קרן אלישקביץ, יצחק שפירא, שלמה ברלינר

המח' לרפואה פנימית ד' והיחידה לטיפול בנוגדי קרישה, מרכז רפואי תל אביב סוראסקי והפקולטה לרפואה סאקלר, אוניברסיטת תל אביב

הקשר בין היפרליפידמיה ומחלות לב וכלי דם מוכח וידוע. פחות מוכרת העובדה, שהיפרליפידמיה קשורה בשינויים המוריאולוגיים שעשויים לגרום להאטת זרימת הדם בנימיות. הטיפול בהיפרליפידמיה עשוי לשפר את ההיבטים ההמוריאולוגיים הנ"ל ובכך לתרום להאצת הזילוח הריקמתי. לאור החשיבות הרבה שמייחסים לטיפול תזונתי ותרופתי בהיפרליפידמיה, ולאור התוצאות המיטיבות של טיפול זה, ברצוננו לסכם את ההיבטים ההמוריאולוגיים הקשורים בו. יש בכך כדי להדגיש היבט נוסף המקשר בין היפרליפידמיה ומחלות איסכמיות שונות.

בסקירה זו, נתרכז בהיבטים השונים הקשורים בכדוריות הדם האדומות.

דב גפל (1,4), יצחק שפירר (2), יוסי הלל (3)

(1) המח' לרפואה פנימית ג', בי"ח ברזילי, אשקלון, (2) מכון ריאות, בי"ח אסף הרופא, צריפין, (3) המח' לגד"ש וגנטיקה, הפקולטה לחקלאות ברחובות, האוניברסיטה העברית, ירושלים, (4) בית הספר לתזונה, הפקולטה לחקלאות ברחובות, האוניברסיטה העברית, ירושלים

הגנום האנושי מורכב מ-3.2 מיליארד זוגות של נוקליאוטידים, אך רק כ-10% הם גנים תיפקודיים המקדדים לחלבונים. תפקיד שאר הרצפים אינו ברור וכנראה שחלקם משתתפים בבקרת הביטוי של הגנים התיפקודיים ובייצוב הכרומוסומים. בשנות ה- 60 של המאה ה-20, התגלו בדנ"א מיקטעים הנשנים מספר רב של פעמים ולכן נהוג לכנותם סטליטים (DNA satelites). באמצע שנות ה-80 זוהו על ידי Jeffreys וחב' רצפים בהם האורך של כל יחידה נשנית הוא קצר יותר מהסטליטים (כ-15 נוקליאודיטים בלבד) ועל כן כינויים הוא מיניסטליטים (minisatellities). מעקובות דנ"א אלה חוזרות על עצמן מספר רב של פעמים באתרים שונים בגנום. קבוצת חוקרים זו מצאה, שמספר החזרות של רצף הבסיסים (נוקליאוטידים) באתר מסוים של מיניסטליט שונה בין פרט לפרט. באמצעות שיטות מולקולתיות הם הראו, שניתן לקבל דגם פסים דמוי "ברקוד" שהוא ייחודי לכל אדם, וכך נקבע המונח טביעות האצבעות של הדנ"א (DNA fingerprints).

Selective Embolization of Hepatic Arteries in the Management of Severe Liver Trauma

Avraham Yitzhak¹, Gadi Shaked², Liliana Lupu³, Soli Mizrahi, Yoram Kluger⁴

¹Department of Surgery A, ²Trauma Service, ³Interventional Radiology, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, and Trauma Service⁴, Tel Aviv Medical Center, Tel Aviv University, Tel Aviv, Israel

Two cases of severe hepatic injury in which selective hepatic artery embolization was used to control hemorrhage are presented. The first case is that of a 35 year old patient who sustained a severe liver injury after a car accident. A CAT scan of the abdomen revealed an AAST grade 5 liver injury, pooling of contrast material within the liver parenchyma, and blood within the peritoneal cavity. The patient was given fluid resuscitation and taken to angiography where bleeding from branches of the right hepatic artery was demonstrated. While angiography was being undertaken the hemodynamic status of the patient deteriorated, blood transfusion was started, and a selective embolization of the right hepatic artery was performed. The bleeding stopped promptly and hemodynamic stability was regained.

The second case is that of a 40 year old pedestrian run over by a car. Abdominal ultrasound revealed free fluid in the peritoneal cavity and the patient was rushed to the O.R. Crushed right lobe of the liver, and inferior vena cava and bowel tears were found. After perihepatic packing and resection of the right and sigmoid colons retrohepatic vena cava tear was repaired and perihepatic packing restored. The abdominal cavity was closed and the patient was taken to the ICU for the correction of hypothermia, metabolic acidosis, and coagulopathy that had developed during the surgery. After 8 hours in the ICU the patient was transferred for angiography and a selective embolization of branches of the right hepatic artery was performed.

The clinical course of the patients after angiographic embolization of the hepatic arteries is described and the literature that discusses the use of angiography and embolization of hepatic arteries after traumatic hepatic bleeding is reviewed.

התפיסה המקובלת היא, כי חיתוך דופן אלקטיבי אשר נעשה ללא הוריה רפואית הוא פעולה פסולה. בעשור האחרון למאה ה-20, הובעו דעות שחלקו על תפיסה זו והתעורר ויכוח לגבי מקומה של הלידה הלדנית במאה ה- 21. הוויכוח אשר זכה לתהודה תקשורתית רבה החל בבריטניה והתעורר אף בישראל, בה שיעור חיתוכי הדופן עולה בהתמדה. עפ"י הנתונים שנאספו ע"י יו"ר החוג לרפואה סב-לידתית והוצגו בכינוס השנתי האחרון (7 ביולי 2000), היה השיעור הממוצע של חיתוכי הדופן בשנת 1999 כדי 14.6% מכלל הלידות בישראל, פי שלושה מהשיעור בשנת 1977 (5.5%) ובשליש יותר לעומת השיעור חמש שנים קודם לכן (11.3%). בסקירה של בן-הרוש וחב' (בגיליון זה), נדונה השאלה של ניהול לידה פעיל בתקופתנו. לאור הוויכוח לגבי חיתוך-דופן עפ"י בקשת היולדת (cesarean section upon maternal request) נראית שאלה זו לכאורה ארכאית. לפיכך, בצד ניהול לידה פעיל, יש להכיר את הוויכוח לגבי אופייה של הלידה הלדנית במאה ה- 21.

Long-Term Sequelae of Malignant Tumors in Childhood

N. M. Peretz, H. Goldberg, A. Kuten, I. Meller, E. Krivoi, A. Lorber, L. Bentur, A. Lightman, V. Gorenberg, M. Ben Arush-Weyl

Pediatric Hematology-Oncology Dept., Oncology Center, Pediatric Cardiology Unit, Pulmonology and Gynecology Depts., and Pediatric Endocrinology Unit; Rambam Medical Center and Technion-Israel Institute of Technology, Haifa; and Orthopedic-Oncology Unit, Tel Aviv-Sourasky Medical Center and Tel Aviv University

110 children with malignant diseases (leukemia excepted) who survived 5-20 years (median 9) post-therapy were followed (1996-1998). Median age during follow-up was 15 years (range 5-23). The most common malignancies were brain tumors, lymphoma, retinoblastoma and Wilm's tumor.

The 174 late side-effects included endocrine disorders (19%), cognitive impairment (14%), orthopedic dysfunction (12%), alopecia (12%), dental damage (11%), psychological (8%) and neurological (8%) disturbances, and azoospermia or amenorrhea (5%). There was no cardiac or renal damage and no second malignancy.

29% of side-effects were severe. There was significant reduction in quality of life in 54 (49%), in 27 of whom it was severe enough to require psychological intervention. Treatment of brain tumor caused 98 late side-effects in 28 patients (sequelae-to-patient ratio [SPR] 3.3). Most cognitive, endocrine and neurological disorders, and most cases of alopecia, dental and psychological difficulties were in these patients. There were frequent late complications in those treated for retinoblastoma (SPR 1.8), and bone or soft tissue sarcomas (SPR 0.8). Those treated for Wilm's tumor had few side-effects (SPR 0.4).

Late side effects were most frequent after radiation, reaching as high as SPR 2.4. It averaged only 0.5 in those treated with chemotherapy alone or in combination with surgery.

Reduction of late side-effects in these patients requires using less toxic modalities, as long as cure rate is not compromised. When considering secondary strategies, screening for early detection of late complications would enable immediate solutions, such as hormonal replacement or providing compensating skills for post-treatment disability.
 

Pulmonary Adenocarcinoma in Myasthenia Gravis - Auto-Immunity and Late Development of Malignancy

Yitzhak Rosen, Yair Levy, Yehuda Shoenfeld

Dept. of Internal Medicine B, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

We report a 75-year-old man with myasthenia gravis for many years, who was hospitalized because of cough, fever, and dyspnea. Chest x-ray revealed a bilateral pleural effusion. Adenocarcinomatous cells were found in the pleural fluid. Computerized tomography of the chest showed widespread pulmonary dissemination of the tumor.

The relationship between myasthenia gravis, an autoimmune disease involving the motor end-plate, and malignancy (thymoma) has been widely recognized. Current literature documents few reports of lung malignancies with concurrent development of myasthenia gravis. A tentative explanation, based on current research, is provided for the possible role of myasthenia gravis and the late development of lung cancer. Moreover, a model for the autoimmune phenomenon and the development of late malignancies will be provided with explicit explanations. It is important to search for occult, developing malignancies in newly diagnosed autoimmune diseases.

Acute Lymphoblastic Leukemia in Adults Treated with German Multicenter Study Group Protocols

G. Goldstein, O. Shpilberg, P. Raanani, A. Chetrit, I. Ben-Bassat

Institutes of Hematology and of Clinical Epidemiology, Sheba Medical Center and Sackler Faculty of Medicine, Tel Aviv University

Acute lymphoblastic leukemia (ALL) is a malignant disease whose incidence is relatively low among adults, unlike in children. Adults with ALL have a lower rate of long-term disease-free survival. During the last 20 years, a German multicenter group has shown that their protocol have achieved good results in adult ALL.

We reviewed the medical records of 35 ALL patients, aged 19-63 years, whome we treated with these protocol (1988-1997). The remission rate was 94%. At a median follow-up of 46 months the 2-year overall survival was 54% and the disease-free survival was 94%. Although 2 patients died of bone marrow transplant complications, no death was directly associated with drug toxicity. The main grade 3 or 4 side effects (WHO classification) were neutropenia (91%), thrombocytopenia (71%) and anemia (71%).

With there protocols we achieved high overall and disease-free survival rates, especially in comparison with other reports. Despite the high rate of severe treatment toxicity, there were no fatalities directly related to treatment. These results emphasize the need to concentrate treatment of adult ALL patients in large medical centers with expertise in the use of the complicated treatment protocols required.

High-Dose Chemotherapy and Autologous Stem Cell Trans-Plantation for Refractory and Relapsing Hodgkin's Disease

A. Avigdor, I. Hardan, O. Shpilberg, P. Raanani, I. Grotto, I. Ben-Bassat

Hematology Institute and Hemato-oncology Unit, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

High dose chemotherapy and autologous stem cell transplantation are widely used in relapsed and primary refractory Hodgkin's disease. We transplanted 42 patients with Hodgkin's disease between 1990-1998. Median follow-up was 31 months (range 1-102). 29 (69%) were transplanted after relapse and 13 (31%) were refractory to first line therapy. Median age at transplantation was 29 years (range 19-58) and 23 (55%) were males.

All were treated with the BEAM protocol (carmustine, etoposide, cytarabine and melphelan). 18 who were in remission received radiotherapy following transplantation. The source of the stem cells was bone marrow in 17% and peripheral blood in 83%. At initial diagnosis: 57% had stage III-IV disease and B symptoms were present in 52%. 75% were treated with MOPP, ABVD or with related versions. Radiotherapy followed in 52%. Prior to transplantation, 45% of the relapsed group were in the advanced stage. 33% and 12% of all patients had lung and bone involvement, respectively.

The complete remission rate was 86% for the 2 groups. 2 (5%) died from transplant-related complications and MDS/AML developed in 2 (5%) after transplantation. The 3-year overall survival (OS) and disease-free survival (DFS) were 68% and 60%, respectively. The 3-year OS for the relapsed group was 64% compared with 76% for the refractory group, and the 3-year DFS for the relapsed group was 60% vs. 42% for the refractory group (neither difference significant). Radiotherapy following transplantation did not have a beneficial effect on DFS. No prognostic factors for outcome of transplantation were found, most probably due to the limited number of patients and the high variability of disease characteristics.

We conclude that high dose chemotherapy and autologous stem cell transplantation are effective and relatively safe for relapsed or primary refractory Hodgkin's disease. The DFS at 3 years was longer for those transplanted after relapse than those with primary refractory disease, but not significantly. Patients with primary refractory disease can be salvaged with high dose chemotherapy.

Aortopexy for Tracheomalacia in Infants and Children

I. Vinograd, B. Klin, A. Silbiger, G. Eshel

Depts. of Pediatric Surgery, and Anesthesia, Dana Children's Hospital, Sourasky-Tel Aviv Medical Center;  Dept. of Pediatric Surgery and Intensive Care Unit, Assaf Harofeh Medical Center, and Sackler Faculty of Medicine, Tel Aviv University

During the past 12 years (1985-1998), 28 infants and children were operated on here for tracheomalacia. The diagnosis was made in all using rigid bronchoscopy. During the examination the infants breathed spontaneously, but the trachea collapsed on forced expiration.

Indications for surgery were repeated cyanotic spells ("dying spells") in 22, recurrent pneumonia, and inability to extubate (in 8). In 11 there were more than 1 indications. Age at surgery was from 7 days to 3 years (average 11.7 months).

All 28 children underwent bronchoscopy and guided aortopexy via a left-third intercostal approach. The ascending aorta and aortic arch (and in 6 the proximal innominate artery as well) were lifted anteriorly, using 3-5 non-absorbable sutures (5.0). The sutures were placed through the adventitia of the great vessels and then passed through the sternum.

Respiratory distress was significantly improved in 21. Another 2 required external tracheal stenting with autologous rib grafts, and in 1 other an internal Palmaz stent was introduced for tracheal stability. In 4 aortopexy failed, 1 of whom had tracheobronchomalacia throughout, and another 3 had laryngomalacia which required tracheostomy to relieve the respiratory symptoms.

Postoperative complications were minor: pericardial effusion in 1 and relaxation of the left diaphragm in another. 1 infant subsequently died, of unknown cause 10 days after operation, after having been extubated on the 1st postoperative day. On long-term follow-up (6 months to 12 years) 25 were found free of residual respiratory symptoms and 3 remained with a tracheostomy.

Thus, infants and children with severe tracheomalacia associated with severe respiratory symptoms, can be relieved by bronchoscopic guided suspension of the aortic arch to the sternum.

Breast Tumors Demonstrated by Tc-99m Sestamibi Scintimammography 

Itzhak Pappo, Tifha Horne, Herbert Merdad, Ruben Orda

Dept. of Surgery A, Institute of Nuclear Medicine and Dept. of Pathology, Assaf Harofeh Medical Center, Zrifin; and Sackler Faculty of Medicine, Tel Aviv University

Breast cancer can be detected by scintimammography using Tc-99m sestamibi (MIBI). The method is highly accurate, sensitive and specific. Histologically, most of the tumors have been adenocarcinomas.

We present 2 women with rare breast tumors, primary squamous cell carcinoma and malignant phyllodes tumor. In both, mammography and cytological biopsy were not diagnostic, but MIBI scintimammography demonstrated focal uptake in the diseased breast.

Color Doppler Imaging of Central Retinal Artery in Retinopathy of Prematurity

Alon Harris, Hanna J. Garzozi, Mira Harris-Izhak, Nir Shoham, Daniel R. Holland

Depts. of Ophthalmology, Indiana University School of Medicine, Indianapolis and of HaEmek Medical Center, Afula; and Eye Health Northwest, Portland, Oregon

Color Doppler imaging (CDI) is a noninvasive technique, combining 2-dimensional brightness-modulated (B-mode) ultrasound evaluation of eye and orbital structures, with simultaneous color-coded Doppler imaging of orbital blood flow. It has been used to characterize various ophthalmic disorders in adults. Currently there is no data describing orbital blood flow parameters in either normal children or in those with ophthalmic disease, such as the retinopathy of prematurity (ROP).

We evaluated blood flow in the central retinal artery of preterm infants undergoing examination for ROP. We also investigated whether useful readings could be obtained on a consistent basis, and the reproducibility of differences in central retinal artery blood flow between subjects with and without ROP (including the influence of "plus" disease).

We obtained hemodynamic readings in 43 of 46 eyes of preterm infants. 13 eyes had no signs of ROP; 18 had ROP (at least stage 1) without "plus" disease, and 12 had ROP with "plus" disease. There were no statistically significant differences in systolic blood flow velocity within the 3 groups. However the average velocity was slower in the "plus" disease group, correlating with the clinical finding of dilated and tortuous blood vessels which characterize the posterior retina of ROP eyes with "plus" disease.

Preflight Assessment by Hypoxic Inhalation Test in Cardio-Pulmonary Patients 

J. Lebzelter, G. Fink, E. Kleinman, I. Rosenberg, M.R. Kramer

Pulmonology Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva

Flying may expose passengers to hypoxic conditions, which may induce hypoxemia, particularly in those with chronic heart and/or lung disease. Onset of dyspnea, wheezing, chest pain, cyanosis and right heart failure can lead to urgent need for oxygen during flight. The hypoxia inhalation test (HIT) provides a safe and simple means of identifying those who may develop hypoxemia during flight.

We report our experience with 48 self-reporting patients who underwent HIT prior to pre-planned air travel. They inhaled for 15-minute periods a reduced oxygen concentration (F₁O₂ 15%) under normobaric conditions, during which O₂ saturation was monitored by pulse oximeter; electrocardiogram, blood pressure and symptoms were also monitored. O₂ saturation of 85% (PaO₂ 50 mm Hg) was considered a positive test. In the 8 cases (17%) with a positive test, 5 had chronic obstructive pulmonary disease and 3 had cardiovascular and/or combined heart-lung disease.

We calculated predicted O₂ partial pressure in altitude (PaO₂ ALT) and compared it to actual results in the 8 patients with a positive HIT. In 5, use of the predicted formula would have under-diagnosed the hypoxemia that developed during the HIT. Thus, the results of the HIT changed treatment strategy in these patients. We recommend that patients with positive tests use O₂ (2LPM or 4LPM) during flight.

HIT is practical and of potential benefit in the objective assessment of patients with various degrees of heart, lung or combined heart-lung disease. Clinicians should be aware of the relative risk of hypoxia during flight in such patients, and of the value of HIT in identifying them, leading to increase in its use.

Acute Ischemia of the Lesser Gastric Curvature 

D. Czeiger, A. Ariche, G. Shaked, N. Sion-Vardi, I. Levi

Trauma Service, Dept. of Surgery, and Pathology Institute, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer Sheba

The rich blood supply of the stomach protects it from ischemia and necrosis. Acute gastric ischemia, an emergency with high mortality, is rare. Atherosclerosis is the leading cause of acute ischemia, and the lesser curvature of the stomach is more vulnerable due to its relatively lesser blood supply. Reduction in gastric blood supply usually presents as chronic disease characterized by gastritis, gastric ulcer, or gastroparesis.

Gastroscopy can identify lesions of the gastric mucosa, and angiography demonstrates occluded vessels. Treatment of acute gastric ischemia is surgical, with total gastrectomy preferred over partial resection.

Non-Penetrating Deep Sclerectomy without Collagen Implantfor Glaucoma

Ben Zion Silverstone, Isaac Aizenman, Carmit Landau, Yaacov Rozenman

Ophthalmology Dept., Shaare Zedek Medical Center, Jerusalem

Deep sclerectomy (DS) can be used in glaucoma with increased intraocular pressure when medical treatment fails. It involves removing part of the ocular drainage apparatus. Resistance to intraocular fluid drainage is decreased, improving drainage and decreasing intraocular pressure. By avoiding anterior chamber penetration, DS diminishes frequency of the complications of filtering surgery.

24 eyes of 23 patients underwent DS for primary or secondary open angle glaucoma with elevated intraocular pressure not controlled medically. It included preparation of a 4.0 x 4.0 mm limbal-based external scleral flap, dissecting and removing most of an internal scleral flap (leaving it 1 mm smaller than the external flap), unroofing Schlemm's canal and removing fine endothelial tissue lining its inner walls. The external scleral flap was then repositioned and sutured. Collagen implants were not used. In some cases DS was combined with extracapsular cataract extraction and intra-ocular lens implantation.

Mean intraocular pressure decreased from 24.8‏3.9 mmHg initially to 12.8‏4.4 mmHg 6 months after operation (p<0.0001). There was no difference in postoperative intra-ocular pressure between DS as a single procedure or as part of a combined operation. Comations were mild and of short duration.

If long-term follow-up shows that lowered intraocular pressures are maintained, DS should be a surgical option in earlier stages of glaucoma.

Presurgical Neuropsychological assessment in Epilepsy: The Wada Test

Fani Andelman, Miri Neufeld, Irith Reider-Groswasser, Uri Kremer, Yoram Segev, Itzhak Fried

Functional Neurosurgery and EEG and Epilepsy Units, Section of Neuroradiology; and Pediatric Neurology Unit; Tel Aviv-Sourasky Medical Center, Tel Aviv

37 candidates for epilepsy surgery underwent the intra-carotid amytal procedure (IAP; also known as the Wada test) to determine hemispheric speech dominance and memory capacity. 31 demonstrated left hemisphere speech dominance, 2 showed evidence for bilateral language and 4 demonstrated right hemispheric language dominance.

Our study supports a correlational relationship between handedness, lesion laterality and age of onset of seizures, as reported in earlier studies. Left-handed patients with a left hemisphere lesion whose seizures began to an early age had a strong tendency for reversed language dominance.

Asymmetry of at least 20% in performing the memory test was taken as the cutoff score for demonstrating laterality of lesions. The asymmetry score correctly predicted laterality of lesions in all 28 patients; 6 did not have asymmetry scores and 3 were examined for language only. None of the patients who successfully passed the Wada memory test had any significant postsurgical memory deficits; 1 had transient reduction in verbal memory and 4 who did not pass the test were not operated on for this reason.

Our results demonstrate the importance of the Wada test in determining cerebral speech dominance, in predicting post-surgical amnesia, and support its usefulness in predicting laterality of seizure focus in candidates for temporal lobectomy.