Israel Medical Association Journal

Background: Routine prenatal ultrasound has increased the frequency of prenatal diagnosis of congenital cystic lung malformation, such as cystic adenomatoid malformation, pulmonary sequestration, congenital lobar emphysema, and bronchogenic cyst.

Objectives: To evaluate the methods of postnatal diag­nosis, the optimal age for operation since surgery is always required, and the optimal extent of lung resection.

Methods: The clinical courses of 11 patients with congenital lung cysts who underwent surgical lung resection (8 lobectomies and 3 segmentectomies) were reviewed.

Results: The diagnosis was confirmed by computed tomography scan in all. In nine patients the diagnosis was made prenatally. Chest X-ray was normal postnatally in all patients except for two who had recurrent pneumonia. Post­operative follow-up showed excellent recovery in all operated children. One patient who underwent surgery for CCAM following episodes of severe pneumonia died from another cause 5 months later. Postoperative chest CT scan showed no residual disease in eight patients. In two who had undergone limited resection, tomography showed a small segment of residual disease in one and a suspected residual lesion in the other.

Conclusion: With prenatal ultrasound the true frequency of congenital cystic lung anomaly appears to be higher than previously reported. Postnatal CT is mandatory to confirm or to rule out the diagnosis. The mere presence of cystic lung malformation is an indication for surgery. Complete removal of the affected lung lobe is recommended. Segmental resection may be inadequate. Early operation is tolerated well by infants and small children and we recommend that surgery be performed in children between 6 and 12 months of age.

Background: Charts of fetal measurements are widely used in the follow-up of pregnant women, however no charts have been constructed for the Israeli population.

Objectives: To establish growth charts for fetal femur size and biparietal diameter.

Methods: A prospective cross-sectional study of 1,422 singleton pregnancies was conducted.

Results: A total of 1,143 pregnancies met the inclusion criteria. Femur length and biparietal diameter were measured. A linear cubic model was fitted to construct growth charts for the different centiles. The charts were compared with previously published data.

Conclusions: We have constructed new fetal measure­ment charts for femur length and biparietal diameter that are unique for the Israeli population. These charts have been found to be similar to those published for other Caucasian populations.
 

Background: Hepatitis C virus is the major cause of acute and chronic hepatitis in patients with end-stage renal disease receiving replacement therapy.

Objectives: To define the prevalence of HCV RNA in a population of patients on dialysis in Israel, to determine the relative risk of acquiring HCV infection while treated by hemodialysis or chronic ambulatory peritoneal dialysis, and to define the HCV genotypes in this population.

Methods: During 1995 we studied 162 dialysis patients. Information was obtained regarding the mode of dialysis, years of treatment, number of blood transfusions, and results of serological testing for HCV, hepatitis B virus, and human immunodeficiency virus. Anti-HCV antibodies were tested by a third-generation microparticle enzyme immunoassay. HCV RNA was determined by polymerase chain reaction. HCV genotyping was performed by a hybridization assay.

Results: HCV RNA was detected in 18% of the HD group and 7% of the CAPD group. The number of HCV RNA-positive patients was significantly higher in the HD than the CAPD group (P < 0.05). HCV RNA-positive HD patients were treated longer than the HCV RNA-negative patients (P < 0.02).

Conclusions: Third-generation immunoassay proved to be highly sensitive (94%) and specific (91%) in identifying HCV RNA positivity. Several HCV subtypes were detected, lb being the most frequent. Identification and isolation of infected HCV patients may minimize its spread in dialysis units and prevent cross-infection.

Background: Congenital subependymal pseudocysts are incidental findings that are found in 05-5.2% of neonates during postmortem examination or head ultrasonography. In our institution we detected 10 neonates with CSEPC.

Objective: To investigate associated etiological factors, morphologic characteristics and outcome of CSEPC.

Methods: We performed a meta-analysis of the literature on CSEPC (1967-98), including our 10 cases.

Results: A total of 256 cases of CSEPC were analyzed. Ultrasound diagnosed 77.6% of CSEPC 48.8% were bilateral and 53.4% were located in the caudothalamic groove or head of caudate nucleus. Altogether, 93.5% resolved during 1-12 months of ultrasonographic follow-up. Compared to the general neonatal population, the following features were more prevalent in the CSEPC population: prematurity, maternal vaginal bleeding, preeclamptic toxemia, intrauterine growth restriction, asphyxia, fetal cytomegalovirus and rubella infec­tions, congenital malformations, chromosomal aberrations, infant mortality, and neurodevelopmental handicap. The risk for neurodevelopmental handicap was significantly higher when CSEPC were associated with fetal infections, IUGR, malformations and chromosomal aberrations, or persistence of CSEPC during follow-up. CSEPC infants without any of these four conditions had a low risk for neurodevelopmental handi­cap.

Conclusions: CSEPC are morphologic features of various underlying conditions encountered in the fetus. Association of CSEPC with IUGR, fetal infections, malformations and chromosomal aberrations or persistence of CSEPC indicates a higher risk for future neurodevelopmental handicaps, probably because of the deleterious effects on the fetal brain that are inherent in these conditions. A favorable outcome is expected in the absence of these risk factors.
 

Background: Autism is a pervasive developmental dis­order. The incidence rate and other related epidemiological characteristics of the Israeli population are not available.

Objectives: To assess the incidence rate of autism in the Haifa area and to compare family characteristics with previous reports from other countries.

Methods: We approached facilities in the Haifa area that are involved with the diagnosis and treatment of autism. The study group comprised children born between 1989 and 1993. Records of the children were scrutinized and 69% of the mothers were interviewed. Live-birth cohorts of the same years were employed for incidence computation.

Results: An incidence rate of 1/1000 was derived. Male to female ratio was 4.2:1. Pregnancy and perinatal periods were mostly uneventful. A low prevalence of developmental and emotional morbidity was reported for family members.

Conclusions: The epidemiological characteristics found in the Haifa area are similar to those reported from non-Israeli communities. This finding supports an underlying biological mechanism for this disorder. These data can be used for future trend analyses in Israel.
 

Background: Parental knowledge of their child’s heart disease, while often overlooked, contributes to compliance and reduces anxiety. Prior studies have shown that 36% of parental diagnostic descriptions are incorrect.

Objectives: To assess parental knowledge and attitudes among outpatients at a hospital pediatric cardiology clinic.

Methods: Seventy-four families completed a questionnaire in which they described their child’s condition and stated their attitude towards dental hygiene and future prenatal diagnosis.

Results: Eighteen percent of the parents failed to describe their child’s malformation correctly. We found that parental understanding of the heart defect correlated with parental education. Future prenatal diagnosis was considered by 88% of families, and termination of pregnancy by 40%. Only 40% of children were aware of their heart problem. Children of parents who were ignorant about the condition tended to lack knowl­edge themselves. An additional finding was that 68% of Jewish families turn to non-medical personnel for medical advice - an interesting finding not hitherto addressed.

Conclusions: Ignorance of their child’s problem did not correlate with its severity or complexity but rather with parental background: the less educated the parent, the more likely was the problem perceived incorrectly.
 

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: Inflammatory mediators, including cytokines and reactive oxygen species. are associated with the pathology of chronic liver disease. Hepatocytes are generally considered as targets but not producers of these important mediators.

Objectives: To investigate whether cells of hepatocellular lineage are a potential source of various cytokines we estimated the expression and secretion of tumor necrosis factor alpha, transforming growth factor beta 1 and interleukins I beta, 6 and 8 in the culture of well-differentiated human HepG2 cells treated for 24 hours with ethanol, acetaldehyde and lipopolysaccharide. Lipid peroxidation damage, glutathione content and glutathione perox­idase, catalase and superoxide dismutase activity were also determined.

Methods: HepG2 cells were treated for 24 hours with ethanol (50 mM), acetaldehyde (175 ìM) and LPS (1 ìg/ml). TNF-á, TGF­-â, L-1â, IL-6 and IL-8 mRNA were determined by reverse transcriptase polymerase chain reaction and secretion by en­zyme-linked immunoassay. Lipid peroxidation damage, glutathione content and antioxidant enzyme activities were determined spectrophotometrically.

Results: Exposure to ethanol for 24 hours induced the expression of TNF-á and TGF- â1. secretion of IL-1â and TGF-â₁ and decreased catalase activity. Acetaldehyde markedly increased TNF-á and IL-8 expression, stimulated IL-1â and IL-8 secretion, increased lipid peroxidation damage and decreased catalase activity, while LPS exposure induced the expression of TNF-á. TGF- â₁, IL-6 and IL-8, the secretion of TGF-â₁, IL-1â, IL-6 and IL-8, and a decrease in catalase activity. No change in GSH, GSHPx or SOD was found in any experimental condition.

Conclusions: The present studies confirm and extend the notion that hepatocytes respond to ethanol, acetaldehyde and LPS-producing cytokines. Oxidative stress produced by the toxic injury plays an important role in this response through up­regulation of inflammatory cytokines.

Objective: To study whether retinolpalmitate, beta-car­otene or lycopene could prevent liver cirrhosis induced by thioacetamide in rats.

Methods: In the control group liver cirrhosis was induced in male Wistar rats by intraperitoneal injections of TAA 200 mg/ kg for 12 weeks. The three study groups received in addition to TM either beta-carotene, lycopene or retinolpalmitate by gavage through an orogastric tube. Histopathological analysis and determination of the hydroxyproline contents of the livers were performed at the end of the protocol.

Results: Rats treated with beta-carotene and TAA had lower histopathologic scores and reduced levels of hepatic hydroxyproline (P= 0.02) than those treated by TAA alone. A trend of decreased fibrosis was observed in the rats treated with lycopene and TAA although this lacked statistical significance.

Conclusions: Beta-carotene attenuated liver cirrhosis induced by TAA in rats. The mechanism may be related to effects on hepatic stellate cells or to scavenging of free radicals by beta-carotene. Retinolpalmitate and lycopen had no significant beneficial effect.

The Management of a 750-bed tertiary care university hospital that serves the Jerusalem area and nationwide referrals initiated a total overhaul of all its supporting systems. This program, with parallel contingency plans, ensured a smooth transition of all computer-depended and othe services into the year 2000. Because this extraordinary project proved successful, its outcomes are noe being utilized as a unique impetus for implementation of hospital-wide continuous quality improvement programs. This paper reports how the established QI procedures, which were introduced also during the campaign, are now being activated from the baseline of those outcomes that have provided absolute efficacy in all hospital activities. The success of the campaign was achieved through the total involvement of all staff. This involvement was enhanced by the popular appeal of the dramatic deadline of the date 2000, as well as by focusing attention on personnel dynamics. Strategies for sustaining the momentum must be considered.

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.