Israel Medical Association Journal

Background: Amyloidosis of familial Mediterranean fever (FMF) may lead to end-stage renal failure, culminating in kidney transplantation. Since amyloidosis is prompted by high serum amyloid A (SAA) levels, increased SAA is expected to persist after transplantation. However, no data are available to confirm such an assumption.

 Objectives: To determine SAA levels in kidney-transplanted FMF-amyloidosis patients and evaluate risk factors for the expected high SAA levels in this patient group.

Methods: SAA, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values were obtained from 16 kidney-transplanted FMF-amyloidosis patients, 18 FMF patients without amyloidosis and 20 kidney-transplanted patients with non-inflammatory underlying disease. Demographic, clinical and genetic risk factors evaluation was based on data extracted from files, interviews and examination of the patients.

Results: SAA level in FMF patients who underwent kidney transplantation due to amyloidosis was elevated with a mean of 21.1 ± 11.8 mg/L (normal ≤ 10 mg/L). It was comparable to that of transplanted patients with non-inflammatory disorders, but tended to be higher than in FMF patients without amyloidosis (7.38 ± 6.36, P = 0.08). Possible risk factors for the elevated SAA levels in kidney transplant patients that were excluded were ethnic origin, MEFV mutations, gender, age and disease duration.

Conclusions: Kidney-transplanted patients with FMF-amyloidosis and with other non-FMF causes displayed mildly elevated SAA levels, possibly resulting from exposure to foreign tissue rather than from various FMF-related factors. 

Background: Since the identification of the MEFV gene 198 mutations have been identified, not all of which are pathologic. The screening methods used in Israel to test patients suspected of having FMF include a kit that tests for the five main mutations (M694V, V726A, M680Ic/g, M694I, E148Q), and the sequencing of MEFV exon 10 in combination with restriction analysis for detecting additional mutations.

Objectives: To determine the contribution of testing for five additional mutations – A744S, K695R, M680Ic/t, R761H and P369S – to the molecular diagnosis of patients clinically suspected of having FMF.

Methods: A total of 1637 patients were tested for FMF mutations by sequencing exon 10 and performing restriction analysis for mutations E148Q and P369S.

Results: Nearly half the patients (812, 49.6%) did not have any detectable mutations, 581 (35.5%) had one mutation, 241 (14.7%) had two mutations, of whom 122 were homozygous and 119 compound heterozygous, and 3 had three mutations. Testing for the additional five mutations enabled us to identify 46 patients who would have been missed by the molecular diagnosis kit and 22 patients who would have been found to have only one mutation. Altogether, 4.3% of the patients would not have been diagnosed correctly by using only the kit that tests for the five main mutations.

Conclusions: This study suggests that testing for the additional five mutations as well as the five main mutations in patients with a clinical presentation of FMF adds significantly to the molecular diagnosis of FMF in the Israeli population.
 

Intussuception is the most common cause of intestinal obstruction in early childhood. The cause of most intussusceptions is unknown but it can complicate the course of Henoch-Schonlein purpura (HSP) as a result of the vasculitic process. Familial Mediterranean fever (FMF), a most common disease in Israel is also associated with HSP. In a few patients, particularly in children, HSP has been reported to precede the diagnosis of FMF. We describe two patients with an unusual clinical course of severe abdominal pain as a result of intusucception. The correlation between intusucception, HSP and FMF are discussed.
 

Background: Ultraviolet B (UVB) rays are required by the skin for the production of vitamin D. The intensity of UVB at the Dead Sea area is the lowest in the world. Low vitamin D levels are often associated with musculoskeletal symptoms.

Objectives: To assess the effectiveness of climatotherapy at the Dead Sea on the production of vitamin D in Norwegian patients suffering from various rheumatic diseases and to investigate possible associations between increased vitamin D serum levels, musculoskeletal symptoms and disease severity.

Methods: Sixty Norwegian patients who came to the Dead Sea area for 21 days of medical rehabilitation were divided into three groups according to their diagnosis: chronic pain syndromes, i.e., low back pain or fibromyalgia (Group 1, n=33); rheumatoid arthritis (Group 2, n=16); and osteoarthritis (Group 3, n=11). Serum 25-hydroxyvitamin D (25-OH-D) levels were determined at arrival and prior to departure. The treatment protocol included daily sun exposure (climatotherapy), bathing in the Dead Sea and mineral spring water (balneotherapy), mud applications and fitness classes.

Results: 25-OH-D serum levels increased significantly from 71.3 ± 26.6 nM at arrival to 89.3 ± 23.2 nM prior to departure (P < 0.001). Adjusted for the initial levels of pain (assessed by a visual analog scale) and disease severity, a direct correlation was observed between increased 25-OH-D serum levels and pain reduction (P = 0.012) and reduction of disease severity (P = 0.02).

Conclusions: Climatotherapy at the Dead Sea induces significant changes in vitamin D. Increased 25-OH-D serum levels are associated with reduced musculoskeletal pain and disease severity.
 

Background: Rapid reperfusion of an infarct-related artery is crucial for the successful treatment of ST elevation myocardial infarction. Every effort should be made to shorten door-to-balloon time.

Objectives: To investigate whether bypassing the emergency room (ER) has a positive influence on door-to-balloon time in patients presenting with ST elevation myocardial infarction (STEMI) and whether the reduction in door-to-balloon time improves patients’ clinical outcome.

Methods: We analyzed data of 776 patients with STEMI[1] from the 2004 and the 2006 Acute Coronary Syndrome Israeli Survey (ACSIS) registry. The ACSIS[2] is a biennial survey on acute myocardial infarction performed in all 25 intensive cardiac care units in Israel during a 2-month period. Twenty-five percent of patients (193 of 776) arrived directly to the intensive cardiac care unit (ICCU) and 75% (583 of 776) were assessed first in the ER[3]. We compared door-to-balloon time, ejection fraction, 30 days MACE (major adverse cardiac and cerebrovascular events) and 30 days mortality in the two study groups.

Results: There was significantly shorter door-to-balloon time in the direct ICCU group as compared with the ER group (45 vs. 79 minutes, P < 0.002). Patients in the direct ICCU group were more likely to have door-to-balloon time of less than 90 minutes in accordance with ACC/AHA guidelines (88.7% vs. 59.2%, P < 0.0001). Moreover, patients in the direct ICCU group were less likely to have left ventricular ejection fraction < 30% (5.4% vs. 12.2%, P = 0.045) and less likely to have symptoms of overt congestive heart failure. Lastly, 30 days MACE[4] was significantly lower in the direct ICCU group (22 vs. 30%, P < 0.004).

Conclusions: There is significant reduction of the door-to-balloon time in the direct ICCU admission strategy. This reduction translates into improvement in clinical outcome of patients. It is reasonable to apply the direct ICCU strategy to patients with STEMI.

Background: Internet use by patients as a source of information on health and disease is expanding rapidly with obvious effects on the doctor-patient relationship. Many of these effects remain undocumented or are poorly understood.

Objectives: To assess the use of the internet  for health information by patients in primary care in Israel and their perception of the effects of internet use on their relationship with their doctor.

Methods: A cross-sectional survey was conducted among a convenience sample of patients visiting 10 primary care clinics in central Israel using a questionnaire developed for this survey. The survey examined attitudes to using the internet for health-related information and attitudes to sharing this information with doctors. Associations between demographic variables, internet use and patient satisfaction with the doctor’s response were tested using the chi-square statistic and t-tests.

Results: Completed questionnaires were received from 138 patients; the response rate was 69%. Patients in the study sample had a high rate of internet access (87%), with many using the internet as a source of health information (41%) although most patients using the internet never share this information with their doctor (81%). Among those who share information with the doctor, most felt that this has a positive effect on the relationship (87%). Few patients reported being referred to websites by the doctor (28%).

Conclusions: Internet use is prevalent in this population, though physicians may be unaware of this. Future study may examine the effects of doctors who ask patients actively about their internet use and inform them of relevant health information sources online.

Background: Community-acquired pneumonia requiring hospitalization is a severe illness with high mortality, especially if the appropriate treatment is delayed. Sometimes diagnosis is difficult due to an equivocal clinical picture or chest film, or to accompanying diseases that mask or simulate pneumonia.

Objectives: To assess the usefulness of certain inflammatory markers to differentiate pulmonary edema from pneumonia throughout the hospital stay in patients admitted for pneumonia or pulmonary edema of non-infectious origin and to monitor the response to treatment.

Methods: The study group comprised 50 patients admitted for pneumonia, 50 admitted for pulmonary edema and 30 healthy individuals. Blood samples for determination of leukocyte count, erythrocyte sedimentation rate (ESR), fibrinogen, C-reactive protein (CRP), albumin, sCD14 and oxidized fibrinogen were drawn upon admission, at 48 and 72 hours after admission, and at discharge from the intensive care unit.

Results: The levels of sCD14 were similar in both patient groups but higher than control levels during the first 48 hours (P < 0.03). They decreased gradually with hospital stay. The concentration of oxidized fibrinogen was similar in both patient groups and significantly lower than that of the healthy control group throughout the hospitalization period.

Conclusions: Oxidized fibrinogen and sCD14 are not reliable markers for the diagnosis of pneumonia, for its differential diagnosis from pulmonary edema, and for patient follow-up throughout hospitalization. The finding of elevated levels of oxidized fibrinogen in the group of healthy controls warrants further study to identify the factors responsible for altering fibrinogen oxidation. The other markers are more indicative.
 

Background: Esophageal perforations and postoperative esophageal leaks are associated with substantial morbidity and mortality and pose a difficult therapeutic challenge. 

Objectives: To evaluate the outcome of removable self-expanding metallic stents (SEMS) as a treatment for postoperative leaks and perforations of the esophagus and stomach.

Methods: We conducted a retrospective study of all patients in one medical center who underwent temporary insertion of a covered plastic stent for postoperative leaks and perforations of the esophagus and stomach from June 2009 to February 2010. Data were retrieved from hospital and outpatient clinical data charts. Data included indication for insertion, post-insertion outcome including stent complications, and follow-up after stent removal.

Results: The indications for stent insertion were postoperative leak in four patients and postoperative esophagopleural fistula in one patient. Three of the patients had a leak at the gastro-esophageal junction following laparoscopic sleeve gastrectomy. In all cases the stent insertion was completed successfully. In three patients the stent migrated distally. In two of these three it was repositioned or replaced endoscopically, and in the third it was excreted in the feces. Stents were removed electively after 6 to 7 weeks. All patients recovered fully and were discharged from the hospital.

Conclusions: SEMS insertion may have an important role in the management of postoperative leaks and perforations of the esophagus and stomach and should be considered in such cases.
 

There are major dilemmas regarding the optimal modalities for breast cancer screening. This is of particular relevance to Israel because of its high-risk population. It was suggested that an avenue for further research would be to incorporate advances in signal processing through the fast Padé transform (FPT) to magnetic resonance spectroscopy (MRS). We have now applied the FPT[1] to time signals that were generated according to in vitro MRS[2] data as encoded from extracted breast specimens from normal, non-infiltrated breast tissue, fibroadenoma and cancerous breast tissue. The FPT is shown to resolve and precisely quantify the physical resonances as encountered in normal versus benign versus malignant breast. The FPT unambiguously delineated and quantified diagnostically important metabolites such as lactate, as well as phosphocholine, which very closely overlaps with glycerophosphocholine and phosphoethanolamine, and may represent a magnetic resonance-visible molecular marker of breast cancer. These advantages of the FPT could clearly be of benefit for breast cancer diagnostics via MRS. This line of investigation should continue with encoded data from benign and malignant breast tissue, in vitro and in vivo. We anticipate that Padé-optimized MRS will reduce the false positive rates of MR-based modalities and further improve their sensitivity. Once this is achieved, and given that MR entails no exposure to ionizing radiation, new possibilities for screening and early detection emerge, especially for risk groups. For example, Padé-optimized MRS together with MR imaging could be used with greater surveillance frequency among younger women with high risk of breast cancer.

The cause for gender differences in the epidemiology, natural history and response to therapy in many diseases is unknown and has seldom been investigated in depth. Sex hormones are blamed for many of these changes, mostly without any scientific evidence. In this review I will describe some of the evidence for gender differences in gastrointestinal diseases. Gender medicine and its application for gastroenterology is a new field and one warranting research.