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.

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.

אורי שולמן, רם סילפן, אברהם אמיר, דניאל האובן

המח' לכירורגיה פלסטית והיח' לכוויות, קמפוס בילינסון, מרכז רפואי רבין, פתח-תקווה

מלאנומה ממארת של העור (ממ"ע) היא שאת ששיעור היארעותה עולה בקצב מהיר בעולם כולו והיא מהווה אתגר טיפולי נרחב. כיום, הניתוח הוא הטיפול העיקרי בממ"ע, ואם השאת מאובחנת ומטופלת בשלב מוקדם, לפני חדירה עמוקה לשיכב הדרמיס, היפגעות קישיות לימפה והתהוות גרורות מרוחקות, הרי שסיכויי ההישרדות גבוהים.

ממ"ע באזור ראש-צוואר המתהווה בשכיחות של כ-20% מתוך כלל החולים במלאנומה ממארת, שונה במספר מובנים מאשר באזורים אחרים בגוף: כריתה נרחבת של השאת מוגבלת בגודלה עקב המיקום האנטומי באזור ראש-צוואר, הניקוז הלימפטי עשיר ביותר, ההשלכות האסתטיות עלולות להיות מרחיקות לכת וההשפעות התיפקודיות יכולות להיות בלתי הפיכות.

ממ"ע באזור ראש-צוואר מתרחשת בשכיחות שווה בנשים ובגברים. השאת ממוקדת בעיקר בפנים, ובשכיחות יורדת באזור הצוואר, הקרקפת והאוזניים.

קיימים מספר גורמי סיכון להתהוות מלאנומה ממארת בכל אזורי הגוף, ביניהם אנשים עם שומות מלאנוציטיות מרובות, שומה מלידה גדולה בקוטר מעל 20 ס"מ (giant congenital nevi), שומה דיספלסטית (dysplastic nevi) בעלי עור, עיניים ושיער בהירים עם נטייה להיכוות לאחר חשיפה קצרה לקרני השמש, בעלי עור עם נמשים, אנשים שנחשפו רבות לקרני השמש במהלך חייהם, אנשים בעשור החמישי לחייהם ואילך, אנמנזה משפחתית של מלאנומה ממארת המגבירה את הסיכון ללקות במחלה בשיעור של פי 2-8, אנמנזה של סרטני עור בעבר ואנשים עם דיכוי המערכת החיסונית. הסיכון במהלך החיים להתהוות מלאנומה ממארת בפעם השנה הוא 1%-8%.

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.
 

Aggressive Surgical Approach in Pancreatic Cancer - Is it Justified?

V. Catz-Snir, P. Schachter, M. Shimonov, Y. Avni, G. Gvirtz, A. Czerniak

Depts. of Surgery, Gastroenterology, and Diagnostic Radiology, Wolfson Medical Center, Tel Aviv and Sackler Faculty of Medicine, Tel Aviv University

Resection presents the only possible cure for pancreatic cancer. An aggressive surgical approach may extend the limits of resection and offer cure for more patients. 37 women and 28 men, mean age 67 years (range 33-84) with focal lesions underwent pancreatic resection (1993-1999). Cancer of the pancreatic head was found in 45, in the ampulla in 4 and in the body or tail in 16. There was a tumor larger than 5 cm in 9, vascular involvement in 8, and a combination of both in 6.

All were evaluated prior to exploration by standard imaging techniques and 44 by laparoscopic ultrasound. 42 underwent pancreatico-duodenectomy, 16 distal subtotal pancreatectomy and 3 local excision of an ampullary tumor. Benign lesions were found in 8 (focal pancreatitis in 4 and a serous cystic lesion in 4).

Curative resection (microscopically negative margins, negative lymph nodes) was achieved in 44. 2 died 1-2 months after operation of septic complications (2% operative mortality). The most frequent complication (in 8) was pancreatic fistula. Additional complications included anastomotic-line bleeding (3), intra-abdominal abscess (2), and 1 developed portal vein thrombosis (treated surgically).

1- and 2-year survival in those after curative pancreatic resection was 81% and 55% respectively. 2-year survival in those after palliative resection (positive resection margins or positive lymph nodes) was 50% and 11%, respectively.

After proper selection of those in whom it is possible to perform curative resection, regardless of size or vascular involvement, an aggressive surgical approach is justified.
 

Antioxidant Profile of Human Saliva and its Biological Significance

R. M. Nagler, A. Z. Reznick

Dept. of Oral and Maxillofacial Surgery, Salivary Clinic and Oral Biochemistry Laboratory; Rambam Medical Center and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa

Saliva is the first biological medium to come in contact with materials entering the body through the oral cavity. These materials are contained in food and drink (or inhaled as volatile ingredients). Accordingly, saliva contains various defense mechanisms which have been thoroughly investigated. They include immunological and enzymatic systems aimed at pathological microorganisms. Saliva also can protect the mucosa against mechanical insults and when required, promote its healing via agents such as the epidermal growth factor.

Another defense mechanism in saliva which has been gaining increased attention and seems to be of paramount importance is its antioxidant system. We discuss both the molecular and enzymatic components of the salivary antioxidant system in respect to mixed, parotid, submandibular and sublingual saliva and under various physiological conditions of secretion.

Preservation of the Larynx in Advanced Cancer

Edward Rosenblatt, Nava Siegelmann-Danieli, Jemal Zidan, Nisim Haim, Abraham Kuten

Oncology Dept., Rambam Medical Center and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa

The effectiveness of sequential chemo-radiotherapy in preserving the larynx in advanced laryngeal carcinoma was assessed. 4 Unselected patients (19 men and 2 women, mean age 60 years) with advanced squamous cell carcinoma of the larynx (T3-4/N0-3) received induction chemotherapy consisting of 2-3 cycles of cisplatin (100 mg/m²) and 5-flourouracil (1000 mg/m²/day) as a continuous infusion on days 1-5 followed by definitive radiotherapy: 50 Gy to the whole neck, 70 Gy to the larynx and clinically involved nodes, using a combination of 6 MV photons and 9-12 MeV electrons.

19 of The 21 patients responded to combined therapy but there was no response to induction therapy in 2 (10%) and 2 did not complete therapy due to severe toxicity. At a mean follow-up of 40 months, 7 had undergone total laryngectomy (33%), for an overall 5-year laryngeal preservation rate of 66%. Reasons for total laryngectomy in 2 patients were no response and in 5 tumor recurrence.

Mean survival was 39 months (range 11-46 months); at last follow-up 17 of 21 were alive and disease-free, 11 of whom had a functional larynx (65% of survivors). 2 died due to disease progression and 1 due to a cardiovascular event. Sequential chemo-radiation allows laryngeal preservation in about 2/3 of surviving patients without compromising survival.

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.

Ent of Femoral Artery Pseudo-Aneurysms 

G. Szendro, A. Klimov, A. Lennox, B. Jonathan, L. Avrahami, B. Yechieli, M. Griffin, S. Yurfest, Y. Charach, L. Golcman, A.N. Nicolaides

Vascular Surgery Dept., Soroka Medical Center, Beer Sheba; Irvine Laboratory for Cardiovascular Investigation and Research, St. Mary's  Hospital, Imperial College Medical  School, London; Vascular Laboratory, Soroka Medical Center, Beer Sheba; and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

The femoral artery remains the most used peripheral site for radiological catheter access. With a greater number of both diagnostic and therapeutic procedures being performed by interventional radiologists and cardiologists, and with larger catheters being used for stenting and endovascular grafting, the incidence of iatrogenic pseudo-aneurysms reported has reached as high as 0.5-2%. Ideally, they should thrombose spontaneously. However, when this does not occur, management options include: observation, ultrasound-guided obliterative compression, direct thrombin injection, embolization, stent graft insertion, and very rarely- surgery.

During a 7-year period (1992-1999) we treated 131 cases of femoral artery false aneurysms. Until 1998 ultrasound-guided compression-obliteration, with a 95% success rate, was our method of choice. Since 1998, direct thrombin injection, with 100% success in 24 cases, has become our preferred method. It is pain-free, fully successful even in anticoagulated patients, and is currently our treatment of choice.

Laparoscopic Ultrasound in Predicting Resectability of Choriocarcinoma

M. Shimonov, P. Schachter, G. Gvirtz, Y. Avni, A. Rosen, A. Czerniak

Depts. of Surgery, Ultrasound, and of Gastroenterology, Wolfson Medical Center, Holon and Sackler Faculty of Medicine, Tel Aviv University

Cholangiocarcinoma accounts for about 1% of all malignant tumors. They are difficult to diagnose because of their small size and their location. Although surgical resection is the best therapeutic approach, most patients undergo unnecessary exploratory laparotomy due to incorrect preoperative diagnosis.

We present our experience with laparoscopic ultrasound (LU) in the evaluation of cholangiocarcinoma and determination of tumor spread and vascular involvement. Of 25 patients referred for surgery, 6 were excluded following LU and were referred instead for palliative treatment. Diagnosis of the tumor was successful in 92%, and vascular involvement was diagnosed in 46%. LU should be an integral diagnostic test in the evaluation of choriocarcinoma.

Multiresistant Escherichia Coli from Elderly Patients

Ilana Slucky-Shraga, Moshe Wolk, Sofia Volis, Israel Vulikh, David Sompolinsky

Dept. of Medicine and Microbiology Laboratory, Mayanei Hayeshua Hospital, Bnei Brak; Central Laboratories, Ministry of Health, Jerusalem; and Faculty of Life Sciences, Bar Ilan University, Ramat Gan

We examined all ceftriaxone-resistant Escherichia coli isolates obtained from clinical samples during 16 months (1 Dec. '97 - 31 Mar. '99). A total of 97 resistant isolates from 36 patients were obtained, mostly from urine specimens. Of these patients, 35/36 were over 75 years old, most lived in nursing homes, were dependent on nursing in their daily lives, and were incontinent and/or had indwelling catheters.

All 97 isolates had similar susceptibility profiles: resistant to ciprofloxacin, gentamicin, ampicillin, amoxycillin/clavulanate, tricarcillin/clavulanate, aztreonam, and cefuroxime; decreased susceptibility to ceftazidime and cefepime; and susceptible to imipenem and meropenem. Double-disc tests indicated that all strains produced extended spectrum beta-lactamase(s). All the isolates belonged to 1 of 3 E. coli serotypes: 79 were 0153:H31, 13 were 0142:H10, and 5 were 0102:H6.

נתן רוז'נסקי, אברהם בן-שושן

מח' לרפואת נשים ויולדות, ביה"ח הדסה, עיןכרם, הפקולטה לרפואה של האוניברסיטה העברית, ירושלים

Tacrolimus does not Accentuate Hepatic Damage due to Hypoperfusion 

Ron Ben Abraham, Ivgeni Isartal, Richard Nakache, Vallery Rudick, Daniel Ogorek, Gideon Paret, Avi Weinbroum

Dept. of Anesthesiology and Critical Care Medicine, Organ Transplantation and Postoperative Care Units, Tel Aviv-Sourasky Medical Center; and Pediatric Intensive Care Units, Sheba Medical Center, Tel Hashomer; and Sackler Faculty of Medicine, Tel Aviv University

Deterioration of hepatic function following liver transplantation is a known complication, sometimes attributed to the use of cyclosporin A. Reaction to tacrolimus (Prograf), a relatively new and effective immunosuppressant drug, is thought to result in a much lower grade of organ dysfunction, especially in the transplanted liver.

Using the ex-vivo rat model of isolated perfused liver, we evaluated hepatocellular damage and oxygen extraction when tacrolimus was administered following liver hypoperfusion. Tacrolimus did not worsen hepatic dysfunction caused by the hypoperfusion. Therefore using tacrolimus in the perioperative period might be safer than cyclosporin A, which tends to worsen hepatic damage in the presence of hypoperfusion.

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.

Laparoscopic Approach in Treating Hepatic Cysts 

P. Schachter, V. Sorin, M. Shimonov, A. Rosen, A. Czerniak

Dept. of Surgery A, Wolfson Medical Center, Holon

Solitary and multiple hepatic cysts are now more commonly found because of advances in imaging techniques. Most hepatic cysts are asymptomatic, but when they do cause symptoms they require surgical intervention. The advent of laparoscopy and of laparoscopic ultrasonography allow comprehensive evaluation and treatment of the cysts.

12 patients with hepatic cysts were treated laparoscopically. 8 with single cysts underwent successful subtotal cyst resection without signs of recurrence (up to 20 years of follow-up). 4 with polycystic liver disease underwent sub-total resection of superficial cysts. Deep cysts were unroofed and drained under laparoscopic ultrasound guidance. In this group, 1 experienced recurrence of symptoms and required partial hepatectomy of the involved segment. In another, a connection between a deep cyst and bile ducts was demonstrated and cystojejunostomy was performed.

The laparoscopic approach in the management of patients with liver cysts is effective and safe, and we recommend it as the procedure of choice for single hepatic cysts. In polycystic liver disease the procedure is much less successful.