Israel Medical Association Journal

Background: Laron Syndrome, first described in Israel, is a form of dwarfism similar to isolated growth hormone deficiency caused by molecular defects in the GH[1] receptor gene.

Objective: To characterize the molecular defects of the GH-R[2] in Laron syndrome patients followed in our clinic.

Methods: Of the 63 patients in the cohort, we investigated 31 patients and 32 relatives belonging to several ethnic origins. Molecular analysis of the GH-R gene was performed using the single strand conformation polymorphism and DNA sequencing techniques.

Results: Eleven molecular defects including a novel mutation were found. Twenty-two patients carried mutations in the extracellular domain, one in the transmembrane domain, and 3 siblings with typical Laron syndrome presented a normal GH-R. Of interest are, on one hand, different mutations within the same ethnic groups: W-15X and 5, 6 exon deletion in Jewish-Iraqis, and E180 splice and 5, 6 exon deletion in Jewish-Moroccans; and on the other hand, identical findings in patients from distinct regions: the 785-1 G to T mutation in an Israeli-Druze and a Peruvian patient. A polymorphism in exon 6, Gly168Gly, was found in 15 probands. One typical Laron patient from Greece was heterozygous for R43X in exon 4 and heterozygous for Gly168Gly. In addition, a novel mutation in exon 5: substitution of T to G replacing tyrosine 86 for aspartic acid (Y86D) is described.

Conclusions: This study demonstrates: a) an increased focal incidence of Laron syndrome in different ethnic groups from our area with a high incidence of consanguinity; and b) a relationship between molecular defects of the GH-R, ethnic group and geographic area.

Background: The mortality rate associated with congenital heart surgery is apparently related to caseload.

Objective: To determine whether an increase in caseload over the long term at a single center affects management and outcome in children undergoing cardiac surgery.

Methods: Data were collected prospectively over a 4 year period from the computerized registry of the hospital’s pediatric intensive care unit. Five parameters were analyzed: age at surgery, type of surgery, preventive measures (open chest), surgery-related and other complications (diaphragm paralysis and acute renal failure, respectively), and mortality. The data of a single-type surgery (arterial switch) were analyzed for bypass time and mechanical ventilation on an annual basis.

Results: The age distribution changed over the years, with more children under 1 year of age (20% newborns) undergoing surgery by the fourth year of the study. The caseload increased from 216 in the first year to 330 in the fourth, with a concomitant decrease in mortality rate from 4.9% to 3.2%. The chest was left open in 3.2% of patients in the first year and in 9.2% in the fourth year. The rate of diaphragm paralysis decreased from 6% to 2.4%. Death due to acute renal failure in patients requiring dialysis decreased from more than 80% in the first 2 years to 36% in the last two. These changes show an improvement but failed to reach statistical significance. Regarding the arterial switch operation, there was a significant improvement in pump time and duration of mechanical ventilation.

Conclusions: The increase in caseload in pediatric cardiac surgery was accompanied by improved management, with a lower complications-related mortality rate. We suggest that for optimal care of children with congenital heart disorders, quality management resources should be concentrated in centers with high caseloads.
 

The ethical chapter of the Israel Medical Association has recently issued guidelines with regard to exual relationships between doctors and patients or past patients. This paper juxtaposes the paternalistic and severe attitude to doctor-patient sex with the relaxation and individualization of decisions regarding doctors' involvement in assisted suicide, passive and active euthanasia. The discussion bears on our concepts of palliative care and our expectations from it.

Background: Eldercare often necessitates the presence of a family caregiver at the senior's visit to a doctor’s office. Studies indicate that some caregivers are not satisfied with these encounters or with as An understanding of the dynamics of these complex interactions is required.

Objectives: To explore family physicians’ attitudes to interfacing family caregivers of the elderly, to identify factors within the family patient-caregiver encounters in the office setting that for physicians,  to ascertain factors that might be problematic for physicians, to ascertain factors that might contribute to doctors’ behaviors and concerns, and to propose possible solutions for optimizing the outcomes of these visits.

Method: A questionnaire for self-administration was mailed to 200 family physicians in Montreal, Canada who are affiliated with two community secondary care and one tertiary care hospital and involved in geriatric office practice. The survey focused on family physician attitudes, concerns and observations on the interactions among themselves, elderly patients and their family caregivers during office visits.

Results: A total of 142 completed questionnaires were returned with a 71% response rate. Most family doctors felt that it was their responsibility to respond to caregiver concerns (90.6%) and that they were generally meeting their needs (94.2%). In contrast, 81% found this activity stressful and that as few as three such encounters per day were sufficient to generate stress. Causes of stress included: a) concern regarding misdiagnosis, b) different agendas or conflicting responses of patient and caregiver to doctors’ suggestions, and c) reluctance of the elderly or the caregiver to use community resources. A common physician strategy was reliance on acquired professional experience to solving problems of the elderly or of their caregivers.

Conclusions: Despite the stress involved, physicians are interested in assisting caregivers in the management of the elderly. Many doctors lack adequate knowledge about or confidence in community resources. Clinicians may require enhanced skills in conflict resolution necessary to achieve optimal outcomes.

Background: The free-to-total prostate-specificantigen ratio is the best marker for optimizing prostate cancer detection. The main problem with studies of percent free PSA is the variability of reported cutoff values.

Objectives: To evaluate the influence of prostate size on the ratio of free to total PSA.

Methods: The study group included 58 patients (mean age 66.4 years) with clinically localized prostate cancer treated surgically at our institution. Total PSA and free PSA levels were measured by a solid phase enzyme immunoassay test (Hoffman-La Roche, Basel, Switzerland). The percent free PSA was compared with prostate size as determined from the surgical specimen.

Results: A direct relation was noted between prostate size and the percent free PSA value (r=0.49, P=0.0001). Mean percentage free PSA was 9%0.004 in men with normal-sized gland while in men with large prostate (60 g) the average percent free PSA was 15.90.09 (P=0.001).

Conclusions: In patients with prostate cancer the percent free PSA level is influenced by the gland size. The larger the prostate the higher the proportion of the free PSA. Such information may have influence on the recommendation for prostate biopsy in screening programs for early detection of prostate cancer.