Biomedical subjects

M Younes

Publications and source records attributed to M Younes.

At least 73 records · Page 4Linked to original sources

PubMed1997

Lack of prognostic significance of histological grade in node-negative invasive breast carcinoma.

Histological grade (HG), as modified by Elston and Ellis (Histopathology, 19: 403-410, 1991), was shown to be a significant prognostic indicator in a large group of women with invasive breast cancer, who had node-negative as well as node-positive tumors and included special types of breast cancer. The aim of this study was to determine the utility of HG as a prognostic indicator in node-negative invasive breast cancer, no special type (NN-BCA-NST), which represents the majority of cases seen in clinical practice. One hundred eighty-two women with NN-BCA-NST and who had 28-106 months follow-up (mean, 73 months; median, 71 months) were entered in the study. Bilateral and multifocal cancers, and cancers with distant metastases, were excluded. Nuclear grade (NG), tubule formation (TF), mitotic index (MI), and HG were determined and scored as described by Elston and Ellis (Histopathology, 19: 403-410, 1991). Survival analysis was performed by the Kaplan-Meier method and the log-rank test. Regression analysis was used to determine the relationship between NG, TF, and MI. There was significant correlation between NG and MI (R = 0.667, P < 0.0001) and between TF and MI (R = 0.416, P < 0.0001). NG, TF, MI, and HG did not have significant prognostic value (P = 0.3771, P = 0.7972, P = 0.2953, and P = 0.7946, respectively). HG was of no significant prognostic value even after women who received adjuvant therapy were excluded from the analysis (P = 0.3917). Our data show that the HG is not a reliable prognostic indicator in NN-BCA-NST.

Age Factors↗

PubMed1996

Wide expression of the human erythrocyte glucose transporter Glut1 in human cancers.

Glucose uptake has been found to be increased in cancer cells. Previous work has shown increased expression of the human erythrocyte glucose transporter (Glut1) mRNA in some human cancers, indicating that Glut1 may play a significant role in glucose uptake by these tumors. The distribution of Glut1 protein in normal and malignant human tissues is still largely unknown. Using immunohistochemistry, we found that Glut1 is largely undetectable in normal epithelial tissues and benign epithelial tumors but is expressed in a significant proportion of a variety of human carcinomas. We hypothesize that Glut1 expression by human carcinomas indicates an increased glucose uptake, and probably increased utilization of energy, which may correlate with an aggressive behavior. The biological significance of Glut1 expression needs to be determined.

Blotting, Western↗

PubMed1996

Comparative studies on the toxicity of mercury, cadmium, and copper toward the isolated perfused rat liver.

The toxic effects of cadmium, mercury, and copper were compared over the over range 0.01, 0.03, and 0.1 mM using the isolated perfused rat liver preparation. All metals caused similar changes in various parameters used to describe general toxicity. Thus reductions in oxygen consumption, perfusion flow, and biliary secretion were found, while lactate dehydrogenase release into the perfusate, as well as liver weight, increased also in a dose-dependent fashion. Each metal caused similar magnitudes of changes and exerted similar potency. Measurement of other parameters indicating more specific injury revealed a number of differences. Although all metals reduced hepatic ATP concentration, mercury and cadmium were more potent than copper in this respect. Cadmium was the most potent at decreasing reduced glutathione levels. Mercury was most effective at increasing tissue calcium content, while copper was less so, and cadmium ineffective. Only copper significantly increased tissue malondialdehyde (MDA) content, while all metals increased its release into perfusate. Furthermore, whereas cadmium seemed the most potent metal in increasing MDA release, it was least efficacious, while copper was the most. Antioxidants such as superoxide dismutase, catalase, and Trolox C only reduced cadmium's influence on MDA in perfusate; however, they did not affect cadmium's ability to alter most other parameters of vitality. Albumin reversed the toxic effects of copper and mercury, but not cadmium. While metal-induced reductions in perfusion flow accounted for some of the toxic effects of the metals investigated, the results as a whole supported the suggestion that all metals exerted toxicity at the mitochondria, since ATP levels were reduced in a manner that could not be reproduced by perfusion flow reduction alone. Lipid peroxidation appears to play little role in determining toxicity induced by any of these metals. Furthermore, albumin may play an important physiological role in preventing hepatic injury that might otherwise be induced through acute metal intoxication.

Adenosine Triphosphate↗

PubMed1996

Ventilatory stability during sleep studied with proportional assist ventilation (PAV).

We propose the use of proportional assist ventilation (PAV) as a method to quantitate ventilatory stability. The PAV amplification factor required to produce periodic breathing is the reciprocal of overall loop gain. Using this approach in 12 normal subjects we found that, after stabilization of upper airway with continuous positive airway pressure (CPAP) (5.2 +/- 2.0 cm H2O), overall loop gain was very low (< 0.3) indicating that sleep. per sc, is not destabilizing under normal conditions.

Electroencephalography↗

PubMed1996

Response of ventilator-dependent patients to different levels of proportional assist.

Proportional-assist ventilation (PAV) is a form of ventilatory support in which airway pressure increases in proportion to patient effort. Because it effectively reduces the mechanical load to an adjustable extent, PAV permits the study of the pattern of breathing in patients with respiratory disease when unconstrained by abnormal respiratory mechanics. We studied 11 patients with assorted medical problems requiring ventilatory support. The patients were switched to PAV, and the level of support was varied from near-maximal levels to the lowest tolerable level. Each level was maintained for several minutes while ventilation (VE), tidal volume (VT), and respiratory rate (f) were monitored. The breathing pattern observed with the highest assist varied substantially among patients. The ranges (and means) of VE, VT, and f were 5.6-18.7 (12.8) l/min, 203-844 (517) ml, and 18-33 (25) breaths/min, respectively. The correlation between VT and VE at the highest assist was very high (r = 0.91), suggesting that ventilatory demand is the most important determinant of VT variability. There were no systematic changes in breathing pattern as the level of assist was altered; at the highest and lowest levels of support, VE, VT, and f were, respectively, 12.8 +/- 5.4 (SD) vs. 11.6 +/- 4.3 l/min, 517 +/- 217 vs. 459 +/- 175 ml, and 25.0 +/- 4.2 vs. 25.7 +/- 3.9 breaths/min. These results indicate that within each patient, in a given state, there exist unique values for a desired VE, VT, and f that are largely independent of the mechanical load; if assist is increased, patient effort is decreased to maintain the desired ventilatory targets.

Adult↗

PubMed1996

Respiratory control during volume-cycled ventilation in normal humans.

The purpose of this study was to evaluate the extent of inhibition to respiratory rhythm associated with high volumes of ventilation during volume-cycled mechanical ventilation (neuromechanical inhibition). Two approaches were used. 1) In 18 normal awake subjects, ventilator tidal volume (VT) in the assist/control mode (A/C) was increased in steps from the minimum tolerable level up to 80% of the subject's inspiratory capacity or ventilator's maximum VT. We looked for appearance of intermittent apnea or a reduction in spontaneous rate (f). 2) Another 18 normal awake subjects were placed on controlled mechanical ventilation (CMV). When apnea was established, we abruptly terminated CMV and measured the time before the appearance of the next spontaneous effort. In the assist mode (protocol 1), we did not observe intermittent apnea because VT was increased from [from 944 +/- 198 to 1,867 +/- 277 (SD) ml], and there was only a modest reduction in f (14.1 +/- 3.9 to 12.4 +/- 4.0 breaths/min). End-tidal PCO2 (PETCO2) decreased precipitously as VT was increased. In protocol 2, we did not observe apnea after discontinuation of CMV in any subject. Total breath duration of the first breath after discontinuation did not differ significantly from total breath duration during A/C in the same subjects (4.84 +/- 2.2 vs. 5.2 +/- 2.0 s). This similarly applied regardless of route of breathing (nose vs. mouth) or PETCO2 level at time of discontinuation. We conclude that neuromechanical inhibition is quite weak and provides very little negative feedback that may help control PCO2 in the face of excessive VT and f demands of the subject.

Adult↗

PubMed1996

Effects of breathing route, temperature and volume of inspired gas, and airway anesthesia on the response of respiratory output to varying inspiratory flow.

The determinants of the response of the respiratory output to inspiratory flow rates (VI) were examined in awake normal subjects. Subjects were connected to a volume-cycle ventilator in the assist/control mode, and VI was increased in steps from 30 to 90 L/min and then back to 30 L/min. VI pattern was square, and all breaths were subject-triggered. In six subjects the effects of breathing route (nasal or mouth) and temperature and volume of inspired gas (Protocol A) and in 8 subjects the effects of airway anesthesia (upper and lower airways; Protocol B) on the response of respiratory output to varying VI were studied. In Protocol B, in order to calculate muscle pressure during inspiration (Pmus), respiratory system mechanics were measured using the interrupter method at end-inspiration. Independent of conditions studied, breathing frequency increased significantly and end-tidal concentration of CO2 decreased as VI increased. The response was graded and reversible and not affected by breathing route, temperature and volume of inspired gas, and airway anesthesia. With and without airway anesthesia (Protocol B), neural inspiratory and expiratory time and neural duty cycle, estimated from Pmus waveform, decreased significantly as VI increased. At all conditions studied, the rate of change in airway pressure prior to triggering the ventilator tended to increase as VI increased. The changes in timing and drive were nearly complete within the first two breaths after transition, with no evidence of adaptation during a given VI period. We conclude that VI exerts an excitatory effect on respiratory output which is independent of breathing route, temperature and volume of inspirate, and airway anesthesia. The response most likely is neural in origin, mediated through receptors not accessible to anesthesia, such as those located in the chest wall or below the airway mucosa.

Adult↗

PubMed1996

Noninvasive positive-pressure ventilation in acute respiratory distress without prior chronic respiratory failure.

We evaluated the efficacy of noninvasive mechanical ventilation (NIMV) in alleviating distress and avoiding intubation in patients with de novo acute respiratory failure complicating primary medical disorders. Eleven consecutive patients with severe respiratory distress were entered. In all patients a decision to intubate on an urgent basis had been made, but NIMV could be initiated within minutes. The patients suffered from acute pulmonary edema (five), sepsis/ARDS (two), status asthmaticus (two), and severe pneumonia (two). Dyspnea score (max=10) was (+/- SD) 8.4 +.- 1.6, scale for accessory muscle use (max=5) was 4.2 +/- 0.7, and respiratory rate was 37.6 +/- 3.8 min -1. Pa CO2, pH, and base excess (BE) were 48 +/- 18 mm Hg, 7.27 +/- 0.13, and -5.5 +/- 7.4, respectively, with five patients showing severe metabolic acidosis (BE < - 10). NIMV was applied using proportional assist ventilation. There were three early failures. These included the two patients with sepsis/ARDS who did not tolerate the mask. One patient failed because Pa CO2 and pH deteriorated despite subjective improvement. The remaining eight patients demonstrated progressive improvement, and none required intubation. The duration of NIMV was 3 h to 2 d. We conclude that when NIMV is made available on a "few minutes" basis, selected patients with severe de novo respiratory distress/failure caused by reversible medical disorders, who would otherwise have been intubated, can be given substantial relief and be spared intubation.

Acid-Base Imbalance↗

PubMed1996

Effects of non-REM sleep on the response of respiratory output to varying inspiratory flow.

It has been shown in mechanically ventilated awake normal humans that increasing inspiratory flow rate (VI) exerts an excitatory effect on respiratory output. It is not known if this effect persists during sleep. To test this, seven normal adults were studied during wakefulness and non-rapid eye movement (non-REM) sleep. Subjects were connected through a nose mask to a volume-cycled ventilator in the assist/control mode, and VI was increased in steps (3 to 4 breaths each) from 30 to 70 L/min and then back to 30 L/min. VI pattern was square, and all breaths were subject-triggered. Forty-one trials during non-REM sleep and 10 during wakefulness were analyzed. Both during sleep and wakefulness minute ventilation increased and total breath duration (Ttot) decreased significantly in a graded and reversible manner as VI increased. These changes were complete in the first breath after VI transition. The response was significantly less during sleep than during wakefulness (p < 0.050; at 30 L/min Ttot, expressed as percent of that at 70 L/min, was 110.2 +/- 1.3% during sleep and 127.8 +/- 3.9% during wakefulness. During wakefulness, the rate of change in airway pressure before triggering the ventilator (dp/dt), an index of respiratory drive, increased significantly (p < 0.05) with increasing VI. During sleep dp/dt was not affected by VI changes. In four sleeping subjects the increase in VI was sustained for 1.5 to 2 min. There was no evidence for adaptation of the response; Ttot, averaged over the last three breaths, did not differ from that obtained with VI was sustained for only 3 to 4 breaths. We concluded that VI exerts an excitatory effect on respiratory output, mediated by a reflex neural mechanism, and the gain of this reflex is attenuated by sleep.

Adaptation, Physiological↗

PubMed1996

Overexpression of the human erythrocyte glucose transporter occurs as a late event in human colorectal carcinogenesis and is associated with an increased incidence of lymph node metastases.

Energy metabolism of human colon cancer in vivo relies predominantly on glucose. Although studies have revealed increased expression of Glut1 mRNA in colon cancer, Glut1 protein (Glut1) expression in the large intestine and its significance are still unknown. The objective of this work was to determine whether Glut1 is present in human colorectal neoplasms and whether that presence is of biological significance. Formalin-fixed, paraffin-embedded tissue sections of 53 colonic adenocarcinomas, 82 adenomas, 46 hyperplastic polyps, and 38 normal colon samples were immunostained with the anti-Glut1 antibody MYM. The localization was carried out using the avidin-biotin immunoperoxidase technique. No Glut1 immunoreactivity was present in normal colonic mucosa or in hyperplastic polyps, whereas 8 (10%) of 82 adenomas showed such immunoreactivity. The frequency of Glut1 expression in adenomas increased with villous morphology and with the size of the adenoma. Forty-four (83%) of 53 colorectal adenocarcinomas expressed Glut1, and, of these, tumors in which >50% of the cancer cells expressed Glut1 had a significantly higher incidence of metastasis to the lymph nodes (P = 0.0001). It is concluded that (a) Glut1 is expressed as a late event in the carcinogenesis process in human colorectal cancer, and (b) expression of Glut1 in a high proportion of cancer cells is associated with a high incidence of lymph node metastases.

Adenocarcinoma↗

PubMed1995

p53 protein accumulation in tumors of the ampulla of Vater.

BACKGROUND: Accurate preoperative diagnosis of tumors of the ampulla of Vater is difficult because ampullary biopsies have a high false-negative rate. Recently, it has been suggested that p53 mutations in tumors of the ampulla of Vater are associated with the transformation of adenomas and low grade carcinomas to high grade carcinomas. The purpose of this study was to determine the extent of p53 protein accumulation in tumors of the ampulla of Vater, and to determine whether p53 accumulation can be detected in false-negative biopsies. METHODS: Using a monoclonal anti-p53 antibody, sections of 4 normal ampullas, 5 adenomas, 17 carcinomas, and 9 initial biopsies of 9 of the tumors of the ampulla of Vater that had no morphologic evidence of carcinoma were immunostained. RESULTS: None of the 4 normal ampullas (0%), 2 of 5 adenomas (40%), and 16 of 17 carcinomas (94%) were positive for p53. This p53 positivity was present through all stages of ampullary carcinoma. Of the nine initial biopsies negative for carcinoma, seven were positive for p53 and, of these, six (86%) were found to be carcinomas upon resection. CONCLUSIONS: 1) The molecular events leading to p53 accumulation in tumors of the ampulla of Vater occur early in the neoplastic process. 2) Tumors of the ampulla of Vater with biopsies negative for malignancy but positive for p53 are very likely to be carcinomas.

Adenoma↗

PubMed1995

p53 accumulation in benign breast biopsy specimens.

Several studies of benign breast lesions using methacran-fixed, paraffin-embedded tissues and cytological preparations have suggested that p53 accumulation in these lesions as detected by immunohistochemical (IHC) staining is rare to absent. As a result, several different investigators have suggested that p53 immunoreactivity in breast specimens infers a diagnosis of malignancy or may identify premalignant lesions. We immunostained 271 breast biopsy specimens from 271 patients with the monoclonal anti-p53 antibody BP-53-12 and found positive nuclear staining in seven of 23 malignant lesions (30%) and 39 of 248 benign biopsy specimens (16%). Of the benign lesions, 30% of fibroadenomas, nonpremalignant breast lesions, were positive. Long-term follow-up information was available on 48 patients with benign biopsy specimens and showed that 12% of those positive and 7% of those negative for p53 developed breast carcinoma. This difference was not significant (P > .2). We conclude that (1) p53 immunoreactivity in breast lesions should not be used as exclusive evidence of malignancy and (2) p53 immunoreactivity in benign breast lesions may not identify a subset of patients at increased risk for breast carcinoma.

Antibodies, Monoclonal↗

PubMed1995

The role of biomarkers in derivation of WHO-guidance values for air pollutants.

The Air Quality Guidelines for Europe (AQG) have provided a basis for the control of air pollution, and have contributed to the maintenance and improvement of public health in several countries. The process of updating and revision of the AQG will be completed by 1996. The applicability of biomarkers for derivation of health-based guidelines will depend on the validation of biomarkers also at low (environmental) levels of exposure, the availability of adequate population studies using biomarker information, and the development of better quantitative relationships between ambient levels, biomarker concentrations and, ideally, effects.

Air Pollutants↗

PubMed1995

Short- and long-term repeatability of Visioptic Alcon EyeMap (Visioptic EH-270) corneal topographer on normal human corneas.

The purpose of this study was to examine the short-term and long-term (6 months) repeatability of the Alcon EyeMap (Visioptic EH-270)a Computerized Corneal Topographer on normal eyes. Three measurements were taken on both eyes of 39 subjects with the corneal topographer. Both eyes of seven of these subjects were measured 6 months later in order to evaluate long-term repeatability. The data showed that short-term reliability of the instrument was acceptable with a mean standard deviation (SD) < or = 0.5 D up to 3 mm (6-mm optical zone) from the center of the normal cornea. Beyond that distance, SD's of repeated measures increased systematically, making the results less useful. Long-term repeatability of the instrument over a 6-month period was acceptable clinically, although statistically significant differences were noted.

Adult↗

PubMed1995

Association between mucosal hyperplasia of the appendix and adenocarcinoma of the colon.

Mucosal hyperplasia of the appendix is a seemingly benign change of poorly understood significance, at times found in patients with colorectal malignancy. To determine the incidence of this change and its association with colonic adenocarcinoma, we have examined the appendiceal mucosa in 122 ileocolectomy specimens gathered between 1987 and 1990, and in 273 consecutive appendectomies carried out during 1990 at The Methodist Hospital in Houston, Texas. We found that 23 out of 122 ileocolectomies (18.8%) showed mucosal hyperplasia of the appendix and, of these, 17 (77%) were associated with colorectal malignancy, predominantly of the right side. Moreover, 24 of 273 appendectomies (8.8%) exhibited the presence of mucosal hyperplasia and, of these, six (25%) also were associated with adenocarcinoma of the colon. On the basis of this significant rate of association, we feel that a concomitant colorectal carcinoma should be ruled out in patients who exhibit mucosal hyperplasia of the appendix.

Adenocarcinoma↗

PubMed1995

Exercise- and cold-induced asthma.

Exercise- and cold-induced asthma are commonly recognized respiratory disorders. The asthmatic response includes several factors contributing to airway narrowing, and thus increased airway resistance. These include airway smooth muscle contraction, mucus accumulation, and bronchial vascular congestion as well as epithelial damage and vascular leakage. The etiology for these disorders is nonantigenic. The primary stimulus is probably a combination of airway cooling and drying (leading to hypertonicity of airway lining fluid). Symptoms generally do not occur during the stimulus period (e.g., exercise) itself. This protection may in part be due to increased catecholamine levels during exercise. The early phase response, which occurs 5 to 15 min poststimulus, may be mediated through a combination of (a) direct influences, (b) vagal reflexes triggered by airway sensory receptors, or (c) responses to mediator release. Spontaneous recovery occurs within 30 min to 2 hrs. There is usually a refractory period of about 1 to 2 hrs during which responses to further stimuli are attenuated. This may be due to depletion of histamine and other mediators. As well, prostaglandin release (mediated via LTD4 which is released during exercise) inhibits further airway narrowing. A late phase response has been reported 4 to 10 hrs poststimulus in some patients. These reactions are accompanied by a second release of histamine and other mediators that cause inflammatory responses and epithelial damage. However, the exercise dependence of this response is debated.

Airway Resistance↗

PubMed1995

Role of ventilatory response to exercise in determining exercise capacity in COPD.

The progression of chronic obstructive pulmonary disease (COPD) is generally associated with decreased exercise capacity. Differences in forced expired volume in 1 s (FEV1) among patients account for only a fraction of the variability in maximal oxygen consumption (VO2max). We hypothesized that variability in ventilatory response to exercise and in inspiratory mechanics and body mass index contributes importantly to variability in VO2max in this disease. We analyzed the files of 53 patients with established diagnosis of COPD who underwent a recent symptom-limited exercise test. We used inspiratory capacity and maximum inspiratory flow as measures of variability in inspiratory mechanics. The minute ventilation (VE) at the subject's VO2max was divided by the predicted in a normal subject at the same VO2 to obtain a ratio (VE,max/VE,pred). The ventilatory response during exercise provided the best correlation with peak VO2 (r = 0.62). FEV1 and inspiratory capacity also correlated with peak oxygen consumption but not as well as the ventilatory response (r = 0.49 and r = 0.46, respectively). Maximum inspiratory flow and body mass index showed only weak positive correlations (r = 0.23, not significant). The stepwise analysis generated the following equation: VO2max (%predicted) = (77.26 x VE,pred/VE,max) + [0.45 x FEV1 (%predicted)] - 23.66; r = 0.76, P < 0.001. We conclude that variability in the ventilatory response during exercise is one of the main determinants of variability in exercise capacity in COPD patients.

Adult↗

PubMed1995

Respiratory response to CO2 in the hypocapnic range in awake humans.

The response of respiratory motor output to CO2 in the hypocapnic range (< 36 Torr PCO2) in the absence of hypoxemia is not well characterized in awake normal humans. We induced hypocapnia with hyperoxia in 16 normal volunteers by placing them on a volume-cycled ventilator in the assist mode. Subjects were not aware of the purpose of the study. All subjects continued rhythmic breathing despite high tidal volumes and severe hypocapnia (approximately 25 Torr alveolar PCO2). Inspired CO2 fraction was increased in steps, and changes in respiratory motor output were quantitated from changes in airway pressure at constant volume and flow, changes in respiratory rate, and change in rate of decline in airway pressure before triggering (dP/dt). There was a significant increase in respiratory muscle pressure, but not in respiratory rate, from 26 to 36 Torr PCO2. The slope of the response increased gradually from 26 to 41 Torr PCO2. Respiratory rate significantly increased only above 36 Torr. We conclude that the response to PCO2 in the hypocapnic range is basically nonlinear with no clear CO2 threshold and the CO2 responsiveness extends well below eupneic CO2 levels.

Adult↗