Israel Medical Association Journal

Ghrelin, a 28 amino acid acylated peptide predominantly produced by the stomach, displays strong growth hormone-releasing activity mediated by the hypothalamus-pituitary GH[1] secretagogue receptors that were found to be specific for a family of synthetic, orally active GH secretagogues. The discovery of ghrelin brings us to a new understanding of the regulation of GH secretion. However, ghrelin is much more than simply a natural GH secretagogue. It also acts on other central and peripheral receptors and exhibits other actions, including stimulation of lactotroph and corticotroph secretion, orexigenia, influences gastroenteropancreatic functions, and has metabolic, cardiovascular and anti-proliferative effects. Knowledge of the whole spectrum of biologic activities of this new hormone will provide new understanding of some critical aspects of neuroscience, metabolism and internal medicine. In fact, GHS[2] were born more than 20 years ago as synthetic molecules, eliciting the hope that orally active GHS could be used to treat GH deficiency as an alternative to recombinant human GH. However, the dream did not become reality and the usefulness of GHS as an anabolic anti-aging intervention restoring the GH/IGF-I[3] axis in somatopause is still unclear. Instead, we now face the theoretic possibility that GHS analogues acting as agonists or antagonists could become candidate drugs for the treatment of pathophysiologic conditions in internal medicine totally unrelated to disorders of GH secretion. 

Background: Recent years have brought significant progress to the development of hormonal therapies for the treatment of breast cancer. Several new agents have been approved for the treatment of breast cancer in the metastatic setting, among which is the new non-steroidal aromatase inhibitor, anastrozole, introduced for clinical use in Israel in March 1997.

Objectives: To evaluate the response rate and survival duration of patients treated with anastrozole for metastatic breast cancer, who had previously received at least one line of hormonal therapy.

Methods: Anastrozole was administered to 37 patients with metastatic breast cancer. The median age was 64 years. Estrogen receptor was positive in 20 patients, negative in 10 and unknown in 7. All patients were previously treated with tamoxifen in the adjuvant setting or as first-line hormonal therapy for metastatic disease. Anastrozole was given orally, 1 mg/day. Response was evaluated 2 months after the initiation of treatment and reevaluated every 2 months. Therapy was given until disease progression. Ten ER[1]-negative patients were excluded from the final analysis.

Results: Twenty-seven patients were eligible for response and toxicity analysis. The median follow-up was 20 months. One patient (3.7%) achieved complete response and remains free of disease 28 months after start of therapy. No partial responses were seen. Twenty patients (74%) had stable disease. Two year actuarial survival was 57%. Median survival was 26.5 months after starting therapy and median progression free survival was 11 months. The toxicity was mild: one patient (3.7%) complained of weight gain and one patient (3.7%) had mild fatigue.

Conclusion: Although the response rate was low, hormonal therapy with anastrozole seems to be beneficial in terms of disease stabilization, freedom from progression, and overall survival without serious toxicity.  

Background: Family physicians coordinate the care of their patients and follow them in a longitudinal manner. Do they have a role to play while their patients are hospitalized? Does the system of care expect them to play a role, and how does it support or integrate it?

Objectives: To discuss the various models of relations between hospital and primary care physicians in the world as compared to those in Israel.

Method: Short cases are reported describing the author’s personal experiences and difficulties encountered in a family practice.

Discussion: Identifying and defining problems encountered, as well as their origin and development within the history and evolution of the system of delivery of care in Israel, will lead to some suggestions for a possible solution. Maturation of the system, especially education of the junior staff within the hospital system, is still needed to facilitate the hospital-physician relationship.

Conclusion: More active participation of the family physician offers added value to patients’ management during their hospital stay and is welcomed by them. The full implementation of a system promoting continuity of care requires further attempts at developing suitable models of cooperation between hospital and family physicians.
 

Background: Each winter influenza activity is a major cause of morbidity and mortality both in Israel and worldwide.

Objectives: To identify the influenza viruses active in Israel during the winter season and to assess the extent of influenza morbidity.

Methods: Information was collected on a population of 18,684 individuals enrolled in two community clinics in central Israel. It included the total number of visits for acute respiratory infection – including influenza and influenza-like illness (ARI/flu-like) – during a 20 week surveillance period (23 November 1997 to 27 March 1998) and the percent of influenza virus isolates in nasopharyngeal specimens from a sample of patients with ARI/flu-like collected on a weekly basis during the same period.

Results: A total of 5,947 visits for ARI/flu-like were recorded among 18,684 enrolled patients in two community clinics (18.1%). The progressive increase in the number of visits for ARI/flu-like reached a peak on week 2/98 with 597 visits and a rate of 31.95 visits per 1,000 population. After this, a decrease to the initial values was evident by week 12/98. Most affected patients were in the age groups 5–14 and 65 years and over, with a rate of 733.5 and 605.3 visits per 1,000 population, respectively. Influenza virus was isolated from 92 of the 426 nasopharyngeal specimens (21.6%). The most commonly detected strain was A/Sydney/5/97(H₃N₂) like (77.2%). The peak rate of isolates was recorded at the beginning of January (01/98).

Conclusions: A/Sydney/5/97(H₃N₂) like-strain was the dominant influenza virus. Its presence did not prevent the simultaneous activity of influenza A/H₁N₁ virus. The dynamic of the clinical disease as expressed by the weekly visit rate for ARI/flu-like was similar to the temporal pattern of the virological findings. The extent of morbidity suggests moderate epidemic activity.
 

In countries in which a primary care-oriented system has developed, general practitioners, family physicians, and other primary care doctors are the keystone of an approach that aims to achieve high quality and satisfaction with relatively low costs. Despite this new trend, medical schools still produce excessive numbers of sub-specialists rather than prinary care physicians. Among multiple reasons influencing a career choice either towards or away from primary care (institutional, legislative, and market pressures), the present article discusses ways in which medical school curricula may affect students in their perceptions of the role of primary care physicians. Since students are greatly influenced by the cultures of the institutions in which they train, the negative attitude of university towards family medicine may negatively affect the number of students going into this specialty. Examples from Israeli faculties are presented.

Background: Familial Mediterranean fever is a genetic disease in which some characteristic gene mutation have been found.

Objective: To analyze the phenotype-genotype correlations in North African Jews and Armedians with FMF.

Methods: We studied MEFV gene mutations and phenotype-genotype correlations in North African Jews and Armedians with Familial Mediterranean Fever living in France.

Results: M694V mutation was the most common mutation in Jews and in Armenians. Patients with M6801 homozygosity or M6801/M694V compound heterozygosity had a phenotype as severe as patients with M694V homozygosity.

Conclusions: This study characterizes the phenotype-genotype in specific ethnic groups of patients with FMF.

Background: Appropriateness of hospital admission has both clinical and economic relevance, especially in light of the growing pressure for increased efficiency of health services utilization. In Israel, the number of referrals and use of the emergency room continue to rise along with an increase in hospital admissions and the number of inappropriate admis­sions. Using evaluation protocols, such as the Pediatric Appropriateness Evaluation Protocol, international studies have shown that 10-30% of hospital admissions are medically unnecessary. Inappropriate hospitalizations have an economic impact as well as medical and psychological effects on the child and the family.

Objectives: To assess the extent and characteristics of inappropriate pediatric admissions to a tertiary care facility in Israel.

Methods: We conducted a prospective study using chart review of pediatric admissions to Soroka University Medical Center on 18 randomly selected days in 1993, and evaluated the appropriateness of admissions using the PAEP.

Results: Of the 221 pediatric admissions 18% were evaluated as inappropriate. The main reason for such an evaluation was that the problem could have been managed on an ambulatory basis. Inappropriate admissions were asso­ciated with hospital stays of 2 or less days, children older than 1 year of age, Jewish children, and self-referrals to the pediatric emergency room.

Conclusions: The assessment and identification of characteristics of inappropriate hospital admissions can serve as indicators of problems in healthcare management and as a basis for improving quality of care and developing appropriate medical decision-making processes.