Search PubMed⌕ Search

Biomedical subjects

E Cole

Publications and source records attributed to E Cole.

At least 19 recordsLinked to original sources
PubMed2000

Vancomycin dosage requirements among pediatric intensive care unit patients with normal renal function.

PURPOSE: The purpose of this study was to determine a vancomycin dosage regimen among pediatric intensive care unit (PICU) patients with normal renal function resulting in desired peak and trough serum concentration and to determine the predictability of vancomycin peak concentrations based on reported trough concentrations. MATERIALS AND METHODS: The medical records of all PICU patients who received vancomycin over a 12-month period were identified through a hospital computer search and were obtained from the hospital's Department of Medical Records. Demographic and laboratory data as well as the patient's vancomycin dosing history were recorded. Patients who lacked appropriately timed vancomycin peak and trough concentrations or who exhibited renal dysfunction were excluded from the study population. The optimal vancomycin dose and the predictability of peak concentrations based on trough concentrations were assessed. RESULTS: A total of 135 patients were identified as having received vancomycin therapy during their PICU hospitalization between June 1997 and June 1998. Fifty-nine patients were excluded due to renal dysfunction or inappropriate vancomycin concentrations resulting in 76 patients representing our study population. The initial mean dose of vancomycin was 47 mg/kg/day resulting in a mean peak and trough serum concentration of 19 and 6 microg/mL, respectively. A mean of 2.2 (range, 1 to 5) and 2.1 (range, 1 to 5) peak and trough serum concentrations were reported for each patient, respectively. A mean of 1.1 (range, 0 to 4) dosing changes per patient was noted resulting in a final mean dose of 60 mg/kg/day corresponding to a mean peak and trough serum concentration of 26 and 8 microg/mL, respectively. A vancomycin trough concentration >5 microg/mL was highly predictive for a corresponding peak concentration >20 microg/mL (P > .0001). Eighty percent of the trough concentrations <5 microg/mL were associated with peak concentrations <20 microg/mL, whereas 81% of trough concentrations >5 microg/mL were associated with corresponding peak concentrations >20 microg/mL. CONCLUSIONS: PICU patients required higher doses of vancomycin than are typically prescribed to achieve conventionally accepted peak and trough vancomycin serum concentrations. In the absence of renal impairment, we recommend an initial dosage regimen of 60 mg/kg/day divided every 8 hours. Vancomycin trough concentrations are highly predictive of corresponding peak concentrations and therefore may negate the need to obtain routine peak concentrations.

Anti-Bacterial Agents↗
PubMed2000

Portal venous and enteric exocrine drainage versus systemic venous and bladder exocrine drainage of pancreas grafts: clinical outcome of 40 consecutive transplant recipients.

OBJECTIVE: To test the hypothesis that pancreas transplantation using the more physiologic method of portal venous-enteric (PE) drainage could be performed without compromising patient and graft outcome, compared with the standard method of systemic venous-bladder (SB) drainage. METHODS: Between November 1995 and November 1998, the authors prospectively followed up 20 consecutive patients with SB drainage followed by 20 consecutive patients with PE drainage. All patients underwent simultaneous pancreas-kidney transplantation, and all were immunosuppressed with antilymphocyte serum, cyclosporin, azathioprine, and steroids. RESULTS: The actuarial patient survival rate at 1 year was 95% in the SB group and 100% in the PE group. Death-censored kidney graft survival was 100% in both groups; pancreas graft survival was 95% in the SB group and 100% in the PE group. The mean initial hospital stay was 15 days for both groups. However, during the first 6 months after transplantation, the SB group required more medical day-unit visits, mostly for treatment of metabolic acidosis and dehydration. The incidence of urinary tract infections was similar in both groups. The incidence of cytomegalovirus infections was significantly less in the PE group. The incidence of acute rejection was 37% in the SB group and 15% in the PE group. Mean serum creatinine levels 6 months after transplantation were significantly lower in the PE group than in the SB group. Glycemic control was excellent in both groups, but fasting serum insulin levels were significantly lower in the PE group. CONCLUSIONS: The PE method of pancreas transplantation can be performed with excellent patient and graft outcomes.

Adolescent↗
PubMed1999

Outcome of kidney transplantation from high-risk donors is determined by both structure and function.

METHOD: Despite the need to expand the donor pool, it is unclear what parameters should be used. The value of donor renal pathology and calculated creatinine clearance (CrCl) in determining recipient outcome was assessed in 57 kidney transplants from 34 donors in whom pretransplant renal biopsies were performed because of age > or =60, hypertension, and/or vascular disease. We retrospectively compared clinical outcomes in these recipients and 57 control recipients selected to have the same baseline demographics but receiving transplants from low risk donors who were significantly younger (32+/-13.9 vs. 61+/-7.3 years) and lighter weight (71+/-18.1 vs. 84+/-20.2 kg) than the high-risk donors (P<.001 for both). RESULTS: Recipients of high-risk kidneys had a higher incidence of delayed graft function, defined by a <10% fall in serum creatinine (Cr) in the first 24 hr, (56% vs. 30%, P<.01), a higher incidence of rejection (60% vs. 37%, P = .02) and a higher Cr level (197+/-64 vs. 144+/-54 micromol/L at 18 months, P<.005). Graft and patient survival were similar; 12% and 5% vs. 91% and 9% in high-risk vs. control groups, respectively (P = NS). Donor renal pathology was scored 0-3 (none to severe disease) in four areas: glomerulosclerosis, interstitial fibrosis, tubular atrophy, and vascular disease. A donor vessel score of 3/3 was associated with a 100% incidence of delayed graft function and a mean 1-year Cr level of 275+106 micromol/L (compared with 43% and 192+54 micromol/L in those with lower vessel scores, P<.05). Calculated donor CrCl <100 ml/min was associated with higher recipient Cr levels at 1 year, 240+/-95 micromol/L vs. 180+/-54 micromol/L in recipients of kidneys from donors with CrCl levels >100 ml/min (P<.05). The mean 1-year Cr level was 320+/-102 micromol/L in recipients with both a vascular score of 3/3 and a donor CrCl <100 ml/min and 184+/-63 micromol/L in those with neither factor (P = .001). CONCLUSION: Calculated donor CrCl and donor vascular pathology predict recipient graft function and may be helpful in selecting high-risk donors for single kidney transplantation.

Aged↗
PubMed1999

Ethnicity and outcome of psychosis.

BACKGROUND: An excess of psychotic illness in Black people has been found in cross-sectional studies. Little is known about the outcome of psychosis in different ethnic groups in the UK. AIMS: To compare the incidence, nature and long-term outcome of psychosis in different ethnic groups. METHOD: A five-year, prospective study of an epidemiological cohort of people with a first contact for psychosis. RESULTS: Age-standardised incidence rates for schizophrenia and non-affective psychosis were higher for Black and Asian people than Whites. Stability of diagnosis and course of illness were similar in all ethnic groups. During the fifth year, Black people were more likely than others to be detained, brought to hospital by the police and given emergency injections. CONCLUSIONS: The nature and outcome of psychotic illness is similar in all ethnic groups but Black people experience more adverse contacts with services later in the course of illness.

Adolescent↗
PubMed1999

The conjusome: a novel structure in Tetrahymena found only during sexual reorganization.

A unique structure, the conjusome, has been identified and initially characterized in Tetrahymena thermophila. The conjusome appears only during a specific phase of conjugation. Immunofluorescence microscopy reveals that the conjusome is strongly labeled by antibodies to the protein Pdd1p. Pdd1p is a chromodomain protein and participates in the formation of chromatin-containing structures in developing macronuclear anlagen. Recent studies suggest that Pdd1p is physically associated with the elimination of specific germ-line sequences from developing macronuclei (anlagen) and may play a role in heterochromatin assembly. The conjusome contains Pdd1p, but it is devoid of any detectable DNA. The conjusome appears before DNA elimination begins in the developing anlagen and after Pdd1p is found in the parental macronucleus. Transmission electron microscopic observations reveal that the conjusome is not a membrane-bounded structure. The conjusome ranges in size from about 1 microm to sizes approaching 7 microm, depending on its maturity. It is composed of a coarse reticulum of a fibrous, electron dense material, interspersed with apparent background cytoplasm. Our initial characterization does suggest a number of possible functions for what may be a new, transient organelle.

Animals↗
PubMed1998

Ribavirin inhibits viral-induced macrophage production of TNF, IL-1, the procoagulant fgl2 prothrombinase and preserves Th1 cytokine production but inhibits Th2 cytokine response.

Ribavirin, a synthetic guanosine analogue, possesses a broad spectrum of activity against DNA and RNA viruses. It has been previously shown to attenuate the course of fulminant hepatitis in mice produced by murine hepatitis virus strain 3. We therefore studied the effects of ribavirin on murine hepatitis virus strain 3 replication, macrophage production of proinflammatory mediators including TNF, IL-1, and the procoagulant activity (PCA), fgl2 prothrombinase; and Th1/Th2 cytokine production. Although ribavirin had inhibitory effects on viral replication (<1 log), even at high concentrations complete eradication of the virus was not seen. In contrast, at physiologic concentrations (up to 500 microg/ml), ribavirin markedly reduced viral-induced parameters of macrophage activation. With ribavirin treatment, the concentrations of PCA, TNF-alpha and IL-1beta all decreased to basal concentrations: PCA from 941 +/- 80 to 34 +/- 11 mU/10(6) cells; TNF-alpha from 10.73 +/- 2.15 to 2.74 +/- 0.93 ng/ml; and IL-1beta from 155.91 +/- 22.62 to 5.74 +/- 0.70 pg/ml. The inhibitory effects of ribavirin were at the level of gene transcription as evidenced by Northern analysis. Both in vitro and in vivo, ribavirin inhibited the production of IL-4 by Th2 cells, whereas it did not diminish the production of IFN-gamma in Th1 cells. In contrast, ribavirin had no inhibitory effect on TNF-alpha and IL-1beta production in LPS-stimulated macrophages. These results suggest that the beneficial effects of ribavirin are mediated by inhibition of induction of macrophage proinflammatory cytokines and Th2 cytokines while preserving Th1 cytokines.

Animals↗
PubMed1998

Safety and tolerability of cyclosporine and cyclosporine microemulsion during 18 months of follow-up in stable renal transplant recipients: a report of the Canadian Neoral Renal Study Group.

BACKGROUND: There has been concern that the increased drug exposure associated with treatment with cyclosporine microemulsion (CsA-ME) would lead to an increase in adverse events. METHODS: The long-term safety and tolerability of conventional cyclosporine (CsA) and CsA-ME were compared in a randomized, multicenter, pharmacoepidemiologic study involving 1097 stable renal transplant patients after 18 months of follow-up. RESULTS: No significant difference was seen in change in serum creatinine or calculated creatinine clearance between the two groups. Episodes of deterioration in renal function (change in serum creatinine > or = 20%) were categorized with the following results for CsA-ME versus CsA, respectively: acute rejection, 4.5% vs. 4.5%; chronic rejection, 8% vs. 11%; CsA nephrotoxicity, 12% vs. 7% (P=0.008); transient changes, 17% vs. 12%; other causes, 4% vs. 6%. During the first 6 months of the study, a transient increase in the incidence of gastrointestinal and neurological adverse events was seen in the CsA-ME group compared with the CsA group. Up to 18 months, patients in the CsA group reported significantly fewer hearing and vestibular disorders, but more cardiovascular problems than those in the CsA-ME group (P=0.035). CONCLUSIONS: Tolerance to CsA and CsA-ME was similar. Renal function over 18 months was not adversely affected by the increased drug exposure with CsA-ME, although there was a transient increase in nephrotoxicity. The frequency of acute and chronic rejection did not change.

Administration, Oral↗
PubMed1998

Resistance to murine hepatitis virus strain 3 is dependent on production of nitric oxide.

The strain-specific spectrum of liver disease following murine hepatitis virus type 3 (MHV-3) infection is dependent on inflammatory mediators released by macrophages. Production of nitric oxide (NO) by macrophages has been implicated in resistance to a number of viruses, including ectromelia virus, vaccinia virus, and herpes simplex virus type 1. This study was undertaken to define the role of NO in MHV-3 infection. Gamma interferon-induced production of NO inhibited growth of MHV-3 in a murine macrophage cell line (RAW 264.7). Viral inhibitory activity was reproduced by the NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP), whereas N-acetyl-DL-pencillamine (NAP), an inactive analog of SNAP, had no effect. Electron microscopy studies confirmed the inhibitory effects of NO on viral replication. Peritoneal macrophages isolated from A/J mice known to be resistant to MHV-3 produced a fivefold-higher level of NO and higher levels of mRNA transcripts of inducible NO synthase in response to gamma interferon than macrophages from susceptible BALB/cJ mice. SNAP inhibited growth of MHV-3 in macrophages from both strains of mice to similar degrees. In vivo inhibition of NO by N-monomethyl-L-arginine resulted in loss of resistance to MHV-3 in A/J mice. These results collectively demonstrate a defect in the production of NO in macrophages from susceptible BALB/cJ mice and define the importance of endogenous NO in resistance to MHV-3 infection in resistant A/J mice.

Animals↗
PubMed1998

Barriers to organ donation in the Jewish community.

It has long been recognized that members of the Jewish community generally do not sign organ donor cards or consent to the donation of the organs of their family members. In order to address this issue, the position of Jewish law on organ donation was examined and a sample of the Jewish population of Toronto was surveyed in an attempt to better understand the reasons for the observed reluctance to donate within this community. The results confirmed that the rate of signing organ donor cards was much lower in the Jewish community than in the general population, and although other reasons do exist, the major barrier to donation was a perception that Jewish law prohibits such action. The study of Jewish law revealed that organ donation is permitted and, in fact, encouraged by all branches of modern Judaism. Finally, in response to these results, a guide titled "Organ Donation: A Jewish Perspective" was compiled to help explain both the religious and medical aspects of organ donation for Jewish people and transplant personnel.

Adult↗
PubMed1998

Factors influencing long-term primary cadaveric kidney transplantation--importance of functional renal mass versus avoidance of acute rejections--the Toronto Hospital experience 1985-1997.

1. The 5-year actuarial graft, patient and functional graft survival rates were analyzed in 743 consecutive primary cadaveric kidney transplants from The Toronto Hospital between January 1985-December 1997. 2. Recipient age > or = 55 years, male recipient sex, recipient diabetes mellitus, CIT > 36 hours and delayed graft function were found to significantly decrease patient survival. 3. Recipient age > or = 55 years, sensitization to HLA antigens (peak PRA > 50%), donor/recipient HLA antigen mismatches, CIT > 36 hours, delayed graft, function and 6-month SCr > 200 mumol/L were found to significantly decrease graft survival. 4. Acute rejection episodes had no significant impact on overall 5-year patient or graft survival. 5. The observation that serum creatinine > 200 mumol/L had a major adverse influence on long-term outcome reflects the importance of functional renal mass on graft survival.

Adult↗
PubMed1997

Serum-dependent and cell cycle-dependent expression from a cytomegalovirus-based mammalian expression vector.

Cytomegalovirus-based mammalian expression vectors are widely used to drive the expression of transfected genes in cultured cells. Immunofluorescent staining of the WT1 protein in 3T3 and 293 cell clones, stably transfected with a cyomegalovirus (CMV) expression vector carrying a cDNA coding for the tumour suppressor protein WT1, showed extreme cell to cell variation in the amount of recombinant protein expressed, indicative of cell cycle dependence. This was investigated further by Western blot and FACS analysis which showed that WT1 protein expression was highest in S phase and almost absent in G0/G1. Northern blot analysis of cell clones expressing sense or antisense WT1 cDNAs regulated by the CMV promoter/enhancer showed that RNA expression was also cell cycle-dependent. Western blotting of cells expressing a luciferase reporter gene driven by the CMV promoter/enhancer also showed apparent cell cycle-dependent expression. We further demonstrated that the expression of these gene constructs was serum responsive with a 10-fold increase in expression occurring 2 h after the addition of serum. These results show that the CMV promoter/enhancer system varied in its response to serum and the cell cycle state. Therefore, care must be taken when interpreting any phenotypic alterations (or lack of them) produced in cells transfected with CMV-based expression vectors.

3T3 Cells↗
PubMed1997

Transplantation in the elderly: a review.

PURPOSE: 1. To review current knowledge about patient and graft survival, complication rates, patient selection and management protocols in patients aged 60 years or more with a renal transplant. 2. To review the advantages and disadvantages of cadaveric organ retrieval from older donors. DATA SOURCES: Evidence was obtained from published articles identified using a MEDLINE search from 1976 to 1996; expert opinion and citations from previous review articles. RESULTS: Survival rates have improved with time and now range from 54 to 75% 5-year patient survival and 52-74% 5-year graft survival. The most common reason for graft loss is patient death as both acute and chronic rejection is less commonly seen in older patients. Censored graft survival (if death with a functioning graft is treated as censored data) is higher in elderly patients compared to younger ESRD patients. Based on cohort data from an administrative database a survival advantage is seen in older dialysis patients accepted for transplantation even after matching for comorbidity. Post-transplant morbidity is mainly attributable to infectious complications and an increased prevalence of malignancy. There is insufficient data about the most optimal immunosuppression regime and further research is required in this direction. The evidence currently supports the use of kidneys from older donors because of a relative lack of cadaveric organs from younger donors although a worse patient and graft outcome is recognized in the long term. Insufficient evidence exists to support a firm conclusion regarding age matching or targeting of older organs to special groups.

Age Factors↗
PubMed1997

Germline and somatic transformation of mating Tetrahymena thermophila by particle bombardment.

Mating Tetrahymena thermophila were bombarded with ribosomal DNA-coated particles at various times in development. Both macronuclear and micronuclear transformants were recovered. Optimal developmental stages for transformation occurred during meiosis for the micronucleus and during anlagen formation for the macronucleus. Evidence is given for transient retention of the introduced plasmid. Genetic and molecular tests confirmed that sexually heritable transformation was associated with integration at the homologous site in the recipient micronuclear chromosome.

Animals↗
PubMed1997

First-onset psychotic illness: patients' and relatives' satisfaction with services.

BACKGROUND: Despite the growth in patient satisfaction studies, scant attention has been paid to the satisfaction of patients with a first episode of psychotic illness soon after presentation to services. We were particularly interested in any ethnic differences in satisfaction at this seminal stage in patient care. METHOD: Using multi-item questionnaire, face-to-face interviews were conducted with patients and relatives 12 months after first contact with psychiatric services. Relatives were also questioned on support and advice issues related to after-care. RESULTS: Most patients and relatives were generally satisfied with the treatment, and with the 'humane' qualities of psychiatric staff, but were less satisfied with the 'hotel' aspects of hospital care. Patients, and particularly relatives, were most concerned about levels of information and advice received. Relatives were dissatisfied with after-care. There were no significant differences between Black and other patients, but some differences between their relatives. Patients born abroad were significantly more satisfied than those born in Britain, irrespective of ethnicity. Compulsory detention under the Mental Health Act was also significant in determining low satisfaction for patients and especially for their relatives. CONCLUSIONS: For improved care in the community patients and their relatives need to be seen as partners in care rather than as passive recipients. The issue of information-giving by psychiatric services demands serious attention. Black patients and their relatives were not especially likely to be dissatisfied.

Black or African American↗
PubMed1997

Treatment of Kaposi's sarcoma after solid organ transplantation.

PURPOSE: This retrospective review of all patients who developed Kaposi's sarcoma (KS) after solid organ transplantation at a single institution was undertaken to define the clinical presentation of this malignancy in the setting of iatrogenic immunodeficiency, and to determine the most appropriate treatment for patients in this clinical setting. MATERIALS AND METHODS: The records of 2,099 patients who underwent heart, lung, liver, or kidney transplantation at The Toronto Hospital between January 1, 1981 and June 30, 1995, were reviewed. Twelve patients were identified who developed biopsy-proven KS in the posttransplantation period. Five patients who had disseminated KS who had not responded to either reduction or withdrawal of immunosuppression or to local radiotherapy were treated with combination chemotherapy consisting of doxorubicin 20 to 30 mg/m2, bleomycin 10 mg/m2, and vincristine 2 mg (ABV) administered intravenously every 3 weeks. RESULTS: Eight of 12 patients were male and nine were of Italian origin. KS was limited to a localized area of the skin for only six patients, all after kidney transplantation. Visceral KS was present in three patients. Four of five patients responded to ABV chemotherapy (two complete and two partial remissions). The fifth patient responded to second-line etoposide and cisplatin. The median duration of response was in excess of 13 months (range, 8+ to 45+ months). Toxicity was limited to grade 1 neurotoxicity and grade 1 skin toxicity. CONCLUSION: KS is an uncommon but recognized complication of solid organ transplantation. Combination chemotherapy is a safe and effective treatment for patients with disseminated or visceral KS that fails to respond to changes in immunosuppression.

Adult↗