Israel Medical Association Journal

Background: The transfer of therapeutic genes into malignant brain tumors has been the subject of intense pre­clinical and clinical research in recent years. Most approaches have used direct intratumoral placement of a variety of vectors and genes, such as retroviruses or adenoviruses carrying drug-susceptibility genes, modified replication-competent herpes virus, and several vectors carrying tumor suppressor genes such as the p53 gene. However, clinical results have so far been disappointing, mainly due to the limited ability to effectively distribute the genetic material into the target cell population. Accordingly, alternative delivery approaches into the central nervous system, e.g., intravascular, are under investigation. Genetic vectors administered intravascularly are unlikely to penetrate the blood-brain barrier and transfer a gene into brain or tumor parenchyma. However, intravascular delivery of vectors may target endothelial cells lining the blood vessels of the brain. Since endothetial cells participate in a variety of physiological and pathological processes in the brain, their modulation by gene transfer may be used for a variety of therapeutic purposes. Angiogenically stimulated endothelial cells within tumors replicate rapidly and hence may become targets for retroviral-mediated gene transfer.

Objective: To assess the anti-tumor effect of transferring a drug-susceptibility gene into endothelial cells of the tumor vasculature.

Methods: As a model for this approach we delivered concentrated retroviral vectors carrying a drug-susceptibility gene via the internal carotid artery of rats with malignant brain tumors. The safety and efficacy of this approach, without and with subsequent treatment with a pro-drug (ganciclovir). was evaluated.

Results: No acute or long-term toxicity was observed after intraarterial infusion of the vector. Treatment with ganciclovir resulted in variable hemorrhagic necrosis of tumors, indicating preferential transduction of the angiogenically stimulated tumor vasculature. This was accompanied by severe toxicity caused by subarachnoid hemorrhage and intracerebral hemorrhage in vascular territories shared by the tumor and adjacent brain.

Conclusion: The data indicate that endothelial cells can be targeted by intraarterial delivery of retroviral vectors and can be used for devising new gene therapy strategies for the treatment of brain tumors.

Background: Balneotherapy has been successfully used to treat various rheumatic diseases, but has only recently been evaluated for the treatment of fibromyalgia. Since no effective treatment exists for this common rheumatic disease, comple­mentary methods of treatment have been attempted.

Objectives:To assess the effectiveness of batneotherapy at the Dead Sea area in the treatment of patients suffering from both fibromyalgia and psoriatic arthritis.

Methods: Twenty-eight patients with psoriatic arthritis and fibromyalgia were treated with various modalities of bat­neotherapy at the Dead Sea area. Clinical indices assessed were duration of morning stiffness, number of active joints, a point count of 18 fibrositic tender points, and determination of the threshold of tenderness in nine fibrositic and in four control points using a dolorimeter.

Results: The number of active joints was reduced from 18.4+10.9 to 9+8.2 (P< 0.001). The number of tender points was reduced from 12.6+2 to 7.1±5 in men (P<0.003) and from 13.1+2 to 7.5+3.7 in women (P<0.001). A significant improvement was found in dolorimetric threshold readings after the treatment period in women (P< 0.001). No correlation was observed between the reduction in the number of active joints and the reduction in the number of tender points in the same patients (r= 0.2).

Conclusions: Balneotherapy at the Dead Sea area appears to produce a statistically significant substantial improvement in the number of active joints and tender points in both male and female patients with fibromyalgia and psoriatic arthritis. Further research is needed to elucidate the distinction between the benefits of staying at the Dead Sea area without balneotherapy and the effects of balneotherapy in the study population.

Background: Narcotic abuse has steadily become more prevalent in Israel and may result in an increasing number of children exposed prenatally to narcotics, with a consequent increase in the number of infants born with neonatal abstinence syndrome.

Objective: To report our experience with infants born to narcotic-addicted women between the years 1995 and 1998 at the Soroka University Medical Center.

Methods: The medical records of 24 newborns and their drug-addicted mothers admitted to our Medical Center for parturition were analyzed retrospectively. A diagnosis of NAS was established on the basis of the clinical presentation and anamnesis. The Finnegan Neonatal Abstinence Scoring System was used to assess drug withdrawal. Urine toxicological analysis for narcotics was done only for year 1998.

Results: Of the 24 newborn infants exposed prenatally to narcotics 23 (96%) developed NAS, and 78% (18 of the 23) had a Finnegan score of 8 or more. These 18 infants were treated pharmacologically (tincture of opium and/or Phenobarbital) until the score was reduced to less than 8, after which they received supportive treatment. In one child who became lethargic after the first dose of tincture of opium, the medication was stopped and supportive treatment alone was given. Four of the five neonates with scores of 7 and less were given supportive treatment. One of five infants who had a low Finnegan score at birth nevertheless received pharmacological therapy to prevent further deterioration of his physical state since he was born with severe dyspnea. Ten of the 24 children (42%) were followed for lengths of time ranging from 6 to 22 months after discharge, all of whom showed normal development.

Conclusion: About three-quarters of newborns exhibiting withdrawal syndrome required pharmacological therapy. Previous information on maternal drug abuse is a crucial criterion for early detection and treatment.
 

Background: Proximal femur fractures represent a challenging medical problem worldwide. In recent years numerous reports have documented. a progressive increase in the incidence of hip fractures. In Jordan, this problem has not received sufficient attention, and to my knowledge, this is the first study to address the problem.

Objective: To analyze the predisposing factors involved in the occurrence of proximal femur fractures seen at a major medical center in Jordan.

Methods: A retrospective analysis was conducts of all patient admitted with hip fractures to King Hussein Hospital and the Royal Jordanian Rehabilitation Center at the King Hussein Medical Center over a 2 year period (1 January 1995 to 31 December 1996). We determined the associated chronic diseases and medications, mechanisms of injury, types of fractures and other circumstances in order to suggest preventive measures to decrease the incidence of this clinical problem.

Results: We identified 216 cases of fracture: 43% occurred in people over the age of 80 years, 95% were due to low energy injuries (falls), and 69.5% occurred in females. Two or more co-morbid medical conditions were present in 70% of the cases.

Conclusion: Since fractures of the hip in the study population in Jordan occurred predominantly as low energy injuries in the elderly, preventive measures should focus on fall avoidance.
 

Objective: To investigate the clinical, laboratory and radiological findings of the disease.

Methods: During the years 1995-88 five patients with primary epiploic appendigitis were diagnosed at our institution. The clinical, laboratory and imaging results were summarized and compared to previously reported series. Emphasis was placed on the computed tomography findings, which are the gold standard for diagnosis.

Results: All our patients (two males and three females, mean age 47 years) presented with left lower quadrant abdominal pain. CT proved to be the imaging modality of choice in all patients by showing a pericolic fatty mass with an increased attenuation as compared to normal abdominal fat. In all cases the mass was surrounded by a high attenuation rim, and focal stranding of the fat was observed. In no case was there thickening of the adjacent bowel wall. This serves as an important, and previously unreported, clue for diagnosis.

Conclusion: Primary epiploic appendagitis is a relatively rare condition that may be clinically misdiagnosed, resulting in unnecessary surgical intervention. Judicious interpretation of CT may lead to early diagnosis and ensure proper conservative treatment.

Background: The frequent coexistence of two or more sexually transmitted diseases in one patient has been reported in non-dermatological literature, mostly in languages other than English. Identification of Ureaplasma urealyticum, Chlamydia trachomatis and Mycoplasma hominis in men with other STDs is important, since these bacteria have been implicated in a variety of diseases such as non-gonococcal urethritis, premature rupture of fetal membranes, and infertility in female sexual partners of these patients.

Objective: To assess the frequency of concomitant STD, particularly urethral colonization of U. urealyticum, C. trachomatis and M. hominis, in men consulting for suspected STD-related symptoms.

Methods: All patients attending our dermatology clinic for STD-related symptoms during a 12 month period in 1996–97 underwent systematic clinical and laboratory screening for syphilis, gonorrhea, NGU, prostatitis, genital herpes simplex infection, Condyloma acuminatum, urethral carriage of U. urealyticum, C. trachomatis and M. hominis, as well as serological screening for HIV, and hepatitis B and C infections.

Results: A total of 169 men with STD-related symptoms were enrolled in the study. The following clinical diagnoses were established: NGU in 109 men, C. acuminatum in 40, genital herpes simplex in 10, prostatitis in 7, latent syphilis in 6, primary syphilis in 1, and Behcet’s disease in 1. No clinical evidence of STD was found in 13 patients. Of the 169 patients, 39 (23%) had two or more concomitant STDs, of whom 27 (69%) had C. acuminatum associated with one or more of the urethral pathogens. A positive U. urealyticum culture was found in 67.5% (27/40) of the men with C. acuminatum as compared to 42% (40/96) among the patients with NGU who did not have C. acuminatum (P=0.004, X² test). Conversely, the prevalence of C. acuminatum among patients positive for U. urealyticum was significantly higher than the prevalence among those who were negative – 27/75 (36%) vs. 13/94 (14%), P<0.0009, X² test. About half of the U. urealyticum-positive patients with C. acuminatum had no clinical signs or symptoms of urethritis.

Conclusion: Our findings suggest that patients with C. acuminatum should be assessed for U. urealyticum carriage and, when identified, their sexual contacts should be actively sought and treated.

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* Dr. Zvulunov is now with the Department of Pediatrics, Joseftal Hospital, Eilat, Israel.

STDs = sexually transmitted diseases

NGU = non-gonococcal urethritis

Background: A previous study on Hodgkin's lymphoma in southern Israel found that Bedouin patients had an increased rate of Epstein-Barr virus expression in their tumor cells.

Objectives: To determine the influence of the patients' communities on the pattern of disease in HL.

Methods: We compared the clinical features, demographic data, stage at diagnosis, treatment modality and outcome, as well as laboratory findings, in four community-based subgroups. These groups comprised kibbutz residents (n=11), Bedouin (n=19), new immigrants from the former USSR (n=22), and town-dwellers (n=82).

Results: The Bedouin patients differed significantly from the new immigrants and town-dwellers, particularly regarding the rate of EBV sequences in the tumor tissues, and a poorer response to treatment. The kibbutz patients did not differ significantly from the other populations regarding most of the parameters studied, but showed an intermediate expression of EBV antigens compared to Bedouin patients and the rest of the cohort.

Conclusions: This study indicates that HL may behave differently in different population groups in a given geographic area. Notably, the Bedouin patients showed markedly different clinical and biological patterns of this malignancy. 

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HL= Hodgkin's lymphoma

EBV= Epstein-Barr virus