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: 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: Chronic nicotine administration has a dual effect on inflammatory bowel disease: augmentation of jejunitis and amelioration of colitis. We previously showed that chronic nicotine administration has divergent regional effects on small bowel and colonic mucosal mediators and blood flow.

Objective: To examine the effects of nicotine administration on cytokine levels in normal rat small bowel mucosa, colonic mucosa, and blood.

Methods: Male Sprague-Dawley rats weighing 200–250 g were given nicotine (12.5 μg/ml) that was dissolved in tap water. Rats were sacrificed on days 1, 2, 7 and 14 after nicotine initiation; blood was withdrawn, and small bowel and colon were resected, washed and weighed. Mucosal scrapings were extracted in 2 ml Krebs-Hemselest buffer for determination of interleukins-2, 6 and 10 using the Biosource International Immunoassay Kit.

Results: Nicotine decreased IL-10[1] and increased IL-6 levels in small bowel mucosa (from 3.5 ±  0.5 to 0.4 ± 0.1 pg/ml and from 1.9±0.4 to 13.6±0.4 pg/ml respectively; P < 0.05). Nicotine decreased IL-2 levels in the colon (from 15.8±3.0 to 7.9±1.0 pg/ml; P < 0.05), having no effect on IL-10 or IL-6 levels. Rats treated with nicotine had lower IL-6 and IL-2 blood levels compared to control rats.

Conclusions: Nicotine has different regional effects on small bowel and colonic cytokine mucosal levels, which might explain some of its opposite effects on small bowel and colonic inflammation.

Background: The prediction that Duchenne muscular dystrophy patients have out-of-frame deletions and Becker muscular dystrophy patients have in-frame deletions of the dystrophin gene holds well in the vast majority of cases. Large in-frame deletions involving the rod domain only have usually been associated with mild (BMD[1]) phenotype.

Objectives: To describe unusual cases with large in-frame deletions of the rod-shaped domain of the dystrophin gene associated with severe (Duchenne) clinical phenotype

Methods: Screening for dystrophin gene deletion was performed on genomic DNA by using multiplex polymerase chain reaction. Needle muscle biopsies from the quadriceps were obtained using a BergstrÖm needle. The biopsies were stained with histologic and histochemical techniques as well as monoclonal antibodies to dystrophin 1, 2 and 3.

Results: In three children with large in-frame deletions of the rod domain (exons 10–44, 13–40 and 3–41), early-onset weakness and a disease course suggested the DMD[2] phenotype.

Conclusions: This observation emphasizes the uncertainty in predicting the Becker phenotype in a young patient based on laboratory evaluation, and that the clinical picture should always be considered.

Background: Complementary medicine is gaining popularity, yet medical school curricula usually ignore it.

Objectives: To determine whether senior medical students are interested in learning principles of complementary or alternative medicine, to check their degree of familiarity with it, and to suggest a format for such studies in the medical curriculum.

Methods: Senior medical students (n = 117) were surveyed by an anonymous questionnaire.

Results: Seventy-nine percent of the senior medical students were interested in studying complementary or alternative medicine in medical school, and 65% were interested in applying these techniques to treat patients. Eighty-seven percent of students were familiar with some techniques of complementary medicine.

Conclusions: Senior medical students are interested in studying complementary and alternative medicine in medical school and in applying these techniques in practice.
 

During September 2002, Israel began its current revaccination program against smallpox, targeting previously vaccinated “first responders” among medical and emergency workers. In order to identify the potential strengths and weaknesses of this program and the conditions under which critical decisions were reached, we conducted a SWOT analysis of the current Israeli revaccination program, designed to identify its intrinsic strengths and weaknesses, as well as opportunities for its success and threats against it. SWOT analysis – a practical tool for the study of public health policy decisions and the social and political contexts in which they are reached - revealed clear and substantial strengths and weaknesses of the current smallpox revaccination program, intrinsic to the vaccine itself. A number of threats were identified that may jeopardize the success of the current program, chief among them the appearance of severe complications of vaccination. Our finding of a lack of a generation of knowledge on smallpox vaccination urgently calls for improved physician education and dissipation of misconceptions that are prevalent in the public today.