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עמוד בית
Thu, 18.07.24

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February 2001
Marcia Hiriat, MD, PhD, Roman Vidaltamayo, PhD and M.Carmen Sanchez-Soto, MSc

Trophic factors such as nerve and fibroblast growth factors are important modulators of 13 cell physiology. These two factors induce the extension of neurite-Iike processes in primary cultures of adult rat 13 cells. Moreover, both NGF and FGF enhance glucose-induced insulin secretion. Since â cells synthesize NGF and pancreatic islet cells produce FGFs, it is possible that autocrine/paracrine interactions may be major regulators of insulin secretion, and impairment of these interactions could lead to pathological states such as diabetes mellitus.

Zvi R. Cohen, MD, Revital Duvdevani, PhD, Dvora Nass, MD, Moshe Hadani, MD and Zvi Ram, MD

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.

Carlos Alberto Aguilar-Salinas, MD, Onix Arita Melzer, MD, Leobardo Sauque Reyna, MD, Angelina Lopez, BSc, Ma Luisa Velasco Perez, RN, Luz E. Guillen, BSc, Francisco Javier Gomez Perez, MD and Juan A. Rull Rodrigo, MD

Background: Information is lacking on the effects of hormone replacement therapy in women with diabetes, especially during moderate chronic hyperglycemia.

Objectives: To study the effects of HRT on the lipid profile and the low density lipoprotein subclass distribution in women with type 2 diabetes under satisfactory and non-satisfactory glycemic control.

Methods: Fifty-four postmenopausal women after a 6 week run-in diet were randomized to receive either placebo(HbAlc <8%, n=13 HbAlc >8%, n=17) or HRT (HbAlc<8%, n=11 HbAlc >8%, n=13) for 12 weeks. HRT consisted of cyclical conjugated estrogens 0.625 mg/day plus medrogestone 5 mg/day. At the beginning and at the end of each treatment period the LDL subclass distribution was estimated by density gradient ultracentrifugation.

Results: At the baseline and during the study, the HbAlc level was significantly higher in hyperglycemic patients than in the near-normoglycemic controls (baseline 10.2±2.9 vs. 6.5±0.7%, P<0.01). They showed a trend for higher total and LDL cholesterol, triglycerides and lower high density lipoprotein-cholesterol compared to near-normoglycemic con­trols, as well as significantly higher triglyceride concentrations in very low density lipoprotein, intermediate density lipoprotein and LDL-1 particles and cholesterol content in LDL-1 and -2 particles. HRT decreased LDL-cholesterol in both groups. In the normoglycemic patients a small increase in HbAlc was observed (6.5±0.7 vs. 7.4+1%, P=004). In all cases, HRT did not modify the proportion of LDL represented by denser LDLs.

Conclusions: HRT did not modify the LDL subclass distribution, even in the presence of moderate chronic hyperglycemia in women with type 2 diabetes.

Ram Silfen, MD, Jerome Keslin, MB, ChB and Haim Gutman, MD
January 2001
Gabriel Szendro MD FRCS, Luis Golcman MD, Alex Klimov MD, Charach Yefim MD, Batsheva Johnatan RVT, Elizabeth Avrahami RVT, Batsheva Yechieli RVT and Shemuel Yurfest MD

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.
 

Yuksel Cavusoglu, MD, Bulent Gorenek, MD, Seref Alpsoy, MD, Ahmet Unalir, MD, Necmi Ata, MD and Bilgin Timuralp, MD

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.
 

Matityahu Lifshitz MD, Vladimir Gavrilov MD, Aharon Galil MD and Daniella Landau MD

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.
 

Ofer Nativ MD, Edmond Sabo MD, Ralph Madeb MSc, Sarel Halachmi MD, Shahar Madjar MD and Boaz Moskovitz MD

Objective: To evaluate the feasibility of using combined clinical and histomorphometric features to construct a prognostic score for the individual patient with localized renal cell carcinoma.

Patients and Methods: We studied 39 patients with pT1 and pT2 RCC who underwent radical nephrectomy between 1974 and 1983. Univariate and multivariate analyses were used to determine the association between various prognostic features and patient survival.

Results: The most important and independent predictors of survival were tumor angiogenesis (P=0.009), nuclear DNA ploidy (P=0.0071), mean nuclear area (P=0.013), and mean elongation factor (P=0.0346). Combination of these variables enabled prediction of outcome for the individual patient at a sensitivity and specificity of 78% and 89% respectively.

Conclusion: Our results indicate that no single parameter can accurately predict the outcome for patients with localized RCC. Combination of neovascularity, DNA content and morphometric shape descriptors enabled a more precise stratification of the patients into different risk categories.
 

Hani S. Shakhatreh MD

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.
 

Abraham Matitiau, MD, Einat Birk, MD, Ludmyla Kachko, MD, Leonard C. Blieden, MD and Elchanan Bruckheimer, MB, BS

Background: Secundum atrial septal defect is a common congenital heart defect that causes right heart volume overload and produces symptoms usually after the third decade of life. Treatment until the last few years has been open heart surgery.

Objective: To review our early experience with transcatheter closure of ASD2 using the Amplatzer septal occluder.

Methods: Between November 1999 and February 2000, 20 children and young adults with a median age of 9.1 years (4.2-35.1 years) were referred for transcatheter closure of ASD2. Diagnosis was established by transthoracic echocardiography. Implantation was performed under general anesthesia through the femoral vein with the guidance of transesophageal echocardiography and fluoroscopy. Femoral arterial puncture was performed for blood pressure monitoring during the procedure. The device size chosen was similar to the balloon-stretched diameter of the ASD2.

Results: Implantation was completed successfully in 18 patients. Two patients were referred for elective surgery: one had an unsuitable anatomy for transcatheter closure by TEE in the catheterization laboratory and the device could not implanted properly, the other patient had a large multiperforated septal aneurysm that was retrieved. Mean ASD2 diameter by TTE and TEE was similar (13.9 + 3 mm, 13.4 + 3.5 mm) and mean stretched diameter was 18.3 + 4.3 mm. Mean Qp:Qs (pulmonary flow: systemic flow) was 2.2 + 0.6. Mean fluoroscopy time for the procedure was 14.8 + 4.8 minutes.

The patients were discharged the day after the procedure.

Four patients had a tiny leak immediately post-procedure, and none had a leak at one month follow-up. The only complication was a small pseudoaneurysm of the femoral artery in one patient, that resolved spontaneously.

Conclusion: Transcatheter closure of ASD2 with the Amplatzer septal occluder is a safe and effective alternative to surgical closure. Long-term outcome has to be evaluated.

Eran E. Weinmann, MD and Arie Bass, MD
Rasmi Magadle, MD, Paltiel Weiner, MD, Alexander Sotzkover, MD and Noa Berar-Yanay, MD
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