Israel Medical Association Journal

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: The number of child adoptions from abroad is increasing, but the adverse living conditions of these children prior to the adoption raise questions on their medical and neurodevelopmental status, particularly since there are no guidelines for pre- or post-adoption medical evaluation.

Objectives: To describe the condition of a cohort of young children who were candidates for adoption in East European orphanages and foster homes, and to determine those attributes associated with a family's decision to adopt or refuse a particular child.

Methods: Eighty-two young children, median age 11 months, were evaluated by Israeli pediatricians in Eastern Europe between 3 weeks and 6 months prior to their adoption. The evaluation consisted of comprehensive medical and neurodevelopmental testing on site using a battery of standardized assessment tools, and observation of free play and social interactive behaviors recorded on videotape. Laboratory tests included complete blood count, chemistries, serology screening, and metabolic and genetic testing.

Results: The children were growth-retarded. Medical problems were classified as resolved (pneumonia and diarrhea) in 32.8%; or ongoing, such as hepatitis B and (3, failure to thrive, organomegaly, and visual and hearing disorders, in 14.8%. Neuromotor status was grossly abnormal in 13.4%. Twenty-two percent of the children were rejected for adoption by families in Israel. Factors associated with the adoption decision were performance skills on developmental testing (P = 0.0001), present medical status (P = 0.002), and weight )P = 0.016(.

Conclusions: Pre-placement comprehensive screening of children eligible for foreign adoption, which includes developmental screening, helps to identify a wide variety of strengths and impairments in a child's background before the adoption procedure is finalized. A family's decision to adopt or not was associated with the child's performance on Bayley Scales, weight, and current medical status, but not with language delays, serious past medical history or suspect family background.
 

Background: Dizziness and vertigo can be a complaint in various psychiatric conditions, where it usually constitutes only one of the features of the syndrome. Lately, a somatoform disorder characterized by almost mono-symptomatic dizziness and unsteadiness has been described. Since phobic postural vertigo usually presents without anxiety or other psychological symptomatology, patients with this condition seek help at neurologic and otolaryngologic clinics where they are often misdiagnosed as suffering from organic vertigo.

Objectives: To present the clinical features of 55 consecutive patients diagnosed with phobic postural vertigo at our clinic during 1998–2002.

Methods: We conducted a retrospective review of patients’ medical records and report two typical cases as illustration.

Results: The patients presented with complaints of unsteadiness with or without dizziness, and attacks of sudden veering that caused them to grasp for support. Accompanying anxiety was admitted by only 5% and vegetative symptoms were reported in 18%. In 16% the symptoms resulted in avoidance behavior. A stressful life event or an unrelated somatic disease triggered the onset of PPV[1] in 35% of patients, whereas a vestibular insult preceded the symptoms in 13%. The mean duration of symptoms was 26.7 ± 39.1 months (range 0.5–20 years). In 72% of patients the symptoms resolved after the psychological mechanism of their symptoms were explained to them; 24% improved with antidepressant treatment (selective serotonin reuptake inhibitors or tricyclic antidepressants), and only in 4% did the symptoms persist.

Conclusions: Since PPV is a frequently encountered diagnosis at some specialized dizziness clinics, familiarity with this entity resulting in early diagnosis can avoid unnecessary examinations and lead to effective treatment.

Background: The precise genes involved in conferring prostate cancer risk in sporadic and familial cases are not fully known.

Objectives: To evlauate the genetic profile within several candidate genes of unselected prostate cancer cases and to correlate this profile with disease parameters.

Methods: Jewish Israeli prostate cancer patients (n=224) were genotyped for polymorphisms within candidate genes: p53, ER, VDR, GSTT1, CYP1A1, GSTP1, GSTM1, EPHX and HPC2/ELAC2, followed by analysis of the genotype with relevant clinical and pathologic parameters.

Results: The EPHX gene His113 allele was detected in 21.4% (33/154) of patients in whom disease was diagnosed above 61 years, compared with 5.7% (4/70) in earlier onset disease (P < 0.001). Within the group of late-onset disease, the same allele was noted in 5.5% (2/36) with grade I tumors compared with 18% (34/188) with grade II and up (P = 0.004). All other tested polymorphisms were not associated with a distinct clinical or pathologic feature in a statistically significant manner.

Conclusions: In Israeli prostate cancer patients, the EPHX His113 allele is seemingly associated with a more advanced, late-onset disease. These preliminary data need to be confirmed by a larger and more ethnically diverse study.

Background:  One of the major reasons for the shortage of organs for transplantation in Israel is the failure to identify potential donors. According to the World Health Organization, the expected number of potential donors in Israel is 300 per year. In recent years an average of only 200 donors (2/3) has been identified.

Objective: To identify the reasons for the gap between the potential and the actual number of organ donors.

Methods: We reviewed the medical records of all potential donors at the Soroka University Medical Center between October 1997 through September 1999.

Results: The total of 183 death records was consistent with the minimal inclusion criteria for potential organ donation, of which 41 were suspected to be potential brain death (PBD) In 31 cases an ad hoc committee had declared brain death, and the patients were evaluated for organ donation. However, in 10 cases no committee was formed. We found that 24.4% (10/41) of the potential donors had not been designated as such by their medical team.

Conclusion: We believe that a comprehensive education program for medical and nursing staff might increase awareness for organ donation and may eliminate the gap between the potential and actual number of organ donors.

Background: Recent advances in immunosuppressive therapy have led to a substantial improvement in the outcome of kidney transplantation. Living unrelated donors may become a source of additional organs for patients on the kidney waiting list.

Objectives: To study the impact of combination of calcineurin inhibitors and mycophenolate-mofetile, together with steroids, on outcomes of living related and unrelated transplants. 

Methods: Between September 1997 and January 2000, 129 patients underwent living related (n=80) or unrelated (n=49) kidney transplant. The mean follow-up was 28.2 months. Immunosuppressive protocols consisted of MMF[1] with cyclosporine (41%) or tacrolimus (59%), plus steroids. Patient and graft survival data, rejection rate, and graft functional parameters were compared between the groups.

Results: LUD[2] recipients were older (47.8 vs. 33.6 years) with higher number of re-transplants (24.5% vs. 11.2% in LRD[3] recipients, P < 0.05). Human leukocyte antigen matching was higher in LRD recipients (P < 0.001). Acute rejection developed in 28.6% of LUD and 27.5% of LRD transplants (P = NS). Creatinine levels at 1, 2 and 3 years post-transplant were 1.6, 1.7 and 1.7 mg/dl for LRD patients and 1.5, 1.5 and 1.3 mg/dl for LUD recipients (P = NS). There was no difference in patient survival rates between the groups. One, 2 and 3 year graft survival rates were similar in LRD (91.3%, 90% and 87.5%) and LUD (89.8%, 87.8% and 87.8%) recipients.

Conclusions: Despite HLA[4] disparity, rejection and survival rates of living unrelated transplants under current immunosuppressive protocols are comparable to those of living related transplants.

Background: Vaginal symptoms are a leading reason for a patient to visit her gynecologist. Little is known about the prevalence of the different causes of vaginitis and the risk factors for this entity in Israel.

Objective: To determine the prevalence in a gynecologic practice in Israel of the main forms of vaginitis: vulvovaginal candidiasis, bacterial vaginosis, and trichomoniasis.

Methods: We evaluated 208 patients presenting with vaginal symptoms to a gynecologic clinic; 100 asymptomatic women who attended the clinic for routine check-up served as controls. Demographic, medical and gynecologic histories were obtained, and a pelvic examination was performed in all patients. Vaginal specimens were tested for pH and amine reaction, smeared for Gram-staining and cultured for yeasts and Trichomonas vaginalis. Bacterial vaginitis was diagnosed using the Nugent scoring system. candida infection was diagnosed by microscopic examination and by culture.

Results: Candida spp. was the most common pathogen, documented by microscopy and culture in 35.5% of symptomatic women and 15% of asymptomatic controls (P < 0.001). Detection by culture only (negative microscopy) was documented in 18.7% of symptomatic patients and 15% of controls (P = 0.5). Bacterial vaginosis (Nugent score ≥ 7) was diagnosed in 23.5% of patients and 13% of controls (P = 0.04). Trichomoniasis was present in 8.1% of symptomatic women and 4% of controls (P = 0.1). The main risk factors were antibiotic use for candidiasis and lack of use of oral contraception and condom use for trichomoniasis.

Conclusion: Candida was by far the most common pathogen detected in our population. A statistically significant difference between patients and controls was noted for the prevalence of microscopically diagnosed candidiasis and bacterial vaginosis.
 

Background: Acute myocardial infarction is rare in people under the age of 30.

Objective: To determine the clinical features and outcome in young patients presenting with AMI.

Methods: All patients aged 30 years and younger hospitalized with AMI during a period of 8 years (1993–2000) were evaluated for clinical features and outcome.

Results: Of the 3,758 patients with AMI, 15 were 30 years old or younger (0.4%). The mean age was 28 (range 21–30 years) and all were male. Eight had normal coronary arteries on angiogram; seven had obstructive coronary artery disease. Patients with OCA[1] had more classical risk factors for coronary disease. A complete diagnostic work-up was abnormal in four patients with NCA[2]: thrombophilia in two patients, spasm due to alcohol withdrawal and hyperthyroidism in one patient each. All patients presented with typical new-onset chest pain. None had a previous history of angina. All patients with OCA received reperfusion therapy as compared to one patient with NCA. Peak creatine phosphokinase in NCA and OCA was 504 ± 547 and 1,328 ± 440 respectively (P < 0.01). All patients with NCA had good left ventricular function on follow-up echocardiography, compared to only three in the OCA group (P = 0.02). There was one death due to cardiogenic shock in a patient with OCA. Follow-up of 4 ± 2 years demonstrated recurrent acute coronary syndromes in four of seven patients with OCA versus none in the NCA patients (P = 0.02).

Conclusions: AMI is rare in very young patients, and more than half have NCA. A thrombophilic tendency or spasm should be considered. Young patients with NCA have an excellent prognosis.