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Biomedical subjects

L Gordon

Publications and source records attributed to L Gordon.

At least 19 recordsLinked to original sources
PubMed2006

Reduced-dose rasburicase (recombinant xanthine oxidase) in adult cancer patients with hyperuricemia.

Recombinant urate oxidase (rasburicase) lowers uric acid levels rapidly to very low levels at the labeled dose of 0.15-0.2 mg/kg daily for 5 days. Our past experience showed that a lower dose (3 mg) lowered uric acid levels sufficiently in most patients. A retrospective review was conducted to determine the effect of a fixed 3 mg dose of rasburicase in 43 adult patients with cancer undergoing hematopoietic stem cell transplantation or receiving chemotherapy who had elevated or rising uric acid levels (6.4-16.8 mg/dl; median 9.6). Six patients received a second dose of rasburicase (3 mg in four patients and 1.5 mg in two patients) 24 h later. Patients received allopurinol, adequate hydration, as well as other supportive therapy as required. Uric acid levels declined by 6-95% (median 43%) within the first 24 h after rasburicase administration, and levels at 48 h were 9-91% (median 65%) lower than the baseline levels. Serum creatinine changed by < or =10% in 21 patients, increased by >10% in four patients and decreased by >10% in 18 patients. No significant renal dysfunction developed in any of the patients. We conclude that rasburicase is effective in lowering uric acid levels at a fixed dose of 3 mg, which is much lower than the recommended dose.

Adult↗
PubMed2006

A cost-effectiveness analysis of two community models of care for patients with venous leg ulcers.

AIM: To conduct a cost-effectiveness analysis based on data from a randomised controlled trial comparing traditional community home nursing with a community Leg Club model for chronic venous leg ulcer management in the south-east metropolitan area of Queensland, Australia. METHOD: Participants were randomised to the Leg Club (n=28) or home visits (n=28). Data were obtained on resources/related costs incurred by the service provider, clients and carers, and the community. RESULTS: From the collective perspective (service provider, clients and carers, and the community), at six months the incremental cost per healed ulcer was dollars AU515 (Euros 318) and the incremental cost per reduced pain score was dollars AU322 (Euros 199). For the service provider, Leg Club intervention resulted in cost savings and better health effects when compared with home nursing. CONCLUSION: On both clinical and economic grounds, the Leg Club model appears to be more cost-effective than traditional home nursing for the treatment of chronic venous leg ulcers. However, clients and the local community contribute substantial financial and in-kind support to the operation of both services.

Aged↗
PubMed2005

Can the stem cell mobilization technique influence CD34+ cell collection efficiency of leukapheresis procedures in patients with hematologic malignancies?

A total of 415 leukaphereses in 201 patients stimulated with growth factor (GF; n = 119) or chemotherapy-GF (n = 296) were studied to determine CD34+ cell collection efficiency (CE). The pre-apheresis leukocyte count was 1-93 x 10(9)/l (median 20), and peripheral blood CD34 count (PBCD34) was 1-1104/microl (median 19). The total number of CD34+ cells collected was 4-6531 x 10(6) (median 151); corresponding to 0.1-111.4 x 10(6) (median 2.3) per kg. There was strong correlation between PBCD34 and the number of CD34+ cells collected (r = 0.9; P < 0.0001). CE was 7-145% (median 46). On multiple regression analysis, a higher leukocyte count (P < 0.0001) was the most important predictor of lower CE. CE with leukocytes < 20 was 7-145% (median 53%) compared to 10-132% (median 40%) with leukocyte > or = 20 (P < 0.0001). In all, 61% of the apheresis procedures performed after chemotherapy-GF occurred when leukocytes were < 20 compared to 21% of those performed after GF alone (P < 0.0001). We conclude that mobilizing patients with the combination of chemotherapy and GF rather than GF alone leads to leukapheresis being performed when the leukocyte count is low -- in a range that results in optimum CD34+ cell CE. Autologous stem cells should be mobilized with chemotherapy-GF rather than GF alone whenever possible.

Adult↗
PubMed2004

How long after neutrophil recovery should myeloid growth factors be continued in autologous hematopoietic stem cell transplant recipients?

Growth factors are routinely used after autotransplantation to accelerate hematopoietic recovery, and are continued until the absolute neutrophil count (ANC) is >/=0.5 x 10(9)/l on 3 consecutive days. Since ANC often increases to very high levels with this strategy, we discontinued growth factor on the first day ANC reached 0.5 x 10(9)/l in 45 patients (Study Group), and compared their subsequent ANC to 108 historic controls who received growth factor longer. While ANC on the day after reaching 0.5 x 10(9)/l was comparable between groups, ANC on the third day was significantly higher in the Control Group (2.3 vs 4.9 x 10(9)/l; P=0.0003). When compared to the first day, ANC in the Study Group was higher by a median of 140% on the third day and by 450% in the Control Group (P=0.0002). A significantly higher proportion of patients experienced a decline in ANC after the first day in the Study Group. However, only one patient in the Study Group became neutropenic transiently and ANC recovered spontaneously the next day. The incidence of fever and hospitalization were comparable. We conclude that growth factors can be discontinued after autotransplantation the day the ANC reaches 0.5 x 10(9)/l, without compromising neutrophil recovery.

Adult↗
PubMed2003

Factors associated with survival in patients with progressive disease following autologous transplant for lymphoma.

Our objectives were to assess survival and predictors for survival among lymphoma patients whose disease had progressed after autologous bone marrow (ABMT) or stem cell transplantation (ASCT). Patients transplanted at Hadassah University Hospital between October 1983 and February 1999 were included. We compared survival of patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) after relapse or progression. Predictors for survival were assessed in a multivariate model. Of 88 transplanted patients with HD and 152 with NHL, relapse/progression occurred in 27 (31%) and 75 (49%), respectively. Median survival postrelapse was 25 months for HD and 7.5 months for NHL (P=0.12). Seven relapsed patients with HD (26%) and 10 (13%) with NHL survived >4 years. In NHL, longer postrelapse survival was associated with indolent histologies (P=0.007). On multivariate analysis, factors associated with survival included attainment of remission postrelapse (for both diseases), use of prophylactic immunotherapy (for HD), LDH level and time from transplant to relapse (for NHL). The short-term prognosis for patients with disease progression postautologous transplant may be somewhat better for HD compared to NHL. Long-term survival is poor in both diseases. However, the survival times in the current study are twice as long as those previously reported. Treatment regimens with the potential for achieving remission may have an impact on survival.

Disease-Free Survival↗
PubMed2002

Cobe Spectra is superior to Fenwal CS 3000 Plus for collection of hematopoietic stem cells.

One hundred and seventy-seven stem cell apheresis procedures performed on 91 patients using the Fenwal CS 3000 Plus cell separator and 61 procedures performed on 37 patients using the Cobe Spectra cell separator were studied to compare the CD34(+) cell collection efficiencies (CE; the proportion of the total CD34(+) cell content in the blood volumes processed that is harvested) of the two machines. The absolute peripheral blood CD34(+) cell count was comparable for the two groups (P = 0.27). A strong correlation was seen between the blood CD34(+) cell count and the total number of CD34(+) cells collected for the Spectra (r(2) = 0.59; P < 10(-6)) and for the CS 3000 Plus (r(2) = 0.60; P < 10(-6)). No significant correlation emerged between the peripheral blood CD34(+) cell count and the CE of either machine. The total number of CD34(+) cells collected per procedure was comparable (P = 0.51): median 113 x 10(6) for CS 3000 Plus and median 218 x 10(6)for Spectra. CE was significantly higher with the Spectra (median 45.7%, range 9.8-98.6%) than the CS 3000 Plus (median 30.3%, range 1.7-89.3%; P < 0.00001). We conclude that the CD34(+) cell CE of the Spectra is superior to that of the CS 3000 Plus. Therefore, under the usual clinical conditions, Cobe Spectra should be used preferentially for peripheral blood progentor cell collection to maximize the number of hematopoietic stem cells collected.

Blood Cell Count↗
PubMed2002

Rarity of toxigenic Clostridium difficile infections after hematopoietic stem cell transplantation: implications for symptomatic management of diarrhea.

Diarrhea is a common complication of high-dose chemotherapy and hematopoietic stem cell transplantation (HSCT). The frequent and prolonged use of multiple antibiotics in this setting can predispose to infection with toxigenic Clostridium difficile and the development of pseudomembranous colitis. Anti-motility agents are usually not administered in this setting until C. difficile infection has been excluded. The objective of this study was to determine the incidence of C. difficile toxin (CDT) positivity at the time of initial diarrhea in HSCT recipients, and to see if the practice of ensuring negative CDT assays prior to initiating symptomatic management of diarrhea needs modification. One hundred and nineteen patients with malignant diseases undergoing autologous or allogeneic HSCT were studied to determine the incidence of diarrhea and CDT positivity with initial diarrhea. One hundred and nine (91%) had diarrhea. Of these, only seven (6%) were CDT+ at the time of initial diarrhea. The median interval between onset of diarrhea and starting symptomatic anti-diarrheal therapy was 1 day. There were no significant differences between the patients with CDT+ diarrhea and the others in terms of timing or severity of diarrhea, number or duration of antibiotic usage, or leukocyte count. The infection resolved in all patients with metronidazole therapy. Our data suggest that the incidence of CDT+ diarrhea is low in HSCT recipients. Concern about C. difficile infection should not delay symptomatic therapy of initial diarrhea in HSCT recipients.

Adolescent↗
PubMed2002

Bullying in Jerusalem schools: victims and perpetrators.

The objectives of this study were to determine the prevalence of bullying among adolescents studying in Jerusalem schools and to identify the characteristics of its victims and perpetrators. Pupils in the 8th and 10th grade (ages 14-16 y) in 11 schools in Jerusalem (n=1182) anonymously completed the World Health Organization questionnaire from the 'Health Behavior in School Children' study. Bullying others or being bullied at least once in the last term was reported. The independent variables studied were socio-demographic characteristics, and personal and school-related factors. Bullying was reported by 57.1% of boys and 27.0% of girls, and being bullied by 50.3% of boys and 39.5% of girls. The factors associated with bullying others were lack of support from teachers for both genders and poor mental health among boys. Variables related to social exclusion among girls and social isolation among boys were associated with being bullied. Health professionals should be active in all levels of prevention to deal with this problem that affects the health and well-being of so many children and adolescents.

Adolescent↗
PubMed2002

Reciprocal congenics defining individual quantitative trait Loci for sedative/hypnotic sensitivity to ethanol.

BACKGROUND: We have identified four major genes or quantitative trait loci (QTLs) that determine duration of loss of righting reflex (LORR), induced by sedative doses of ethanol: Lore1, Lore2, Lore4, and Lore5. Together these genes explain more than 50% of the phenotypic variance for sensitivity to the sedative/hypnotic effects of ethanol between the Inbred Long Sleep (ILS) and Inbred Short Sleep (ISS) strains of mice. The derivation of these strains is reviewed here. METHODS: Each QTL has been bred onto the opposite background (ILS or ISS) through 10 rounds of backcrossing by using QTL-marker-assisted counter selection to produce reciprocal congenic strains. Mice were genotyped for markers that flanked each of the QTLs. Selection for the donor at the desired QTL, and against donor markers at the other four QTLs, allowed rapid fixation of the genetic background. Phenotypic assessment in the ISS-recipient congenic strains was conducted throughout the backcross. RESULTS: By the N5 generation, phenotypic assessments failed to detect significant effects in some sublines; these sublines were discarded and positive lines split to create new replicate sublines. In the N10, all sublines retained the phenotypic difference between heterozygotes and ISS homozygotes; however, the expected additive effect was not found in the Lore1 congenics. On the ILS background, each Lore was captured, as shown by the expected differential LORR. Two strains on the ILS background, and one on the ISS, exhibited the differential effect on blood ethanol concentration associated with the donor strain. CONCLUSIONS: Congenic strains represent an important resource for confirmation of previously identified QTLs, for identification and mapping of additional phenotypes, and for exclusion of candidate genes. QTL-marker-assisted selection rapidly stabilized the genetic background within four generations (based on phenotypic assessments); however, phenotypic selection during the backcrossing to generate congenic strains did not contribute to the successful capture of the ISS QTLs.

Animals↗
PubMed2001

A practical method to achieve prostate gland immobilization and target verification for daily treatment.

PURPOSE: A practical method to achieve prostate immobilization and daily target localization for external beam radiation treatment is described. METHODS AND MATERIALS: Ten patients who underwent prostate brachytherapy using permanent radioactive source placement were selected for study. To quantify prostate motion both with and without the presence of a specially designed inflatable intrarectal balloon, the computerized tomography-based coordinates of all intraprostatic radioactive sources were compared over 3 consecutive measurements at 1-min intervals. RESULTS: The placement and inflation of the intrarectal balloon were well tolerated by all patients. The mean (range) displacement of the prostate gland when the intrarectal balloon was present vs. absent was 1.3 (0-2.2) mm vs. 1.8 (0-9.1) mm (p = 0.03) at 2 min respectively. The maximum displacement in any direction (anterior-posterior, superior-inferior, or right-left) when the intrarectal balloon was inflated vs. absent was reduced to < or =1 mm from 4 mm. CONCLUSIONS: Both prostate gland immobilization and target verification are possible using a specially designed inflatable intrarectal balloon. Using this device, the posterior margin necessary on the lateral fields to ensure dosimetric coverage of the entire prostate gland could be safely reduced to 5 mm and treatment could be set up and verified using a lateral portal image.

Brachytherapy↗
PubMed2001

Human chromosome 19 and related regions in mouse: conservative and lineage-specific evolution.

To illuminate the function and evolutionary history of both genomes, we sequenced mouse DNA related to human chromosome 19. Comparative sequence alignments yielded confirmatory evidence for hypothetical genes and identified exons, regulatory elements, and candidate genes that were missed by other predictive methods. Chromosome-wide comparisons revealed a difference between single-copy HSA19 genes, which are overwhelmingly conserved in mouse, and genes residing in tandem familial clusters, which differ extensively in number, coding capacity, and organization between the two species. Finally, we sequenced breakpoints of all 15 evolutionary rearrangements, providing a view of the forces that drive chromosome evolution in mammals.

Animals↗
PubMed2001

Homology-driven assembly of a sequence-ready mouse BAC contig map spanning regions related to the 46-Mb gene-rich euchromatic segments of human chromosome 19.

Draft sequence derived from the 46-Mb gene-rich euchromatic portion of human chromosome 19 (HSA19) was utilized to generate a sequence-ready physical map spanning homologous regions of mouse chromosomes. Sequence similarity searches with the human sequence identified more than 1000 individual orthologous mouse genes from which 382 overgo probes were developed for hybridization. Using human gene order and spacing as a model, these probes were used to isolate and assemble bacterial artificial chromosome (BAC) clone contigs spanning homologous mouse regions. Each contig was verified, extended, and joined to neighboring contigs by restriction enzyme fingerprinting analysis. Approximately 3000 mouse BACs were analyzed and assembled into 44 contigs with a combined length of 41.4 Mb. These BAC contigs, covering 90% of HSA19-related mouse DNA, are distributed throughout 15 homology segments derived from different regions of mouse chromosomes 7, 8, 9, 10, and 17. The alignment of the HSA19 map with the ordered mouse BAC contigs revealed a number of structural differences in several overtly conserved homologous regions and more precisely defined the borders of the known regions of HSA19-syntenic homology. Our results demonstrate that given a human draft sequence, BAC contig maps can be constructed quickly for comparative sequencing without the need for preestablished mouse-specific genetic or physical markers and indicate that similar strategies can be applied with equal success to genomes of other vertebrate species.

Animals↗
PubMed2001

High-throughput sequence identification of gene coding variants within alcohol-related QTLs.

Low initial response to alcohol has been shown to be among the best predictors of development of alcoholism. A similar phenotypic measure, difference in initial sensitivity to ethanol, has been used for the genetic selection of two mouse strains, the Inbred Long-Sleep (ILS) and Inbred Short-Sleep (ISS) mice, and for the subsequent identification of four quantitative trait loci (QTLs) for alcohol sensitivity. We now report the application of high throughput comparative gene sequencing in the search for genes underlying these four QTLs. To carry out this search, over 1.7 million bases of comparative DNA sequence were generated from 68 candidate genes within the QTL intervals, corresponding to a survey of over 36,000 amino acids. Eight central nervous system genes, located within these QTLs, were identified that contain a total of 36 changes in protein coding sequence. Some of these coding variants are likely to contribute to the phenotypic variation between ILS/ISS animals, including sensitivity to alcohol, providing specific new genetic targets potentially important to the neuronal actions of alcohol.

Alcoholism↗
PubMed2001

Ovulation induction and risk of endometrial cancer: a pilot study.

OBJECTIVE: To determine whether women with endometrial carcinoma are more likely to have been exposed to fertility drugs, in particular clomiphene, than healthy population controls. STUDY DESIGN: A nationwide case-control, pilot study. About 128 living women 35-64 years old, with a histologically confirmed diagnosis of endometrial carcinoma that was first diagnosed and reported to The Israel Cancer Registry between 1 January 1989 and 31 December 1992 were enrolled. The controls were 255 women from the same dialing areas selected by random digit dialing. A variety of demographic and clinical parameters were compared between cases and controls. A multivariate logistic model, controlling for age, was used to assess the independent effects of factors found to be significantly associated with endometrial cancer on univariate analysis. RESULTS: About 7 women with endometrial carcinoma (5.5%) and 10 healthy controls (3.9%) reported that they had used any fertility drug (crude odds ratio (OR) 1.4; 95% confidence interval (CI) 0.47-4.2). Use of fertility drugs did not meet the criteria for entry into the logistic model. The following parameters were found to be independently associated with endometrial cancer controlling for age, European-American background OR=2.2, (95% CI 1.3-3.7, P=0.004); nulliparity OR=2.7 (95% CI 1.1-6.5, P=0.03); history of infertility OR=1.8 (95% CI 1.0-3.3, P=0.05); BMI> or =27 OR=2.3 (95% CI 1.4-3.9, P=0.001). The use of oral contraceptives and IUD were found to be protective, OR=0.29 and 0.37, respectively, (95% CI 0.14-0.61, P=0.001 and 0.19-0.70, P=0.003, respectively). CONCLUSIONS: We found no evidence that the use of ovulation induction agents, including clomiphene citrate, are associated with a higher risk of endometrial carcinoma. The association between infertility drugs and endometrial carcinoma should be examined in other, larger studies.

Case-Control Studies↗
PubMed2001

Clearing of cells bearing the bcl-2 [t(14;18)] translocation from blood and marrow of patients treated with rituximab alone or in combination with CHOP chemotherapy.

PURPOSE: Patients who were PCR-positive for B-cell leukemia-lymphoma 2 (bcl-2) gene rearrangement [t(14;18)] were evaluated for responses to rituximab alone or combined with CHOP. PATIENTS AND METHODS: Patients had relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma (IWF: A-D). The single-agent trial used 375 mg/m2 weekly x 4; combination therapy included six cycles of CHOP and six 375 mg/m2 infusions of rituximab. Bcl-2 analyses of bone marrow (BM) and peripheral blood (PB) samples at base-line and following therapy were performed using a PCR assay. RESULTS: In the single-agent trial, of 70 patients whose peripheral blood (PB) was bcl-2 positive at baseline, 36 became bcl-2-negative, 13 remained positive, and 21 varied between positive and negative. The overall response rates (ORRs) were 72%, 31%, and 57%, respectively. Twelve of twenty-two patients with repeat bone marrow (BM) samples were bcl-2-negative three months post-treatment. Of 18 patients in the combination trial, 8 were bcl-2 positive in PB and/or BM. All of seven patients positive in PB at baseline and six of seven patients positive in BM were negative at the end of therapy; all patients responded to treatment (100% ORR). CONCLUSIONS: Rituximab, alone or combined with CHOP, eradicated bcl-2 positive cells from PB and BM in over half of the patients treated and was associated with a high overall clinical response rate. The impact on disease-free and overall survival awaits long-term follow up.

Adult↗
PubMed2001

Fluoranthene degradation in Pseudomonas alcaligenes PA-10.

Pseudomonas alcaligenes strain PA-10 degrades the four-ring polycyclic aromatic hydrocarbon fluoranthene, co-metabolically. HPLC analysis of the growth medium identified four intermediates, 9-fluorenone-1-carboxylic acid; 9-hydroxy-1-fluorene carboxylic acid; 9-fluorenone and 9-fluorenol, formed during fluoranthene degradation. Pre-exposure of PA-10 to 9-fluorenone-1-carboxylic acid and 9-hydroxy-1-fluorene-carboxylic acid resulted in increases in fluoranthene removal, while pre-exposure to 9-fluorenone and 9-fluorenol resulted in a decrease in fluoranthene degradation. The rate of indole transformation was similarly affected by pre-exposure to these metabolic intermediates, indicating a link between fluoranthene degradation and indigo formation in this strain.

Biodegradation, Environmental↗