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Biomedical subjects

M Farhat

Publications and source records attributed to M Farhat.

At least 19 recordsLinked to original sources

Cavitation bubble dynamics inside liquid drops in microgravity.

We studied spark-generated cavitation bubbles inside water drops produced in microgravity. High-speed visualizations disclosed unique effects of the spherical and nearly isolated liquid volume. In particular, (1) toroidally collapsing bubbles generate two liquid jets escaping from the drop, and the "splash jet" discloses a remarkable broadening. (2) Shock waves induce a strong form of secondary cavitation due to the particular shock wave confinement. This feature offers a novel way to estimate integral shock wave energies in isolated volumes. (3) Bubble lifetimes in drops are shorter than in extended volumes in remarkable agreement with herein derived corrective terms for the Rayleigh-Plesset equation.

Journal Article↗

False-positive tuberculin skin tests: what is the absolute effect of BCG and non-tuberculous mycobacteria?

BACKGROUND: Despite certain drawbacks, the tuberculin skin test (TST) remains in widespread use. Important advantages of the TST are its low cost, simplicity and interpretation based on extensive published literature. However, TST specificity is reduced by bacille Calmette-Guérin (BCG) vaccination and exposure to non-tuberculous mycobacteria (NTM). METHODS: To estimate TST specificity, we reviewed the published literature since 1966 regarding the effect of BCG vaccination and NTM infection on TST. Studies selected included healthy subjects with documented BCG vaccination status, including age at vaccination. Studies of NTM effect had used standardised NTM antigens in healthy subjects. RESULTS: In 24 studies involving 240,203 subjects BCG-vaccinated as infants, 20,406 (8.5%) had a TST of 10+ mm attributable to BCG, but only 56/5639 (1%) were TST-positive if tested > or =10 years after BCG. In 12 studies of 12,728 subjects vaccinated after their first birthday, 5314 (41.8%) had a false-positive TST of 10+ mm, and 191/898 (21.2%) after 10 years. Type of tuberculin test did not modify these results. In 18 studies involving 1,169,105 subjects, the absolute prevalence of false-positive TST from NTM cross-reactivity ranged from 0.1% to 2.3% in different regions. CONCLUSIONS: The effect on TST of BCG received in infancy is minimal, especially > or =10 years after vaccination. BCG received after infancy produces more frequent, more persistent and larger TST reactions. NTM is not a clinically important cause of false-positive TST, except in populations with a high prevalence of NTM sensitisation and a very low prevalence of TB infection.

Adjuvants, Immunologic↗

Eph and ephrin expression in normal placental development and preeclampsia.

Eph receptors and their ephrin ligands play a fundamental role in embryogenesis. Their functions include cell targeting and angiogenesis. In placental development, trophoblasts migrate and invade maternal tissue and spiral arteries, where they play a role in both anchoring the placenta to the uterus and increasing blood flow to the developing fetus (interstitial and endovascular invasions). We investigated the cellular distribution and expression patterns of representative Eph and ephrin RNA and protein in an effort to identify the molecules involved in trophoblast migration during normal placental development and placental pathologies. We found ephrin-A1 expressed exclusively in the invasive extravillous trophoblast (EVT) cell lineage. We therefore proceeded to investigate ephrin-A1 in placental pathologies with defects in EVT invasion. In preeclampsia, where trophoblast invasion is shallow, we observed ephrin-A1 expression similar to normal placenta. Furthermore, in initial experiments on the deeply invading trophoblasts of placenta accreta, which lacks decidua, ephrin-A1 is found to be expressed highly in extravillous trophoblasts that have invaded the myometrium. In addition, we found the prototype ephrin-A1 receptor, EphA2, localized in several placental cell types. EphB4 and ephrin-B2 molecules, which have specific expression patterns during artery and vein development, respectively, were also expressed in the placenta. The cell specific distribution of ephrin-A1 suggests that it may play a role in targeting and migration of trophoblasts, and in the vascular remodeling induced by the invading extravillous trophoblasts. Failure of ephrin-A1 expression is unlikely to be the primary cause in defective migration of trophoblasts observed in preeclampsia. Specific roles for other Eph and ephrin proteins remain to be investigated.

Blotting, Northern↗

Successful pregnancy following replacement of embryos previously refrozen at blastocyst stage: case report.

We present the first reported clinical pregnancy following transfer of embryos that had been subjected to two freeze-thaw cycles: the first at day 3 after insemination, and the second after culturing to the blastocyst stage. A 25-year-old woman undergoing IVF treatment for male factor infertility opted for intracytoplasmic sperm injection (ICSI). ICSI treatment resulted in the successful production of 19 early cleavage embryos, all of which were frozen. After thawing, the embryos were cultured to the blastocyst stage. Thereafter, the blastocysts were refrozen and again thawed prior to embryo transfer. Embryos surviving a day 3 freeze-thaw cycle developed to the blastocyst stage and survived the second freeze-thaw cycle. Successful clinical pregnancy resulted following two sequential freeze-thaw cycles. This finding shows that it is possible to refreeze supernumerary blastocysts for subsequent transfer.

Adult↗

Intermediate-dose intravenous melphalan and blood stem cells mobilized with sequential GM+G-CSF or G-CSF alone to treat AL (amyloid light chain) amyloidosis.

AL amyloidosis patients ineligible for dose-intensive melphalan (200 mg/m2) were enrolled on a phase 11 trial to be treated with two cycles of intermediate-dose melphalan (IDM 100 mg/m2) and mobilized blood stem cells (BSC). For mobilization patients were randomized to either GM-CSF 250 microg/m2 for 3 d followed by G-CSF 10 microg/ kg for 3 d (GM+G), or G-CSF 10 microg/kg for 6 d (G-alone), with leukaphereses on days 5, 6 and 7. To minimize morbidity, we planned to support each cycle with 3 5 x 106 CD34+ cells/kg and had a collection target of 7 x 10(6) CD34+ cells/kg. Those who did not achieve the target were treated with one cycle of IDM. 30 patients, a median of 62 years old and 7 months from diagnosis, were enrolled. Both mobilization regimens were generally well tolerated, and similar in terms of CD34+ cells and CFU-GM collected, but only 6/28 patients achieved the collection target (GM+G four, G-alone two). Despite a 19% incidence of grade 4 toxicities, IDM therapy was well tolerated. At a median follow-up of 24 months (19-36) 57% of patients had survived, 17% with durable complete haematological responses and 40% with improved or stable amyloid organ involvement, including 3/9 patients with predominant cardiac amyloid who are alive 2-3 years after treatment. The 100 d mortality was 20%. In conclusion, no definitive differences were identified between the mobilization regimens and IDM was an active regimen in AL for selected patients.

Adult↗

Intracytoplasmic sperm injection pregnancy with trisomy 20p and monosomy 22q in a newborn resulting from a balanced paternal translocation.

In infertile men who carry a balanced reciprocal translocation, intracytoplasmic sperm injection (ICSI) may induce a pregnancy with an abnormal karyotype. This report describes a previously unreported paternal reciprocal translocation leading to a chromosomally unbalanced ICSI pregnancy. The triplet pregnancy resulted in 1 normal girl, 1 physically normal boy with the same balanced paternal translocation, and a severely malformed boy with trisomy 20p and monosomy 22q who died in the neonatal period.

Chromosomes, Human, Pair 20↗

Heliox tolerance in spontaneously breathing neonates with bronchopulmonary dysplasia.

The use of a gas mixture in which helium is substituted for nitrogen allows a decrease in pulmonary resistances and in resistive work of breathing. This treatment might allow a reduction in energy expenditure in infants with bronchopulmonary dysplasia (BPD) and spare calories for growth. In a preliminary study designed to assess tolerance to Heliox(R), 4 infants with BPD and 4 controls were studied firstly when breathing air and secondly when breathing Heliox(R), at 10, 20 and 30 min exposure (T10, T20, T30). The following parameters were recorded: respiratory and cardiac rates, room (RT) and skin temperatures (ST) and transcutaneous (Tc) blood gases. When breathing air, TcPO2 was normal in the two groups (mean +/- SEM: 70 +/- 4 mm Hg in BPD vs. 78 +/-4 in controls). TcPCO2 was higher in the BPD group (41 +/- 2 vs. 35 +/- 1 mm Hg in controls; p = 0.028). Spontaneously breathing Heliox had immediate consequences such as wakening, crying, decrease in ST and hypoxia. Hypoxia was more serious and more rapid in the BPD group. At the 10-min exposure, mean TcPO2 was 39 +/- 4 mm Hg in BPD vs. 69 +/- 7 in controls (p = 0.042). Hypoxia was immediately corrected when breathing room air. TcPCO2 was unchanged in both groups.

Behavior↗

Oestradiol inhibition of vascular myointimal proliferation following immune, chemical and mechanical injury.

The lower incidence of coronary artery disease in premenopausal women and in postmenopausal women treated with oestrogen supports the hypothesis that oestrogen protects the vasculature from injuries or from responding to injuries with arteriosclerosis. The mechanism remains unknown, although currently the most frequent suggestion is that oestrogen induces beneficial quantitative and qualitative changes in serum lipoprotein concentrations. We studied other mechanisms and in particular the direct effects of 17 beta-oestradiol on vascular smooth muscle and the endothelium. Our focus has been on the vascular response to injury by myointimal and medial thickening, leading to narrowing or occlusion of the vessel. This is frequently seen in coronary arteries within months following angioplasty and a few years following cardiac transplantation. We find that oestradiol treatment protects and reduces the vascular response to injury in three in vivo and one in vitro models: (1) in the rabbit cardiac allograft where oestrogen inhibits accelerated graft atherosclerosis; (2) in monocrotaline- or hypoxia-induced pulmonary hypotension in the rat, where oestrogen attenuates pulmonary artery pressure, right ventricular hypertrophy and medial thickening of the pulmonary artery; (3) oestrogen protects against balloon injury in rabbit aorta; and (4) it inhibits smooth muscle cell proliferation in the porcine left anterior descending coronary artery.

Animals↗

The interaction between endothelium-derived relaxing factor (EDRF) and eicosanoids in the regulation of the mesenteric microcirculation.

Locally produced eicosanoids and endothelium-derived factors are believed to be the mediators of vascular tone of various vascular beds including the mesentery. Using a small vessel isometric myograph which allows direct measurement of microvascular reactivity, the interaction of eicosanoids and endothelium-derived relaxing factor (EDRF) in regulating vascular tone of mesenteric microcirculation of the rat was characterized. The microvascular response to various vasoactive agents before and after inhibition of prostacyclin production with indomethacin (INDO, 5 microM) and inhibition of EDRF synthesis with N omega-nitro-L-arginine methyl ester (L-NAME, 50 microM) was compared. Analysis of dose-response curves for prostaglandin F2 alpha (PGF2 alpha), U46619, a stable thromboxane analog, and norepinephrine (NE) after pretreatment with INDO demonstrated that inhibition of endogenous eicosanoids significantly attenuated the vasoconstrictor response to PGF2 alpha and U46619 but not to NE. Inhibition of EDRF synthesis with L-NAME potentiated the vasoconstrictor response to PGF2 alpha, U46619, and NE. These results suggest that EDRF acts as the primary mediator of vasodilator tone in the mesenteric microcirculation rather than vasodilator cyclooxygenase products such as prostacyclin. It also appears that the vasoconstrictor action of PGF2 alpha and U46619 may be mediated by a release of an endogenous indomethacin-sensitive factor.

Animals↗

Effect of N-substituted arginine compounds on blood pressure in anesthetized rats.

Inhibition of endothelium-dependent relaxation by NG-monomethyl L-arginine (L-NMMA) and its reversal by excess L- but not D-arginine is used to support the hypothesis that the endothelium-derived relaxing factor (EDRF) is generated exclusively from the metabolism of L-arginine. However, in freshly isolated vascular tissues, L-arginine is a poor vasodilator when compared to the N-substituted arginine compound, N alpha-benzoyl L-arginine ethyl ester (BAEE). Here, we show that such N-substituted compounds are potent hypotensive agents in anesthetized rats. In contrast, L-arginine elicits hypotensive effect only at higher concentrations (greater than 100 mg/kg). This effect of L-arginine is not antagonized by L-NMMA. Furthermore, D-arginine, L-homoarginine and L-lysine also have hypotensive effects at these concentrations. Indomethacin treatment partially attenuates the hypotensive effects of the basic amino acids. In contrast, the hypotensive effect of BAEE is antagonized by L-NMMA in a dose-dependent manner and by methylene blue, which is an inhibitor of soluble guanylate cyclase. In addition, substitution at the arginine moiety determines the hypotensive effect. When the amino acid glycine is inserted between the benzoyl group and arginine as in benzoyl-glycine-arginine, significant attenuation of the hypotensive effect is observed. These data demonstrate that compounds such as BAEE generate an EDRF-like agent in vivo and basic amino acids such as L-arginine elicit hypotension at concentrations above 100 mg/kg by mechanisms other than the generation of EDRF.

Amino Acids↗

Effect of N alpha-benzoyl-L-arginine ethyl ester on coronary perfusion pressure in isolated guinea pig heart.

N alpha-Benzoyl-L-arginine ethyl ester (BAEE) when compared to L-arginine significantly decreased coronary perfusion pressure of isolated guinea pig heart in a dose dependent and reproducible manner. This effect of BAEE was antagonized by haemoglobin and N-monomethyl L-arginine, both inhibitors of endothelium dependent relaxation. These results support the notion that the mechanism of relaxation elicited by BAEE is due to the generation endothelium dependent relaxing factor (EDRF) like agents.

Animals↗

Pharmacologic profile of BN 50739, a new PAF antagonist in vitro and in vivo.

The effect of a new PAF antagonist BN 50739 was studied on PAF-induced [3H]-serotonin release from washed rabbit platelets in vitro and on PAF-induced hypotension in vivo. BN 50739 competitively inhibited PAF-induced [3H]-serotonin release from the platelets in a dose-dependent manner. In the presence of 4, 10 and 50 nM of BN 50739, the concentration of PAF inducing 50% maximal [3H]-serotonin release from the platelets (EC50) increased from 2.15 nM to 5.10, 45.10 and 900 nM, respectively. The IC50 of BN 50739 for PAF (10 nM) induced [3H]-serotonin release was 3.67 nM. Under the same experimental condition, the IC50s of BN 50726, BN 50730, BN 50741, WEB 2086, SRI 63-441 and BN 52021 were 5.40, 4.61, 6.88, 5.98, 40.90 nM and 14.90 microM, respectively. PAF-induced hypotension in conscious rats was also inhibited dose-dependently by i.p. pretreatment of BN 50739 (3 and 10 mg/kg). PAF-induced hypotension was diminished both in magnitude and duration in rats pretreated with BN 50739. These data taken together indicate that BN 50739 is a most potent PAF antagonist in vitro and in vivo.

Animals↗

Platelet activating factor (PAF) and tumor necrosis factor-alpha (TNF alpha) interactions in endotoxemic shock: studies with BN 50739, a novel PAF antagonist.

BN 50739, a new PAF receptor antagonist, was tested in vitro and in vivo for its capacity to block PAF, endotoxin and recombinant human tumor necrosis factor-alpha (rTNF)-mediated effects. In vitro, BN 50739 blocked PAF-induced platelet aggregation by 60 to 100% at 0.2-1 x 10(-7) M (P less than .002), respectively. In the conscious rat, pretreatment (30 min) with BN 50739 (n = 5-13) dose-dependently attenuated PAF-induced hypotension (-5 +/- 5 vs. - 43 +/- 2 mm Hg, P less than .01) and shortened the recovery time of mean arterial pressure (22 +/- 13 vs. 325 +/- 46 sec, P less than .01). BN 50739 (10 mg/kg i.p., n = 5-11) prevented endotoxin (14.4 mg/kg) induced-hemoconcentration (54 +/- 1 vs. 46 +/- 1%, P less than .01) and reduced 24-hr mortality (100 vs. 60%, P less than .05). Only partial protection was conveyed by BN 50739 against the hypotensive response to endotoxin (115 +/- 3 vs. 91 +/- 4 mm Hg, P less than .03). Also, BN 50739 attenuated the lipopolysaccharide-induced elevation of plasma thromboxane B2 (21.2 +/- 0.8 vs. 46.7 +/- 11.8 pg/100 microliters, P less than .01) and tumor necrosis factor-alpha (7523 +/- 3983 vs. 26,430 +/- 3541 U/ml, P less than .05), whereas leukopenia and thrombocytopenia remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Protective effect of BN 50739, a new platelet-activating factor antagonist, in endotoxin-treated rabbits.

Platelet-activating factor (PAF) has been demonstrated in the circulation and organs of animals exposed to gram negative endotoxins, whereas PAF antagonists have been shown to exhibit some efficacy in modifying the course of endotoxemia. In this study we evaluated BN 50739, a novel specific PAF antagonist, for its capacity to block PAF or lipopolysaccharide endotoxin (LPS)-mediated effects in rabbits. Pretreatment with BN 50739 (3 and 10 mg/kg i.p.) inhibited PAF (500 pmol/kg i.v.)-induced thrombocytopenia, leukopenia and plasma thromboxane B2 elevation in a dose-dependent manner. The inhibitory effect lasted 3.5 to 4.5 hr. BN 50739 (10 mg/kg) prevented the early phase of LPS (50 micrograms/kg i.v.)-induced thrombocytopenia and thromboxane B2 elevation, and reduced the 24-hr mortality rate from 75 to 22% (P less than .05). Post-treatment with BN 50739 increased the 10-hr survival rate from 33 to 87% (P less than .05); however, it had no effect on the 24-hr mortality. BN 50739 did not affect LPS-induced leukopenia or the elevation in plasma tumor necrosis factor. Our data support possible therapeutic efficacy of PAF antagonists in septic shock despite their inability to prevent the generation of tumor necrosis factor.

Animals↗

[Hydatid cysts of the lung treated surgically].

Pulmonary echinococcosis is still widespread in Tunisia as in most countries of North Africa. The segment of population affected is young; 198(74%) of 268 patients studied by the authors were less than 30 years old. There were no symptoms in 8% of patients and 92% presented with some complication. The treatment of choice is surgical but conservative pericystectomy was performed in 204 (76%) patients and resection in 64 (24%). Operative mortality was 1.5% and postoperative complications were noted in 8% of patient with an infected cyst. If it is impossible to prevent the disease, the authors recommend early detection, permitting surgical treatment without complications.

Adolescent↗