תוצאת חיפוש

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.

Intravenous Immunoglobulins Treatment of Patients with Graves' Ophthalmopathy

Adi Leibe, Yair Levy, Yehuda Shoenfeld

Department of Medicine B and Research Unit of Autoimmune Diseases, Chaim Sheba Medical Center, Affiliated to Sackler Faculty of Medicine, Tel-Aviv University

Graves' ophthalmopathy is an autoimmune disease manifested as exophthalmus, lid lag and diplopia. As in the accompanying autoimmune thyroid disease, there is an autoimmune homoral and cellular attack on the orbita, mainly the retro-orbital tissues.

Steroids are the comerstone of therapy. We reviewed the evidence for a similar therapeutic effect of I.V., immunoglobulins (IVIGs) and their better side affect profile as compared to steroids. We also described an impressive therapeutic success with IVIG given to a patient with resistant ophthalmopathy. The clinical picture of Graves' ophthalmopathy is attributed to a pathologic hyper - activation of orbital fibroblasts, deposition of collagen and glycosaminoglycans in the extra-cellular matrix and eventually fibrosis. These are mediated by leucoregulin, IL-1, IFN-gamma, and TGF-beta - all secreted by lymphocytes and mast cells in the retorbital space.

Another mode of cell activation is by binding of autoantibodies (presumably thyroid stimulating Ab's) to an antigenic determinant on the surface of fibroblasts.

I.V. immunoglobulins, known today to be active in a variety of autoimmune processes, exert their effect on autoantibodies, complement, phagocytic cells etc. IVIGs also inhibit orbital lymphocytes and fibroblasts through inhibition of IL-1 or/and TGF-beta.

Traumatic Brain Injury: The National Trauma Registry*

Einat Peles, Vita Barell, Valentina Boyko, Arnona Ziv, Giora Kaplan

Health Services Research Unit, Ministry of Health, Sheba Medical Center Tel-Hashomer

Background: Traumatic Brain Injury (TBI) has been established as a category in reporting systems. Uniform data systems case definition has been suggested for hospital discharge data surveillance systems cases based on ICD-9-CM diagnostic codes. These include fractures and specific mention of intracranial injuries such as contusion, laceration, hemorrhage, and concussion. Inspection of data from the Israel National Trauma Registry suggested that two diagnostic groups of very different severity and outcome were being unjustifiably combined.

Aim: To evaluate the validity of categorizing TBI into two discrete groups, using the presence of specific mention of intracranial injury and/or loss of consciousness for more than one hour as the definition of definite TBI. Possible TBI includes skull fractures with no mention of intracranial injury and/or concussion with no loss of consciousness.

Methods: The study population includes all traumatic injuries admitted to hospital, dying in the ER or transferred to other hospitals and recorded in the 1998 Trauma Registry in all 6 level I trauma centers in Israel and two level II centers.

Results: The significant difference in severity between groups supports the validity of sub-dividing the TBI classification into definite and possible subcategories. As a result, we obtain two different severity groups without measuring specific severity scores which are limited in the reporting system.

Conclusion: The groups were significantly different in severity, hospital resource use, immediate outcome, demographic and injury circumstances.

*           Level I: Rambam, Beilinson-Schneider, Sheba, Ichilov (Tel Aviv Sourasky Medical Center), Hadassah Ein Karem and Soroka.

            Level II: Hillel Yaffe and Kaplan

Retinal Injury Induced by Laser Pointers

D. Israeli, Y. Hod, O. Geyer

Eye Dept., Carmel Medical Center, Haifa

Laser pointers originally designed for use during presentations are ubiquitous and are even sold as toys (such as pens or on key chains) in drug stores. Though reported as safe, the laser pointers still carry the risk of potential damage to the eye. We report a 16-year-old boy with bilateral retinal injury caused by 20-30 seconds of exposure to a laser pointing-device. Immediately thereafter, vision was blurred bilaterally and he noted a central red scotoma in each eye. Symptoms resolved spontaneously within 2 days but the retinal scars remained all during the 10 months of follow-up.

It is clear from our report and 3 other publications that retinal damage can develop from misusing laser pointers. Laser hazards and safety should be stressed for the general public. We recommend that laser-pointers should not be available as toys to children and teenagers.

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.

Cortical Blindness Following Coronary Angiography 

Addie Ron, Simcha Meisel, Myra Shapiro-Feinberg,Herman O. Klein

Depts. of Medicine, Cardiology and Diagnostic Imaging,Meir Medical Center, Kfar Saba

Cortical blindness has been occasionally reported as a complication after cerebral angiography, but is rare after coronary angiography. The contrast agent is believed to be responsible for the sudden development of blindness. Although the exact mechanism is unknown, it appears that the contrast agent disrupts the blood brain barrier, mostly in the occipital areas.

We report a 77-year-old man who suddenly developed transient, bilateral cortical blindness 4 hours after coronary angiography. Using contrast enhancement, the CT scan showed typical, symmetrical involvement of both occipital lobes. There were no other neurological deficits. Vision and CT findings returned to normal within 48 hours.

Causes of Blindness in Israel 

Y. Hod, Y. Corcia, Y. Yassur, O. Geyer

Depts. of Ophthalmology, Carmel Medical Center, Haifa and Rabin Medical Center, Petah Tikva; Israel Ministry of Labor and Social Affairs, Jerusalem; and Rehabilitation Services Administration, Services for the Blind

Of the world population, 38 million are blind and another 110 million are visually impaired. Even in the developed countries there are 3.5 million who are blind.

This study of blindness in Israel is based on the National Blind Registry. At the end of 1998, 15,937 were registered as blind, 0.3% of the total population; 776 (5%) of them were 18 years old or younger; 6,426 (40%) 18-65 years old; and 8,735 (55%) 65 years or older.

The leading causes of blindness in Israel are glaucoma (2,074, 13%), macular degeneration (1,954, 12%) and diabetes mellitus (1,680, 11%). Since glaucoma and diabetes, and to a lesser extent glaucoma, respond to treatment, blindness could have been avoided in most cases. National screening programs for early diagnosis and treatment of these diseases would reduce prevalence of the newly blind.

Early Detection of Glaucoma by a Mobile Unit

S. Kurtz, M. Goldenfeld, S. Melamed

Sam Rothberg Glaucoma Center, Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer

Glaucoma, the third leading cause of blindness in the western world, is characterized by painless, gradual loss of visual fields which may lead to severe visual impairment or even blindness. In 4 years of operation of a mobile glaucoma unit for screening and early diagnosis of glaucoma, 10,037 subjects aged 18-95 years were screened (4504 women, 45%); 55% were under 50 years (Graph 1).

Ocular hypertension was diagnosed in 8.0%; primary open angle glaucoma (POAG) in 0.8%, with 2/3 already under treatment, the rest newly diagnosed. Pseudo-exfoliative glaucoma was diagnosed in 0.2%; only 2 cases had closed angle glaucoma; 91% of those screened were normal (Fig. 4; age stratification, Graph 3).

POAG increased with age, from 0.2% in those under 40 years to 10% in those over 80; POAG was more common in men, but OHT was similar in both sexes (6.0% vs. 5.3%). There was no correlation between incidence of POAG and place of work except in the Sorek Nuclear Center (1.9% vs. 0.8%, p=0.11). Other conditions significantly more frequent in POAG than normals were diabetes mellitus (x 2.5), systemic hypertension (x 4), myopia (x 2) and history of intraocular surgery (x 6).

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.

Corneal Infection - Causes and Effects on Vision

Y. Domniz, R. Avisar, H. Savir

Ophthalmology Depts., Assaf Harofeh Medical Center, Zerifin, and Hasharon Hospital, Petah Tikva

We conducted a retrospective 5-year survey of corneal infections treated in the ophthalmology ward of Hasharon Hospital. The most frequent type of corneal infection was corneal abscess; the most frequent cause was Staphylococcus albus, although this bacterium is not reported as a frequent cause of corneal infections.

There was improvement in visual acuity in 69.2% and no change in 15.4%. Corneal infection by Pseudomonas aeruginosa was the most frequent cause of worsening of corneal acuity (23.08%). The greatest improvement of visual acuity was in those with corneal ulcers. The worst visual acuity was in those with corneal abscesses. Pseudomonas aeruginosa was the main cause of infection in contact-lens wearers.

In the world medical literature, Staphylococcus albus is considered of very low virulence. This bacterium was the most frequent cause of corneal infections in our study so it may have greater virulence in Israel.

Retinal Lesion due to Excessive Exposure to Sunlight

Irene Krasniz, Itzchak Beiran, Benjamin Miller

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

Retinal damage caused by direct exposure to the sun's rays is well recognized by the ophthalmic community. Although functional ability in solar retinopathy is usually regained within weeks, some suffer long-term visual impairment. Anatomic damage to the retina, even in those who regain full vision, is permanent. We describe 2 cases of solar retinopathy, 1 of which remained with permanent loss of vision. The role of medical education in preventing damage from solar retinal hazards is stressed.

Evaluation of Clinical Findings in Occupational Health Examinations

Rafael Carel, Eynat Scheiner

Dept. of Occupational Medicine, Kupat Holim, Negev Region and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

Findings in occupational health examinations of a regional service are analyzed. The service provides pre-employment, surveillance and work-capacity evaluations for about 150,000 workers from many types of work-sites and occupations. The average number of pre-employment examinations (during 1993-97) was 4,800/year, and there were relevant pathological findings in about 6.6%. Most findings involved the respiratory (11%) and cardiovascular systems (10%) or eyes (10%).

The average annual number of surveillance system examinations was 10,750. There were relevant findings in about 16%, mainly of the respiratory system (17%) and noise-induced hearing damage (about 80%).

Work-capacity examinations constituted about 35% of the work-load (9,250 examinees/year). In 53% a significant health problem affecting an individual's job performance was identified. Pathological findings were found in the musculoskeletal (21%), cardiovascular (7.5%), respiratory (3%), and neurological systems (2%).

Occupational health examinations can identify areas in which prevention and intervention or cooperation with other medical specialties are indicated, as well as specific topics requiring further training of occupational physicians.

Superficial Skin Necrosis in Short Bowel Syndrome

Arie Eisenman, Rafael Enat

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

Short bowel syndrome causes a complex of symptoms due to compromise of small intestinal nutrient absorption. A 60-year-old woman underwent major resection of the small intestine due to a road accident 3 years ago. The sole manifestation of short-bowel-syndrome was superficial skin necrosis due to vitamin K deficiency. She was asymptomatic for a long time, until treatment with antibiotics further intensified initially subclinical malabsorption.

It is not clear why there had been no other symptoms and why the main impact was on the fibrinolytic system rather than the coagulation system, as is usually the case. It is recommended that patients after major resection of the small intestine be closely monitored for coagulation function if an oral antibiotic is prescribed.

Brucellosis Presenting as Acute Abdomen

Nathan Kaufman, Noga Reichman, Edith Flatau

Dept. of Medicine B, HaEmek Medical Center, Afula

Usually symptoms of brucellosis are nonspecific and characterized by a wide range of complaints. Although the disease in Israel is almost exclusively food borne (caused by Brucella melitensis in unpasteurized goat milk products) so the main route of infection is the gastrointestinal tract, but gastrointestinal complications are rare, and only sporadic cases of ileitis or colitis have been described.

We present a 43-year-old woman with an acute abdomen, probably due to diverticulitis. It was diagnosed only after blood cultures were positive for Brucella melitensis. We believe that its protean manifestations should be consin addition to the other bizarre presentations of this disease, important in our region.

Nonpenetrating Deep Sclerectomy

Orna Geyer

Ophthalmology Dept., Tel Aviv-Sourasky Medical Center

This is the first report from Israel of nonpenetrating deep sclerectomy (DS), a new operation for the surgical management of glaucoma. It facilitates ocular fluid drainage without entering the eye. It involves performance of a conjunctival flap and creation of a 565 mm superficial scleral flap. A deeper scleral flap is dissected off the scleral bed together with the roof of the canal and corneal stroma, leaving behind the wall of the canal and membrane. Aqueous will flood the dissected area. A collagen device is then sutured to the scleral bed, the superficial scleral flap sutured into position and the conjunctiva closed. With this procedure, the surgeon can avoid the common complications of conventional glaucoma surgery.

We report a 6-month follow-up of 15 patients after DS. Mean preoperative intraocular pressure was 26.7+2.5 mm Hg, which decreased to 15.5+4.7. After 6 months there was no change in visual acuity after surgery. DS is associated with good middle-term intraocular pressure control and a low rate of postoperative complications. It is therefore a good alternative to standard glaucoma surgery.