Israel Medical Association Journal

Background: Both diagnostic and therapeutic options in the management of iatrogenic false aneurysms have changed dramatically in the last decade, with surgery being required only rarely.

Objective: To describe our experience, techniques and results in treating pseudoaneurysms at a large medical center with frequent arterial interventions. We emphasize upper limb lesions.

Materials and Methods: We reviewed the data of all consecutive patients diagnosed by color-coded duplex Doppler between August 1992 and July 1998 as having upper limb and lower limb pseudoaneurysms (mainly post- catheterization). We accumulated 107 false aneurysms (mainly post- catheterization lesions): 5 were upper limb lesions and 102 were groin aneurysms.

Results: In the lower limb cases 94 of the 102 lesions were not operated upon (92.1%). Seventy lower limb cases were treated non-operatively by ultrasound-guided compression obliteration with a 95.7% success rate (67 cases). Two cases were treated by  percutaneous thrombin injection (2%) and 23 by observation only (22.5%). Altogether 12 patients underwent surgery (11.2%): 4 upper extremity and 8 lower extremity cases. None of the lower limb group suffered serious complications regardless of treatment, but all five upper limb cases did, four of them necessitating surgical intervention. Three of the five upper limb cases had a grave outcome with severe or permanent or neurological damage.

Conclusion: Most post- catheterization pseudoaneurysms can be managed non-surgically. False aneurysms in the upper extremity are rare, comprising less than 2% of all lesions. However, upper extremity pseudoaneurysms present a potentially more serious complication and require early diagnosis and prompt intervention to minimize the high complication rate and serious long-term sequelae. Prevention can be achieved by proper puncture technique and site selection, and correct post-procedure hemostatic compression with or without an external device. Some upper limb lesions are avoidable if the axillary artery is not punctured.
 

Background: inflammation is an important feature of atherosclerotic lesions and increased production of the actuephase reactant. The contribution of coagulation factor to the development of coronary artery disease has not yet been clearly established.

Objective: To test whether C-reactive protein, fibrinogen and antithrombin-III are associated with angiograpic CAD, history of myocardial infarction and extensive atherosclerotic involvement.

Methods: Blood samples were tested for CRP, fibrinogen and AT-III levels from 219 individuals undergoing coronary angiography.

Results: CRP was higher in patients with CAD (0.95 + 1.31, n=180, vs. 0.39 + 0.61 mg/dl, n=39, P<0.0001) and in those with a history of MI (1.07 + 1.64, n=96, vs. 0.65 + 0.72 mg/dl, n=84, P<0.05) than in control subjects. The patients who developed unstable angina had higher CRP levels than the patients with stable CAD (2.07 + 2/38, n=7, vs. 0.80 + 1.13 mg/dl, n=173, P<0.001).

Fibrinogen was significantly higher in patients with CAD (298 + 108 vs. 258 + 63 mg/dl, P<0.01). In patients with CAD, mean AT-III value was less than in patients without CAD, but this difference was found in CRP, fibrinogen and AT-III values among the patients with single, double or triple vessel disease.

Conclusion: CRP is elevated in patients with CAD and a history of MI. Elevated levels of CRP at the time of hospital admission is a predictive value for future ischemic events.

There is an association between higher levels of fibrinogen and CAD. The association of AT-III levels with CAD needs testing in further studies.
 

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: A high rate of consanguineous marriages exists within the Israeli Arab community, with approximately half occurring between first cousins. This contributes towards a high incidence of congenital malformations and autosomal recessive diseases, many of which are detectable at prenatal diagnosis.

Objectives: To assess the levels of both awareness and acceptance regarding prenatal diagnosis and termination of pregnancy among a group of Arab women in order to devise the optimal means of providing genetic counseling and general health services.

Methods: A total of 231 Arab women of childbearing age were interviewed 3 days postpartum to assess their knowledge of prenatal diagnosis and termination of pregnancy, their willingness to undergo prenatal diagnosis, and their opinions on termination of pregnancy in the event of a severely affected fetus.

Results: Half the women believed that prenatal testing is not an effective (or accurate) tool for diagnosing an affected fetus. A quarter had poor knowledge on prenatal diagnosis, and a quarter believed that prenatal diagnosis does provide the correct diagnosis. Ninety-five percent said they would agree to undergo prenatal diagnosis; and in the event of a severely affected fetus, 36% said they would agree to a termination of pregnancy, 57% said they would not, and 7% were undecided.

Conclusions: There is a need for special intervention programs, with guidance by health professionals, geneticists and religious authorities, that will inform this population on the increased risk associated with consanguinity, stress the importance and effectiveness of prenatal testing to identify severe congenital malformations, and help them to accept prenatal diagnosis and termination of pregnancy if indicated.

Background: Exposure of newborn animals to high concentrations of oxygen leads to diffuse alveolar damage similar to that seen in bronchopulmonary dysplasia in human infants. Therefore, neonatal rats are a suitable practical model of hyperoxic lung damage in human infants.

Objective: To determine the involvement of tumor necrosis factor-alpha and interleukin-6 in lung injury in neonatal rats exposed to 100% O2 concentration.

Methods: A randomized controlled study was designed in which litters of term Sprague-Dawley rat pups were assigned to experimental or control groups. The pups in the experimental group were placed in 100% O2 from birth for 9 days, while the control pups were placed in room air. Twelve to 15 pups from each group were sacrificed on day 1, 3, 6, 9 and 13 after birth for bronchoalveolar lavage collection and lung histologic study. The bronchoalveolar lavage fluid was assayed for TNFα and IL-6.

Results: Newborn rats exposed to 100% O2 for the first 9 days of life showed severe pulmonary edema and hypercellularity on days 1 and 3, which then improved to nearly complete resolution on days 6 and 9. Pulmonary TNFα was produced early on O2 exposure (day 3) and pulmonary IL-6 later (days 6 and 9).

Conclusions: Hyperoxia induces sequential production of pulmonary TNFα and IL-6, which corresponds to the severity of the pathological findings and the known inflammatory and anti-inflammatory role of these cytokines.

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TNFα= tumor necrosis factor-alpha

IL-6= interleukin-6

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: Spectral analysis of heart rate variability has been shown to be a reliable non-invasive test for quantitative assessment of cardiovascular autonomic regulatory responses, providing a window reflecting the interaction of sympathetic and parasympathetic tone. Alterations in autonomic function are associated with a variety of physiologic and pathophysiologic processes and may contribute substantially to morbidity and mortality. Our previous study shows that patients with post-traumatic stress disorder have significantly lower HRV compared to controls, reflecting a basal autonomic state characterized by increased sympathetic and decreased parasympathetic tone.

Objectives: To apply this tool to PTSD patients treated with selective serotonin re-uptake inhibitors in order to assess the impact of such treatment on the autonomic dysregulation characterizing these patients.

Methods: Standardized heart rate analysis was carried out in nine PTSD patients treated with SSRI agents and compared to that in a matched control group of nine healthy volunteers and in nine untreated PTSD patients, based on a 15 minute resting electrocardiogram.

Results: Our preliminary results show that the HRV parameters indicating autonomic dysregulation, which characterize PTSD patients at rest, are normalized in responding patients by use of SSRIs. Neither the clinical implications of these findings nor their physiological mechanisms are clear at present, although we presume that they reflect a central effect, since the peripheral autonomic effects of SSRIs are relatively negligible.   

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HRV = heart rate variability

PTSD = post-traumatic stress disorder

SSRI = selective serotonin re-uptake inhibitor

Background: The etiology of bone marrow failure, a prominent feature of paroxysmal nocturnal hemoglobulinuria, is presently unknown.

Objectives: To evaluate the possible influence of cellular immune mechanisms in the bone marrow failure of PNH.

Methods: We studied marrow erythroid colony formation in a patient with paroxysmal nocturnal hemoglobinuria without hypoplastic/aplastic marrow complications.

Results: In vitro assays revealed a pronounced inhibition of primitive erythroid (BFU-E) progenitor cell growth by marrow T lymphocytes. Removal of T cells prior to culture resulted in a 4.5-fold enhancement of BFU-E numbers. Reevaluation of in vitro erythropoiesis during steroid administration indicated a persistent, albeit less prominent, T cell inhibitory effect.

Conclusion: Our findings provide the first direct evidence for a cellular immune inhibitory phenomenon accompanying PNH.

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PNH= paroxysmal nocturnal hemoglobinuria

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.

Background: Prenatal lead exposure (umbilical cord blood lead concentration 10 (μg/dl) may impair cognitive development. Childhood lead poisoning is infrequent in Israel, and there are no data on lead exposure in immigrants to Israel from the former Soviet Union.

Objectives: To evaluate prenatal blood lead concentrations in Israeli newborns whose mothers were born in Israel and in those whose mothers recently immigrated from Russia, and to compare data of prenatal lead exposure in Israel with those reported from other countries.

Methods: We compared the UCBLC of 35 newborns of new immigrants from Russia with a group of 35 newborns whose mothers were born in Israel. Venous BLC was also measured in 50 mothers. Data are compared with similar reports on prenatal lead exposure internationally.

Results: The UCBLC in all 70 newborns (mean±SD) was 3.53±1.6 μg/dl, and mothers' BLC (mean±SD) was 3.90±1.39 μg/dl. UCBLC and BLC in the 50 mother-newborn pairs correlated (γ=0.36, P<0.01). All newborns except one had UCBLC<8.0 μg/dl. There was no significant difference between UCBLC in the two groups.

Conclusions: Prenatal lead exposure among the study subjects in both groups was low. In this sample the newborns of mothers born in Israel and those whose mothers recently immigrated from Russia were not found to be at risk for lead poisoning. Prenatal lead exposure in this sample was low compared to that reported from various parts of the world.