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Biomedical subjects

M Huberman

Publications and source records attributed to M Huberman.

At least 19 recordsLinked to original sources
PubMed2005

Electrogastrography in patients with Parkinson's disease.

BACKGROUND: Impaired gastrointestinal motility in Parkinson's disease may affect absorption of levodopa and contribute to the disabling response fluctuations (RF). In this study gastric myoelectric activity was recorded with electrogastrography in patients with PD and correlated with the duration, severity and the presence of RF. METHOD: Electrogastrography (EGG) was performed in 36 patients with PD of which 22 were men. The mean age was 67 years (48-81), mean duration of disease was 7.07 years (1-20), and mean duration of treatment with levodopa was 5.07 years (1-20). Gastric dysrhythmia was diagnosed when either preprandial or postprandial dysrhythmia for more than 30% of the recording period was detected. RESULTS: The EGG was abnormal in 24 of 36 patients. Significant association was found between preprandial dysrhythmia and duration of disease (P=0.002); duration of levodopa treatment (P=0.003), severity of 86RF (P=0.001), but not with age (P=0.076). Out of 18 patients with RF, 17 had at least one pattern of dysrhythmia. In 11 out of the 18 patients without RF, the EGG was normal while the remaining seven had at least one pattern of dysrhythmia. CONCLUSION: Abnormal EGG was quite common in this group of patients with PD, particularly in those with RF. The most common pattern of abnormality was preprandial dysrhythmia, which was positively associated with disease duration and length of levodopa treatment. Although frequently asymptomatic, preprandial dysrhythmia leading to impaired gastric emptying may contribute to irregular absorption of levodopa from the small intestine and contribute to disabling response fluctuations.

Aged↗
PubMed2002

Comparison of surgery alone with surgery and adjuvant radiotherapy for pT3N0 prostate cancer.

OBJECTIVE: To compare the outcome between patients with pT3N0 adenocarcinoma of the prostate treated with radical prostatectomy (RP) and those receiving RP followed by a planned course of postoperative radiation therapy (RT). PATIENTS AND METHODS: During a period of 22 years 622 patients with pT3N0 prostate cancer were treated in one medical centre by RP. Of these, 199 (32%) were treated with surgery alone while 423 (68%) received planned postoperative pelvic RT (median 48 Gy). Patients were selected for RT by having a higher incidence of adverse prognostic factors than those undergoing RP alone. These prognostic factors included pathological stage (P = 0.001) preoperative prostate specific antigen (PSA) level (P < 0.001) and Gleason score (P = 0.18). The patients' median age was 66 years; the median follow-up was 6.1 years for all patients, 7 years for RP + RT and 5 years for the RP-alone. RESULTS: The 5- and 10-year actuarial survival was 92% and 73%, respectively, for RP + RT patients, and nearly identical for those in the RP-alone group (P = 0.73). The 5- and 10-year disease-free survival (DFS; PSA < 0.05 ng/mL) was 69% and 51%, respectively, for the former, and 71% and 60%, respectively, for the latter group. There was no significant difference in DFS between the treatment groups by pathological stage and Gleason score (P = 0.77). Likewise, there was no significant difference in mean and median time to relapse. A preoperative PSA level of < 10 vs 10-25 vs > 25 ng/mL did not influence overall survival but a PSA of > 25 ng/mL was predictive of DFS (P = 0.02). In a multivariate analysis the Gleason score was the most important predictor for overall survival and DFS (P < 0.001), while pathological stage was predictive of clinical recurrence and DFS (P < 0.001). After controlling for pathological stage and Gleason score, RP + RT patients were predicted to recur at 92% of the rate of RP-alone patients (P = 0.65). In all, 43 (10%) patients developed a clinical recurrence in the RP + RT group, including 30 (7%) patients with distant metastases alone, 13 (3%) with local recurrence, with an additional 88 (21%) who had PSA recurrence (PSA > 0.05 ng/mL). This compared with 13 (6.5%) patients with clinical recurrence, including seven (3.5%) with local recurrence and 23 (11.6%) with PSA > 0.05 ng/mL in the RP-alone group. Postoperative RT was well tolerated and did not add to the incidence of surgical complications. CONCLUSION: We propose that postoperative RT, as described here, helped to reduce the incidence of local recurrence and improved DFS to equal that of a lower-risk group of patients treated with RP alone. A randomized comparison is needed to define the role of adjuvant RT in patients with pT3N0 disease.

Adenocarcinoma↗
PubMed2001

Nonrandomized comparison of surgery with and without adjuvant pelvic irradiation for patients with pT3N0 adenocarcinoma of the prostate.

The purpose of this study was to evaluate the outcome of radical prostatectomy alone and compare it with that of surgery followed by planned adjuvant radiotherapy in patients with pT3N0 prostate cancer (CaP). A total of 402 patients with CaP were treated with prostatectomy, including 311 (77%) who received a planned course of adjuvant radiotherapy (RT) (surgery [S] + RT) to the prostatic fossa (median dose: 48 Gy) and 91 (23%) who had surgery alone. Patients in the former group had worse risk factors than those in the latter group, such as a higher clinical and pathologic stage (p = 0.001), higher Gleason score (p = 0.09), and higher preoperative prostate-specific antigen (PSA) level (p = 0.0001). PSA failure was defined as more than 0.05 ng/ml. Median follow-up was 59 months. The 5- and 10-year overall survival for the 311 S+RT patients was 91% and 81%, respectively, and it was similar for those 91 in the surgery-alone group, p = 0.59. The 5- and 10-year probability of freedom from PSA and/or clinical failure for the former group was 70% and 53%, respectively, whereas it was 66% and 46%, respectively, for the latter group, p = 0.72. Any recurrence developed in a total of 96 (31%) patients in the S+RT group as compared with 23 (25%) in the surgery-alone group. Local recurrence was noted in 10 (3.2%) S+RT and in 6 (6.6%) surgery-alone patients (N.S.). The time to clinical or chemical recurrence was also similar for both treatment groups (median time: 3.0 versus 3.8 years). Patients with pT3b tumors had relatively poor 5- and 10-year disease-free survival (53% and 32%, respectively, for S+RT and 38% and 0%, respectively, for surgery alone, p = 0.82). In multivariate analyses, pathologic stage and Gleason score were independent predictors of recurrence, each with p < 0.001 after controlling for the other. The worst prognostic category included patients with pT3bN0, Gleason score 7-10 disease who had 5.0 times the risk of recurrence as compared with pT3aN0, Gleason score 2-6 patients. No significant difference in disease-free survival by the treatment group was seen in Cox regression analysis controlling for pathologic stage (p = 0.59), Gleason score (p = 0.99), and PSA (p = 0.28). S+RT patients were predicted to have disease recurrence at 83% the rate of surgery-alone patients, p = 0.42. Preoperative PSA (>25 ng/ml) was predictive of recurrence (2.0 x risk) in univariate analysis, but it was not a significant predictor in multivariate analysis. It appears that moderate-dose, localized fields postoperative irradiation reduced the incidence of local recurrence in patients who were at a higher risk of recurrence as compared with those treated with surgery alone. New treatment strategies need to be developed to manage pT3bN0, Gleason score 7-10 patients whose 10-year disease-free survival was poor.

Adenocarcinoma↗
PubMed2000

Motor and non-motor sequence learning in patients with basal ganglia lesions: the case of serial reaction time (SRT).

In order to address the question of whether the basal ganglia are involved exclusively in regulation of motor sequence learning, or if they are involved in non-motor sequence learning as well, two versions of the serial reaction time (SRT) task were administered: First is the standard version of the SRT task in which the sequence is executed motorically, and the second is a non-motor version of the task which requires response only to a particular position of the sequence. Sixteen patients with damage restricted to the region of the basal ganglia and 16 matched control subjects participated in this study. In addition to the motor and non-motor SRT tasks, two declarative memory tests (Visual Paired Associates and Rey Auditory-Verbal Learning Test) were administered to the participants. Results indicate that the two groups did not differ either on learning rate of the two declarative tasks, or on the declarative component of the SRT tasks (i.e., 'generate'). However, the control group was significantly superior to the basal ganglia (BG) group in learning a specific sequence in the motor and non-motor SRT tasks. Results suggest that the basal ganglia are involved in the regulation of non- motor as well as motor sequence learning.

Adult↗
PubMed1999

Application of the missing-indicator method in matched case-control studies with incomplete data.

A common practice in matched case-control studies with incomplete data is to perform two analyses in parallel: a matched analysis of the complete pairs and an unmatched analysis of all subjects carried out after breaking the matching in the complete pairs. The missing-indicator method, which has the advantage of making use of the data in the incomplete pairs while still preserving the matching in the complete pairs, is recommended as an alternative method of analysis. It is shown here that its estimate of the odds ratio is a compromise between the odds ratios estimated by a matched analysis of the complete pairs and an unmatched analysis of the incomplete pairs. The method is illustrated using data from a matched case-control study of the risk of childhood leukemia from exposure to residential electric and magnetic fields.

Biometry↗
PubMed1999

Correcting for exposure measurement error in a reanalysis of lung cancer mortality for the Colorado Plateau Uranium Miners cohort.

The exposure estimates used to date for the analysis of lung cancer mortality in the Colorado Plateau Uranium Miners cohort were developed from radon progeny measurements taken in mines beginning in 1951. Since uranium miners were often exposed over long periods of time and since mines were not continuously monitored, much extrapolation and/or interpolation of measured dose-rates was needed in order to develop estimates of exposure for each of the miners in the cohort. We have recently re-examined the interpolation scheme used to create the histories in the light of the fit of a statistical model for the radon progeny measurements taken in mines within the Plateau, and we have computed revised exposure estimates for the large majority of miners in the cohort. This report describes the use of these new model-based revised exposure estimates in the analysis of lung cancer mortality, using follow-up data current through 1990. Specific issues addressed here are (1) the strength of the association between exposure and risk of lung cancer mortality; (2) effects of attained age and time since exposure upon risk of lung cancer mortality; and (3) exposure-rate effects upon risk. Results using the revised exposure estimates are compared to those obtained fitting the same models using the original Public Health Service (PHS) exposure estimates. We found evidence that the new exposure histories provide a better fit to the lung cancer mortality data than do the histories based upon the original PHS dose-rate estimates. In general, the new results show a stronger overall relationship (larger slope estimate) between lung cancer mortality and exposure per unit exposure compared to those obtained with the original estimates, while displaying similar age at exposure and time since exposure effects. In the reanalysis the impact of low dose-rate exposure is found to be relatively unchanged before and after exposure error correction, while the estimate of the effect of high dose-rate exposure is considerably increased. Even after applying our measurement error corrections, evidence of inverse dose-rate effects is found, since the estimate of the impact of high dose-rate exposure is still below that of the low dose-rates. The magnitude and statistical significance, however, of the dose-rate effect estimates are diminished when fit using the revised exposure estimates.

Adult↗
PubMed1999

Ascertainment bias in rate ratio estimation from case-sibling control studies of variable age-at-onset diseases.

Motivated by a Finnish case-control study of early onset diabetes in which diabetic children are matched to sibling controls, we investigate ascertainment bias of the usual rate ratio estimator from case-control data under simplex complete ascertainment of families during a fixed interval of time. Analytic results indicate that the assumptions necessary for valid estimation are that the disease is rare and the factors under study are exchangeable--essentially that the covariate distribution does not depend on calendar time or birth order. Further, we found that the rare disease assumption could be dropped by restricting to cases that were diagnosed during the enrollment period of the study or including all cases but eliminating the proband as a control for non-enrollment-period cases. An important consequence of this work is that standard family-based case-control studies are subject to ascertainment bias if exchangeability of the covariates under investigation does not hold.

Age of Onset↗
PubMed1998

The immunomodulator AS101 restores T(H1) type of response suppressed by Babesia rodhaini in BALB/c mice.

The immunomodulator AS101 has been previously shown to confer protection upon BALB/c mice infected with the intraerythrocytic parasite Babesia rodhaini (B. rodhaini). The present study focuses on the effect of AS101 administration on the acute phase of babesial infection where T helper cell subset patterns-TH1/TH2-were assessed in heavily infected mice. Secretion of cytokines of the TH1 subset (IL-2, IFN-gamma, IL-12) and of the TH2 subset (IL-10, IL-4) as well as TGF-beta was measured following the administration of AS101 2 weeks before parasite infection. Our results demonstrate that the parasites suppress IL-2 protein and IL-12 mRNA and that AS101 upregulates their secretion: IL-2, 8 u/ml vs 34 u/ml, respectively; IFN-gamma protein, 2370 pg/ml vs 4777 pg/ml, respectively. Conversely, babesial infection results in the upregulation of IL-10 and IL-4 proteins and TGF-beta transcripts, whereas AS101 downregulates their production: IL-10, 1800 pg/ml vs 360 pg/ml, respectively; IL-4, 58.3 pg/ml vs 24.5 pg/ml, respectively. A possible escape mechanism induced by B. rodhaini is suggested, starting with IL-10 inhibition of macrophage activities leading to a suppression of the TH1 response and of IL-2 in particular. It is therefore possible that AS101 may protect infected mice by activating cellular-mediated immunity and concurrently balancing the TH subset responses. It is suggested that AS101 may be effective as an antiparasitic drug.

Adjuvants, Immunologic↗
PubMed1997

Beta-amyloid peptide induces tumor necrosis factor-alpha and nitric oxide production in murine macrophage cultures.

We investigated the effect of beta-amyloid peptide (betaA) on the activation of the murine-derived monocyte/macrophage J774 cell-line. BetaA induced tumor necrotic factor-alpha (TNF alpha) in these cells in a dose-dependent manner. Incubation of cells with betaA slightly increased nitric oxide (NO) production, an effect that was significantly enhanced by the addition of interferon-gamma (IFN gamma). Substitution of betaA4 with TFN alpha and incubation of the cultures with IFN gamma resulted in significant NO production, although this was lower than that obtained in the presence of the peptide. Incubation of cultures with a monoclonal antibody (mAb) against TNF alpha abrogated NO production. Our results suggest that betaA4-induced TNF alpha production is a crucial event in the activation of peripheral macrophages.

Amyloid beta-Peptides↗
PubMed1997

Essential fatty acid preparation improves biochemical and cognitive functions in experimental allergic encephalomyelitis rats.

This study examined the possible effects of a novel mixture of fatty acids, SR-3 (a specific ratio of alpha-linolenic acids), on brain biochemistry and on learning deficits induced by injection of an agent that induces experimental allergic encephalomyelitis. Treatment with SR-3 caused a decrease in myelin and changes in the fatty acid profile of brain synaptosomes, and a learning deficit. Eighteen days of treatment with SR-3 reversed the biochemical and learning deficit significantly, but did not restore them to normal levels. We propose that, most probably, the main action of SR-3 is the modulation of the cholesterol level, which in turn causes the modulation of the fatty acid profile and enhances learning by allowing improved neuronal communication.

Analysis of Variance↗
PubMed1996

Trials of 9-amino-20(S)-camptothecin in Boston.

9-Amino-20(S)-camptothecin (9-AC) is an analog of camptothecin with limited water solubility which has shown significant preclinical activity in a variety of human solid tumor xenografts. A Phase I trial using a soluble formulation of 9-AC, given as a 72-hour continuous infusion, has been completed. Thirty-one patients with resistant cancers received 5-60 micrograms/M2/h at three week intervals. The Maximum Tolerated Dose (MTD) was 45 micrograms/M2/hour. Neutropenia was the dose limiting toxicity, with few significant non-myelosuppressive toxicities. Minor responses were seen in 3/31 patients. Pharmacokinetic studies of 9-AC lactone (closed ring) showed substantial interpatient variability with a predicted half-life of 36 hours. A phase I/II trial of the same formulation of 9-AC is ongoing in refractory leukemia. Stomatitis and diarrhea are the non-myelosuppressive dose limiting toxicities. Evidence of antineoplastic activity has been seen in 3/15 patients. A Phase II trial in previously untreated metastatic breast cancer is also underway. A Phase I trial of a colloidal dispersion formulation, not yet completed, is better tolerated with a MTD > 45 micrograms/M2/h as a 72-hour continuous infusion. Evidence of antineoplastic activity has also been demonstrated.

Adult↗
PubMed1996

5-Fluorouracil and alpha-interferon in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major cause of mortality worldwide, and no effective systematic therapy currently exists. Recombinant alpha-interferon (IFN) has been suggested to have some antitumor efficacy in this illness, and synergism with 5-fluorouracil (5-FU) has been reported in several gastrointestinal malignancies. We therefore treated 10 patients with advanced HCC with combination therapy consisting of 5-FU 750/mg/m(2) weekly and IFN 9 X 10(6) units three times weekly. Toxicity was substantial in this cirrhotic population, and included mucositis as well as neurologic and hematologic side effects. There were no sustained antitumor responses. Median survival among this heavily pretreated population was 10 months. We were therefore unable to demonstrate any significant benefit to treatment with 5-FU and IFN in patients with HCC.

Antimetabolites, Antineoplastic↗
PubMed1995

T lymphocyte subpopulations and activation markers correlate with severity of Alzheimer's disease.

In this study we investigated immune-associated antigens of peripheral lymphocytes from patients with Alzheimer's disease (AD). The patients were divided into two groups--mild and moderately severe--according to severity of disease stage, and their lymphocytes were compared to those of elderly controls. In the mild stage of the disease we observed a slight increase in the HLA-DR marker (9.5 +/- 2.4% vs 6.5 +/- 1.1%; P = 0.06), but no changes in the CD4, CD8, and interleukin-2 receptor (IL-2R) markers. In the moderately severe stage, we observed a significant increase in the HLA-DR (18.5 +/- 2.7%) and CD4 markers (55.2 +/- 3.5% vs 43.5 +/- 2.1%, P < 0.01), and a slight decrease in the CD8 subset (19.5 +/- 1.4% vs 22.3 +/- 1.3%, P = 0.05). In the same group, following stimulation with the mitogen PHA, we observed a marked reduction in IL-2R expression (30.9 +/- 4.7% vs 41.1 +/- 2.7%, P = 0.05) and in the proliferative ability of lymphocytes (21131 +/- 4676 cpm vs 47909 +/- 1107 cpm, P < 0.04). However, mitogen-induced IL-2 secretion levels from the same lymphocytes were significantly elevated (17.4 +/- 4.8 U/ml vs 8.6 +/- 4.3 U/ml, P < 0.01). Marked changes in immunological parameters in the moderately severe group support the hypothesis of a peripheral immune reaction in AD which may be correlated with the clinical stage of the disease.

Aged↗
PubMed1995

IL-2 and IL-6 secretion in dementia: correlation with type and severity of disease.

The production of interleukin-2 (IL-2) and interleukin-6 (IL-6) by peripheral blood mononuclear cells (MNC) was assessed in patients with Alzheimer's disease (AD) who were subdivided into two groups--mild and moderately-severe--according to the severity of the disease, probable vascular dementia (VaD) patients and elderly control subjects. No differences in IL-2 secretion were found between mild AD patients and controls. However, there was a significant increase in IL-2 production both in the moderately-severe AD group and in the VaD group. IL-6 levels in AD patients of both groups were similar and significantly higher than those of VaD and controls. Our results suggest that increased levels of IL-2-production correlate with severity of the dementia, whereas increased levels of IL-6 production seem to be related to AD and thus may play a role in AD pathogenesis.

Aged↗