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Biomedical subjects

S Khoury

Publications and source records attributed to S Khoury.

At least 19 recordsLinked to original sources

Multifetal pregnancies.

Parturients with multiple gestation challenge all members of the perinatal team. Satisfactory maternal and fetal outcome require the experience and expertise of the obstetrician, anesthesiologist and neonatologist, all of whom must be well informed in terms of the total care and management plan.

Anesthesia, Obstetrical

Kinetics of expression of costimulatory molecules and their ligands in murine relapsing experimental autoimmune encephalomyelitis in vivo.

We studied the kinetics of expression of costimulatory molecules and cytokines in the central nervous system (CNS) in murine relapsing experimental autoimmune encephalomyelitis (EAE). During the natural course of EAE, B7-2 expression in the CNS correlated with clinical signs, while B7-1 was exclusively expressed during remissions. Interestingly, B7-1 was expressed on infiltrating mononuclear cells as well as neuronal cells in the CNS. In the periphery, B7-1 expression on APCs peaked with clinical disease but decreased on T cells. CD28 and CTLA4 molecules, the two known ligands for B7-1 and B7-2, had distinct expression patterns in the CNS; CD28 was highly expressed and correlated with B7-2 expression on APCs (macrophages/microglia as well as astrocytes) and with the clinical signs of EAE. CTLA4, on the other hand, was expressed by substantially fewer cells during the effector phase of disease and peaked during remission, which is consistent with the emerging role of this molecule in the termination of immune responses. The expression of CD40 and CD40L in the CNS was increased during clinical attacks. The expression of IL-12, IFN-gamma, and TNF-alpha correlated with disease activity and severity, while TGF-beta was the only factor that was up-regulated during the recovery phase. Interestingly, TGF-beta was also expressed by neurons during remission. This is the first study demonstrating the kinetics of the in vivo expression of costimulatory molecules, their ligands, and cytokines in an autoimmune disease model characterized by remissions and relapses. Our data suggest that the targeting of costimulatory molecules to block an immune response must take into account the expression patterns in the target organ.

Abatacept

Proliferating cell nuclear antigen (PCNA) in cerebral cavernomas: an immunocytochemical study of 42 cases.

BACKGROUND: The natural history and growth mechanisms of cerebral cavernous angiomas are unclear, which makes them difficult to manage. We attempted to evaluate the evolutive potential of cavernomas by studying the proliferative capacity of cells. METHODS: We studied 42 histologically verified cavernomas with monoclonal antibody to proliferating cell nuclear antigen (PCNA), an accessory protein of the cell cycle, the rate of which is increased in proliferative cells. The PCNA Labeling Index (PCNA LI) was calculated in each case, and the results were compared with histologic findings (lacy areas, thick walls, thrombi, hemosiderin) and clinical features (epilepsy, hematomas, pseudotumorous signs). RESULTS: Thirty-six of 42 cases (85.7%) revealed stained cells. PCNA LI ranged from 1 to 48% (mean: 23.39%). Statistical analyses showed a positive correlation between PCNA LI and the extent of lacy areas (p < 0.05). On the contrary, collagenous-walled and thrombotic areas rarely showed positively stained cells. We found no relationship between PCNA LI and clinical features. CONCLUSIONS: A proliferative capacity of endothelial cells does exist in some areas of cavernomas and may explain, besides thromboses and hemhorrages, the growth and even de novo appearance of these lesions. Occurrence of fragile blood cavities, thickening of others, and changes in blood flow may influence the evolution of lesions. Our results suggest that in cavernomas, some areas may undergo specific changes, which makes them more dynamic lesions than previously thought.

Adolescent

Assessment of hormone refractory prostate cancer.

OBJECTIVES: To define guidelines for the assessment of treatment in patients with hormone-refractory prostate cancer (HRPC). METHODS: In the light of modern research, and taking new treatment options into account, the Committee essays to specify different categories of patients entering clinical trials, and to define response criteria and those endpoints that are relevant in phase III studies and in short-term follow-up. RESULTS: HRPC comprises a range of disease states with varying responsiveness to therapy and length of survival. Patients with progression as evaluated by increasing prostate-specific antigen (PSA) values alone have a more favorable prognosis than those presenting with increasing tumor spread. In the assessment of these patients, the modes of previous therapy and the kind of tumor progression must be taken into account. The benefit of treatment of HRPC is often modest. While duration of survival remains the main and ultimate endpoint, the means of measuring short-term responsiveness to therapy are limited. A minority of patients have measurable tumor lesions. Decrease of PSA or other biochemical tumor markers may indicate depression of the tumor activity, but is not always associated with prolongation of survival. A variety of new treatments in HRPC are being investigated. They affect measurable tumor parameters in different ways. CONCLUSIONS: When a new agent is to be tested, it is important to measure all possible parameters before deciding which particular ones are appropriate for future investigations of this agent. In symptomatic patients, evaluation of subjective parameters, for example, relief of pain or improvement of performance status, is often the most reliable measure of treatment effect. However, these parameters should be clearly defined.

Antineoplastic Agents, Hormonal

Familial cavernous malformations in a large French kindred: mapping of the gene to the CCM1 locus on chromosome 7q.

OBJECTIVES: To characterise clinically a large French family affected with cerebral cavernomas and to check for linkage of this condition to chromosome 7. METHODS: A family, originating from Normandy and in which five members had undergone surgery for cavernomas, was extended. All members older than 18 were studied clinically and by neuroimaging. Genetic linkage analysis was conducted using 11 polymorphic microsatellite markers located between D7S502 and D7S479. RESULTS: The family included three generations. Among the 25 members investigated, 11 had an abnormal cerebral MRI, eight of them being symptomatic, and 12 were asymptomatic with a normal MRI. The status of the two remaining members could not be established on the basis of clinical and MRI data. The family reported shares some striking features with other previously linked families--namely, a high clinical penetrance and the presence of multiple lesions within most of the affected members. A lod score of 4.04 was obtained with marker D7S657 with no recombinant. Significant lod scores were also obtained with D7S524 (Zmax=3.32 at 0=0.00) and D7S630 (Zmax=3.44 at 0=0.00). These results establish linkage of the condition found in this family to chromosome 7. Haplotype analysis strongly suggests that the gene is telomeric to D7S802 and centromeric to D7S479. CONCLUSIONS: These data confirm linkage of cerebral cavernous malformations to chromosome 7 in a non-Hispanic family.

Adolescent

The endemicity of Leishmania tropica (zymodeme MON-137) in the Eira-Yarqa area of Salt District, Jordan.

The endemicity of cutaneous leishmaniasis (CL) caused by Leishmania tropica was ascertained in a focus of the disease around Eira and Yarqa in Salt District, Jordan. This focus is about 10 km to the east of another focus of CL, where L. major is the causative agent. As CL occurs sporadically in the study area, with nine cases diagnosed between 1993 and 1995, it is probably zoonotic. Each case had one or two lesions and most lesions were on the face. Isoenzymatic electrophoresis showed that all the parasites isolated in the Eira-Yarqa focus and identified to zymodeme level belonged to zymodeme MON-137 and therefore differed from all the L. tropica isolates identified in other regions of Jordan. Eight species of Phlebotomus (P. alexandri, P. major, P. sergenti, P. papatasi, P. perfiliewi, P. jacusieli, P. canaaniticus and P. arabicus), two members of the Sergentomyia dentata group and S. tiberiadis and S. taizi were collected in the focus, using castor-oil traps. The epidemiological significance of the sandflies collected is discussed.

Adolescent

Ischaemia of the hand after radial artery monitoring.

Percutaneous radial artery cannulation is commonly used for continuous monitoring of blood pressure and estimation of arterial blood gases. The purpose of this study is to define the incidence of radial artery thrombosis and associated hand ischaemia after cannulation. A prospective study of 40 patients who underwent radial artery cannulation was carried out with patients examined before and after cannulation for radial and ulnar pulses. Doppler waveforms, and finger/brachial and finger/wrist pressure indices were obtained. After cannulation 27.5% of patients developed abnormal radial artery flows with 10% having absent pulses and none having any symptoms of hand ischaemia. Radial artery cannulation is a safe procedure when performed properly and is associated with a very low incidence of hand ischaemia, despite a 27.5% incidence of abnormal radial artery flow after cannulation.

Adolescent

Epidemiology of cutaneous leishmaniasis in Jordan: 1983-1992.

BACKGROUND: The extent of the problem of cutaneous leishmaniasis in Jordan during the decade 1983 to 1992 was investigated. METHODS: Data were collected from the dermatology departments and the laboratories of the Royal Medical Services and the Ministry of Health as well as from private dermatologists. Two thousand two hundred and ninety-five cases were verified of whom men represented 80%. The majority (80%) were < 25 years with the highest percentage (31%) occurring in the 16 to 20-year age group. RESULTS: The lowest number of cases was reported in June compared to the maximum in October, and the highest number recorded per year was 463 in 1992. For the decade, the Jordan Valley was the most important locality where 43% of the cases occurred. The incidence rate per 100,000 ranged from 1.89 in 1989 to 14.39 in 1984 and the period prevalence for the decade was 5.36 per 100,000. The time-lag between the appearance of a lesion and the first diagnosis extended from 0 to 23 months with the average being 2 months. The number of lesions per patient ranged from one to 45; 24% were located on the face, 28% on the upper extremity, 36% on the lower extremity, and 12% on other sites. CONCLUSIONS: The factors that contributed to the findings include infected rodent, nonexposed army recruits and farm workers, land reclamatory and relaxation of preventative measures.

Adolescent

Relative androgenicity, blood pressure levels, and cardiovascular risk factors in young healthy women.

To test the hypothesis that androgens may play a role in the pathogenesis of atherosclerosis and hypertension, we investigated the association of delta 5 dehydroepiandrosterone sulfate [DHEAS]) and delta 4 (free testosterone [FT]) androgens with the resting, seated blood pressure (BP) levels and cardiovascular risk factors in 280 young, healthy women 18 to 24 years of age. After application of multiple regression analysis, systolic BP was positively and independently correlated with the ratio of dehydroepiandrosterone sulfate to free testosterone (DHEAS/FT), fasting insulin levels, and the diastolic BP with DHEAS/FT only. The DHEAS/FT ratio proved to be a stronger predictor of the BP levels than either hormone alone. Further, uric acid concentrations and HDL/total cholesterol ratio were independently correlated with both FT and body mass index in these young women. Serum triglycerides were independently correlated with FT and central body fat distribution. These data suggest that serum androgen concentrations are important independent predictors of cardiovascular risk factors and that the ratio of dehydroepiandrosterone sulfate to free testosterone ratio is an independent predictor of blood pressure levels in young women.

Acetone

Incrimination of Phlebotomus papatasi as vector of Leishmania major in the southern Jordan Valley.

The status of sandflies as vectors of cutaneous leishmaniasis in the southern Jordan Valley was investigated during 1992. Sandflies were collected from domestic habitats and from burrows of Psammomys obesus. Of 686 Phlebotomus papatasi females collected from burrows, fourteen harboured promastigotes in their guts. On the other hand, none of 1446 P.papatasi females collected from domestic habitats were found infected. The highest infection rate (5.5%) was recorded in November at the end of the sandfly season. Six leishmanial stocks isolated from P.papatasi females were typed by cellulose acetate electrophoresis using the six enzymes G6PDH, 6PGDH, PGI, PGM, FK and ME. Five of the leishmanial stocks were identical to a Leishmania major reference strain (MHOM/SU/73/5-ASKH). The sixth isolate was a 6PGDH variant of L.major. These findings present the first direct evidence of the role of P.papatasi as a vector of L.major in Jordan.

Animals

The status of bladder-preserving therapeutic strategies in the management of patients with muscle-invasive bladder cancer.

The recommended treatment for medically fit patients with muscle-invading bladder cancer is usually radical cystectomy. However, transurethral resection of the tumor, partial cystectomy, irradiation and systemic chemotherapy are each effective in some patients. These latter treatments allow bladder preservation and cure as an alternative to radical cystectomy although when used unselectively the survival rates are inferior to those of radical cystectomy. The updated results of conservative surgery, radiation therapy and systemic chemotherapy as monotherapy, as well as strategies of combined modality treatment were reviewed. Based on this review many areas of consensus were reached which include: 1. The primary goal of any treatment for a patient with muscle-invading bladder cancer is survival; bladder preservation in the interest of quality of life is a secondary objective. 2. Only a small proportion of carefully selected patients may be cured by transurethral surgery alone, or by partial cystectomy alone. 3. Radiation therapy is currently the standard bladder-preserving therapy against which all other bladder-preserving methods must be compared. 4. Systemic chemotherapy as monotherapy is inadequate and cannot be recommended. 5. The addition of cisplatin-containing systemic chemotherapy to radiation therapy or conservative surgery appears to improve local control. While no multi-modality therapeutic regimen has yet been shown to be clearly optimal with regard to local efficacy and minimizing toxicity, monotherapy for bladder preservation is probably not desirable as a routine approach. 6. Deferring the patient from immediate cystectomy does not appear to compromise survival, nor does the addition of primary systemic chemotherapy appear to significantly increase the morbidity of cystectomy or radiotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined Modality Therapy

Phase I trial of high-dose fosfestrol in hormone-refractory adenocarcinoma of the prostate.

Androgen deprivation displays the mean therapy of advanced stage prostatic cancer. The development of hormone-resistant disease leads to a fatal tumor progression. High-dose fosfestrol (diethylstilbestrol disphosphate) has been suggested to circumvent hormone resistance and to induce a direct cytotoxic effect. Twenty-one patients with hormone-refractory prostate cancer were enrolled in a phase I trial of continuous infusion of high, daily escalating dose of fosfestrol. Fosfestrol was given in a 3.5 hr infusion in 0.9% normal saline at a starting dose of 1.5 g/d. The dose was increased daily in the same patient according to the following schedule: 1.5, 1.8, 2.4, 3.0, 3.6, 3.9, 4.5, 5.1 and 5.7 g/d. The duration of the infusion was prolonged to 7 or 10.5 hr, if a major side effect occurred. There was neither hematological nor cardiovascular toxicity. The main dose-limiting toxicities were nausea/vomiting in 17 patients, edema in 2 patients, and more than 5% weight gain in 3 patients. The planned maximal dose was reached in 10 patients during a 3.5 hr infusion, and in 3 additional patients, after infusion prolongation. Seven patients experienced a subjective improvement: Prostatic acid phosphatase and prostatic specific antigen decreased in 4 out of 11 and in 7 out of 12 patients, respectively. The suggested dose to phase II trial is 4 g/d in 3.5 hr infusion for a duration of up to 10 days.

Acid Phosphatase

Cost effectiveness of 24-hour ambulatory blood pressure monitoring in evaluation and treatment of essential hypertension.

We wanted to determine if use of ambulatory blood pressure monitoring (ABPM) was cost effective, preventing unnecessary drug therapy in patients misdiagnosed as having essential hypertension, with elevated office blood pressures and normal ambulatory blood pressure. To address this issue we surveyed costs to the patient for antihypertensive drug therapy in 1990 of five local pharmacies in southeastern Michigan. Patients studied (n = 192) were seen in a private, general internal medicine practice in rural southeastern Michigan and received ABPM to assess the presence of hypertension and the adequacy of blood pressure treatment. We ascertained the average, minimal, and maximal drug cost to the patient per unit dose at the local pharmacies. The average yearly cost for patients on antihypertensive medications at pharmacies in southwestern Michigan was $578.40, with figures varying from $94.90 to $4361.75. Although there is no standard reimbursement amount for ABPM, at $188 per monitoring, the cost of monitoring this entire group of patients would offset exactly the cost of medication for the group of patients found to have only office hypertension. As such, third-party insurance carriers should consider reimbursement for ABPM in hypertension to decrease pharmaceutical cost and its attendant potential side effects. In conclusion, our study results suggest that ABPM is cost effective in an outpatient setting in preventing unwarranted drug therapy and the inappropriate diagnosis of hypertension.

Ambulatory Care