Israel Medical Association Journal

Background: Tumor necrosis factor is associated with various local and systemic inflammatory sequelae following snakebite. Xanthine oxidase is a principal mediator of remote tissue injury (e.g., lungs, heart, liver).

Objective: To investigate in a snakebite-like animal model the as yet unexplored role of TNF and XO in mediating organ damage following snakebite.

Methods: Sprague-Dawley rats were injected intramuscularly with a non-lethal 500 g/kg dose of Vipera aspis venom (n=10) or saline (n=10). Blood pressure and heart rate were continuously monitored, TNF- was measured in the blood, and total XO + xanthine dehydrogenase activity was assessed in various tissues. Lung histology and permeability indices were analyzed.

Results: Venom injection caused a significant (P0.05) reduction in both heart rate and invasive arterial pressure. The blood circulating TNF levels were significantly higher in the intoxicated group (P0.05 vs. saline group), with changes seen at 30 minutes from intoxication in both groups. Total XO + XDH activity in the kidney, lung and liver of the venom-injected group was significantly (P0.05) higher than in the saline group, while the activity in the heart was similar.

Conclusions: The mediation of remote organ and hemodynamic changes following intramuscular injection of a non-lethal dose of Vipera aspis venom can be attributed partly to TNF and partly to XO. More research is needed to better understand the role of either compound and the time frame of their activity before specific antagonists can be introduced for snakebite management.
 

Background: Familial dysautonomia is a genetic disease in which there is a defect in the autonomic and sensory nervous systems. These systems have a major role in the reproductive system.

Objective: To study the inter-relationship of autonomic and sensory dysfunction and gynecological function.

Methods: The gynecological histories of 48 women with familial dysautonomia were analyzed retrospectively. Their mean age was 22.25 years (range 12-47). Thirty-three women (65%) were available for further questioning and investigation of hormonal status.

Results: Menarche had occurred in 32 of the 48 (66.7%). Their average age of menarche was significantly delayed as compared to their unaffected mothers (15.5 vs. 13.6 years respectively, P=0.002). The most prominent finding was the very high prevalence, 81.2%, of premenstrual symptoms. Seven of 26 had premenstrual syndrome symptoms of dysautonomic crisis. Blood sex hormone levels were normal in 27 of the 33 patients studied. None reached natural menopause. One patient had adenomyosis, and another, dysgerminoma. Three patients became pregnant and delivered healthy infants.

Conclusion: Menarche is delayed in women with FD, and the physiological monthly hormonal fluctuations may disturb autonomic homeostasis sufficiently to precipitate dysautonomic crisis.

Background: Uterine rupture is a catastrophic obstetric complication, most often associated with a preexisting cesarean section scar. Although a vaginal birth after a cesarean is considered safe in modern obstetrics, it is not known whether repeated VBACs increase the risk of rupture, or whether the first VBAC proves the strength and durability of the scar, predicting further successful and less risky vaginal deliveries.

Objectives: To evaluate the effect of repeated vaginal deliveries on the risk of uterine rupture in women who have previously delivered by cesarean section.

Methods: In this retrospective study, 26 VBAC deliveries complicated by uterine rupture were matched for age, parity, and gravidity with 66 controls who achieved VBAC without rupture. The histories, demography, pregnancy, labor and delivery records, as well as neonatal outcome were compared.

Results: We found that the risk of rupture decreases dramatically in subsequent VBACs. Of the 40 cases of uterine rupture recorded during the 18 year study period, 26 occurred during VBAC deliveries. Of these, 21 were complicated first VBACs. We also found that the use of prostaglandin-estradiol, instrumental deliveries, and oxytocin had been used significantly more often during deliveries complicated with rupture than in VBAC controls.

Conclusions: Once a woman has achieved VBAC the risk of rupture falls dramatically. The use of oxytocin, PGE2 and instrumental deliveries are additional risk factors for rupture, therefore caution should be exerted regarding their application in the presence of a uterine scar, particularly in the first vaginal birth after cesarean.

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VBAC= vaginal birth after cesarean section

PGE2= prostaglandin-estradiol

Background: Articular cartilage is incapable of undergoing self-repair since chondrocytes lose their mitotic ability as early as the first year of life. Defects in articular cartilage, especially in weight-bearing joints, will predictably deteriorate toward osteoarthritis.  No method has been found to prevent this deterioration. Drilling of the subchondral bone can lead to fibrocartilage formation and temporary repair that slowly degrades. Animal experiments indicate that introducing proliferating chondrocytes such as cultured articular chondrocytes can reliably reconstruct joint defects.

Objectives: To describe our clinical experience in culturing and transplanting autologous chondrocytes. 

Methods: Biopsies were obtained from 10 patients, aged 18–45, undergoing a routine arthroscopy in which a cartilage defect was identified with indications for cartilage transplantation. The biopsies were further processed to establish chondrocyte cultures. ACT was performed in 8 of the 10 patients because of persistent symptoms for at least 2 months post-arthroscopy. All patients (6 men and 2 women) had a grade IV cartilage defect in the medial or lateral femoral condyle, and three had a defect in the trochlear region as well. Biopsies were removed from the lateral rim of the superior aspect of the femur, and cells were cultured in a clean room. Following a 2 order of magnitude expansion, cells were implanted under a periosteal flap.

Results: The eight patients implanted with autologous cells were followed for 6 months to 5 years (average 1 year). Complaints of giving-way, effusion and joint locking resolved in all patients, and pain as assessed by the visual analogue score was reduced by an average of 50%. Follow-up magnetic resonance imaging studies in all patients revealed that the defects were filled with tissue having similar signal characteristics to cartilage.

Conclusions: Chondrocyte implantation is a procedure capable of restoring normal articular cartilage in cases with isolated joint defects. Pain can be predictably reduced, while joint locking and effusion are eliminated. The effect on osteoarthritis progression in humans has not yet been elucidated.

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ACT = autologous chondrocyte transplantation

Background: The course and outcome of appendicitis in the elderly differs from that of the general population. The rates of perforated appendices, error in diagnosis, postoperative complications and mortality may be related to the time lapse between onset of symptoms and admission, and hence delay in surgery.

Objectives: To evaluate if these factors have improved in recent years.

Methods: A retrospective study was carried out of all 61 patients over age 60 who underwent appendectomies in a major metropolitan hospital during 1988-98.

Results: We found that most patients had appendectomies within the first 24 hours of admission and within 3 days of symptoms. Rate of perforation was 43%, error 5.6%, morbidity 41%, and mortality 3.2%.

Conclusions: The high rate of appendix perforation in the elderly is not due to delay. The literature reveals little improvement in the statistics of the disease over the last five decades, despite advances in imaging and surgical technique. This may be explained by the increasing inclusion of octogenarian patients.
 

Objective: To evaluate the contribution of computerized tomography to the diagnosis of Takayasu's arteritis.

Methods: A retrospective analysis of the diagnostic process was recently conducted in three consecutive patients diagnosed over the last 3 years.

Results: Three females of Arab origin with Takayasu's arteritis were recently identified by CT. In two of the three patients the imaging procedure was performed for different working hypotheses, and the radiological findings (wall thickening, perivascular edema, and segmental intraluminal obliteration of the aorta and its major branches) were unexpected. In these two patients, repeated physical examination following the imaging procedure disclosed initially missed findings that could have led to an earlier consideration of Takayasu's arteritis (bruits above the epigastrium, subclavian and carotid arteries, and absent brachial pulses). Retrospective analysis of the patients' symptoms following CT revealed the true nature of the patients' misinterpreted complaints (e.g., typical abdominal angina replaced a faulty obtained history compatible with renal colic or dyspepsia). In the third patient CT was performed for the evaluation of an epigastric bruit associated with constitutional complaints. The diagnosis of aortitis, based upon the presence of diffuse aortic wall thickening and edema of the surrounding fat, without intraluminal narrowing, could have been missed by angiography, the traditional "gold standard" diagnostic procedure. All three patients complained of ill-defined epigastric abdominal pain and had epigastric tenderness during examination.

Conclusions: CT has the potential for detecting Takayasu's disease and may be superior to angiography, particularly at the early non-obliterative stage. Since the diagnosis of Takayasu's disease is rarely considered, the expanding use of CT and MRI technologies may reveal missed cases that are evaluated for other plausible diagnoses. The true incidence of Takayasu's arteritis in Israel may be much higher than reported, particularly in the Arab population. Our findings suggest that epigastric tenderness, originating from active inflammatory reaction in the abdominal aortic wall, should be considered as a diagnostic criterion of Takayasu's aortitis.

Objectives: To report the experience at the first Israeli Linear Accelerator Radiosurgery Unit in the management of 44 patients with acoustic neurinomas.

Methods: We analyzed the clinical records and imaging studies of all patients undergoing radiosurgery for acoustic neurinomas between 1993 and 1997, and quanitified the changes in tumor volume, hearing status, and facial and trigeminal nerve function. The contribution of radiation dose and original tumor volume upon those variables was also studied.

Results: At a mean follow-up of 32 months (range 12–60), 98% of the tumors were controlled (75% had shrunk; 23% had stable volume). The actuarial hearing preservation rate was 71%. New transient facial neuropathy developed in 24% of the patients, persisting in mild degrees in 8%. Neuropathy correlated primarily with tumor volume. Tumors with volumes 4 ml were at high risk when marginal radiation doses were 1,400 cGy. Dose reduction to a maximum of 1,400 cGy produced no neuropathies in the last 20 patients, still preserving tumor control rates.

Conclusions: Radiosurgery is an effective and cost-efficient therapeutic modality for newly diagnosed acoustic neurinomas in the elderly or medically infirm population, and for all residual or recurrent tumors after conventional surgery.