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.

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.

Secondary Bone Grafting in Cleft Lip and Palate

M. Peled, D. Aisenbud, D. Goldstein, A. Rachmiel, D. Laufer

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

Results of reconstruction of residual alveolar bone defects in 52 patients operated between 1990-1998 were evaluated clinically and radiographically in a retrospective study.

Ages ranged between 9-37; 30 were males. The donor site of bone grafts in all was particulate cancellous marrow from the anterior iliac crest. 32 had unilateral clefts and 20 bilateral. Total cleft sites treated was 72.

Best results were achieved when bone grafting was carried out prior to the eruption of the canine tooth. The cleft space was closed and oro-nasal fistulas were eliminated in 42 (80%). Success rates in unilateral and bilateral cases were significantly different.

Reactions of Patients to Complementary Medicine

Bella Bar-Cohen, Freda DeKeyser, Nurit Wagner

Division of Nursing and School of Nursing, Hadassah Medical Center, Jerusalem

350 patients attending 11 large out-patient clinics completed questionnaires evaluating attitudes to, and experience with complementary medicine. 129 (36%) respondents reported using complementary medicine. 14% of them used complementary medicine for the current medical problem for which they were attending the clinic.

Pain was the most common medical problem for which complementary medicine was used, followed by respiratory problems and cancer. Common therapeutic modalities used were acupuncture, homeopathy, nutrition and herbal medicine.

Women, the secular as opposed to the religious, and those with higher education were more apt to use complementary medicine. No differences were found in age, national origin, length of living in Israel, and diet (vegetarian, natural foods or regular diet) between those who used complementary medicine and those who did not. No relationship was found between the use of complementary medicine and perceived poor health status, locus of control, or satisfaction with the doctor-patient relationship.

Corneal Infection in Wearers of Contact Lenses

Y. Domniz, R. Avisar, H. Savir

Assaf Harofeh Medical Center, Zerifin; and Hasharon Hospital, Petah Tikva

This is a 5-year retrospective survey of corneal infection in wearers of optical contact lenses (OCL). 23 of the 61 patients (38%; Hasharon Hospital) with positive cultures wore OCL. Visual acuity improved in 15 (65%), no change was noted in 4 (17.5%) and there was deterioration in 4 (17.5%), as compare with status on admission.

Pseudomonas aeruginosa was the most common cause of infections among OCL wearers. The improvement in visual acuity expected due to wearing OCL was affected by infections. After Staphylococcus albus infections had the highest rate (100%) of improvement in visual acuity and after Ps. aeruginosa the lowest rate (57.2%) of improvement, as well as the highest rate of deterioration (42.8%) found following recovery.

OCL wearers are at higher risk for damage to visual acuity following corneal infection, and highly virulent infections in OCL wearers are responsible for a high risk of damage to visual acuity.

Life-Threatening Echovirus 11 Infection During First Month of Life

U. Rubinstein, M. Weisbrod, B. Garty

Neonatal Dept., Laniado Hospital, Kiriat Zans, Natanya; and Pediatrics B, Dept., Schneider Children's Medical Center, Petah Tikva

Infection with Echovirus 11 is mostly asymptomatic, but it may cause a wide variety of clinical diseases, from gastroenteritis to serious diseases such as meningitis and myocarditis. In small infants, especially during the first days of life, echovirus infection may appear as a sepsis-like illness, and cause disseminated intravascular coagulopathy and shock.

We present 2 infants with severe echovirus 11 infections. A 3.5-month old died within 24 hours of shock and probably myocarditis. The other, 6-days old, presented with meningitis, hepatitis and disseminated intravascular coagulopathy. It recovered after treatment with intravenous immunoglobulin.

Echovirus 11 may cause life-threatening infections in small infants. Pediatricians should be alert to the special characteristics of this disease.

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.

Combined Approach in Management of Penetrating Injury of Vertebral Artery

Y. Kluger, B. Sagie, D. Soffer, N. Hai, D. Oron

Rabin Trauma Center and Division of Invasive Radiology, Tel Aviv Medical Center

Penetrating injuries of the vertebral artery are not common. Although surgical control of this type of injury is well- documented, the combined approach (surgery and packing for temporary control of bleeding, followed by angiography and embolization for permanent control) is now recognized and practiced.

We describe a 40-year-old man who was stabbed in the neck. He was rushed to the operating theater in hemorrhagic shock. A vertebral artery injury was identified and packed. Angiography and embolization permanently controlled the bleeding.

The combined approach is safe and we recommend it in those in whom bleeding from the vertebral artery is initially well controlled with packing.

Dermatitis from Contact with Agave Americana

Haim Golan, Marina Landau, Ilan Goldberg, Sara Brenner

Dermatology Dept., Tel Aviv-Sourasky Medical Center

Various plants induce dermatitis in man. There have been only a few published cases of contact dermatitis caused by Agave americana (AA).

We report intentional exposure to AA in a soldier seeking sick leave, and review our previously reported cases. Treatment with oral antihistamines and topical saline compresses resulted in subsidence of the systemic symptoms within 24h and regression of cutaneous manifestations in 7-10 days.

Physicians should be alert to the possibility of self-inflicted contact dermatitis induced by exposure to plants, especially to A. americana. Systemic signs may accompany the cutaneous lesions.

Thrombocytopenic Purpura as Sole Manifestation of Brucellosis in a Child

Ronen Marom, Dan Miron, Herzel Gabriel, Yosef Horowitz

Pediatric Dept. A, Pediatric Infectious Disease Service, and Pediatric Hemato-Oncology Unit, HaEmek Medical Center, Afula and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa

Thrombocytopenic purpura associated with brucellosis has rarely been described in children. The thrombocytopenic purpura is usually part of the array of manifestations of brucellosis, such as fever, malaise, arthralgia, arthritis, hepatosplenomegaly and lymphadenopathy.

We describe a 4-year-old girl in whom severe thrombocytopenic purpura was the only manifestation of brucellosis which resolved after appropriate antibiotic therapy. We conclude that brucellosis should be included in the differential diagnosis of thrombocytopenic purpura in areas endemic for brucellosis, and when there is a history of exposure to infected food products.

Experience with 100 Liver Transplant Recipients 

Ezra Shaharabani, Ziv Ben-Ari, Nathan Bar-Nathan, Alex Yusim, Rivka Shapira, Ran Tur-Kaspa, Zaki Shapira, Eytan Mor

Transplantation Dept., Liver Institute, Rabin Medical Center; and Pediatric Gastroenterology Institute, Schneider Children's Medical Center, Petah Tikva

Liver transplantation is the treatment of choice for end- stage liver disease. During the past 8 years we performed 102 liver transplants in 84 adults and 16 children. In the adults, 9 were combined transplants: 1 a liver-pancreas transplant for type I diabetes, and 8 liver-kidney transplants. In the children, transplants included 5 whole-livers, 5 left-lateral liver segments from living-related donors, 4 reduced-grafts of right or left lobes, and 2 split left-lateral segments.

At a mean follow-up of 31 months (range 1-96) 70 were alive, 3 had died during surgery and 15 during the first postoperative months. Mortality was due to primary graft non-function (7), sepsis (10), intracranial hemorrhage (1), tumors (4), recurrent hepatitis B (2), biliary strictures (2) and chronic rejection (1). The 1- and 4-year survival rates were 79.5% and 69.6%, respectively.

After transplantation, 10 developed biliary stricture (5 corrected by balloon dilatation) and 8 anastomotic stricture (7 corrected by surgery), and there were 2 multiple intra-hepatic strictures. There was hepatic artery thrombosis in 5, including 4 children. In 3, grafts were salvaged by thrombectomy and 2 others underwent re-transplantation. In those who survived transplantation by more than 1-month, recurrent hepatitis B was seen in 6 of 17 (35%) and recurrent hepatitis C in 12 of 19 (63%).

Thus, results of our first 100 liver transplants are similar to those reported by larger centers, showing that in an appropriate setting good results can be achieved by small transplant programs.

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.

Cells-Preliminary Report Immunohistochemical Identification of Testicular Germ

Batia Bar-Shira Maymon, Gedalia Paz, Leah Yogev, Ron Hauser, Letizia Schreiber, Amnon Botchan, Haim Yavetz

Institute for Fertility Study, Lis Maternity Hospital; Pathology Institute, Tel Aviv-Sourasky Medical Center; and Sackler Faculty of Medicine, Tel Aviv University

The use of testicular spermatozoa for intracytoplasmic sperm injection introduced a new treatment modality for management of male infertility.

Since testicular biopsies of non-obstructive azoospermic men are not homogenous in their histological patterns, identification with certainty of focal spermatogenesis might be difficult, particularly in those with small foci of spermatogenesis. We used an immunohistochemical marker of the male germ line, an antibody generated against RBM (RNA-binding-motif), to recognize with high precision the presence of germ cells in the biopsy. Biopsies of 30 men with azoospermia, most with non-obstructive azoospermia and a few with obstruction of the vas deferens, were evaluated.

Immunohistochemical staining for RBM protein contributed to the detection and accuracy of the identification of germ cells. Furthermore, this immunohistochemical technique aided the histopathologist to focus on even small foci of spermatogenesis. Absence of the protein expression confirmed the diagnosis of Sertoli-cell-only syndrome. The results indicate that expression of RBM can be a diagnostic marker for identifying the germ cells of small concentrations of spermatogenesis. This method can enhance the accuracy of histopathological evaluation of testicular biopsies that had formerly relied mainly on hematoxylin-and-eosin staining.

Penile Prosthesis for Erectile Dysfunction: Long-Term Follow-Up 

Ofer N. Gofrit, Ofer Z. Shenfeld, Ran Katz, Amos Shapiro, Ezekiel H. Landau, Dov Pode

Urology Dept., Hadassah University Hospital, Jerusalem

Our armamentarium for the treatment of erectile dysfunction has recently been expanded by addition of Viagra and the MUSE. However, their long-term results are still unknown. The insertion of a penile prosthesis is invasive, expensive, and irreversible, but under optimal condition provides an acceptable, definitive solution for erectile dysfunction. We evaluated our long-term results with penile prosthesis insertion (PPI).

From 1987-1998, 57 patients underwent PPI in our department. Mean age was 55 years and the common causes of erectile dysfunction were atherosclerotic disease (23), radical pelvic surgery (15), and diabetes mellitus (14). Semirigid prostheses were inserted in 12 and inflatable prostheses in 45, including 42 single-component and 3 multi-component prostheses.

Recently we interviewed these patients by telephone, using a standard questionnaire. Those not satisfied with the surgical results (83% of the living patients) were examined in our clinic. Mean follow-up was 53 months. In 37 (84%) the prosthesis was mechanically functional (rates after 1, 5 and 10 years were 87.8%, 80%, and 75%, respectively). In only 2 (2.5%) had serious complications led to prosthesis removal.

All mechanical failures had occurred in those with inflatable prostheses after a mean of 48.5 months (range 4-113). At the time of the survey 68% were sexually active and 64% were satisfied with the surgical result. We conclude that PPI is safe treatment for erectile dysfunction. Although the rate of mechanically functioning prostheses decreases with time, modern multi-component prostheses may lead to better mechanical results.

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.