-2 was eliminated as Li+ concentrations up to 10 mM had no effect on the dye's fluorescence signal. A possible explanation for these findings is that Li+ displaces Mg2+ from intracellular binding sites. Having considered the binding constants for Mg2+ and Li+ to ATP, we conclude that Li+ can displace Mg2+ from Mg-ATP, thus causing a rise in [Mg2+]i. This work has implications for other studies where Li+ is used as a Na+ substitute.

Animals↗