Israel Medical Association Journal

Background: The beneficial effect of aprotinin, a naturally occurring protease inhibitor, on preservation of organs such as the liver, kidney and lung has been documented.

Objective: To explore the effects of hepatic ischemia and reperfusion on both liver and myocardial function, using a dual isolated perfused organ model with and without aprotinin.

Methods: Isolated rat livers were stabilized for 30 minutes with oxygenated modified Krebs-Henseleit solution at 37°C. Livers were then perfused continuously with KH or KH + aprotinin 10⁶ KIU/L for an additional 135 min. Livers of two other groups were made globally ischemic for 120 min, then perfused for 15 min with KH or with KH + aprotinin. Isolated hearts (Langendorff preparation) were stabilized for 30 min and then reperfused with KH or KH + aprotinin exiting the liver for 15 min.  The liver’s circuit was disconnected, and hearts were re-circulated with the accumulated liver + heart effluent for an additional 50 min.

Results: In the ischemia and ischemia + aprotinin groups, portal vein pressure (1 and 15 min reperfusion) was 331±99% and 339±61% vs. 308±81% and 193±35% of baseline, respectively (P<0.03 vs. ischemia). There were no other differences in the enzyme leakage  between aprotinin-treated or untreated ischemic livers. Left ventricular pressure was stable in the controls.

However, LV pressure in groups perfused with ischemic liver effluent declined within 65 min reperfusion, whether aprotinin treated or not (84±8% and 73±5% of baseline, respectively, P<0.004 only for ischemia vs. control)

Conclusion: When aprotinin was used, LV pressure was inclined to be higher while liver portal vein pressure was lower, thus providing protection against liver and heart reperfusion injury. 

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* These authors contributed equally to the article

KH = Krebs-Henseleit

LV = left ventricular

Background: The increasing utilization of general internal medicine hospital wards in Israel during the last decade is a source of concern for health policy makers.

Objectives: To report on the distribution of selected main and secondary diagnoses among GIM inpatients, and to estimate the proportion of disorders for which appropriate care in the community will reduce the need for hospital admissions and re-admissions.

Methods: Data from the Health Information and Computer Services of the Israel Ministry of Health (national hospitalization database) for a one year period were analyzed by distribution of diagnostic entities (ICD-9-CM) in GIM and in medical subspecialty wards.

Results: Of the 313,824 discharges from hospital divisions of medicine in 1995, 256,956 (81.9%) were from GIM and 56,868 (18.1%) from specialty wards. Main and secondary discharge diagnoses were available for 188,807 GIM and 35,992 specialty patients. Of all main diagnoses in GIM wards, 27% were coded as "general or systemic symptoms and signs" or as "abnormal laboratory or ill defined manifestations" (ICD-9-CM codes 780-799, 276,277), and heart diseases comprised another 27%. The remaining main diagnoses covered almost all medical conditions. The combined proportion of "ambulatory care sensitive hospital admissions" (bronchial asthma, hypertension, congestive heart failure, chronic obstructive pulmonary disease, diabetes) constituted 12% of all main diagnoses in GIM, and respiratory symptoms or signs comprised another 11%. A by-product of this analysis was an insight into the experience of undergraduate medical students in GIM.

Conclusions: Assuming that 12-75% of admissions for "ambulatory care sensitive disorders" are preventable, an improved review before hospital discharge and a closer outpatient follow-up may reduce the load on GIM wards by 1-17%. This wide range justifies controlled trials to determine the effect of improved community care on hospital utilization. GIM wards offer valuable learning opportunities, but they cannot be a substitute for primary care clinics. The unexplained high proportion of GIM inpatients who were discharged with an unspecified main diagnosis could be detrimental for the accuracy of hospitalization statistics, and justifies investigation by chart audits into physicians' habits of documentation.

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GIM= general internal medicine

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: Over a 12 month period, the Israel Transplant Center doubled the number of donors by assigning a nurse coordinator to each of 22 hospitals around the country and by using kidneys from elderly donors.

Objective: To evaluate the impact of our "marginal donors" policy on the results immediately following transplantation.

Methods: Between October 1997 and September 1998, 140 cadaveric kidney transplantations from 72 donors were performed in Israel. We defined two groups of recipients: patients with immediate graft function and patients with either delayed graft function requiring >1 week of dialysis post-transplant or with primary graft non-function. We compared the following parameters between groups: donor and recipient age and gender, cause of donor’s death, length of stay in the intensive care unit, vasopressor dosage and creatinine levels before harvesting, cold ischemic time, and the number of recipient grafts.

Results: There were 102 recipients (72.8%) with immediate graft function and 38 with either PNF (n=13, 9.3%) or DGF (n=25, 17.9%). On regression analysis, donor age >50 year and retransplantation were significant risk factors for PNF or DGF (odds ratio 4.4 and 2.8, respectively). Of the 56 kidneys from donors >50 years old, 21 (37.5%) developed either PNF (n=9) or DGF (n=12).

Conclusions: We conclude that kidneys from donors over age 50 are at increased risk for graft non-function or delayed function. Better assessment of functional capacity of kidneys from “aged” donors may help to choose appropriate donors from that pool.

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PNF = primary graft non-function

DGF = delayed graft function

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 compared the cost of treating anemia of prematurity in two consecutive 12-month periods: before and after the introduction of EPO therapy in our unit. The cost of blood bank charges as well as disposable items and the cost of EPO were compared.

Results: A significantly smaller number of infants required blood transfusions in the EPO group (2 of 25 vs. 9/21 before EPO was introduced). The cost of therapy for anemia of prematurity was significantly smaller in the EPO group (128±168 US$ per infant vs. 151±189 US$ per infant before the introduction of EPO).

Conclusion: We conclude that EPO is an efficient and cost-effective alternative to blood transfusions in VLBW infants.

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(1) VLBW = very low birthweight

(2) EPO = erythropoietin