Israel Medical Association Journal

Background: Several in vitro studies have reported on the efficacy of combined liposomal encapsulated doxorubicin (Doxil® or Caelyx®, MedEquip, UK) and hyperthermia over Doxil alone.

Objectives: To document the beneficial effect of Doxil-HT over Doxil alone in mice and to investigate the length of time HT[1] should be delivered.

Methods: M/109 lung tumor cells were injected into both leg pads of Balb/c female mice at age of 6–7 weeks. Two weeks later i.v. Doxil in a dose of 8 mg/kg (20–25 µg per mouse) was given and 4 HT sessions (2–3 days apart) were delivered during the subsequent 2 weeks at 2–3 days apart. HT was given to the left pad only for either 5 or 30 minutes (HT5 and HT30 respectively). Five weeks after tumor injection the mice were sacrificed and tumor volume and weight in both pads were measured. Internal comparisons between mice in the same treatment group and comparisons between different treatment cohorts were performed.

Results: In the combined Doxil-HT5 and Doxil-HT30 cohorts the tumor volume and weight in both pads were similar and did not differ from those achieved by Doxil alone. In the Doxil-HT30 cohort the tumor weight, but not the tumor volume, were smaller than those in Doxil-HT5 and Doxil alone (P = 0.006 and 0.01 respectively).

Conclusions: The combined Doxil-HT30 treatment is more effective then Doxil-HT5 or Doxil alone. Additional studies with different time scheduling and different temperatures are warranted.

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[1] HT = hyperthermia

Background: Infant mortality in Israel is twofold higher among non-Jews than Jews.

Objectives: To determine the impact of congenital malformations and Mendelian diseases on infant mortality.

Methods: We compared the causes of infant mortality in a 4 year period among Jewish and non-Jewish Israeli citizens. Classification was done by analyzing all the death reports according to whether or not the child had any known major malformation, Mendelian disease and/or a syndrome, irrespective of the immediate cause of death.

Results: The infant mortality among non-Jews was double that among Jews (9 versus 4.4 per 1,000 live births). The rate of children with malformations/genetic syndromes was 3.1 times higher among non-Jews than among Jews (2.94 vs. 1.25 per 1,000 live births). The most significant difference was in the rate of Mendelian diseases, which were 8.3 times more frequent in non-Jewish children (0.16 vs. 1.33 per 1,000 live births respectively). A Mendelian disease was diagnosed in almost 15% of the non-Jewish infants and in less than 5% of the Jewish infants.

Conclusions: The most striking difference between the Jewish and non-Jewish infants was the incidence of congenital malformations and Mendelian diseases parallel to the differences in the consanguinity rates between the two populations.
 

Background: The osteoporosis-pseudoglioma syndrome is a rare autosomal recessive disorder characterized by severe juvenile-onset osteoporosis and congenital or early-onset blindness. Other manifestations include muscular hypotonia, ligamentous laxity, mild mental retardation and seizures. The gene responsible was recently identified to be the low density lipoprotein receptor-related family member LRP5 on chromosome 11q11-12.

Objective: To measure bone density in two siblings with the OPPG[1] syndrome as well as in their family members (parents and siblings).

Methods: Bone mineral density was determined in the lumbar spine (antero-posterior), femoral neck, two-thirds distal forearm (>95% cortical bone) and ultradistal forearm (predominantly trabecular bone) by dual-energy X-ray absorptiometry.

Results: The studies revealed osteoporotic changes both in the patients and the carriers.

Conclusion: The findings demonstrate that OPPG carriers have reduced bone mass, which is a risk factor for development of early osteoporotic changes.

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Background: Bleeding in the first trimester of pregnancy is a common phenomenon, associated with early pregnancy loss. In many instances a subchorionic hematoma is found sonographically.

Objective: To evaluate the possible benefit of bed-rest in women with threatened abortion and sonographically proven subchorionic hematoma, and to examine the possible relationship of duration of vaginal bleeding, hematoma size, and gestational age at diagnosis to pregnancy outcome.

Methods: The study group consisted of 230 women of 2,556 (9%) referred for ultrasound examination because of vaginal bleeding in the first half of pregnancy, who were found to have a subchorionic hematoma in the presence of a singleton live embryo or fetus. All patients were advised bed-rest at home; 200 adhered to this recommendation for the duration of vaginal bleeding (group 1) and 30 continued their usual lifestyle (group 2). All were followed with repeated sonograms at 7 day intervals until bleeding ceased, the subchorionic hematoma disappeared, or abortion occurred. The groups were compared for size of hematoma, duration of bleeding, and gestational age at diagnosis in relation to pregnancy outcome (spontaneous abortion, term or preterm delivery).

Results: The first bleeding episode occurred at 12.6 ± 3.4 weeks of gestation (range 7–20 weeks) and lasted for 28.8 ± 19.1 days (range 4–72 days). The women who adhered to bed-rest had fewer spontaneous abortions (9.9% vs. 23.3%, P = 0.006) and a higher rate of term pregnancy (89 vs. 70%, P = 0.004) than those who did not. There was no association between duration of vaginal bleeding, hematoma size, or gestational age at diagnosis of subchorionic hematoma and pregnancy outcome.

Conclusions: Fewer spontaneous abortions and a higher rate of term pregnancy were noted in the bed-rest group. However, the lack of randomization and retrospective design of the outcome data collection preclude a definite conclusion. A large prospective randomized study is required to confirm whether bed-rest has a real therapeutic effect.

Background: Cystinuria is an autosomal recessive disease that is manifested by the development of kidney stones. Mutations in SLC3A1 cause type I disease, while mutations in SLC7A9 are associated with non-type I disease. In Israel cystinuria is especially common among Libyan Jews who suffer from non-type I disease.

Objectives: To compare clinical manifestations of patients with mutations in SLC3A1 to those with mutations in SLC7A9, and to assess the carrier rate among unaffected Libyan Jewish controls.

Methods: Clinical manifestations were evaluated in patients with mutations in SLC3A1 and in patients with mutations in SLC7A9. Carrier rates for two SLC7A9 mutations were assessed in 287 unaffected Libyan Jewish controls.

Results: Twelve patients with mutations in SLC3A1 were compared to 15 patients with mutations in SLC7A9. No differences were detected between the patients with mutations in SLC3A1 and those with mutations in SLC7A9 in relation to the age of disease onset, the estimated number of stones, the number of invasive procedures, the number of patients receiving drug therapy, or the patients’ urinary pH. Eleven of the unaffected Libyan Jewish controls were found heterozygotes for the V170M mutation, establishing a carrier rate of 1:25. The 1584+3 del AAGT mutation was not found in any of the Libyan Jewish controls.

Conclusion: Mutations in SLC3A1 and SLC7A9 cystinuria patients result in indistinguishable disease manifestations. The high carrier rate among Libyan Jews is a result of a single missense mutation, V170M.
 

Background: The chronic progressive course of peripheral arterial occlusive disease with its limb-threatening and life-threatening potential is associated with physical, psychological and social distress for elderly patients and their families.

Objective: To evaluate the influence of infra-inguinal bypass surgery for limb salvage, and social support, on quality of life in elderly patients (over 60 years old).

Methods: Sixty patients aged 60 years and above diagnosed with limb-threatening ischemia were evaluated using the SF-36 generic questionnaire for quality of life, and the MOS-SS questionnaire for social support. Thirty patients (group I) were evaluated in the hospital prior to reconstructive surgery and 30 postoperative patients (group II) were evaluated at home at least 6 months after infra-inguinal bypass operations. Both groups were comparable in terms of age, gender, prevalence of ischemic heart disease, diabetes, and other atherosclerosis risk factors.

Results: All quality of life parameters were higher among patients who underwent limb salvage surgery (group II) as compared to preoperative patients (group I), yet the obtained values were lower than those in the general population. Patients in the surgical intervention group had higher levels of function, lower pain levels, and higher emotional and social well-being and, in addition, were spared limb amputation. The findings also indicate that the social support dimensions (emotional support, receipt of information, affection and positive social interaction), as measured in terms of perceived availability, do not operate as one entity. Different types of social support were more beneficial along different stages of the disease.

Conclusion: Peripheral arterial occlusive disease causes severe impairment of the quality of life in elderly patients. Arterial reconstructive surgery improves the quality of life though it still remains low compared to the general population. Social support is beneficial in the treatment of these patients, and the social worker in the vascular surgery department has a key role in identifying the various needs of the patients along the path of their chronic illness.
 

Background: Primary hyperparathyroidism in elderly patients is usually associated with additional co-morbidity that increases operative risk, and thus many geriatric patients are denied the benefit of surgery for a single parathyroid adenoma.

Objectives:  To evaluate the safety and efficacy of accurate single photon emission computed tomography sestamibi scintigraphy, enabling precise localization of a single adenoma, in the geriatric population

Methods: Twenty-two patients aged 70 years and over with biochemically proven PHPT[1] and with a single parathyroid adenoma identified by localization studies (sestamibi SPECT[2] scan and ultrasonography) underwent 23 operations over 29 months (out of a total of 140 patients operated upon during the same period). Immediate preoperative sestamibi scintigraphy and marking of focal adenoma uptake followed by intraoperative hand-held gamma probe were used for the removal of the parathyroid adenoma by unilateral minimal access surgery. Associated major co-morbid conditions and pre- and postoperative calcium, phosphorus and parathormone levels were recorded. Indications for surgery were listed and operative and postoperative complications were noted. The patients were followed for a mean period of 17.7 months using the same parameters.

Results: The 22 patients with PHPT had a mean age of 76.3 ± 5.9 years (range 70–88 years)  and a female to male ratio of 13:9. Associated co-morbidity included ischemic heart disease (n=15), hypertension (n=22), non-insulin-dependent diabetes mellitus (n=9), chronic obstructive pulmonary disease (n=3), and previous neck surgery (n=3). Mean preoperative serum calcium, phosphorous and PTH[3] were 11.7 ± 1.3 mg/dl, 2.5 ± 0.5 mg/dl and 160.9 ± 75.4 pg/ml respectively. In 20 of the 22 patients, surgery was successful in curing PHPT (91%). One patient had persistent hypercalcemia due to a missed adenoma, and repeat operation (by focused minimal access surgery) was successfully performed 2 weeks later. There were no complications and no morbidity postoperatively. Mean postoperative serum calcium, phosphorous and PTH were 9.6 ± 1.2 mg/dl, 3.0 ± 0.5 mg/dl and 35.2 ± 24 pg/ml respectively. In all patients, serum calcium levels remained normal (9.7 ± 1.3 mg/ml) after long-term follow-up (mean 17.7 ± 9.6 months).

Conclusions: Minimally invasive, radio-guided focused parathyroidectomy for a single adenoma is a safe and effective method to cure hyperparathyroidism in the elderly. Success of surgery is directly related to the surgeon's experience and to the precise localization marking provided by sestamibi scintigraphic SPECT localization and concurrent sonographic findings.

Background: Risk factors for injurious falls among elderly people differ from those for falls in general. The characteristics of falls play an important role in determining the risk of hip fracture.

Objective: To investigate the risk factors associated with the fall characteristics known to be associated with the majority of hip fractures, e.g., a lateral fall and a subsequent impact on the greater trochanter.

Methods: In this 6 month prospective observational case-control study 101 individuals aged 65 years and over hospitalized following a hip fracture were interviewed 7–14 days after the accident. Data were also obtained from medical records, focusing on known predisposing and situational risk factors for the fall. We compared the risk factors between two groups: patients who suffered a lateral fall and subsequent impact on the greater trochanter of the femur, and patients who suffered other types of falls.

Results: Only 51.5% of the hip fracture patients reported that they had fallen directly to the side. Apart from age, there were no significant differences between the groups in other factors studied. When considering both fall direction and the area that took the main impact, we found that the majority of patients (85%) reported having fallen onto the posterolateral aspect and/or a fall with an impact on the greater trochanter.

Conclusion: Our findings did not show differences (except for age) in the factors studied between the groups. This study suggests that both fall direction and the area that takes the main impact should be considered in the characteristics of falls that might cause a hip fracture. Characteristics associated with greatest fracture risk include a fall onto the posterolateral aspect and/or a fall with an impact on the greater trochanter. More studies are needed to evaluate potential risk factors associated with this type of injury.

Background: With the aging of the population and the increase in the number of elderly patients under the care of primary care physicians in the community, it is essential that the physician be aware of the preventive medicine recommendations for this group of patients. Accepted evidence-based guidelines have been developed for the older patient and adherence to these guidelines may play a significant role in decreasing morbidity and mortality in the elderly.

Objectives: To determine whether elderly patients in community clinics are aware of the preventive medicine practices that are relevant and available to them, and to assess which factors influence their decision to use such interventions. Of particular interest was to evaluate the role of the doctor-patient relationship on the degree of patient compliance with preventive procedures.

Methods: Patients attending community clinics of the Clalit Health Services in Jerusalem were interviewed. Background information was obtained and the patients were questioned regarding the use of the following preventive medicine recommendations: screening for occult blood in the stool, testing of vision and hearing, influenza and pneumococcal immunization, thyroid-stimulating hormone testing, digital rectal examination for prostate cancer, and calcium supplementation. The patients were questioned regarding the use of aspirin or oral anticoagulation where relevant. Factors influencing their level of compliance were examined.

Results: The study group comprised 205 patients with an average age of 74.5 years. Overall the rates of compliance were high, with 78% undergoing visual assessment, 87% fecal occult blood testing, and 81% influenza immunization. Pneumococcal immunization had been administered to 49% of those interviewed and 56% had their hearing tested. Digital rectal examination had been performed in 45% of patients. Calcium supplementation was used in 60% of patients. Almost all the patients (91–100%) noted that the physician had initiated the procedure and that non-compliance was due to patient preferences. Of the 172 patients who were assumed to benefit from aspirin use, 153 (89%) used the medication, and 87% of 23 patients with atrial fibrillation were on chronic anticoagulation.

Conclusions: A high level of compliance with preventive medicine recommendations was found among this group of elderly patients. The doctor-patient relationship had a positive effect on the patients' compliance.
 

Background: Training in geriatric psychiatry constitutes a fundamental element toward further development of this relatively new branch of medicine. However, it varies both in quantity and quality among different countries, healthcare providers and medical schools.

Objectives: To describe the demographic and professional characteristics of participants in postgraduate diploma courses in geriatric psychiatry, and the perceived contribution of the courses; and to compare these variables among the participants in 1 year and 3 year courses, and between psychiatrists and non-psychiatrists.

Methods: A retrospective self-administered questionnaire was mailed to the 153 physicians who participated in the two courses. The 60 questionnaires completed and returned were analyzed.

Results: Participants in the courses constituted a heterogenous group in terms of demographic and professional characteristics, with no differences between 1 year and 3 year course participants, or between psychiatrists vs. non-psychiatrists (with the exception of more involvement of non-psychiatrists and 1 year course participants in old-age homes). Most responders indicated both the theoretical and practical benefits and application to daily practice of the material learned. Similarly, most responders indicated that after the courses they definitely used general assessment scales to a much greater extent, particularly cognitive scales, as well as operational diagnostic criteria for dementia. Participants in the 3 year course reported more significant use of assessment scales compared with 1 year participants, and 3 year participants and psychiatrists used the cognitive scales more often. There were no other significant differences between 1 year and 3 year participants and between psychiatrists’ and non-psychiatrists’ reports regarding general and more specific contributions of the courses.

Conclusion: Postgraduate diploma courses in geriatric psychiatry seem to have a favorable effect on participants, irrespective of course duration or specialty. However, course duration positively influenced the implementation of assessment scales in general, and cognitive scales in particular. A prospective comparative study on this subject is warranted, with stricter definitions of participants’ pre-course and post-course background, attitudes, knowledge and benefits.