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Biomedical subjects

G Kaplan

Publications and source records attributed to G Kaplan.

At least 91 records · Page 5Linked to original sources
PubMed1998

Selective increase in plasma tumor necrosis factor-alpha and concomitant clinical deterioration after initiating therapy in patients with severe tuberculosis.

The initiation of antituberculosis treatment in patients with severe tuberculosis may be accompanied by clinical deterioration and even death before any improvement occurs. To investigate this phenomenon, newly diagnosed human immunodeficiency virus-negative adults with severe tuberculosis were followed for the first 42 days of standard short-course therapy. Clinical status, serum lactate, plasma cytokine, and plasma cytokine receptor levels were monitored on days 0, 3, and 7 and then weekly for up to 42 days. Following 7 days of antituberculosis therapy, a significant transient decrease in mean Karnofsky score (P < .001), a concomitant increase in serum lactate (P = .06), a decrease in patient weight (P = .02), and an increase in plasma tumor necrosis factor-alpha (TNF-alpha) concentrations (P = .04) were observed. Plasma levels of soluble interleukin-2 receptor, interferon-gamma, interleukin-6, and TNF-alpha receptor decreased over the 42-day study period. These observations suggest that increases in plasma TNF-alpha levels may be associated with clinical deterioration observed early in the treatment of severe tuberculosis.

Adult↗
PubMed1998

Dose response of various radiation detectors to synchrotron radiation.

Accurate dosimetry is particularly difficult for low- to medium-energy x-rays as various interaction processes with different dependences on material properties determine the dose distribution in tissue and radiation detectors. Monoenergetic x-rays from synchrotron radiation offer the unique opportunity to study the dose response variation with photon energy of radiation detectors without the compounding effect of the spectral distribution of x-rays from conventional sources. The variation of dose response with photon energies between 10 and 99.6 keV was studied for two TLD materials (LiF:Mg,Ti and LiF:Mg,Cu,P), MOSFET semiconductors, radiographic and radiochromic film. The dose response at synchrotron radiation energies was compared with the one for several superficial/orthovoltage radiation qualities (HVL 1.4 mm Al to 4 mm Cu) and megavoltage photons from a medical linear accelerator. A calibrated parallel plate ionization chamber was taken as the reference dosimeter. The variation of response with x-ray energy was modelled using a two-component model that allows determination of the energy for maximum response as well as its magnitude. MOSFET detectors and the radiographic film were found to overrespond to low-energy x-rays by up to a factor of 7 and 12 respectively, while the radiochromic film underestimated the dose by approximately a factor of 2 at 24 keV. The TLDs showed a slight overresponse with LiF:Mg, Cu, P demonstrating better tissue equivalence than LiF:Mg, Ti (maximum deviation from water less than 25%). The results of the present study demonstrate the usefulness of monoenergetic photons for the study of the energy response of radiation detectors. The variations in energy response observed for the MOSFET detectors and GAF chromic film emphasize the need for a correction for individual dosimeters if accurate dosimetry of low- to medium-energy x-rays is attempted.

Biophysical Phenomena↗
PubMed1998

Differential gene expression in response to adjunctive recombinant human interleukin-2 immunotherapy in multidrug-resistant tuberculosis patients.

Administration of low-dose recombinant human interleukin 2 (rhuIL-2) in combination with multidrug chemotherapy to patients with multidrug-resistant tuberculosis (MDR TB) induces measurable changes in in vitro immune response parameters which are associated with changes in the clinical and bacteriologic status of the patients. To determine the molecular basis of these changes, we have used semiquantitative reverse transcriptase-initiated PCR (RT-PCR) and differential display technology. During rhuIL-2 treatment of MDR TB patients, decreased levels of gamma interferon (IFN-gamma) mRNA in peripheral blood mononuclear cells (PBMC) relative to baseline levels were observed. However, at the site of a delayed-type hypersensitivity (DTH) response to purified protein derivative of tuberculin (PPD), the expression of cellular IFN-gamma and IL-2 mRNAs was increased during rhuIL-2 therapy. Levels of other cytokine mRNAs were not significantly affected by rhuIL-2 administration. Using differential-display RT-PCR, we identified several genes expressed at the DTH skin test site which were up- or down-regulated during rhuIL-2 treatment. Cytochrome oxidase type I mRNA was increased in response to rhuIL-2 therapy relative to baseline levels, as was heterogeneous nuclear ribonuclear protein G mRNA. CD63, clathrin heavy chain, and beta-adaptin mRNAs, all of which encode proteins associated with the endocytic vacuolar pathway of cells, were also differentially regulated by rhuIL-2 administration. The differential effects of IL-2 were confirmed in vitro by using PBMC obtained from PPD-positive individuals stimulated with Mycobacterium tuberculosis and IL-2. The differential expression of genes may provide a surrogate marker for leukocyte activation at a mycobacterial antigen-specific response site and for the development of an enhanced antimicrobial response which may result in improved outcomes in MDR TB patients.

Adult↗
PubMed1998

Hydroceles identified prenatally: common physiologic phenomenon?

Though the reported frequency of infant hydrocele has varied, the frequency of hydrocele in the fetus has not been studied. Our purpose was to determine the frequency of fetal hydrocele in the third trimester and subsequent outcome. Of the 123 fetuses studied, 19 fetuses had hydroceles. Of these, 14 babies were normal at follow-up, one baby had a persistent hydrocele, and four babies were lost to follow-up. Our study suggests that hydrocele is a relatively common finding in the third trimester in utero. Moreover, it suggests that parents can be reassured that, in the absence of other abnormalities, a hydrocele is usually a physiologic finding which resolves spontaneously.

Female↗
PubMed1998

HHV8 status in Kaposi's sarcoma associated with multiple myeloma.

Kaposi's sarcoma in its sporadic or HIV-related form is due to a gamma herpesvirus, the human herpes virus 8 (HHV8). No data have been published on the potential role of the HHV8 in Kaposi's sarcoma occurring in multiple myeloma patients. A case is reported of a patient in whom four serum samples taken between the diagnosis of multiple myeloma and the occurrence of a Kaposi's sarcoma one year later tested positive for antibody to the HHV8. Similar findings have been reported in patients with other types of Kaposi's sarcoma. PCR studies for HHV8 DNA were positive on a Kaposi's sarcoma biopsy but negative on a bone biopsy, militating against a role for the HHV8 in the genesis of multiple myeloma.

Aged↗
PubMed1997

The metabolic and immunologic effects of short-term thalidomide treatment of patients infected with the human immunodeficiency virus.

Thalidomide therapy has been shown to cause increases in body weight in patients with HIV and tuberculosis infections. To examine the nature of this weight gain and its immunological correlates in patients with HIV infection, we studied a cohort of 13 patients with minimally symptomatic HIV disease. Patients were admitted to the Rockefeller University General Clinical Research Center and maintained on strict isocaloric diets to achieve weight stabilization before a 14-day course of thalidomide treatment. Mean percentage weight increase was 3.6% on day 14 of thalidomide therapy (p = 0.002). Weight gain was associated with a reduction in mean daily urinary nitrogen excretion of 1.81 g (p = 0.017). Resting energy expenditure was unaffected by thalidomide. Body composition analysis suggested some extracellular fluid retention in the first week of thalidomide therapy, followed by an expansion of lean tissue mass during the second week. Remarkably, total lymphocyte counts and CD8+ T cell counts increased following treatment with the drug from 1578 +/- 185 to 2617 +/- 265 and from 938 +/- 146 to 1369 +/- 231, respectively. Modest increases in CD4+ T cell counts were also observed. Levels of circulating TNF-alpha were not elevated at baseline. A significant increase in mean plasma levels of soluble interleukin 2 receptor (sIL-2r), from 1918 +/- 250 to 3816 +/- 411 pg/ml (p = 0.0022), occurred in response to thalidomide, suggesting drug-induced immunological activation. In conclusion, thalidomide treatment of patients with HIV infection caused weight gain and lean tissue anabolism, even when caloric intake was kept constant. The nature of the association between thalidomide treatment-induced metabolic changes and the immunomodulatory effects of the drug has yet to be elucidated.

Body Composition↗
PubMed1997

Thalidomide and thalidomide analogs reduce HIV type 1 replication in human macrophages in vitro.

Thalidomide is currently being evaluated for efficacy in alleviating some manifestations of HIV-1 infection. To determine whether thalidomide has any direct effects on HIV-1 infection, we investigated the effect of thalidomide and also of three structural analogs of thalidomide on HIV-1 replication in vitro in human monocyte-derived macrophages. The thalidomide analogs were previously shown to inhibit TNF-alpha production in vitro at much lower concentrations than thalidomide. In HIV-1-infected macrophages treated with thalidomide or thalidomide analogs, viral replication was reduced by 60 to 80% as determined by measuring viral RT activity in the culture supernatants. In all experiments the analogs inhibited HIV-1 replication more efficiently than did thalidomide. The drugs also reduced HIV-1 gag mRNA expression. Furthermore, the drugs caused a decrease in NF-kappaB-binding activity in nuclear extracts of HIV-1-infected macrophages. The role of NF-kappaB in the drug-induced inhibition of HIV-1 replication was confirmed using an NF-kappaB-defective mutant virus to infect macrophages.

Anti-HIV Agents↗
PubMed1997

Foot-and-mouth disease virus-infected but not vaccinated cattle develop antibodies against recombinant 3AB1 nonstructural protein.

Foot-and-mouth disease (FMD) vaccines induce antibodies against structural and some nonstructural proteins present in vaccine preparations. To differentiate between FMDV-infected and vaccinated animals, we developed immunochemical assays capable of detecting antibodies against a FMDV nonstructural protein. Recombinant nonstructural 3AB1 protein was expressed in E.coli and in insect cells and used to detect anti-3AB1 antibodies. ELISA and Western blot analysis showed that sera from cattle infected with FMDV reacted with recombinant 3AB1 protein whereas sera from cattle which had been vaccinated against FMDV, mock-infected, or infected with different bovine viruses did not recognize the 3AB1 protein. In contrast, anti-virus infection associated antigen (VIAA) antibodies were present in both FMDV-infected and vaccinated animals. Detection of anti-3AB1 antibodies in sera of experimentally infected cattle obtained between 7 and 560 days postinfection indicated that immunological tests based on the detection of recombinant 3AB1 protein could be used for the diagnosis of FMDV infection.

Animals↗
PubMed1997

Effect of cytokine modulation by thalidomide on the granulomatous response in murine tuberculosis.

SETTING: Experimental murine tuberculosis. OBJECTIVE: To evaluate the effect of cytokine modulation by thalidomide on the progression of the lung granulomatous response following aerosol tuberculosis infection in mice. DESIGN: Mice infected by the respiratory route with 200-500 viable Mycobacterium tuberculosis Erdman were treated with daily subcutaneous injections of thalidomide (30 mg/kg) or saline for 4 weeks. The bacillary load, granulomatous response and cytokine production in the lungs were evaluated. RESULTS: Aerosol M. tuberculosis infection resulted in a progressive granulomatous response in the lungs. At 28 days after infection, large granulomata with central necrosis and no apoptosis were observed. The infection induced high serum and lung cytokine mRNA levels. Thalidomide treatment resulted in a significant reduction in tumor necrosis factor-alpha, interleukin 6 (IL-6) and IL-10 protein levels (blood) and mRNA expression (lungs). IL-12 and interferon-gamma were unaffected. The lungs of thalidomide-treated mice had smaller granulomata with apoptotic cells and no necrosis. Thalidomide treatment did not change the bacillary load. CONCLUSION: Thalidomide immunomodulation reduces inflammatory cytokines and concomitant lung pathology following acute aerosol M. tuberculosis infection, without increasing the bacillary load.

Acute Disease↗
PubMed1997

rhuIL-2 adjunctive therapy in multidrug resistant tuberculosis: a comparison of two treatment regimens and placebo.

SETTING: Low-dose recombinant human interleukin 2 (rhuIL-2) adjunctive immunotherapy in multidrug resistant tuberculosis (MDR-TB) patients. OBJECTIVE: Evaluation of the effects of daily versus pulse-administered rhuIL-2 compared to placebo. DESIGN: MDR-TB patients on best available antituberculous chemotherapy received rhuIL-2 for 30 consecutive days (daily therapy), or for 5 days followed by a 9-day 'rest', for three cycles (pulse therapy). Placebo control patients received diluent. The cumulative total dose of rhuIL-2 given to each patient in either rhuIL-2 treatment group was the same. Patient immunologic, microbiologic, and radiologic responses were compared. RESULTS: The three treatment schedules induced different results. Immune activation was documented in patients receiving daily rhuIL-2 therapy. Numbers of CD25+ and CD56+ cells in the peripheral blood were increased in these patients, but not in patients receiving pulse rhuIL-2 or placebo. In addition, 5/8 (62%) patients receiving daily rhuIL-2 demonstrated reduced or cleared sputum bacterial load while only 2/7 (28%) pulse rhuIL-2 treated and 2/8 (25%) controls showed bacillary clearance. Chest radiographs of 7/12 (58%) patients receiving daily rhuIL-2 indicated significant improvement over 6 weeks. Only 2/9 (22%) pulse rhuIL-2-treated patients and 5/12(42%) placebo controls showed radiologic improvement. CONCLUSION: Daily low dose rhuIL-2 adjunctive treatment stimulates immune activation and may enhance the antimicrobial response in MDR-TB.

Adult↗
PubMed1997

Nucleotide sequence of the P1 region of foot-and-mouth disease virus strain O1 Caseros.

It has been shown that variation of antigenic site I in VP1 of foot-and-mouth disease virus (FMDV) plays an important role in the antigenic diversification of this virus. However, the O1 Campos strain is able to efficiently cross-protect cattle against the O1 Caseros strain, despite having a different sequence in the site I. In this paper we report and compare the P1 coding region for the capsid proteins of FMDV O1 Caseros and O1 Campos. The deduced amino acid sequence showed a total of 31 amino acid differences. Eight of them are located in surface-exposed loops that have been implicated in antigenic sites. This study should help to identify additional sites to be considered in the development of a new generation of FMDV vaccines.

Amino Acid Sequence↗
PubMed1997

Aging or disease? Cardiovascular reactivity in Finnish men over the middle years.

Cardiovascular responses to psychological events may mediate the influence of stress on cardiovascular disease. In this study the authors asked whether cardiovascular responses to psychological challenge changed with age and whether such changes were intrinsic to aging or could be attributed to the influence of disease and medications. Cardiovascular reactivity to mental challenge was examined in 902 men ranging in age from 46 to 64 years who participated in the Kuopio Ischemic Heart Disease Risk Factor Study. A battery of 4 tasks was used to induce cardiovascular responses. Current disease status, age, and medication use were entered into hierarchical regression analyses to assess their relation with measures of cardiovascular reactivity. Age and hypertension contributed independent, approximately equal, but small amounts of variance in the cardiac and vascular reactivity indexes. Medications also influenced reactivity independently of age and disease. Performance on the tasks was more consistently altered by age than by disease or medication. Cardiac and vascular reactivity increased with increasing age and the presence of hypertension. The authors conclude that both age and disease state must be considered when examining cardiovascular reactivity as a risk factor for disease.

Aging↗
PubMed1997

Adverse reactions to thalidomide in patients infected with human immunodeficiency virus.

Thalidomide is emerging as a useful agent in the management of several complications of disease due to human immunodeficiency virus (HIV). We conducted three prospective studies of 56 HIV-infected patients who were treated with thalidomide for 14-21 days; 24 (43%) of these patients discontinued therapy owing to adverse reactions. Cutaneous and/or febrile reactions were the most frequent toxicities, arising in 20 (36%) of the patients. These reactions occurred after a mean interval (+/-SD) of 10 +/- 3 days and were associated with significantly lower CD4 T lymphocyte counts in reactors than in nonreactors (median count, 52.5/mm3 vs. 242 cells/mm3, respectively; P = .009). Four of four rechallenged patients experienced accelerated hypersensitivity; hypotension occurred in one case. Although sedation was an almost universal side effect among the patients, it was moderate or severe in only seven (13%); constipation was moderate or severe in five (9%) of the patients. Severe neuropathic symptoms and mood changes were each noted in two (4%) of the 56 patients. We conclude that the increasing use of thalidomide to treat HIV-infected patients must be accompanied by recognition of the drug's increased potential for toxicity in this population.

Adult↗
PubMed1997

Use of acupuncture by American physicians.

OBJECTIVES: Little is known about the characteristics of American physicians who currently practice acupuncture. We asked: (1) Do the demographics of physicians practicing acupuncture differ from the general physician population? (2) Do these physicians use or endorse other alternative therapies? (3) For which conditions is acupuncture most commonly used? (4) For which conditions is acupuncture perceived to be most efficacious? DESIGN: Mailed survey of physicians who incorporate acupuncture into their practice. PARTICIPANTS: Membership of the American Academy of Medical Acupuncture (AAMA). OUTCOME MEASURES: Demographic information regarding physicians and practice characteristics; specific illnesses treated, and perceived efficacy; use of other complementary modalities; personal reasons for practicing acupuncture. RESULTS: Compared with national data, respondents were more likely to be nonspecialists, in private practice, and age 35 to 54. There was an equal proportion of men and women. Most had been doing acupuncture for < 5 years; most use it on < 25% of their patients. Endorsement or use of other complementary methods (spinal manipulation, herbal medicine, supplements, homeopathy) was common. Acupuncture was more commonly used for pain conditions than general medical problems or addiction management. Reasons for use included: efficacy of the technique, an alternative in cases of inadequacy of standard medical approach, and a multidimensional approach to health care. CONCLUSIONS: Physicians surveyed in this study who incorporate acupuncture into their practice do so mainly to treat pain problems. They are more likely to be in the 35 to 54 age group, nonspecialists, and in private practice when compared with national averages. These physicians are also more likely to use or endorse other complementary modalities.

Acupuncture Therapy↗
PubMed1997

Juvenile chronic arthritis: diagnosis and management of tibio-talar and sub-talar disease.

The aim of this study was to compare clinical evaluation of the site of hindfoot synovitis with contrast-enhanced magnetic resonance imaging (MRI) findings in children with juvenile chronic arthritis (JCA), and to evaluate the efficacy of selective guided intra-articular steroid injections. Thirteen symptomatic ankles of 11 consecutive JCA patients were examined clinically and with contrast-enhanced MRI. Pannus was demonstrated on MRI in both tibio-talar and sub-talar joints in 10 ankles, in the tibio-talar joint only in one ankle and in neither joint in two ankles. Correlation of clinical and MRI findings was good for the tibio-talar joint with concordance in 11/13 cases. Correlation was poor for the sub-talar joints. Of the 10 sub-talar joints shown to have pannus on MRI, only two were thought to have had definite clinical evidence of synovitis. Guided intra-articular steroid injection resulted in at least 6 months remission in 6/9 ankles compared with 1/10 ankles which had had previous unguided injections. We therefore recommend the use of image guidance for intra-articular triamcinolone hexacetonide injection in children with hindfoot synovitis.

Adolescent↗
PubMed1997

Perforin, a cytotoxic molecule which mediates cell necrosis, is not required for the early control of mycobacterial infection in mice.

Host defense against mycobacterial infection requires the participation of monocytes and T cells. Both CD4+ and CD8+ T cells have been shown to be important in resistance to mycobacterial infection in vivo. The main contribution of CD4+ T cells to the protective antituberculosis response involves the production of Th1-type cytokines, including interleukin-2 (IL-2) and gamma interferon (IFN-gamma). CD8+ T cells have been considered to be responsible primarily for cytotoxicity mediated by toxic molecules, including perforin. CD8+ T cells may also elaborate Th1-type cytokines, such as IFN-gamma, in response to the infection. To elucidate the contribution of perforin-mediated target cell death to the control of mycobacterial infection in vivo, mice with a disruption in the perforin gene (P-/-) were infected with Mycobacterium bovis BCG or M. tuberculosis Erdman for 5 and 13 weeks, respectively. At 1, 3, 5, and 13 weeks postinfection, the number of viable mycobacteria in the lungs, spleens, and livers of mice were determined by CFU assay. The infected tissues were examined histologically, and cytokine mRNA levels in the spleens of these mice were determined. Similar studies were carried out in Fas receptor-defective (CBA/lpr(cg)) mice to evaluate the contribution of this alternative cytotoxic pathway to the control of mycobacterial infection. The absence of either perforin gene function or Fas receptor gene function did not modify the course of experimental mycobacterial infection in these mice. In addition, both P-/- and Fas receptor-defective mice appeared to have a compensatory activation of cytokine genes, even in the absence of the experimental infection. P-/- mice had a mean 3.4- to 5-fold increase in mRNA levels for IL-10, IL-12p35, IL-6, and IFN-gamma. Similarly, Fas receptor-defective mice had a mean 3- to 3.6-fold increase in mRNA levels for IFN-gamma, IL-12p35, and IL-10. Our results indicate that both perforin-mediated cytotoxicity and Fas-mediated cytotoxicity do not appear to be necessary for the early control of mycobacterial infection in vivo.

Animals↗