Israel Medical Association Journal

Background: Endobronchial stents are used to treat symptomatic patients with benign or malignant airway obstructions.

Objectives: To evaluate the safety and outcome of airway stent insertion for the treatment of malignant tracheobronchial narrowing.

Methods: The files of all patients with malignant disease who underwent airway stent insertion in our outpatient clinic from June 1995 to August 2004 were reviewed for background data, type of disease, symptoms, treatment, complications, and outcome.

Results: Airway stents were used in 34 patients, including 2 who required 2 stents at different locations, and one who required 2 adjacent stents (total, 37 stents). Ages ranged from 36 to 85 years (median 68). Primary lung cancer was noted in 35% of the patients and metastatic disease in 65%. Presenting signs and symptoms included dyspnea (82%), cough (11.7%), hemoptysis (9%), pneumonia (5.9%), and atelectasis (3%). The lesions were located in the left mainstem bronchus (31%), trachea (26%), right mainstem bronchus (26%), subglottis (14.3%), and bronchus intermedius (2.9%). Conscious sedation alone was utilized in 73% of the patients, allowing for early discharge. Eighteen patients (50%) received brachytherapy to the area of obstruction. Complications included stent migration (one patient) and severe or minimal bleeding (one patient each). Ninety-four percent of the patients reported significant relief of their dyspnea. Three of the four patients who had been mechanically ventilated before the procedure were weaned after stent insertion. Median survival from the time of stent placement was 6 months (range 0.25–105 months).

Conclusion: Stent placement can be safely performed in an outpatient setting with conscious sedation. It significantly relieves the patient's symptoms and may prolong survival.
 

Objectives: To identify subpopulations with a sedentary lifestyle and low levels of adherence to physical activity recommendations.

Methods: The Israel Center for Disease Control performed two national surveys during 2002–2003, interviewing 7,307 Jewish Israelis and 1,826 Arab Israelis over age 21. Respondents were asked if they engaged in physical activity lasting at least 20 consecutive minutes, and if so how frequently: less than once a week, once or twice a week, nearly every day or every day.

Results: Arab respondents were less physically active than Jewish respondents after adjusting for gender, age, level of religiosity, marital status, education, self-reported health, smoking, body mass index, and type of survey. Multiple logistic regression analysis run separately for Jews and Arabs found a more sedentary lifestyle, in both groups, among women, the less educated, those who were married and those with poor subjective health. Among Jews, younger people, increased religiosity, smoking and high BMI[1] were associated with a sedentary lifestyle.

Conclusions: The Jewish population is in need of more targeted and specific interventions for lower adhering subpopulations, such as women, the less educated and those with other risk factors. In the Arab population a more thorough understanding of the benefits of physical activity is needed; however, it seems that a general intervention is required to decrease the prevalence of a sedentary lifestyle all round.

Melanoma is the leading cause of death from skin tumors worldwide, with an annual increase in incidence over the past decade. The molecular mechanisms involved in melanoma pathogenesis are beginning to be unraveled. While a family history of melanoma and exposure to ultraviolet irradiation have been known for years as risk factors in melanoma development, the precise genes involved in inherited predisposition were defined only in the past decade. Germline mutations in two genes that play a pivotal role in controlling cell cycle and division – CDKN2A and cyclin-dependent kinase 4 (CDK4) – have been detected in autosomal, dominant, high penetrance familial melanoma cases. In addition to these two highly penetrant genes, germline mutations and polymorphisms in a few low penetrance genes have been reported in familial melanoma cases: melanocortin-1 receptor, epidermal growth factor, glutathione s-transferase M1, cytochrome p450 debrisoquine hydroxylase locus (CYP2D6) and vitamin D receptor.

Background: Transcobalamin II is a serum transport protein for vitamin B₁₂. Small variations in TC-II[1] affinity were recently linked to a high homocysteine level and increased frequency of neural tube defects. Complete absence of TC-II or total functional abnormality causes tissue vitamin B₁₂ deficiency resulting in a severe disease with megaloblastic anemia and immunologic and intestinal abnormalities in the first months of life. This condition was described in hereditary autosomal-recessive form. Low serum TC-II without any symptoms or clinical significance was noted in relatives of affected homozygotes.

Objectives: To study 23 members of a four-generation family with hereditary vitamin B₁₂ deficiency and neurologic disorders.

Methods: Thorough neurologic, hematologic and family studies were supplemented by transcobalamin studies in 20 family members.

Results: Partial TC-II deficiency was found in 19 subjects. Apo TC- II (free TC-II unbound to vitamin B₁₂) and total unsaturated B₁₂ binding capacity were low in all tested individuals but one, and holo TC-II (TC-II bound by vitamin B₁₂) was low in all family members. The presentation of the disease was chronic rather than acute. Early signs in children and young adults were dyslexia, decreased IQ, vertigo, plantar clonus and personality disorders. Interestingly, affected children and young adults had normal or slightly decreased serum vitamin B₁₂ levels but were not anemic. Low serum B₁₂ levels were measured in early adulthood. In mid-late adulthood megaloblastic anemia and subacute combined degeneration of the spinal cord were diagnosed. Treatment with B₁₂ injections resulted in a significant improvement. The pedigree is compatible with an autosomal-dominant transmission. This family study suggests a genetic heterogeneity of TC-II deficiency.

Conclusions: We report the first family with a hereditary transmitted condition of low serum TC-II (partial TC-II deficiency) associated with neurologic and mental manifestations in childhood. Partial TC-II deficiency may decrease the amount of stored cobalamin, resulting in increased susceptibility to impaired intestinal delivery of cobalamin and predisposing to clinically expressed megaloblastic anemia at a later age. Partial TC-II deficiency should be suspected in families with megaloblastic anemia and in individuals with neurologic and mental disturbances – despite normal serum vitamin B₁₂ levels. Low serum UBBC[2] and apo TC-II should confirm the diagnosis. Early vitamin B₁₂ therapy may prevent irreversible neurologic damage.

Background: Decreased elasticity of the aorta is associated with aging and several risk factors of atherosclerosis. The data regarding this phenomenon in patients with familial hypercholesterolemia are rather sparse.

Objectives: To evaluate non-invasively the elasticity of the proximal ascending aorta of 51 heterozygous FH[1] patients compared to 42 normal age and gender-matched controls.

Methods: Aortic elasticity was estimated by transthoracic echocardiography using the “pressure-strain” elastic modulus and aortic strain formulas.

Results: The elastic modulus score was higher in the FH group than in the controls (1.12 ± 0.91 10⁶ dynes/cm² vs. 0.65 ± 0.46 10⁶ dynes/cm² respectively, P = 0.01). This was consistent in both the pediatric (0.5 ± 0.2 10⁶ dynes/cm² vs. 0.4 ± 0.1 10⁶ dynes/cm² respectively, P = 0.009) and adult subgroups (1.3 ± 1.0 10⁶ dynes/cm² vs. 0.8 ± 0.5 10⁶ dynes/cm² respectively, P = 0.0004). Aortic strain was significantly lower in patients with FH than in controls (6 ± 4% vs. 9 ± 5% respectively, P = 0.0002). These findings reflected decreased elasticity of the proximal ascending aorta in the FH patients. In multivariate analysis, age, serum cholesterol level and serum triglycerides level were the independent predictors of the elastic modulus score, whereas age was the predictor of aortic strain.

Conclusions: The elasticity of the proximal ascending aorta is decreased in heterozygous FH patients.

Background: The incidence of malignant musculoskeletal tumors during pregnancy is very low. The paucity of data precludes the drawing of solid conclusions regarding a standard approach.

Objectives: To summarize our experience treating 13 pregnant women with malignant soft tissue or bone tumors.

Methods: We conducted a retrospective analysis of 13 cases of patients with either soft tissue or bone sarcoma that developed or progressed during pregnancy or immediately after delivery.

Results: The clinical presentation of the tumors was either a growing mass and/or increasing pain and disability. Most of the masses were located in the lower part of the body and of considerable size. Treatment given during gestation was limited to wide excision of the mass in the 28th week of gestation in one patient. All the patients reported disease progression during gestation. Vaginal delivery was possible in eight patients with no complications, cesarean section was carried out in three women, spontaneous miscarriage occurred in one and termination of pregnancy was performed in one patient.

Conclusions: The diagnostic and therapeutic approaches should be tailored specifically in every pregnant woman in whom sarcoma is suspected.
 

Micronutrient deficiencies have reoccupied the center stage of public health policy with the realization that folic acid deficiency results in neural tube defects and possibly other birth defects as well as ischemic heart disease. These, in turn, have raised an older debate on food fortification policy for the elimination of iodine, iron and vitamin D deficiencies. Data from the First Israeli National Health and Nutrition Survey (MABAT 2000) provided an impetus to develop an active national nutrition policy aimed to improve the nutritional status of iodine, iron, vitamins A and D and B-vitamins, including folate. In this paper we examine some of the MND[1] issues in Israel and their implications for public health, and suggest options for the formulation of policy.

Background: Granulocyte colony-stimulating factor has had a major impact on the management of severe chronic neutropenia – a collective term referring to congenital, idiopathic, or cyclic neutropenia. Almost all patients respond to G-CSF[1] with increased neutrophils, reduced infections, and improved survival. Some responders with congenital neutropenia (termed Kostmann’s syndrome herein) and Shwachman-Diamond syndrome have developed myelodysplastic syndrome and acute myeloid leukemia, which raises the question of the role of G-CSF in pathogenesis. The issue is complicated because both disorders have a propensity for MDS[2] or AML[3] as part of their natural history.

Objective and Methods: To address this, the Severe Chronic Neutropenia International Registry used its large database of chronic neutropenia patients treated with G-CSF to determine the incidence of malignant myeloid transformation in the two disorders, and its relationship to treatment and to other patient characteristics.

Results: As of January 2001, of the 383 patients with congenital forms of neutropenia in the Registry, 48 had MDS or AML (crude rate, about 12.5%). No statistically significant relationships were found between age at onset of MDS or AML and patient gender, G-CSF dose, or duration of G-CSF therapy. What was observed, however, was the multistep acquisition of aberrant cellular genetic changes in marrow cells from Kostmann’s syndrome patients who transformed, including activating ras oncogene mutations, clonal cytogenetic abnormalities, and G-CSF receptor mutations. The latter in murine models produces a hyperproliferative response to G-CSF, confers resistance to apoptosis, and enhances cell survival.

Conclusions: Since Kostmann’s syndrome and Shwachman-Diamond syndrome are inherited forms of bone marrow failure, G-CSF may accelerate the propensity for MDS/AML in the genetically altered stem and progenitor cells, especially in those with G-CSF receptor and ras mutations (82% and 50% of Kostmann’s syndrome patients who transform, respectively). Alternatively, and equally plausible, G-CSF may simply be an innocent bystander that corrects neutropenia, prolongs patient survival, and allows time for the malignant predisposition to declare itself. Only careful long-term follow-up of the cohort of patients receiving G-CSF will provide the answer.

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[1] G-CSF = granulocyte colony-stimulating factor

[2] MDS = myelodysplastic syndrome

[3] AML = acute myeloid leukemia