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M Khoury

Publications and source records attributed to M Khoury.

At least 19 recordsLinked to original sources

Genomics and public health at CDC.

Genomics is the study of the entire genome, including all genes and their interactions with each other and with the environment. The scope of public health genomics is even broader, encompassing genetic variation in populations, both human and microbial. Molecular typing of pathogens--a mainstay of infectious disease surveillance, prevention, and control--already is used to trace epidemics, provide information for vaccine development, and monitor drug resistance. Now genomic research is producing powerful new tools for public health; for example, a newly described, microchip-based method promises to diagnose influenza infection, distinguish among viruses of human or animal origin, and detect mutations that suggest increasing virulence--all in a matter of hours.

Centers for Disease Control and Prevention, U.S.↗

A comparative study on intra-articular versus systemic gene electrotransfer in experimental arthritis.

BACKGROUND: Electric pulse mediated gene transfer has been applied successfully in vivo for increasing naked DNA administration in various tissues. To achieve non-viral gene transfer into arthritic joint tissue, we investigated the use of electrotransfer (ET). Because anti-inflammatory cytokine strategies have proven efficient in experimental models of arthritis, we compared the therapeutic efficiency of local versus systemic delivery of the interleukin-10 (IL-10) using in vivo ET. METHODS: A plasmid vector expressing IL-10 was transferred into DBA/1 mouse knee joints by ET with 12 pulses of variable duration and voltage. The kinetics of transgene expression were analyzed by specific enzyme-linked immunosorbent assay (ELISA) in sera and knees. Optimal conditions were then used to deliver increasing amounts of IL-10 plasmid intra-articularly (i.a.) in the collagen-induced arthritis (CIA) mouse model. The therapeutic efficiency was compared with the potency of intra-muscular (i.m.) ET. RESULTS: Following i.a. ET, local IL-10 secretion peaked on day 7 and dropped 2 weeks after. A second ET produced the same kinetics without enhancing gene transfer efficiency, while transgene was still detected in injected muscles 4 weeks after ET. Only the i.m. ET of 25 microg of IL-10 significantly inhibited all the clinical and biological features of arthritis. The i.a. ET only showed mild improvement of arthritis when 100 microg of IL-10 plasmid were electrotransfered weekly from day 18 following arthritis induction. CONCLUSIONS: The present results suggest that gene transfer into arthritic joints by ET is an effective means to deliver anti-inflammatory cytokines. However, short duration of transgene expression impedes a significant effect for the treatment of arthritis, making i.m. ET more potent than i.a. ET for clinical benefit in CIA.

Animals↗

Adeno-associated virus pseudotype 5 vector improves gene transfer in arthritic joints.

The potential for gene delivery to joints, using recombinant adeno-associated virus (rAAV) vectors for the treatment of rheumatoid arthritis (RA), has received much attention. Different serotypes have different virion shell proteins and, as a consequence, vary in their tropism for diverse tissues. The aim of this study was to compare the transduction efficiency of different AAV serotypes encoding murine secreted alkaline phosphatase (mSEAP) or Escherichia coli beta-galactosidase for intraarticular gene delivery in an experimental model of arthritis. The vectors contained AAV2 terminal repeats flanking the reporter gene in an AAV1, AAV2, or AAV5 capsid, producing the pseudotypes rAAV-2/1, rAAV-2/2, and rAAV-2/5. Left knee joints of mice with collagen-induced arthritis were injected and transgene expression was analyzed by chemiluminescence or direct in situ staining of frozen sections. We show for the first time that intraarticular gene transfer with AAV- 2/5 was far more efficient than with the other serotypes tested. Transgene expression was detectable as early as 7 days after injection, reached a maximum at 21 days, and was stably expressed for at least 130 days, whereas AAV-2/1- and AAV-2/2-mediated expression levels were barely detectable. These findings provide a practical application for future local AAV-mediated gene therapy trials in RA.

Alkaline Phosphatase↗

The probiotic E. coli strain Nissle 1917 for the treatment of collagenous colitis: first results of an open-label trial.

BACKGROUND: Collagenous colitis is clinically characterized by watery diarrhoea and can histologically be diagnosed by a thickening of the subepithelial collagen layer and an inflammatory infiltrate in the lamina propria. So far, the pathogenesis of collagenous colitis and the role of luminal factors remain unclear. METHODS: This clinical pilot investigation was conducted with an open-label design to monitor the clinical effects of EcN on stool frequency and stool consistency in 14 patients (11 female, 3male; age: 58.1 +/- 9.6 years). Due to the open-label protocol EcN was administered at different doses (1 - 6 capsules/day containing 2.5 - 25 x 10 (9) viable bacteria each). Except for two patients who discontinued treatment, therapy duration was at least 4 weeks. RESULTS: The results indicate a marked clinical response to the oral administration of EcN with a reduction of the stool frequency > or = 50 % in 9/14 (64 %) patients. Stool frequency clearly (p = 0.034) decreased from 7.6 +/- 4.8/day to 3.7 +/- 5.8/day at the end of therapy (between 4 and 18 weeks). Moreover, stool consistency changed in 7/14 patients from watery or slimy to soft (6 pts) and normal (1 pt), respectively. CONCLUSION: With respect to the preliminary data from this trial, the probiotic E. coli strain Nissle 1917 (EcN) seems to be of therapeutic clinical benefit in collagenous colitis. This may be explained with the recently shown antagonistic effect of EcN against Yersinia species, since a relevant number of patients suffering from collagenous colitis showed positive titres of serum IgG and IgA antibodies against Yersinia species. Further studies on the effects of EcN on mucosal collagen metabolism and long-term follow-up are warranted.

Colitis↗

Right congenital diaphragmatic hernia a well-known pathology?

In right congenital diaphragmatic hernia (RCDH), several clinical diagnostic pitfalls are possible and should be known to those caring for infants and children with this disorder. The records of the 18 patients at Hotel Dieu de France Hospital with a history of CDH between 1990 and 1999 were collected; those of the ten who had a RCDH were reviewed retrospectively. The mean age at diagnosis was 6 months; the male-to-female ratio was 2:3. The delay between the first symptom and the diagnosis ranged between 0 and 10.5 months (mean 4.5 months). An acute presentation was observed in four cases, consisting of respiratory distress in three; the 4th presented with gastric volvulus and intestinal obstruction. The presenting symptoms were mild in four cases; recurrent respiratory infections in three and failure to thrive in one. The diagnosis was incidental in two cases during the evaluation of respiratory symptoms attributed to an atrial septal defect. The radiologic findings provided by a chest radiograph (CxR) were sufficient to make an accurate diagnosis in eight cases and peritoneography was useful in one. In six cases, the presenting CxR had been misinterpreted as normal or acute lobar pneumonia. Pathologic findings at surgery consisted of lateral and posterior right diaphragmatic defects in nine cases; the defect was lateral and anterior in one. A hernia sac was found in seven cases; malrotation was present in three. Surgical correction was done by an abdominal approach in nine cases and a thoracic approach in one. The diaphragmatic defect was repaired by transverse closure in six cases, diaphragm plication in three and prosthetic closure in one. The postoperative outcome was uneventful in eight cases. Two patients died. Thus, RCDH seems to cause less severe symptoms than left-sided LCDH. It usually manifests beyond the neonatal period as respiratory or gastrointestinal symptoms. The diagnosis should be made easily by a CxR. The presence of a hernia sac correlated with a mild presentation. An abdominal surgical approach is preferred.

Female↗

Pediatric HIV infection.

Explore the source record for details and available documents.

AIDS-Related Opportunistic Infections↗

Carotid endarterectomy based on duplex ultrasound in patients with and without hemispheric symptoms.

Carotid endarterectomy is the most commonly performed vascular procedure. This retrospective study was conducted to determine the efficacy of duplex imaging as the sole diagnostic study for preoperative evaluation of symptomatic and asymptomatic patients who underwent carotid endarterectomy. We conducted a retrospective case series analysis in a community teaching hospital. From January 1994 to September 1998, 316 patients underwent carotid endarterectomy for carotid stenosis. A total of 177 patients were symptomatic and 139 patients were asymptomatic. Angiography was performed routinely in the beginning of the study but later was performed only in selected patients. Preoperative duplex ultrasound of carotid artery was performed by a laboratory accredited by the Intersocietal Commission for the Accreditation of Vascular Laboratories. Data were reviewed to obtain morbidity and mortality rates, and duplex imaging results were compared with operative findings. Cost and risk analysis of carotid angiography reviewed. This study reviewed variables of age, sex, race, diabetes, smoking, hypertension, hypercholesterolemia, coronary artery disease, and renal failure. Five patients had a lesion in the proximal portion of the carotid artery by duplex imaging criteria. Duplex ultrasound results were grossly confirmed intraoperatively in all patients except in one patient who was found to have complete occlusion of carotid artery whose duplex was read as high-grade stenosis. The duration of stay ranged from two to 30 days. This duration was influenced by patients' comorbid conditions, postoperative complications or simultaneous coronary artery bypass graft. Four patients had a stroke within 30 days of surgery making the stroke rate of 1.26 per cent. There has been considerable debate on the use of duplex ultrasound as the only method of preoperative evaluation of carotid stenosis before carotid endarterectomy. Our study demonstrates that it is safe to perform carotid endarterectomy based on neurologic history and duplex ultrasound with good technical quality performed in an accredited vascular laboratory. This approach eliminates the cost and risk associated with angiography. Proximal carotid and intrathoracic lesions are rare and can be predicted by the duplex study. We think that carotid angiography is required only when duplex imaging is suboptimal or equivocal in the presence of atypical symptoms or uncommon vascular abnormalities.

Adult↗

[Application of a preoperative evaluation model in patients undergoing elective abdominal surgery].

We used a preoperative evaluation model based on the clinical history in order to determine the clinical characteristics of the patients. We also estimated the prevalence of asymptomatic disease in ASA1 patients and described the frequency of diagnosis that motivated suspension of the surgery during the preoperative time. Another purpose was to establish the perioperative complications according to the risk index and to detect the medical reasons for suspension of surgery during hospitalization. A total of 777 patients having an indication of surgery were evaluated in this program. Only 507 completed the preoperative evaluation. Of these, 57.79%, had at least one known disease or were diagnosed by their clinical history. Preoperative tests were indicated according to age in ASA1 patients. Complementary studies were indicated in relationship to the history and physical examination in ASA2 and ASA3 patients. After the evaluation, 27 surgeries were suspended: 21 were considered high risk, 2 suffered unknown active infections, and 4 ASA1 patients had severe asymptomatic anemia. A total of 328 patients were admitted for surgery. In 5 of these patients the anesthesiologist stopped the procedure in the operating room. The causes were acute decompensations of known pathologies. There were no complications or deaths related to unknown diseases and no patients died from cardiopulmonary or metabolic complications. In ASA1 patients, there were no complications related to this evaluation. This study allowed us to determine the clinical status of the patients and in consequence high-risk surgeries were canceled. In admitted patients a few surgeries were canceled for clinical reasons. This program probably decreased patient morbimortality, unnecessary hospitalization and costs.

Adolescent↗

[Community-acquired pneumonia in the elderly requiring hospitalization. Clinical features and prognosis].

We evaluated retrospectively 96 patients older than 64 years admitted with the diagnosis of Community Acquired Pneumonia (CAP) in order to describe the clinical features, evaluate severity and assess prognostic factors. During an 18-month period 100 cases of CAP were included. Average age was 82.3 years +/- 8.3 (+/- SD). By the time of admission, cough and fever were found in 35% of cases and 48% had altered mental status. Fourteen per cent needed mechanical ventilation. Etiology was determined in 21% of cases. Most common pathogens were S. pneumoniae (38.1%), S. aureus (19%) and H. infuenzae (14.3%). Overall mortality was 29%. The most commonly present criteria of severity were tachypnea (respiratory rate > 30) and a PaO2/FIO2 ratio < 250. Severe pneumonia was found in 60% of patients and mortality in that group was 40%. Multivariate analysis demonstrated that some independent prognostic factors were associated with higher mortality: requirement of vasopressors (Odds Ratio [OR] = 22.0; 95% confidence interval [CI] = 1.9-249.5), oliguria (OR = 9.9; CI = 1.5-66.2), previous neurologic disease (OR = 8.2; CI = 1.8-36.6), PaCO2 > 44 mm/Hg (OR = 6.9; CI = 1.1-43.2), and creatinine > 1.4 mg/dl (OR = 4.7; CI = 1.2-19.1). We conclude that CAP features in elderly patients requiring hospitalization are atypical, severe presentations are frequent and mortality is high. Prognostic factors as found in this study can help the evaluating physician to identify those who require special care.

Aged↗

Gillespie syndrome phenotype with a t(X;11)(p22.32;p12) de novo translocation.

PURPOSE: To report a patient with a phenotype suggestive of Gillespie syndrome and with a chromosomal abnormality. METHODS: Clinical evaluation showed bilateral superior coloboma, foveal hypoplasia, and inferior cerebellar hypoplasia. Karyotyping as well as investigation of the PAX6 gene were performed. RESULTS: The karyotype of the patient disclosed a de novo translocation t(X;11)(p22.32;p12). Fluorescent in situ hybridization and the search for mutations excluded direct implication of the PAX6 gene. CONCLUSION: This is, to our knowledge, the first report of a chromosomal abnormality detected in a patient with a Gillespie syndrome phenotype.

Abnormalities, Multiple↗

Phrenic nerve dysfunction after cardiac operations: electrophysiologic evaluation of risk factors.

BACKGROUND AND STUDY OBJECTIVE: Phrenic nerve injury may occur after cardiac surgery; however, its cause has not been extensively investigated with electrophysiology. The purpose of this study was to determine by electrophysiologic means the importance of various possible risk factors in the development of phrenic nerve dysfunction after cardiac surgical operations. DESIGN: A prospective study was conducted. SETTING: A tertiary teaching hospital provided the background for the study. PATIENTS: Sixty-three cardiac surgery patients on whom surgical operations were performed by the same surgical team constituted the study group. Mean (+/-SD) age and ejection fraction were 63+/-5 years and 50+/-10%, respectively. INTERVENTIONS: Measurement of phrenic nerve conduction latency time after transcutaneous stimulation preoperatively and at 24 h and 7 and 30 days postoperatively. RESULTS: Thirteen patients had abnormal phrenic nerve function postsurgery, 12 on the left side and one bilaterally. Logistic regression analysis revealed that among the potential risk factors investigated, use of ice slush for myocardial preservation was the only independent risk factor related to phrenic nerve dysfunction (p=0.01), carrying an 8-fold higher incidence for this complication. In contrast, age, ejection fraction of the left ventricle, operative/bypass/aortic cross-clamp time, left internal mammary artery use, and diabetes mellitus were not found to be associated with phrenic neuropathy. The postoperative outcome of patients who received ice slush compared with that of those who had cold saline solution did not differ in terms of early morbidity and mortality. CONCLUSION: Among the risk factors investigated, only the use of ice slush was significantly associated with postoperative phrenic nerve dysfunction. Therefore, ice should be avoided in cardiac surgery, since it does not seem to provide additional myocardial protection.

Aged↗

Low-dose amiodarone-related complications after cardiac operations.

OBJECTIVE: High-dose preoperative amiodarone therapy has been implicated as a risk factor for serious complications after cardiac operations. To investigate the effect of preoperative low-dose amiodarone treatment on early postoperative outcome after cardiac operations, we prospectively studied 88 patients. METHODS: Forty-four patients were receiving amiodarone (mean daily dose +/- standard deviation, 205 +/- 70 mg/day) and 44 patients were controls matched in pairs. The following parameters were recorded after the operation in all patients: (1) the ratio of oxygen tension to inspired oxygen fraction on arrival in the intensive care unit and 2, 4, 6, 10, 14, 18, and 22 hours thereafter; (2) the occurrence of acute respiratory distress syndrome; (3) early postoperative cardiac complications; and (4) the type and number of inotropic agents or vasopressors (or both) needed. RESULTS: No difference in the ratio of oxygen tension to inspired oxygen fraction was noted at the various time intervals between amiodarone-treated patients and control patients. Overall, only one patient had acute respiratory distress syndrome in the amiodarone group, but he had multiple other factors known to predispose to acute lung injury. Several cardiac complications, such as pulmonary edema, temporary pacing, and need for intraaortic balloon pump counterpulsation, were observed more frequently in amiodarone-treated patients than in control patients. In addition, amiodarone-treated patients required more frequent inotropic support (73% vs 43%, p = 0.003) and more inotropic drugs or vasopressors (or both) per patient than did control patients (1.4 +/- 1.1 vs 0.6 +/- 0.8, p = 0.002). CONCLUSION: Preoperative low-dose amiodarone therapy does not seem to be related to significant postoperative lung toxicity, but it is associated with various cardiac complications and an increased need for more intense inotropic support after cardiac operations. These findings may be related to the drug's depressant effect on the myocardium.

Amiodarone↗

Error rates in Australian chemical pathology laboratories.

OBJECTIVE: To measure transcription and analytical errors made by Australian chemical pathology laboratories. DESIGN: Retrospective data collection covering the period 1 November 1993 to 1 April 1994. SETTING AND PARTICIPANTS: Fourteen pathology laboratories in five Australian States (seven in the public sector, and seven in the private sector). MAIN OUTCOME MEASURES: Error rates in transcribing information from request forms to computer record systems, and laboratory performance on chemical analysis. RESULTS: Pathology laboratories had a transcription-error rate of up to 39% and an error rate of up to 26% for analytical results. The worst-performing laboratory had errors (of patient identification or results of analysis) in 46% of requests. The three best-performing laboratories achieved 85% error-free reporting, with one achieving 95%. CONCLUSIONS: Error rates in Australian pathology laboratories vary widely, but may be as high as 46% for all specimens in some laboratories. The types of errors reported were under the control of the laboratory, and would affect the accuracy of reported pathology test results, with potential adverse outcomes for patient care and inefficient use of health-care resources. There is a need to establish broader quality assurance programs and performance requirements to reduce these types of error.

Australia↗

The surveillance of birth defects: the usefulness of the revised US standard birth certificate.

To assess the sensitivity and positive predictive value of birth defects reported on the 1989 revision of the US Standard Birth Certificate, a population of 76,862 Atlanta-area births during 1989 and 1990 was used as the basis for comparing 771 birth certificates that reported birth defects with 2428 live-born infant records in a birth defects registry that uses multiple sources of case ascertainment. Only 14% of birth defects in the registry records were reported on birth certificates. After the analysis was restricted to defects recognizable at birth, the sensitivity and positive predictive value of the birth certificates were 28% and 77%, respectively. Birth certificates underestimate birth defect rates and should be used cautiously for birth defect surveillance and epidemiological studies.

Birth Certificates↗