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.

ויקטוריה פורר(1), פסח ליכטנברג(1,2), אוריאל הרסקו-לוי(1,2)

הפקולטה לרפואה "הדסה", האוניברסיטה העברית, ירושלים (1), ביה"ח "הרצוג", ירושלים (2)

דיסקינזיה מאוחרת (ד"מ) היא הפרעה מוטורית המאופיינת במיגוון תנועות חריגות, בלתי רצוניות, בעיקר באזור הפנים והפה ולפעמים בגו ובגפיים. ההשפעה דווחה לראשונה בשנות החמישים, כחמש שנים לאחר שתרופות נירולפטיות קלאסיות הוכנסו לשימוש. בשנות ה-70 המוקדמות הוכרה ד"מ כפרי יפול נירולפטי ממושך.

העיוותים בפנים ובתנועות הנגרמים מחמת ד"מ משפיעים לרעה על איכות החיים של החולים ומדרבנים חוקרים להבין את ההשפעה על גורמיה והשלכותיה וגם למצוא טיפולים מתאימים.

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.

Pulmonary Adenocarcinoma in Myasthenia Gravis - Auto-Immunity and Late Development of Malignancy

Yitzhak Rosen, Yair Levy, Yehuda Shoenfeld

Dept. of Internal Medicine B, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

We report a 75-year-old man with myasthenia gravis for many years, who was hospitalized because of cough, fever, and dyspnea. Chest x-ray revealed a bilateral pleural effusion. Adenocarcinomatous cells were found in the pleural fluid. Computerized tomography of the chest showed widespread pulmonary dissemination of the tumor.

The relationship between myasthenia gravis, an autoimmune disease involving the motor end-plate, and malignancy (thymoma) has been widely recognized. Current literature documents few reports of lung malignancies with concurrent development of myasthenia gravis. A tentative explanation, based on current research, is provided for the possible role of myasthenia gravis and the late development of lung cancer. Moreover, a model for the autoimmune phenomenon and the development of late malignancies will be provided with explicit explanations. It is important to search for occult, developing malignancies in newly diagnosed autoimmune diseases.

Acute Ischemia of the Lesser Gastric Curvature 

D. Czeiger, A. Ariche, G. Shaked, N. Sion-Vardi, I. Levi

Trauma Service, Dept. of Surgery, and Pathology Institute, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer Sheba

The rich blood supply of the stomach protects it from ischemia and necrosis. Acute gastric ischemia, an emergency with high mortality, is rare. Atherosclerosis is the leading cause of acute ischemia, and the lesser curvature of the stomach is more vulnerable due to its relatively lesser blood supply. Reduction in gastric blood supply usually presents as chronic disease characterized by gastritis, gastric ulcer, or gastroparesis.

Gastroscopy can identify lesions of the gastric mucosa, and angiography demonstrates occluded vessels. Treatment of acute gastric ischemia is surgical, with total gastrectomy preferred over partial resection.

Prioritizing Suspected Diagnosis of Both Brain and Abdominalinjuries: Is it a Problem?

Leon Levi, Moshe Michaelson

Dept. of Neurosurgery and Trauma Unit, Rambam Medical Center, Haifa

Current guidelines for management of suspected head and abdominal injuries are based on retrospective studies like that of Wisner & al, Following a recent review in this journal by Y. Kluger & al, which was based on non-Israeli data, we decided to define the current status at our trauma center.

We compare our data of 18 months of hospital admissions for acute trauma in which head CTs were done with those of 5 articles advocating specific protocols for decisions in pre-laparotomy diagnosis.

In the 861 cumulated cases, compared with the 800 of Wisner & al, craniotomy was required in 15% vs 7% (p<0.05); laparotomy was much less frequent, 2.7% vs 12.9% (p<0.05). The chance of finding a case requiring both craniotomy and laparotomy was 1 in 300.

As the clinical condition of multiple trauma involving the head and abdomen is becoming less frequent and includes diverse situations, a comprehensive algorithm might be inaccurate. Good clinical judgment of the clinician and teamwork are therefor preferable.

Diabetic Ketoacidosis during the Ramadan Fast 

I. Friedrich, Y. Levy

Dept. of Medicine A, HaEmek Medical Center, Afula, and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa

We report a 15-year-old Muslim boy with insulin-dependent diabetes mellitus (IDDM) who presented with diabetic ketoacidosis (DKA) during the Muslim Ramadan month of day-time fasting. DKA apparently occurred due to omitting pre-lunch insulin combined with dehydration and overeating during the permitted sunset-to-sunrise meals.

It is well-known that fasting accelerates development of lipolysis and ketosis and increases glucagon levels. Thus, these pathophysiological aberrations related to fasting in ketosis-prone patients, in conjunction with fasting, endanger metabolic control in IDDM.

Transarterial Oil Chemoembolization for Hepatocellular Carcinoma 

Izhar Levy, Anthony Verstandig, Talia Sasson, Dana Wolf, Ilia Krichon, Eugin Libson, Pinchas Levensart, Orit Papo, Oded Yurim, Ahmed Id, Daniel Shouval

Division of Medicine, Liver Unit and Invasive Radiology, Radiology, Pathology and Surgery Depts., Hadassah University Hospital, Ein Kerem, Jerusalem

Hepatocellular carcinoma (HCC) is a common malignancy with a grave prognosis. Most patients have both the malignant tumor as well as hepatic cirrhosis. Liver transplantation or hepatectomy are considered the only curative procedures, but can be applied in fewer than 10% of patients. In recent decades the most common treatments of HCC are transarterial chemoembolization with oil (TOCE) and percutaneous ethanol injection (PEI). We summarize our retrospective study of 100 patients (mean age 64) 3‏ treated by TE.

In 271 procedures between 1989-1998, in 16 patients hepatectomy was combined with TOCE and in 8 PEI was combined with TOCE, while the rest were treated by TOCE alone. Tumor mass was reduced in 36% of those treated by TOCE (tumor volume reduced 24-75%). Alpha-feto protein (AFP) was reduced 25-90% in 20/32 of those with elevated AFP levels. Median survival for the 100 in the entire group was 19 months (10.9 months in those with conservative treatment). Median survival in the 57 in Okuda stage 1 and the 43 in stages 2 or 3 was 30.1 months and 10.9 months, respectively (p<0.0001). Of the 57 in stage 1, 16 underwent hepatectomy in addition to TOCE and 41 were treated only by TOCE (median survival 15 and 26 months, respectively, p not significant).

Comparing Okuda 1 patients treated by TOCE only with the natural history of the disease and historical controls (Okuda 1 patients treated conservatively in 1984) median survival was 26 and 10 months respectively (p<0.001). The side effects of TOCE were relatively mild. There was 1 fatality (3 days after treatment), and quality of life was maintained. Despite progress in the treatment of HCC by TOCE, PEI, and liver transplantation, long-term survival has remained unsatisfactory.

Patient Satisfaction and Hospital Services Evaluation by Regular and Private Patients

Sara Carmel, Jonathan Halevy

Dept. of the Sociology of Health, Faculty of Health Sciences, Ben-Gurion University of

the Negev, Beer Sheba; Sha'are Zedek Medical Center and Hebrew University-Hadassah Medical School, Jerusalem

"Sharap" is a private medical service integrated within our public clinic and hospital services. Clients may choose their physician by paying a fee in addition to what their health insurance agency (Kupat Holim) pays for. All other hospital services are supplied to all patients alike. The main purpose of this study was to evaluate the extent to which this declared policy is maintained in practice.

During 5 months in 1997, 198 Sharap patients and 198 regular patients were interviewed in the the general surgery, cardiac surgery, ENT, cardiology, newborn and gynecology wards of this hospital. Both groups were similar in regard to cause of hospitalization, gender, age group (10-year age ranges), and length of hospitalization (at least 24 hours).

Similar levels of satisfaction with hospitalization in general and with the nursing service and with supportive services were found in both groups. However, Sharap patients were more satisfied with their physicians than regular patients (87% vs 74%, respectively). Similar results were also found using indirect measures of satisfaction. About 86% in both groups reported having achieved the goal of improvement in health. A high proportion of respondents from both groups (82% and 88%, respectively) could not distinguish between Sharap and regular patients in the ward. However, a greater proportion of regular patients (35% vs 21%) wanted more extensive explanations from their physicians regarding their treatment.

Sharap patients belonged to higher socio-economic classes than regular patients. Our evaluation indicates that although the Sharap service enables the affluent to choose their preferred physician, resulting in a different doctor-patient relationship, the service does not create a significant feeling of discrimination among hospitalized patients, and does not interfere with the high level of health services available to the public at large.

Relapse of Sarcoidosis after Alternative Medical Treatment

Georgy Edelson, Yair Levy, Yehuda Shoenfeld

Dept. of Medicine B, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

Reference to alternative medicine frequently appears in newspaper headlines, advertisements and in articles in medical journals. The practice of alternative medicine has increased, even as the number of critical articles warning of deleterious effects have also increased. Public demand is strong and growing, but there are no clear rules as to what is not permissible, particularly when treatment is not by qualified physicians. There are still no clear indications and contra-indications for complementary (not alternative) medicine in patients with organic injuries and life-threatening conditions. However, it is obvious that in these patients complementary medicine should not be substituted for conventional therapy.

We present a 32-year-old man with sarcoidosis who discontinued conventional therapy on his own initiative and began alternative medicine (homeopathy) with subsequent deterioration in his condition. He was hospitalized for a relapse of his sarcoidosis which required large doses of corticosteroids.

Malignant Nodular Hidradenoma (Sweat Gland Tumor)

Anat Engel, Yaron Bar-Dayan, Santiago Engelberg, Yair Levi

Depts. of Medicine B, Pathology, and Disease Research Unit, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

Malignanhidradenoma is a very rare tumor that originates from sweat glands. We present a 61-year-old man with an ulcerated tumor in his right flank, 4 cm in diameter, that was excised with a wide free margin. Histopathologic study showed an ill-defined, epithelial neoformation, formed by lobules of clear polygonal cells in the deep dermis and subcutaneous tissue, diagnosed as malignant nodular hidradenoma.

1.5 years after excision there was enlargement of the right axillary and inguinal lymph nodes, which showed metastatic, adnexal neoplastic cells. Axillary resection and superficial dissection of the right inguinal nodes were performed. After 3 months the tumor had spread to other lymph nodes and acute obstructive renal failure required insertion of a pig-tail catheter into the right ureter. Radiotherapy was followed by chemo-therapy, but he died from end-stage metastatic disease in multi-organ failure.

Exhaustion of Motor Cortex after Head Injury Revealed by Trans-Cranial Magnetic Stimulation

M. Elron, G. Levi, M. Trovnick, J.F. Soustiel, H. Hafner, A. Chistyakov, M. Feinsod

Center for Treatment and Applied Research in Head Injury, Dept. of Neurosurgery, Rambam Medical Center and Rappaport Faculty of Medicine, The Technion, Haifa

We evaluated the pattern of motor evoked potentials elicited by single-pulse and slow-rate (1 Hz) repetitive, transcranial, magnetic stimulation (RTMS) in minor head injuries. The motor response to a single magnetic stimulus in patients with minor head injury was characterized by a significantly higher threshold than in healthy subjects. However, central and peripheral motor conduction was normal in all patients. A stable pattern of MEP throughout the RTMS session was the most prominent feature in the control group. A progressive decrease in MEP amplitude and irregular alternation of large and very small MEPs over the course of RTMS was observed in minor head injury. The higher threshold of the motor response and the abnormal patterns of MEP behavior revealed by RTMS may reflect impaired excitability and enhanced exhaustion of the motor cortex in patients with minor head injuries, which improve with time.

Portal and Mesenteric Vein Thrombosis after Splenectomy for Idiopathic Thrombocytopenic Purpura

Eldad Silberstein, Alexander Smolikov, Itzhac Levi

Surgery B Dept. and Nathanzon Institute of Radiology, Soroka Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

Mesenteric and portal vein thrombosis are rare complications of splenectomy. Their presentation depends on the underlying disease. It is most frequent in lymphoproliferative disorders but extremely rare in trauma. We describe a 22-year-old man and a 49-year-old woman who underwent splenectomy for idiopathic thrombocytopenic purpura and developed mesenteric and portal vein thromboses. Both were treated successfully with anticoagulants for 3 months until the thrombi regressed, as shown by CT scan. During a year of follow-up they were asymptomatic.

Pulmonary Hypertension and Multi-Valvular Damage Caused by Anorectic Drugs

Serge E. Goldstein, Yair Levy, Yehuda Shoenfeld

Medical Dept. B and Institute for Immunological Disease Research, Chaim Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

Marked obesity is an independent risk factor for multisystem morbidity. The use of anorectic drugs is an aggressive strategy for weight reduction. It appears to be an easy way of dealing with the problem, because the patient needn't change his behavior. However, such treatment is not harmless. At the end of the 60's an outbreak of pulmonary hypertension was associated with the drug aminorex, and it was soon withdrawn from the market. 30 years later it became clear that new-generation anorectic drugs (fenfluramine, dexfenfluramine, phentermine), which were being used world-wide, lead to both pulmonary hypertension and valvular damage.

We describe a woman of 70 with both these complications which developed after prolonged anorectic therapy with a fenfluramine-phentermine combination.

Viagra, the First Oral Treatment for Impotence

Y. Assouline-Dayan, Y. Levi, Y. Shoenfeld

Medical Dept B, Chaim Sheba Medical Center and Sackler Faculty of Medicine, Tel Aviv University

Impotence, a common problem especially among older men, can now be treated with Viagra, This oral pill, unlike previous approved treatments mostly involving local injections, does not directly cause penile erection, but increases response to sexual stimulation. It acts by enhancing the relaxant effects of nitric acid on smooth muscle, and thus increases blood flow to certain areas of the penis, leading to erection. It has been evaluated in many randomized trials and in all was more successful in inducing erection than placebos. The most common side-effects include headache, flushing and indigestion, but there have also been reports of fatalities.

We describe a 75-year-old man who had an acute myocardial infraction in the past and who had maturity-onset diabetes and hypertension. In the week prior to admission he had a cardiac scan following a few weeks of exacerbation of anginal pain for which he had been taking nitrites. He took a Viagra pill without prescription or medical advice and 2 hours later, during intercourse with his wife, developed audible respiratory distress and lost consciousness. His wife started cardiac massage but not mouth-to-mouth breathing. The emergency team found ventricular fibrillation and gave 5 electrical shocks and amines and atropine. He remained unconscious, but his pulse returned and he was hospitalized. He then had several generalized convulsions treated with IV valium. 20 minutes after admission there was asystole and all attempts at resuscitation failed.

Cardiovascular status must be considered prior to prescribing Viagra, and the associated risk evaluated.