תוצאת חיפוש

בן-עמי סלע

המכון לכימיה פתולוגית, מרכז רפואי שיבא, תל-השומר; החוג לביוכימיה קלינית, הפקולטה לרפואה סאקלר, אוניברסיטת תל-אביב

נזק ריקמתי או תהליך דלקתי משרים בפלסמת הדם עלייה בריכוז מספר אנליטים במה שמוגדר כתגובת acute phase. וכן נמדדת במצבי-דחק עלייה בלתי-סגולית ברמות של החלבון amyloid A, פיברינוגן, הפטוגלובין, צרולופלסמין, neopterin, ציטוקין IL-6, ואף ferritin.

בן עמי סלע

המכון לכימיה פתולוגית, מרכז רפואי שיבא, תל-השומר; החוג לביוכימיה קלינית, הפקולטה לרפואה סאקלר, אוניברסיטת תל-אביב

מדי שנה, כ-40% מכלל המעשנים מנסים, או לפחות מצהירים על רצונם להיגמל מעישון, אך רק כ-6% מתוכם אכן מצליחים במשימה זו לטווח ארוך. גם שיטות הגמילה עם תחליפי-הניקוטין, כגון טבליות הלעיסה או הדיסקיות המוצמדות לעור, העלו את שיעור הנגמלים פי 1.4 עד 2.6 בהשוואה לנוטלי האינבו, אך 80%-70% מבין אלה שחדלו לעשן באמצעות תחליפי-ניקוטין, חזרו תוך שנתיים לשיגרת העישון.

ניסויים לגמילה מעישון באמצעות תרופות נוגדות-דיכאון נמצאים לאחרונה בקו-עלייה. כך לדוגמה, התכשיר nortriptyline התלת-ציקלי, נמצא מכפיל את שיעורי הגמילה, ותוצאות מבטיחות התקבלו עם doxepin ו-fluoxtein. ייתכן, שההצלחה היחסית של נוגדי-דיכאון בגמילה מעישון, מקורה בקשר הגורדי בין דיכאוניות ועישון: מעשנים עם רקע דיכאוני תלויים יותר בניקוטין והצלחתם בגמילה פחותה, שכן דיכאון הוא אחד מתסמיני הגמילה הבולטים אצלם. עישון סיגריות מביא גם כן להפחתת פעילות האנזים monoamine oxidase B במוח במנגנון שאינו שאינו קשור לניקוטין, ובכך משתמרת יותר רמת הדופאמין, בעלת השלכות נוגדות-דיכאון.

בן-עמי סלע

המכון לכימיה פתולוגית, מרכז רפואי שיבא, תל-השומר; החוג לביוכימיה קלינית, הפקולטה לרפואה סאקלר, אוניברסיטת תל-אביב

החשיבות של יציבות המירקם החוץ-תאי (extracellular matrix, להלן EMC) בשמירת שלמות דופן כלי הדם מוכרת היטב, בין השאר מהבנת מחלות בהן נפגעת שלמות EMC, כמו לדוגמה בתיסמונת Marfan. כשמעלים את נושא ה- EMC, מוזכרת בנשימה אחת קבוצת אנזימי המירקם נושאי האבץ, MMP, בשל חשיבות פעולתם הפרוטאוליטית בפירוק של רוב המרכיבים החלבוניים במירקם האמור. על חשיבותם האבולוציונית של אנזימי MMP תעיד העובדה, שעד היום זוהו 66 אנזימים כאלה החל ביצורים ירודים כמתגים מסוימים, ועד לאדם, בו התגלו עד כה 21 אנזימים ממשפחה זו. במקביל נתגלו  4 חלבוני ריקמה (tissue inhibitors of MMP, או TIMP), היוצרים קשר לא-קוולנטי עם האנזימים האמורים ומנטרלים את פעולתם. אנזימי MMP מופרשים כזימוגנים בלתי-פעילים אנזימית, ושיפעולם נעשה באמצעות פרוטאינאזות אחרות כפלסמין, טריפסין ולפחות MMP ממברנתי אחד שכינויו –MT-MMP, המבקעים פפטיד קצר בזימוגן, ומביאים להתמרתו ל- MMP פעיל. בסקירה קודמת בעיתון זה, ייחדנו מקום לחשיבותם של אנזימי המירקם הללו בתהליך הסרטני, ואילו בסקירה הנוכחית יורחב הדיון למשמעויות של אנזימי MMP בהיבטים אחדים של כלי הדם.
 

Treatment of Phenyl-Ketonuria due to Dihydropteridinereductase Deficiency 

B. Sela, J. Blonder, I. Peled, G. Schwartz

Institute for Pathological Chemistry and Child Development, Sheba Medical Center, Tel Hashomer; Clinical Biochemistry Dept., Sackler Faculty of Medicine, Tel Aviv University

Most cases of hyper-phenylalaninemia are due to deficiency of phenyl-alanine hydroxylase that converts phenyl-alanine to tyrosine. This enzymic reaction is facilitated by the co-factor tetrahydrobiopterin (BH₄). A defect in the latter substrate leads to increased phenyl-alanine in 1-2 cases per million live births. Such cases are characterized by a degenerative brain process, and pronounced neurologic symptoms that cannot be prevented by a low phenyl-alanine diet alone.

In 3 male newborns a deficiency of dihydropteridine reductase (DHPR) activity was diagnosed, the last in a sequence of 3 enzymes involved in the formation of BH₄. Successful outcome of treatment as well as the results of failure to diagnose and treat affected newborns are described, with emphasis on the logistic problems involved in mass screening.

Nutritional Status and Vitamin B⁶ Supplementation in the Institutionalized Elderly

Felicia Stern, Yitshal N. Berner, Zeev Polyak, Sophya Bernadiner, Margarita Komarnitsky, Ben Ami Sela, Ram Doolman, Yoseph Dror

Institute of Biochemistry, Food Science, and Nutrition, Hebrew University of Jerusalem; Subacute Dept. and Clinical Nutrition, Hartzfeld Geriatric Hospital, Kaplan Medical Center, Gedera; and Institute of Chemical Pathology, Sheba Medical Center, Tel Hashomer

Nutritional status and vitamin B⁶ status were assessed in 18 men and 32 women, average age 84, living in a home for the aged. Average proportion of energy derived from protein was higher than the recommended; fiber intake was very low. Also low were intakes of calcium, magnesium, zinc, copper, vitamins D and E, thiamin, folic acid and vitamin B⁶.

Supplementation with vitamin B⁶ (10mg/d) for 28 days in those with the lowest B⁶ status assessed by B⁶ intake, activation coefficient of aspartate transaminase and plasma pyridoxamine concentrations led to improved B⁶ status (marked decrease in activation coefficient) and increased synthesis and decreased degradation of many short-lived neutrophil proteins. Though our elderly enjoy a variety of foods, some have marginal deficiencies that can be improved. Therefore, in the institutionalized elderly, micronutrient supplementation should be administered at a level low enough to be safe (below recommended upper level of intake) but high enough to be effective.

בן-עמי סלע

המכון לכימיה פתולוגית, המרכז הרפואי שיבא, תל השומר; החוג לביוכימיה קלינית, הפאקולטה לרפואה סאקלר, אוניברסיטת תל-אביב

Gyrate Atrophy of Choroid and Retina, and Hyperornithinemia 

B-A. Sela, J. Zlotnik, T. Masos, G. Yablonski, F. Abraham

Institute of Chemical Pathology and Goldschlager Eye Institute, Sheba Medical Center, Tel Hashomer; and Sackler Faculty of Medicine, Tel Aviv University

Gyrate atrophy of the choroid and retina is a rare degenerative disease, characterized biochemically by a marked increase in blood ornithine levels, due to deficiency of ornithine S-amino transferase. 4 men aged 35, 36, 48 and 62 years are described with different stages of myopia, night blindness and loss of peripheral vision, which progressed to tunnel vision and partial blindness. Onset of the disease was at ages 3, 10 and 15 years, respectively, while in the 4th patient there was delayed expression starting at about age 50. Most had posterior subcapsular cataracts, and the ocular fundus exhibited demarcated circular areas of chorioretinal degeneration. So far the only patients described in Israel have been of Iraqui origin. Our fourth patient originated from Istanbul, and he may represent a hitherto undescribed variant with a much delayed expression of the disease.

Alpha-Amino Adipic Aciduria: a Rare Psycho-Motor Syndrome

Ben-Ami Sela, Tamar Massos, Dov Fogel, Joseph Zlotnik

Pathological Chemistry and Child Development Institutes, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

A 3.5-year-old boy with developmental motor retardation, hypotonicity, and severe speech disturbance had alpha-amino adipic acid in his blood and very high levels in his urine. In only 20 cases has this catabolite of lysine and hydroxylysine been found in high concentrations in urine, due to enzymatic block.

The clinical features associated with alpha-amino adipic aciduria may include mental retardation, developmental and motor delay, learning difficulties, convulsions, speech problems and ataxia. 3 siblings had milder symptoms of psychomotor delay and intermediate degrees of alpha amino-adipic aciduria, suggesting that the described developmental deficits could be related to this metabolite or its derivatives.

Danaparoid-Sodium for Dialysis in Heparin-Associated Thrombocytopenia

Ronen Ben Ami, Ruth Rachmimov, Shlomo Berliner

Medicine Dept. D and Anticoagulation Therapy Unit, Tel Aviv-Souraski Medical Center, and Nephrology Institute, Sheba Medical Center, Tel Hashomer

Danaparoid sodium is an anticomposed of 3 glycosaminoglycans: heparan sulfate, dermatan sulfate and chondroitin sulfate. Similar to heparin, operates by activating antithrombin 3, but does not contain heparin or heparin fragments, and is therefore antigenically distinct.

Danaparoid has been advocated as a safe and effective anticoagulant for heparin-associated thrombocytopenia. However, there is little experience in its use as a substitute for heparin in hemodialysis.

We report 2 men, aged 82 and 73 years, respectively, who developed thrombocytopenia while undergoing hemodialysis with heparin, and who subsequently underwent successful dialysis with danaparoid. There was a rise in platelet levels in both while receiving danaparoid, and dialysis was completed without hemorrhagic or thrombotic complications. Danaparoid is a safe and effective substitute for heparin, and may be used as an anticoagulant in hemodialysis.

D-Lactic Acidosis in Short Bowel Syndrome

Ben-Ami Sela, Joseph Zlotnik, Tamar Masos, Joseph Danieli, Sarah Mazia-Beni, Anita Jonas

Institute of Chemical Pathology and Pediatric Intensive Care and Gastroenterology Units, Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv University

A boy of 20 months and a girl of 27 months who had previously undergone massive bowel resection due to congenital intestinal obstruction are described. During grad-ual reduction of total parenteral nutrition and initiation of oral feeding, both developed severe, acute metabolic acidosis, accompanied by encephalopathy and ataxia. After the laboratory identification of massive amounts of the d-Disomer of lactic acid in urine and blood, both were successfully treated with IV bicarbonate, and metronidazole to suppress the overgrowth of colonic lactobacilli responsible for the metabolic crisis.

Meningitis Due to Streptococcus Bovis Type 2

Anat Ben-Ami, Gera Gandelman, David Ergaz, Zev Shtoeger

Dept. of Medicine B, Kaplan Hospital, Rehovot (Affiliated with the Hadassah-Hebrew University Medical School)

Meningitis due to Streptococcus bovis is rare. Only 14 cases having been reported in the English literature. All patients (including the patient described) had an underlying disease or were treated by pharmacological agents that predisposed the patient to the infection. Most were treated by monotherapy with penicillin G (or amoxicillin) and recovered.

We describe a 74-year-old woman who had splenectomy as treatment for hairy cell leukemia 6 months before hospitalization for meningitis and sepsis by S. bovis type 2. She was successfully treated with intravenous amoxicillin. There was neither evidence of endocarditis nor carcinoma of the colon. Although the association between S. bovis meningitis and endocarditis or carcinoma of the gastrointestinal tract is not well established, we recommend a full work-up for GI malignancy and endocarditis in every patient with S. bovis meningitis.

Diagnosis and Treatment of Heart Failure within the Communuity

Haim Ben-Ami, Yehuda Edoute

Dept. of Medicine C, Rambam Medical Center and Technion Faculty of Medicine, Haifa

Congestive heart failure causes substantial morbidity and mortality. Symptoms and physical findings can help in diagnosis, but have limited sensitivity and specificity. Objective measurement of ventricular function is essential in virtually all patients in whom heart failure is suspected; reversible causes of heart failure must be sought.

Out-patient management includes education and counseling, emphasis on and assessment of compliance with diet, and pharmacological treatment. Angiotensin-converting enzyme inhibitors are the mainstay of treatment but are underused, and maximal doses are not given, apparently because of concern about side-effects. Diuretics should be administered only as needed to manage fluid overload. Calcium channel blockers are relatively contraindicated in patients with impaired ventricular function. Patient follow-up should be guided by results of the medical history and physical examination. Routine serial testing of ventricular function and exercise performance is discouraged.

Paroxysmal Nocturnal Hemoglobinuria

Haim Ben-Ami, Yehuda Edoute

Medical Dept. C, Rambam Medical Center and Bruce Rappaport Faculty of Medicine, The Technion, Haifa

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disorder of blood cells which originate from an abnormal hematopoietic stem cell. The condition is characterized by nocturnal hemoglobinuria, chronic hemolytic anemia, and thrombosis. We describe a 60-year-old woman with PNH admitted with abdominal pain and jaundice, who had dark urine on arising after a night's sleep. The diagnosis was established by the typical clinical story and a positive Ham test. She was successfully treated with Halotestin and folic acid. Although PNH is rare, it should be considered in the differential diagnosis of hemolytic anemia. Early diagnosis and treatment are important.

Carnitine Deficiency in Inborn Errors of Metabolism

B.-A. Sela, T. Lerman-Sagie, M. Berkovitz

Institute of Chemical Pathology, Chaim Sheba Medical Center and Section of Clinical Biochemistry, Sackler School of Medicine, Tel Aviv University; Pediatric Neurology Unit, Wolfsohn Medical Center, Holon; and Children's Ambulatory Clinic, Assaf Harofeh Medical Center, Zrifin

Several conditions, considered as inborn errors of metabolism, involve severe deficiencies in carnitine in both plasma and muscle. In the absence of evidence suggesting primary carnitine deficiency due to a biosynthetic enzymatic defect in the liver, the various diseases with carnitine deficiency are related to genetic defects in organic acid metabolism leading to blocked mitochondrial b oxidation. We describe a 4.5-year-old boy and 2 female infants with glutaric aciduria type I, isovaleric acidemia, and long-chain acid dehydrogenase deficiency, in whom severe carnitine deficiency was apparent. In all 3, long-term carnitine treatment proved to be vital and eliminated most of the symptoms.