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Biomedical subjects

R Altman

Publications and source records attributed to R Altman.

At least 73 records · Page 4Linked to original sources
PubMed1988

Why single daily dose of aspirin may not prevent platelet aggregation.

The effect of different doses of aspirin on the synergistic activity of sodium arachidonate plus platelet activating factor (paf) ADP or collagen in platelet aggregation was studied in human volunteers. Aggregation studies in platelet rich plasma (PRP) showed that aspirinated platelets, unresponsive to arachidonate, when stirred with threshold concentrations of paf, ADP or collagen, reacted differently according to the dose of aspirin and the time elapsed since ingestion. After a single or daily 50 mg dose for 7-10 days independent of elapsed time until blood withdrawal, a complete synergistic activity was obtained. In PRP samples obtained 24 hours after the last aspirin intake, a complete synergistic aggregation was achieved after a single dose or after 7-10 days of 500 mg aspirin ingestion; synergistic effect did not appear when blood was drawn 2.5 hours after intake. The thromboxane B2 concentrations were very low in all samples after PRP stimulation with sodium arachidonate or paf or both. As rationale is that platelet activation in vivo occurs in response to several stimuli, the therapeutic implications of our results is that aspirin may not prevent the agonist potentiation effect when low dose or daily high dose (500mg) are administrated. This may explain the erratic results of most aspirin trials in which this drug was used to suppress platelet function.

Adult↗
PubMed1988

Segregation of lymphocyte low-molecular-weight DNA and antinuclear-antibodies in a family with systemic lupus erythematosus in first cousins.

All patients with systemic lupus erythematosus (SLE) demonstrated two classes of newly synthesized DNA in sucrose density gradients of PHA (phytohemagglutinin)-stimulated lymphocytes: a large-molecular-weight fraction that comigrates with control DNA and an excess low-molecular-weight DNA (LMW-DNA) fraction not found in control lymphocytes. Excess LMW-DNA was independent of disease activity or drug therapy. LMW-DNA and serologic abnormalities were studied in a four-generation family in which two first cousins had SLE. Excess LMW-DNA was found in the cousins with SLE, sibling parents of the SLE patients, a common grandparent, four of nine siblings of one patient, and five of seven at risk children. Both males and females had excess LMW-DNA. Male-male transmission was observed. The expression of excess LMW-DNA in stimulated lymphocytes is inherited as an autosomal dominant genetic trait in this family. All unaffected adult family members with the marker had positive antinuclear antibodies (ANAs) except the grandmother. However, none of the five children with excess LMW-DNA showed positive ANAs. Excess LMW-DNA precedes the appearance of ANAs when found in children of adults with excess LMW-DNA, and may be a predisposing factor in the development of the immunologic responses of systemic lupus erythematosus.

Antibodies, Antinuclear↗
PubMed1988

Diltiazem potentiates the inhibitory effect of aspirin on platelet aggregation.

Platelet aggregation in vivo occurs through the combined effects of many agonists. Aspirin inhibits platelet aggregation but its antiaggregate effects can be overcome by the synergistic action of sodium arachidonate (AA) plus platelet activating factor (PAF). We tested the effect of a calcium entry-blocking agent, diltiazem, on AA-PAF-induced platelet aggregation in platelet-rich plasma from seven healthy volunteers. The studies were done before and after aspirin (100 mg/day) administration for 7 to 10 days. Stimulation of platelet was done in vitro by AA, PAF, or both. Before aspirin treatment, diltiazem (2 micrograms/ml) added in vitro to the platelet-rich plasma inhibited platelet aggregation induced by AA (0.75 mmol/L) by 50%. When PAF was used the inhibition of aggregation was obtained at a lower concentration of diltiazem (0.4 to 1 microgram/ml). After aspirin treatment, AA-induced aggregation was inhibited, and PAF alone (30 nmol/L) produced a first-wave aggregation followed by complete disaggregation. When AA and PAF were added together a full aggregation of postaspirin treatment platelets was obtained. Diltiazem added in vitro at the clinically attainable concentration of 0.1 microgram/ml produced a complete inhibition of this AA-PAF synergism on platelet aggregation. These results suggest that administration of a combination of low-dose aspirin and diltiazem may be of greater benefit than aspirin alone for prophylaxis of cardiovascular diseases where platelets are involved in the pathogenesis.

Arachidonic Acids↗
PubMed1988

Human T-cell leukemia virus types I and II exhibit different DNase I protection patterns.

Human T-cell leukemia virus types I (HTLV-I) and II (HTLV-II) are human retroviruses which normally infect T-lymphoid cells. HTLV-I infection is associated with adult T-cell leukemia-lymphoma, and HTLV-II is associated with an indolent form of hairy-cell leukemia. To identify potential transcriptional regulatory elements of these two related human retroviruses, we performed DNase I footprinting of both the HTLV-I and HTLV-II long terminal repeats (LTRs) by using extracts prepared from uninfected T cells, HTLV-I and HTLV-II transformed T cells, and HeLa cells. Five regions of the HTLV-I LTR and three regions of the HTLV-II LTR showed protection by DNase I footprinting. All three of the 21-base-pair repeats previously shown to be important in HTLV transcriptional regulation were protected in the HTLV-I LTR, whereas only one of these repeats was protected in the HTLV-II LTR. Several regions exhibited altered protection in extracts prepared from lymphoid cells as compared with HeLa cells, but there were minimal differences in the protection patterns between HTLV-infected and uninfected lymphoid extracts. A number of HTLV-I and HTLV-II LTR fragments which contained regions showing protection in DNase I footprinting were able to function as inducible enhancer elements in transient CAT gene expression assays in the presence of the HTLV-II tat protein. The alterations in the pattern of the cellular proteins which bind to the HTLV-I and HTLV-II LTRs may in part be responsible for differences in the transcriptional regulation of these two related viruses.

Base Sequence↗
PubMed1988

Adenovirus transcriptional regulatory regions are conserved in mammalian cells and Saccharomyces cerevisiae.

The adenovirus early region 3 (E3) promoter is an early viral promoter which is strongly induced by the adenovirus transactivator protein E1A. DNase I footprinting with HeLa cell extracts has identified four factor-binding domains which appear to be involved in basal and E1A-induced transcriptional regulation. These binding domains may bind TATA region-binding factors (site I), the CREB/ATF protein (site II), the AP-1 protein (site III), and nuclear factor I/CTF (site IV). Recently, it has been shown that the DNA-binding domain of transcription factor AP-1 has homology with the yeast transcription factor GCN4 and that the yeast transactivator protein GAL4 is able to stimulate transcription in HeLa cells from promoters containing GAL4-binding sites. These results suggest an evolutionary conservation of both transcription factors and the mechanisms responsible for transcriptional activation in Saccharomyces cerevisiae and higher eucaryotic organisms. To determine whether similar patterns of transcriptional regulation were seen with the E3 promoter in HeLa and yeast cells, the E3 promoter fused to the chloramphenicol acetyltransferase (cat) gene was cloned into a high-copy-number plasmid and stably introduced into yeast cells. S1 analysis revealed that similar E3 promoter mRNA start sites were found in yeast and HeLa cells. DNase I footprinting with partially purified yeast extracts revealed that four regions of the E3 promoter were protected. Several of these regions were similar to binding sites determined by using HeLa cell extracts. Oligonucleotide mutagenesis of these binding domains indicated their importance in the transcriptional regulation of the E3 promoter in yeast cells. These results suggest that similar cellular transcription factor-binding sites may be involved in the regulation of promoters in both yeast and mammalian cells.

Adenoviridae↗
PubMed1988

Correlates of amylase and lipase levels in chronic dialysis patients.

Serum lipase and amylase isoenzymes were measured in 44 chronic hemodialysis patients, 16 CAPD patients and 22 normal volunteers. The enzyme levels of the two patient groups were similar and were significantly higher than those of the volunteer group. The ratio of pancreatic to salivary amylase was similar in all three groups. Anuric patients in both dialysis groups had higher enzyme levels than those with residual urine output. Linear regression analysis was done to attempt to identify factors which were good predictors of enzyme levels. Although no such factors were found in the hemodialysis group, in the CAPD group there were significant correlations between the degree of azotemia and the magnitude of enzyme elevations. Further studies are needed to determine the relative importance of oversecretion and underexcretion in the genesis of the amylase and lipase elevations found in dialysis patients.

Amylases↗
PubMed1987

The effect of a school entry law on mumps activity in a school district.

Sixty-three cases of clinical mumps occurring in a New Jersey school district presented an opportunity to determine compliance with the state's 1978 mumps "new entrants" school immunization law, investigate the effect of the law on the pattern of the outbreak, estimate the efficacy of mumps vaccine, and quantitate the economic impact of the outbreak. Only students in kindergarten (K) through grade 5 would have been affected by the immunization law. Students in the sixth grade were nearly seven times more likely to develop mumps than students in grades K through 5. The observed differences between the sixth graders and those in grades K through 5 most likely reflect the fact that sixth graders were not covered by the school law. Vaccine efficacy was estimated to be 91% (95% confidence interval = 77% to 93%). The total direct cost of the outbreak was $10,937 (clinic costs plus total cost to households). This outbreak demonstrates the significant impact of appropriate school vaccination laws on limiting the morbidity and economic and social costs of mumps.

Adolescent↗
PubMed1987

The effects of long- and short-term maternal caffeine ingestion on human fetal breathing and body movements in term gestations.

The possible effects of long- and short-term maternal ingestion of caffeine during normal human pregnancy on the breathing and body movements of third-trimester fetuses were studied in 14 patients, selected by a dietary questionnaire, and divided into two equal groups: high consumers (greater than 500 mg/day) (group 1) and low consumers (less than 250 mg/day) (group 2). All mothers followed a standard study protocol and underwent overnight fasting; studies began with a 30-minute control period, followed by oral administration of 200 mg caffeine, and a 180-minute subsequent observation period with continued maternal fasting. Blood samples for glucose and caffeine were obtained every 30 minutes and continuous recording of fetal breathing and body movements were entered on a microcomputer for off-line analysis. The two groups were similar for all obstetric outcome features. Plasma glucose levels were similar and constant in both groups whereas caffeine levels increased significantly at 60 minutes after administration; mean plasma caffeine levels were significantly higher in group 1 than in group 2 at all intervals. Fetal breathing rates and body movement incidences were similar in both groups before and after caffeine administration. Fetal breathing movement incidence decreased significantly in group 2 but was sustained at baseline levels in group 1 throughout the study. High long-term ingestion of caffeine during pregnancy is associated with higher maternal plasma caffeine levels and fetal breathing activity when compared with low caffeine ingestion. Short-term administration of 200 mg caffeine does not appear to have a significant physiologic impact on these activities.

Caffeine↗
PubMed1987

Changing cigarette habits and bladder cancer risk: a case-control study.

With the use of data from the 8,764 subjects in the National Bladder Cancer Study, the separate contribution of various aspects of a person's cigarette smoking history to his increased risk of bladder cancer was estimated. These estimates have not been previously available, owing to the smaller sizes of earlier studies. Our data indicated that people who have only smoked unfiltered cigarettes have higher risks than those who have only smoked filtered cigarettes but that people who have switched from unfiltered to filtered have experienced no reduction in risk. Our data also indicated that smoking cessation substantially reduced the risk. The former smoker appeared to benefit both because he stopped adding to the burden of irreversible damage and because he ceased being exposed to some reversible hazard. Thus the former smoker had a lower risk than the current smoker even though they had smoked the same number of cigarettes daily for the same number of years, but the former smoker's risk remained higher than the risk of a person who never smoked. Our data suggest that one-half of the bladder cancer occurring among men in the United States and one-third of that among women is caused by cigarette smoking.

Adult↗
PubMed1987

Occupation and lung cancer risk among New Jersey white males.

The association of occupation with lung cancer risk was examined in a case-control study conducted in six areas of New Jersey. The study included 763 white males with incident histologically confirmed primary cancer of the trachea, bronchus, and lung and 900 general population white male controls selected from driver's license and death certificate files. Altogether, 27 employment categories had a smoking-adjusted odds ratio (OR) of 1.3 or greater; five of these with significantly high OR contributed to an occupational population attributable risk of 13%. Masons and tilesetters; janitors and cleaners; printing workers; and trucking service, warehousing, and storage workers had significantly high risks overall and for longer durations of employment. Shipbuilding workers had significantly high risk overall and for short duration of employment. Although the excess risk for all shipbuilding workers was primarily among those with reported exposure to asbestos, the risk was also high among welders, burners, sheet metal workers, and boilermakers with no reported asbestos exposure.

Asbestos↗
PubMed1987

Bladder cancer, drinking water source, and tap water consumption: a case-control study.

Data from a population-based case-control interview study of incident bladder cancer in 10 areas of the United States were used to estimate relative risks among white men (2,116 cases, 3,892 controls) and women (689 cases, 1,366 controls) according to beverage intake level and type of water source. Individual year-by-year profiles of water source and treatment were developed by linking lifetime residential information with historical water utility data from an ancillary survey. Risk of bladder cancer increased with intake level of beverages made with tap water. The odds ratio (OR) for the highest vs. lowest quintile of tap water consumption was 1.43 [95% confidence interval (CI) = 1.23, 1.67; chi 2 for trend = 26.3, P less than .001]. The risk gradient with intake was restricted to persons with at least a 40-year exposure to chlorinated surface water and was not found among long-term users of nonchlorinated ground water. The ORs for the highest vs. lowest quintiles of tap water intake were 1.7 and 2.0, respectively, among subjects with 40-59 and greater than or equal to 60 years' exposure. Duration of exposure to chlorinated surface water was associated with bladder cancer risk among women and nonsmokers of both sexes. Among non-smoking respondents with tap water consumption above the population median, the OR increased with exposure duration to a level of 3.1 (CI = 1.3, 7.3; chi 2 for trend = 6.3, P = .01) for greater than or equal to 60 years of residence at places served by chlorinated surface water (vs. non-chlorinated ground water users). These results extend findings of earlier epidemiologic studies and are consistent with environmental chemistry and toxicologic data demonstrating the presence of genotoxic by-products of chlorine disinfection in treated surface waters.

Chlorine↗
PubMed1987

Animal model of acute pulmonary thromboembolism treated by local recirculation of streptokinase through the lung.

Massive acute pulmonary thromboembolism has a high mortality within the first few hours. Surgical intervention can remove only larger thrombi. Systemic fibrinolytic administration requires many hours for adequate treatment. We describe an anesthetized dog model of acute, massive, disseminated pulmonary thromboembolism achieved by injection of 1.7 ml/kg of 1-hour-old thrombi directly into the pulmonary artery. The emboli were lysed with 50,000 IU streptokinase recirculated for 20 minutes through the isolated pulmonary vascular bed by use of a roller pump while the systemic bed was supported by conventional cardiopulmonary bypass. On reestablishing natural circulation all hemodynamic parameters returned to preembolism values. Success of lysis was histologically confirmed. Perfusion of the pulmonary vascular bed without inclusion of streptokinase in the perfusate worsened the hemodynamic state of the animals compared with an untreated nonperfused control group.

Acute Disease↗
PubMed1986

Synergistic actions of PAF-acether and sodium arachidonate in human platelet aggregation. 1. Studies in normal human platelet rich plasma.

The effect of sodium arachidonate and paf-acether in the activation of human platelet was studied. Concentrations of paf-acether which induced a reversible aggregation in normal human platelet rich plasma (0.029-0.0029 microM) and subthreshold concentrations of sodium arachidonate (0.25-0.35 mM), produced full aggregation when added together. Pre-exposition of platelets to paf-acether that renders them insensitive to paf-acether supresed the synergism. With full aggregation a markedly increase of thromboxane synthesis was detected by RIA. In vitro addition of aspirin (200 micrograms/ml) or indomethacin (12 microM) prevented aggregation and thromboxane formation by the joint action of sodium arachidonate plus paf-acether. Specific inhibition of 12-lipoxygenase by esculetin (10 microM) did not affect the synergistic action of paf-ace-ther and sodium arachidonate. These findings suggest that synergism between both agonists is mediated by active derivatives of arachidonic acid via cyclooxygenase.

Adult↗
PubMed1986

Synergistic actions of paf-acether and sodium arachidonate in human platelet aggregation. 2. Unexpected results after aspirin intake.

The effect of sodium arachidonate and paf-acether on the activation of human platelet rich plasma from volunteers 2.30 to 36 hours after 500 mg of aspirin intake was studied. Concentrations of paf-acether which induce a reversible aggregation in platelet rich plasma (PRP) (0.29-0.029 microM) and concentrations of sodium arachidonate (AA) which don't produce aggregation (0.75-1mM) on the PRP from these volunteers, induced full aggregation when added together. But no cooperation activity was achieved in the 2.30 hours sample. Contrarily to the in vitro studies performed in human normal PRP, ASA (200 micrograms/ml) or indomethacin(12 microM) added to the PRP were unable to suppress the cooperative aggregation effect; neither did apyrase (12U/ml), esculetin (10 microM) or nordihydroguaiaretic acid (0.1 microM) have any action on the activated platelets but the synergistic action is completely suppressed by BW 755C (0.1 mM). TXB2 formation is very low in all these activated samples and insufficient to cause platelet aggregation. These results suggest 2 behaviors of platelets: synergistic activity of paf-acether and exogenous AA in vitro on normal human PRP is mediated mainly through active metabolites of AA formed via cyclooxygenase, as was previously published. When cyclooxygenase is inhibited in vivo by administration of 500 mg ASA, the cooperative effect of agonists is still present but the active aggregating product(s) is probably, formed through a pathway different of that of the cyclooxygenase or lypoxygenase.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1986

International experiences with diclofenac in osteoarthritis.

Despite a wide range of study designs, a multiplicity of international trials of diclofenac in osteoarthritis have disclosed similar results. These include double-blind comparisons with indomethacin, aspirin, naproxen, ibuprofen, sulindac, and diflunisal, as well as open trials from European field studies. The results of this review document that diclofenac is as effective as other nonsteroidal anti-inflammatory drugs in the treatment of osteoarthritis.

Aspirin↗
PubMed1986

Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association.

For the purposes of classification, it should be specified whether osteoarthritis (OA) of the knee is of unknown origin (idiopathic, primary) or is related to a known medical condition or event (secondary). Clinical criteria for the classification of idiopathic OA of the knee were developed through a multicenter study group. Comparison diagnoses included rheumatoid arthritis and other painful conditions of the knee, exclusive of referred or para-articular pain. Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop sets of criteria that serve different investigative purposes. In contrast to prior criteria, these proposed criteria utilize classification trees, or algorithms.

Adult↗
PubMed1985

Identification of platelet inhibitor present in the melon (Cucurbitacea cucumis melo).

An active fraction was isolated from an aqueous melon extract (Cucurbitacea cucumis melo) and was shown that it inhibits human platelet aggregation induced by epinephrine, ADP, collagen, thrombin, sodium arachidonate, prostaglandin endoperoxide analogue U-46619 and PAF-acether. Identification of the active substance as adenosine was indicated by TLC which gave identical Rf value compared to adenosine, by the UV spectrum, because the inhibitory effect on platelet aggregation disappeared after the addition of adenosine-deaminase and because the substance under study and adenosine produced the same spectra in the mass spectroscopy.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗