Israel Medical Association Journal

Quantitative chimerism testing has become an indispensable tool for following the course and success of allogeneic hematopoietic stem cell transplants. In this paper, we describe the current laboratory approach to quantitative chimerism testing based on an analysis of short tandem repeats, and explain why performing this analysis longitudinally is important and feasible. Longitudinal analysis focuses on relative changes appearing in the course of sequential samples, and as such exploits the ultimate potential of this intrinsically semi-quantitative platform. Such an analysis is more informative than single static values, less likely to be confused with platform artifacts, and is individualized to the particular patient. It is particularly useful with non-myeloablative conditioning, where mixed chimerism is common. When longitudinal chimerism analysis is performed on lineage-specific subpopulations, the sensitivity, specificity and mechanistic implications of the data are augmented. Importantly, longitudinal monitoring is a routinely feasible laboratory option because multiplex STR-PCR[1] kits are available commercially, and modern software can be used to perform computation, reliability testing, and longitudinal tracking in a rapid, easy to use format. The ChimerTrack© application, a shareware program developed in our laboratory for this purpose, produces a report that automatically summarizes and illustrates the quantitative temporal course of the patient’s chimeric status. Such a longitudinal perspective enhances the value of quantitative chimerism monitoring for decisions regarding immunomodulatory post-transplant therapy. This information also provides unique insights into the biological dynamics of engraftment underlying the fluctuations in the temporal course of a patient’s chimeric status.

Background: Ethnicity has been associated with variance in warfarin treatment regimens in various settings.

Objectives: To determine whether ethnicity is associated with variance in patient management in Israel.

Methods: Data were extracted from the electronic patient records of Clalit Health Services clinics in the Sharon Shomron region. The study group comprised all patients treated with warfarin who performed international normalized ratio tests for at least 6 months in 2003. The proportion of tests of each patient within the target range was calculated, as was the crude average rates and 95% confidence intervals for Jewish and Arab patients. The data were then stratified by patient's gender, specialty of attending physician, patient's age, and the country where the physician studied medicine.

Results: We identified 2749 Jews and 293 Arabs who met the inclusion criteria of the study. The crude average rate of patients’ INR[1] tests within the target range was 62.3% among Jews (95% CI[2] 61.5–63.1) and 52.7% (95% CI 49.9–55.5) among Arabs. When stratified by gender, age, and the treating physician's specialty and country of education, the stratum-specific rates among Jewish patients were consistently higher than among Arabs.

Conclusions: These results suggest that cultural differences regarding adherence to recommendations for drug therapy in addition to genetic factors may be associated with this variance.

Background: Halofuginone is a novel antifibrotic agent that can reserve the fibrotic process by specific inhibition of collagen type I synthesis.

Objectives: To evaluate the effect of Halo on the development of glomerulosclerosis and interstitial fibrosis in the 5/ 6 nephrectomy rat model.

Methods: Male Wistar rats were assigned to undergo 5/6 NX or sham operation, and then divided into three groups: 5/6 NX rats (NX-Halo and NX-Control) and sham. Systolic blood pressure proteinuria and body weight were determined every 2 weeks. At sacrifice (10 weeks) creatinine clearance was evaluated and remnant kidneys removed for histologic examination, Sirius red staining and in situ hybridization.

Results: Systolic blood pressure increased progressively in both 5/6 NX groups. Halo slowed the increase in proteinuria in 5/6 NX rats. As expected, creatinine clearance was lower in 5/6 NX groups when compared to sham rats. Creatinine clearance was significantly higher in the NX-Halo group at the end of the study period. Histologic examination by light microscopy showed significantly less severe interstitial fibrosis and glomerulosclerosis in Halo-treated rats. The increase in collagen α1 (I) gene expression and collagen staining after nephrectomy was almost completely abolished by Halo.

Conclusions: Halofuginone reduced proteinuria as well as the severity of interstitial fibrosis and glomerulosclerosis in 5/6 NX rats. The renal beneficial effect of Halo was also demonstrated by the blunted decrease in creatinine clearance observed in the treated animals.  
 

Objectives: To describe how an HMO[1] used its health information technology in a way that enables its management to receive updated online information on the demands of the insured, according to their distribution throughout the country during the time of the war in Lebanon in July-August 2006.

Methods: Data were derived from the computerized medical records of Maccabi Healthcare Services – the second largest HMO in Israel, providing care to more than 1.7 million members nationwide. Data on healthcare utilization by northern members were compared to the geographic distribution of clinics.

Results: The war was characterized by the massive evacuation of citizens southwards. During this period there was an abrupt decline in the utilization of medical services by northern members in the northern region. This decline returned to normal 10 days after the ceasefire. A reciprocal increase was noted in the use of health services by citizens from the north in other regions. This increase returned to normal after the war. No such pattern was noticed during the same period in 2005.

Conclusions: Real-time surveillance of trends in consumption of health services by citizens in times of regular daily living as well as during emergencies and wars is a vital management tool for medical directors responsible for providing health services.

Objectives: To evaluate the criteria used to select surgical versus medical management for SICH.

Methods: We retrospectively reviewed the files of 149 consecutive patients admitted with SICH[1] from January 2004 through January 2006 to our medical center. Their mean age was 66 (range 3–92 years), and 62% were male. SICH localization was lobar in 50% of patients, thalamus in 23%, basal ganglia in 15%, cerebellum in 13%, intraventricular in 6%, and pontine in 1%. Mean admission Glasgow Coma Score was 9 (range 3–15). Risk factors included hypertension in (74%), diabetes mellitus (34%), smoking (14%) and amyloid angiopathy (4%). Fifty percent of patients were on anticoagulant/antiplatelet therapy, including enoxaparin (3%), warfarin (7%), warfarin and aspirin (9%), or aspirin alone (34%).      

Results: Craniotomy was performed in 30% of patients, and ventriculostomy alone in 3%. Rebleed occurred in 9% of patients. Six months after the treatment 36% of operated patients were independent, 42% dependent, and 13% had died. At 6 months, 37% of non-operated patients were independent, 15% dependent, and 47% had died.

Conclusions: One-third of the SICH patients, notably those who were experiencing ongoing neurologic deterioration and had accessible hemorrhage, underwent craniotomy. The results are good, considering the inherent mortality and morbidity of SICH.