Pseudomembranous Colitis: Clinical, Endoscopic and Radiological Correlation - A 2 - Year Experience

Fabiana Benjaminov MD⁽¹⁾, Rivka Zissin MD⁽²⁾, Benjamin Novis MD⁽¹⁾

⁽¹⁾Gastroenterology Institute and ⁽²⁾CT Unit, Meir Hospital, Sapir Medical Center, Kfar-Saba, affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

Abstract: The incidence rates of pseudomembranous colitis are rising. Early diagnosis and treatment are required for management of this potentially life-threatening disease. This report outlines our 2-year experience (1997-1998) at the gastrointestinal institute with 43 patients diagnosed with pseudomembranous colitis and describes the clinical course and imaging studies.

The group consisted of 25 women and 18 men, aged 34-93 years (mean: 67). Thirty-nine patients were treated with antibiotics. Twelve patients were referred directly to an endoscopic examination with a presumed clinical diagnosis of pseudomembranous colitis (diarrhea, fever and abdominal pain) that was confirmed by colonoscopy. Thirty-one were referred to colonoscopy following abdominal imaging performed to clarify cause of fever and abdominal pain. Twenty-nine patients had an abdominal CT, one had an US and one a barium follow-through. The CT finding suggesting pseudomembranous colitis included colonic mural thickening in 28 patients (71% diffuse versus 29% segmental colitis), with an average wall thickness of 16 mm. Sixteen patients (59%) had pericolonic fat changes and 15 patients (51%) had ascites. All of these patients, except one, had endoscopic findings consistent with pseudomembranous colitis.

Five patients (11.6 %) died due to the severe PMC.

To conclude, as an abdominal CT is often performed in the acutely ill patient, it may arouse the diagnosis of pseudomembranous colitis in the proper clinical setting. Such a suspected diagnosis justifies endoscopic evaluation, which is the most reliable diagnostic examination.

The Effect of Gastro-Esophageal Reflux Therapy on Respiratory Diseases in Children

Y. Levin¹, A. Mandelberg², A. Gornstein³, F. Srour³, S. Reif⁴

¹The Sackler Faculty of Medicine, Tel-Aviv University, ²The Unit of Pediatric-Pulmonology, Wolfson Hospital, ³The Unit of Pediatric-Surgery, Wolfson Hospital, ⁴The Unit of Pediatric-Gastroenterology, Dana Children's Hospital

In order to examine the effect of reflux therapy on Hyper Reactive Airway Disease (HRAD) and apnea severity, 107 children, 78 with HRAD and 29 with apnea, underwent pH monitoring in the Pediatric Surgery Unit of Wolfson Hospital and the Dana Children's Hospital during the years 1995-1998. Pathological reflux was defined by means of the Boix-Ochoa and RI (Reflux Index) scores. In patients with positive reflux, anti-reflux treatment was initiated. Prior to and following pH monitoring, the respiratory status of all patients (both with and without reflux) was evaluated by a pediatric pulmonologist employing commonly used scores to determine severity.

Results: Subject age ranged between one day and 15 years (mean: 15.44±29 months, median: 6.37 months). In HRAD, following anti-reflex treatment the reflux positive group showed a significant score improvement, from an average of 2.9±1.1 units to 1.54±1.2 units (p<0.0001); a decrease in the number of patients treated with oral corticosteroids (p<0.01); a close to significant decrease (p=0.069) in the average dose of inhaled corticosteroids; and a decrease in the number of patients using bronchodilators (p=0.042). The reflux-negative group, not treated for reflux, displayed no significant improvement, with only a decrease in the severity scores from 2.44±1.0 to 1.78±1.2 units (p=0.14), and no change on any of the other parameters.

In apnea, all patients improved, from an average score of 2.34±0.77 to 0.03±0.19 units (p<0.0001), with no significant difference between the reflux positive and the reflux negative groups.

In view of these findings, it is postulated that anti-reflux therapy may have an additive effect on HRAD severity, beyond that of spontaneous respiratory improvement. We therefore find it appropriate for every severe HRAD patient (frequent exacerbations or high corticosteroid dose) to undergo pH monitoring in order to treat those with proven reflux. In respect to apnea, we cannot attribute any significance to the existence of reflux or to anti-reflux treatment.

(1,2) ניר פלד, (1,2) צ'רלס נקר, (2) שי אשכנזי, (1) פאול מרלוב

(1) המח' לילודים, מרכז רפואי רבין, קמפוס בילינסון, (2) מרכז רפואי "שניידר" לילדים, פתח תקווה, הפקולטה לרפואה סאקלר, אוניברסיטת ת"א

בשני העשורים האחרונים, נרשמו תנודות חדות בשכיחות העולמית של מחלת העגבת בכלל ועגבת הילוד בפרט. בראשית שנות התשעים, אובחנה עגבת הילוד בכל 1/10,000 לידות של ילודים חיים בארה"ב. התמותה במחלת עגבת הילוד מגיעה לכדי 40% (תוך- וחוץ-רחמית), ואף השורדים לוקים בתחלואה קשה. לפיכך, ממליץ המרכז לבקרת המחלות בארה"ב (CDC) על סקר נוגדנים בלתי סגולי לעגבת לכל אם הרה במהלך השליש הראשון להריון, או בתחילת המעקב ההריוני, הסקר נערך באמצעות תבחין בלתי-סגולי למחולל העגבת, Treponema pallidum, לרוב תבחין VDRL.

נוכח העלייה הנרשמת בשיעור חולים אלה בישראל, דנה סקירה זו במעקב ההריוני וניהול היילוד שאמו בעלת תבחין VDRL המפורש כחיובי.

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.
 

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.
 

In Vitro Interferon-Gamma Release in Diagnosis of Cutaneous Adverse Drug Reactions

S. Halevy, A. D. Cohen, N. Grossman

Dermatology Dept, Skin Bank and Investigative Dermatology Laboratory, Soroka University Medical Center and Faculty of Health Sciences; Ben-Gurion University of the Negev, Beer Sheba

Diagnosis of cutaneous adverse drug reactions is an accepted terminology. Is a challenge. Drug-specific T-cell clones (CD4+ or CD8+), with a Th1- or a Th2-type cytokine-release pattern, may be generated from the peripheral blood in CADRs. In vitro drug-induced cytokine-release suggests a drug-specific immune response, and may implicate the drug as a possible inducer of the skin reaction.

We evaluated the diagnostic role of in vitro drug-induced interferon-gamma (IFN-γ) release from peripheral blood lymphocytes in patients with CADRs. We studied 22 patients with CADRs following intake of 45 drugs (1-4 drugs per patient). Drugs were classified into 3 categories of suspicion. 17 patients who took 39 drugs of the same type (1-4 drugs per patient) without developing adverse reactions, served as controls. In vitro drug-induced release of IFN-γ from peripheral blood lymphocytes, following in vitro challenge with the unmodified drugs, was evaluated.

The mean IFN-γ increase following 45 drug tests (60.8±85.2%) was higher (p<0.05) than in controls after 39 drug tests (30.1±27.7%). Significance was greater (p<0.005) when the mean IFN-γ increase for the 24 highly suspected drugs (75.1±93.4%) and that for the controls were compared.

This study suggests that the in vitro drug-induced IFN-γ release test may serve as a diagnostic tool in CADRs.

בעשור האחרון, פורסמו מספר עבודות, בהן הודגם, כי בקרב חולים עם תחלואה של חלל הפה, ובייחוד דלקת מיסב-השן – דמ"ש (דלקת מיסב השן – periodontitis) ודלקת חניכיים, קיימת היארעות מוגברת באופן משמעותי של טרשת העורקים וביטוייה הקליניים השונים: מחלת לב כלילית, אוטם בשריר הלב ואירוע מוחי. במקביל להצטברות המידע האפידמיולוגי, חלה בשנים האחרונות התקדמות רבה בכל הקשור להבנת התהליכים שביסוד טרשת העורקים.

בתוך הרובד הטרשתי קיימים תהליך דלקתי ותגובה חיסונית פעילה, שבהם נוטלים חלק, בין השאר, לימפוציטים מסוג T ומאקרופאגים משופעלים. מאמץ מחקרי רב נעשה על מנת לאתר את מחוללי הנזק הראשוני בדופן כלי הדם ואותם אנטיגנים, נגד אנטיגנים זרים (ממקור חיידקי, נגיפי וכיו"ב); לחלופין, ייתכן שמדובר בתגובה-צולבת כנגד אנטיגנים עצמוניים.

נסקור את התאוריות השונות לגבי הקשר בין מחלות חלל הפה ומיסב-השן ובין טרשת העורקים. תאוריות אלו מדגימות היטב את מרכזיותו של הגירוי הזיהומי והתגובה החיסונית כלפיו בהתהוות מחלת טרשת העורקים.
 

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.
 

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.

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.

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.

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.

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.