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Biomedical subjects

M Herman

Publications and source records attributed to M Herman.

At least 37 records · Page 2Linked to original sources

Photodynamic treatment of neoplastic lesions of the gastrointestinal tract. Recent advances in techniques and results.

Photodynamic therapy (PDT) is a form of cancer treatment based on the selective accumulation of a photosensitizer (by exogenous or endogenous means) in neoplastic tissue. Subsequent activation of the photosensitizer by a specific wavelength of light results in tumor cell death. Activation of a photosensitizer to the appropriate energy state results in the production of singlet oxygen, a powerful oxidizing agent. PDT can kill cells by three mechanisms: direct cell death by photooxidation, apoptosis, or as a consequence of vascular shutdown. The toxicity of PDT is site specific and dependent on the organ being irradiated and the selectivity of the photosensitizer for target tissue over normal tissue. However, there are also reactions related to the sensitizer per se that are independent of those related to the treatment site. Such reactions include cutaneous photosensitization, nausea, vomiting, hypotension, and altered liver 'function' tests. Excitation of photosensitizer by an incident photon produces reemission of a fluorescent photon, which can be used to detect a tumor that is not ordinarily evident. The major limiting factor in using PDT is the depth of tumor kill. The majority of clinical experience involving PDT of the gastrointestinal tract involves patients who are considered to be poor operative risks, and reported follow-ups after treatment are not only limited but also variable.

Cell Survival↗

CD40 ligation induces tissue factor expression in human vascular smooth muscle cells.

Tissue factor (TF) instigates the extrinsic pathway of blood coagulation. Plaque disruption and exposure of circulating factor VII/VIIa to subendothelial procoagulants such as TF leads to intravascular thrombosis, a frequent cause of acute atherosclerotic events. Although the expression of TF in the intima of human atherosclerotic lesions is well established, little is known about the mechanisms of TF regulation in vascular smooth muscle cells (SMC). We demonstrate here that TF colocalizes with the receptor CD40 on lesional SMC within atherosclerotic lesions in situ. In cultured vascular SMC, ligation of CD40 with native CD40 ligand (CD40L) derived from activated T lymphocytes or recombinant human CD40L (rCD40L) induced the transient expression of TF on the cell surface (as determined by FACS analysis) in a concentration- and time-dependent manner and enhanced total cell-associated TF (as determined by ELISA). CD40L-induced TF on vascular SMC is functional and activates coagulation. In accordance with the increased TF activity, stimulation of vascular SMC with rCD40L did not affect either protein expression or activity of tissue factor pathway inhibitors. In summary, these findings demonstrate the potential of the CD40/CD40L signaling pathway to augment the procoagulant activity in human vascular SMC. Because TF and CD40 colocalize on lesional SMC in human atheroma, CD40/CD40L signaling may contribute to the TF expression and hence to increased thrombogenicity of plaques during the inflammatory responses of atherogenesis and arterial injury.

Arteriosclerosis↗

A randomized, controlled trial of transcutaneous carbon dioxide monitoring during ERCP.

BACKGROUND: Pulse oximetry, used to monitor oxygen saturation during endoscopy, does not directly measure hypoventilation. Study goals were to determine whether transcutaneous carbon dioxide (PtcCO(2)) monitoring during endoscopic retrograde cholangiopancreatography (ERCP) prevents severe hypoventilation and to assess the accuracy of clinical observation and pulse oximetry in detecting hypoventilation. METHODS: All patients received intensive clinical and electronic monitoring including pulse oximetry. Supplemental oxygen was administered for pulse oximetry < 90%. Patients were randomized to a treatment arm (group 1) where PtcCO(2) monitoring guided sedation or a control arm (group 2) where PtcCO(2) was recorded but unavailable for guiding sedation. RESULTS: Group 1 had significantly fewer episodes of severe carbon dioxide retention (rise in PtcCO(2) >/=40 mm Hg above baseline) than group 2 (0 of 199 versus 5 of 196, respectively, p = 0.03), as well a shorter mean duration of procedure discomfort (8.3% of procedure duration rated as "uncomfortable" versus 11.5%, p = 0.04). Correlations between clinical observation and objective measures of ventilation were poor: level of sedation versus PtcCO(2) (R = 0.3) or pulse oximetry (R = 0.06); slowest respiratory rate versus PtcCO(2) (R = 0.4) or pulse oximetry (R = -0.4). PtcCO(2) rises of greater than 20 mm Hg occurred without oxygen desaturation in 10.7% of patients receiving supplemental oxygen. CONCLUSIONS: Carbon dioxide retention during ERCP is not reliably detected by clinical observation or by pulse oximetry in patients receiving supplemental oxygen. The addition of PtcCO(2) monitoring prevents severe carbon dioxide retention more effectively than intensive clinical monitoring and pulse oximetry alone. The clinical relevancy of this observation needs to be determined in an appropriately designed outcome study.

Blood Gas Monitoring, Transcutaneous↗

Haemolysis in haemodialysis patients: evidence for impaired defence mechanisms against oxidative stress.

BACKGROUND: Uraemic patients have a decreased ability to withstand oxidative stress. It is postulated that their antioxidant capacity is reduced, yet the mechanism remains unclear. Recently 33 haemodialysis (HD) patients were exposed to chloramine contamination in the water supply. This led to haemolysis in 24 patients, while nine were unaffected. In the former group haemoglobin decreased from 11.7+/-1.1 to 8.5+/- 1.4 g/dl (P<0.0001) and returned to 11.4+/-0.9 g/dl (P<0.0001) following recovery. During haemolysis, haptoglobin was 38.4+/-10.6 vs 138.1+/-8.3 ng/dl (P<0.0001) following recovery. METHODS: To explore the factors affecting the severity of haemolysis we studied extracellular and intracellular anti-oxidant defence mechanisms 3 months after recovery. In 29 patients and 20 controls we determined plasma glutathione (GSH), and the erythrocyte enzymes glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rx), and superoxide dismutase (SOD). Serum malondialdehyde (MDA) was measured as a marker of oxidative stress. RESULTS: Plasma GSH was lower in patients as compared to controls (5.49+/-0.26 vs 7.4+/-0.5 micromol/l, P<0.005). There was an inverse correlation between GSH and the degree of haemolysis (r=-0.42, P<0.02). Patients had higher GSH-Rx (4.64+/-0.15 vs 3.97+/-0.12 U/gHb, P<0.02), lower GSH-Px (29. 7+/-1.85 vs 35.5+/-1.62 U/gHb, P<0.001), and similar SOD (0.63+/-0. 02 vs 0.51+/-0.02 U/mgHb) as compared to controls. There was no correlation between the enzyme levels and the degree of haemolysis. MDA was higher in patients (2.37+/-0.07 vs 0.97+/-0.1 nmol/ml, P<0. 0001). There was a correlation between MDA and the years patients were on HD (r=0.43, P<0.02). CONCLUSIONS: These data indicate that HD patients have an impaired anti-oxidant response, which may be attributed in part, to plasma GSH deficiency. Patients with the lowest plasma GSH levels are more susceptible to oxidative stress and consequent haemolysis.

Adult↗

Sodium intake is increased by social stress and the Y chromosome and reduced by clonidine.

The objectives were to determine 1) if female rats have higher Na intake than males and if social stress increases Na intake, 2) if the sympathetic nervous system (SNS) mediates the stress effects and the gender effect, and 3) if the Y chromosome (Yc) from a hypertensive father increases Na intake. Four rat strains (n = 10/group) of both sexes were used: 1) Wistar Kyoto normotensive (WKY), 2) an F(16) backcross with a Yc from a hypertensive father (SHR/y), 3) spontaneously hypertensive rat (SHR), and 4) an F(16) backcross with a Yc from a normotensive father (SHR/a). Females showed greater baseline Na intake than males (hypertensive strains), intruder stress increased Na intake, and clonidine decreased Na intake, but not in WKY or SHR females. SHR/y males had higher baseline Na intake compared with WKY males. In conclusion, the higher Na intake in females during baseline and stress was partially mediated through the SNS in hypertensive strains and the SHR Yc was partially responsible for the increased Na intake in SHR/y and SHR males compared with WKY.

Animals↗

Erythropoietin, folic acid deficiency and hyperhomocysteinemia: is there a possible relationship in chronically hemodialyzed patients?

AIMS: To examine the possible relationships between recombinant human erythropoietin (rhEPO) therapy, serum folic acid and homocysteine levels in a cohort of stable, chronically hemodialyzed patients. MATERIAL AND METHODS: The study was cross-sectional in its first phase and consisted of 3 groups of subjects (group 1:6 healthy controls; group 2:7 dialyzed patients not receiving rhEPO; group 3: 14 patients on rhEPO therapy). Hematological and biochemical parameters were taken after an overnight fast in all subjects. The second phase of the study was prospective, and included 8 dialyzed patients, and investigated the effects of a 6-month period of folic acid supplementation (10 mg, 3 times a week) on the same parameters examined in the first phase of the study. RESULTS: In the first part of the study hemoglobin levels were near-normal, or normal, in all patients. No differences in hemoglobin or hematocrit values were observed in the 3 groups. 80% of all hemodialyzed patients had low serum folic acid levels, irrespective of whether they were receiving rhEPO. Serum erythropoietin level was elevated in group 3 (23.3+/-10.4 mIU/ml). In group 2, serum erythropoietin level was not different from that of the healthy controls (13.5+/-11.2 vs. 8.0+/-5.4 mIU/ml, p = n.s.). Total serum homocysteine levels were elevated in all dialyzed patients (group 2: 24.7+/-9.2 micromol/l; group 3: 31.6+/-14.4 micromol/l), with a significant difference seen when comparing controls and those dialyzed patients on rhEPO therapy (8.7+/-2.2 vs. 31.6+/-14.4 micromol/l; p<0.05). Significant correlations (ANOVA) were observed between serum erythropoietin and folic acid levels (r = -0.382; p = 0.049), and between folic acid and homocysteine levels (r = -0.560; p = 0.002). In the second part of the study folic acid supplementation led to a highly significant reduction in homocysteine levels (20.9+/-4.9 vs. 11.9+/-2.5 micromol/l; p<0.0005). Two of 3 patients receiving rhEPO therapy, had rhEPO discontinued after commencing folic acid, as hemoglobin levels remained adequate, even without rhEPO. CONCLUSIONS: In hemodialyzed patients, the presence of a near-normal hemoglobin level, irrespective of rhEPO therapy, implies efficient erythropoiesis. Without adequate folic acid reserves, folic acid deficiency may develop in these patients and this will aggravate already high homocysteine levels. Therefore, folic acid supplementation is warranted in hemodialyzed patients, especially in those patients with hemoglobin levels approaching normal. This treatment is safe and effective in reducing homocysteine levels, especially when given in high doses for prolonged periods of time.

Analysis of Variance↗

Expression of stromelysin-3 in atherosclerotic lesions: regulation via CD40-CD40 ligand signaling in vitro and in vivo.

Stromelysin-3 is an unusual matrix metalloproteinase, being released in the active rather than zymogen form and having a distinct substrate specificity, targeting serine proteinase inhibitors (serpins), which regulate cellular functions involved in atherosclerosis. We report here that human atherosclerotic plaques (n = 7) express stromelysin-3 in situ, whereas fatty streaks (n = 5) and normal arterial specimens (n = 5) contain little or no stromelysin-3. Stromelysin-3 mRNA and protein colocalized with endothelial cells, smooth muscle cells, and macrophages within the lesion. In vitro, usual inducers of matrix metalloproteinases such as interleukin-1, interferon-gamma, or tumor necrosis factor alpha did not augment stromelysin-3 in vascular wall cells. However, T cell-derived as well as recombinant CD40 ligand (CD40L, CD154), an inflammatory mediator recently localized in atheroma, induced de novo synthesis of stromelysin-3. In addition, stromelysin-3 mRNA and protein colocalized with CD40L and CD40 within atheroma. In accordance with the in situ and in vitro data obtained with human material, interruption of the CD40-CD40L signaling pathway in low density lipoprotein receptor-deficient hyperlipidemic mice substantially decreased expression of the enzyme within atherosclerotic plaques. These observations establish the expression of the unusual matrix metalloproteinase stromelysin-3 in human atherosclerotic lesions and implicate CD40-CD40L signaling in its regulation, thus providing a possible new pathway that triggers complications within atherosclerotic lesions.

Animals↗

Rotation-Vibration Constants for the nu1, nu22, nu24, nu22 + nu24, and Ground States in Pyrrole (12C4H5N).

We have recorded the infrared absorption spectrum of pyrrole at 0.005 cm-1 spectral resolution using a Fourier transform interferometer. The rotational analysis of the symmetric out-of-plane C-H bend 22(1)0 fundamental band at 722.132993(5) cm-1 was performed, allowing 6760 lines to be assigned. These lines were fitted simultaneously to literature data on nu1 [A. Mellouki, R. Georges, M. Herman, D. L. Snavely, and S. Leytner, Chem. Phys. 220, 311-322 (1997)] and microwave lines [G. Wlodarczak, L. Martinache, J. Demaison, and B. P. Van Eijck, J. Mol. Spectrosc. 127, 200-208 (1988)]. A set of rotation parameters was determined for the ground state in Ir and IIIr representations, together with vibration-rotation constants for the v1 = 1 and v22 = 1 vibrational states. The fine structure in the strongest of the hot bands in that range was highlighted by division, from the experimental data, of the spectrum of the 22(1)0 band, computed using the vibration-rotation parameters. The rotational assignment of 930 lines in the strongest hot band was performed. The 22(1)024(1)1 vibrational assignment is proposed, leading to x22,24 = 1.90 cm-1. The transition dipole matrix element for the 22(1)0 band is estimated to || || = 2 x 10(-4) D. Copyright 1999 Academic Press.

Journal Article↗

Effective Rotation-Vibration Parameters for the nu8 and nu4 + nu12 Bands of Ethane.

The jet-cooled spectrum of ethane in the region of the nu8 perpendicular fundamental vibration at 1472 cm-1 was recorded with a Fourier transform spectrometer at 0.01 cm-1 instrumental resolution. About 1150 lines were assigned to 18 subbands of nu8 ranging from K"DeltaK = -9 to +8. About 160 lines were assigned to three subbands (K"DeltaK = 0 to +2) of the nu4 + nu12 combination band near 1481 cm-1. Torsional splittings were observed for the majority of the transitions. A stack-by-stack analysis was performed, resulting in effective rovibrational parameters for the upper states nu8 and nu4 + nu12. A number of perturbations was observed and is discussed. Copyright 1999 Academic Press.

Journal Article↗

Weak Combination Bands in the 3-µm Region of Ethane.

The infrared spectrum of ethane in the region of the CH-stretching fundamental vibrations, between 2600 and 3300 cm(-1), was recorded with a Bruker IFS120HR Fourier transform spectrometer. Jet-cooled and room-temperature conditions were used at 0.01 and 0.005 cm(-1) instrumental resolution, respectively. Ten weak combination bands were observed and vibrationally assigned, in addition to the three principal bands in the region (nu(5), nu(7), and nu(8) + nu(11) ( parallel component)). A stack-by-stack analysis was performed for five of the combination bands. Their origins were determined as follows: nu(8) + nu(12) ( parallel component) at 2665.1512(30) cm(-1), nu(2) + nu(6) at 2753.326(32) cm(-1), nu(6) + nu(11) at 2844.13069(75) cm(-1), nu(8) + nu(11) ( perpendicular component) at 2930.705(90) cm(-1), and nu(4) + nu(10) at 3255.568(50) cm(-1). Effective rovibrational parameters were obtained for the corresponding upper states. New information was also obtained on the five remaining combination bands. Their approximate origins are: nu(8) + nu(12) ( perpendicular component) at 2660 cm(-1), nu(2) + nu(4) + nu(12) at 2860 cm(-1), nu(4) + 2nu(9) + nu(12) at 3090 cm(-1), 3nu(4) + nu(8) + nu(9) at 3157 cm(-1), and nu(4) + 2nu(8) at 3225 cm(-1). Copyright 1999 Academic Press.

Journal Article↗

Rotational Analysis of the nu(7) Band in Furan (C(4)H(4)O).

We recorded and analyzed the absorption spectrum of the nu(7) fundamental band in furan, observed around 995 cm(-1). Fourier transform (FT) spectroscopy was used at ULB to record the spectrum under room-temperature conditions, at 0.01 cm(-1) instrumental resolution. Diode-laser (DL) spectroscopy in a supersonic jet was used to record some portions of the band at Lille, revealing the fine structure around the band center. Pure rotation (MMW) data in the upper state were also recorded at Lille. Some 5559 FT, 101 DL, and 23 MMW data were assigned in this work. We fitted, on one hand, the MMW and DL data together and, on the other hand, the MMW, DL, and FT data simultaneously using a weighted procedure, constraining the ground state constants to their value determined from the microwave data in the literature. The results from these fits are provided and the constants discussed. Ab initio calculations are also performed to provide a force field which is used to support the very strong increase with the vibrational excitation observed in the inertial defect determined from the experimental rotational constants. Copyright 1999 Academic Press.

Journal Article↗

Calcium balance during pulse alfacalcidol therapy for secondary hyperparathyroidism in CAPD patients treated with 1.0 and 1.25 mmol/L dialysate calcium.

Hypercalcemia frequently occurs in continuous ambulatory peritoneal dialysis (CAPD) patients treated with calcium carbonate and vitamin D metabolites. To reduce the incidence of this complication, it has been proposed to use dialysate solutions with a low calcium concentration. However, there is concern that these solutions may lead to a negative calcium balance. We measured calcium balance in 13 CAPD patients with secondary hyperparathyroidism who were treated with calcium carbonate and alfacalcidol, 2 microg twice weekly, while using 1.0- (1.0 group) and 1.25-mmol/L (1.25 group) dialysate calcium solutions. Calcium absorption was measured after the administration of Ca47. Results for the 1.0 (n = 6) and 1.25 (n = 7) groups included fractional calcium absorptions of 0.14 (range, 0.09 to 0.27) and 0.08 (range, 0.03 to 0.40; P = not significant [NS]) and calcium absorptions of 380 +/- 92 and 331 +/- 83 mg/d (P = NS). Dialysate calcium losses were 93 +/- 20 and 91 +/- 26 mg/d, and total calcium losses (dialysate and urine) were 106 +/- 16 and 108 +/- 40 mg/d (P = NS). Calcium balance was positive in all patients (274 +/- 92 and 223 +/- 65 mg/d; P = NS). These data suggest that the use of 1.0- and 1.25-mmol/L calcium solutions in conjunction with calcium carbonate and pulse alfacalcidol therapy is associated with a positive calcium balance in CAPD patients.

Absorption↗