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M el-Khatib

Publications and source records attributed to M el-Khatib.

14 recordsLinked to original sources

High frequency ventilation.

High frequency ventilation (HFV) is a general term that refers to a family of mechanical ventilation techniques that involves ventilator rates that are supraphysiological (more than 60 breaths/minute), and utilizes tidal volumes that are equal or less than the anatomical dead space of the airways. This paper is a review of the different HFV techniques, along with the mechanisms of oxygenation and ventilation, the clinical applications, and management strategies for different disease entities, and possible complications of HFV.

Animals↗

High frequency ventilation in five different neonatal pathologies.

High frequency ventilation (HFV) has been used for the last two decades. Several questions related to its optimal use, comparative efficacy of different types of HFV, as well as the role of HFV in different diseases are still debated and under investigation. Literature reviews discussing the controversies in high frequency ventilation have rather emphasized the importance of a disease strategy rather then the type of HFV. In this article, a presentation and discussion of five patients with different HFV strategies admitted and managed with HFV at the American University of Beirut-Medical Center.

Female↗

A new cut-off point of thyromental distance for prediction of difficult airway.

BACKGROUND: Difficult intubation, often unexpected, remains a primary concern for the anesthesiologist. None of the bedside tests have proven to be efficacious and highly predictive. The prupose of this study was to correlate the full range of thyromental distance with both the Cormack grade and the Mallampati score. METHODS: One hundred and sixty patients undergoing general anesthesia were included in the study. Patients with abnormal atlanto-occipital extension, small chin size and mouth opening were excluded from the study. The thyromental distance, the Mallampati score, and the Cormack grade were determined in all patients. The correlation between the thyromental distance and each of the Cormack grade and the Mallampati score was determined, as well as the correlation between the Mallampati score and the Cormack grade. The cut-off value of the tyromental distance that discriminated best between patients with easy glottic visualization (Cormack grade 1,2) vs. difficult visualization (Cormack grade 3,4) was derived. RESULTS: A significant and high correlation was observed between the thyromental distance and the Cormack grade (r = -0.72). In contrast, a lower correlation was observed between the thyromental distance and the Mallampati score (r = -0.41) and the Mallampati score and the Cormack grade (r = 0.47). A cut-off value for the TMD of 4 cm was the best in discriminating between patients with difficult and easy glottic visualization. The combination of TMD < or = 4 cm and Mallampati score of 3,4 predicted the patients with the most difficult glottic visualization. CONCLUSION: Patients with a thyromental distance greater than 4 cm can be easily intubated. In contrast, when the TMD < or = 4 cm, tracheal intubation is difficult in 48% of patients if the Mallampati score is 1,2 and in 79% if the Mallampati score is 3 or 4.

Adolescent↗

Evaluation of predictors of weaning from mechanical ventilation in pediatric patients.

Objective criteria for ending mechanical ventilation have not been established for infants and children. A recent study in adult patients developed two new indexes, the Rapid Shallow Breathing Index (RSB) and the CROP Index for predicting success or failure of extubation. We decided to evaluate the applicability of these indices to intubated, mechanically ventilated pediatric patients. For this evaluation the indices were adapted to the physiology of infants and children. A pneumotachograph was used to measure spontaneous tidal volume, respiratory rate and dynamic compliance. The tidal volume and the dynamic compliance were corrected for the patient's body weight. Based on the data collected a cutoff value for each index was determined. Of 47 sets of patient data, 38 (81%) were collected during successful extubations, 9 (19%) during failed extubations. A modified CROP index value of > or = 0.1 ml x mmHg/bpm/kg and a modified RSB index value of < or = 11 bpm/mlkg were identified as predictive of successful extubation. The modified CROP cutoff value produced a sensitivity and specificity of 1.0; respective values for the modified RSB cutoff value are 0.79 and 0.78. Cutoff values of > or = 0.1 and < or = 11 for the modified CROP index and RSB index, respectively, appear to be predictive of successful extubation in the pediatric population. Our data identifies the modified CROP index as a superior discriminator between successful and unsuccessful extubation.

Adolescent↗

Regulation of T-cell death genes: selective inhibition of FasL- but not Fas-mediated function.

Activation-induced cell death (AICD) requires coexpression of Fas and FasL. Hybridoma T-cells express detectable FasL mRNA 3 to 5 hr after culture in anti-CD3-coated wells. High and steady expression of FasL mRNA was observed after 8-10 hr of activation. Expression of FasL cytotoxicity and AICD is consistent with the time-course of FasL mRNA induction. Fas-Ig was effective in inhibiting AICD when added no later than 5 hr after activation, but was ineffective when added after 8-10 hr of activation. These observations suggest that FasL gene activation is a critical step for AICD. By contrast, Fas was constitutively expressed and the time-course study did not support the idea that up-regulation of Fas is critical for AICD. The critical role of FasL gene activation for AICD was confirmed by studies using inhibitors of AICD. Dexamethasone (Dex) inhibited FasL induction and Fas up-regulation, but not basal Fas expression of hybridoma T-cells. All-trans retinoic acid (RA) inhibited FasL induction, but had little effect on Fas up-regulation. Both agents inhibited FasL cytotoxicity. The Fas-mediated death pathway distal to Fas/FasL interactions remained intact in the protected hybridoma T-cells. These results demonstrate that FasL gene activation, but not Fas up-regulation, is critical for AICD and that Dex and all-trans RA selectively inhibits FasL but not Fas function. The system may prove useful for the identification of critical factors regulating T-cell death genes. It may also serve as a useful system to study gene regulation in AICD-dependent phenomena.

Animals↗

Characterization of lpr-derived T cell hybridomas: Fas-deficient hybridomas are deathless, growth-arrested, and cytotoxic upon activation.

T cell hybridomas that are deathless upon TCR crosslinking were generated from lpr mice. The deathless hybridomas (1.4 and 5D5) expressed extremely low Fas even after anti-CD3 activation, whereas activation-induced cell death (AICD) was observed for Fas-expressing hybridomas. The deathless hybridomas were activated to produce FasL and IL-2, indicating that the intrinsic defect in Fas expression or up-regulation resulted in AICD blockade. The deathless hybridoma cells expressed longer and stronger FasL cytotoxicity than AICD-sensitive hybridomas. Although deathless, activated 5D5 cells were arrested at the G1/S border. Growth arrest lasted for at least 5 days, but some cells eventually recovered and proliferated. The deathless 5D5 cells were used to demonstrate that AICD includes a fratricidal mechanism that kills AICD-sensitive bystanders. The deathless T cell hybridomas are useful tools for studying T cell activation-dependent functions sensitive to AICD.

Animals↗

Glycosphingolipid synthesis and proliferation in a renal cell line grown in high glucose.

We evaluated the role of sphingolipids as potential mediators of the renal epithelial growth response to growth in high-glucose media. The mouse cortical tubule (MCT) cell line was studied under high-glucose (450 mg/dl) and normal glucose (100 mg/dl) conditions. In cells plated at low-density, high-glucose media stimulated cell proliferation as measured by DNA, protein, and cell number and [3H]thymidine incorporation with a corresponding increase in glucosylceramide (GlcCer). The GlcCer synthase inhibitor, 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), blocked the proliferative response to high glucose in association with a decrease in endogenous GlcCer and an increase in ceramide concentrations. Addition of N-acetylsphingosine, a short-chain homologue of natural ceramides, increased the levels of endogenous ceramides and inhibited proliferation. In contrast, the beta-glucosidase inhibitor conduritol B epoxide resulted in increased cell GlcCer but did not increase proliferation. We conclude that MCT cells proliferate when grown in the presence of high glucose. GlcCer levels increase and ceramide levels decrease in concert with the proliferative response. Pharmacologically increasing endogenous levels of ceramide inhibits the proliferative response to high glucose, but increasing endogenous levels of GlcCer does not stimulate proliferation.

Animals↗

Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation.

Receptor crosslinking of T-cell hybridomas induces cell activation followed by apoptosis. This activation-induced cell death requires de novo synthesis of RNA and proteins, but the actual gene products that provide the death signal have not been identified. We show here that receptor crosslinking induces Fas ligand and upregulates Fas, and that the ensuing engagement of Fas by Fas ligand activates the cell-death programme. Cell death, but not activation, can be selectively prevented by a soluble Fas-immunoglobulin fusion protein. Thus, Fas and Fas ligand are the death-gene products, and their interaction accounts for the molecular mechanism of activation-induced T-cell death.

3T3 Cells↗

The molecular mechanism of FasL-mediated cytotoxicity by CD4+ Th1 clones.

Murine CD4+ Th1 clones require de novo synthesis of proteins to express a cytotoxicity that is mediated by de novo synthesized Fas ligand (FasL). The cytotoxic process of the CD4+ Th1 effectors can be separated into four stages, namely conjugate formation, activation, lethal hit, and effector-independent target cell death. The present study describes the cytotoxic process in terms of FasL induction and Fas/FasL molecular interactions for death signal transduction. Fas-Ig fusion proteins, cycloheximide, actinomycin D, and EGTA+MgCl2 were used to analyze each stage of the cytotoxic process in terms of FasL/Fas participation. The results demonstrate that the activation-induced de novo mRNA and protein synthesis were for FasL, which provided the predominant cytotoxic activity of CD4+ Th1 effectors. Once activated, Th1 effectors express cytotoxic activity in the presence of EGTA+MgCl2, an experimental [Ca2+]ext-independent condition characteristic of FasL-mediated cytotoxicity. The ability of Fas-Ig to inhibit target lysis declined rapidly after conjugate formation, indicating that FasL-mediated lethal hit is critically dependent on conjugate formation and, once delivered, the effector-independent target lysis proceeds. After the lethal hit stage, transduction of Fas-mediated death signal was independent of de novo synthesis of macro-molecules in targets because treatments that inhibited more than 98% of the macromolecule synthesis had little effect on target lysis. Our study provides the first molecular view in terms of FasL/Fas of the cytotoxic process of CD+ Th1 cells.

Animals↗

Pregnancy-related complications in women with reflux nephropathy.

Three hundred and forty-five pregnancies in 137 women with reflux nephropathy have been studied. All pregnancies took place after 1971. Overall foetal loss was 48 (14%) of which only 6 (2%) were therapeutic abortions. Maternal complications (urine infection, hypertension, proteinuria, oedema, deterioration in renal function, hematuria or renal stones) occurred alone or in combination in 39% of pregnancies. Fifty-two pregnancies took place in women with plasma creatinine (P.Cr > 0.11 mmol/l) prior to conception. Foetal loss after 12 weeks gestation (excluding therapeutic abortions) was 18% compared with 8% in the 104 pregnancies where maternal P.Cr was known to be < or = o.11 per/l at conception (p < 0.05). Maternal complications were also more common in the impaired renal function group (p < 0.001). Comparison of pregnancies in women with unilateral versus bilateral renal scarring revealed no significant difference in foetal loss but an increased incidence of over 50% maternal complications in the bilateral renal scar group (p < 0.01). The incidence of pre-eclampsia was higher in women with bilateral renal scars, 50 (24%) than in women with unilateral scars 8 (7%) (p < 0.001). Persistent vesicoureteric reflux was not associated with increased foetal loss or maternal risk. Impaired renal function prior to conception is associated with increased foetal and maternal complications in pregnancy. Bilateral renal scarring is associated with increased maternal complications during pregnancy.

Abortion, Spontaneous↗

The cytotoxic process of CD4 Th1 clones.

Previous studies have demonstrated that murine CD4 Th1 cells lack perforin and use a pathway distinctive from CD8 CTL to express cytotoxicity. Whether the cytotoxic process of Th1 cells can be separated into identifiable stages and how these differences affect this process were determined in this study. We have resolved the cytotoxic process of Th1 clones into three stages identical with those of CD8 CTL, namely, conjugate formation/activation, lethal hit, and effector-independent programming for target DNA fragmentation. By comparing the cytotoxic processes between Th1 clones on Ag-pulsed targets and (PMA+A23187)-activated Th1 clones on unpulsed targets, we have also demonstrated that 1) the requirement of CD4 Th1 cells for de novo synthesis of cytotoxic machinery was partly responsible for the lag time in the induction of target DNA fragmentation by Th1 clones; 2) lethal hit was delivered rapidly; 3) lethal hit under forced contact by centrifugation did not need extracellular Ca2+ and Mg2+; 4) without centrifugation, lethal hit required extracellular Mg2+, but not Ca2+; 5) the average functional half life of the cytotoxic machinery was 54 +/- 24 (n = 4) min. The data demonstrate that the cytotoxic process of Th1 clones uses an activation-dependent cytotoxic machinery to deliver a short-lived, short-ranged, and quick-acting lethal hit to target, which induces a program in target for DNA fragmentation.

Animals↗

A novel cytotoxicity of CD4+ Th1 clones on heat-shocked tumor targets. I. Implications for internal disintegration model for target death and hyperthermia treatment of cancers.

A novel cytotoxicity, which is normally hidden but unveiled upon interacting with heat-shocked tumor target, has been identified in CD4+ Th1 cells. When TNF-resistant, Ag-presenting tumor targets were heat shocked, the cytotoxicity by specific Th1 clones was significantly enhanced. Interestingly, the DNA of heat-shocked, unpulsed targets including Ia- tumor cells were also fragmented by Th1 clones. In contrast to the Ag-dependent, MHC-restricted cytotoxicity, the heat-shock-induced sensitivity to Th1 clones was a) Ag independent and MHC unrestricted, b) insensitive to CD4-mAb, c) resistant to actinomycin D and cycloheximide, and d) greatly enhanced by cholera toxin, PGE1, PGE2, and dibutyryl cAMP. This novel cytotoxicity was inhibited by mAb specific to lymphocyte function-associated Ag-1 and intercellular adhesion molecule-1. Upon culturing at 37 degrees C, mildly heat-shocked target cells gradually recovered, indicating that the heat-shock-induced sensitivity was transient and reversible. The implication of this study for a signal-induced internal disintegration mechanism for target death is discussed. The novel cytotoxicity of CD4+ Th1 cells may be an important mechanism of immune regulation under febrile conditions and an underlying mechanism for the hyperthermia treatment of cancers.

Animals↗