Israel Medical Association Journal

Background: Cell-mediated immunity is impaired in uremia. Cell-matrix interactions of immune cells such as CD4+T lymphocytes with extracellular matrix are an important requirement for an intact immune response. The adherence of CD4+T cells of healthy subjects (normal T cells) to ECM components is inhibited in the presence of uremic serum. Such decreased adhesive capacity is also found in T cells of dialysis patients. Various chemokines and cytokines affect the attachment of CD4+T cells to ECM.

Objective: To evaluate chemokine (MIP-1β and RANTES) and tumor necrosis factor α-induced adhesion of CD4+T cells to ECM in a uremic milieu.

Methods: We examined adhesion of normal CD4+T cells (resting and activated) to intact ECM in response to soluble or bound chemokines (MIP-1β and RANTES) and to TNF-α following incubation in uremic versus normal serum. Thereafter, we evaluated the adhesion of resting CD4+T cells from dialysis patients in a similar fashion and compared it to that obtained from a healthy control group.

Results: Addition of uremic serum diminished soluble and anchored chemokine-induced attachment of normal resting and activated CD4+T cells to ECM compared to a normal milieu (a peak response of 10–11% vs. 24–29% for soluble chemokines, P<0.001; 12–13% vs. 37–39% for bound chemokines on resting cells, P<0.01; and 18–20% vs. 45–47% for bound chemokines on activated cells, P<0.02). The same pattern of response was noted following stimulation with immobilized TNF-α (7 vs. 12% for resting cells, P<0.05; 17 vs. 51% for activated cells, P<0.01).  Adherence of dialysis patients’ cells to ECM following stimulation with both bound chemokines was reduced compared to control T cells (15–17% vs. 25–32%, P<0.0000). In contrast, adherence following stimulation by TNF-α was of equal magnitude.

Conclusions: Abnormal adhesive capacity of T lymphocytes to ECM in uremia may, in part, be related to a diminished response to MIP-1β, RANTES and TNF-α. However, whereas reduced adhesion to chemokines was present in both normal CD4+T cells in a uremic environment and in dialysis patients’ T cells, TNF-α-induced adhesion was found to be inhibited only in normal cells in a uremic milieu.

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ECM = extracellular matrix

TNF-α = tumor necrosis factor-a

Background: Previous studies have suggested that prolactin may serve as an indicator of disease progression in breast cancer.

Objectives: To evaluate the use of PRL as a serum tumor marker in patients with breast cancer.

Methods: PRL serum level was determined in 99 breast cancer patients and compared with CA 15-3 serum level.

Results: Elevated serum level of PRL (>20 ng/ml) was found in 8 of 99 patients (8.1%). A stratified analysis of prolactin levels according to therapy revealed that PRL levels was increased in 8 of 55 untreated patients (14.5%), but not in patients who received hormonal or chemotherapy in the 3 months preceding the test (0/42 patients, P=0.009). However, mean PRL level was similar in patients with no evidence of disease activity and in patients with active disease (10.2 vs. 8.2 ng/ml, NS). In comparison, CA 15-3 mean level was significantly lower in patients with no evidence of disease as compared to patients with active disease (18.2 vs. 144.7 units/ml, P<0.001). PRL level was increased in 6 of 60 patients (10%) with no evidence of disease and in 2 of 39 (5.2%) with active disease (NS). In comparison, CA 15-3 level was increased in 3 of 60 patients (5%) with no evidence of disease and in 24 of 39 (61.5%) with active disease (P<0.001).

Conclusions: PRL levels are decreased following hormonal or chemotherapy in patients with breast cancer and there is no correlation between PRL serum level and the state of disease. Further studies are needed to clarify a possible clinical significance of hyperprolactinemia in a subset of patients with breast cancer.

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PRL = prolactin

Background: The course and outcome of appendicitis in the elderly differs from that of the general population. The rates of perforated appendices, error in diagnosis, postoperative complications and mortality may be related to the time lapse between onset of symptoms and admission, and hence delay in surgery.

Objectives: To evaluate if these factors have improved in recent years.

Methods: A retrospective study was carried out of all 61 patients over age 60 who underwent appendectomies in a major metropolitan hospital during 1988-98.

Results: We found that most patients had appendectomies within the first 24 hours of admission and within 3 days of symptoms. Rate of perforation was 43%, error 5.6%, morbidity 41%, and mortality 3.2%.

Conclusions: The high rate of appendix perforation in the elderly is not due to delay. The literature reveals little improvement in the statistics of the disease over the last five decades, despite advances in imaging and surgical technique. This may be explained by the increasing inclusion of octogenarian patients.
 

Background: Anti-endomysial antibodies are sensitive and specific markers for celiac disease. This antibody has recently been identified as an antibody to tissue transglutaminase, an enzyme that cross-links and stabilizes extracellular matrix proteins.

Objectives: To evaluate the clinical usefulness of an enzyme-linked immunoassay for anti-transglutaminase antibodies, and to compare the results with those of AEA, the current gold standard serological test for celiac disease.

Methods: Serum samples were collected from 33 patients with biopsy-proven celiac disease and AEA tests were performed. Control samples for anti-transglutaminase were obtained from 155 patients. An ELISA test for immunoglobulin A anti-transglutaminase utilizing guinea pig liver transglutaminase was developed and performed on all sera.  Cutoff values for the test were performed using logistic regression and receiver operating curves analysis.

Results: An optical density cutoff value of 0.34 was established for the assay. The mean value was 0.18±0.19 optical density for controls, and 1.65±1.14 for patients with celiac disease (P<0.001). Sensitivity and specificity of the assay were both 90%, while AEA had a sensitivity and specificity of 100% and 94%, respectively.

Conclusions: A tissue transglutaminase-based ELISA test is both sensitive and specific for  detection of celiac disease.

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AEA = anti-endomysial antibody

Background: Recurrent abdominal pain is a common pediatric diagnostic problem.  Endoscopy is sometimes performed as part of the evaluation. Although gastritis and/or Helicobacter pylori infection is often present, it is not known if they contribute to the symptomatology.

Objectives: To evaluate the role of either gastritis or H. pylori infection in the symptomatology of children with RAP.

Patients and Methods: We retrospectively studied two groups of patients, 70 children in each, who had undergone endoscopy. One group was evaluated endoscopically for RAP and the other was a heterogeneous group that underwent endoscopy for indications other than RAP. Biopsies were taken during endoscopy and Giemsa staining was performed for the presence of H. pylori. Triple therapy was given as indicated, and the children were followed for an average of 6 months.

Results: Microscopic gastritis was diagnosed in 39 patients (55.7%) of the RAP group and in 31 of the heterogeneous group (44.2%) (NS), and H. pylori was found in 32 patients of the RAP group and in 16 of the heterogeneous group (45.7% vs. 22.8%, P<0.01). All children with H. pylori, except one in the heterogeneous group, had accompanying gastritis. On the other hand, gastritis without H. pylori infection was seen in 7 children in the RAP group and in 15 of the other. Endoscopy revealed macroscopic abnormalities in 52 of the 70 children with microscopic gastritis. There was a clinical improvement after triple therapy in 28 of 33 children with H. pylori-associated gastritis (84.85%), in 4 of 8 children with gastritis unassociated with H. pylori (50%), and in 8 of 15 without gastritis or H. pylori (53.3%) (P<0.01 between the H. pylori-associated gastritis and each of the other groups).

Conclusions: H. pylori infection and gastritis may be associated with RAP in a selected subgroup of children. We recommend a complete work-up, including endoscopy and invasive or non-invasive diagnostic modalities for H. pylori, and treatment of the infection.

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RAP = recurrent abdominal pain

Background: Burn trauma occurs mostly in young children. Burn injury in the pediatric age group has multiple-aspect sequelae.

Objectives: To characterize the profile of the injured pediatric burn patient, thus targeting the most vulnerable pediatric group.

Methods: Between 1 January and 31 December 1996, a total of 9,235 pediatric patients were admitted for various traumatic injuries (burns, lacerations, fractures, etc.) to the Emergency Medicine Department of Schneider Children’s Medical Center. We conducted a retrospective study of the patients’ charts, including demographic data, which were stored in a computerized database, for statistical evaluation. The characteristics of pediatric burn patients were examined and compared with other pediatric trauma patients.

Results: Of the total patient population, 282 (3.1%) suffered from burns (37% females, 63% males). The most frequent burn injury was scald burn (58%). The pediatric group that was most exposed to burns was 13–18 month old males.

Conclusions: Having identified the high risk group among the pediatric burn patients, we suggest that prevention programs be directed towards this group in order to reduce further risk of burn injury.

Objective: To describe the clinical and epidemiological features of hepatitis B virus infection in Israeli children, and to evaluate their response and compliance to therapy.

Methods: We retrospectively studied 51 patients (34 males, 17 females), aged 2–18 years, from several medical centers in Israel.

Results: Of the 51 patients, 38 with elevated transaminase, positive hepatitis B e antigen and/or HBV DNA, and histologic evidence of liver inflammation were treated. Interferon was administered by subcutaneous injections three times a week for 3-12 months (dosage range 3–6 MU/m²). Only 16% were native Israelis, while 78% of the children were of USSR origin. A family history of HBV infection was recorded in 25 of the 51 patients (9 mothers, 16 fathers or siblings). Five children had a history of blood transfusion. The histological findings were normal in 3 patients, 24 had chronic persistent hepatitis, 14 had chronic active hepatitis and 2 had chronic lobular hepatitis. Five children also had anti-hepatitis D virus antibodies. Twelve of the 38 treated patients (31.5%) responded to IFN completely, with normalization of the transaminase levels and disappearance of HBeAg and HBV DNA. In no patient was there a loss of hepatitis B surface antigen. The main side effects of IFN were fever in 20 children, weakness in 10, headaches in 9, and anorexia in 6; nausea, abdominal pain, and leukopenia were present in 3 cases each. The response rate was not affected by age, country of origin, alanine/aspartate aminotransferase levels, or histological findings. However, a history of blood transfusion was a predictor of good response, 60% vs 27% (P<0.05).

Conclusions: We found IFN to be a safe and adequate mode of treatment in children with chronic HBV infection, regardless of their liver histology and transaminase levels. Therefore, in view of the transient side effects associated with this drug, we recommend considering its use in all children with chronic hepatitis B. 

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HBV = hepatitis B virus

IFN = interferon

HBeAg = hepatitis B e antigen

Methods: We attempted to investigate plasma oxidation and plasma and erythrocyte glutathione and glutathione enzymes in 20 patients with NIDDM, compared with euglycemic matched controls. Plasma oxidation was analyzed both basally (without) and as induced by 2,2'-azobis,2-amidopropane hydrochloride measured by the generation of thiobarbituric acid reactive substances and lipid peroxides.

Results: There was a significant increase in oxidation both basally (without) and as induced by AAPH. Plasma glutathione was lowered by 50% (P<0.01) and erythrocyte glutathione peroxidase, glutathione s-transferase and glutathione reductase activities were lower by 30%, 27% and 46%, respectively (P<0.01) in the patients with NIDDM.

Conclusions: Confronted by increased oxidation, patients with NIDDM show an abnormal plasma and erythrocyte antioxidative capacity, which may result in an accelerated rate of complications.

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NIDOM= non-insulin-dependent diabetes mellitus

Objectives: To suggest a simple outpatient technique for evaluating the response of arterial oxygen saturation to exercise for use as a marker of disease severity.

Patients and methods: Ninety-six patients with various degrees of COPD¹ were divided into three groups: mild (forced expiratory volume in 1 sec >65%), moderate (FEV1² between 50 and 65%), and severe (FEV1 <50%). Using continuous oximeter recording we measured oxygen saturation during 15 steps of climbing, and quantified  oxygen desaturation by measuring the “desaturation area”, defined as the area under the curve of oxygen saturation from the beginning of exercise through the lowest desaturarion point and until after recovery to the baseline level of oxygen percent saturation. Desaturation was correlated to spirometry, lung gas volumes, blood gas analysis, and 6 min walking distance.

Results A good correlation was found between severity of COPD and baseline SaO2³, lowest SaO2, recovery time, and desaturation area.  A negative correlation was found between desaturation area and FEV1 (r=-0.65), FEV1/forced vital capacity (r=-0.58), residual volume to total lung capacity (r=0.52), and diffusing lung capacity for carbon monoxide (r=-0.52). In stepwise multiple regression analysis only FEV1 correlated significantly to desaturation area.  A good correlation was noted between 6 min walking distance and desaturation area with the 15 steps technique (r=0.56).

Conclusions: In patients with severe COPD, arterial hypoxemia during exercise can be assessed by simple 15 steps oximetry. This method can serve both as a marker for disease severity and to determine the need for oxygen supplementation.

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COPD = chronic obstructive pulmonary disease

FEV1 = forced expiratory volume in 1 sec

SaO2 = arterial oxygen saturation

Objectives: To analyze the factors that influence the success of physicians in the ATLS®¹ written tests.

Methods: A retrospective study was conducted of 4,475 physicians participating in the Israeli ATLS® training program between 1990 and 1996. Several variables in the records of these physicians were related to their success or failure in the final written examination of the course.

Results: Age, the region of medical schooling, and the medical specialty were found to significantly influence the successful completion of the ATLS® course.

Conclusions: Physicians younger than 45 years of age or with a surgical specialty are more likely to graduate the ATLS® course. The success rate could be improved if the program’s text and questionnaires were translated into Hebrew. 

¹ATLS® = Advanced Trauma Life Support