Israel Medical Association Journal

In recent years, umbilical cord blood has emerged as an alternative source of hematopoietic progenitors (CD34+) for allogeneic stem cell transplantation, mainly in patients who lack an human leukocyte antigen-matched marrow donor. Since 1998, about 2,500 patients have received UCB[1] transplants for a variety of malignant and non-malignant diseases. The vast majority of recipients were children with an average weight of 20 kg, however more than 500 UCB transplantations have already been performed in adults. The “naive” nature of UCB lymphocytes may explain the lower incidence and severity of graft versus host disease encountered in UCBT[2] compared to the allogeneic transplant setting. Furthermore, UCB is rich in primitive CD16^-CD56⁺⁺ natural killer cells, which possess significant proliferative and cytotoxic capacities and can be expanded using interleukin-12 or 15, so as to mount a substantial graft versus leukemia effect. The major disadvantage of UCB is the low yield of stem cells, resulting in higher graft failure rates and slower time to engraftment compared to bone marrow transplantation. A rational approach thus involves ex vivo expansion of UCB-derived hematopoietic precursors.

Background: Ovarian vein embolization was recently suggested as the preferred treatment for chronic pelvic pain syndrome.

Objective: To evaluate the technical feasibility, complications and early clinical and radiographic results of ovarian vein embolization in women with pelvic pain syndrome.

Methods: Percutaneous transcatheter ovarian vein embolization with coils was performed in six patients aged 27–53 years who presented with pelvic pain syndrome. All had lower abdominal pain, and pelvic varicosities were found on Doppler ultrasound and retrograde ovarian vein venography. Embolization was done unilaterally in three patients (on the left side) and bilaterally in three. Mean follow-up by telephone questionnaire was 7.3 months.

Results: The procedure was technically successful in all patients. Two patients reported partial relief of symptoms (33.3%) and three had complete relief (50%), for a total of 5 patients (83.3%) with some measure of improvement. There were no complications following the procedure.

Conclusions: Percutaneous transcatheter ovarian vein embolization seems to be safe and feasible for the treatment of pelvic pain syndrome. The procedure is performed on an outpatient basis and is well tolerated by patients.

Background: Nasal colonization with methicillin-resistant Staphylococcus aureus in the community is being increasingly reported, but there is a general lack of data on MRSA[1] colonization in children in chronic care institutions and on colonization rates in Israeli children.

Objectives: To define the rate of MRSA nasal colonization in a generally healthy pediatric population in Jerusalem, to compare it with that of children in chronic care institutions, to define risk factors for colonization, and to compare community and hospital-acquired MRSA strains.

Methods: Anterior nares culture for the presence of methicillin-sensitive and methicillin-resistant S. aureus was taken from 831 healthy children attending primary pediatric clinics or emergency department and 118 children hospitalized in three chronic care institutions in Jerusalem.

Results: Of the 831 healthy children, 195 (23.5%) were colonized with S. aureus, as compared to 43 of 118 (36.4%) chronically institutionalized children (P < 0.005). Five of the 195 S. aureus isolates from healthy children (2.6%) were MRSA, as compared to 9 of 43 (21%) from chronically institutionalized children (P < 0.001). Older age and a family member who is a healthcare worker were associated with S. aureus colonization in the population of healthy children, and older age was associated with MRSA colonization in the chronically institutionalized children. The antibiotic susceptibility pattern was similar for both groups, and pulsed field gel electrophoresis of the isolates showed a wide and random distribution in both groups.

Conclusions: MRSA colonization in the studied pediatric community in Jerusalem was very low, whereas that of patients hospitalized in chronic care institutions was significantly higher. In the small number of isolates detected, no significant differences were found in antibiotic susceptibility or PFGE[2] pattern between hospital-acquired and community-acquired strains.

Background: Reperfusion practices have changed markedly over the last few years with the introduction of primary percutaneous coronary intervention. This technique has gained growing popularity in Israel, but little published data are available regarding the delays to primary PCI[1] in real life in this country.

Objectives: To examine temporal trends in time to reperfusion achieved in a large tertiary center over 6 years.

Results: Between 1997 and 2002, 1,031 patients were admitted to our hospital with ST elevation myocardial infarction. Of these, 62% underwent thrombolysis and 38% primary PCI. The proportion of patients referred for primary PCI increased steadily, from 14% in 1997 to 68% in 2002. Door to treatment time among patients referred for thrombolysis or primary PCI was 54 ± 42 and 117 ± 77 minutes, respectively (P < 0.00001). The door to needle time in patients given thrombolysis remained virtually unchanged during the study period at around 54 minutes. In contrast, the door to balloon time has progressively and substantially decreased, from 175 ± 164 minutes in 1997 to 96 ± 52 minutes in 2002.

Conclusions: There is a steady increase in the proportion of patients referred for primary PCI than for thrombolysis. The door to needle delay in patients given thrombolysis substantially exceeds the recommended time. The door to balloon time has declined considerably but still slightly exceeds the recommended time. Given the inherent delay between initiation of lysis and arterial recanalization, it appears from our experience that PCI does not substantially delay arterial reperfusion as compared to thrombolysis. Efforts should continue to minimize delays to reperfusion therapy.

Background: The treatment of osteoporosis among postmenopausal women represents a major public health challenge since long-term therapy is needed to prevent fractures and chronic disability.

Objectives: To assess compliance with osteoporosis drug therapy among Israeli postmenopausal women treated with either a bisphosphonate (alendronate) or a selective estrogen receptor modulator (raloxifene); to identify factors affecting compliance among these patients; and to compare adherence to the treatment in these two groups.

Methods: Our study included 178 consecutive patients aged 67.41 ± 8.52 years who were treated for osteoporosis with alendronate or raloxifene in the Metabolic Bone Diseases Unit. All the patients received supplement with calcium carbonate 1,500 mg and 600 IU vitamin D daily. Compliance was assessed at a clinic visit 6 months after starting therapy.

Results: The dropout rate was 23% (41 patients): 20 patients (31%) in the raloxifene group and 21 (18%) in the alendronate group (P = 0.0041). The main reasons for dropout were side effects and/or non-compliance, 16 and 24 patients (39% and 58.53%), respectively. The most frequent side effect was abdominal pain in 9 patients (42.8%) who discontinued alendronate use. The reasons for non-compliance were a fear of side effects and high drug price in 6 (30%) and 4 (20%) patients respectively in the raloxifene group, and inconvenience caused by medication use in 3 (14.3%) patients in the alendronate group. Logistic regression analysis of factors that may influence compliance included age, previous fractures, family history of osteoporosis, bone density T-score less than -2.5, and presence and number of concomitant diseases. Age was the only statistically significant parameter in this model: 67.8 ± 8.8 in non-compliant versus 64.11 ± 7.4 in compliant patients (P = 0.029).

Conclusion: At least 20% of the patients discontinued chronic treatment for osteoporosis during the initial 6 months of therapy. The main reasons were gastrointestinal side effects in the alendronate group, and fear of side effects and high drug price in the raloxifene group. Older age was the only statistically significant factor influencing compliance.

Background: The humanized SCID mouse model is an attractive tool for testing gene therapy to combat human immunodeficiency virus infection in vivo.

Objectives: To devise a more specific gene therapy directed against HIV, replacing the formerly used interferon with either soluble CD4 molecule immunoadhesin (sCD4-IgG) and/or anti-gp41 monoclonal antibody (2F5), or negative transdominants (Tat, Rev).

Methods: Human monocytoid cell line (U937) was transfected with IFNa[1], b or g genes. 3T3 murine fibroblastic cell line was transfected with sCD4-IgG or 2F5, or both genes, and a human T4 cell line (CEM) was grafted to SCID mice. Negative transdominant genes (Tat, Rev or both) were also transduced in CEM T cell line. Animals were then challenged with HIV-1[2]. Viral load was followed.

Results: IFNa or b were potent anti-HIV, reducing viral load in vivo and inhibiting reverse transcriptase activity in human-removed cells from animals. sCD4-IgG immunoadhesin and gp41 monoclonal antibody resulted in a dramatic reduction of HIV-1 cellular and plasmatic viral load in humanized SCID mice. The simultaneous introduction of negative Tat and Rev genes resulted in a synergistic inhibition of HIV-1 replication in vivo.

Conclusions: Despite the marked reduction of HIV-1 propagation by IFN genes or by negative Tat and Rev transdominants, the gene therapy using soluble CD4 immunoadhesin or anti-gp41 was a more efficient preventive treatment against HIV infection.

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.

The human placenta is the interface between the mother and fetus in the uterus. Until recently it was generally believed that the uterus provides a protective environment for the fetus. It is now accepted that any chemical substance, including any therapeutic agent, administered to a mother is able to permeate across the placental barrier. Unfortunately, the placental transfer of substances and their distribution in the placenta is not well established. Understanding the structure of placental transporters and their function may serve as the ideal tool for drug development and the cure of mother and fetus during pregnancy.