Israel Medical Association Journal

Background: Metastatic melanoma is an aggressive and highly malignant cancer. The 5 year survival rate of patients with metastatic disease is less than 5% with a median survival of only 6–10 months. Drugs like dacarbazin (DTIC) as a single agent or in combination with other chemotherapy agents have a response rate of 15–30%, but the duration of response is usually short with no impact on survival. Interleukin-2-based immunotherapy has shown more promising results. The National Institutes of Health recently reported that lymphodepleting chemotherapy, followed by an adoptive transfer of large numbers of anti-tumor specific tumor-infiltrating lymphocytes, resulted in an objective regression in 51% of patients.

Objectives: To introduce the TIL[1] technology to advanced metastatic melanoma patients in Israel.

Methods: We generated TIL cultures from tumor tissue, choosing those with specific activity against melanoma and expanding them to large numbers.

Results: TIL cultures from nine patients were established and examined for their specific activity against the patients' autologous tumor cells. Twelve TIL cultures derived from 5 different patients showed the desired anti-tumor activity, making those 5 patients potential candidates for the therapy.

Conclusions: Pre-clinical studies of the TIL technology in a clinical laboratory set-up were performed successfully and this modality is ready for treating metastatic melanoma patients at the Sheba Medical Center's Ella Institute.

Background: Diabetic macular edema causes visual loss in almost one-third of diabetic patients. There is currently no treatment for the accompanying cystoid foveal changes.

Objectives: To assess the clinical outcome, i.e., change in visual acuity, in patients treated with steroids for long-standing diabetic macular edema with foveal cystoid changes.

Methods: In the ophthalmology department of a tertiary care university‑affiliated medical center and the ophthalmology service of a health management organization, 46 diabetic subjects (56 eyes) who had diabetic macular edema with cystoid foveal changes received one intravitreal injection of 4 mg triamcinolone acetonide.

Results: The mean baseline (pre‑injection) visual acuity of 0.21 increased to 0.31 and 0.48 at 1 and 3 months, respectively, after which it decreased to 0.33 at 6 months. The mean intraocular pressure was 15.07 mmHg at baseline, 15.83 at day 1, gradually rising to 17.16, 18.38 and 18.57 mmHg at 1, 3 and 6 months respectively. Three patients suffered immediate visual decline after the injection.

Conclusions: Intravitreal triamcinolone acetonide may be a therapeutic option for long‑standing diabetic macular edema with foveal cystoid changes.
 

Background: Cardiovascular disease is now well established as a multifactorial disease. In a given individual, the level of cardiovascular risk is due to the interaction between genetic and environmental components. The BIP cohort comprised 3000 patients with cardiovascular disease who were tested for the benefits of bezafibrate treatment. This cohort has the data for the lipid profile of each individual, fibrinogen, Insulin, as well as clinical, demographic and lifestyle parameters

Objectives: To genotype up to 64 variable sites in 36 genes in the BIP cohort. The genes tested in this assay are involved in pathways implicated in the development and progression of atherosclerotic plaques, lipid and homocystein metabolism, blood pressure regulation, thrombosis, rennin-angiotensin system, platelet aggregation, and leukocyte adhesion.

Methods:  DNA was extracted from 1000 Israeli patients from the BIP cohort. A multilocus assay, developed by the Roche Molecular System, was used for genotyping. Allele frequencies for some of the markers were compared to the published frequencies in a healthy population (the French Stanislas cohort, n=1480).

Results: Among the 26 comparable alleles checked in the two cohorts, 16 allele frequencies were significantly different from the healthy French population: ApoE (E3, E2, E4), ApoB (71ile), ApoC (3482T, 455C, 1100T, 3175G, 3206G), CETP (405val), ACE (Del), AGT (235thr), ELAM (128arg); p<0001 and LPL (93G, 291Ser, 447ter); p < 005.

Conclusions: Although a comparable healthy Israeli population study is needed for more precise interpretation of these results, frequency differences in these polymorphic alleles, associated with lipid metabolism, renin-angiotensin system and leukocyte adhesion mechanism, between CVD patients and healthy individuals nevertheless implicate these candidate genes as predisposing for CVD.lic safety.
 

The first Trauma Unit in Israel was founded at the Hadassah (Ein Kerem) Medical Center in 1992 - the result of increased awareness to the new concept of optimal care for the injured patient.

Background: The prevalence of morbid obesity is increasing rapidly. Weight reduction is very difficult using diet restriction and physical activity alone. Sibutramine has been shown to be effective and safe as an adjuvant therapy to diet restrictions.

Objectives: To describe our experience using sibutramine in weight reduction treatment of adolescents suffering from morbid obesity.

Methods: The study group comprised 20 young persons (13 females, mean age 15 years 4 months, range 13–18 years) with morbid obesity (body mass index over the 95th percentile for age and/or ≥ 30 kg/m²) were treated with sibutramine 10 mg once a day for 1 year.

Results: Mean BMI[1] was 40 ± 5.6 kg/m² (range 30.1–49.5 kg/m²) at the beginning of treatment. Most patients showed an early weight reduction to mean BMI 39.3 ± 4.9 and 35.9 ± 5.7 at 3 and 6 months respectively, but stopped losing weight over the next 6 months. During the follow-up period 17 patients discontinued the treatment. The main reason for dropout was the slow rate of weight reduction after 6 months. Patients suffering from concomitant disorders (severe asthma, hypertension, sleep obstructive apnea) showed improvement after weight reduction. Adverse reactions from the treatment were transient, mild and well tolerated.

Conclusions: Sibutramine may help in achieving weight reduction for a short period and in improving concomitant health problems, however its long-term effect is limited.

Background: Chlorpromazine is a dopamine-receptor antagonist antipsychotic agent. Because of its strong alpha-blocking and sedative actions, it has also been used as emergency therapy for extreme arterial hypertension. Published reports to date have included very small numbers of patients (i.e., 5–30).

Objectives: To analyze data on almost 500 patients who received intravenous chlorpromazine for the emergency treatment of uncontrolled symptomatic hypertension in the pre-hospital setting.

Methods: We reviewed data from 496 consecutive patients who received intravenous chlorpromazine as emergency therapy for uncontrolled symptomatic hypertension. Chlorpromazine was injected intravenously. The dose was 1 mg every 2–5 minutes until the systolic pressure was -<140 mmHg and the diastolic pressure -<100 mmHg with alleviation of symptoms.

Results: The mean dose of chlorpromazine administered was 4.5 +- 5 mg (range 1–50 mg). Only 33 patients (7%) required >10 mg. Chlorpromazine reduced the systolic blood pressure from 222.82 +- 26.31 to 164.93 +- 22.66 mmHg (P < 0.001) and the diastolic blood pressure from 113.5 +- 16.63 to 85.83 +- 11.61 mmHg (P < 0.001). The sinus rate decreased from 97.9 +- 23.5 to 92.2 +- 19.7 beats per minute (P < 0.001). These results were achieved within the first 37 +- 11 minutes.

Conclusions: Intravenous chlorpromazine is safe and effective when used as emergency treatment for uncontrolled symptomatic hypertension.

Objectives: To report our experience in the treatment of pelvic fractures.

Methods: Between October 1998 and September 2001, 78 patients with pelvic fractures were admitted to our hospital. The age range of the 56 male and 22 female patients was 16–92 (mean 42 years). The cause of injury was road accident in 52 patients, fall from a height in 15, a simple fall in 9, and gunshot wounds in 2 patients. The Glascow Coma Scale score on arrival at the hospital was 3–15 (average 12). Twenty-five patients (32%) were admitted to the intensive care unit, 38 (48%) to the orthopedic department, 5 (6.4%) to neurosurgery and the remainder to a surgical department.

Results: Twenty-six patients (33.3%) received blood transfusion in the first 24 hours. Of the 25 patients (32%) with associated head trauma, 6 had intracranial bleeding; 29 patients (37%) had associated chest trauma, 28 (35.9%) had associated abdominal trauma, 16 (20.5%) had vertebral fractures and 40 (51.2%) had associated limb fractures. Pelvic angiography was performed in 5 patients (6.4%), and computed tomography-angiography of the cervical arteries and chest was performed in 1 and 5 patients respectively. Overall, a CT scan was performed in 56 patients (71.8%), of whom 25 (32%) had a pelvic CT on admission. Injury Severity Score was 4–66 (median 20). Laparotomy was performed in 14 patients (18%), spinal fusion in 5 (6.4%), limb surgery in 16 (20.5%), cranial surgery in 4 (5.02%), pelvic surgery in 10 (12.8%), chest surgery in 3 (3.85%), and facial surgery in 2 patients (2.56%). Seven patients (9%) died during the course of treatment.

Conclusion: Pelvic fracture carries a high morbidity rate. Associated chest, abdomen and limb injuries are often encountered. A multidisciplinary approach is needed to improve survival and outcome in patients with pelvic fractures. 

Objectives: To compare the hemostatic efficacy of the second-generation surgical sealant (Quixil™ in Europe and Israel, Crosseal™ in the USA) to that of nasal packing in endonasal surgery.

Methods: We conducted a prospective randomized trial that included 494 patients (selected from 529 using exclusion and inclusion criteria and completed follow-up) undergoing the above-mentioned endonasal procedures. Patients were assigned to one of three surgical groups: septoplasty + conchotomy + nasal packing or fibrin sealant (Group 1); ESS[1] + nasal packing or fibrin sealant (Group 2); and ESS + septoplasty + conchotomy + nasal packing or fibrin sealant (Group 3). The hemostatic effects were evaluated objectively in the clinic by anterior rhinoscopy and endoscopy and assessed subjectively by the patients at follow-up visits.

Results: Postoperative hemorrhage occurred in 22.9–25% of patients with nasal packing vs. 3.12–4.65% in the fibrin sealant groups (late hemorrhage only). Drainage and ventilation of the paranasal sinuses, which are impaired in all cases of packing, remained normal in the fibrin sealant group. There were no allergic reactions to the sealant.

Conclusions: Our results show that fibrin sealant by aerosol spray in endonasal surgery is more effective and convenient than nasal packing. It requires no special treatment, i.e., antibiotics, which are usually used if nasal packing is involved.

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[1] ESS = endoscopic sinus surgery

Objectives: To examine whether a military medic, using a structured questionnaire and an algorithm, can appropriately triage patients to receive over-the-counter medications and refer more complicated cases to a physician.

Methods: The study group comprised 190 consecutive soldiers who presented to a military primary care clinic with symptoms of ARVI. Using a questionnaire, a medic recorded the patient's history and measured oral temperature, pulse rate and blood pressure. All patients were referred to a doctor. Physicians were “blind” to the medic’s anamnesis and to the algorithm diagnosis. We compared the medic’s anamnesis and therapeutic decisions to those of the doctors.

Results: Patients were young (21.1 ± 3.7 years) and generally healthy (93% without background illness). They usually had a minor disease (64% without fever), which was mostly diagnosed as viral ARVI (83% of cases). Ninety-nine percent were also examined by a physician. According to the patients' data, the medics showed high overall agreement with the doctors (83–97.9%). The proposed algorithm could have saved 37% of referrals to physicians, with a sensitivity of 95.2%. Had the medics been allowed to examine the pharynx for an exudate, the sensitivity might have been 97.6%.

Conclusions: Medics, equipped with a questionnaire and algorithm but without special training and without performing a physical examination, can appropriately triage patients and thereby reduce the number of referrals to physicians.

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[1] ARVI = acute respiratory viral infection