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Biomedical subjects

A Cherif

Publications and source records attributed to A Cherif.

At least 55 records · Page 3Linked to original sources

Halogenated analogues of tamoxifen: synthesis, receptor assay, and inhibition of MCF7 cells.

This study was conducted to develop a ligand for imaging estrogen-receptor-positive breast tumors by positron emission tomography or single photon emission computed tomography. We synthesized fluoro and iodo analogues of tamoxifen, and these halogenated analogues produced greater affinity for binding to the receptor than tamoxifen. Values of the inhibition affinity constants were as follows: tamoxifen, 15,000 nM; fluoromethyl-N,N-diethyltamoxifen, 2500 nM for the cis isomer and 500 nM for the trans isomer; and iodomethyl-N,N-diethyltamoxifen, 1500 nM for the cis isomer and 1000 nM for the trans isomer. In studies of human MCF7 breast tumor cell growth, concentrations that inhibited tumor growth in 50% of the cases were as follows: tamoxifen, 11 microM; fluoromethyl-N,N-diethyltamoxifen, 4.5 and 11.8 microM for the cis and trans isomers, respectively; and iodomethyl-N,N-diethyltamoxifen, 2.4 and 6.3 microM for the cis and trans isomers, respectively. These studies suggest that both fluoro and iodo analogues of tamoxifen may be useful diagnostic compounds for predicting the response of estrogen-receptor-positive breast tumors to tamoxifen analogues used in chemotherapy.

Animals↗

Continuous positive airway pressure (CPAP) vs. intermittent mandatory pressure release ventilation (IMPRV) in patients with acute respiratory failure.

Intermittent Mandatory Pressure Release Ventilation (IMPRV) is a positive pressure spontaneous breathing ventilatory mode in which airway pressure is released intermittently and synchronously with patient's spontaneous expiration in order to provide ventilatory assistance. Eight critically ill patients free of any factor known to alter chest wall mechanics (group 1) and 8 critically ill patients whose spontaneous respiratory activity was markedly altered by a flail chest, or by a C5 quadraplegia and/or by the administration of opioids (group 2) were studied prospectively. CPAP and IMPRV were administered to each patient in a random order during a 1 h period using a CESAR ventilator. Gas flow, tidal volume, tracheal pressure, esophageal pressure, end-expiratory lung volume and hemodynamic parameters were measured. In group 1 patients, the ventilatory assistance provided by IMPRV was associated with a significant decrease in spontaneous tidal volume whereas all other respiratory parameters remained unchanged. In group 2 patients, IMPRV increased minute ventilation from 8.0 +/- 2.61/min to 12.2 +/- 1.81/min (p less than 0.05), decreased PaCO2 from 46 +/- 7.3 mmHg to 38 +/- 6.8 mmHg (p less than 0.05) and reduced respiratory frequency from 21 +/- 10 bpm to 14 +/- 5.7 bpm (p less than 0.07). These results show that IMPRV provides significant ventilatory assistance to patients with mild acute respiratory failure either by decreasing patient's contribution to minute ventilation or by increasing alveolar ventilation in presence of respiratory depression of central or peripheral origin.

Acute Disease↗

N-(5,5-diacetoxypentyl)doxorubicin: a novel anthracycline producing DNA interstrand cross-linking and rapid endonucleolytic cleavage in human leukemia cells.

The cytotoxic and DNA-damaging effects of a novel alkylating anthracycline, N-(5,5-diacetoxypentyl)doxorubicin, were quantified in HL-60 human leukemia cells and in an intercalator-resistant daughter line, HL-60/AMSA. The new drug was cytotoxic to both lines at doses as low as 50 nM for 1 h. N-(5,5-Diacetoxypentyl)doxorubicin produced DNA interstrand cross-linking in both lines. The cross-linking appeared to increase in both lines following drug treatment, but the increase was greater in the resistant line. This appeared to be due to an underestimation of cross-linking, particularly in sensitive HL-60, secondary to time-dependent DNA fragmentation that followed drug removal. This time-dependent DNA fragmentation was probably endonucleolytic cleavage (a feature of apoptosis) as characteristic nucleosomal ladders were produced by N-(5,5-diacetoxypentyl)doxorubicin treatment in a cotemporal time-dependent fashion. This novel anthracycline is the first of a family of alkylating anthracyclines designed to be water soluble, easy to formulate, and capable of producing DNA interstrand cross-linking. Because this last characteristic has previously been associated with doxorubicin analogues of great potency and low toxicity, these newer, more readily formulated drugs may have great clinical utility.

Alkylating Agents↗

[Small intestine occlusion caused by the silent opening of liver hydatid cysts into the peritoneum. Apropos of an uncommon case].

The authors report one exceptional case of organic small bowel occlusion. The etiological diagnosis was performed by ultrasonographic examination and showed two hydatid cysts of the liver opened into the peritoneum and a peritoneal fluid collection corresponding to the hydatid fluid. The authors emphasize the absence of clinical symptoms during the opening of the hydatid cysts of the liver into the peritoneum and the usefulness of emergency ultrasonographic examination of the entire abdomen in cases of small bowel obstruction without any evident etiology.

Adult↗

Hypoglycemia during prolonged exercise in normal men.

Hypoglycemia (blood glucose less than 45 mg per deciliter [less than 2.5 mmol per liter]) occurred in seven of 19 healthy men who exercised to exhaustion on a cycle ergometer at 60 to 65 per cent of maximal aerobic power. The hypoglycemic subjects exercised for 15 to 70 minutes despite blood glucose levels of 25 to 48 mg per deciliter (1.4 to 2.7 mmol per liter), and their exhaustion time (mean +/- S.E.M., 142 +/- 15 minutes) was not significantly different from that of the euglycemic group (165 +/- 11). Plasma epinephrine was inversely related to blood glucose (P less than 0.01) and was three times higher in the hypoglycemic subjects (P less than 0.05). Glucose ingestion (40 or 80 g per hour) prevented the hypoglycemia and resulted in a smaller rise in plasma epinephrine but did not alter perceived exertion or consistently delay exhaustion. We conclude that hypoglycemia occurs in normal subjects during prolonged exercise and results in an exaggerated rise in plasma epinephrine. However, hypoglycemia fails to effect endurance, and its prevention does not consistently delay exhaustion.

Adolescent↗

[Coronary artery disease in Takayasu's disease. Report of an operative case].

A 39-years-old woman with Takayasu's arteritis confirmed by histological examination was admitted in our hospital because of angina pectoris. Selective coronary arteriograms reveled a 90% isolated stenosis in the right coronary ostium. The patient underwent a right coronary artery bypass grafting using the saphenious vein. The post operative clinical course was uncomplicated. On follow-up over 14 months the patient has been completely free from anginal chest-pain.

Adult↗