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P Greenberg

Publications and source records attributed to P Greenberg.

At least 19 recordsLinked to original sources
PubMed2006

Cautionary tales in the interpretation of systematic reviews of therapy trials.

This is the second in a series of articles emphasizing the cautions in the interpretation of health-care studies. Systematic reviews are presented as comprehensive, unbiased summaries of evidence and are often referred to by clinicians, guideline developers and health policy-makers. Their strengths and limitations, and how their results can be subject to bias and misinterpretation, are discussed.

Humans↗
PubMed2006

Effects of selective attention on perceptual filling-in.

After few seconds, a figure steadily presented in peripheral vision becomes perceptually filled-in by its background, as if it "disappeared". We report that directing attention to the color, shape, or location of a figure increased the probability of perceiving filling-in compared to unattended figures, without modifying the time required for filling-in. This effect could be augmented by boosting attention. Furthermore, the frequency distribution of filling-in response times for attended figures could be predicted by multiplying the frequencies of response times for unattended figures with a constant. We propose that, after failure of figure-ground segregation, the neural interpolation processes that produce perceptual filling-in are enhanced in attended figure regions. As filling-in processes are involved in surface perception, the present study demonstrates that even very early visual processes are subject to modulation by cognitive factors.

Adult↗
PubMed2005

Pharmacogenomic assessment of treatment options in gestational diabetes.

Gene expression profiles offer a multidimensional view of metabolic diseases, typically characterized by a single parameter, and can provide a basis for choosing between therapies yielding a common clinical end point. We applied such an approach in gestational diabetes mellitus (GDM). Gene expression was examined in four maternal tissues and placentas from normal patients and euglycemic GDM patients, undergoing elective Cesarean sections at term, treated either by diet or diet plus insulin. Deviations from normal were 11-fold greater for the patients treated by diet, alone, than for patients treated by diet plus insulin. Assuming the achievement of a "normal" gene expression profile, in addition to euglycemia, is a desirable outcome of treatment, insulin treatment appears to have a beneficial effect in the treatment of GDM. Subsequently, we utilized the expression data to identify serum biomarkers that provide ways to monitor the benefits of insulin treatment in GDM.

Adipose Tissue↗
PubMed2003

Opportunities for Trisenox (arsenic trioxide) in the treatment of myelodysplastic syndromes.

Arsenic trioxide (ATO) has a long history of efficacy as an antileukemic agent. However, with the advent of modern therapy, it had been relegated to a historical footnote. In the 1990s, investigators in China reported that ATO was safe and had dramatic efficacy in patients with acute promyelocytic leukemia (APL). Preclinical investigations indicate that the biological targets of this novel drug extend to a variety of malignancies other than APL and include induction of apoptosis, nonterminal differentiation, and suppression of proliferation and angiogenesis. The myelodysplastic syndromes (MDSs) present a particular therapeutic challenge. Ineffective hematopoiesis predominates in patients with low-grade prognostic scores. The survival of those patients with high-grade disease is compromised by a high risk of leukemia transformation. Although a number of therapeutic options have been investigated, none has emerged as being broadly efficacious and having an acceptable toxicity profile. No drug has yet received approval by the Food and Drug Administration for this indication. Biologic features of MDS, which include accelerated apoptotic potential, limited maturation capacity, and medullary neovascularity, create a strong scientific rationale for the investigation of ATO in MDS. This report describes the history and scientific basis for ATO treatment of hematologic malignancies, enumerates the potential benefits of ATO in MDS, and discusses the direction of ongoing trials of this novel antineoplastic agent.

Antineoplastic Agents↗
PubMed2002

Soluble TNF receptor fusion protein (etanercept) for the treatment of myelodysplastic syndrome: a pilot study.

Blockade of tumor necrosis factor (TNF)alpha by a soluble TNF receptor fusion protein (etanercept; Enbrel) improved in vitro hemopoiesis from the marrow of patients with myelodysplastic syndrome (MDS). Therefore, we enrolled 14 MDS patients (4 RA, 2 RARS, 6 RAEB, 2 CMML), 44-80 (median 60) years old, in a pilot trial. Etanercept, 25 mg, was given twice a week s.c. for 16 weeks (increased to three times a week if no response at 8 weeks). Among 12 evaluable patients, four had rises in hemoglobin by 1-1.5 gm/dl (three) or decreased transfusion requirements (one). Two patients had increased platelet counts (54% and 73%), and two increased neutrophils (63% and 120%). Baseline TNFalpha levels, determined in all patients, did not correlate with responses. Among eight marrows available for sequential in vitro assays, four showed increases in CFU-GM of 1.5- to 5-fold at 8 weeks, whereas three showed 3- to 10-fold decrements relative to baseline. Thus, etanercept treatment resulted in moderate improvements of cytopenias in some patients, while cell counts declined in others. Additional trials are needed to evaluate its clinical efficacy in MDS.

Adult↗
PubMed2001

Treatment of myelodysplastic syndrome with agents interfering with inhibitory cytokines.

Results of these trials provide evidence for biological activity and some clinical efficacy of agents potentially blocking inhibitory cytokines in patients with MDS. However, given the limited responses, it appears that factors additional to TNFalpha inhibitory activity contribute to the development of cytopenias in these patients. Further studies are warranted using anti-TNFalpha/anti-inhibitory cytokine approaches, either alone or in combination with other agents, capable of abrogating the effects of additional inhibitory mechanisms in MDS.

Etanercept↗
PubMed2000

Savings in direct medical costs from the use of tobramycin solution for inhalation in patients with cystic fibrosis.

OBJECTIVE: Two identical 24-week, double-blind, placebo-controlled trials of tobramycin solution for inhalation (TOBI [PathoGenesis Corporation, Seattle, Washington]) in cystic fibrosis patients with chronic Pseudomonas aeruginosa infection were conducted in the United States. The aim of the present study was to extrapolate the US trial data to a Canadian setting, using Canadian costs to estimate the savings in direct medical costs that might result from use of a similar 24-week TOBI regimen versus usual care in 2 Canadian provinces. BACKGROUND: Cystic fibrosis is a genetic disease in which persistent respiratory infection, usually due to P. aeruginosa infection, is the major cause of morbidity and mortality. METHODS: The US trials demonstrated that TOBI produced significant improvements in pulmonary function test results, reduced sputum levels of P. aeruginosa, and resulted in a 26% reduction in the probability of hospitalization (95% CI, 2%-43% vs placebo in the clinical trials). Individual patient data from the US trials were used to calculate the mean number of days in hospital as well as the mean number of days of home intravenous or oral antibiotic therapy. To adjust for Canadian pricing, pertinent economic data were obtained from Statistics Canada and the Ontario and Quebec health ministries. Demographic and baseline data were obtained from health surveys conducted by the Canadian Cystic Fibrosis Foundation. RESULTS: Economic analysis showed that the use of TOBI for 24 weeks would result in estimated mean per-patient savings in direct medical costs (in Canadian dollars) of $4055 in Ontario and $4916 in Quebec, which would substantially offset the Canadian acquisition price of $8602 for the same 24-week period. CONCLUSIONS: Assuming that the percentage of reduction in hospital days observed in the US trials would also occur in the Canadian clinical setting, use of TOBI would reduce the use of health care services, particularly hospital days, and lead to substantial savings in direct medical costs that would offset its acquisition price. Whether this reduction actually occurs after TOBI enters the Canadian market is a subject for future investigation.

Administration, Inhalation↗
PubMed2000

The impact of antidepressant use on social functioning: reboxetine versus fluoxetine.

Depression compromises affected individuals' functional well-being and impairs their level of social and workplace performance. Improved social functioning in depressed patients may improve their work productivity. This study evaluated the differential effects of two antidepressants on social functioning outcomes for patients with major depression comparing reboxetine, a non-tricyclic, selective noradrenaline reuptake inhibitor and fluoxetine, a commonly prescribed selective serotonin reuptake inhibitor. A model using data from 284 depressed patients (138 reboxetine, 146 fluoxetine) in two 8-week clinical trials was developed to predict the percentage change over time in continuous outcome assessments as measured by a 21-item self-rating scale called the Social Adaptation Self-evaluation Scale (SASS). The percentage change from baseline SASS score was modelled as a function of both time-invariant and time-varying covariates. Results suggest that, by mid-study, the more severely ill subjects benefitted more from reboxetine treatment in terms of the outcome improvement rate and, by study-end, this effect also extended into the less severely ill population. In addition, a significant relationship was identified between the change in depression symptom severity as measured by the standard Hamilton Depression Rating Scale score and the change in social functioning per the SASS.

Adrenergic Uptake Inhibitors↗
PubMed1999

Treatment of poor prognosis AML patients using PSC833 (valspodar) plus mitoxantrone, etoposide, and cytarabine (PSC-MEC).

The failure of convenional chemotherapy in relapsed or refractory and other poor risk AML patients has been linked to expression of the multidrug resistance gene (mdr 1) product P-glycoprotein (P-gp). PSC 833 is a non-competitive inhibitor of P-gp and has been shown in vitro and in vivo to restore sensitivity of resistant tumor cells to anticancer drugs (ACDs). Induction chemotherapy consisting of cytarabine (C) in combination with PSC 833 and escalating doses of mitoxantrone (M) and etoposide (E) over 5 or 6 days were tested in two phase I/II studies in poor prognosis AML. Overall, 59 patients were evaluated: their age ranged between 18 and 70 years. Fourteen patients had primary refractory disease, 25 had relapsed within 9 months from first complete remission (CR), 5 were in second relapse, 10 had secondary AML, and 4 had relapsed post-bone marrow transplantation. PSC 833 was given as a constant i.v. infusion at a rate of 10 mg/kg/24 h for 5 or 6 days, depending on the duration of chemotherapy. In both studies a loading dose of 2 mg/kg of PSC 833 was given on day 1. In the 5-day regimen, the final study doses of the cytotoxic agents were C 1 g/m2/d, M 4.0 mg/m2/d, and E 40 mg/m2/d. In the 6-day regimen, the final study doses of the cytotoxic agents were C 1 g/m2/d, M 4.5 mg/m2/d and E 30 mg/m2/d. The combined efficacy results of both studies indicate that PSC-MEC is active in all treatment indications, complete remission being achieved in 2/5 (40%) second relapses, 8/25 (32%) early relapses, 3/10 (30%) secondary AML, 3/15 (20%) refractory patients and 1/4 (25%) post-BMT relapses. Based on historical controls, this observed overall CR rate (29%) is higher than expected in this high risk patient population. Our data indicate that, in refractory/relapsed AML patients, PSC-MEC regimens had encouraging antileukemic effects, is well tolerated, and has led to Phase III trials in this setting.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Protection from pathogenic SIV challenge using multigenic DNA vaccines.

To assess DNA immunization as a strategy for protecting against HIV infection in humans, we utilized SIVmne infection of Macaca fascicularis as a vaccine challenge model with moderate pathogenic potential. We compared the efficacy of DNA immunization alone and in combination with subunit protein boosts. All of the structural and regulatory genes of SIVmne clone 8 were cloned into mammalian expression vectors under the control of the CMV IE-1 promoter. Eight M. fascicularis were immunized twice with 3 mg of plasmid DNA divided between two sites; intramuscular and intradermal. Four primed macaques received a further two DNA immunizations at weeks 16-36, while the second group of four were boosted with 250 microg recombinant gp160 plus 250 microg recombinant Gag-Pol particles formulated in MF-59 adjuvant. Half of the controls received four immunizations of vector DNA; half received two vector DNA and two adjuvant immunizations. As expected, humoral immune responses were stronger in the macaques receiving subunit boosts, but responses were sustained in both groups. Significant neutralizing antibody titers to SIVmne were detected in one of the subunit-boosted animals and in none of the DNA-only animals prior to challenge. T-cell proliferative responses to gp160 and to Gag were detected in all immunized animals after three immunizations, and these responses increased after four immunizations. Cytokine profiles in PHA-stimulated PBMC taken on the day of challenge showed trends toward Thl responses in 2/4 macaques in the DNA vaccinated group and in 1/4 of the DNA plus subunit vaccinated macaques; Th2 responses in 3/4 DNA plus subunit-immunized macaques; and Th0 responses in 4/4 controls. In bulk CTL culture, SIV specific lysis was low or undetectable, even after four immunizations. However, stable SIV Gag-Pol- and env-specific T-cell clones (CD3+ CD8+) were isolated after only two DNA immunizations, and Gag-Pol- and Nef-specific CTL lines were isolated on the day of challenge. All animals were challenged at week 38 with SIVmne uncloned stock by the intrarectal route. Based on antibody anamnestic responses (western, ELISA, and neutralizing antibodies) and virus detection methods (co-culture of PBMC and LNMC, nested set PCR- of DNA from PBMC and LNMC, and plasma QC-PCR), there were major differences between the groups in the challenge outcome. Surprisingly, sustained low virus loads were observed only in the DNA group, suggesting that four immunizations with DNA only elicited more effective immune responses than two DNA primes combined with two protein boosts. Multigenic DNA vaccines such as these, bearing all structural and regulatory genes, show significant promise and may be a safe alternative to live-attenuated vaccines.

Animals↗