Israel Medical Association Journal

Background: Coronary stenting was recently introduced as a primary intervention for acute myocardial infarction. Several randomized controlled studies have shown that stenting may be superior to balloon angioplasty for the treatment of AMI[1]. However, routine stenting may also cause deterioration of coronary flow.

Objective: To analyze the clinical characteristics and the outcome of patients who were treated with stenting for AMI in our center in the recent era of stenting.

Methods: Fifty-five patients with AMI were treated by stent implantation between January 1998 and December 1999. Adverse clinical events were recorded, including death, recurrent infarction, coronary artery bypass grafting, cerebrovascular accident, and target vessel revascularization. In-hospital, 1 month, 6 month and 1 year follow-up was performed in all patients. Repeated coronary angiography was performed according to clinical indications.

Results: Baseline angiographic results showed Thrombolysis in Myocardial Infarction (TIMI) 0 flow in 39 patients (70.9%), TIMI I flow in no patient and TIMI II/III flow in 16 patients (29.1%). TIMI grade 3 flow was achieved in 90.9% of patients at the end of the procedure. In-hospital mortality rate was 5.4% (2.1% in patients without cardiogenic shock). There was no evidence of re-infarction or TVR[2]. The rates of bleeding complication (all of them minor), CVA[3], and CABG[4] were 9.1%, 3.6% and 1.8% respectively. The 6 month mortality rate remained the same. Rates of re-infarction, restenosis, TVR and CABG were 3.6%, 14.5%, 14.5% and 5.4% respectively. The 1 year mortality rate was 7.3%. Restenosis rate was 18% and CABG 7.3%. One year event-free survival was 70.9%.

Conclusions: This study suggests that stenting is a safe and effective mode of therapy in the setting of AMI associated with a high rate of revascularization and a low short and long-term outcome.

Background: Non-gonococcal urethritis is the most common clinical diagnosis for men seeking care at sexually transmitted disease clinics.

Objective: To identify the pathogens involved in NGU[1] among males attending an Israeli STD clinic.

Methods: During 19 months spanning September 1996 to July 1998 we investigated a cohort of 238 male patients attending the Bnai Zion Medical Center STD[2] clinic with a clinical presentation of urethritis. Intraurethral swab specimens were tested for Neisseria gonorrhea, Ureaplasma urealyticum, Mycoplasma hominis, and Trichomonas vaginalis by culture and for herpes simplex virus by antigen detection. First voiding urine for Chlamydia trachomatis was done by polymerase chain reaction. The specific seropositivities of HSV[3] types 1 and 2 were tested by enzyme-linked immunosorbent assay.

Results: From among 238 males with dysuria or urethral discharge an etiology for urethritis was found for 71 (29.8%). N. gonorrhea was recovered in only three men (4.2%). In the remaining 68 NGU patients C. trachomatis (35/68, 51.5%) and U. urealyticum (31/68, 45.6%) were the most common infecting and co-infecting pathogens (P < 0.0001). M. hominis and T. vaginalis were found in 9/68 (13.2%), and 1 patient, respectively. HSV was recovered from the urethra in 7/68 males (10.3%) – 3 with HSV-1, 2 with HSV-2, and 2 were seronegative for HSV. None of these males had genital lesions. Although a single etiologic agent was identified in 45/68 infected men (66.2%), co-infection was common: 2 organisms in 15 (22%) and 3 organisms in 8 (11.8%).

Conclusion: C. trachomatis and U. urealyticum were the most common infecting and co-infecting pathogens in this cohort of men with NGU. Unrecognized genital HSV infections are common in males attending our STD clinic and symptomatic shedding of HSV occurs without genital lesions. Still, the microbial etiology in this group remains unclear in many patients despite careful microbiologic evaluation.

Background: Experimental and clinical protocols are being developed for the cryopreservation of human hematopoietic progenitor cells. However, the effect of these procedures on the potential for HPC[1] to repopulate bone marrow is unknown.

Objectives: To examine the effect of cryopreservation on the ability of fetal human liver HPC, which include CD34+ cells and long-term culture-initiating cells, to repopulate immunodeficient non-obese diabetic/severe combined immunodeficiency mouse bone marrow.

Methods: Groups of sublethally irradiated NOD[2]/SCID[3] mice were injected intravenously with cryopreserved or freshly isolated fetal human liver HPC.

Results: Seven weeks after transplantation, flow cytometric analysis of bone marrow samples showed that mice that received the transplanted cells (either cryopreserved or freshly isolated) demonstrated both lymphoid and myeloid differentiation as well as the retention of a significant fraction of CD34+ cells. Conclusions: Cryopreserved fetal human liver-derived HPC appear to be capable of initiating human cell engraftment in NOD/SCID mouse bone marrow and open the possibility of using cryopreserved fetal human liver HPC for gene manipulation, gene transfusion therapy, and transplantation purposes.

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[1] HPC = hematopoietic progenitor cells

[2] NOD = non-obese diabetic

[3] SCID = severe combined immunodeficiency

Background: The prevalence of traumatic hyphema as well as the distribution of its severity varies between different patient populations. Treatment recommendations in the literature differ significantly among various published reports. This lack of a uniformly accepted treatment probably reflects the different characteristics of this pathology among the populations investigated and calls for a population-adjusted treatment recommendation.

Objectives: To report the characteristics and functional outcome of patients with traumatic hyphema and to discuss possible recommendations regarding the use of ε‑aminocaproic acid.

Methods: A prospective, non-randomized study was conducted among 154 consecutive patients with traumatic hyphema, including data collection of ophthalmic status at various time points, the presence or absence of secondary hemorrhage, and final visual acuity.

Results: Of the 154 eyes studied over 3½ years, nearly 90% had hyphema of grade 1 or less, 3 (3.25%) experienced rebleeding, and 2 (1.3%) – neither of which rebled – needed surgical intervention. None of the four patients who experienced final visual acuity of 6/40 or less suffered rebleeding.

Conclusion: The use of ε‑aminocaproic acid in the studied population was unjustified and routine use of e-aminocaproic acid in our patient population is probably not indicated. A treatment policy regarding e-aminocaproic acid use should be adjusted to the population being treated.

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

Background: Cigarette smoking is a well-known risk factor for the development of endothelial dysfunction and the progression of atherosclerosis. Oxidative stress and inflammation have recently been implicated in endothelial dysfunction.

Objectives: To assess the concomitant contribution of polymorphonuclear leukocytes to systemic oxidative stress and inflammation in cigarette smokers.

Methods: The study group comprised 41 chronic cigarette-smoking, otherwise healthy males aged 45.0 ± 11.5 (range 31–67 years) and 41 male non-smokers aged 42.6 ± 11.3 (range 31–65) who served as the control group. The potential generation of oxidative stress was assessed by measuring the rate of superoxide release from separated, phorbol 12-myristate 13-acetate-stimulated PMNL[1] and by plasma levels of reduced (GSH) and oxidized (GSSG) glutathione. Inflammation was estimated indirectly by: a) determining the in vitro survival of PMNL, reflecting cell necrosis; b) in vivo peripheral PMNL counts, reflecting cell recruitment; and c) plasma alkaline phosphatase levels, indicating PMNL activation and degranulation.

Results: PMA[2]-stimulated PMNL from cigarette smokers released superoxide at a faster rate than PMNL from the controls. Smokers had decreased plasma GSH[3] and elevated GSSG[4] levels. In vitro incubation of control and smokers' PMNL in sera of smokers caused necrosis, while control sera improved smoker PMNL survival. Smokers' PMNL counts, although in the normal range, were significantly higher than those of controls. Plasma ALP[5] levels in smokers were significantly higher than in controls and correlated positively with superoxide release and PMNL counts.

Conclusions: Our study shows that PMNL in smokers are primed in vivo, contributing concomitantly to systemic oxidative stress and inflammation that predispose smokers to endothelial dysfunction, and explains in part the accelerated atherosclerosis found in smokers.

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[1] PMNL = polymorphonuclear leukocytes

[2] PMA = phorbol 12-myristate 13-acetate

[3] GSH = reduced glutathione

[4] GSSG = oxidized glutathione

[5] ALP = alkaline phosphatase

Background: Genes that confer mild or moderate susceptibility to breast cancer may be involved in the pathogenesis of sporadic breast cancer, modifying the phenotypic expression of mutant BRCA1/BRCA2 alleles. An attractive candidate is the insulin-like growth factor I, a known mitogen to mammary ductal cells in vivo and in vitro, whose serum levels were reportedly elevated in breast cancer patients.

Objective: To evaluate the contribution of the IGF-1 gene polymorphism to breast cancer risk by genotyping for a polymorphic allele size in breast cancer patients and controls.

Methods: We analyzed allele size distribution of the polymorphic CA repeat upstream of the IGF-I gene in 412 Israeli Jewish women: 268 women with breast cancer (212-sporadic and 56 carriers of either a BRCA1:or BRCA2 mutation), and 144 controls. Genotyping was accomplished by radioactive polymerase chain reaction of the relevant genomic region and size fractionation on polyacrylamide gels with subsequent auloradiography,

Results: Among women with breast cancer, with or without BRCA germline mutations, 196 and 198 basepair alleles were present in 4.7% (25/536 alleles), compared with 9% (26/288) controls (P = 0.02). This difference was more pronounced and significant in the non-Ashkenazi population. Conversely, the smaller size allele (176 bp) was present in the breast cancer group only {3/536, 0.6%).

Conclusions: The IGF-I polymorphism may serve as a marker for breast cancer risk in the general Jewish population, in particular non-Ashkenazi Jews, but extension and confirmation of these preliminary data are needed.
 

Background: Although Listeria monocytogenes is widely distributed in nature, it rarely causes clinical infection in previously healthy people. This microorganism. however, may cause severe invasive disease in pregnant women and newborns.

Objectives: To investigate – in our pregnant population – the impact, severity and outcome of listeriosis on both mother and fetus.

Method: The study was carried out at a level III, university two-hospital complex, In a retrospective chart review of 65,022 parturients during a 10 year period (1990-1999), we identified and: evaluated 11 pregnant patients and their offspring with Listeria infection;

Results: Chorioamnionitis with multiple. placental abscesses were observed in all five placentae examined. Clinically 4 of 11 parturients had a cesarean section for fetal distress (36.3%), as compared to the 14% mean CS rate in our general population. Two of 11 had a fate abortion (18.1%), as compared with the 4% rate in our hospital. Four of 11 had premature labor (36%), which was about four times the rate in our population. Finally, although no intrauterine feta1 death was recorded in our series, there was one neonatal death of a term infant. (1/11, 9%), which is about 10 times higher than our corrected perinatal mortality rate.

Conclusions: If not promptly and adequately treated, listeriosis in pregnancy may present serious hazards to the fetus and newborn through direct infection-of the placenta and chorioamnionitis.