Search PubMed⌕ Search

Biomedical subjects

M Younes

Publications and source records attributed to M Younes.

At least 91 records · Page 5Linked to original sources
PubMed1995

Esophageal adenocarcinoma associated with Barrett's esophagus: long-term management with laser ablation.

We report the use of neodymium:yttrium-aluminum-garnet (Nd:YAG) laser ablation to treat high-grade dysplasia and intramucosal esophageal adenocarcinoma associated with Barrett's esophagus in a patient who refused surgery. Throughout laser therapy, the patient received omeprazole 40 mg/day. After 1 1/2 yr, five laser treatments totaling 22,055 J given over a period of 13 months achieved squamous reepithelialization and absence of malignant transformation in the first area in which carcinoma was diagnosed. Squamous reepithelialization was maintained 1 yr later, confirming recent reports that photoablation plus omeprazole can achieve regression of Barrett's esophagus. During the last year of follow-up, a second contiguous area discovered to contain carcinoma was treated three times by photoablation, with a total of 13,164 J; biopsy showed only low-grade dysplasia in this area after two laser treatments totaling 8,108 J. No complications were seen during or after any of the laser sessions, and the patient remained asymptomatic 2 1/2 yr after the first photoablation and 3 yr after presentation.

Adenocarcinoma↗
PubMed1994

Effect of antioxidant treatment in rats with acute hemorrhagic pancreatitis.

The purpose of this study was to evaluate the effect of free radical ablation therapy in acute hemorrhagic pancreatitis. Acute pancreatitis was induced in 64 rats by retrograde injection of 5% sodium taurocholate. Thirty animals were pretreated with 100,000 units/kg/hr of superoxide dismutase (SOD) and 400,000 units/kg catalase within the first 3 hr. After 0.5, 3.5, and 12 hr of observation time, serum enzymes and the tissue content of conjugated dienes, malondialdehyde, reduced and oxidized glutathione, as well as ATP, ADP and AMP were measured. In addition, tissue samples were examined by light microscopy. Untreated rats (N = 34) developed within 12 hr an acute hemorrhagic necrotizing pancreatitis with a concomitant increase in serum enzyme levels and a decrease in reduced glutathione and ATP. Within the 12-hr observation period, 57% of the animals died. Scavenger treatment improved the tissue damage and attenuated the increase of the serum enzyme levels and the decrease in reduced glutathione and ATP. Moreover, the lethality rate was significantly lower. Oxygen radicals seem to be instrumental for the development of acute hemorrhagic pancreatitis. Thereby, antioxidant treatment reduces tissue damage, biochemical alterations and extrapancreatic complications, thus improving the final outcome.

Acute Disease↗
PubMed1994

The role of glutathione and protein thiols in CBrCl3-induced cytotoxicity in isolated rat hepatocytes.

The role of glutathione (GSH) and protein thiols in the pathobiochemical process of CBrCl3 cytotoxicity was investigated in isolated hepatocytes. Administration of 0.5, 1.0 and 1.5 mmol/l CBrCl3 affected cellular viability as assessed by trypan blue exclusion, release of lactate dehydrogenase and loss of intracellular potassium in a dose-dependent manner. Intracellular glutathione and the capacity to reduce 3-(4,5-dimethylthiazolyl-2-)-2,5-diphenyltetrazolium bromide (MTT, thiazolyl blue) decreased almost independently of the CBrCl3 concentration. Protein thiols were not markedly oxidized in the presence of CBrCl3. However, compromising cellular defence mechanisms by either inhibition of glutathione regeneration or depletion of glutathione enhanced the cytotoxicity of CBrCl3 and induced a loss of protein thiols in the late phase of cellular injury. Under these conditions the thiol-dependent Na+,K+ATPase revealed high sensitivity towards CBrCl3. Thus, glutathione proved to exert effective cytoprotection, and sulfhydryl groups of particular proteins were supposed to be an important target of radical attack.

Animals↗
PubMed1994

Protection by albumin against ischaemia- and hypoxia-induced hepatic injury.

In previous studies using isolated perfused rat livers, we have shown that reactive oxygen species are involved in hypoxic and ischaemic liver damage. Since albumin was shown to possess strong antioxidant properties we now investigated the capacity of albumin to prevent ischaemic and hypoxic damage in isolated perfused rat livers. Both, partial ischaemia and hypoxia/reoxygenation, resulted in marked hepatic injury as evidenced by an increased release of hepatic enzymes (GPT, LDH), by a strong decline of bile flow and by a decrease in hepatic GSH levels. With partial ischaemia, hepatic ATP depletion and calcium accumulation were also observed. Bovine serum albumin, added to the perfusate at concentrations of 0.1 or 1%, provided nearly complete protection against both types of liver injury. The same level of protection was also afforded by sulfhydryl-blocked and fatty acid-free bovine albumin preparations and by human albumin. In conclusion, the protective effect of albumin in our models of oxidative liver injury is neither due to the thiol moiety nor to the presence of oxidizable fatty acids in the albumin fraction. More likely, albumin provides protection by an unspecific binding of redox-active transition metal ions capable of catalyzing reactions which yield hydroxyl or hydroxyl-like radicals. Besides, unspecific sacrifice reactions of albumin with highly reactive oxygen species or other endogenous compounds may also be implicated.

Adenosine Triphosphate↗
PubMed1994

Role of central respiratory muscle fatigue in endurance exercise in normal subjects.

The role of central respiratory muscle fatigue in determining endurance time (ET) of steady-state ergometry, ventilation (VE), and breathing pattern during exhaustive submaximal exercise is not known. Six normal subjects exercised on a cycle ergometer to exhaustion at 72-82% of maximal power output on three occasions. During the second test, inspiratory muscle load was reduced (approximately 50% of baseline load) for all but the last 3 min of exercise. ET was determined, and VE, tidal volume (VT), respiratory rate (f), and sense of breathing effort (Borg scale) were assessed at different points during the assisted exercise and compared with the values obtained at the same time in identical tests without assist, carried out before and after the assisted test (different days). Borg scale rating was less and there was a nonsignificant trend for VT and VE to be higher and for f to be lower when the assist was in place than at the same time during the unassisted runs. In the last 3 min of exercise, when the respiratory load was comparable (assist removed) but ventilatory work history was different, there were no significant differences in sense of respiratory effort, VE, VT, or f between the experimental and control tests, and ET was also similar. We conclude that central respiratory muscle fatigue plays no role in determining ET, sense of respiratory effort, or breathing pattern in normal subjects during exhaustive submaximal exercise.

Adult↗
PubMed1994

An approach to the study of upper airway function in humans.

Current methods for testing upper airway (UA) collapsibility in humans tend to produce intervention-related changes in some of the variables that affect UA stability. Therefore, their results may not reflect UA stability under the experimental conditions of interest. In the proposed method, the subject lies in a body enclosure with head and neck out. Pressure is altered in brief (approximately 0.2-s) pulses to avoid behavioral responses. The collapsibility of UA under "static" conditions is tested by delivering identical pressure pulses simultaneously to the airway and body surface inside the shell. Because the pressure applied to the respiratory system is not altered, cessation of flow indicates closure, and the pressure at which this happens is Pclosure. Collapsibility under dynamic conditions is tested by applying brief negative pulses to the shell only, thereby forcing an increase in inspiratory flow. Ten normal awake subjects were tested. None of the subjects developed closure when negative pulses (0 to -16 cmH2O) were applied to both airway and shell during inspiration or expiration with either nose or mouth breathing. There were only small reductions in flow, indicating minor narrowing. By contrast, pressure pulses of similar magnitude applied to the shell alone were associated with closure in 5 of 10 subjects. We conclude that the UA of normal awake humans is fairly stable under the influence of statistically applied pressure but susceptible to collapse under conditions of increased flow. Pclosure determined under static conditions underestimates the vulnerability of the UA to collapse under dynamic conditions.

Adult↗
PubMed1994

HAM56 antibody: a tool in the differential diagnosis between colorectal and gynecological malignancy.

HAM56, a monoclonal antibody first used to identify macrophages and endothelial cells, also stains many carcinomas (except those arising in the digestive tract). This property is useful in the differentiation between primary ovarian and metastatic colonic carcinomas in the ovary, or between gynecological (ovarian and endometrial) and colonic implants and lymph node metastases. This distinction is important as the prognoses of colorectal and gynecological malignancies differ significantly. Sixteen primary ovarian carcinomas (10 with peritoneal implants and 3 with lymph node metastases), eight cases of primary colonic carcinomas (four metastatic to ovary, four with peritoneal implants, and four with lymph node metastases), and three primary endometrial carcinomas, all with metastases to the ovary, were immunostained with the HAM56 antibody using the ABC immunoperoxidase technique. Linear membranous immunostaining was considered positive, whereas staining of mucin and debris was regarded as negative. Using these parameters, 15/16 ovarian primaries, 9/10 ovarian implants, 3/3 ovarian lymph node metastases, and 3/3 endometrial primaries and their ovarian metastases were positive. Colonic primaries, their ovarian metastases, peritoneal implants, and lymph node metastases were all negative. It is concluded that the HAM56 antibody is a useful tool in the distinction between colorectal and ovarian malignancies in those cases where the routine histological appearance may be ambiguous.

Adenocarcinoma↗
PubMed1993

The value of the preoperative mucosal biopsy in the diagnosis of colorectal mucinous adenocarcinoma.

BACKGROUND: As a rule, mucinous colorectal adenocarcinomas tend to be at a more advanced stage at the time of discovery than their nonmucinous counterparts. This study assesses the potential value of the preoperative biopsy in the diagnosis of such mucinous adenocarcinomas. METHODS: The preoperative biopsy specimens and the corresponding resection specimens of 189 patients with colorectal carcinomas were examined and compared by conventional light microscopic study. The stage of the tumor, using the modified Dukes classification of Astler and Coller, was correlated with the percentage of mucinous component (MC) in the resection specimens. The MC in the preoperative biopsy was assessed by the presence of: (1) malignant-appearing glands disrupted by the presence of abundant extruded intraluminal mucin; (2) pools of mucin in the connective stroma of the adenocarcinoma; and (3) superficial pools of mucin containing ribbons or clusters of neoplastic epithelial cells. RESULTS: The presence of a significant (more than 25%) MC in the resection specimen correlated well with an advanced stage of the tumor; 82% of tumors with more than 25% MC were at the B2 or higher stage, compared with 64% of tumors with less than 25% MC (P < 0.05). Finding MC in the preoperative biopsy correlated well with a similar finding in the resection specimen and with a B2 or higher stage of the tumor in such specimens; 83% of MC-positive biopsy specimens exhibited more than 25% MC in the corresponding resection specimen, whereas only 10% of MC-negative biopsy specimens were associated with a surgical specimen containing more than 25% MC (P < 0.001). Similarly, 83% of such MC-positive biopsy specimens revealed a carcinoma at the B2 or higher stage upon resection, compared with 63% of the MC-negative biopsy specimens (P < 0.02). CONCLUSIONS: Colorectal adenocarcinomas showing MC in the preoperative biopsy are significantly more likely to reveal a high mucin content and to be at an advanced stage at resection. Thus, such preoperative findings should be recorded and made available on a prospective basis to the treating physicians.

Adenocarcinoma, Mucinous↗
PubMed1993

p53 protein accumulation in Barrett's metaplasia, dysplasia, and carcinoma: a follow-up study.

BACKGROUND: There is a significant interobserver and intraobserver variation in grading dysplasia in Barrett's metaplasia. New markers are needed to optimize the assessment of potential risk of cancer development in these patients. The aim of this study is to explore the use of p53 as a marker of neoplastic progression in Barrett's metaplasia. METHODS: Immunohistochemistry was used to study p53 protein accumulation in 114 specimens from 54 patients with Barrett's metaplasia. RESULTS: Positive staining was found in 0% of the cases negative for dysplasia, 9% of those with low-grade dysplasia, 55% of those with high-grade dysplasia, and 87% of those with adenocarcinoma. Follow-up was available on 24 patients. Two patients who showed low-grade dysplasia and who were positive for p53 on biopsy showed high-grade dysplasia in follow-up biopsies. Of 21 patients who had biopsy specimens negative of p53, only one showed high-grade dysplasia on subsequent biopsy specimens. CONCLUSIONS: Our data support the hypothesis that p53 plays an important role in the progression of Barrett's metaplasia to adenocarcinoma. The follow-up study indicates that positive immunostaining for p53 may be an objective marker of neoplastic progression in Barrett's metaplasia.

Adenocarcinoma↗
PubMed1993

Cardiotoxic effects of nitrofurantoin and tertiary butylhydroperoxide in vitro: are oxygen radicals involved?

Langendorff rat hearts were perfused for 15, 30 or 75 min. with the oxygen radical generators nitrofurantoin (0.25 or 0.5 mmol/l) or tertiary butylhydroperoxide (0.25 mmol/l). Both agents reduced the force of contraction and increased the release of glutathione, oxidized glutathione, lactate dehydrogenase and creatine phosphokinase into the perfusion fluid. The tissue concentration of glutathione was reduced. While there were no signs of an increased production of conjugated dienes, the tissue concentration of malondialdehyde was greater than in control experiments. The variability of the latter effect was large, however, and in most cases the increase was not statistically significant. Addition of catalase (100 mU/ml) or catechin (0.5 mmol/l) to the perfusion medium abolished the nitrofurantoin induced release of oxidized glutathione but did not not prevent or attenuate enzyme leakage from the cells and the development of a negative inotropic effect. These results suggest that the cardiotoxic effects of nitrofurantoin and tertiary butylhydroperoxide cannot be explained by the appearance of oxygen radicals alone and that an increased lipid peroxidation is not the mechanism which is primarily responsible for cell death.

Animals↗
PubMed1993

Respiratory response to pulmonary vascular congestion in intact conscious dogs.

Clinical disorders associated with pulmonary venous hypertension frequently result in tachypnea and hyperpnea. The response to pulmonary vascular congestion (PVC) in anesthetized or decerebrate animals has consisted of modest and bidirectional changes in respiratory rate with no hyperpnea. We hypothesized that anesthesia or decerebration in previous animal experiments may have attenuated the hyperpneic response that would otherwise have been evident. A conscious dog model was developed in which the left lower lobe (LLL) pulmonary circulation could be reversibly isolated and pressurized. Occluders were placed outside the LLL pulmonary artery (PA) and vein. Two fine catheters were introduced through the wall of the LLLPA distal to the arterial occluder. A pleural catheter was used to monitor pleural pressure swings. After recovery from surgery PVC was initiated by inflation of the occluders and injection of warm saline or fresh warm blood through one of the catheters. PVC resulted in decreased breathing frequency and hypopnea in six of seven intact unanesthetized dogs. The remaining dog exhibited a transient rapid shallow breathing pattern. In four dogs tested using the same preparation under anesthesia, the response to PVC was an increase instead of a decrease in breathing frequency. We conclude that the presence of higher brain function does not promote tachypnea or hyperpnea in response to PVC. Mechanisms other than PVC, per se, likely account for the tachypnea and hyperpnea observed in clinical disorders associated with pulmonary venous hypertension.

Air Pressure↗
PubMed1993

Steady-state ventilatory responses to expiratory resistive loading in quadriplegics.

Patients with quadriplegia have a limited capacity to recruit expiratory muscles and are deprived of respiratory-related feedback from the rib cage and abdominal wall. We wished to evaluate the compensatory strategies available to such patients during expiratory resistive loading (ERL) and to compare their responses with those of normal healthy individuals. In addition, to determine whether the quadriplegic subjects have a blunted sensory appreciation of added ERL, we also compared sensory detection thresholds (delta R50). Steady-state ventilatory responses to ERL (delta R = 12 cm H2O/L/s) were compared in seven quadriplegic patients (level of injury, C6, C7) and six age-matched normal subjects. Highly significant intergroup differences were evident in the extent of prolongation of expiratory time (TE) and total cycle duration (Ttot) during ERL; values of delta TE and delta Ttot in quadriplegics were, on average, 46% of those of normals (p < 0.001). Minute ventilation (VE) was defended to an equal or better extent in quadriplegics. ERL-induced changes in tidal volume, inspiratory duration, mean inspiratory and expiratory flows, and end-expiratory lung volume (EELV) were not significantly different. Average delta R50 in quadriplegics and normals were (mean +/- SD), 1.73 +/- 0.039 cm H2O/L/s and 1.62 +/- 0.4 cm H2O/L/s, respectively (p = ns). Quadriplegics, therefore, despite substantial sensory and motor deficits, defend ventilation and EELV as effectively as normal individuals and show no attenuation in the ability to detect an added expiratory resistance.

Adult↗
PubMed1992

The toxicological relevance of paracetamol-induced inhibition of hepatic respiration and ATP depletion.

In order to elucidate the role of mitochondrial dysfunction in paracetamol-induced hepatotoxicity, the effects of paracetamol on the oxygen consumption and ATP content of the isolated perfused rat liver were correlated with parameters of hepatic viability and hepatotoxicity. Paracetamol at 5 g/L reduced the oxygen consumption of the livers by about 80% and hepatic ATP content by 96%. Hepatotoxicity was evident from the nearly complete interruption of bile secretion, a marked release of enzymes [glutamate-pyruvate transaminase (GPT), lactate dehydrogenase (LDH)] in the perfusate, a depletion of hepatic glutathione and an accumulation of calcium in the liver. Paracetamol-induced hepatotoxicity could be prevented completely by using livers from non-fasted rats as well as by addition of fructose to the perfusate of livers from fasted animals. Both treatments resulted in an increased energy supply from anaerobic glycolysis as evidenced by a large release of lactate and pyruvate into the perfusate, but did not inhibit paracetamol-induced decline of oxygen consumption. The decrease in hepatic oxygen consumption depended on the dose of paracetamol and occurred first at a concentration of 0.2 g/L (-10%). LDH and GPT release, on the other hand, was elevated at 2 and 5 g/L and calcium accumulation occurred at 5 g/L paracetamol only. Inhibition of mixed-function oxidases by dithiocarb did not prevent the decrease in oxygen consumption and the resulting hepatic injury induced by paracetamol. The oral administration of the high dose of 5 g/kg paracetamol in vivo to rats exerted strong hepatotoxicity but produced maximal serum levels of 800 mg/L paracetamol only and did not decrease hepatic oxygen consumption as measured in vitro. Our results show that in the isolated perfused rat liver in vitro, only high concentrations of paracetamol can produce "chemical hypoxia" by attacking mitochondria so as to cause hepatic injury. Such high concentrations of paracetamol are not attained in vivo, however. "Chemical hypoxia", thus, seems not to be relevant to the well-known hepatotoxic action of paracetamol.

Acetaminophen↗
PubMed1992

Effect of antioxidants on hypoxia/reoxygenation-induced injury in isolated perfused rat liver.

Isolated perfused livers from rats fasted overnight were subjected to 30 min. of hypoxia followed by reoxygenation for 60 min., resulting in marked cytotoxicity as evidenced by an enhanced release of cytosolic enzymes (lactate dehydrogenase: 14-fold over controls, glutamate-pyruvate-transaminase: 12-fold over controls) and glutathione (twofold over controls) into the perfusate, by calcium accumulation (by a factor of 1.4) in the tissue and by an 80% inhibition of bile secretion. Virtually no mitochondrial injury became apparent and no evidence for lipid peroxidation could be found. In the presence of ascorbate, an augmentation of hepatic injury was observed. This might be due to the pro-oxidant activity of ascorbate in the presence of ionized iron, which is easily released from high molecular weight stores under reductive (e.g. hypoxic) conditions. The water soluble vitamin E analogue trolox C as well as propyl gallate clearly protected the liver against hypoxia/reoxygenation injury, yielding further evidence for a causative role of oxidative stress in this model. Due to their water solubility and their high efficacy as free radical scavengers, these antioxidants might be of therapeutic value.

Animals↗
PubMed1992

Mechanism of detection of resistive loads in conscious humans.

Conscious humans easily detect loads applied to the respiratory system. Resistive loads as small as 0.5 cmH2O.l-1.s can be detected. Previous work suggested that afferent information from the chest wall served as the primary source of information for load detection, but the evidence for this was not convincing, and we recently reported that the chest wall was a relatively poor detector for applied elastic loads. Using the same setup of a loading device and body cast, we sought resistive load detection thresholds under three conditions: 1) loading of the total respiratory system, 2) loading such that the chest wall was protected from the load but airway and intrathoracic pressures experienced negative pressure in proportion to inspiratory flow, and 3) loading of the chest wall alone with no alteration of airway or intrathoracic pressure. The threshold for detection for the three types of load application in seven normal subjects was 1.17 +/- 0.33, 1.68 +/- 0.45, and 6.3 +/- 1.38 (SE) cmH2O.l-1.s for total respiratory system, chest wall protected, and chest wall alone, respectively. We conclude that the active chest wall is a less potent source of information for detection of applied resistive loads than structures affected by negative airway and intrathoracic pressure, a finding similar to that previously reported for elastic load detection.

Adult↗
PubMed1992

Proportional assist ventilation, a new approach to ventilatory support. Theory.

The relation between inspiratory effort and ventilatory return (flow and volume) is usually abnormal in patients who require ventilatory support because of respiratory distress. Although all available support methods provide the patient with greater ventilation than would obtain with the same effort while unsupported, the relation between instantaneous effort and ventilatory consequences is not normalized. We describe an approach with which the ventilator simply amplifies patient instantaneous effort throughout inspiration while leaving the patient with complete control over all aspects of breathing pattern (tidal volume, inspiratory and expiratory durations, and flow patterns). This approach is implemented by monitoring the instantaneous rate (V) and volume (V) of gas flow from ventilator to patient and causing applied pressure (P) to change according to the equation of motion [P = f1(V) + f2(V)], where f1 and f2 are appropriately selected functions for the relation between pressure and volume (elastic assist) and pressure and flow (resistive assist). There are several potential advantages to this approach: (1) greater comfort; (2) reduction of peak airway pressure required to sustain ventilation and, hence, the potential for avoiding intubation; (3) less likelihood of overventilation; (4) preservation and enhancement of patient's own reflex, behavioral, and homeostatic control mechanisms since the ventilator essentially becomes an extension of the patient's own muscles; and (5) improved efficiency of negative pressure ventilation.

Humans↗
PubMed1992

Proportional assist ventilation. Results of an initial clinical trial.

The response to proportional assist ventilation (PAV) was tested in four normal subjects during heavy exercise and in five ventilator-dependent patients recovering from assorted medical disorders. The apparatus consisted of a rolling-seal piston coupled to a motor that generated pressure in proportion to inspired flow and inspired volume, with the gains adjusted such that the proportionality between airway pressure (Paw) and instantaneous patient-generated pressure (Pmus) was approximately 1:1 (i.e., machine-amplified patient effort by a factor of 2). Normal subjects responded to PAV by decreasing their own effort, as judged from esophageal pressure, such that the changes in ventilation and breathing pattern were rather small (VE: 64.8 +/- 3.6 during PAV versus 56.0 +/- 4.3, p less than 0.01; VT: 2.39 +/- 0.24 versus 2.02 +/- 0.17, p less than 0.05; f: 27.5 +/- 1.9 versus 28.0 +/- 2.2, NS). In patients, elastance ranged from 20 to 35 cm H2O cm/L, resistance ranged from 5 to 10 cm H2O/L/s, and maximal inspiratory pressure ranged from -16 to -65 cm H2O. After a period of observation during synchronized intermittent mechanical ventilation (SIMV) the patient was switched to PAV and maintained on it for 1 to 3 h. No patient had to be replaced on SIMV because of discomfort or deterioration in any of the monitored variables. During PAV peak airway pressure was less than half the value observed with the IMV breaths (16.6 +/- 2.4 versus 35.4 +/- 3.4 cm H2O, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗