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Biomedical subjects

M Bloom

Publications and source records attributed to M Bloom.

At least 19 recordsLinked to original sources
PubMed2000

The recovery of cognitive function after remifentanil-nitrous oxide anesthesia is faster than after an isoflurane-nitrous oxide-fentanyl combination in elderly patients.

UNLABELLED: We tested the hypothesis that remifentanil-nitrous oxide (N(2)O) anesthesia shortens postoperative emergence and recovery compared with an isoflurane-N(2)O-fentanyl combination in elderly patients undergoing spinal surgery. A total of 60 patients (>65 yr old) were randomly assigned to one of two groups for maintenance of anesthesia. After the induction with 3.6 +/- 1.2 mg/kg IV thiopental and endotracheal intubation facilitated with 1.4 +/- 0.5 mg/kg succinylcholine, patients were maintained with either 0.5%-1.5% isoflurane, 70% N(2)O, and up to 7 microg/kg fentanyl (iso/fent group) or 48 +/- 11 microg/kg remifentanil and 70% N(2)O (remi group). A mini-mental status examination was used to assess cognitive ability preoperatively, at 15, 30, and 60 min after arrival at the postanesthesia care unit and again 12-24 h postoperatively. The time from the conclusion of anesthesia to spontaneous respiration was similar in both groups. Times to eye opening (4.8 +/- 2.6 vs 2.3 +/- 1.1 min), extubation (6.8 +/- 3.8 vs 3.2 +/- 2.1 min), and verbalization (9.9 +/- 6.2 vs 3.9 +/- 2.6 min) were significantly shorter for the remi group (P < 0.05). Postoperative mini-mental status examination scores were significantly lower in the iso/fent group at 15 (16.3 +/- 5.8 vs 23. 7 +/- 3.3), 30 (20.2 +/- 5.2 vs 26.3 +/- 2.7), and 60 min (23.5 +/- 4.4 vs 27.5 +/- 2.0) (P < 0.001); however, the scores equalized after 12 h. Requirements for postoperative analgesics were similar in the two groups. More patients in the remi group were treated with antiemetics (21 vs 7, P = 0.06). Use of remifentanil-N(2)O for maintenance did not shorten the overall length of stay in the postanesthesia care unit; a stay is often related to multiple administrative issues, rather than cognitive recovery. IMPLICATIONS: Maintenance of anesthesia with remifentanil-nitrous oxide (N(2)O), compared with isoflurane-N(2)O-fentanyl, can safely shorten postoperative recovery of cognitive function in a geriatric population. Earlier recovery may facilitate postoperative neurological assessment. Use of remifentanil-N(2)O for maintenance did not shorten the overall length of stay in the postanesthesia care unit, a stay often related to multiple administrative issues, rather than cognitive recovery.

Aged↗
PubMed1999

Tumor necrosis factor-alpha and CD95 ligation suppress erythropoiesis in Fanconi anemia C gene knockout mice.

Fanconi anemia (FA) is a genetic syndrome predisposing to hematopoietic failure. Little is known about the pathophysiology of FA, except that tumor necrosis factor-alpha (TNF-alpha) is overexpressed in patients. FA group C (Fac) gene knockout mice have been developed in order to model the human disease, but the mice do not spontaneously exhibit aplasia. To investigate secondary influences on hematopoiesis in the Fac-null mice, we studied the sensitivity of hematopoietic progenitor cells (HPC) to death receptor triggering by TNF-alpha and Fas receptor (CD95) ligation. Previously we had found that overexpression of a human FAC transgene protects hematopoietic progenitors from Fas-mediated apoptosis (Wang et al., 1998, Cancer Res 58:3538-3541). In the present experiments with Fac-null mice, growth of erythroid burst-forming units (BFU-E) was significantly inhibited by TNF-alpha and CD95 ligation. Flow cytometric analysis revealed that CD95 was induced more readily in the Fac-null CD34+ cell fraction. Apoptosis induced by TNF-alpha alone or with CD95 ligation also occurred more frequently in null mouse HPC. We then bred null mice against transgenic mice overexpressing TNF-alpha (at serum levels in the range of 100 pg/ml). Resultant Fac-null mice that overexpressed TNF-alpha not only yielded decreased numbers of BFU-E but also expressed higher levels of CD95 in the CD34+ fraction. We conclude that mutation in the Fac protein induces heightened sensitivity to TNF-alpha and Fas receptor ligation, results that may explain the mechanism of anemia in FA-C patients.

Animals↗
PubMed1999

Evidence for the unique function of docosahexaenoic acid during the evolution of the modern hominid brain.

The African savanna ecosystem of the large mammals and primates was associated with a dramatic decline in relative brain capacity associated with little docosahexaenoic acid (DHA), which is required for brain structures and growth. The biochemistry implies that the expansion of the human brain required a plentiful source of preformed DHA. The richest source of DHA is the marine food chain, while the savanna environment offers very little of it. Consequently Homo sapiens could not have evolved on the savannas. Recent fossil evidence indicates that the lacustrine and marine food chain was being extensively exploited at the time cerebral expansion took place and suggests the alternative that the transition from the archaic to modern humans took place at the land/water interface. Contemporary data on tropical lakeshore dwellers reaffirm the above view with nutritional support for the vascular system, the development of which would have been a prerequisite for cerebral expansion. Both arachidonic acid and DHA would have been freely available from such habitats providing the double stimulus of preformed acyl components for the developing blood vessels and brain. The n-3 docosapentaenoic acid precursor (n-3 DPA) was the major n-3-metabolite in the savanna mammals. Despite this abundance, neither it nor the corresponding n-6 DPA was used for the photoreceptor nor the synapse. A substantial difference between DHA and other fatty acids is required to explain this high specificity. Studies on fluidity and other mechanical features of cell membranes did not reveal a difference of such magnitude between even alpha-linolenic acid and DHA sufficient to explain the exclusive use of DHA. We suggest that the evolution of the large human brain depended on a rich source of DHA from the land/water interface. We review a number of proposals for the possible influence of DHA on physical properties of the brain that are essential for its function.

Animals↗
PubMed1998

Terfenadine and fexofenadine reduce in vitro ICAM-1 expression on human continuous cell lines.

BACKGROUND: Epithelial cells and fibroblasts play an important role in allergic inflammation. Modulation of surface expression of adhesion molecules on epithelial cells by antiallergic drugs has been shown by both in vivo and in vitro studies. OBJECTIVE: The aim of the study was to evaluate the effect exerted by terfenadine and fexofenadine on adhesion molecules expression (CD54/ICAM-1 and CD29) of a human continuously cultured conjunctival epithelial cell line (WK) and a fibroblast cell line (HEL). METHODS: By means of flow cytometry analysis, we evaluated ICAM-1 and CD29 expression by WK and HEL epithelial cells in basal condition (at baseline) or after IFN gamma or TNF alpha stimulation in the presence or in the absence of terfenadine and fexofenadine. We also performed immunoenzymatic assays in order to evaluate soluble ICAM-1 released by WK cells and procollagen type I and III and IL6 released by HEL cells. RESULTS: Terfenadine and fexofenadine significantly reduced ICAM-1 basal expression on WK cells at the concentration of 1 microg/mL and 50 microg/mL, respectively. In addition, both terfenadine and fexofenadine were able to decrease soluble ICAM-1 levels in IFN gamma-stimulated WK cells. On HEL fibroblasts, fexofenadine only was able to inhibit ICAM-1 upregulation induced by IFN gamma. Concerning the release of fibroblast products, we observed a dose-dependent decrease of spontaneous IL6 release only in the presence of fexofenadine. CONCLUSION: This study shows that terfenadine and fexofenadine exert a biologic effect directly on epithelial cells and fibroblasts reducing ICAM-1 expression and partially reducing soluble ICAM-1 release.

Cell Line↗
PubMed1998

Correlation of transcranial Doppler sonography mean flow velocity with cerebral blood flow in patients with intracranial pathology.

Several studies suggest that relative changes in cerebral blood flow (CBF) may be assessed via transcranial Doppler sonography (TCD). The present study investigates the correlation between changes in TCD-mean flow velocity (Vm) and changes in CBF in patients with a variety of types of intracranial pathology undergoing cerebrovascular reactivity tests. After informed consent was obtained, 32 patients presenting with stenoses of brain-supplying arteries (n = 13), cerebral vascular malformations (n = 6), surgical decompression for subarachnoid hemorrhage (n = 2), brain edema after closed head injury (n = 8), or hepatic encephalopathy (n = 3) were studied. The patients were divided into two groups for different reactivity tests. Patients in group 1 (awake or sedated, n = 18) received a 1-g dose of acetazolamide intravenously. In group 2 (n = 14), mechanical ventilation was adjusted to produce a 20% decrease in arterial CO2 tension compared with baseline. Regional CBF was measured using xenon-enhanced computed tomography (Xe-CT). Xe-CT scans at the levels of the basal ganglia and the lateral ventricles were performed during a 4.5-min xenon wash-in period. Bilateral flow velocity was measured in the middle cerebral artery using a 2-MHz pulsed TCD system. Mean arterial blood pressure, heart rate, and end-tidal CO2 were continuously recorded during the procedure. After baseline measurements and either alteration of CO2 or application of acetazolamide, the cerebrovascular reactivity was assessed at 20 min by a second measurement of CBF, TCD, and all other physiologic variables. The correlation coefficient for relative changes of MCA territory CBF versus Vm and for the overall population was r = 0.82. In groups 1 and 2, the r values were 0.39 and 0.5, respectively. Correlation coefficients did not exceed r = 0.4 in any subgroup-classification based on diagnosis. The close correlation between changes in CBF and Vm (r = 0.82) in patients with heterogeneous intracranial pathology seems to show that TCD is a measure of CBF. However, in groups 1 and 2 and in subgroups formed of patients classified according to diagnoses, data dispersion suggests that the actual correlation is weaker. Relation of changes in Vm to those in CBF may depend on the underlying diagnosis. These data indicate that the correlation between Vm and CBF may vary with intracranial pathology.

Acetazolamide↗
PubMed1997

Regulation of a graft-versus-leukemia effect by major histocompatibility complex class II molecules on leukemia cells: HLA-DR1 expression renders K562 cell tumors resistant to adoptively transferred lymphocytes in severe combined immunodeficiency mice/nonobese diabetic mice.

To understand the role of key molecules in determining the strength and nature of allogeneic T-cell response to leukemia, we transfected HLA-DR1 into the major histocompatibility complex (MHC)-deficient, natural killer (NK)-cell sensitive K562 leukemia cell line. Untransfected K562 cells stimulated NK proliferation in vitro and formed subcutaneous tumors in severe combined immunodeficiency/non-obese diabetic (SCID/NOD) mice. Tumor growth was inhibited by adoptive intravenous transfer of fresh unprimed peripheral blood mononuclear cells (PBMC). In contrast, HLA-DR1 transfected cells stimulated CD4(+) T cells, but not NK-cell proliferation in vitro and formed tumors resistant to fresh PBMC in SCID/NOD mice. Tumors not expressing MHC were infiltrated with CD16(+)CD56(+) lymphocytes whereas nonregressing HLA-DR1 expressing tumors showed only a scanty infiltration with both T-cell and NK-cell subsets. The results indicate that MHC class II expression by leukemia cells can determine the effector cell type that it engages. In vivo MHC class II expression rendered K562 cell tumors resistant to NK-cell mediated antitumor reactivity.

Adoptive Transfer↗
PubMed1997

Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane, and alfentanil in healthy volunteers.

BACKGROUND: The bispectral index (BIS), a value derived from the electroencephalograph (EEG), has been proposed as a measure of anesthetic effect. To establish its utility for this purpose, it is important to determine the relation among BIS, measured drug concentration, and increasing levels of sedation. This study was designed to evaluate this relation for four commonly used anesthetic drugs: propofol, midazolam, isoflurane, and alfentanil. METHODS: Seventy-two consenting volunteers were studied at four institutions. Volunteers were given either isoflurane, propofol, midazolam, or alfentanil. Each volunteer was administered a dose-ranging sequence of one of the study drugs to achieve predetermined target concentrations. A frontal montage was used for continuous recording of the EEG. At each pseudo-steady-state drug concentration, a BIS score was recorded, the participant was shown either a picture or given a word to recall, an arterial blood sample was obtained for subsequent analysis of drug concentration, and the participant was evaluated for level of sedation as determined by the responsiveness portion of the observer's assessment of the alertness/ sedation scale (OAAS). An OAAS score of 2 or less was considered unconscious. The BIS (version 2.5) score was recorded in real-time and the BIS (version 3.0) was subsequently derived off-line from the recorded raw EEG data. The relation among BIS, measured drug concentration, responsiveness score, and presence or absence of recall was determined by linear and logistic regression for both the individual drugs and, when appropriate, for the pooled results. The prediction probability was also calculated. RESULTS: The BIS score (r = 0.883) correlated significantly better than the measured propofol concentration (r = -0.778; P < 0.05) with the responsiveness score. The BIS provided as effective correlation with responsiveness score of the OAAS as did the measured concentration for midazolam and isoflurane. None of the volunteers given alfentanil lost consciousness and thus were excluded from the pooled analysis. The pooled BIS values at which 50% and 95% of participants were unconscious were 67 and 50, respectively. The prediction probability values for BIS ranged from 0.885-0.976, indicating a very high predictive performance for correctly indicating probability of loss of consciousness. CONCLUSIONS: The BIS both correlated well with the level of responsiveness and provided an excellent prediction of the loss of consciousness. These results imply that BIS may be a valuable monitor of the level of sedation and loss of consciousness for propofol, midazolam, and isoflurane.

Adult↗
PubMed1997

Effect of terfenadine on TNF alpha release from peripheral blood mononuclear cells during cow's milk allergy.

BACKGROUND: In infants with cow's milk allergy and intestinal symptoms, peripheral blood mononuclear cells stimulated in vitro with cow's milk proteins, secrete large amounts of the proinflammatory cytokine TNF alpha thus altering intestinal barrier capacity. Terfenadine, an antihistaminic drug, inhibits the release of several inflammatory mediators, including histamine, prostaglandins and leukotrienes. OBJECTIVES: To test the potential ability of terfenadine to inhibit TNF alpha secretion by mononuclear cells from infants with cow's milk allergy. METHODS: Mononuclear cells from infants allergic to cow's milk proteins were stimulated in vitro for 6 days by a mixture of milk proteins (beta-lactoglobulin, alpha-lactalbumin and casein) with or without terfenadine (0.1-1 microM) and culture supernatants were assayed for TNF alpha by enzyme immunoassay. The effect of culture supernatants on intestinal barrier capacity was evaluated by measuring the electrical resistance (index of integrity) of filter-grown HT29-19 A intestinal cells in Ussing chambers. RESULTS: During active cow's milk allergy, mononuclear cells stimulated with cow's milk proteins secreted large amounts of TNF alpha which significantly reduced the electrical resistance of HT29-19 A intestinal cells. There was a dose-dependent decrease in TNF alpha secretion in the presence of terfenadine, with a maximal inhibition of 62% of this secretion at 1 microM. Accordingly, terfenadine-treated mononuclear cells supernatants did not alter the electrical resistance of intestinal HT29.19 A cells. CONCLUSION: These results indicate that in infants with intestinal dysfunction due to cow's milk allergy, terfenadine is a potent inhibitor of the TNF alpha secretion induced by sensitizing milk protein antigens. This inhibition prevents the degradation of intestinal function as measured in an intestinal cell line, in vitro.

Animals↗
PubMed1996

Intermediate filament-mediated stretch-induced changes in chromatin: a hypothesis for growth initiation in cardiac myocytes.

Excessive stretching of the myocardium leads to hypertrophy, but how the stretch message is communicated to hypertrophy-initiating genes is unknown. Candidates hypothesized as couplers of physical stretch to growth initiation include neural and hormonal factors, stretch-activated and stretch-inactivated ion channels, microtubules, microfilaments, and contractile activity. Upon investigation, however, all were ruled out. We provide evidence here that it is the intermediate filaments in the mechanically stressed myocyte that transmit the stretch message to the chromatin. Using rat myocytes and an immunogold desmin-lamin-labeling technique, we found that when cardiac myocytes are stretched there are changes in the spatial arrangement of both the desmin-lamin intermediate filament network and the nuclear-envelope-associated chromatin. We hypothesize that (a) by physically linking the sarcomere to chromatin, the desmin-lamin intermediate filament network couples sarcomere length to chromatin distribution, and (b) stretch-induced changes in chromatin (mediated by the intermediate filament network) activate hypertrophy-associated genes. Further investigation is needed to test this hypothesis.

Animals↗
PubMed1996

Correlation between lipid plane curvature and lipid chain order.

The 1-palmitoyl-2-oleoyl-phosphatidylethanolamine: 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPE:POPC) system has been investigated by measuring, in the inverted hexagonal (HII) phase, the intercylinder spacings (using x-ray diffraction) and orientational order of the acyl chains (using 2H nuclear magnetic resonance). The presence of 20 wt% dodecane leads to the formation of a HII phase for the composition range from 0 to 39 mol% of POPC in POPE, as ascertained by x-ray diffraction and 2H nuclear magnetic resonance. The addition of the alkane induces a small decrease in chain order, consistent with less stretched chains. An increase in temperature or in POPE proportion leads to a reduction in the intercylinder spacing, primarily due to a decrease in the water core radius. A temperature increase also leads to a reduction in the orientational order of the lipid acyl chains, whereas the POPE proportion has little effect on chain order. A correlation is proposed to relate the radius of curvature of the cylinders in the inverted hexagonal phase to the chain order of the lipids adopting the HII phase. A simple geometrical model is proposed, taking into account the area occupied by the polar headgroup at the interface and the orientational order of the acyl chains reflecting the contribution of the apolar core. From these parameters, intercylinder spacings are calculated that agree well with the values determined experimentally by x-ray diffraction, for the variations of both temperature and POPE:POPC proportion. This model suggests that temperature increases the curvature of lipid layers, mainly by increasing the area subtended by the hydrophobic core through chain conformation disorder, whereas POPC content affects primarily the headgroup interface contribution. The frustration of lipid layer curvature is also shown to be reflected in the acyl chain order measured in the L alpha phase, in the absence of dodecane; for a given temperature, increased order is observed when the curling tendencies of the lipid plane are more pronounced.

Biophysical Phenomena↗
PubMed1996

Inhibition of mediator and cytokine release from dispersed nasal polyp cells by terfenadine.

The mechanism of action of H1-blockers requires elucidation because they may possess properties unrelated to the blockage of histamine at its receptor level. A study was performed with enzymatically dispersed cells obtained from nasal polyps to examine the effect of terfenadine (0.1-10 mumol) on the release of leukotrienes (LT) (LTC4/D4 and LTB4) after stimulation by anti-IgE, and on the spontaneous release of cytokines (granulocyte/macrophage-colony stimulating factor [GM-CSF] and tumor necrosis factor-alpha [TNF-alpha]) released from cells cultured for 6 h. Terfenadine inhibited significantly, and in a dose-dependent manner, the release of LTC4/D4, LTB4, TNF-alpha, and GM-CSF. IC50 values were determined for LTC4/D4 (8 mumol), LTB4 (9.9 mumol), TNF-alpha (6.1 mumol), and GM-CSF (4 mumol). Terfenadine was found to possess new antiallergic properties with a novel in vitro model which mimics more closely inflammatory cells of allergic rhinitis or asthma.

Adolescent↗
PubMed1996

Cerebral SPECT imaging: effect on clinical management.

This study, performed in 94 consecutive patients referred for evaluation, demonstrates the clinical utility of cerebral SPECT imaging. In a significant percentage of patients (47%), the additional information provided by SPECT resulted in an alteration in clinical management. Long-term follow-up will be necessary to determine the effect of these management decisions on patient outcome.

Brain↗
PubMed1994

A model membrane approach to the epidermal permeability barrier.

The permeability barrier of mammalian skin is found in unusual intercellular domains in the upper layers of the epidermis, and is composed mainly of three lipid classes: ceramide, cholesterol, and free fatty acid. These are organized as lamellae, but the details of lipid organization are not precisely known. To examine the relationship between lipid composition and phase behavior, aqueous dispersions of bovine brain ceramide, cholesterol, and perdeuterated palmitic acid were examined by 2H NMR and compared to analogous systems in which sphingomyelin replaced ceramide. The sphingomyelin systems give rise as expected to a stable fluid lamellar signal over the temperature range 20-75 degrees C and pH 5.2-7.4, whereas the ceramide dispersions show complex polymorphism as a function of both temperature and pH. Prominent features of the ceramide dispersions containing cholesterol are phase coexistence and the presence of a "solid" phase in which molecular motion is more inhibited than in a classical phospholipid gel phase: T1z measurements indicate that lateral diffusion of the palmitic acid probe effectively does not occur. In the absence of cholesterol, a fluid lamellar signal is not observed, but the appearance of a "solid" signal is also influenced by the pH. In the presence of cholesterol, a fluid lamellar signal is present at 50 degrees C, and the 2H NMR order parameter profile is very similar to that derived from the analogous sphingomyelin dispersions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Fragmentation of phospholipid bilayers by myelin basic protein.

Human myelin basic protein (MBP) is shown to disrupt multilamellar phosphatidylcholine bilayers into small lipoprotein particles in a manner similar to the cytolytic peptide melittin (Dufourc, E. J., Smith, I. C. P., & Dufourcq, J. (1986) Biochemistry 25, 6448-6455). This bilayer fragmentation, as monitored by 31P nuclear magnetic resonance, is temperature-dependent and completely inhibited by the presence of small amounts of negatively charged phosphatidylserine. The stabilizing property of phosphatidylserine is lost with the neutralization of its negative charges upon membrane binding of cationic species such as calcium ions. No MBP-induced fragmentation is observed with bilayers of negative or zwitterionic lipid mixtures which mimic the myelin lipid composition. The membrane fragmentation observed in vitro in the presence of MBP could play a role in vivo in demyelinating diseases.

Calcium↗