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Biomedical subjects

R Levi

Publications and source records attributed to R Levi.

At least 37 records · Page 2Linked to original sources

Bilateral jugular venous thromboembolism and pulmonary emboli in a patient with severe ovarian hyperstimulation syndrome.

We report here a case of severe ovarian hyperstimulation syndrome with massive ascites in a 25-year-old woman with a history of primary infertility after an IVF-ET cycle. At the 9th gestational week she presented with neck pain and dyspnea and duplex Doppler sonographic examination of the neck veins revealed bilateral jugular venous thrombosis. Despite prompt administration of low-molecular weight heparin, pulmonary emboli developed a few days later.

Adult↗

Thiamine deficiency in patients with B-chronic lymphocytic leukaemia: a pilot study.

Malignancy associated primary thiamine deficiency has been documented in several experimental tumours, sporadic clinical case reports, and in a number of patients with fast growing haematological malignancies. Thiamine status was assessed prospectively in 14 untreated B-chronic lymphocytic leukaemia (CLL) patients, and in 14 age matched control patients with non-malignant disease. Patients with any known cause of absolute, relative, or functional thiamine deficiency were excluded. High (>15%) thiamine pyrophosphate effect (TPPE), indicating thiamine deficiency, was found in five out of 14 CLL patients (35.7%) and in none of the controls (p=0.057). Mean (SD) TPPE in the thiamine deficient patients group was 21.6 (3.4)%. In all the patients, thiamine deficiency was subclinical. No correlates for the thiamine deficiency have been found save for an increment of more than 20% in the total leucocyte count over the preceding three months, which was found in all five thiamine deficient patients compared with only one of the nine non-thiamine deficient CLL patients. Thus, CLL patients may be prone to develop primary thiamine deficiency possibly promoted by the increased leucocytes span, which may increase thiamine consumption. Since even subclinical thiamine deficiency may be detrimental to the patient's clinical course, and in view of the theoretical danger of thiamine promoted tumour cell proliferation, further large scale studies are warranted to confirm this observation, and to elucidate the issue of thiamine supplementation to CLL patients.

Aged↗

Targeting of an expressed neurotoxin by its recombinant baculovirus.

AaIT, an insect-selective neurotoxic polypeptide derived from scorpion venom, has recently been used to engineer recombinant baculoviruses for insect pest control. Lepidopterous larvae infected with an AaIT-expressing baculovirus reveal symptoms of paralysis identical to those induced by injection of the native toxin. However, the paralyzed larvae treated by the recombinant virus possess an approximately 50-fold lower hemolymph toxin concentration than insects paralyzed by the native toxin. The mechanism of this potentiation effect was studied using immunocytochemistry, electrophysiology and toxicity assays. (i) Light microscopy, using peroxidase-conjugated antibodies, revealed the presence of toxin in virus-susceptible tissues, including tracheal epithelia located close to the central nervous system and beyond its lamellar enveloping sheath. (ii) High-resolution immunogold electron microscopical cytochemistry clearly revealed the presence of recombinant AaIT toxin inside the thoracic and abdominal ganglia on neuronal cell bodies and axonal membranes. (iii) Ventral nerve cords dissected from silkworm larvae infected with the recombinant baculovirus exhibited a high degree of excitability, expressed as enhanced frequency and bursting mode of their spontaneous activity, when compared to nerve cords infected with the wild-type virus. We conclude that the recombinant-virus-infected tracheal epithelia, outbranching in the body of an infected insect, (i) locally supply a continuous, freshly produced toxin to its neuronal receptors and (ii) introduce the expressed toxin to the insect central nervous system, thus providing it with critical target sites that are inaccessible to the native toxin.

Animals↗

Successful pregnancy in an infertile woman with endometrial hyperplasia and embryo transfer. A case report.

BACKGROUND: Successful pregnancy in a woman with complex endometrial hyperplasia with atypia was treated conservatively with gestagens. CASE: The patient was initially diagnosed with complex hyperplasia of the endometrium with atypia by endometrial curettage and treated with several cycles of different gestagens. After repeated endometrial curettage, in vitro fertilization and embryo transfer were introduced for immediate treatment of the patient's infertility in order to avoid the risk of recurrent hyperplasia of the endometrium from estrogens. A single pregnancy was achieved after transfer of embryos obtained from intracytoplasmic sperm injection. This was performed due to poor semen characteristics. The patient delivered a normal, healthy male infant at term. CONCLUSION: Conservative treatment of complex endometrial hyperplasia with atypia in young women wishing to preserve fertility should be considered in carefully selected cases.

Adult↗

Wind direction coding in the cockroach escape response: winner does not take all.

Cockroaches respond to the approach of a predator by turning away and then running. Three bilateral pairs of giant interneurons are involved in determining the direction of the sensory stimulus and setting the turn direction. Each of these six interneurons has a different directional response to wind stimuli. We have tested whether these six cells use a winner-take-all mechanism to perform this directional determination: that is, each of these cells suppressing the motor response that each of the other cells promotes. Such a mechanism is found in similar behaviors of some other animals. By adding spikes to identified giant interneurons through intracellular stimulation during the sensory-induced behavior and analyzing the resulting directional leg movements, we find that a winner-take-all is not used in this system. Rather, directional determination appears to be based on collaborative calculation of direction by the giant interneurons as a group.

Action Potentials↗

Population vector coding by the giant interneurons of the cockroach.

We tested two alternative models of integration among the cockroach giant interneurons (GIs) for determining the directions of wind-evoked escape turns. One model, called steering wheel, pits contralateral GIs against one another; the other, called population vector model, involves a vector computation among the GIs. In testing each model theoretically, the population vector was found to account far better for the actual behavior. Both models could account for the results of previous behavioral-physiological experiments in which spikes had been added to the right GI3 together with wind stimuli from the right side. The two models revealed a critical behavioral-physiological experimental test that we then performed; namely, when delivering wind from the right side, adding spikes experimentally to the right GI2 should increase turn size according to the steering wheel model but should decrease turn size according to the population vector model. The latter result was obtained. The population vector, but not the steering wheel, model also could account for previous behavioral-physiological experiments in which spikes were added experimentally to a GI contralateral to the wind stimuli. The results support the population vector model as accounting for direction determination among the cockroach GIs.

Action Potentials↗

Influence of the target on distribution and functioning of the varicosities of Helix pomatia metacerebral cell C1 in dissociated cell culture.

The serotonergic metacerebral giant cell (C1) of Helix pomatia was isolated with its bifurcate axon and plated in culture under five conditions: (i) with no target; (ii) with the appropriate target B2 near the stump of the bigger branch (CBC); (iii) with B2 near the stump of the smaller branch (CC); (iv) with a wrong target (C3) near the stump of the CBC branch and (v) with B2 and C3 positioned near the CBC and CC stump, respectively. The counting of anti-serotonin antibody-labelled varicosities of the C1 neuron showed that the presence of the appropriate target in either axonal domain both down-regulated the number of varicosities of the contralateral neuritic field, and increased their average size, whereas the wrong target induced an overall reduction of the number of C1 neuron varicosities, and inhibited the evoked transmitter release. The action potential-evoked calcium concentration increase in the neuritic terminals of the C1 neuron cultured alone, or in presence of the appropriate target, reached a value significantly higher than that reached in presence of the wrong target. These results provide evidence that the postsynaptic neuron regulates both morphological and functional development of presynaptic terminals.

Action Potentials↗

Sildenafil citrate potentiates the hypotensive effects of nitric oxide donor drugs in male patients with stable angina.

OBJECTIVE: We sought to study the effects of a single oral dose of sildenafil citrate (50 mg) on blood pressure (BP) in men taking the nitric oxide (NO) donor drugs isosorbide mononitrate (ISMN) or glyceryl trinitrate (GTN) for stable angina. BACKGROUND: Sildenafil, a selective phosphodiesterase type 5 inhibitor, is an orally effective treatment for erectile dysfunction. The presence of phosphodiesterases in the vasculature suggests the possibility of an interaction between sildenafil and NO donor drugs. METHODS: Two double-blind, placebo-controlled, randomized, two-way crossover trials were undertaken. Sixteen male patients received oral ISMN (20 mg twice a day) for five to seven days before their dose of sildenafil or placebo and continued receiving ISMN daily until administration of the alternate drug seven days later. For the second study, 15 male patients received sublingual GTN (500 microg) 1 h after sildenafil or placebo on each of two study days, which were seven days apart. Sitting or standing BP was measured before and for 6 h after the administration of the study drug. RESULTS: The effects of sildenafil plus ISMN on BP (standing mean maximum reductions from baseline in systolic/diastolic BP, -52/-29 mm Hg) were greater than the effects of placebo plus ISMN on BP (-25/-15 mm Hg; p < 0.001). Sildenafil plus GTN also resulted in greater sitting mean maximum reductions from baseline in systolic/diastolic BP (-36/-21 mm Hg) compared with placebo plus GTN (-26/-12 mm Hg; p < 0.01). CONCLUSIONS: Coadministration of sildenafil with ISMN or GTN produced significantly greater reductions in BP than ISMN or GTN alone. Based on these data, sildenafil should not be administered to patients taking nitrates.

3',5'-Cyclic-GMP Phosphodiesterases↗

Semen retrieval and analysis in men with myelomeningocele.

The introduction of advanced assisted reproduction technologies (ART) has created opportunities for the treatment of infertility among patients with myelomeningocele (MMC). The aim of this study was to assess the possibility of semen retrieval and to analyse the semen quality in men with MMC. Nine men, aged 22 to 39 with MMC participated in the study. Two participants were able to achieve unassisted ejaculation. Vibratory stimulation was unsuccessfully attempted in the remaining seven participants who then underwent electroejaculation under general anaesthesia. In total, enough spermatozoa for intracytoplasmic spermatozoa injection were retrieved from five participants. In four cases, no spermatozoa were observed in the ejaculates. Testicular biopsies, however, revealed spermatogenesis, and thus a reproductive potential, in one of these men. Therefore, in six of the nine men with MMC, fatherhood seemed possible with modern ART, despite the semen quality generally being very poor.

Adult↗

Conservative management of ovarian cystic teratoma during pregnancy and labor.

OBJECTIVE: Our goal was to evaluate the adequacy of conservative management during pregnancy and labor in women with an ultrasonographically diagnosed ovarian cystic teratoma. STUDY DESIGN: Forty-nine women with ultrasonographically diagnosed ovarian cystic teratoma <6 cm were followed for detection of possible complications through pregnancy and labor. Serial ultrasonographic examinations before pregnancy, during pregnancy, and after delivery were performed to detect changes in the size of the cystic teratoma. RESULTS: In a group of 49 women with dermoid cysts (mean age, 30 years), 68 pregnancies resulted. Of the 68 pregnancies, 4 ended in miscarriages, 1 was electively terminated, and in the remaining 63 pregnancies, a total of 64 healthy infants were delivered. Five patients needed treatment with assisted reproductive techniques. Fifty-five pregnancies ended in normal vaginal deliveries and 8 were delivered by cesarean (cesarean delivery rate of 16%). None of the classical complications attributed to dermoid cysts such as torsion, dystocia, or rupture occurred in the study group. In a follow-up of 56 dermoid cysts throughout pregnancy, cyst size remained unchanged. CONCLUSIONS: Ovarian dermoid cysts <6 cm are not expected to grow during pregnancy or to cause complications in pregnancy and labor.

Adult↗

Laparoscopic adrenalectomy for primary hyperaldosteronism during pregnancy.

Laparoscopic adrenalectomy was performed early in the second trimester of pregnancy in a woman with an aldosteronoma causing hypertension (254/154 mm Hg). The patient was later delivered of a healthy baby. With suitable precautions and timing, major laparoscopic surgery can be performed safely during pregnancy.

Adenoma↗

Therapeutic potential of H(3)-receptor agonists in myocardial infarction.

Sympathetic over-activity accompanied by excessive noradrenaline (NA) release within the heart is a recognised cause of dysfunction in myocardial ischaemia. Myocardial infarction is often accompanied by arrhythmias with high morbidity and mortality. Indeed, NA enhances intracellular Ca(2+) by increasing its influx through voltage-dependent channels, mobilising it from intracellular stores and favouring its inward transport by Na(+)/Ca(2+) exchange. Ca(2+) overload eventually results in dysrhythmia and uncoordinated myocyte contraction. Moreover, NA increases metabolic demand. In concert with other contributing factors, this will aggravate the primary ischaemia and initiate a vicious cycle that can culminate in myocardial damage and heart failure. Therefore, reduction of NA release from cardiac sympathetic nerves is an important protective measure. Adrenergic nerves possess inhibitory receptors, such as alpha(2)-adrenoceptors, adenosine A(1)-receptors and histamine H(3)-receptors (H(3)R). In myocardial infarction, NA is released by both exocytotic (Ca(2+)-dependent) and carrier-mediated (Na(+)/H(+) exchange-dependent) mechanisms, associated with short-term and protracted ischaemia, respectively. Unlike alpha(2)-adrenoceptor agonists that reduce NA exocytosis, but enhance carrier-mediated NA release, H(3)R agonists inhibit both exocytotic and carrier-mediated NA release. Moreover, unlike adenosine A(1)-receptor agonists, H(3)R agonists do not depress sinoatrial and atrioventricular nodes, nor cause bronchoconstriction. Therefore, stimulation of H(3)R on cardiac sympathetic nerve endings is an important new way to protect the heart from the consequences of ischaemia and infarction. Although H(3)R agonists alleviate reperfusion arrhythmias in isolated hearts by reducing NA release, this protective action needs to be demonstrated in classical in vivo models of occlusion/reperfusion. Regardless, H(3)R agonists offer the promise of a novel strategy in the treatment of myocardial ischaemia and infarction.

Animals↗

Histamine H(3)-receptors: a new frontier in myocardial ischemia.

In protracted myocardial ischemia, sympathetic nerve endings undergo ATP depletion, hypoxia and pH(i) reduction. Consequently, norepinephrine (NE) accumulates in the axoplasm, because it is no longer stored in synaptic vesicles, and intraneuronal Na(+) concentration increases, as the Na(+)/H(+) exchanger (NHE) is activated. This forces the reversal of the Na(+)- and Cl(-)-dependent NE transporter, triggering a massive carrier-mediated release of NE and thus, arrhythmias. Indeed, NE overflow in myocardial ischemia directly correlates with the severity of arrhythmias. Histamine H(3)-receptors (H(3)R) have been identified as inhibitory heteroreceptors in adrenergic nerve endings of the heart. In addition to inhibiting NE exocytosis from sympathetic nerve endings, selective H(3)R agonists attenuate carrier-mediated release of NE in both animal and human models of protracted myocardial ischemia. Whereas H(3)R-mediated attenuation of exocytotic NE release involves an inhibition of N-type Ca(2+)-channels, H(3)R-mediated reduction of carrier-mediated NE release is associated with diminished NHE activity. In addition to inhibiting NE release, H(3)R stimulation significantly attenuates the incidence and duration of ventricular fibrillation. Although other presynaptic receptors also modulate NE release from sympathetic nerve endings, H(3)R stimulation reduces both exocytotic and carrier-mediated NE release, whereas alpha(2)-adrenoceptor agonists attenuate NE exocytosis but enhance carrier-mediated NE release. Furthermore, unlike adenosine A(1)-receptors, whose activation reduces both exocytotic and carrier-mediated NE release, H(3)R stimulation is devoid of negative chronotropic and dromotropic effects (i.e., sinoatrial and atrioventricular nodal functions are unaffected). Because excess NE release can trigger severe arrhythmias and sudden cardiac death, negative modulation of NE release by H(3)R agonists may offer a novel therapeutic approach to myocardial ischemia.

Animals↗

Angiotensin-converting enzyme-independent angiotensin formation in a human model of myocardial ischemia: modulation of norepinephrine release by angiotensin type 1 and angiotensin type 2 receptors.

Angiotensin II (Ang II) promotes norepinephrine (NE) release from cardiac sympathetic nerve endings. We assessed in a human model in vitro whether locally formed Ang II contributes to NE release in myocardial ischemia. Surgical specimens of human right atrium were incubated in anoxic conditions. After 70 min of anoxia, NE release (carrier-mediated; caused by NE transporter reversal) was 8-fold greater than normoxic release. Angiotensin-converting enzyme inhibition with enalaprilat failed to reduce anoxic NE release. In contrast, prevention of chymase-dependent Ang II formation with chymostatin, Bowman-Birk inhibitor, or alpha(1)-antitrypsin significantly inhibited anoxic, but not exocytotic, NE release. Two mast-cell stabilizers, cromolyn and lodoxamide, markedly reduced NE release, implicating cardiac mast cells as a major source of chymase. Angiotensin type 1 receptor (AT(1)R) blockade with EXP3174 inhibited NE release, whereas angiotensin type 2 receptor (AT(2)R) blockade with PD123319 did not. Interestingly, PD123319 reversed the inhibitory effect of EXP3174. Furthermore, synergisms were uncovered between EXP3174 and an AT(2)R agonist, and between EXP3174 and a Na(+)/H(+) exchanger inhibitor. Thus, angiotensin-converting enzyme-independent Ang II formation via chymase is important for carrier-mediated ischemic NE release in the human heart. Locally generated Ang II promotes NE release by acting predominantly at AT(1)Rs, which are likely coupled to the Na(+)/H(+) exchanger. Effects of Ang II at AT(2)Rs, seemingly opposite to those resulting from AT(1)R activation, are uncovered when AT(1)Rs are blocked. Because NE release is associated with coronary vasoconstriction and arrhythmias, and mast-cell density and chymase content increase in the ischemic heart, the notion that chymase-generated Ang II plays a major role in carrier-mediated NE release may have important clinical implications.

Aged↗

Right-left discrimination in a biologically oriented model of the cockroach escape system.

We present a biologically oriented model that accounts for left-right discrimination in the cockroach's escape behavior. The model includes the main groups of neurons found to be involved in the escape response. Each one of the included neurons is described by the actual processes taking place in an individual neuron (formation of an action potential, transmitter release, conductance changes, etc.). Furthermore, realistic chemical synapses (excitatory or inhibitory and able to undergo different types of modulation) connect the various neurons. With this model, we ere able to achieve, for a wide range of inputs representing different wind directions, behavior which resembles that found experimentally. The model indicates that several synaptic properties, in particular postsynaptic inhibition and presynaptic facilitation, play a key role in the discrimination of wind direction.

Animals↗