PubMed Health⌕ Search

Biomedical subjects

B Weisz

Publications and source records attributed to B Weisz.

14 recordsLinked to original sources
PubMed2006

Ultrasound-guided injection and occlusion of the trachea in fetal sheep.

OBJECTIVES: To access the fetal sheep trachea by ultrasound-guided transthoracic injection in order to deliver gene therapy vectors or occlude the trachea with a detachable balloon. METHODS: Fetal sheep were operated on at a mean gestational age of 102 (range, 81-116) days (term = 145 days). Under ultrasound guidance, either a 20-G spinal (for vector delivery) or a 16-G Kellett (for placement of an occlusive balloon) needle was inserted via the fetal thorax into the fetal trachea. RESULTS: Using the 20-G spinal needle the trachea was accessed successfully in 33/36 fetuses, with 97% survival. Failure to inject was related to fetal position and gestational age. Blood vessel damage causing significant morbidity occurred in two fetuses (6%). Tracheal occlusion was achieved by puncturing the trachea with the 16-G needle and advancing an endoluminal balloon in three out of five attempts in a mean time of 17 (range, 16-19) min, with 100% survival. In one case, the balloon became sited within the accessory lobe bronchus and was not inflated. At postmortem examination 21 days later, all balloons remained inflated and occluded the trachea, and the lung-to-body weight ratio and airways morphometric indices were consistent with relative pulmonary hyperplasia in the obstructed lungs. CONCLUSIONS: Ultrasound-guided transthoracic tracheal puncture is a reliable technique in fetal sheep, with low morbidity and mortality. Using this technique, a detachable endotracheal balloon can be placed to provoke pulmonary growth. Advances in needle design and balloon size may improve the success rate.

Animals↗
PubMed2006

Clinically applicable procedure for gene delivery to fetal gut by ultrasound-guided gastric injection: toward prenatal prevention of early-onset intestinal diseases.

Targeting gene therapy vectors to the fetal intestinal tract could provide a novel means toward prevention of the early postnatal intestinal pathology of cystic fibrosis and other conditions, such as congenital enteropathy, that cause intestinal failure. Among these conditions, cystic fibrosis is by far the most common lethal genetic disease. It is caused by a functional absence or deficiency of the cystic fibrosis transmembrane conductance regulator and manifests in the gut as meconium ileus. Prenatal treatment of genetic disease may avoid early-onset tissue damage and immune sensitization, and may target cells that are less accessible in the adult. We investigated gene transfer to the fetal gut, using a minimally invasive injection technique. First-generation replication-deficient adenoviral vectors encoding the beta-galactosidase gene and transduction-enhancing agents were injected into the stomach of early-gestation fetal sheep (n = 8, 60 days of gestation; term, 145 days) under ultrasound guidance. Reporter gene expression was observed 2 days after injection in the villi of the gastrointestinal epithelia after 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside staining and beta-galactosidase immunohistochemistry of fetal tissues. Expression of beta-galactosidase, as measured by enzyme-linked immunosorbent assay, was enhanced after pretreatment of the fetal gut with sodium caprate, which opens tight junctions, and after adenovirus complexation with DEAE-dextran, which confers a positive charge to the virus. Instillation of the fluorocarbon perflubron after virus delivery resulted in tissue transduction from the fetal stomach to the colon. Using a clinically relevant technique, we have demonstrated widespread gene transfer to the fetal gastrointestinal epithelia.

Adenoviridae↗
PubMed2005

Gene therapy progress and prospects: fetal gene therapy--first proofs of concept--some adverse effects.

Somatic gene delivery in utero is a novel approach to gene therapy for genetic disease based on the hypothesis that prenatal intervention may avoid the development of severe manifestations of early-onset disease, allow targeting of otherwise inaccessible tissues including expanding stem cell populations, induce tolerance against the therapeutic transgenic protein and thereby provide permanent somatic gene correction. This approach is particularly relevant in relation to prenatal screening programmes for severe genetic diseases as it could offer prevention as a third option to families faced with the prenatal diagnosis of a genetically affected child. Most investigations towards in utero gene therapy have been performed on mice and sheep fetuses as model animals for human disease and for the application of clinically relevant intervention techniques such as vector delivery by minimally invasive ultrasound guidance. Other animals such as dogs may serve as particular disease models and primates have to be considered in immediate preparation for clinical trials. Proof of principle for the hypothesis of fetal gene therapy has been provided during the last 2 years in mouse models for Crigler Najjar Disease, Leber's congenital amaurosis, Pompe's disease and haemophilia B showing long-term postnatal therapeutic effects and tolerance of the transgenic protein after in utero gene delivery. However, recently we have also observed a high incidence of liver tumours after in utero application of an early form of third-generation equine infectious anaemia virus vectors with SIN configuration. These findings highlight the need for more investigations into the safety and the ethical aspects of in utero gene therapy as well as for science-based public information on risks and benefits of this preventive gene therapy approach before application in humans can be contemplated.

Animals↗
PubMed2004

Tailored management of twin reversed arterial perfusion (TRAP) sequence.

OBJECTIVE: To describe our management of pregnancies complicated by twin reversed arterial perfusion (TRAP) sequence. METHODS: This was a retrospective study involving all cases of TRAP sequence referred to our fetal medicine unit in a 3-year period (2000-2002). Patients were routinely managed by repeat sonographic surveillance with sonographic anatomical evaluation and detailed echocardiography. Cases with signs of impending cardiac failure were treated by in-utero YAG-laser coagulation of the umbilical vessels of the acardiac twin. RESULTS: Six cases were studied. Three patients in whom there were no signs of deterioration in the status of the pump twin, and in whom the acardiac twin was smaller than the pump twin, were managed conservatively. However, one of these with monoamniotic twins ended in intrauterine fetal death of the pump twin. The other two cases presented with spontaneous cessation of blood flow in the umbilical artery of the acardiac twin. Both delivered at term normal neonates whose follow-up revealed no signs of neurological sequelae. One case of quadruplet pregnancy (with TRAP sequence and two dichorionic twins) was treated by selective termination of the monochorionic twins. Two cases with signs of impending cardiac failure were treated by in-utero YAG-laser occlusion of the vessels in the acardiac mass. Both interventions had a favorable outcome. CONCLUSIONS: Conservative treatment is suitable for milder cases of TRAP sequence in which the pump twin is the larger one. Cases in which the acardiac twin is larger have a poorer prognosis and should be treated by invasive intervention and cord occlusion.

Adult↗
PubMed2004

[Perinatal group B streptococcal disease: a review and revised guidelines for prevention].

Group B Streptococcus (GBS) is a common inhabitant of the maternal genital and gastrointestinal tracts, and colonizes approximately 20% of pregnant women. About 50% of infants born to colonized women will become colonized at birth. Early onset GBS disease affects 5/1000 newborns, and is related to a 5-16% mortality rate and severe morbidity. Selective intra-partum chemoprophylaxis can prevent most cases of GBS early-onset disease. In 1996, the federal Centers for Disease Control and Prevention (CDC), the American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics (AAP) recommended either a culture-based or risk-based approach for prevention of early onset GBS disease. Understanding the epidemiology of the disease and comparing efficacy of the two prevention strategies may elucidate the dispute surrounding this issue. Accordingly, new recommendations from the CDC and the ACOG were published, and their implementation in Israel should now be considered.

Anti-Bacterial Agents↗
PubMed2001

Topoisomerase II immunostaining as a prognostic marker for survival in ovarian cancer.

OBJECTIVE: This study aimed to evaluate topoisomerase II compared to Ki-67 expression as a marker for tumor behavior and for prognosis of patients with ovarian cancer. METHODS: In order to screen for potential prognostic markers, two groups of patients with advanced stage (FIGO stages III and IV) epithelial ovarian carcinoma were selected based on differences in survival (mean survival, 11 years versus 2 years). Pathology slides were reviewed, and immunohistochemistry using antibodies to topoisomerase II and Ki-67 was performed on the original cell blocks. No patients were lost to follow-up. RESULTS: Detectable expression of topoisomerase II was present in 70.0 +/- 30.3% of cells in patients with rapidly progressing disease, compared to only 12.3 +/- 12.4% of cells in long-term survivors (P = 0.0001). Ki-67 expression was also more frequent in short-term survivors compared to long-term survivors, but the difference was less prominent than with topoisomerase II (P = 0.01). Specificity and sensitivity as prognostic factors reached 88.2 and 93.8% for topoisomerase II, compared to 55.6 and 88.2% for Ki-67. CONCLUSIONS: Topoisomerase II expression as detected by immunohistochemistry in tumor samples emerged as a promising clinically relevant biomarker for survival in advanced epithelial ovarian cancer.

Biomarkers, Tumor↗
PubMed2001

Accuracy of the preoperative diagnosis in 100 emergency laparoscopies performed due to acute abdomen in nonpregnant women.

STUDY OBJECTIVE: To assess the validity of preoperative diagnosis in the emergency room in relation to the surgical diagnosis at laparoscopy. DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: One hundred consecutive nonpregnant women who underwent emergency laparoscopy for acute abdomen between 1997 and 1999. Intervention. Emergency diagnostic laparoscopy. MEASUREMENTS AND MAIN RESULTS: The preoperative diagnosis was confirmed by laparoscopy in 29 (44%) of 66 cases of ovarian torsion, 9 (82%) of 11 cases of ovarian cyst, and 12 (80%) of 15 cases of bleeding corpus luteum. Unsuspected diagnoses among nonconfirmed cases were ovarian cysts (24), adhesions (5), bleeding corpus luteum (3), degenerative myomas (3), pelvic inflammatory disease (2), and appendicitis (1). The preoperative diagnosis was confirmed by emergency laparoscopy in 56% of all patients. Diagnoses most likely to be predicted accurately were ovarian cysts and bleeding corpora lutea. Ovarian torsion was most difficult to diagnose preoperatively, as it was not confirmed during laparoscopy in over half patients. Ovarian cysts and adhesions were the most common unsuspected findings. CONCLUSION: Patients and surgeons alike should be aware of difficulty making accurate preoperative diagnoses of acute gynecologic pathologies in the emergency room. (J Am Assoc Gynecol Laparosc 8(1):92-94, 2001)

Abdomen, Acute↗
PubMed2001

One or two hours postprandial glucose measurements: are they the same?

OBJECTIVE: This study was undertaken to compare the rate of abnormal glucose levels measured after 1 hour (>140 mg%) with those measured after 2 hours (>120 mg%) postprandially in women with gestational diabetes mellitus (GDM). STUDY DESIGN: Sixty-eight women were included in this study. All had GDM based on the criteria of Carpenter-Coustan. Women with fasting glucose levels of 105 mg% or more were excluded from the study. All women were initially treated by diet. All women measured daily capillary blood glucose levels when fasting as well as 1 hour and 2 hours postprandially for 1 week, immediately after diagnosis of GDM. Glucose levels were obtained by memory-based glucometers. All women were followed in a specialized gestational-diabetes clinic throughout the pregnancy. Insulin therapy was started on an individual basis according to common clinical criteria. Epidemiologic and perinatal data were collected from medical charts. RESULTS: The average age of the women was 30.8 +/- 5.4 years. Thirty-five percent of participants were primipara. The mean gestational age at diagnosis was 28.8 +/- 5.4 weeks. Glucose measurements included 618 readings during fasting and 2730 either 1 hour or 2 hours postprandial. Rates of abnormal glucose (>95 mg% when fasting; >140 mg% 1 hour or >120 mg% 2 hours after each meal) per person were the following: fasting, 27.1% abnormal glucose measurements; postbreakfast, 22.4% abnormal levels after 1 and 8.5% after 2 hours (P < .01); postlunch, 16.4% abnormal levels after 1 hour and 18.2% after 2 hours (not significant); postdinner, 16.3% abnormal levels after 1 hour and 30.1% after 2 hours (P < .01). CONCLUSION: The rate of abnormal values was 2.5-fold greater 1 hour postbreakfast than 2 hours postbreakfast, in contrast to an opposite ratio of a 2-fold increase in the rate of abnormal values 2 hours postdinner versus 1 hour postdinner. Therefore, differential measurement (1 hour after breakfast and 2 hours after dinner) might impose stricter criteria for controlling blood glucose levels. Further clinical research should explore whether differential measurements might reduce the rate of diabetes-associated complications.

Adult↗
PubMed1999

A new functional Ras antagonist inhibits human pancreatic tumor growth in nude mice.

Constitutively active Ras proteins, their regulatory components, and overexpressed tyrosine kinase receptors that activate Ras, are frequently associated with cell transformation in human tumors. This suggests that functional Ras antagonists may have anti-tumor activity. Studies in rodent fibroblasts have shown that S-trans, transfarnesylthiosalicylic acid (FTS) acts as a rather specific nontoxic Ras antagonist, dislodging Ras from its membrane anchorage domains and accelerating its degradation. FTS is not a farnesyltransferase inhibitor, and does not affect Ras maturation. Here we demonstrate that FTS also acts as a functional Ras antagonist in human pancreatic cell lines that express activated K-Ras (Panc-1 and MiaPaCa-2). In Panc-1 cells, FTS at a concentration of 25-100 microM reduced the amount of Ras in a dose-dependent manner and interfered with serum-dependent and epidermal growth factor-stimulated ERK activation, thus inhibiting both anchorage-dependent and anchorage-independent growth of Panc-1 cells in vitro. FTS also inhibited tumor growth in Panc-1 xenografted nude mice, apparently without systemic toxicity. Daily FTS treatment (5 mg/kg intraperitoneally) in mice with tumors (mean volume 0.07 cm3) markedly decreased tumor growth (after treatment for 18 days, tumor volume had increased by only 23+/-30-fold in the FTS-treated group and by 127+/-66-fold in controls). These findings suggest that FTS represents a new class of functional Ras antagonists with potential therapeutic value.

Animals↗
PubMed1999

Growth inhibition of ras-dependent tumors in nude mice by a potent ras-dislodging antagonist.

A lipophilic farnesyl moiety attached to the carboxyl terminal cysteine of ras proteins structurally supports their membrane anchorage, required for ras-dependent growth-factor signaling and for transforming activity of ras oncoproteins. It has been shown that inhibition of ras farnesylation can block tumor growth in nude mice but that some ras-dependent tumors escape such blockage as a result of prenylation of ras. S-trans-transfarnesylthiosalicylic acid (FTS) is a potent ras-dislodging antagonist that does not affect ras prenylation but rather acts on the mature, membrane-bound ras and facilitates its degradation. Here we demonstrate that FTS induces reappearance of stress fibers in H-ras-transformed rat-1 cells (EJ cells) in vitro, inhibits their anchorage-independent growth in vitro, and blocks EJ-tumor growth in nude mice. The anchorage-independent growth of cells expressing ErbB2 (B104), but not that of v-raf-transformed cells, is also inhibited by FTS, suggesting specificity towards activated ras. FTS treatment (5 mg/kg i.p. daily) caused inhibition (75-80%) of tumor growth in nude mice implanted with EJ, but not in mice implanted with v-raf-transformed cells, with no evidence of systemic toxicity. Moreover, FTS treatment increased the survival rate of EJ-tumor-bearing mice from 48 to 68 days. Here we demonstrate anti-tumor potency in a synthetic, non-toxic, ras-dislodging antagonist acting independently of farnesyltransferases.

3T3 Cells↗
PubMed1996

[Complications of exchange transfusion in term and preterm newborns].

Exchange transfusion has an important role in the treatment of hyperbilirubinemia of the newborn. It is used in attempts to prevent kernicterus when bilirubin levels are high. We describe our experience in 203 exchange transfusions performed on 143 infants (81 males and 62 females) with hyperbilirubinemia during 1983-1992. In only 30% of cases was there a specific etiological diagnosis of the jaundice based on a positive Coombs test, G6PD deficiency, or the presence of sepsis or maternal diabetes; the rest were idiopathic. 57% of the neonates were premature (26-36 weeks of gestation). Premature neonates underwent more transfusions than full-term infants (1.6 vs 1.2). There was no direct death from exchange transfusion; morbidity was 6.3% (including bradycardia, apnea, thrombocytopenia, hypoglycemia and hyponatremia). Most complications occurred in preterm infants and those severely ill. All complications were treated immediately and there were no sequelae.

Exchange Transfusion, Whole Blood↗
PubMed1994

[Intussusception in infants].

Intussusception, the invagination of a portion of the intestine into an adjacent segment, is the most common cause of intestinal obstruction in post neonatal children. Most cases are idiopathic, but in about 2-12% the intussusception evolves secondary to an underlying abnormality. Classically, there is sudden onset of attacks of screaming, accompanied by pallor, vomiting, and irritability in a previously health child. Some gradually become weaker and lethargic. We evaluated variations in presenting symptoms and outcome as related to age and time until admission. There were incidence peaks in the spring and autumn. 48% developed irritability, while 42% were described as apathetic. These results emphasize the importance of awareness that apathy can be a major presenting symptom. The younger the child, the greater the rate of success of reduction by hydrostatic pressure. In those admitted within 24 hours of onset, the rate of reduction was twice that in those admitted later. Awareness of atypical symptoms and early diagnosis may affect treatment and improve prognosis.

Humans↗
PubMedDate not supplied

Cancer in pregnancy: maternal and fetal implications.

Cancer is the second leading cause of death in women during their reproductive years, and complicates approximately 0.1% of all pregnancies. When cancer occurs during gestation it poses immense pressure on the pregnant patient, her relatives and her physicians. As cancer is diagnosed during gestation, it raises conflicts between optimal maternal therapy and fetal well-being. In this review, the available data are analysed regarding the impact of pregnancy on the course of the disease, and the effects of the malignant process and its treatment on both the mother and her fetus. Here, attention is focused on the most common malignancies associated with pregnancy; cervical and breast cancer, malignant melanoma and lymphoma. In addition, attention is focused on the available data regarding the impact of cytotoxic and radiation treatments on the mother and fetus.

Adult↗