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Biomedical subjects

J Greene

Publications and source records attributed to J Greene.

At least 19 recordsLinked to original sources
PubMed2006

Two cases of progressive multifocal leukoencephalopathy after allogeneic hematopoietic cell transplantation and a review of the literature.

Progressive multifocal leukoencephalopathy (PML) is a rare subacute demyelinating disorder of the central nervous system (CNS) caused by the DNA JC human polyomavirus. In immunocompromised hosts, PML is caused by reactivation of a latent infection rather than de novo primary exposure. PML in the setting of hematopoietic cell transplantation (HCT) is exceedingly rare. PML should be considered in the differential diagnosis of HCT recipients, autologous or allogeneic, presenting with worsening of neurological symptoms, especially associated with post-transplant neurodegenerative findings. Although DNA polymerase chain reaction (PCR) of the cerebrospinal fluid (CSF) has emerged as a promising tool for detecting JC virus, a negative result does not rule out PML. Brain biopsy remains the most reliable and accurate method for diagnosing JC virus-associated PML. Presently, there is no universally effective antiviral therapy against JC virus and outcome is fatal in the majority of cases. We hereby describe two cases of PML developing after allogeneic HCT and provide a comprehensive review of the literature.

Adult↗
PubMed2006

Valganciclovir is safe and effective as pre-emptive therapy for CMV infection in allogeneic hematopoietic stem cell transplantation.

Despite significant advances in prevention and therapy, cytomegalovirus (CMV) infection continues to be an important cause of morbidity and mortality in the hematopoietic stem cell transplant (HSCT) recipient. The standard drug for pre-emptive therapy is intravenous ganciclovir (GCV). Valganciclovir (VGC), the oral pro-drug of GCV, has excellent bioavailability and is ideal for oral therapy. Since March 2002, VGC was adopted in our center for outpatient pre-emptive therapy in all patients undergoing allogeneic HSCT. Fifty-two allogeneic HSCT recipients were followed weekly via Digene hybrid capture assay. Patients with a positive assay were treated with VGC 900 mg p.o. b.i.d. x 14 days followed by 900 mg p.o. QD until at least 7 days after a negative test. Eighteen patients (14 sib, four MUD) had 30 episodes of CMV DNA detection treated with oral VGC. Median duration of therapy was 21 days (range 10-21 days). The rate of response was 93% (28/30) as confirmed by a negative assay within 14 days. No significant toxicity was encountered. Two patients failed oral VGC. One case of CMV enteritis was diagnosed in a patient with acute GVHD. Pre-emptive therapy of CMV infection with oral VGC is safe and effective in allogeneic HSCT recipients.

Administration, Oral↗
PubMed2004

Counting individual 41Ca atoms with a magneto-optical trap.

Atom trap trace analysis, a novel method based upon laser trapping and cooling, is used to count individual atoms of 41Ca present in biomedical samples with isotopic abundance levels between 10(-8) and 10(-10). The method is calibrated against resonance ionization mass spectrometry, demonstrating good agreement between the two methods. The present system has a counting efficiency of 2x10(-7). Within 1 h of observation time, its 3-sigma detection limit on the isotopic abundance of 41Ca reaches 4.5x10(-10).

Calcium Radioisotopes↗
PubMed2003

Pharmacologic pre-conditioning and controlled reperfusion prevent ischemia-reperfusion injury after 30 minutes of hypoxia/ischemia in porcine hearts.

BACKGROUND: Hearts from non-heart-beating organ donors are not transplanted because of risk of ischemia-reperfusion injury. We tested whether pharmacologic pre-conditioning with adenosine and the Na(+)/H(+) exchanger inhibitor, cariporide, combined with controlled reperfusion, would prevent injury in porcine hearts that had sustained 30 minutes of hypoxia/ischemia in closed-chest animals. METHODS: Hearts from Yorkshire pigs (100 kg) were studied in 3 groups. Group 1 (control) hearts were surgically removed while beating. Group 2 hearts were harvested from animals made hypoxic by discontinuing mechanical ventilation for 30 minutes. Group 3 hearts were hypoxic as in Group 2, but these animals received adenosine (40 mg) and cariporide (400 mg) 10 minutes before stopping ventilation. Cardiac function in all groups was assessed ex vivo in a working heart apparatus in which pressure and flow measurements were made over 3 hours. Controlled reperfusion in Group 3 hearts used leukocyte-depleted blood perfusate containing free radical scavengers. Myocardial injury was assessed on the basis of perfusate creatine phosphokinase activity and histopathologically determined injury score. RESULTS: Groups 1 and 3 hearts could be resuscitated to perform work equivalently during the entire reperfusion period and showed positive responses to increases in pre-load and norepinephrine. Group 2 hearts could not perform work. After 3 hours, Group 2 hearts showed significantly higher creatine phosphokinase and histopathologic injury scores compared to with Groups 1 and 3, which were not significantly different from each other. CONCLUSIONS: Pharmacologic pre-conditioning and controlled reperfusion effectively protect non-beating porcine hearts from injury after 30 minutes of hypoxia/ischemia in situ.

Adenosine↗
PubMed2003

Physician diagnosed asthma, respiratory symptoms, and associations with workplace tasks among radiographers in Ontario, Canada.

BACKGROUND: Medical radiation technologists (MRTs) or radiographers have potential exposure to chemicals including sensitisers and irritants such as glutaraldehyde, formaldehyde, sulphur dioxide, and acetic acid. AIMS: To determine the prevalence of asthma and work related respiratory symptoms among MRTs compared with physiotherapists, and to identify work related factors in the darkroom environment that are associated with these outcomes. METHODS: As part of a two component study, we undertook a questionnaire mail survey of the members of the professional associations of MRTs and physiotherapists in Ontario, Canada, to ascertain the prevalence of physician diagnosed asthma, and the prevalence in the past 12 months of three or more of the nine respiratory symptoms (previously validated by Venables et al to be sensitive and specific for the presence of self reported asthma). Information on exposure factors during the past 12 months, such as ventilation conditions, processor leaks, cleanup activities, and use of personal protective equipment was also collected. RESULTS: The survey response rate was 63.9% among MRTs and 63.1% among physiotherapists. Most analyses were confined to 1110 MRTs and 1523 physiotherapists who never smoked. The prevalence of new onset asthma (since starting in the profession) was greater among never smoking MRTs than physiotherapists (6.4% v 3.95%), and this differed across gender: it was 30% greater among females but fivefold greater among males. Compared with physiotherapists, the prevalence of reporting three or more respiratory symptoms, two or more work related, and three or more work related respiratory symptoms in the past 12 months was more frequent among MRTs, with odds ratios (ORs) (and 95% confidence intervals) adjusted for age, gender, and childhood asthma, of 1.9 (1.5 to 2.3), 3.7 (2.6 to 5.3), and 3.2 (2.0 to 5.0), respectively. Analyses examining latex glove use indicated that this was not likely to account for these differences. Among MRTs, respiratory symptoms were associated with a number of workplace and exposure factors likely to generate aerosol or chemical exposures such as processors not having local ventilation, adjusted OR 2.0 (1.4 to 3.0); leaking processor in which clean up was delayed, 2.4 (1.6 to 3.5); floor drain clogged, 2.0 (1.2 to 3.2); freeing a film jam, 2.9 (1.8 to 4.8); unblocking a blocked processor drain, 2.4 (1.6 to 3.7); and cleaning up processor chemical spill, 2.8 (1.9 to 4.2). These outcomes were not associated with routine tasks unlikely to generate exposures, such as working outside primary workplace, loading film into processor, routine cleaning of processors, or removing processed film. Males reported that they carried out a number of tasks potentially associated with irritant exposures more frequently than females, consistent with the marked increase in risk for new onset asthma. CONCLUSIONS: These findings suggest an increase of work related asthma and respiratory symptoms shown to denote asthma among MRTs, which is consistent with previous surveys. The mechanism is not known but appears to be linked with workplace factors and may involve a role for irritant exposures.

Adult↗
PubMed2002

Unexpected behavior of heavy-ion fusion cross sections at extreme sub-barrier energies.

The excitation function for fusion evaporation in the (60)Ni+ (89)Y system was measured over a range in cross section covering 6 orders of magnitude. The cross section exhibits an abrupt decrease at extreme sub-barrier energies. This behavior, which is also present in a few other systems found in the literature, cannot be reproduced with present models, including those based on a coupled-channels approach. Possible causes are discussed, including a dependence on the intrinsic structure of the participants.

Journal Article↗
PubMed2002

Analysis of mismatch repair defects in the familial occurrence of lymphoma and colorectal cancer.

Hereditary non-polyposis colon cancer (HNPCC) is an autosomal dominant disorder featuring familial clustering of colorectal and/or endometrial cancer, and other malignancies. Except for a rare case report, Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) have not been considered part of HNPCC. Recent murine models for HNPCC have shown an increased incidence of B- and T-cell lymphoma, as well as tumors of the gastrointestinal tract and other organ systems, involving defects in genes resulting in faulty mismatch repair (MMR) of DNA. These MMR genes include MLH1, MSH2, MSH3, MSH6, PMS1 and PMS2. We sought to analyze the occurrence of NHL and HD in families with clusters of colorectal cancers (CRC). Probands from 21 kindreds were classified as HNPCC (3), HNPCC-like (5), and HNPCC-variant (13); seen and followed by Clinical Genetics at Memorial Hospital the kindreds were assessed for the occurrence of NHL or HD. Of the 21 pedigrees, a total of 37 patients were identified who were diagnosed with leukemia, lymphoma, or HD. Fourteen of the 37 patients with a diagnosis of NHL or HD were further classified and showed varying histologies ranging from chronic lymphocytic leukemia/small lymphocytic lymphoma (2), mycosis fungoides (1), follicular lymphoma (1), extranodal marginal zone lymphoma of MALT type (2), diffuse large B-cell lymphoma (4), nodular sclerosis HD (3), and mixed cellularity HD (1). Microsatellite instability studies were performed on 6 cases but none showed evidence of replication error repair defects. Immunohistochemical stains performed on paraffin sections from these 6 representative cases showed differential protein expression of MLH1, MSH2, MSH6, and PMS2 when compared to normal reactive tissues from the same patient but showed no significant differences when compared to controls of non-familial, sporadic lymphomas. These results suggest that lymphomas arising in the setting of familial CRC do not bear the molecular hallmarks of HNPCC. Further studies are needed to explain the differential patterns of expression of RER-associated proteins in lymphomas, as well as the association of lymphomas and possibly renal cell cancers in a subset of kindreds in which CRC clustering is evident.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Outpatient video EEG recording in the diagnosis of non-epileptic seizures: a randomised controlled trial of simple suggestion techniques.

OBJECTIVE: To assess the yield of recorded habitual non-epileptic seizures during outpatient video EEG, using simple suggestion techniques based on hyperventilation and photic stimulation. DESIGN: Randomised controlled trial of "suggestion" v "no suggestion" during outpatient video EEG recording. SETTING: Regional epilepsy service (tertiary care; single centre). PARTICIPANTS: 30 patients (22 female, 8 male), aged over 16 years, with a probable clinical diagnosis of non-epileptic seizures; 15 were randomised to each group. MAIN OUTCOME MEASURES: Yield of habitual non-epileptic seizures recorded, and requirement for additional inpatient video EEG. RESULTS: 10/15 patients had habitual non-epileptic seizures with suggestion; 5/15 had non-epileptic seizures with no suggestion (p = 0.058; NS); 8/9 patients with a history of previous events in medical settings had non-epileptic seizures recorded during study. Logistic regression analysis with an interaction clause showed a significant effect of suggestion in patients with a history of previous events in medical settings (p = 0.003). An additional inpatient video-EEG was avoided in 14 of the 30 patients (47%). CONCLUSIONS: Habitual non-epileptic seizures can be recorded reliably during short outpatient video EEG in selected patients. Simple (non-invasive) suggestion techniques increase the yield at least in the subgroup with a history of previous events in medical settings. Inpatient video EEG can be avoided in some patients.

Adult↗
PubMed2001

Mitigation of hookworm disease by immunization with soluble extracts of Ancylostoma ceylanicum.

Hookworms are a leading cause of anemia in developing countries, and a strategy aimed at reducing pathology caused by blood-feeding adult parasites would be a valuable addition to global control efforts. This article describes experiments designed to induce resistance to the major clinical sequelae (weight loss and anemia) of Ancylostoma ceylanicum hookworm infection in Syrian golden hamsters of the outbred LVG strain. Previously infected animals acquired long-lived resistance to weight loss and anemia caused by a secondary hookworm infection. Furthermore, transfer of pooled serum from twice-infected hamsters to animals undergoing a primary infection was associated with partial resistance to growth delay and anemia. Active vaccination of hamsters with soluble adult hookworm antigens emulsified in alum led to partial protection from hookworm-associated pathology in the absence of reductions in adult worm burden. This intriguing result may have important implications for human vaccine development.

Ancylostoma↗
PubMed2001

Cytokine and chemokine dysregulation in hyper-IgE syndrome.

Hyper-IgE syndrome is characterized by severe recurrent staphylococcal infections, eczema, bone abnormalities, and markedly elevated levels of immunoglobulin E (IgE). The genetic basis is not known and the central immunologic defect is largely undefined. Reduced neutrophil chemotaxis is often described, and variable T cell defects have been demonstrated in some patients. It has been hypothesized that hyper-IgE is associated with a Th1/Th2 imbalance. We wished to characterize cytokine and chemokine imbalances that might reflect the underlying disease process or reflect ongoing pathologic processes. Nine patients with hyper-IgE syndrome and six controls were studied. Radioimmunoassays, flow cytometry, and gene array analyses were performed to characterize cytokine and chemokine production. Hyper-IgE patients express more IL-12, while ENA-78, MCP-3, and eotaxin are markedly underexpressed. Underexpression of a set of chemokines could explain a number of features of hyper-IgE syndrome and may offer a new paradigm for the understanding of this disorder.

Adolescent↗
PubMed2001

Eccrine porocarcinoma (malignant eccrine poroma): a clinicopathologic study of 69 cases.

The clinicopathologic characteristics of 69 cases of eccrine porocarcinoma (EP) have been studied. Seven cases of purely in situ disease are included. Forty patients were female, 29 male with ages ranging from 29 to 91 years (mean 73 years). The lower extremity represented the single most common site (44%). Other common sites were the trunk (15 cases, 24%) and head (11 cases, 18%). The histologic diagnosis of EP was predicated on the basis of an irregular tumor at least partly formed of characteristic poromatous basaloid epithelial cells displaying ductal differentiation, and significant cytologic atypia. Forty-seven tumors (68%) contained mature well-formed eccrine ducts having an eosinophilic luminal cuticle, with the remaining tumors containing small ill-formed ducts and/or intracytoplasmic lumina. All ducts were discernible via light microscopy and in 49 cases were highlighted with DPAS stain and/or CEA/EMA immunocytochemistry. A variant with a broad pushing tumor margin and marked nuclear pleomorphism showed some resemblance to proliferative bowenoid dysplasia. In 11 cases (18%) the tumors appeared to arise in continuity with a benign preexistent poroma. A variety of histologic patterns were displayed including clear, squamous, and spindle cell differentiation, mucus cell metaplasia, and colonization by melanocytes. Lymphovascular invasion was present in 9 cases (15%). Three cases showed pagetoid extension of malignant cells (epidermotropism) and appeared to be multifocal. Follow-up was available in 54 patients (78%) with 9 (17%) experiencing local recurrence, 10 developing lymph node metastases (19%), and 6 (11%) experiencing distant metastases or death. Mitoses, the presence of lymphovascular invasion, and tumor depth >7 mm were associated with a poorer prognosis. Dividing tumors into those with a "pushing" or "infiltrating" advancing margin was also predictive of outcome with the latter having an increased risk of local recurrence. This report, the largest series of EP to date, suggests that the incidence of aggressive behavior is less than popularly believed. Furthermore, EP can display a wide variety of histologic patterns that may lead to diagnostic error in the unwary. The large number of cases in this series enables a reliable evaluation of prognostic parameters. A more aggressive clinical course may be indicated by more than 14 mitoses per high power field (hazard ratio [HR] for death 17.0, 95% confidence interval [CI] 2.71-107), lymphovascular invasion by tumor (HR 4.41, CI 1.13-17.2), and depth >7 mm (HR 5.49, CI 1.0-30.3). Thus, mitoses, lymphovascular invasion, and tumor depth should be evaluated in these tumors. We also suggest that tumors presenting an "infiltrative" advancing margin are particularly prone to local recurrence and require wide excision with close attention to the surgical margins by the reporting pathologist.

Acrospiroma↗
PubMed2001

Antibiotic susceptibility profiles of Escherichia coli strains lacking multidrug efflux pump genes.

The contribution of seven known and nine predicted genes or operons associated with multidrug resistance to the susceptibility of Escherichia coli W3110 was assessed for 20 different classes of antimicrobial compounds that include antibiotics, antiseptics, detergents, and dyes. Strains were constructed with deletions for genes in the major facilitator superfamily, the resistance nodulation-cell division family, the small multidrug resistance family, the ATP-binding cassette family, and outer membrane factors. The agar dilution MICs of 35 compounds were determined for strains with deletions for multidrug resistance (MDR) pumps. Deletions in acrAB or tolC resulted in increased susceptibilities to the majority of compounds tested. The remaining MDR pump gene deletions resulted in increased susceptibilities to far fewer compounds. The results identify which MDR pumps contribute to intrinsic resistance under the conditions tested and supply practical information useful for designing sensitive assay strains for cell-based screening of antibacterial compounds.

Anti-Infective Agents, Local↗
PubMed2001

Effectiveness of reminder systems on appointment adherence rates.

The aim of this study was to determine the impact of reminder systems on appointment nonadherence rates in an low-income inner-city clinic population. A total of 2,304 consenting patients were randomly assigned to one of three groups: (1) automated telephone reminder, (2) postcard reminder, or (3) no reminder. In contrast with research on other populations, the results of this study demonstrated no significant difference in appointment adherence rates among the three groups. To aid in the development of more effective interventions in the future, individuals not attending their scheduled appointments were interviewed by telephone to determine reason for nonadherence.

Appointments and Schedules↗
PubMed2001

Cloning and characterization of a novel human histamine receptor.

Histamine exerts its numerous physiological functions through interaction with G protein-coupled receptors. Three such receptors have been defined at both the pharmacological and molecular level, while pharmacological evidence hints at the existence of further subtypes. We report here the cloning and characterization of a fourth histamine receptor subtype. Initially discovered in an expressed-sequence tag database, the full coding sequence (SP9144) was subsequently identified in chromosome 18 genomic sequence. This virtual coding sequence exhibited highest homology to the H(3) histamine receptor and was used to generate a full-length clone by polymerase chain reaction (PCR). The distribution of mRNA encoding SP9144 was restricted to cells of the immune system as determined by quantitative PCR. HEK-293 cells transiently transfected with SP9144 and a chimeric G protein alpha-subunit (Galpha(q/i1,2)) exhibited increases in intracellular [Ca(2+)] in response to histamine but not other biogenic amines. SP9144-transfected cells exhibited saturable, specific, high-affinity binding of [(3)H]histamine, which was potently inhibited by H(3) receptor-selective compounds. The rank order and potency of these compounds at SP9144 differed from the rank order at the H(3) receptor. Although SP9144 apparently coupled to Galpha(i), HEK-293 cells stably transfected with SP9144 did not exhibit histamine-mediated inhibition of forskolin-stimulated cAMP levels. However, both [(35)S]GTPgammaS binding and phosphorylation of mitogen-activated protein kinase were stimulated by histamine via SP9144 activation. In both of these assays, SP9144 exhibited evidence of constitutive activation. Taken together, these data demonstrate that SP9144 is a unique, fourth histamine receptor subtype.

Amino Acid Sequence↗