תוצאת חיפוש

Liver Failure with Coagulopathy in an Infant with Tyrosinemia

Moshe Nussinovitch, Gadi Campino, Rivka Shapira, Benjamin Voluvitz, Jacob Amir

Department of Pediatrics, Schneider Children's Medical Center of Israel, Petah Tikva, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

Tyrosinemia is an inherited autsomal recessive condition. We present a 5 week-old boy with this disorder. He was admitted because of a fever, vomiting and lethargy. The laboratory tests confirmed a coagulopathy with prolonged prothrombin time (PT), partial thromboplastin time (PTT) and a decreased serum fibrinogen. The a-fetoprotein level was markedly elevated. To confirm the diagnosis of tyrosinemia, quantitative urinary succinylacetone was measured. Although overt liver failure with coagulopathy may be part of the representation of tyrosinemia, a significant coagulopathy in the absence of overt signs of liver disease has not been emphasized as a clue to the diagnosis of this condition.

Menetrier's Disease in Children

Yossi Rimar, Michael Jaffe, Ron Shaoul

Department of Pediatrics, Bnei-Zion Medical Center, Faculty of Medicine, Technion, Haifa, Israel

Menetrier's disease in children is a rare disorder that is characterized by the presence of marked protein losing gastropathy associated with enlarged and thickened gastric folds. Abnormal regulation of gastric epithelial growth, probably triggered by an infectious agent, has been suggested as an etiology for this disorder. We describe a case of Menetrier's disease in a young child and review the current literature encompassing the different aspects of the disease.

Inflammatory Bowel Disease and Osteoporosis: an Evidence-Based Connection

Eyal Meltzer, Eran Dolev,

Department of Internal Medicine E, Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv, Israel

Inflammatory bowel diseases (IBD) often have chronic or remittent course. Control of symptoms and disease activity often requires the administration of glucocorticoids.

Osteoporosis is a frequent finding in patients with IBD. The evidence-based connection between the two conditions relies on a relatively limited number of cross-sectional and longitudinal studies. The cause of this connection has not been defined completely. Probably, both the chronic inflammation and the steroid therapy contribute to the osteopenia, through an increase in bone resorption without a compensatory increase in bone formation. There is little data regarding the efficacy of therapeutic interventions for the prevention of osteoporosis in patients with IBD. Recently, guidelines for the evaluation and treatment of osteoporosis and IBD have been published. There is need for further research on the relation between these conditions and on the efficacy of current therapy for this unique population.

Animal Models of Psychiatric Diseases: Possibilities, Limitations, Examplesand Demonstration of Use

Haim Einat, RH Belmaker

Beer Sheva Mental Health Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel

Animal models of psychopathology serve as a central tool for psychopharmacologists in their attempts to develop new, more efficient medications for psychiatric disorders, and in the efforts to explore the mechanisms of conventional and novel drugs. The development of efficient models for psychiatric diseases is complicated since the mechanisms of the disorders are not clear, major parts of the diagnosis depend on verbal communication with the patient and many of the symptoms are expressed mainly through the subjective experiences of the afflicted individual.

Inspite of these difficulties, effective models were developed for most psychiatric diseases. The development of such models is based on their validation in three different dimensions: face validity - behavioral similarities between the model and the disorder; construct validity - similarities between the mechanisms related to the model and a mechanistic theory of the disease; predictive validity - that the model response to the conventional medications that are effective in the disease and will not respond to drugs that are not effective in the disease.

The present paper presents three known models of depression; each induced in a different way and therefore represents a group of models:

*     Reserpine-induced hypoactivity - represents the group of pharmacologically induced models.

*     Forced swim test - represents the group of behaviorally induced models.

*     Flinders Sensitive Line - represents the group of genetically induced models.

The use of these models in an attempt to examine the range of action of a new potential antidepressant and its mechanisms of action is demonstrated with a recent set of experiments with inositol.

Laparoscopy as Part of the Management of Gynecologic Neoplasms - Report of Our Clinical Experience

Yehuda Ben David, Moshe Bustan, Eliezer Shalev

The Department of Obstetrics and Gynecology, HaEmek Medical Center, Afula

Introduction: Surgery is the treatment of choice in most early stages of cervical cancer and advanced stages of ovarian cancer. Failing to preoperatively diagnose para-aortic and parametrial metastases in cervical cancer or a non-resectable, ovarian cancer, may results in a superfluous laparotomy.

Aim: To evaluate the advantage of using laparoscopy in cervical and ovarian cancer.

Patients and Methods: Study population includes patients with ovarian or cervical cancer referred between 1997-1999. A CT scan and a trans-vaginal sonography were used to detect involvement of pelvic and para-aortic lymph nodes, parametrium and other metastases. In patients with cervical cancer, para-aortic lymph node dissection was laparoscopically performed. When para-aortic nodes were negative and parametrium was clear, radical hysterectomy and pelvic lymph nodes dissection was conducted through laparotomy. When para-aortic lymph nodes or parametrium were positive, patients were referred for radiation therapy. In ovarian cancer patients, the upper abdomen and the pelvis were examined laparoscopically to evaluate the possibility of optimal debulking surgery. Staging was done for patients who were not candidates for optimal debulking surgery and second debulking surgery was considered.

Results: Nine patients with stage lb-lla cervical cancer were included. Preoperatively, 2 of them were suspected for lymph node involvement. Following laparoscopy one was confirmed to have para-aortic lymph node involvement and the other did not. In the remaining 8 patients, one was found to have parametrial involvement and laparotomy was avoided, while the rest were treated surgically.

Eighteen ovarian cancer patients were included in this study. Laparoscopy revealed an extensive disease in 7 patients and therefore staging laparoscopy was completed. In the remaining 11 patients, laparotomy was performed, operable disease was found and complete debulking surgery was conducted. In only one patient of the 11 complete debulking surgeries was not possible.

Conclusions: In accordance with the experience and skills of the surgical team, we propose utilizing laparoscopy in cases where laparotomy may be avoided.

Following 90 Patients with Antiphospholipid Syndrome: Manifestations of the Disease, Follow-Up of Antibodies Titers and Correlations with Clinical Manifestations in the Israeli Population - Patients in the Sheba Medical Center, Tel Hashomer

Ibrahim Marai, Yair Levi, Gezal Godard, Yehuda Shoenfeld

Department of Medicine B and Research Unit of Autoimmune Diseases, Chaim Sheba Medical Center (affiliated to Tel-Aviv University), Israel.

The antiphospholipid syndrome (APS) is defined by the presence of antiphospholipid antibodies (aPLs) with venous or arterial thrombosis, recurrent pregnancy loss or thrombocytopenia. The syndrome can be either primary or secondary to an underlying condition, most commonly systemic lupus erythematosus (SLE).

The purpose of the study was to review the manifestations of the APS in Israeli patients and to investigate the difference between patients with primary or secondary syndrome. Analysis of the correlation between the manifestations of the disease and the antibody titers [LA (lupus anticoagulant), IgG aCL (anticardiolipin), IgM aCL] was also performed.

In the study there were 90 patients with APS in the Sheba Medical Center. The clinical findings for all patients were recorded according to established protocol.

Results: Arterial thrombotic events were present in 51.1% of the patients; cereberal ischemic attacks were the most frequent arterial events. Venous thrombotic events were present in 45.6% patients; deep venous thrombosis was the most frequent venous event. Obstetric complications were found in 37.3% of patients; the most frequent complication was abortions. The clinical findings of patients with primary or secondary syndrome were similar. Patients with APS associated with lupus had a high prevalence of hemolytic anemia (28.6% v 3.3%; P=0.001), and ANA (antinuclear antibody) (75% v 12.9%; P=0.0001). There was no correlation between the antibody titers (LA, IgG aCL, IgM aCL) and clinical manifestations. The patients received anticoagulant treatment and antiaggregant drugs to prevent recurrence of symptoms. Clinical manifestations in Israeli patients did not differ from those in non-Israeli patients.

Conclusions: Venous or arterial thrombosis and obstetric complications are the most frequent clinical findings in APS. There was no different in clinical manifestations between primary and secondary syndrome. The findings of autoimmune hemolytic anemia and ANA were more frequent in patients with secondary APS. There was no correlation between antiphospholipid antibody titers and manifestations of disease. Overall, the patients require therapy with anticoagulant treatment and antiaggregant drugs. The clinical manifestations were similar in Israeli and non-Israeli patients.

Antidepressive Effect of Pyridoxine (Vitamin B₆) in Neuroleptic-Treated Schizophrenic Patients with Co-Morbid Minor Depression - Preliminary Open-Label Trial

Roni Shiloh¹, Abraham Weizman¹, Nechama Weizer¹, Pnina Dorfman-Etrog¹, Hanan Munitz¹ 

¹Geha Psychiatric Hospital, Felsenstein Medical Research Center, Rabin Medical Center, Beilinson Campus, Petah Tikva; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Background: Minor depression is reported in 20-60% of schizophrenic patients during various stages of their disorders; impairing patients' compliance, response to treatment and worsening their overall prognosis. Various anti-depressive treatments have been proposed for such cases but response rates are usually poor. Pyridoxine (Vitamin B⁶) in essential for the proper metabolism of various neurotransmitters that are considered relevant to the pathophysiology of depression and/or schizophrenia and it has been reported beneficial in ameliorating depressive symptoms as part of major depression, premenstrual syndrome or 'Chinese restaurant syndrome'. We hypothesized that addition of pyridoxine to on-going neuroleptic treatment could improve minor depression in schizophrenic patients.

Method: Nine schizophrenic patients with co-morbid minor depression participated in this study. All participants had a stable unchanged clinical state (changes in Brief Psychiatric Rating Scale (BPRS). Scale for the Assessment of Positive Symptoms (SAPS), and Scale for the Assessment of Negative symptoms (SANS) scores <5%) and all were maintained on unchanged doses of anti-psychotic drugs for at least 4 consecutive weeks prior to initiation of the study.

Participants received, open-label, pyridoxine 150 mg/day in addition to their anti-psychotic treatment for 4 consecutive weeks. Mental status was evaluated before, during, and at the end of 4 weeks of pyridoxine administration using the BPRS, SAPS, SANS and HAM-D.

Results: Two of the nine patients (22%), characterized by higher initial HAM-D and SANS scores, and by older age and longer duration of illness, experienced marked improvements in depressive symptoms (23% and 28% decrease in HAM-D scores) following 4 weeks of pyridoxine administration. In one of these two, the improvement in depressive symptoms was accompanied by a parallel decrease in SANS Scores.

Conclusion: A subgroup of schizophrenic patients with co-morbid minor depression may benefit from pyridoxine addition to their on-going anti-psychotic treatment.

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).

Characteristics of Nasopharyngeal Carriage of Streptococcus Pneumoniae in Children During Acute Respiratory Disease

A. Aran¹, D. Fraser², R. Dagan¹

Pediatric Infectious Disease Unit¹, Epidemiology Department², Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva

Streptococcus pneumoniae is an important cause of pediatric morbidity and its main reservoir is the nasopharynx, from which it can disseminate and cause invasive disease. From November 1997 through March 1998, nasopharyngeal carriage of S. pneumoniae was evaluated in 250 children under the age of 36 months: 123 Jews and 127 Bedouins with acute respiratory disease and in 980 healthy control children (852 Jews and 128 Bedouins).

Carriage rate was higher among sick children. Among Jewish children it was 57% and 35% of sick and healthy children respectively (p<0.01), and among Bedouin children it figured as 80% and 67% respectively (p=0.01). The difference in carriage rate was most prominent in infants under the age of 5 months: among Jewish children it was 60% and 27% of sick and healthy children respectively (p<0.001) and among Bedouins it was 82% and 65% respectively (p=0.05).

Higher carriage rate of penicillin resistant pneumococci (PRP) was also detected in sick children, with no relation to antibiotic treatment in the month prior to sampling. In Jewish children PRP was detected in 12%, 28% (p<0.001) and 36% (p<0.001) of healthy children, sick children with previous antibiotic treatment and sick children with no treatment, respectively.

The seroypes included in the newly developed 7-valent conjugate vaccine: 4, 6B, 9V, 14, 18C, 19F, 23F, that are highly pathogenic and often antibiotic resistant contributed 74% of isolates in sick Jewish children who had previous antibiotic treatment and 39% of isolates in healthy children (p<0.001). In Bedouin children vaccine types carriers rate among the sick children was not higher than in healthy children.

Acute respiratory disease increases the risk of pneumococcal carriage in general and carriage of resistant pneumococci in particular. Previous antibiotic treatment increases the risk of carring one of the pathogenic serotypes included in the 7-valent vaccine. The impact of disease is most prominent in infants under 5 months, since they are usually less exposed to S. pneumoniae carriers than older children.

Since the increase in carriage rate during illness is mostly due to the serotypes included in the newly developed conjugate vaccine, future immunization programme may decrease not only morbidity rate but also nasopharyngeal carriage rate of pneumococci in general and of antibiotic-resistant pneumococci in particular.

The Chemotherapeutic Treatment of Advanced Hodgkin's Disease

R. Epelbaum¹, N. Haim¹, M. Ben-Shahar¹, I. Valtuch¹, D. Faraggi³, A. Sharabi-Nov³, Y. Ben-Arie², Y. Cohen⁴

Departments of Oncology¹ and ²Pathology, Rambam Medical Center, and Faculty of Medicine, Technion-Israel Institute of Technology; ³Department of Statistics, Haifa University, Haifa; and ⁴Department of Oncology, Soroka University Medical Center, Beer Sheba

Between 1972 and 1994, 121 adult patients with advanced Hodgkin's disease received MOPP (M) combination chemotherapy, MOPP alternating with ABVD (M-A) or MOPP and ABV hybrid (M/A). Radiation therapy was given to 1/3 of them. The median age was 35 years, 58% had stage III and 42% had stage IV disease. Failure-free survival at 10 years was 43.9%. It was 66.7%, 48.4% and 29.9% for patients treated by M/A, M-A and M, respectively. Overall survival at 10 years was 40.8%, and 78.2%, 48% and 27.7% for patients treated by M/A, M-A and M, respectively. Multivariate analysis found age (above or below 65 years) and combination chemotherapy (with or without adriamycin) to be significant prognostic factors. M/A combination was more myelotoxic, while M combination caused more second primaries. Today, 80% of patients with advanced Hodgkin's disease may be cured, with low rate of long-term toxicity.

גבריאל דינרי

מנהל המכון לגסטרואנטרולוגיה ותזונה, מרכז שניידר לרפואת ילדים

מחלת קרוהן מאופיינת בדלקת בכל שכבות דופן המעי, היכולה להתהוות בכל חלקי מערכת העיכול. מחלה זו, יחד עם דלקת כרכשת כיבית, מהווה את קבוצת מחלות המעי הדלקתיות (IBD–inflammatory bowel disease). החולים במחלה כרונית זו עלולים ללקות בשלשולים נישנים, דימומים נצורים בין לולאות המעי ובין אברי בטן אחרים או עור הבטן, תת-תזונה, חולשה, ועוד. המחלה מתאפיינת בעליות וירידות בפעילותה, וגורמת סבל רב, מצריכה אישפוזים נישנים, טיפולים יקרים והיעדרות מהעבודה.

יורם אברהמוב

המח' לרפואת נשים ויולדות, המרכז הרפואי הדסה עין-כרם, ירושלים

טיפולי השראת ביוץ באמצעות גונאדוטרופינים מלאכותיים הביאו למהפכה של ממש בטיפולי הפוריות בשנים האחרונות, בכך שהעלו בהרבה את הסיכוי להרות, בעיקר בנשים עם הפרעות בביוץ, אך גם בנשים הלוקות באי-פוריות מגורמים אחרים, כגון עקרות בלתי מוסברת או עקרות הגבר. בנוסף מהווים הגונאדוטרופינים המלאכותיים מרכיב הכרחי בטיפולי ההפריה החוץ-גופית. אחד הסיבוכים היאטרוגנים הקשים של טיפולי השראת ביוץ בכלל ובגונאדוטרופינים בפרט הוא תיסמונת גריית-היתר של השחלות (ovarian hyperstimulation syndrome). תיסמונת זאת, על אף היותה נדירה, גורמת למירב התחלואה והתמותה הקשורות בטיפולי פוריות. התיסמונת מתבטאת בהגדלת השחלות, בחדירות-יתר של נימיות הדם עם דליפת נוזל למדור השלישי ובריכוז-יתר של הדם (hemoconcentration).

ינינה גלבויז (1), שרה שפירו (2), ניצה להט (2), אריאל מילר (1,3)

(1) היחידה לנירואימונולוגיה, המח' לנירולוגיה, (2) היחידה לחקר אימונולוגיה, המרכז הרפואי כרמל, הטכניון – הפקולטה לרפואה, (3) מכון רפפורט למחקר במדעי הרפואה, חיפה

אנזימי המטריקס-מטלופרוטאינאזות (matrix metal-loproteinases - MMP's) (אממ"פ)* הם משפחת אנזימים פרוטאוליטיים אשר, יחד עם מעכביהם הריקמתיים – TIMs, מעורבים בעיצוב המירקם החוץ-תאי (ECM) (מח"ת – מירקם חוץ-תאי) במיגוון מצבים פיזיולוגיים, כגון התפתחות עוברית וריפוי פצע. לאחרונה, מצטברות עדויות למעורבות אממ"פ גם במיגוון רחב של מחלות, כגון התפשטות גרורות, טרשת העורקים, מצבי דלקת ומחלות אוטואימוניות.

בתהליכים דלקתיים של מערכת העצבים המרכזית, האממ"פ הם הגורם העיקרי בהרס מחסום הדם-מוח, בהתהוות בצקת מוחית, בהסננת תאי דלקת, בתהליכי הרס מיאלין ובהתהוות צלקת הגליה במוח. פעילות מוגברת של MMPs אובחנה בבעלי-חיים חולים בדגם ניסיוני של מחלות דה-מיאליניות וטרשת נפוצה. רמות גבוהות של אממ"פ, בעיקר MMP-2 ו-MMP-9, התגלו שינויים בפרופיל האממ"פ דווחו גם בהקשר של דלקות עוצבה חיידקיות ונגיפיות. כמו כן, למרות סתירות מסוימות במימצאים, נראה כי אממ"פ מעורבים גם בתהליכי הצטברות חלבון הביתא-amyloid במחלת אלצהיימר. מעורבות אממ"פ במחלות מערכת העצבים המרכזית מעוררת עניין מיוחד בזכות יכולתם לשמש בסימנים לפעילות המחלה ובזכות הפוטנציאל הטיפולי הטמון בשימוש במעכבי אממ"פ.

מוחמד מחאג'נה, שרון צימרמן-אביצרור, רפאל וייץ

היח' לנירולוגיה של הילד, מרכז שניידר לרפואת ילדים, פתח תקווה

נירופיברומטוזיס סוג 1 (נ"פ-1)* היא אחת המחלות השכיחות על רקע הפרעה בגן יחיד. שכיחות המחלה לפי עבודות שונות נעה בין 1/3,000-1/4,000. התורשה של מחלה זו, היא אוטוסומית שולטנית, אך שכיחות המוטאציות החדשות מגיעה עד ל-50% מהמקרים.

המכון למחלות דרכי העיכול והכבד¹, המח' לאישפוז יום² והמח' לרפואה פנימית³, מרכז רפואי סוראסקי, תל אביב 

TNFα הוא ציטוקין פרו-דלקתי במחלת קרוהן. הפחתה ברמתו מביאה לשיפור במצבם של החולים. Imfliximab הוא נוגדן כימרי חד-שיבטי ל- TNFα

התכשיר ניתן במוסדנו החל בדצבמר 1998 במסגרת פרטנית. עקבנו אחרי החולים ותוצאות הטיפול בהם במטרה להעריך את יעילות ובטיחות התכשיר. התגובה נמדדה על פי מדד פעילות מחלה בחולים שטופלו בשל מחלה פעילה, ועל פי הערכת ההפרשה בחולים שטופלו בשל נצור חיצוני.