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Biomedical subjects

G Friedman

Publications and source records attributed to G Friedman.

At least 73 records · Page 4Linked to original sources
PubMed1995

Effect of transforming growth factor-beta on lipoprotein lipase in rat mesenchymal heart cell cultures.

The effect of recombinant transforming growth factor-beta 2 (rTGF-beta 2) on lipoprotein lipase (LPL) synthesis was studied in mesenchymal rat heart cell cultures. Addition of rTGF-beta 2 to culture medium containing 20% serum resulted in a time-dependent decrease in LPL activity. With 10 ng/ml a 30% fall occurred after 12 h and only 20% of enzyme activity remained after 24 h with 5 or 10 ng/ml. The minimal effective dose of rTGF-beta 2 was 0.1 ng/ml and a 20% decrease occurred after exposure for 24 h. Antibodies specific to TGF-beta 2 blocked this effect. The decrease in enzymic activity was accompanied by a decrease in enzyme mass and LPL mRNA. Addition of rTGF-beta 2 was effective only during the first week in culture, when enzyme activity was increasing but not after 12 days when the cultures were overconfluent, and the enzyme activity was high.

Animals↗
PubMed1995

Clinical and biological significance of interleukin-10 plasma levels in patients with septic shock.

Interleukin-10 is a potent macrophage-deactivating cytokine that inhibits lipopolysaccharide-induced tumor necrosis factor production. We determined the plasma levels of immunoreactive interleukin-10 in 16 patients with septic shock and in 11 patients with circulatory shock of nonseptic origin. In septic shock, interleukin-10 levels peaked during the first 24 h (median: 48 pg/ml) and decreased progressively till Day 5. In nonseptic shock, interleukin-10 plasma levels also increased during the first 24 h but to a lesser extent (median: 17 pg/ml). In septic shock patients, interleukin-10 plasma levels were positively correlated with tumor necrosis factor (r = 0.8, p = 0.01) and with parameters of shock severity including lactate levels (r = 0.56, p < 0.05) and correlated negatively with blood platelet counts (r = -0.65, p < 0.05). The decreased production of tumor necrosis factor-alpha and interleukin-6 after in vitro incubation of whole blood from septic shock patients with lipopolysaccharide was not influenced by in vitro neutralization of interleukin-10. We conclude that interleukin-10 is produced in patients with circulatory shock of septic and nonseptic origin and that the production of this anti-inflammatory cytokine during septic shock correlates positively with the intensity of the inflammatory response.

Adult↗
PubMed1995

European participation in major intensive care journals.

To evaluate the recent evolution of the European contribution to the international literature in intensive care medicine, we reviewed the source of all original articles and case reports published from 1989 to 1993 in 5 major journals: Critical Care Medicine, Intensive Care Medicine, Chest, The American Review of Respiratory Disease and Circulatory Shock. There was an overall decline in the US contributions and a corresponding increase in the European participations to Chest and the American Review of Respiratory Disease, but not to Critical Care Medicine or Circulatory Shock. The European participation to Intensive Care Medicine remained largely predominant. The evaluation of the contributions of major European countries to these 5 journals revealed a progressive increase in the French, Italian and Spanish contributions, whilst the German contribution remained stable and the UK contributions decreased. The UK contribution, which was the first in 1989, became second in 1993, after France.

Authorship↗
PubMed1995

Dehydroepiandrosterone (DHEA) treatment reverses the impaired immune response of old mice to influenza vaccination and protects from influenza infection.

Dehydroepiandrosterone (DHEA) is a native steroid with an immunomodulating activity. Recently it was suggested that its age-associated decline is related with immunosenescence. To examine whether DHEA administration could effectively reverse the age-associated decline of immunity against influenza vaccine, aged mice were simultaneously vaccinated and treated with DHEA. Reversal of the age-associated decline and a significant constant increase of humoral response was observed in treated mice. Increased resistance to post-vaccination intranasal challenge with live influenza virus was observed in DHEA-treated aged mice. Thus, DHEA treatment overcame the age-related defect in the immunity of old mice against influenza.

Adjuvants, Immunologic↗
PubMed1995

Combined measurements of blood lactate concentrations and gastric intramucosal pH in patients with severe sepsis.

OBJECTIVE: To compare the prognostic value of blood lactate concentrations, gastric intramucosal pH, and their combination in patients with severe sepsis. DESIGN: Prospective, noninterventional study. SETTING: Medical/surgical intensive care unit of a university hospital. PATIENTS: The study included 35 consecutive patients (44 to 82 yrs) with severe sepsis as defined by fever or hypothermia (rectal temperature > 38.3 degrees or < 35.5 degrees C), tachycardia (heart rate > 100 beats/min), tachypnea (respiratory rate > 20 breaths/min) or mechanical ventilation, abnormal white blood cell count (> 10 or < 6 x 10(3) cells/mm3), hypotension (systolic arterial pressure < 90 mm Hg), and evidence of organ dysfunction (oliguria or deterioration of mental status). INTERVENTIONS: Arterial lactate concentration and intramucosal pH were measured at the time of study entry, and at 4 and 24 hrs later. Hemodynamic data and oxygen-derived variables were determined at the time of study entry and 24 hrs later. Arterial blood and balloon saline gases were also determined to obtain the pH gap (arterial pH-intramucosal pH) and the PCO2 gap (intramural PCO2-PaCO2). MEASUREMENTS AND MAIN RESULTS: Of the 35 patients, 19 survived the intensive care unit stay. At the time of study admission, 23 (66%) patients had an increased lactate concentration (> 2 mEq/L) and 26 (74%) had a low intramucosal pH (< 7.32). Initially, there were no significant differences in blood lactate concentrations between nonsurvivors and survivors (3.2 +/- 1.5 vs. 2.8 +/- 2.3 mEq/L). Lactate concentrations remained high in nonsurvivors and progressively decreased in survivors (4 hrs: 3.3 +/- 1.1 mEq/L in nonsurvivors vs. 2.2 +/- 0.9 mEq/L in survivors [p < .01]; 24 hrs: 3.5 +/- 2.0 mEq/L in nonsurvivors vs. 1.9 +/- 1.1 mEq/L in survivors [p < .05]). Intramucosal pH was lower in the nonsurvivors than in the survivors initially (7.19 +/- 0.15 in nonsurvivors vs. 7.30 +/- 0.14 in survivors [p < .05]), at 4 hrs (7.18 +/- 0.17 in nonsurvivors vs. 7.29 +/- 0.13 in survivors [p = .06]), and at 24 hrs (7.19 +/- 0.31 in nonsurvivors vs. 7.30 +/- 0.17 in survivors [p < .05]). Of the 23 patients with initially high lactate concentrations, 12 (60%) of the 20 patients with low intramucosal pH died, as compared with one (33%) of the three patients with normal intramucosal pH (p = .052). Of the 14 patients with persistently high lactate concentrations at 24 hrs, all nine (100%) patients with low intramucosal pH, but only two (40%) of five patients with normal intramucosal pH died (p < .001). No significant relationship was found between lactate or intramucosal pH and oxygen-derived variables. Intramucosal pH correlated better with gastric intramural PCO2 (r2 = .58) than with arterial bicarbonate or base deficit/excess. Intramural PCO2 was a more specific predictor of mortality than intramucosal pH. When compared with patients with normal lactate concentrations, those patients with high lactate concentrations had a higher pH gap (0.22 +/- 0.22 vs. 0.07 +/- 0.13 [p < .01]) and PCO2 gap [21.0 +/- 33.9 vs. 1.8 +/- 9.8 torr [2.79 +/- 4.5 vs. 0.24 +/- 1.34 kPa]; p < .01). CONCLUSIONS: Both lactate concentrations and intramucosal pH represent reliable prognostic indicators in severe sepsis, and their combination improves the prognostic assessment in these patients. Both variables are better prognostic indicators than oxygen-derived variables. Intramural PCO2 appears to be a more specific variable than intramucosal pH, which partially reflects systemic metabolic acidosis. Combined determinations of blood lactate concentrations and intramucosal pH or intramural PCO2 may help to predict outcome from severe sepsis.

APACHE↗
PubMed1995

Early hemodynamic course of septic shock.

OBJECTIVE: To assess the relative contributions of changes in vascular tone and changes in cardiac function to hemodynamic recovery from septic shock. DESIGN: Case series, observational study. SETTING: Multidisciplinary department of intensive care in an academic hospital. PATIENTS: Sixty-seven patients with septic shock (prolonged hypotension, signs of tissue hypoperfusion, signs of sepsis, suspected source of infection, or documented bacteremia). In addition to the antibiotic therapy and the removal of the source of sepsis whenever possible, each patient received intravenous fluids and vasoactive agents (dopamine, norepinephrine, and dobutamine). Each patient was also treated with mechanical ventilation. Twenty-four (36%) patients survived their intensive care unit course. INTERVENTIONS: Hemodynamic measurements were obtained at baseline, after initial resuscitation (as soon as apparent hemodynamic stability was achieved), after 12 hrs, and after 24 hrs. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in hemodynamic or oxygen-derived variables at baseline between the survivors and the nonsurvivors. During the initial resuscitation period, only the survivors demonstrated a significant increase in mean arterial pressure (from 69 +/- 17 to 82 +/- 18 mm Hg; p < .02) and left ventricular stroke work index (from 25.2 +/- 11.0 to 35.5 +/- 19.4 g.m/m2; p < .05). The increases in cardiac index and systemic vascular resistance were greater in the survivors than in the non-survivors, but the differences did not reach statistical significance. Study of the left ventricular function curves indicated an improvement of left ventricular function in the survivors but not in the nonsurvivors. CONCLUSION: An early improvement in left ventricular function is a hallmark of the survivors from septic shock.

Adolescent↗
PubMed1994

Clozapine effects on glucose metabolic rate in striatum and frontal cortex.

Eighteen patients with schizophrenia had cerebral metabolic rates assessed with positron emission tomography during a double-blind, placebo-controlled crossover study of clozapine treatment. Relative metabolic rates were increased in the basal ganglia, especially on the right side. In the frontal lobe, metabolic rates were lowered, more on the left than on the right. The anterior nuclei of the thalamus also showed lower metabolic rates after clozapine. We have previously observed patients with schizophrenia to have low metabolic rates in the basal ganglia and to lack the normal right > left asymmetry; in this study, clozapine normalized striatal activity. In the frontal lobe, asymmetry was normalized, but hypofrontal function was, if anything, exaggerated. This effect in the frontal lobe was not observed with haloperidol in earlier studies. The cortical effects of clozapine may be related to its unique clinical properties and suggest important differences between typical and atypical antipsychotic drugs.

Adult↗
PubMed1993

Intensity-related exercise albuminuria in insulin dependent diabetic patients.

Normoalbuminuric insulin-dependent diabetic (IDDM) patients may present higher rates of urinary albumin excretion after submaximal exercise at a standard intensity. To evaluate whether the urinary albumin excretion of IDDM patients is increased after maximal and submaximal exercise when exercise intensities are adjusted according to individual lactate thresholds, 16 normoalbuminuric IDDM patients (mean time from diagnosis 8 years) and 13 normal controls exercised for 20 min at intensities corresponding to 90% of the first and second lactate thresholds and to maximal tolerance on different days. Urinary albumin excretion, blood lactate concentration, heart rate and blood pressure were measured. Metabolic and cardiovascular responses to submaximal and maximal exercise were similar for patients and controls. After exercise at 90% of the first lactate threshold neither patients or controls demonstrated significant changes in urinary albumin excretion. After exercise at 90% of the second lactate threshold both patients and controls demonstrated a similar increase in urinary albumin excretion. After maximal exercise both patients and controls demonstrated marked and similar elevation in the urinary albumin excretion. There was a significant correlation (r = 0.74, P < 0.001) between blood lactate levels at the end of exercise and the decimal logarithm of post-exercise urinary albumin excretion of the diabetic patients. Thus, when exercise intensities are adjusted for lactate thresholds, normoalbuminuric IDDM patients present normal intensity-related urinary albumin excretion during exercise. These data suggest that previously observed differences in exercise induced albuminuria in IDDM patients might be related to inappropriate standardization of submaximal exercise intensities.

Adult↗
PubMed1992

Regulation of lipoprotein lipase by dibutyryl cAMP, cholera toxin, Hepes and heparin in F1 heart-cell cultures.

Regulation of lipoprotein lipase was studied in mesenchymal rat heart-cell cultures. Treatment of the cultures with dibutyryl cyclic AMP or with cholera toxin resulted in an increase in LPL activity and a comparable increase in LPL mRNA. When the cells were exposed to 100 mM Hepes for 24 h, total enzyme activity rose 2-fold and LPL mRNA increased 2.4-fold. After 72 h, there was a 3-fold increase in LPL mRNA and a 4-fold rise in cellular LPL activity, while medium activity increased 20-fold. Exposure of the cultures to heparin for 24 h resulted in a 3.2-fold increase in total activity and a 36-fold increase in medium activity. This increase was not accompanied by any rise in LPL mRNA. Addition of actinomycin D to control dishes for 24 h resulted in a 33% reduction in LPL mRNA and a 43% reduction in enzyme activity. These values were 71% and 56%, respectively, in Hepes-treated cells, indicating that no stabilization of LPL mRNA occurred under these conditions. It can be concluded that in mesenchymal rat heart-cells in culture cAMP and cholera toxin upregulate lipoprotein lipase at the level of transcription. The increase in LPL activity after 24 h exposure to Hepes could be compatible with transcriptional regulation, while exposure to heparin is not accompanied by a change in LPL mRNA.

Animals↗