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עמוד בית Fri, 23.08.19

Mars 2002


Perspective
Sergiu C. Blumen, MD and Nava Blumen, MD

Henri Bergson (1859-1941) was probably the most influential French philosopher at the turn of the twentieth century. In 1927 he was awarded the Nobel Prize for literature. Far beyond the restricted academic philosophical milieu, the impact of his thinking reached personalities as diverse as Claude Debussy, Marcel Proust, George Bernard Shaw, and the impressionists.  His essay The Laughter (Le Rire) is one of the most profound and original ever written on the sense of humor. Bergson’s opinions, with their emphasis on life, instinct and intuition, represented a deviation from the rationalist mainstream of western philosophical tradition. In some circles he was received with skepticism and irony as in Bertrand Russel’s History of Western Philosophy. Today, unbiased by theoretical "bergsonism," neurophysiologic research - as undertaken mainly by Antonio Damasio’s team at Iowa University - confirms many of his hypotheses and elucidates their mechanisms. In this new light, intuition and “recognition by the body” should not be seen as the personal fantasy of an original thinker but as fundamental cognitive tools.

Original Articles
Edward G. Abinader, MD FRCPI, Dawod Sharif, MD, Arie Shefer, MD and Johanan Naschitz, MD

Background: Long-term follow-up in apical hypertrophic cardiomyopathy is rare.

Objective: To study the natural history of the disease.

Methods: We followed 11 patients, 5 women and 6 men, for 5-20 years.

Results: At presentation all 11 patients had typical features of apical hypertrophic cardiomyopathy, with dyspnea in 3 and chest pains in 8, of whom 5 were typical of angina and 3 had myocardial infarction. R-wave voltage and T-wave negativity progressively decreased in magnitude at serial electrocardiograms in four patients. Perfusion defects were detected on thallium myocardial scintigraphy in three, increased apical uptake in two, and normal in one patient. Apical aneurysm with normal coronary arteries developed in a patient who had sustained ventricular tachycardia. All of the 10 catheterized patients had normal coronaries except for one with significant left anterior descending artery stenosis and another with a minor lesion. Symptomatic sustained ventricular tachycardia was found in two patients, one of whom required the implantation of an internal cardioverter-defibrillator.

Conclusions: Apical hypertrophic cardiomyopathy may develop morphologic and electrocardiographic changes with life-threatening arrhythmias necessitating close follow-up and treatment.

Zeev Rotstein, MD, MHA, Rachel Wilf-Miron, MD, MPH, Bruno Lavi BA, Daniel S. Seidman, MD, MMSc, Poriah Shahaf, MD, MBA, Amir Shahar, MD, MPH, Uri Gabay, MD, MPH and Shlomo Noy, MD, MBA

Background: The emergency department is one of the hospital’s busiest facilities and is frequently described as a bottleneck. Management by constraint is a managerial methodology that helps to focus on the most critical issues by identifying such bottlenecks. Based on this theory, the benefit of adding medical staff may depend on whether or not physician availability is the bottleneck in the system.

Objective: To formulate a dynamic statistical model to forecast the need for allocating additional medical staff to improve the efficacy of work in the emergency department, taking into account patient volume.

Methods: The daily number of non-trauma admissions to the general ED[1] was assessed for the period 1 January 1992 to 1 December 1995 using the hospital computerized database. The marginal benefit to shortening patient length of stay in the ED by adding a physician during the evening shift was examined for different patient volumes. Data were analyzed with the SAS software package using a Gross Linear Model.

Results: The addition of a physician to the ED staff from noon to midnight significantly shortened patient LOS[2]: an average decrease of 6.61 minutes for 80–119 admissions (P<0.001). However, for less than 80 or more than 120 admissions, adding a physician did not have a significant effect on LOS in the ED.

Conclusions: The dynamic model formulated in this study shows that patient volume determines the effectiveness of investing manpower in the ED. Identifying bottleneck critical factors, as suggested by the theory of constraints, may be useful for planning and coordinating emergency services that operate under stressful and unpredictable conditions. Consideration of patient volume may also provide ED managers with a logical basis for staffing and resource allocation.






[1] ED = emergency department



[2] LOS = length of stay


Moshe Wald, MD, Sarel Halachmi, MD, Gilad Amiel, MD, Shahar Madjar, MD, Michael Mullerad, MD, Ines Miselevitz, MD, Boaz Moskovitz, MD and Ofer Nativ, MD

Background: The bladder tumor antigen stat is a simple and fast one-step immunochromatographic assay for the detection of bladder tumor-associated antigen in urine.

Objectives: To evaluate the BTA[1] stat in non-bladder cancer patients in order to identify the categories contributing to its low specificity.

Methods: A single voided urine sample was collected from 45 patients treated in the urology clinic for conditions not related to bladder cancer. Each urine sample was examined by BTA stat test and cytology.

Results: The overall specificity of the BTA stat test was 44%, which was significantly lower than that of urine cytology, 90%. The false positive rates for BTA stat test vary among the different clinical categories, being highest in cases of urinary tract calculi (90%), and benign prostatic hypertrophy (73%). Exclusion of these categories from data analysis improved BTA stat specificity to 66%.

Conclusions: Clinical categories contributing to low BTA stat specificity can be identified, and their exclusion improves the specificity of this test.






[1] BTA = bladder tumor antigen


Konstantin Lavrenkov, MD, PhD, Sofia Man, MD, David B. Geffen, MD and Yoram Cohen, MD

Background: Recent years have brought significant progress to the development of hormonal therapies for the treatment of breast cancer. Several new agents have been approved for the treatment of breast cancer in the metastatic setting, among which is the new non-steroidal aromatase inhibitor, anastrozole, introduced for clinical use in Israel in March 1997.

Objectives: To evaluate the response rate and survival duration of patients treated with anastrozole for metastatic breast cancer, who had previously received at least one line of hormonal therapy.

Methods: Anastrozole was administered to 37 patients with metastatic breast cancer. The median age was 64 years. Estrogen receptor was positive in 20 patients, negative in 10 and unknown in 7. All patients were previously treated with tamoxifen in the adjuvant setting or as first-line hormonal therapy for metastatic disease. Anastrozole was given orally, 1 mg/day. Response was evaluated 2 months after the initiation of treatment and reevaluated every 2 months. Therapy was given until disease progression. Ten ER[1]-negative patients were excluded from the final analysis.

Results: Twenty-seven patients were eligible for response and toxicity analysis. The median follow-up was 20 months. One patient (3.7%) achieved complete response and remains free of disease 28 months after start of therapy. No partial responses were seen. Twenty patients (74%) had stable disease. Two year actuarial survival was 57%. Median survival was 26.5 months after starting therapy and median progression free survival was 11 months. The toxicity was mild: one patient (3.7%) complained of weight gain and one patient (3.7%) had mild fatigue.

Conclusion: Although the response rate was low, hormonal therapy with anastrozole seems to be beneficial in terms of disease stabilization, freedom from progression, and overall survival without serious toxicity.  






[1] ER = estrogen receptor


Ido Solt, MD, Sohair Ganadry, MD and Zeev Weiner, MD

Background: Visual interpretation of fetal heart rare monitoring is subject to intra and inter observer variability.

Objective: To examine the effect of intrapartum administration of meperidine and promethazine on fetal heart activity measured by a computerized system.

Methods: Fourteen healthy women with normal pregnancies at term were studied during the active phase of labor. Fetal heart rate was recorded with the Oxford Sonicaid system 8000. Recordings were performed for 40 minutes prior to and after maternal intravenous administration of meperidine 50 mg with promethazine 25 mg.

Results: The combination of meperidine and promethazine caused a significant decrease in the number of accelerations of 10 beats per minute (9.7 versus 2.6, P = 0.002) and 15 beats per minute (5.2 vs. l.4, P = 0.003), time spent in episodes of high variation (14.8 vs. 2.0, P = 0.005) and short-term variation (7.8 vs. 5.0, P = 0.003). On the other hand there was an increase in the time spent in episodes of low variation (5.3 vs. 19.7, P = 0.009).

Conclusions: Maternal administration of meperidine with promethazine has a significant effect on FHR[1] indices during the active phase of normal labor.






[1] FHR = fetal heart rate


Alp Aydinalp, MD, Alice Wishniak, MD, Lily van den Akker-Berman, MD, Tsafrir Or and Nathan Roguin, MD

Background: Myocardial infarction-associated pericarditis is a common cause of chest pain following MI[1], its frequency depending on how it is defined.

Objectives: To investigate the incidence of acute pericarditis and pericardial effusion in the acute phase of ST-elevation MI treated with thrombolytic therapy.

Methods: The study group comprised 159 consecutive patients fulfilling the criteria for acute MI who were admitted to our department during 18 months. Infarct-associated pericarditis was defined as the finding of a pericardial friction rub, a typical pleuropericardial pain, or both. All patients underwent physical examination of the cardiovascular system four times daily for 7 days, as well as daily electrocardiogram and echo Doppler examinations.

Results: Fourteen patients (8.8%) developed a friction rub and 11 patients (6.9%) had a mild pericardial effusion. Six patients (4.0%) had both a friction rub and pericardial effusion. Two patients had a friction rub for more than 7 days. Pleuropericardial chest pain was present in 31 patients (19.5%) but only 7 of them had a friction rub.  The in-hospital mortality rate was 1.3% and no mortality was observed in the acute pericarditis group.

Conclusion: The incidence of signs associated with acute pericarditis was lower in MI patients treated with thrombolysis, compared with historical controls, when a friction rub and/or pericardial effusion was present. There was no significant reduction in the incidence of pleuropericardial chest pain.






[1] MI = myocardial infarction


Guy Amit, MD, Patrizia Cohen, MD and Zvi Ackerman, MD

Background: Nitrofurantoin is a commonly prescribed urinary antiseptic. Hepatic injury has been associated with its use.

Objectives: To present three patients in whom long-term exposure to the drug resulted in chronic active hepatitis, and review the epidemiology, clinical immunology, histopathology, pathogenetic features and treatment of previously reported cases.

Findings: Withdrawing nitrofurantoin once the diagnosis was suspected did not lead to remission of the liver disease and glucocorticoids had to be administered. One patient died of liver failure.

Conclusions: Awareness of this unusual side effect of nitrofurantoin is important and caution should be exerted before prescribing it. Over the past years new insight into the immune nature of this drug has emerged.
 

Reviews
Eliyahu H. Mizrahi, MD, Donald W. Jacobsen, PhD and Robert P. Friedland, MD
Alfred Drukker, MD, PhD

Recent data have shed significant new light on the structural and functional development of the kidneys, as well as on a rare congenital form of bilateral renal hypoplasia called congenital oligomeganephronia. In this renal disorder, few greatly enlarged and hard-working nephrons are found that will ultimately sclerose and lead to end-stage renal failure during early childhood. At the same time it has been recognized that the number of nephrons in the kidneys of various animal species and humans is correlated to renal mass. Therefore, premature babies and/or infants small for gestational age due to intrauterine malnutrition will be born with relatively small kidneys and a certain nephron deficit, a condition called congenital oligonephropathy. Extensive worldwide epidemiologic studies have now shown that these premature or SGA[1] infants have a high incidence of cardiovascular disease, hypertension, hyperlipidemia, diabetes and renal failure in adulthood. Although the pathophysiologic mechanisms responsible for these complications of premature birth are not entirely understood, it has become clear that the described association may pose a possible health problem in the adult population. This review describes the background of COMN[2] and CON[3] as well as the evidence that has accumulated on the adult complications of the latter. In addition, some thoughts are presented on the importance of identifying subjects possibly affected by CON, such that early recognition may alter the ultimate outcome.

_______________________________



[1] SGA = small for gestational age

[2] COMN = congenital oligomeganephronia

[3] CON = congenital oligonephropathy


Kobi Sade, MD and Shemuel Kivity, MD
Edy Stermer, MD

Alcohol is one of the most commonly abused drugs, with a per capita consumption of approximately 10 L pure ethanol per year in the United States and even higher in Spain and France. In terms of mortality, the effect of alcohol on the liver and the pancreas is probably more significant than on the tubular gastrointestinal tract. However, alcohol is a very important cause of morbidity in the tubular gastrointestinal tract. Alcohol influences the motility in the esophagus, stomach and small bowel and has direct effects upon the mucosa of the upper tract. While the stimulation of gastric acid secretion is inversely correlated with the alcohol concentration of the beverage, a direct pathogenetic role in peptic ulcer disease has not been demonstrated. Some alcohols, like red wine, have been shown to possess an anti-Helicobacter pylori effect. Alcohol also has a role in the development of tumors of the gastrointestinal tract.

Transplantation
Alexander Kagan, MD, Nurit Haran, PhD, Ludmila Leschinsky, MD, PhD, Ruty Sarafian, RN, BA, Dan Aravot, MD, Jaffa Dolberg, RN, Ziv Ben-Ary, MD and Jason Rapoport, MB, BS, MRCP

Background: Leptin is a 16 kDa hormone synthesized by adipocytes and involved in body weight regulation.

Objectives: To determine serum leptin concentrations in heart, liver and kidney transplant recipients.

Methods: We investigated 57 patients: 18 male heart transplant recipients (age 25-69 years) at 1-66 months after transplantation, 6 female and 8 male liver transplant recipients (age 33-70) at 11-73 months after transplantation, and 10 female and 15 male kidney transplant recipients (age 20-61) at 3-138 months after transplantation. All recipients were receiving immunosuppressive therapy, including prednisone 0-20 mg/day, azathioprine 75-125 mg/day, cyclosporin 100-250 mg/day or tacrolimus 2-10 mg/day. The results were compared to those of 10 female and 10 male healthy controls. Morning serum concentrations of leptin were measured with a commercial radioimmunoassay (Linco Research Inc., USA), and serum insulin and cortisol levels were measured by radioimmunoassay.

Results: Patients (both men and women) after heart, liver and kidney transplantation exhibited significantly higher serum concentrations of leptin and leptin/body mass index ratios than controls. Serum leptin concentrations were significantly higher in women than in men and correlated very significantly with BMI[1] in all cases. The multivariate stepwise analyses showed that among parameters including BMI, gender, age, time after transplantation, prednisone dose, hematocrit, serum concentrations of glucose, albumin, creatinine, cortisol and insulin, only BMI, gender, cortisol and insulin were significant independent determinants of serum leptin levels in these patients.

Conclusions: This is the first report showing that, in addition to body mass index and gender, basal cortisol and insulin levels affect the hyperleptinemia in transplant patients. The clinical relevance of hyperleptinemia in these patients will require further investigation.






[1] BMI = body mass index



 
Immunology Series
Anna Villa, MD, Christina Sobacchi, PhD and Paulo Vezzoni, MD, PhD

Severe combined immunodeficiencies represent a heterogeneous group of hereditary defects of the immune system that affect both T and B cells and whose etiology has only recently begun to be understood. A portion of these SCID patients bear a defect in either of the two recombination-activating genes, Rag-1 or Rag-2, while others have mutations in a newly identified gene, Artemis. Omenn syndrome is an unusual severe immunodeficiency with T cells but no B cells, and peculiar features also due to a defect in Rag-1 or Rag-2 genes. All these three forms are characterized by an impairment of the VDJ recombination, the process that insures the somatic diversification of immunoglobulin and T cell receptor-encoding genes. Recent findings have enabled us to better understand the pathophysiology of these three immunodeficiencies, which affect the V(D)J recombination process to a different extent and in different ways.

Case Communications
Dov Gefel, MD, Maria Doncheva, MD, Eli Ben-Valid, MD, Abed El Wahab-Daraushe, MD, Gil Lugassy, MD and Ben-Ami Sela, PhD
Kobi Stav, MD, Dan Leibovici, MD, Yoram I. Siegel, MD and Arie Lindner, MD, MPH
Ben-Zion Garty, MD, Itamar Ofer, MD and Yaron Finkelstein, MD
Imaging
Menachem Gross, MD, Abraham Goldfarb, MD and Ron Eliashar, MD
Giselle Zandman-Goddard, MD and Sigal Tal, MD
הבהרה משפטית: כל נושא המופיע באתר זה נועד להשכלה בלבד ואין לראות בו ייעוץ רפואי או משפטי. אין הר"י אחראית לתוכן המתפרסם באתר זה ולכל נזק שעלול להיגרם. כל הזכויות על המידע באתר שייכות להסתדרות הרפואית בישראל. מדיניות פרטיות
ז'בוטינסקי 35 רמת גן, בניין התאומים 2 קומות 10-11, ת.ד. 3566, מיקוד 5213604. טלפון: 03-6100444, פקס: 03-5753303