Israel Medical Association Journal

Background:  One of the major reasons for the shortage of organs for transplantation in Israel is the failure to identify potential donors. According to the World Health Organization, the expected number of potential donors in Israel is 300 per year. In recent years an average of only 200 donors (2/3) has been identified.

Objective: To identify the reasons for the gap between the potential and the actual number of organ donors.

Methods: We reviewed the medical records of all potential donors at the Soroka University Medical Center between October 1997 through September 1999.

Results: The total of 183 death records was consistent with the minimal inclusion criteria for potential organ donation, of which 41 were suspected to be potential brain death (PBD) In 31 cases an ad hoc committee had declared brain death, and the patients were evaluated for organ donation. However, in 10 cases no committee was formed. We found that 24.4% (10/41) of the potential donors had not been designated as such by their medical team.

Conclusion: We believe that a comprehensive education program for medical and nursing staff might increase awareness for organ donation and may eliminate the gap between the potential and actual number of organ donors.

Sepsis is an infection-induced inflammatory syndrome that results in a complex network of adaptive and maladaptive alterations in homeostatic mechanisms. Severe sepsis, defined as sepsis associated with acute organ failure, is a serious disease with a mortality rate of 30–50%. The coagulation system, through complex interactions, has an important role in the final outcome of the sepsis-induced inflammatory cascade. A fine and delicate balance that normally exists between anticoagulant mechanisms and the procoagulant response is altered in sepsis. Activated protein C, an endogenous vitamin K-dependent anticoagulant, plays a major role in the down-regulation of the procoagulant arm. It also possesses anti-inflammatory properties. Endothelial damage during sepsis impairs the endothelium-dependent activation of protein C, thus shifting the balance towards thrombosis. This shift may contribute to the development of sepsis-related multi-organ failure. Evidence suggesting that activation of the coagulation system may contribute to sepsis-related morbidity and mortality has led to extensive research attempting to correct the hemostatic defects seen in septic patients. Indeed, a recent randomized controlled trial demonstrated a reduction in overall mortality in patients with severe sepsis treated with APC[1]. In this review we discuss the pathogenesis of the coagulopathy of sepsis, as well as the new therapeutic approaches aimed at correcting the defects in the coagulation system.

Background: The ¹³C-urea breath test is the best non-invasive test to validate Helicobacter pylori eradication. Serology is unreliable for this purpose due to the slow and unpredictable decline in the antibodies titer.

Objectives: To characterize a specific group of patients who were treated for H. pylori and tested for successful eradication by ¹³C-UBT[1] in our central laboratory and to correlate the eradication success rate with specific drug combinations, and to evaluate other factors that may influence eradication success.

Methods: ¹³C-UBT for H. pylori was performed in the central laboratory of Clalit Health Services. The breath test was performed by dedicated nurses in 25 regional laboratories and the samples were analyzed by a mass spectrometer (Analytical Precision 2003, UK). The physician who ordered the test completed a questionnaire computing demographic data (age, gender, origin), indication, use of non-steroidal anti-inflammatory drugs or proton pump inhibitor, and combination of eradication therapy.

Results: Of the 1,986 patients tested to validate successful H. pylori eradication, 539 (27%) had a positive test (treatment failure group) and 1,447 (73%) had a negative test (successful treatment group). Male gender, older age and European-American origin predicted better eradication rates. Dyspeptic symptoms and chronic PPI[2] therapy predicted treatment failure. Combination therapy that included clarithromycin had a higher eradication rate than a combination containing metronidazole. The combination of omeprazole, amoxicillin and clarithromycin achieved an eradication rate of 81.3%, which was better than the combination of omeprazole, metronidazole and clarithromycin (77.2%) (not significant), or of omeprazole, amoxicillin and metronidazole (66.1%) (P < 0.01).

Conclusion: Gender, age, origin, dyspepsia and PPI therapy may predict H. pylori eradication results. Our findings also support an increase in metronidazole resistance of H. pylori strains in Israel, as described in other countries. We recommend combination therapy with omeprazole, amoxicillin and clarithromycin and avoidance of metronidazole as one of the first-line eradication drugs.

Patients with a compromised immune system suffer a wide variety of insults. Interstitial lung changes are one of the most common and serious complications in this group of patients. The morbidity rate reaches 50% and up to 90% if endotracheal intubation and mechanical ventilation are necessary. Opportunistic and bacterial infections are common causes of pulmonary infiltrates and must be distinguished from other conditions such as drug reactions, volume overload, pulmonary hemorrhage, and malignant diseases. Accurate and prompt diagnosis of potentially treatable causes can be life-saving. Non-invasive diagnostic methods for evaluation are often of little value, and an invasive procedure - such as bronchoalveolar lavage, transbronchial biopsy or even open lung biopsy - is therefore performed to obtain a histologic diagnosis. Yet, even when a specific diagnosis is made it may not improve the patient’s survival. Numerous textbook and review articles have focused on the management of this condition. The present review attempts to provide a comprehensive and systematic picture of current knowledge and an integrated approach to these challenging patients.

Sepsis is an inflammatory syndrome caused by infection. Consequently, anti-inflammatory therapies in sepsis have been a subject of extensive research and corticosteroids have been used for years in the therapy of severe infections. However, studies conducted in the 1980s failed to demonstrate any beneficial effects of high dose, short-term steroid therapy in sepsis and this therapy was therefore abandoned during the last decade. Recently, a new concept has emerged with more promising results - low dose, long-term hydrocortisone therapy – and this approach is now being evaluated in the treatment of septic shock. It is supported by the observation that many sepsis patients have relative adrenal insufficiency. Moreover, the anti-inflammatory effects of steroids and their ability to improve reactivity to catecholamines further contribute to their effects in sepsis. Large randomized clinical trials will be required to determine the exact role of corticosteroids in septic shock.

The addition of methotrexate to treatment protocols in children with acute lymphoblastic leukemia has been found beneficial in preventing central nervous system relapse. However, MTX[1] itself may be associated with neurologic morbidities, the most significant of which is leukoencephalopathy. The present study describes the clinical spectrum of leukoencephalopathy, which ranges from a subclinical disease manifested only radiologically to a progressive, devastating encephalopathy. The interaction of MTX with other components of the treatment protocol is discussed, as is the effect of leucovorin. A summary is presented of the metabolic pathways that may be involved in the development of MTX toxicity. Researchers are still seeking a biochemical marker to aid in the determination of the amount of MTX that may be safely administered.

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Fanconi anemia is a rare autosomal recessive disorder characterized clinically by congenital abnormalities, progressive bone marrow failure, and a predisposition to malignancy. FA cells are sensitive to DNA cross-linking agents. Complementation analysis of FA cells using somatic cell fusion has facilitated the identification of eight complementation groups, suggesting that FA is a genetically heterogeneous disorder. Six genes (FANCA, FANCC, FANCD2, FANCE, FANGF, FANCG) have been cloned so far. The majority of affected patients belong to FA group A. Of the 32 unrelated Israeli patients with FA that we studied, 6 carried the FANCC mutations and 15 the FANCA mutations. Among the Jewish patients, ethnic-related mutations were common. Recent cumulative evidence suggests that the FA proteins are repair proteins. FANCC, FANCA and FANCG bind and interact in a protein complex found in the cytoplasm and nucleus of normal cells. FANCD2 exists in two isoforms; the long active form, FANCD2-L, is absent from FA cells of all complementation groups. FANCD2 co-localized with BRCA1 in unclear foci, probably as part of a large genomic surveillance complex. Studies using FANCA and FANCC knockout mice suggest that bone marrow precursors express interferon-g hypersensitivity and show progressive apoptosis. The definition of the molecular basis of FA in many affected families now enables prenatal diagnosis.

Background: Guidelines are important for keeping family physicians informed of the constant developments in many fields of medicine.

Objectives: To compare the knowledge of gastroenterologists and family physicians regarding the diagnosis and treatment of gastroesophageal reflux disease in order to determine the need for expert guidelines.

Methods: A 25 item questionnaire on the definition, diagnosis and treatment of GERD[1] was presented to 35 gastroenterologists and 35 family physicians. Each item was rated on a four point scale from 1 = highly recommended to 4 = not recommended. A voting system was used for each group on separate occasions. The proportions of correct answers according to the level of recommendation were compared between the groups.

Results: The groups' responses agreed on only 4 of the 25 items; differences between the remaining 21 were all statistically significant. For 14 items, 70% of the gastroenterologists chose the grade 1 recommendation, whereas more than 70% of the family physicians chose mostly grade 2.

Conclusions: The gap in knowledge on gastroesophageal reflux disease between gastroenterologists and family physicians is significant and may have a profound impact on diagnosis and treatment. Clear and accurate guidelines may improve patient evaluation in the community.

Background: Patients’ consent to being part of medical education is often taken for granted, both in primary and secondary care. Formal consent procedures are not used routinely during teaching and patients are not always aware of teaching activities.

Objective: To investigate patients’ attitudes and expectations on issues of consent regarding participation in teaching in general practice, and the influence of a student’s presence on the consultation.

Methods: The study took place in 46 teaching practices during the sixth year clinical internship in family medicine. Patients completed questionnaires at the end of 10 consecutive eligible consultations. The questionnaire contained data on the willingness to participate in teaching, the preferred consent procedure and the effects of the student’s presence. The doctors were asked to estimate the sociodemographic level in their clinic area.

Results: A total of 375 questionnaires were returned; the response rate was not affected by the clinic’s sociodemographic level. Overall, 67% of the patients had come into contact with students in the past; 3.2% of the participants objected to the presence of a student during the consultation; 15% would insist on advance notification of the presence of a student, and another 13.9% would request it; 4% stated that the presence of students had a detrimental influence on the physical examination and history; and 33.6% would refuse to be examined by a student without the doctor’s presence.

Conclusion: Most patients agreed to have a student present during the consultation; some would like prior notification; a minority refused the student’s presence. A large minority would refuse to be examined without the tutor’s presence. Our findings need to be taken into account when planning clinical clerkships.

Background: Alkaline tide is the transient increase in blood and urine pH following stimulation of gastric acid secretion. It is attributed to HC0₃ release from parietal cells in parallel with H+ secretion. The enzyme carbonic anhydrase is thought to be responsible for HC0₃ production from CO₂ and 0H in the parietal cell.

Objective: To examine the effect of pretreatment with the carbonic anhydrase inhibitor, acetazolamide, on the alkaline tide phenomenon.

Methods: Ten patients with dyspepsia and demonstrable alkaline tide were tested on three separate days. The pH and base excess were determined in arterialized venous blood before and 45 minutes after an intramuscular injection of pentagastrin. The pH of the urine was measured before and 120 mm after pentagastrin injection. Measurements were performed after pentagastrin alone on day 1 following pretreatment with acetazolamide 60 mm before pentagastrin on day 2, and after the administration of acetazolamide alone on day 3.

Results: Following the administration of pentagastrin alone, the blood base excess increased by 1.61 +0.2 mEq/L (mean + standard deviation) and the calculated alkaline tide at 45 mm was 33.99 ±4.49 mEq. On day 2 with prior adminis­tration of acetazolamide, base excess decreased by 0.21 + 0.39 mEq/L, and the calculated alkaline tide was -3.28±7.57 mEq, which was significantly lower than on day 1 (P=0 0001). On day 3, following acetazolamide alone, the base excess values decreased by 0.53~0.2 mEq/L and the alkaline tide was -10.05 +3.33 mEq there was no significant difference compared with day 2 (P= 0.44).

Conclusion: Pretreatment with acetazolamide abolished the alkaline tide induced by pentagastrin. This finding supports the view that carbonic anhydrase has a major role in the alkaline tide phenomenon.