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

Alopecia Due to Seroxat 

Leonid Umansky, Abraham Dorevitch, Avner Sella

Psychiatry Chronic Dept., Eitanim Mental Health Center, Jerusalem

There are 2 stages of alopecia, anagen and telogen effluvium, both of which may be associated with medication- related alopecia. We describe massive hair loss in a 51-year-old woman during treatment with Seroxat (paroxetine), which remitted after it was discontinued. Pathological mechanisms of drug-associated alopecia are complex and have yet to be fully elucidated.

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.

Psychogenic Polydipsia Leading to Water Intoxication

L. Umansky, A. Sella

Psychiatry Dept., Eitanim Mental Health Center (Affiliated with the Hebrew University-Hadassah Medical School, Jerusalem)

Psychogenic polydipsia and its frequent complication, water intoxication, are well-known to psychologists. There are biochemical and psychiatric theories of psychogenic polydipsia which often correlate with each other.

A 48-year-old man with chronic paranoid schizophrenia developed symptoms of psychogenic polydipsia. This provoked disturbances in electrolyte balance, resulting in a rapid decrease in serum sodium concentration and eventual death. There is a paucity of information and little awareness of this problem in the professional literature.

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.

Breast Conservation: Safe for Early Breast Cancer

Gil Bar-Sella, Georgetta Fried, Zipora Brotman, Anna Ravkin, Riva Borovik, Abraham Kuten

Dept. of Oncology, Rambam Medical Center; Dept. of Oncology, Lin Medical Center; and Rappaport Faculty of Medicine, Technion, Haifa

Between 1981-1993 581 women with primary breast cancer were treated by breast conservation. Their mean age was 56‏12 years and 63% were postmenopausal and 37% pre- or perimenopausal. The median follow-up time was 56 months. 45% had pathological Stage I disease, 49% Stage II, 2.5% Stage III and 3.5% clinical Stage I-II disease. 54% of lesions were excised with good margins, 10% with close margins (<0.5 cm), 9% with microscopic residual, 3% with macroscopic residual, and in 24% margins were not reported. Adjuvant therapy, consisting of combination chemotherapy and/or hormones, was given to 69%.

Radiotherapy, usually 50 Gy tangential photon irradiation to the whole breast, was given to 564 (97%); an electron or photon "boost" to the tumor with a median dose of 17.5 Gy was given to 378 (65%). Most of those with positive nodes received 50 Gy to the lymphatic drainage system.

1 year after radiotherapy cosmetic results were rated as "good" or "excellent" in 80%, "moderate" in 17% and "poor" in 3%. The 5-year actuarial survival was 97% in Stage I and 88% in Stage II. 37 patients (6.5%) developed breast recurrence; 11 of these (2%) had simultaneous distant metastases. 5 (<1%) developed axillary or supraclavicular lymph node metastases, and 81 (14%) developed distant metastases. Most local recurrences were in those younger than 40, and in those with primary tumors >1.75 cm.

The satisfactory level of local control achieved is attributed to the high doses of radiation (up to 75 Gy) administered to those with high risk lesions.

Information Provided for Informed Consent in Clinical Trials

Avishay Sella

Genitourinary Medical Oncology Unit, Dept. of Oncology, Rabin Medical Center (Beilinson Campus), Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University

The Helsinki Declaration contains recommendations guiding physicians who conduct clinical trials. One is that the requirement for informed consent is essential for approval of a trial. An important component of the informed consent doctrine is that all data required for the participant's decision must be provided. We analyze data of a therapeutic trial, and define 12 data components outlined in, or directly derived from the Helsinki Declaration.

61 instances of informed consent for therapeutic clinical trials from various fields of medicine, from 1994 to 1997, were analyzed. In each the presence of the 12 components was evaluated.

The data demonstrated that there were only 5 components cited in most cases of informed consent: trial objectives, methods, treatment plan, risks, and the option of withdrawing. Benefit to the participant was mentioned in half the cases, while only limited information was provided about other components such as life-threatening and unpredictable risks, and alternative treatment.

Examples of informed consent from 1997 showed statistical improvement since 1994 in the data concerning trial objectives, methods, risks and alternative therapy. Informed consent documents of international multicenter trials compared with local trials showed statistical improvement in the data components of the trial objectives, methods, and risks, including those of potentially life-threatening and unpredictable risks, and alternative therapy. Analysis of informed consent showed that not all components required for a comprehensive decision regarding participation in a clinical trial are included. These data emphasize the need to design a structured informed consent protocol in which all the required data components are specifically outlined for potential participants.

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.

Combination Chemotherapy in Metastatic Urothelial Cancer

A. Sella, D. Flex, D. Gafni, O. Rabinovitz, A. Sulkes, J. Baniel

Genitourinary Medical Oncology Unit, Depts. of Oncology and Urology, Rabin Medical Center, Beilinson Campus, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv

The treatment of metastatic urothelial cancer is based on the combination of cisplatin, methotrexate, vinblastine and adriamycin (M-VAC). From November 1994 to May 1997 we treated 25 patients (51 men, 3 women, aged 50-77) with M-VAC. The tumor originated from the urinary bladder in 14 (56%) and the upper urinary tract in 11 (44%). Disease sites included: primary - 5 (25%), lymph nodes - 17 (68%), lungs - 10 (40%), bones - 8 (32%), pelvic mass and liver each - 4 (16%), with an overall median of 2 (1-5) sites per patient.

9 patients (38%) had complete responses and 8 (32%) had partial responses, for an overall response rate of 68% (95% CI 48.5%-85%). The median duration of response was 15.3 (1.6-29.6+) months. Median survival of responders was 19.1 (4.8-35.7+) months compared to 6.2 (0.7-11.2) for the non-responders (p<0.05). 13 (52%) of patients are alive, of whom 8 (32%) are free of disease and 5 with a single metastatic site on presentation at follow-up.

In the 118 treatment cycles we observed grade III-IV toxicity: myelosuppression 53 (45%), thrombocytopenia 4 (3%), stomatitis 8 (6.7%), diarrhea 3 (2.5%). There were 22 infectious episodes and 1 patient died of sepsis.

We achieved a high response rate with the combination M-VAC. However, only a third had long-term disease-free states and treatment was associated with excessive toxicity. Thera-peutic approaches with new agents are required to improve the response rate and toxicity.

Concept Management in Penetration of Unusually Shaped Foreign Bodies into Extremities

I. Dudkiewicz, M. Salai, A. Chechik

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

During routine emergency room work penetration by foreign objects is frequently encountered, some of which may be very irregular in shape. These may cause further damage if inappropriately removed. It is important to perform a proper X-ray survey.