Process of drug registration in Israel: the correlation between the number of discussions within the Ministry of Health and postapproval variations by EMA and/or FDA.

Objectives: US FDA and EMA allow facilitated regulatory pathways to expedite access to new treatments. Limited supportive data may result in major postapproval variations. In Israel, partly relying on Food and Drug Administration (FDA) and European Medicines Agency (EMA), clinical data are reviewed independently by the Advisory Committee of Drug Registration (ACDR).

Increasing adverse drug reaction reporting-How can we do better?

Adverse drug reactions (ADRs) are associated with morbidity and mortality worldwide. Although national systems for reporting ADRs exist there is a low reporting rate. The aim of the current study was to evaluate an intervention plan for improving ADRs reporting among medical professionals (physicians and nurses).

The effect of an intervention program on the knowledge and attitudes among medical staff regarding adverse drug reaction reporting.

Purpose: Adverse drug reactions (ADRs) are a growing important public health problem; however, underreporting of ADRs is very common. The aim of the current study was to explore the effect of an intervention program on the knowledge and attitudes among physicians and nurses regarding ADRs reporting.

Methods: A multicentre study consisted of three phases: filling out a questionnaire; an intervention program; filling out the same questionnaire again.

Variation in the CYP2D6 genotype is not associated with carvedilol dose changes in patients with heart failure.

What Is Known And Objective: Carvedilol is the standard of care for heart failure (HF) patients. Carvedilol is partially metabolized by the highly polymorphic enzyme, CYP2D6. To reach an effective dose while avoiding adverse drug reactions (ADRs), testing of CYP2D6 genotype prior to carvedilol initiation may be considered.

Medications and glucose-6-phosphate dehydrogenase deficiency: an evidence-based review.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect and one of the most common genetic disorders worldwide, with an estimated 400 million people worldwide carrying a mutation in the G6PD gene that causes deficiency of the enzyme. Although drug-induced haemolysis is considered the most common adverse clinical consequence of G6PD deficiency, significant confusion exists regarding which drugs can cause haemolytic anaemia in patients with G6PD deficiency. In the absence of consensus among physicians, patients are subject to conflicting advice, causing uncertainty and distress.

Appropriate antibiotic prescribing pattern in hospitalized children.

This study analyzes prospectively the antibiotic prescription habits in terms of appropriateness of use and cost pattern effects in the paediatric wards of two different university hospital patient set-ups. Data on demographics, discharge diagnosis, antibiotic utilization and costs were collected prospectively from the children's individual electronic charts at Rambam Health Care Campus (R) and Kaplan Medical Centre (K) in Israel. A total of 505 and 497 children from R and K units, respectively, were screened.

Cigarette smoking and infection.

Background: Infectious diseases may rival cancer, heart disease, and chronic lung disease as sources of morbidity and mortality from smoking. We reviewed mechanisms by which smoking increases the risk of infection and the epidemiology of smoking-related infection, and delineated implications of this increased risk of infection among cigarette smokers.

Methods: The MEDLINE database was searched for articles on the mechanisms and epidemiology of smoking-related infectious diseases.

High fasting glucose levels as a predictor of worse clinical outcome in patients with coronary artery disease: results from the Bezafibrate Infarction Prevention (BIP) study.

Background: A high fasting glucose level may be a marker not only for microvascular complications, but also for macrovascular complications. We evaluated the clinical significance of a high fasting glucose level (> or =110 mg/dL), detected either at baseline or during follow-up, in the Bezafibrate Infarction Prevention (BIP) study.

Methods: The BIP study was a secondary prevention prospective double-blind study comparing bezafibrate to placebo.

[Drug related taste disturbances: emphasis on the elderly].

Background: Taste disturbances are common among the elderly due to physiologic changes, diseases, and medications. As many as 11% of elderly persons using multiple drugs report taste aberrations. The main danger of taste decline and disturbance in the old is food-anhedonia, causing loss of body weight via decreased calorie and nutrient intake.

Genetic polymorphism of CYP2D6 and CYP2C19 metabolism determined by phenotyping Israeli ethnic groups.

Genetic polymorphism of the cytochrome P450 isoenzymes CYP2D6 and CYP2C19 was determined by phenotyping four ethnic groups of the Israeli population. The groups consisted of Ethiopian subjects, Yemenite subjects, and Russian subjects representing first-generation new immigrants and an Israeli Arab group. Dextromethorphan was used as the probe for CYP2D6 activity and mephenytoin was used for CYP2C19 activity.

Existing and new criteria for bioequivalence evaluation of new controlled release (CR) products of carbamazepine.

While the three classical pharmacokinetic (PK) parameters, AUC, Cmax and tmax are adequate to assess bioequivalence of immediate release (IR) formulations, they are not designed to fully characterize the pharmacokinetic (PK) performance of controlled release (CR) formulations and provide only limited insight into the function of carbamazepine (CBZ) CR products. Thus, for reliable assessment of bioequivalence in CR formulations, there is a role for the use of additional criteria (parameters). The following are the proposed new parameters: MRT (mean residence time), Cmax/AUC, plateau time or POT (the time span associated with the concentrations within 25% of Cmax), tapical (the arithmetic mean of the times associated with POT) and Capical (the arithmetic mean of the concentrations within 25% of Cmax).

Acute cholecystitis caused by Campylobacter jejuni.

An 83-year-old man with acute cholecystitis caused by Campylobacter jejuni is described. The patient was cured after undergoing cholecystectomy and intravenous ofloxacin therapy.

Divergent tolerance to metabolic and cardiovascular effects of nicotine in smokers with low and high levels of cigarette consumption.

Cigarette smokers on average weigh less than nonsmokers. However, among smokers, those who smoke the most weigh the most. To better understand the effects of nicotine on body weight, we investigated the pharmacodynamics of intravenous nicotine and cigarette smoking in low-level smokers (10 or fewer cigarettes per day) and high-level smokers (15 to 30 cigarettes per day).

Clinical significance of genetic influences on cardiovascular drug metabolism.

Inherited differences in metabolism may be responsible for individual variability in the efficacy of drugs and the occurrence of adverse drug reactions. Among the cardiovascular drugs reported to exhibit genetic polymorphism are debrisoquine, sparteine, some beta-adrenoceptor antagonists, flecainide, encainide, propafenone, nifedipine, procainamide, and hydralazine. The implications of genetic differences in the metabolism of these drugs for cardiovascular therapeutics is the subject of this review.

Ontogeny of excitotoxic injury to nicotinamide adenine dinucleotide phosphate diaphorase reactive neurons in the neonatal rat striatum.

To further define the ontogeny of "excitotoxic" injury to brain, intrastriatal injection of an N-methyl-D-aspartate agonist (quinolinate) and a non-N-methyl-D-aspartate agonist (quisqualate) was performed in rats at postnatal days 7 and 14, and in adults. Excitotoxic injury was quantified volumetrically and with neuronal counts of nicotine adenine dinucleotide phosphate-containing neurons as this cell population is spared in neonatal hypoxia ischemia. Only postnatal day 7 pups injected with quinolinic acid showed selective sparing of neurons containing the enzyme nicotinamide adenine dinucleotide phosphate.

Selective sparing of NADPH-diaphorase neurons in neonatal hypoxia-ischemia.

Excitatory amino acids have been implicated in ischemic neuronal injury. To test this hypothesis in neonatal hypoxia-ischemia, lesions of the cortex and striatum were induced in 7-day-old rats by unilaterally ligating their carotid arteries and subjecting them to hypoxic conditions for 2 hours. Brains examined 1 week later demonstrated, within the regions of ischemic damage, a striking preservation of neurons that stained histochemically for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity.

In vitro functions of stromal cells from human and mouse bone marrow.

Human fibroblastoid cell strains obtained from primary bone marrow cultures and continuous stromal cell lines recently derived from mouse bone marrow were studied. The incidence of fibroblastoid precursors (CFU-F) varied considerably in human bone marrow samples, and no differences could be detected between marrows from a group of myelodysplastic patients (age range 70-82 years) and groups of age-matched controls or younger individuals. A lack of direct correlation between initial clonogenicity and ultimate capacity of fibroblastoid cells to grow in continuous culture was observed in both the normal and the myelodysplastic groups.