Tuberculous Meningitis in HIV

R. Elazary, Y. Kalish

Medical Dept., Hadassah University Hospital, Ein Karem, Jerusalem

The increase in prevalence of tuberculous meningitis during the past decade has been attributed in part to the increase of AIDS. Failure to diagnose HIV can cause irreversible damage and even death. We describe a man with AIDS admitted through the emergency room because of high fever and headaches for more than a month, He was cachectic and had nuchal rigidity without major neurological deficit. Brain imaging was normal and lumbar puncture showed neutrophils, lymphocytes, hypochloremia, elevated protein, and decreased glucose; cryptococcal antigen was negative but acid-fast staining was positive.

Anti-TB chemotherapy was started using 4 drugs and dexamethasone was also given. Considerable improvement in his general condition followed rapidly.

Use of corticosteroids in tuberculous meningitis has been a major issue. They are added to antimicrobial agents in order to decrease reactivity of inflammatory mediators and thus reduce central nervous system damage.

We review several controlled studies in which steroids were added to treat tuberculous meningitis. The conclusions of most were that they decrease morbidity and mortality, especially of those moderately to severely ill. Most considered as ungrounded the possibility of exacerbating latent tuberculous, or any other opportunistic infection outside the central nervous system. However, it is currently recommended to add prednisone, 1 mg/kg/d for 2-4 weeks when initiating antituberculous treatment.
 

Newer Diagnostic and Therapeutic Methods in Lung Cancer

R. Rubinstein, R. Breuer, R. Chisin

Dept. of Medical Biophysics and Nuclear Medicine, and Institute of Pulmonology, Hadassah University Hospital, Ein Karem, Jerusalem

Positron emission tomography (PET), when used with F-18 fluoro-deoxyglucose (FDG), contributes to the evaluation of patients with lung cancer. This technique of imaging detects active tumor tissue by showing increased radiopharmaceutical uptake by metabolically active cells.

Thus, PET assists in the early diagnosis of pulmonary malignancies that appear only as non-specific findings on CT-scan or chest X-ray. In addition, it is helpful in staging lung cancer before and after resection, chemotherapy or radiotherapy, or their combined use.

We performed 135 FDG-PET studies between July '97-April '99. and present our preliminary results with examples of the main indications for PET in lung cancer.
 

עבד אלנאסר עזב, יורי ירוסלבסקי,

המח' לפארמאקולוגיה קלינית, אוניברסיטת בן-גוריון בנגב, המרכז לבריאות הנפש, באר-שבע

כיום, מצויה ספרות רחבת יריעה המתבססת על עבודות קליניות המצביעה על כך, שליתיום (litium) לא יוכל לתת מענה לכל החולים הלוקים במחלה אפקטיבית דו-קוטבית (מא"ד), ומכך נבע הצורך בחיפוש אחר אפשרויות טיפוליות נוספות. התרופות הראשונות שיעילותן הוכחה במחקרים קליניים מבוקרים (כפולי-סמיות) הן התרופות נוגדות הכיפיון (תנ"כ), קארבאמזפין חדישות, כגון לאמוטריגין (lamorigine), שגם לגביו קיימת עדות קלינית מצטברת והולכת שהוא עוזר לטיפול במחלה אפקטיבית דו-קוטבית.

את מנגנון הפעולה של התנ"כ (המשמשות כיום לטיפול במא"ד) ניתן לסווג באופן כללי לשלושה סוגים: 1) הגבלת הירי החשמלי המתמשך (היח"מ, sustained repetitive firing) של הנירונים, המושגת דרך הארכת תקופת האיבטול של תעלות נתרן. 2) הגברת השפעת (GABA) הגורמת להשפעה מעכבת באותן סינאפסות. 3) חסימה של תעלות סידן, בעיקר של תעלות בעלות סף נמוך (T-type). עם זאת, המנגנון שעומד מאחורי היות התנ"כ הנ"ל תרופות שעוזרות לטיפול במא"ד, עדיין אינו ברור.

חשוב לציין, שהמשותף לכל התנ"כ הללו הוא יכולתן לחסות את תעלות הנתרן (voltage-activeted sodium channel blockade), אך למרות זאת, התרופה פניטואין, החוסמת ביעילות אותן תעלות נתרן, עדיין לא ניתנה כטיפול במא"ד, על אף העובדה שהיא משמשת כתרופה נוגדת כיפיון כבר קרוב לשישה עשורים. לכן, היה עניין רב לבדוק את ההפעה הנטימאנית של פניטואין ובסקירה זו, יובאו התוצאות של עבודה ראשונית שנעשתה לבדיקת השפעות אלו של התרופה בקרב חולים עם מא"ד ובחולים סכיזואפקטיביים, שבהם נמצאה השפעה חיובית של התרופה.
 

A Molecular Method of Diagnosis of Congenital Adrenal Hyperplasia

Shoshana Israel, Chaim Brautbar

Tissue Typing Unit, Hadassah Medical Center, Jerusalem

Congenital adrenal hyperplasia (CAH) is caused mainly by deficiency of the 21-hydroxylase enzyme. The disease may appear in the classical salt-losing, simple virilizing forms or as a mild, nonclassical form. 21-hydroxylase is encoded by the CYP21B gene on the short arm of chromosome 6, in the midst of the human leukocyte antigen (HLA) complex, between HLA Class I and Class II regions.

We describe a method for identifying mutations in the CYP21B gene. It is based on amplification of the gene using the polymerase chain reaction and identification of mutations with sequence-specific oligo-probes. The mutations identified were: V281 and P30L responsible for nonclassical CAH, and I2 splice, Q318X, I172N, cluster E6, and a deletion including 8bP in the third exon (8bP del) responsible for the classical form of CAH.

We also analyzed 2 families affected with the classical form of CAH which demonstrate possible complications in genotyping. Typing for HLA haplotypes can be helpful in certain cases, as demonstrated in 1 of the families presented. In this case it was necessary to distinguish between 2 possible genotypes: 1 with the mutations in tandem on 1 chromosome and the other with the mutated genes on both chromosomes. HLA haplotyping enabled the assignment of the mutations to the relevant chromosomes and thus allowed correct genetic counseling.

The other family demonstrated the importance of CYP21B genotyping in individuals with the nonclassical form of CAH. This form may consist of 1 mild and 1 severe mutation, representing a serious potential for transmitting the classical form of CAH.

Atrophic Gastritis Presenting with Pulmonary Embolism

Muhammad A. Abdul-Ghani, Rima Feldman, Moshe Shai, Jacob Varkel

Dept. of Medicine C, Western Galilee Hospital, Naharia

Atrophic gastritis is an autoimmune gastropathy in which there is destruction of gastric parietal cells. This results in intrinsic factor deficiency and disturbance in vitamin B12 absorption. Its clinical manifestationa are therefore the consequences of B12 deficiency and include anemia and neurological defect. In addition, lack of B12 results in metabolic changes, including disturbances of methionine metabolism and accumulation of homocysteine.

In recent years, there has been increasing evidence suggesting that hyperhomocysteinemia is a risk factor for thrombo-embolic disease. We describe a 51-year-old man with atrophic gastritis, severe B12 deficiency and hyperhomocystein-emia. The initial clinical manifestation was pulmonary embolism, without either anemia or neurological signs. B12 deficiency should therefore be considered in patients being investigated for hypercoagulability.

Advantages of Standardized Protocol for Oral Rehydration in Acute Pediatric Gastroenteritis

Avi Weizman, Ahmed Alsheikh, Laura Herzog, Asher Tal, Rafael Gorodischer

Pediatric Depts. A and B, Soroka Medical Center; and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

Oral rehydration (OR) for acute gastroenteritis in infants and children has been shown to be as effective as IV therapy, with less discomfort and lower costs. In this retrospective study we compared 2 pediatric wards, in 1 of which only a standardized, simplified, bedside protocol, based on American Academy of Pediatrics guidelines, was used.

There were no significant clinical characteristics in the 208 patients. In the ward which used the above protocol, OR utilization was significantly more frequent than in the other ward (48% versus 15%), thus saving equipment costs of nearly $1,000/3 months. There were no significant differences in outcome between the wards.

We conclude that introducing a standardized management protocol may increase OR utilization in hospitalized children with acute diarrhea.
 

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.

Tuberculous Meningitis in Review

Mozes Toledo, Y. Skurnik, A. Razabek, Z. Stoeger

Medical Dept. B, Kaplan Medical Center, Rehovot, (Affiliated with Hebrew University-Hadassah Medical School, Jerusalem)

Tuberculosis meningitis is one of the most dangerous forms of tuberculosis (TB). Due to large waves of immigration, the incidence of TB in Israel has increased in recent years, as has that of TB meningitis. Due to its high mortality, rapid diagnosis of TB meningitis is of paramount importance.

We present a patient admitted with a acute febrile disease which was subsequently diagnosed as TB meningitis.

Acetaminophen Toxicity in Children - A Therapeutic "Misadventure"

Sarit Shahroor, Yigal Shvil, Mely Ohali, Esther Granot

Dept. of Pediatrics, Hadassah University Hospital and Hebrew University Hadassah Medical School, Jerusalem; and Dept. of Pediatrics, Barzilai Medical Center, Ashkelon

Acetaminophen toxicity after repeated administration of amounts that only moderately exceed recommended doses, is being increasingly reported in alcoholic or fasting adults. Pediatric experience with this pattern of acetaminophen toxicity is sparse.

We present 2 children who developed severe hepatic damage, with renal insufficiency as well in 1, after 15-20 mg/kg of acetaminophen, given at 4-hour intervals for 3-4 days during an intercurrent febrile illness. When given in doses as low as 20 mg/kg at frequent intervals for a number of days, the drug puts children who are vomiting or have sharply reduced caloric intakes at increased risk for severe toxicity.

Increased caution and awareness of the toxic effects of acetaminophen are needed, and it should be dispensed with appropriate package-label warnings.

Carbamazepine Hypersensitivity 

Shimon Ivry, Doobi Shteinmintz, Hava Tabenkin

Dept. of Family Medicine, HaEmek Hospital, Afula and National Residency Institute, Ben-Gurion University of the Negev, Beer Sheba

Carbamazepine (C) can cause a characteristic hypersensitivity reaction (CHS}. This multisystem reaction typically presents as fever, mucocutaneous eruption and lymphadenopathy. The syndrome usually develops between 1 week and 3 months after starting therapy, with involvement of the liver, lung, kidney and inappropriate secretion of ADH. The incidence is less than 0.001% in those treated with C and it is diagnosed clinically. With onset of CHS, the drug must be stopped and if there is no improvement, cortico-steroids should be started. When the diagnosis is in doubt, the patch test, lymphocyte transformation test, macrophage migration inhibitor factor, and other tests can be helpful.

The pathogenesis is not known. Similar syndromes have been described with phenytoin and phenobarbital. There is clinical and in-vitro evidence of cross reactions between C and phenytoin. It is not known whether the CHS syndrome should be considered a premalignant state, with increased risk for the development of malignant lymphoma.

Tubulo-Interstitial Nephritis and Uveitis - TINU Syndrome

Paz Yitzhaki

Dept. of Medicine A, Rambam Medical Center, Haifa

Acute tubulo-interstitial nephritis and uveitis (TINU syndrome) in a 53-year-old woman is reported. This rare syndrome was described 27 years ago by Dobrin et al. Since then about 50 cases have been described. The syndrome can appear at any age but most patients are under 20 years; about 75% are females. Clinical characteristics include fatigue, general malaise, weight loss, fever, night sweats, anorexia, nausea and vomiting, pallor, nocturia, polyuria, arthralgia and skin rash. Ocular involvement usually includes anterior uveitis but is sometimes posterior; in most cases the uveitis is bilateral.

The characteristic laboratory findings are anemia, rapid sedimentation rate, decreased glomerular filtration rate with increased serum creatinine and urea. Total protein is increased because of polyclonal gammopathy and elevated b2-microglobulin. Urinalysis characteristically reveals proteinuria and b2-microglobulinuria. The histopathologic features on renal biopsy are characteristic of tubulo-interstitial nephritis. Uveitis can precede, accompany or follow onset of the nephropathy.

The pathogenesis and etiology of the syndrome are as yet unknown. Treatment consists of large doses of corticosteroids, but the necessity for treatment is unclear, since there is evidence of spontaneous improvement. Although the prognosis of the nephropathy is favorable and most cases are reversible, the uveitis tends to recur.

Sclerosing Mesenteritis: An Unusual Cause of Abdominal Pain

Meir Mouallem, Zehavit Turok, Danny Rosin, Bruria Shalmon

Depts. of Medicine E, General Surgery and Transplantation, and of Pathology, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

Sclerosing mesenteritis (SM) is rare and fewer than 300 cases had been reported up to 1997. We describe a 29-year-old woman who had abdominal pain for 1 year and presented with a palpable abdominal mass. The diagnosis of SM was made only after diagnostic laparoscopy and biopsy of the peritoneum.

Acute and Chronic Hepatitis C in Hemodialysis Patients 

Nir Hilzenrat, Marcus Mostoslavsky, David Tovbin

Liver Disease Service - Division of Gastroenterology, Dialysis Unit, Dept. of Nephrology and Division of Internal Medicine, Soroka Medical Center and Ben-Gurion University of the Negev, Beer Sheba

Acquired infection with hepatitis C virus (HCV) in hemodialysis patients has been described lately. In dialysis units in Italy and France, the prevalence and incidence of HCV are 20-60% and 1-2%, respectively. Most infected patients develop chronic hepatitis. The clinical presentation of acute HCV in hemodialysis patients is very mild and therefore the diagnosis is often made only by laboratory tests. Acute infection is usually followed by mild elevation of liver enzymes and the presence of HCV-RNA and anti-HCV in serum.

We report a 48-year-old man on hemodialysis who developed acute hepatitis C. The diagnosis was made by finding mild elevation of liver enzymes and the presence of HCV-RNA in his serum. A few months later, he developed severe hepatitis which was followed by rapid deterioration in liver function. However, the virus was eradicated and liver function tests became normal. Surprisingly, serum anti-HCV antibodies were detected 5 months later.

Nutrition for Women's Health

Dorit Nitzan Kaluski, Alex Levental

Dept. of Nutrition, Public Health Services, Ministry of Health, Jerusalem

Biological, environmental and social factors predispose women to cardiovascular diseases, malignancy, osteoporosis, diabetes, obesity and eating disorders. Their prevention requires that health services recognize women as a risk group and provide appropriate financial and professional resources. To develop and apply intervention programs for women, funding must be allocated for data collection, development and assessment of intervention programs and involving women in decision processes. We address the diseases and conditions in which nutrition may contribute to primary or secondary prevention of the specified diseases.

Extraperitoneal Laparoscopic Adrenalectomy

J. Kuriansky, A. Saenz, D. Rosin, E. Astudillo, L. Fernandez-Cruz

Dept. of General Surgery and Transplantation, Sheba Medical Center, Tel Hashomer, and Dept. of Surgery, Hospital Clinic, Barcelona

Laparoscopic adrenalectomy has recently been shown to be safe and effective for a variety of benign adrenal tumors, such as aldosterone adenoma, pheochromocytoma, nonfunctioning adenoma, Cushing's adenoma and Cushing's syndrome. Recently, laparoscopic surgeons adopted an extraperitoneal approach in which a space is created by the introduction of a trocar with an inflatable balloon tip. This technique with a minimal access procedure provides direct access to the adrenal glands without interfering with intraperitoneal organs.

Laparoscopic adrenalectomy using the extraperitoneal approach was completed in 18/20 consecutive patients. Mean operative time was 95 min (range 80-120) and median hospital stay 3 days. Blood transfusion was not required, and there were no postoperative complications.