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Biomedical subjects

G Khoury

Publications and source records attributed to G Khoury.

At least 19 recordsLinked to original sources

Rectal cancer: 10 years experience at AUB-MC.

In order to study the behaviour of rectal cancer in our country, we have reviewed our experience at AUBMC over a 10-year period. We had 82 patients with rectal cancer, 36 males and 46 females, out of which 69 patients underwent surgical resection. Epidemiologically we have a significantly higher incidence of rectal cancer among females in contrast to western countries. Our operative results with respect to morbidity, mortality, recurrence and survival are discussed and compared to the literature.

Academic Medical Centers

Critical review of the treatment of pyogenic hepatic abscess.

A retrospective review of 29 consecutive patients with pyogenic hepatic abscesses was undertaken to ascertain the efficacy of various treatments. Percutaneous routes were used 25 times (aspiration alone in 16 and with concomitant drainage in nine), as a primary step 22 times and for recurrent abscesses, three times. An operation was required in nine patients; initially in five and after percutaneous treatment in four. Antibiotics alone were used twice. There were seven deaths, two after antibiotics alone and five after initial percutaneous aspirations. There were six recurrent abscesses, all but one after percutaneous aspiration. Our results suggest that antibiotics alone and percutaneous aspiration alone are inadequate in the treatment of pyogenic hepatic abscesses; percutaneous management is valid provided concomitant drainage is used, and that once the abscess has been successfully handled percutaneously, surgical treatment is a safe alternative as a first step, for abscesses recurring after percutaneous management, or for removal of the primary cause of the disease.

Adult

Trauma management in a war zone: the Lebanese war experience.

Lessons learned from the Vietnam and Korean conflicts have emphasized the necessity of an organized preparedness for optimal management of casualties. The present report summarizes the experience of a tertiary care center in the present Lebanese war. Between 1975 and 1986, approximately 30,000 war casualties were treated at the American University of Beirut Medical Center (AUBMC). A disaster plan was implemented whenever more than 25 major trauma victims were received within 1 hour. In-field stabilization and emergency room (ER) thoracotomy were not employed. The results are illustrated by an analysis of 1,500 cases of abdominal trauma, (1,314 high-velocity gunshot wounds, 29 stab wounds, 157 blunt injuries). A total of 1,420 patients were operated on within 6 hours of admission and 711 within the first hour. Overall mortality was 130, 8.7%; 9.5% for gunshot wounds, 3.4% for stab wounds, and 2.5% for blunt trauma. One hundred forty-five patients or 9.7% had negative findings at laparotomy. The factors affecting mortality were hypotension on admission (26.5% for a BP less than 90 mm Hg and 2.8% for a BP higher than 90 mm Hg) and the presence of extra-abdominal injuries (14.4% with and 4.4% without). The chief causes of death were hemorrhage (3.7%), sepsis (2.1%), and ARDS (1.2%).

Abdominal Injuries

[Myocardial revascularization with internal mammary artery graft: analysis of early and late post-operative respiratory morbidity].

To evaluate the respiratory morbidity resulting from myocardial revascularization with internal mammary artery (IMA) graft, we reviewed 153 patients operated on between April and November 1988. There were 124 men with a mean age of 61 years. A bilateral IMA graft was used in 30 patients (20%). During the harvesting of the mammary graft, the homolateral pleura was systematically opened. Acute respiratory failure was more frequent in patients with bilateral IMA (13%) than in patients with unilateral IMA graft (3%) (p less than 0.05). Consequently, the mean duration of mechanical ventilation was longer in patients with bilateral IMA graft: 56 versus 23 hours (p less than 0.05). Lung volume measurements were altered according to a restrictive pattern. On the 9th post-operative day, forced vital capacity was reduced to 59.6% of the pre-operative value in patients with unilateral IMA and to 47.1% in patients with bilateral IMA graft (p less than 0.001). Late results were obtained in 111 patients. After a mean follow-up of 7 months, forced vital capacity was still reduced to 86.8% of the pre-operative value in patients with single IMA and to 78.1% in patients with bilateral IMA graft (p less than 0.001). In conclusion, respiratory morbidity is not negligible. Bilateral IMA grafting should generally be reserved to young patients (less than 65 years) with normal pre-operative pulmonary function tests.

Adult

Myocardial revascularization in patients on renal replacement therapy.

Coronary disease is the main cause of mortality and morbidity among long-term survivors on renal replacement therapy (RRT). Despite the additional risk factors, myocardial revascularization has been recently attempted with various success in some patients on RRT. We report on 26 patients (13 dialyzed and 13 transplanted, mean age: 50 years [range 38-66]) who have undergone either surgical aorto-coronary bypass (CABG) (n = 16) with mammary artery grafts, or percutaneous coronary angioplasty (PTCA) (n = 9), or both procedures (n = 2). Indication was angina pectoris in all but three patients with painless ischemia. Eight patients had unstable angina (NYHA class IV). A previous myocardial infarction was documented in 11 cases. Coronary angiography disclosed mainly multiple vessel disease (81%). Post CABG complications consisted of severe intrathoracic bleeding (n = 3) resulting in death in 2 cases. PTCA entailed no major complication. After the critical postoperative period, the long-term survival was the same as that of non-uremic patients and the clinical improvement, according to the NYHA classification, was highly satisfactory at 6 months and persists up to 2 years. We conclude that coronary angiography and myocardial revascularization should be considered in patients on long-term RRT developing coronary disease.

Adult

Massive hepatic infarction in systemic lupus erythematosus.

Liver disease in systemic lupus erythematosus, as demonstrated by abnormal histopathology, is rare and usually mild; typically, this hepatic disease is of chronic nature and not related to a hypercoagulable state. A patient is described in whom life-threatening hypercoagulability in association with systemic lupus erythematosus resulted in extensive liver infarction. Follow-up radionuclide liver scintigraphy suggested that regenerative recovery in the infarcted areas of the liver may be delayed or absent, but there was no evident functional hepatic impairment.

Adult

Penetrating trauma to the carotid vessels.

Over a 13 year period extending between April 1975 and June 1988, 510 neck injuries were treated at the American University of Beirut Medical Center; the carotid vessels were involved in 48 patients, resulting in 53 carotid injuries. The mean age of the patients was 25.3 years and shrapnel injuries were the commonest (45.8%), followed by bullet wounds (33%). Thirty-nine patients had a laceration and five had complete disruption of the carotid vessels and only three presented in coma. Shock was present in 14 patients, of whom five had a neurological deficit. In six the injured vessels were ligated, three of them were external carotid arteries. Nine patients were not initially operated on. Six of them had a chronic arterio-venous fistula and three were in coma. The remainder underwent surgical repair. Nine patients died, giving an overall mortality rate of 18.8%. Four of these died because of multisystem failure, thus giving a 10.4% mortality rate for the isolated carotid injury. There was definite improvement in the repaired group, but the haemodynamic status seemed to significantly affect the mortality rate (P less than 0.01). Follow-up of surviving patients has revealed five with persistent neurological deficits in the repaired group (33 patients), and four patients with a chronic arterio-venous fistula. Two patients had a false aneurysm. Carotid artery injury seems to have a good prognosis if repaired promptly within 3 h.

Adult

Comparison of the acute effects of captopril and of nifedipine on left ventricular diastolic function in elderly hypertensive patients.

The acute effects of single doses of captopril (C) 12.5 mg, of nifedipine (N) 10 mg, or of their combination (C + N) on parameters of left ventricular (LV) function were assessed in 18 elderly hypertensive subjects using radionuclide ventriculography. Blood pressure (BP) was lowered by C from 177/100 to 164/92 mmHg, by N from 177/100 to 161/91 mmHg (p less than 0.02/less than 0.05 for both C and N) and by C + N from 176/100 to 151/83 mmHg (p less than 0.01/less than 0.01). Nifedipine accelerated heart rate from 74 to 85 and C + N from 74 to 82 beats/min (p less than 0.01 in both cases), whereas C left it unchanged. Left ventricular ejection fraction (EF) was not significantly affected by either drug alone or by both drugs combined. Peak ejection rate (PER) and peak filling rate (PFR) were slightly, but not significantly, enhanced by all treatments. Captopril shortened the time to peak filling rate (TPFR) by 21 msec (p less than 0.05), N by 26 msec (p less than 0.01) and their combination by 22 msec (p less than 0.05); however, when corrected for RR interval or length of diastole, TPFR was shortened only by C (p less than 0.05). Tachycardia induced by acute administration of N may have an unwanted effect on LV diastolic function, which can be partially blunted by the concomitant administration of a converting enzyme inhibitor.

Aged

Dysmyelination in transgenic mice containing JC virus early region.

JC virus (JCV) causes the chronic human demyelinating disease progressive multifocal leukoencephalopathy. Because of host range restrictions, experimental models of JCV-induced demyelination have not been available. The restricted tropism of JCV infectivity has recently been overcome by the production of transgenic mice that contain the early region of JCV in all cells. This portion of the DNA encodes JCV T-antigens. These mice display a dysmyelinating phenotype, the severity of which is related to the level of JCV early region expression in brain. With the use of immunocytochemistry and in situ hybridization, we characterized morphologically myelin-specific and JCV gene expression in a severely affected strain of these mice. Our results suggest that expression of JCV T-antigens occurs predominantly in oligodendrocytes and is the primary cause of dysmyelination. Affected oligodendrocytes do not myelinate axons properly. However, they express myelin-specific genes and display some of the morphological phenotypes of early stages of myelination. A decreased ratio between levels of transcriptional and translational products of genes encoding the major structural proteins of central nervous system myelin was apparent. These results suggest that JCV T-antigens arrest the maturation of oligodendrocytes and inhibit the production of myelin. These results also demonstrate that JCV transgenic mice are a good model for investigating mechanisms of JCV-induced demyelinating lesions in progressive multifocal leukoencephalopathy.

Animals

Nuclear factors in human brain cells bind specifically to the JCV regulatory region.

The human polyomavirus, JCV, differs from other papovaviruses in its tissue tropism for human glial cells. Transcription of the early region of the virus, at least in part, contributes to the tissue specificity of JCV. In this study, we have synthesized oligonucleotides which span the JCV 98 bp repeat unit. Using gel mobility shift and UV cross-linking assays, we have demonstrated that four proteins from a human fetal brain extract interact specifically with the JCV promoter/enhancer. Two proteins of 82 kd and 78/80 kd recognize the 5'- and 3'-terminal regions of the JCV 98 bp repeat sequence, respectively. The mol. wt of these proteins are similar in HeLa and brain extracts. In contrast, the proteins which recognize the central region of the 98 bp enhancer are distinct in HeLa (85 kd) and fetal brain (45 kd) extracts. The possible role of these proteins in tissue-specific expression of the JCV early promoter in brain cells is discussed.

Base Sequence

Regulation of the metastatic phenotype by the E1A gene of adenovirus-2.

We have previously demonstrated that rat embryo cells transformed by the ras oncogene alone are both tumorigenic and highly metastatic when injected into nude mice. In contrast, rat embryo cells transformed with the ras oncogene and the adenovirus 2 (Ad2) Ela gene are tumorigenic but either fail to metastasize, or exhibit a very low metastatic potential. Here we demonstrate that transfection of the Ad2 Ela gene into several of the ras transformed rat embryo cell lines results in a dramatic reduction in metastatic potential relative to the parental cell line. Transfection of cDNAs for the 12S and 13S Ela transcripts showed that both gene products are capable of reducing the metastatic potential of the ras transformed cell lines, however the 12S cDNA was more effective. This effect is specific to the Ad2 Ela gene as ras transformed cell lines expressing the Ad12 Ela gene or the human N-myc gene maintained their high metastatic potential. We hypothesize that the Ad2 Ela gene may regulate the expression of one or more cellular genes that contribute to the metastatic phenotype.

Adenovirus Early Proteins

Internal fixation of an unstable open fracture of a distal phalanx with a Herbert screw.

A 20-year-old patient was seen with an unstable, infected, open fracture of the distal phalanx of the long finger of the right dominant hand. The patient was treated by removal of the nail, debridement of the fracture site, and stabilization of the fracture with a Herbert screw. The Herbert screw compressed the fracture site and allowed early active motion of the distal inter-phalangeal (DIP) joint. The wound healed without incident, and the fracture was radiographically united 6 weeks after the procedure. The Herbert screw is useful in the treatment of unstable fractures of the distal phalanx, since the screw maintains reduction, compresses the fracture site, and allows early active motion of the DIP joint.

Adult

Carboxyl-terminal mutants of the large tumor antigen of simian virus 40: a role for the early protein late in the lytic cycle.

Simian virus 40 (SV40) mutants dl1066 and dl1140 contain deletions within the region encoding the carboxyl terminus of the large tumor (T) antigen. Although these mutations have little effect on the efficiency of viral DNA replication, they decrease the yield of infectious virus particles by 3-4 orders of magnitude [Pipas, J. (1985) J. Virol. 54, 569-575]. Here we show that the level of late RNA is lower by a factor of 5-15 in CV-1P monkey cells infected with these mutants compared to cells infected with wild-type SV40. Consistent with this decrease in RNA, synthesis of late viral structural proteins VP1 and VP3 decreases by a factor of 5-15. In contrast, the synthesis of SV40 agnoprotein decreases by a factor greater than 100. Intercistronic complementation of these mutants with pm1493 and dl121, two SV40 mutants that are defective in agnoprotein but encode wild-type T antigen, results in an increased synthesis of agnoprotein in the infected cells. These results suggest that the carboxyl-terminal portion of T antigen participates in the posttranscriptional regulation of agnoprotein.

Animals

Characterization of cellular factors that interact with the human T-cell leukemia virus type I p40x-responsive 21-base-pair sequence.

Transcriptional activation of the human T-cell leukemia virus type I (HTLV-I) long terminal repeat (LTR) by viral protein p40x requires a 21-base-pair (bp) sequence which is repeated three times within the LTR. This sequence contains a core octanucleotide (TGACGTCT) which has been attributed to be a cyclic-AMP (cAMP)-responsive element. We demonstrate here that the HTLV-I LTR can be specifically stimulated by cAMP regulators and have identified four proteins in HeLa cells that bind to the HTLV-I 21-bp sequence. We correlated the in vitro binding and transcriptional activity of one of these cellular factors (Mr, 180,000) to the trans-activation of the HTLV-I LTR by p40x. Point mutations were generated within the cAMP octanucleotide of the HTLV-I 21-bp sequence that simultaneously abolished biological responsiveness to trans-activation by p40x and to stimulation by cAMP. We found that these mutations also eliminated the binding of the 180-kilodalton HeLa factor to the HTLV-I 21-bp element. In the absence of a demonstrable DNA-binding property for p40x, we hypothesize that cellular proteins are involved, possibly through signal transduction pathways, in its trans-activation of responsive promoters.

Base Sequence

The E1a gene of adenovirus type 2 reduces the metastatic potential of ras-transformed rat embryo cells.

We have previously demonstrated that second-passage rat embryo cells transformed by the ras oncogene alone are both tumorigenic and highly metastatic when injected into nude mice. In contrast, rat embryo cells cotransformed with the ras oncogene and the adenovirus type 2 (Ad2) E1a gene are tumorigenic but either fail to metastasize or exhibit a very low metastatic potential. In this report, we demonstrate that transfection of the Ad2 E1a gene into four independent ras-transformed rat embryo cell lines results in a dramatic reduction in metastatic potential relative to that of the parental cell line. Transfection of cDNAs for the 12S and 13S E1a transcripts showed that the 12S cDNA was highly effective in reducing the metastatic potential of ras-transformed cell lines, while the 13S cDNA showed an effect in only one of the two cell lines tested. This effect is specific to the Ad2 E1a gene, since ras-transformed cell lines expressing the Ad12 E1a gene maintained their high metastatic potential. We hypothesize that the Ad2 E1a gene may regulate the expression of one or more cellular genes that contribute to the metastatic phenotype.

Adenovirus Early Proteins