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Biomedical subjects

M Huberman

Publications and source records attributed to M Huberman.

At least 19 recordsLinked to original sources
PubMed1995

Improved detection of auditory P3 abnormality in dementia using a variety of stimuli.

The purpose of this study was to test the improved sensitivity of P3 abnormality in the detection of dementia using a variety of auditory stimuli. Improved detection was obtained using auditory stimuli that differed in their cognitive attributes and by using several P3 measures. These measures included P3 latencies and amplitudes relative to pure tone evoked P3s. Fourteen demented patients (mean age 79.2 years) and a matched normative group were tested. Abnormality of P3 latency for pure tone targets was found in ten patients, equivalent to a hit-rate of 72%. The hit-rate could be further increased by using phonemically and phonetically different types of auditory stimuli, thought to vary in their cognitive attributes. These findings underscore the importance of using a variety of stimuli in testing demented patients.

Acoustic Stimulation↗
PubMed1991

A phase I study of an outpatient regimen of recombinant human interleukin-2 and alpha-2a-interferon in patients with solid tumors.

This study was undertaken to define the maximum tolerated dose (MTD) of recombinant interleukin-2 (IL-2) that could be combined with a fixed dose of alpha-2a-interferon (alpha-IFN) in an outpatient setting. The schedule called for IL-2 to be given by a 2-hour intravenous infusion 5 days a week for 4 weeks. The alpha-IFN was given at a dose of 6 x 10(6) U/m2/d intramuscularly 3 days per week (Monday, Wednesday, and Friday). The IL-2 dose was escalated in four dose levels from 1 to 4 x 10(6) U/m2/d. The MTD in this study of 17 patients was at the fourth dose level of IL-2 (4 x 10(6) U/m2/d). In addition to the usual IL-2 toxicities, debilitating fatigue limited outpatient administration of this dose. Although the response rate was low, with partial responses seen in only 1 of 15 patients, 2 of 5 patients with melanoma treated at the higher dose levels had objective tumor shrinkage with one partial and one minor response. Thus, an IL-2 dose of 3 x 10(6) U/m2/d combined with a recombinant alpha-2a-IFN dose of 6 x 10(6) U/m2/d is recommended for Phase II studies.

Adult↗
PubMed1990

A phase I study of recombinant human interleukin-2 and alpha-interferon-2a in patients with renal cell cancer, colorectal cancer, and malignant melanoma.

Preclinical data suggest synergy of interleukin-2 (IL-2) combined with alpha-interferon (IFN). In addition, toxicities of IL-2 may be decreased by intermittent continuous infusion. The purpose of this trial was to determine the maximum tolerated dose (MTD) of recombinant IL-2 combined with alpha-IFN in patients with renal cancer, colon cancer, melanoma, and malignant B-cell disease. IL-2 was given by continuous i.v. infusion at an initial dose of 5 X 10(5) units (U)/m2/d for 4 days plus IFN at 6 X 10(6) U/m2/d intramuscularly days 1 and 4 weekly for 4 weeks. Patients who achieved a response or stable disease received an additional 4 weeks of therapy. IL-2 doses were increased to 1, 2, 3, 5, and 7 X 10(6) U/m2/d with three to eight patients at each dose level, at each of the two participating institutions. The dose of IFN was 6 X 10(6) U/m2 days 1 and 4 for all but five patients whose IFN dose was doubled to 12 X 10(6) U/m2/d. Forty-three patients were entered on this study with 34 completing at least 4 weeks of therapy. Six patients were taken off study because of Grades III or IV pulmonary, neurologic, or cardiac toxicity; one for progressive disease; one for CNS metastases, and one for personal reasons. All of the toxicities were reversible. Chills and fever were universal, especially on days 1 and 4. Mild and moderate nausea, vomiting, diarrhea, anorexia, malaise, and cutaneous erythema were present in most patients. Fluid retention and occasional pleural effusions were observed at the higher IL-2 doses but were not dose-limiting. Significant hypotension associated with oliguria was seen, and these patients were treated with vasopressors and colloids. None of the patients required ICU admission. Thirty-four patients were evaluable for response. There were 4/18 (22%) renal cell patients who experienced a partial response. No responses were seen in patients with melanoma, lymphoma, or colorectal cancer. The combined debilitating symptoms of fatigue, diarrhea, hypotension, fluid retention, and anorexia defined the MTD as 5 X 10(6) U/m2/d of IL-2 and 6 X 10(6) U/m2 of alpha-IFN.

Adult↗
PubMed1990

Very low doses of warfarin can prevent thrombosis in central venous catheters. A randomized prospective trial.

OBJECTIVE: To determine whether very low doses of warfarin are useful in thrombosis prophylaxis in patients with central venous catheters. DESIGN: Patients at risk for thrombosis associated with chronic indwelling central venous catheters were prospectively and randomly assigned to receive or not to receive 1 mg of warfarin, beginning 3 days before catheter insertion and continuing for 90 days. Subclavian, innominate, and superior vena cava venograms were done at onset of thrombosis symptoms or after 90 days in the study. RESULTS: One hundred twenty-one patients entered the study, and 82 patients completed the study. Of 42 patients completing the study while receiving warfarin, 4 had venogram-proven thrombosis. All 4 had symptoms from thrombosis. Of 40 patients completing the study while not receiving warfarin, 15 had venogram-proven thrombosis, and 10 had symptoms from thrombosis (P less than 0.001). There were no measurable changes in the coagulation values assayed due to this warfarin dose, except in occasional patients who had become anorectic because of their disease or chemotherapy. CONCLUSIONS: Very low doses of warfarin can protect against thrombosis without inducing a hemorrhagic state. This approach may be applicable to other groups of patients.

Adult↗
PubMed1990

Interferon system and natural killer cell activity in myasthenia gravis.

The autoimmune response in myasthenia gravis is well characterized, but little is known about the mechanisms initiating it. We have studied the interferon system and natural killer cell activity in 25 patients with myasthenia gravis and compared them to 68 healthy subjects and 96 patients with acute viral infections. Forty-four per cent of patients had circulating interferon (greater than 16 mu/ml), and in a similar proportion their peripheral blood mononuclear cells were in an antiviral state, i.e., showed low levels of viral replication when infected by vesicular stomatitis virus. Spontaneous in vitro interferon production by patients' peripheral blood mononuclear cells was also common (greater than 10 mu/ml, 32 per cent), while the response to the alpha-interferon inducer poly I:C was lower than expected, possibly reflecting the already high state of activation of the interferon system. These results were essentially similar to those obtained in patients with viral illnesses and differed significantly from healthy controls. In many myasthenia gravis patients (16 of 22, 73 per cent), a markedly deficient natural killer cell activity was found, with a median cytotoxicity of 6.5 per cent compared to 29 per cent in healthy subjects (p less than 0.005). Thus, many patients with myasthenia gravis have evidence of an activated interferon system and defective natural killer cell activity, suggesting an occult viral infection or reflecting nonspecific stimulation which may nevertheless contribute to the pathogenesis of the autoimmune response.

Acute Disease↗
PubMed1988

MRI parameters in multiple sclerosis patients.

Magnetic resonance imaging (MRI) findings of 20 patients with clinically definite multiple sclerosis (MS) are presented. The studies were performed on a 0.5 Tesla magnet using spin-echo technique. Analysis of the MRI findings included detailed linear measurements of the ventricular and the subarachnoid spaces and reading of the intensity of the grey and white matter and intensity of the MS plaques. The plaques were sorted according to their number and size. The younger patients (20-40 years) had overall more plaques than the older ones (over 40 years). The small plaques were the most numerous and the large ones were the least common. Statistically significant association was found between the number of plaques and the cella media width. The intensity ratios between the non-plaque white matter/grey matter showed a significant correlation with the ventricular score. A significant negative correlation was found between the antero-posterior diameter of the spinal cord and the number of MS plaques in the brain. The plaque/white matter ratio had a significantly negative correlation with the cervical cord's width.

Adult↗
PubMed1986

Vinblastine plus cisplatin in advanced non-small cell lung cancer: lack of advantage for vinblastine infusion schedule.

We have evaluated 31 patients with advanced non-small cell lung cancer treated by short-term 5-day vinblastine infusion combined with bolus cisplatin. Nine of 31 patients (29%) had partial and complete responses. Although five of nine (55%) of the responders were alive at greater than or equal to 1 year, three of the 31 patients experienced drug-related mortality. Our experience, as well as a review of previously reported trials in the literature, suggests that the infusion schedule of vinblastine offers no advantage over the bolus schedule.

Adenocarcinoma↗
PubMed1985

Randomized trial of estrogen vs. tamoxifen therapy for advanced breast cancer.

Forty-three postmenopausal females with advanced breast cancer were studied in a prospective comparative trial of estrogen vs. an anti-estrogen (tamoxifen) therapy with a crossover to the alternative hormone with progressive disease. Ten of 19 patients (53%) responded to primary tamoxifen therapy and six of 24 (25%) responded to primary estrogen therapy. Crossover responses were observed in seven of 19 (37%) on the secondary tamoxifen therapy and in two of 10 (20%) on secondary estrogen therapy, and were not related to the response to the primary hormonal maneuver. Responses were related to the presence of estrogen receptor protein (ERP), particularly for tamoxifen therapy, although responses were observed in three of six ERP negative patients receiving estrogen and in seven of 25 (28%) of patients with an unknown ERP status. Complications were observed in 35 instances with estrogen therapy and in only five instances with tamoxifen therapy. Initial hormonal therapy with tamoxifen in postmenopausal patients with advanced breast cancer and ERP status positive or unknown is superior to primary estrogen treatment. Secondary therapy and response to estrogen or tamoxifen is not necessarily predicted by the initial hormone response, and crossover to the alternative therapy is generally indicated.

Aged↗
PubMed1984

Fate and structure of DNA microinjected into mouse TK-L cells.

Co-microinjection of single linearized molecules of plasmids containing the human beta-globin gene (pRK1) and the herpes simplex virus (HSV) type I thymidine kinase gene (pX1) into the mouse TK-L cell nucleus results in covalent linkage between these (or derived) molecules within the nucleus as revealed by Southern blotting, plasmid rescue, and recovery of plasmid-derived DNA from a Charon 4A phage library of cellular DNA. The microinjected DNA is predominantly found as high molecular weight DNA as determined by Hirt fractionation. Southern blotting data and recombinants from the Charon 4A library suggest that the plasmid DNA is in the form of a head-to-tail linear concatamer of up to 80 copies. Passage of these microinjected cells in selective medium (HAT) results in coordinate amplification of both plasmids, which are maintained in an approx. 3:1 molar ratio of pRK1 to pX1-derived molecules. Hybridization in situ shows the DNA to be integrated on a translocation chromosome, t(4;4). Integration does not appear to be site-specific, since plasmid DNA from another microinjected cell line, C2B, appears on a different translocation chromosome, t(8?;14). Plasmid rescue experiments confirm a previous finding that passage of pBR322 DNA through eukaryotic cells may result in deletions of normally stable plasmid DNA upon subsequent transformation of E. coli. These deletions appear to occur in the bacteria, and originate in a 128 bp region between the Sal I and Hae II sites of pBR322.

Animals↗
PubMed1984

Recurrent neuroleptic malignant syndrome due to tiapride and haloperidol: the possible role of D-2 dopamine receptors.

Two typical recurrent episodes of neuroleptic malignant syndrome (NMS) in the same patient are described. The first episode was caused by a sulpiride derivative, tiapride. This is the first case in which a drug of the benzamide group has been reported to have caused such adverse drug reaction. In the second episode, NMS occurred due to haloperidol in the lowest dose ever reported and was accompanied by highly excessive levels of various muscle enzymes. Involvement of hypothalamic and striatal dopamine system, and particularly of D-2 subtype receptors, is suggested by this case.

Basal Ganglia↗
PubMed1980

Herpes zoster and small cell bronchogenic carcinoma.

In nine of 74 (12 per cent) consecutive, previously untreated patients with small cell bronchogenic carcinoma receiving combination chemotherapy herpes zoster developed. This is the highest frequenzy reported for this viral infection in patients with nonlymphoproliferative solid tumors. Cutaneous dissemination developed in six of the nine patients, but visceral involvement did not occur. The major difference between the patients with herpes zoster and those without was the superior duration of median survival for the infected patients. No relationship could be established between the development of herpes zoster and the extent of neoplastic disease, prior radiotherapy, treatment with specific chemotherapeutic agents or corticosteroids, cutaneous anergy or granulocytopenia. Serum specimens obtained from six of the nine patients prior to their infection demonstrated the preexistence of varicella zoster antibodies. As more effective and intensive chemotherapy prolongs the survival of patients with solid tumors, it is possible that the frequency of herpes zoster infection may approach that observed in patients with lymphoproliferative malignancies.

Adult↗
PubMed1979

Purification and properties of the latent F1-APTase of Micrococcus lysodeikticus.

The latent coupling factor (F1)-ATPase of Micrococcus lysodeikticus has been purified to homogeneity as determined by a number of criteria including, nondenaturing polyacrylamide gel electrophoresis, crossed immunoelectrophoresis and analytical ultracentrifugation. By inclusion of 1 mM phenylmethyl sulfonyl fluoride, a serine protease inhibitor, in the shock-wash step of release of F1 from the membranes, the spontaneous activation of both crude and purified ATPase by endogenous membrane protease(s) can be prevented, thereby yielding a highly latent ATPase preparation. Equilibrium ultracentrifugation of the latent ATPase gave a molecular weight of 400 000. The ATPase contained five different subunits alpha, beta, gamma, delta, and espsilon and their molecular weights determined by SDS-polyacrylamide gel electrophoresis were 60 000, 54 000, 37 000, 27 000 and 9000, respectively. The subunit composition was determined with 14C-labelled, F1-ATPase prepared from cells grown on medium containing [U-14C]-labelled algal protein hydrolysate. Within the limitations of this method the results tentatively suggest a subunit composition of 3 : 3 : 1 : 1 : 3.

Adenosine Triphosphatases↗