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Biomedical subjects

Ariel Hourvitz

Publications and source records attributed to Ariel Hourvitz.

At least 19 recordsLinked to original sources
PubMed2006

Letrozole reduces estrogen and gonadotropin exposure in women with breast cancer undergoing ovarian stimulation before chemotherapy.

CONTEXT: Women with breast cancer are not typically offered embryo or oocyte cryopreservation to preserve their fertility before chemotherapy because of the potential risks associated with high estrogen levels arising from ovarian stimulation. OBJECTIVE: We aimed to determine whether the combination of an aromatase inhibitor with gonadotropin treatment in breast cancer patients produces comparable results to standard in vitro fertilization (IVF), without a significant increase in estradiol levels and delay in the initiation of chemotherapy. PATIENTS AND METHODS: Stages I-IIIA breast cancer patients (n = 47) received 5 mg/d letrozole and 150-300 IU FSH to cryopreserve embryos or oocytes. Age-matched retrospective controls (n = 56) were selected from women who underwent IVF for tubal disease. RESULTS: Whereas letrozole and FSH stimulation resulted in significantly lower peak estradiol levels (mean +/- sd 483.4 +/- 278.9 vs. 1464.6 +/- 644.9 pg/ml; P < 0.001) and 44% reduction in gonadotropin requirement, compared with controls, the length of stimulation, number of embryos obtained, and fertilization rates were similar. The human chorionic gonadotropin administration criteria had to be adjusted to 20 mm after letrozole stimulation, compared with 17-18 mm in the controls. The mean delay from surgery to cryopreservation was 38.6 d, with 81% of all patients completing their IVF cycles within 8 wk of surgery. CONCLUSION: Ovarian stimulation with letrozole and FSH appears to be a cost-effective alternative for fertility preservation in breast cancer patients with reduced estrogen exposure, compared with standard IVF. If patients are referred promptly, they may undergo embryo or oocyte cryopreservation without a delay in chemotherapy.

Adult↗
PubMed2006

Lessons learned from clinical anthrax drills: evaluation of knowledge and preparedness for a bioterrorist threat in Israeli emergency departments.

STUDY OBJECTIVE: Emergency department (ED) physicians and nurses are considered critical sentinels of a bioterrorist attack. We designed a special hospital drill to test EDs' response to inhalational anthrax and assess the level of preparedness for anthrax bioterrorism. We hypothesized that the occurrence of such a drill in an ED would improve the knowledge of its physicians, even those who had not actually participated in the drill. METHODS: We conducted 23 drills at all Israeli general hospitals' EDs. An actor entered the walk-in triage area, simulating a febrile patient with lower respiratory complaints. A chest radiograph with mediastinal widening, as can be seen in early anthrax disease, was planted in the hospital's imaging results system. Patients were instructed to give additional epidemiologic clues, such as having a few friends with a similar syndrome. Either before or after the drills, we distributed multiple choice tests about diagnosis and management of anthrax to the 115 senior emergency physicians at these hospitals. RESULTS: In 91% of EDs, a decision to admit the patient was made. Sixty-one percent included anthrax in the differential diagnosis and activated the appropriate protocols. Only 43% contacted all relevant officials. Average score on the anthrax tests was 58 (of 100). Physicians who were tested before the drill (in their institution) achieved a mean score of 54.5, whereas those who were tested after their ED had been exercised achieved a mean score of 59.3. CONCLUSION: A national framework of drills on bioterrorism can help estimate and potentially augment national preparedness for bioterrorist threats. It is not, on its own, an effective educational tool. More emphasis should be given to formal accredited continuing medical education programs on bioterrorism, especially for emergency physicians and ED nurses, who will be in the front line of a bioterrorist attack.

Anthrax↗
PubMed2006

Role of embryo quality in predicting early pregnancy loss following assisted reproductive technology.

Early pregnancy loss (EPL) significantly reduces the initial success rate of assisted reproduction treatments and increases the psychological burden on the patient. The aim of the current study was to investigate the association between embryo quality and EPL in IVF. A retrospective study of 1471 women undergoing IVF between July 2000 and October 2004 was performed. Multivariate logistic regression models evaluated the effect on EPL of the woman's age, type and cause of infertility, endometrial thickness on the day of oocyte retrieval, performance of intracytoplasmic sperm injection, number of transferred embryos, embryo quality as assessed by the number of blastomeres in the leading transferred embryo at day 3, and the percentage of fragmentation. The 2902 oocyte retrieval-embryo transfer cycles resulted in 816 pregnancies (28.1%; 705 women) constituting the study cohort. Of these, 259 pregnancies (31.7%) ended in EPL and 557 (68.3%) in ongoing pregnancies. EPL risk was significantly associated with advanced (>35 years) maternal age (OR=1.53; 95% CI 1.12-2.09) and five or fewer blastomeres in the leading embryo transferred at day 3 (OR=1.82; 95% CI 1.16-2.85). In conclusion, the quality of transferred embryos, as assessed by the total number of blastomeres in the leading transferred embryo, and maternal age are predictors of EPL.

Abortion, Spontaneous↗
PubMed2005

Post-intoxication vaccination for protection of neurons against the toxicity of nerve agents.

Nerve agents are highly toxic organophosphates (OPs) that can cause severe damage to the central and peripheral nervous systems. The central nervous system insult results in seizures and neuronal death. The glutamatergic system apparently contributes to the neuropathology. Using a model of OP intoxication causing death of retinal ganglion cells in the mouse eye, we show here that intoxication is exacerbated if the mice are devoid of mature T cells. The retinal neurons could be protected from these effects by vaccination, 7 days before or immediately after intoxication, with the copolymer glatiramer acetate (Cop-1), recently found to limit the usual consequences of an acute glutamate insult to the eye. These findings underlie a new therapeutic approach to protection against OP intoxication, based on the rationale that boosting of the adaptive immunity recruited at the site of intoxication helps the local cellular machinery such as resident microglia to withstand the neurotoxic effects.

Animals↗
PubMed2005

Neonatal and obstetric outcome of pregnancies conceived by ICSI or IVF.

Intracytoplasmic sperm injection (ICSI) is currently widely used despite concern regarding pregnancy complications and outcome, specifically congenital malformations. The aim of this study was to compare the obstetric and neonatal outcome of pregnancies conceived by IVF and ICSI. Long-term follow-up was achieved through questionnaires sent to women who conceived after IVF/ICSI treatment. Information was obtained regarding 219 pregnancies (322 children) conceived after ICSI and 145 pregnancies (201 children) conceived after IVF. There were no significant differences between the ICSI and regular IVF pregnancies in regard to the couple's characteristics and the obstetric complications. The mean +/- SD birth weight of the singletons conceived after ICSI was similar to that of singletons conceived after IVF: 3001 +/- 703 versus 3059 +/- 643 g respectively. In both groups there was a high incidence of multiple pregnancies, Caesarean sections, prematurity and low birth weights. The incidence of congenital malformations following IVF or ICSI pregnancies was similar, 6.3 and 7.7% respectively, but was increased compared with the general Israeli population. In summary, concern remains regarding the incidence of congenital malformations after IVF and the long-term outcome of ICSI pregnancies. However, the present results are reassuring with regard to the obstetric and neonatal outcome of pregnancies conceived by ICSI compared with those achieved by IVF.

Abnormalities, Multiple↗
PubMed2005

Inherited and acquired interactions between ACHE and PON1 polymorphisms modulate plasma acetylcholinesterase and paraoxonase activities.

The 5.5 Mb chromosome 7q21-22 ACHE/PON1 locus harbours the ACHE gene encoding the acetylcholine hydrolyzing, organophosphate (OP)-inhibitable acetylcholinesterase protein and the paraoxonase gene PON1, yielding the OP-hydrolyzing PON1 enzyme which also displays arylesterase activity. In search of inherited and acquired ACHE-PON1 interactions we genotyped seven polymorphic sites and determined the hydrolytic activities of the corresponding plasma enzymes and of the AChE-homologous butyrylcholinesetrase (BChE) in 157 healthy Israelis. AChE, arylesterase, BChE and paraoxonase activities in plasma displayed 5.4-, 6.5-, 7.2- and 15.5-fold variability, respectively, with genotype-specific differences between carriers of distinct compound polymorphisms. AChE, BChE and arylesterase but not paraoxonase activity increased with age, depending on leucine at PON1 position 55. In contrast, carriers of PON1 M55 displayed decreased arylesterase activity independent of the - 108 promoter polymorphism. Predicted structural consequences of the PON1 L55M substitution demonstrated spatial shifts in adjacent residues. Molecular modelling showed substrate interactions with the enzyme variants, explaining the changes in substrate specificity induced by the Q192R substitution. Intriguingly, PON1, but not BChE or arylesterase, activities displayed inverse association with AChE activity. Our findings demonstrate that polymorphism(s) in the adjacent PON1 and ACHE genes affect each other's expression, predicting for carriers of biochemically debilitating ACHE/PON1 polymorphisms adverse genome-environment interactions.

Acetylcholinesterase↗
PubMed2004

Pregnancy-associated plasma protein-a production in rat granulosa cells: stimulation by follicle-stimulating hormone and inhibition by the oocyte-derived bone morphogenetic protein-15.

Pregnancy-associated plasma protein-A (PAPP-A) is the major IGF binding protein-4 (IGFBP-4) protease in follicular fluid, consistent with its proposed role in folliculogenesis. Despite growing interest, almost nothing is known about how PAPP-A expression is regulated in any tissue. Here we show that FSH and oocytes regulate PAPP-A expression in granulosa cells (GCs). By in situ hybridization, ovary PAPP-A mRNA was markedly increased by pregnant mare serum gonadotropin treatment, and the message was localized to the membrana GCs but not cumulus GCs (CGCs) of dominant follicles. To explore the mechanism, we used primary cultures of rat GCs. Control (untreated) cells produced little or no PAPP-A spontaneously. Conversely, FSH markedly stimulated PAPP-A mRNA and protein in a dose- and time-dependent fashion. Interestingly, PAPP-A expression in isolated CGCs was also strongly induced by FSH, and the induction was inhibited by added oocytes. To investigate the nature of the inhibition, we tested the effect of oocyte-derived bone morphogenetic protein-15 (BMP-15). BMP-15 alone had no effect on basal levels of PAPP-A expression by cultures of membrana GCs or CGCs. However, BMP-15 markedly inhibited the FSH stimulation of PAPP-A production in a dose-dependent manner. The cleavage of IGFBP-4 by conditioned media from FSH-treated GCs was completely inhibited by anti-PAPP-A antibody, indicating the IGFBP-4 protease secreted by GCs is PAPP-A. These results demonstrate stimulatory and inhibitory roles for FSH and BMP-15, respectively, in regulating PAPP-A production by GCs. We propose that FSH and oocyte-derived BMP-15 form a controlling network that ensures the spatiotemporal pattern of GC PAPP-A expression in the dominant follicle.

Animals↗
PubMed2003

[Using thalidomide against pathological neovascularization].

Thalidomide was first used during the 50's-60's, especially for morning sickness in pregnant women. It was found to be a powerful teratogen only years later and was banned from use. At the same time it was found to have anti-inflammatory and anti-angiogenic properties and was approved as treatment for leprosy. As such, thalidomide might be used against pathological neovascularization, as seen in mustard gas exposure. From past experience we know that the eyes are the most vulnerable organ to mustard gas exposure. In some of the casualties there is a late sequella including pathological corneal neovascularization. So far there is no specific effective treatment against this neovascularization. The purpose of this review is to examine current research about the potential use of thalidomide as an anti-angiogenic agent, including potential role in treating mustard gas eye injury.

Angiogenesis Inhibitors↗
PubMed2003

[Medical aspects of the lacrimator CS].

Since the 1960's, CS has become the main riot control agent in use by police and army forces throughout the world. The first post-exposure symptom is a burning sensation in the eyes, nose and throat. At a later stage, lacrimation, rhinorrhea, conjunctivitis, sore throat and salivation appear. These symptoms are followed by chest pain and dry cough, and if the substance is swallowed, it may cause nausea and vomiting. This article reviews the physical properties of CS, the main dispersing techniques, the clinical signs and symptoms of exposure, including information on mutagenicity, carcinogenesis, pregnancy safety, and will introduce guidelines for treatment after exposure.

Chest Pain↗
PubMed2002

The regulated expression of the pregnancy-associated plasma protein-A in the rodent ovary: a proposed role in the development of dominant follicles and of corpora lutea.

Compelling evidence exists displaying that the intrafollicular IGF-I system constitutes an obligatory mediator of FSH action in the murine ovary. Within this system, the ovarian IGF binding protein-4-directed protease (IGFBP-4ase) may have a critical role. Human IGFBP-4ase has been proved identical to the previously well-characterized pregnancy-associated plasma protein-A (PAPP-A). This communication reports the cloning and sequencing of the mouse PAPP-A cDNA as well as its expression and cellular localization in the mouse ovary. PAPP-A mRNA was undetectable in ovaries of untreated immature 25-d-old mice. Treatment with PMSG led to a marked time-dependent increase in PAPP-A expression in well-defined subsets of granulosa cells and follicles. Specifically, PAPP-A expression was detectable exclusively in centrifugally residing membrana granulosa cells of antral follicles during a 3- to 36-h period post PMSG. PAPP-A expression then fell to nondetectable levels in dominant preovulatory follicles at 48 h post PMSG. Treatment of PMSG-primed mice with human CG caused a rapid reinduction of PAPP-A expression in granulosa cells of dominant follicles and was sustained at relatively high levels throughout the ovulation and luteinization. These results suggest a role for gonadotropin-stimulated PAPP-A gene expression in the physiologic processes of dominant follicle development, ovulation, and luteogenesis in the mammalian ovary. The early onset and extended duration of gonadotropin-dependent PAPP-A expression in granulosa cells may serve to degrade the antigonadotropin IGFBP-4. Accordingly, successful antral follicle development, ovulation, and corpus luteum formation may be contingent on an IGFBP-4-deplete/PAPP-A-replete circumstance, hence resulting in an IGF-I-replete intrafollicular microenvironment.

Amino Acid Sequence↗
PubMed2002

[Ricin--from a Bulgarian umbrella to an optional treatment of cancer].

Ricin toxin, found in the bean of the castor plant, is one of the most toxic and easily produced plant toxin. It is composed of two polypeptide chains linked by a disulfide bond. The toxin irreversibly blocks protein synthesis. Oral intoxication is the most frequent mode of exposure, but direct contact and inhalation have also been described. A single intramuscular exposure was reported, related to an assassination event in 1978. The clinical signs of intoxication begin hours after the exposure, and include gastrointestinal signs, dyspnea, fever, vasculatory collapse, neurological signs, liver necrosis and renal failure. Treatment is mainly supportive. A vaccine has been developed and found effective in animal studies. Ricin may be used as a biological weapon due to its heat stability and worldwide availability. A more friendly use, which has been tested in clinical trials, is the incorporation of ricin-immunotoxin for the treatment of cancer patients.

Bulgaria↗
PubMed2002

Preparedness of the Israeli health system for a biologic warfare event.

The threat of a disease outbreak resulting from biologic warfare has been of concern for the Israeli health system for many years. In order to be prepared for such an event the health system has formulated doctrines for various biologic agents and defined the logistic elements for the procurement of drugs. During the last 4 years, and especially after the West Nile fever epidemic in 2000, efforts to prepare the healthcare system and the relevant organizations were accelerated. The Director-General of the Ministry of Health nominated a Supreme Steering Committee to fill in the gaps and upgrade the preparedness of the health system for an unusual disease outbreak. This committee and its seven subcommittees established appropriate guidelines, communication routes among different organizations, and training programs for medical personnel. The anthrax outbreak in the United States found the healthcare system in the hub of the preparation process, and all modes of action were intensified. Further work by hospitals, primary care clinics and all other institutes should be increased to maintain a state of proper preparedness.

Biological Warfare↗
PubMed2002

Radiation terrorism--the medical challenge.

Ionizing radiation can cause acute as well as chronic and late illnesses, and is a well-known health hazard. Its use by terrorists and nations in the form of a non-conventional weapon is no longer impossible. The release of radioactive materials with the accompanying contamination and radiation has the potential of causing serious medical problems. In analyzing the different radiologic terrorism scenarios, a scheme is proposed for the triage and evacuation of injured, contaminated and non-contaminated casualties from the scene itself as well as from the periphery. Knowledge, plans and drills will lessen the impact of those potential attacks and prepare us to respond to such events.

Emergency Treatment↗
PubMed2002

Adverse reaction to atropine and the treatment of organophosphate intoxication.

Atropine is the drug of choice for treatment of organophosphate nerve agent and insecticide intoxication and has been used for this indication for several decades. Adverse reactions to atropine may occur, and are of two types: toxic and allergic. Toxic reaction, the most common form, results from the anti-muscarinic effects of the drug. Since it is most probably related to interpersonal variation in sensitivity to atropine, toxic effects may appear at the usual therapeutic doses. The second type, allergic reaction, includes local manifestations, usually after the administration of eyedrops, and systemic reaction in the form of anaphylaxis. Since most patients manifest only a mild reaction, allergy testing is not performed and the prevalence of allergy to atropine is therefore not known. Severe allergic reaction to atropine is rare, as evidenced by the small number of case reports in the literature despite the drug's extensive use. Alternative anti-muscarinic drugs recommended for OP poisoning include glycopyrrolate and scopolamine. Glycopyrrolate is a peripheral anti-muscarinic drug that has been studied in comparison to atropine for many clinical indications, while scopolamine is an anti-muscarinic drug with both peripheral and central effects. An acceptable alternative regimen for patients with proven allergy to atropine is a combination of glycopyrrolate with centrally active drugs such as benzodiazepines or scopolamine.

Atropine↗
PubMed2002

Simulation-based training of medical teams to manage chemical warfare casualties.

With chemical warfare becoming an imminent threat, medical systems need to be prepared to treat the resultant mass casualties. Medical preparedness should not be limited to the triage and logistics of mass casualties and first-line treatment, but should include knowledge and training covering the whole medical spectrum. In view of the unique characteristics of chemical warfare casualties the use of simulation-assisted medical training is highly appropriate. Our objective was to explore the potential of simulator-based teaching to train medical teams in the treatment of chemical warfare casualties. The training concept integrates several types of skill-training simulators, including high tech and low tech simulators as well as standardized simulated patients in a specialized simulated setting. The combined use of multistimulation modalities makes this maverick program an excellent solution for the challenge of multidisciplinary training in the face of the looming chemical warfare threat.

Chemical Warfare↗
PubMed2002

Training Israeli medical personnel to treat casualties of nuclear, biologic and chemical warfare.

Recent events have significantly increased concern about the use of biologic and chemical weapons by terrorists and other countries. Since weapons of mass destruction could result in a huge number of casualties, optimizing our diagnostic and therapeutic skills may help to minimize the morbidity and mortality. The national demands for training in medical aspects of nuclear, biologic and chemical warfare have increased dramatically. While Israeli medical preparedness for non-conventional warfare has improved substantially in recent years especially due to extensive training programs, a standardized course and course materials were not available until recently. We have developed a core curriculum and teaching materials for a 1 or 2 day modular course, including printed materials.

Biological Warfare↗
PubMed2002

Organophosphate poisoning: a multihospital survey.

BACKGROUND: Organophosphates are frequently used as insecticides in the household and in agricultural areas, thus posing a risk for accidental exposure. OBJECTIVES: To describe the characteristics, clinical course and outcome of 97 patients admitted to emergency rooms with a diagnosis of acute OP poisoning. METHODS: The clinical details of 97 patients were collected from 6 different hospitals in Israel. Diagnosis of intoxication was based on clinical findings, butyrylcholinesterase levels and, in several cases, the material brought to the hospital. Demographic, intoxication and clinical data were analyzed. RESULTS: The study group comprised 64 men and 33 women whose age range was 1-70 years (mean 19.8 +/- 17.1); more than one-third of the patients were less than 10 years old. Accidental exposure was the cause of intoxication in 51.5% of the patients, and suicide in 20.6% of exposures. Intoxication occurred at home in most patients (67%), and the route of intoxication was oral in 65% of them. The patients arrived at the hospital 20 minutes to 72 hours after intoxication. Nine patients were asymptomatic; 53 presented with mild intoxication, 22 with moderate, and 13 had severe intoxication, 5 of whom died. There was a direct correlation between the degree of inhibition of butyrylcholinesterase levels and the severity of intoxication. Treatment included decontamination and antidotal medication. Duration of hospitalization ranged between 1 and 14 days (average 2.9 days). CONCLUSIONS: Organophosphates may cause severe morbidity and mortality. Medical staff should therefore be aware of the clinical manifestations and the antidotal treatment for this poisoning.

Adolescent↗