Effect of eating on thallium-201 myocardial redistribution after myocardial ischemia

To determine whether eating a high-carbohydrate meal between initial and delayed postexercise thallium-201 (Tl-201) imaging affects detection of Tl-201 redistribution during exercise stress testing, 16 patients with stable angina performed 2 Tl-201 treadmill exercise stress tests within a 14-day interval. Immediately after initial postexercise imaging, patients either drank a commercially available instant breakfast preparation for the intervention test or drank an equivalent volume of water for the control test. Comparable exercise workloads were achieved by exercising patients to the same heart rate for both tests. The order of the 2 (intervention and control) tests were randomized. All patients had at least 1 region of Tl-201 myocardial redistribution on either their eating or control test scans, although only 7 of the 16 had positive treadmill exercise test responses. Forty-six regions showing Tl-201 myocardial redistribution were identified in all 144 regions examined. Significantly more of these regions were identified on control test scans than on eating test scans: 11 of 46 on both test scans, 6 of 46 only on eating test scans and 29 of 46 only on control scans (p less than 0.001). Consistent with results of the quantitative regional analysis, the percentage of Tl-201 clearance over 4 hours in the 46 Tl-201 myocardial redistribution regions was 39 +/- 8% for the eating tests and 29 +/- 8% for control tests (mean +/- standard deviation, p less than 0.003). In 4 patients diagnosis of transient ischemia would have been missed because their 14 Tl-201 myocardial redistribution regions were detected only on the control test scans.(ABSTRACT TRUNCATED AT 250 WORDS)     

Does bioequivalence between modified cyclosporine formulations translate into equal outcomes?

Neoral was replaced with a generic cyclosporine formulation on our hospital formulary. We compared outcomes for de novo kidney transplant recipients who either received Gengraf (n=88) or Neoral (n=100) in a single-center, retrospective review. As compared to patients who received Neoral, patients who received Gengraf were significantly more likely to have an acute rejection episode (39% vs. 25%, P=0.04), more likely to have a second rejection episode (13% vs. 4%; P=0.03), or to have received an antibody preparation to treat acute rejection (19% vs. 8%; P=0.02). Patients treated with Gengraf had a higher degree of intrapatient variability for cyclosporine trough concentrations as determined by %CV (P<0.05). The incidence of acute rejection at 6 months posttransplant was significantly higher in patients who received Gengraf compared to Neoral. A larger, prospective analysis is warranted to compare these formulations of cyclosporine in de novo kidney transplant recipients.     

Living donor transplantation of a pelvic kidney

Pelvic kidneys are uncommon anomalies rarely utilized in kidney transplantation. We describe a successful case of living-donor transplantation using a pelvic kidney in a 17-month-old infant with congenital renal dysplasia. The recipient had exhausted all options for renal replacement therapy, and urgent transplantation was considered a life saving treatment.     

Outpatient Parenteral Antibiotic Therapy (OPAT): the Italian registry

In the early eighties, in the US the advantages (reduced costs, no hospitalisation trauma in children, no immobilization syndrome in elderly, reduction of nosocomial and acquired infections by multi-resistant organisms) of OPAT were identified and suitable therapeutic programs were established. Following the US experience, other countries set up their own OPAT programs which vary considerably from country to country because of different ways in which infections are managed in different parts of the world and because of different reimbursement systems. In order to understand the ways of managing OPAT and its results, a National OPAT Registry was set up in 1999 in Italy belonging to a wider International OPAT database, which collects data also from USA, Canada, Spain, Uruguay and Argentina. Up to now 396 patients and as many antibiotic courses have been included in the National Registry by eight different centres. The analysis of data permits to get information about the criteria of patient's selection, treatment (route of administration, site of care, choice of antibiotic, dosage and duration), outcomes and possible side-effects. Italian results offer a quite peculiar picture of OPAT in this country when comparing data with those of other countries. In contrast with other countries where soft tissue infections and osteomyelitis are the most frequent diagnoses for including patients in OPAT programmes, in Italy pneumonia and bronchitis are the top two amenable infections. Ceftriaxone, Teicoplanin and Amikacin are absolutely the top three antibiotics selected for OPAT in Italy which confirm that a single daily dose regimen represents a great advantage in terms of compliance. Finally, a large percentage of antibiotic courses (50%) are carried out by using the i.m. administration route, which is very unusual in other countries. OPAT Registry is still ongoing and it will give us more detailed information in the future about the management of infections in the outpatient setting, but it already permits to define an actual picture of OPAT in our country and/or to compare and correlate data and information from different countries.     

In vitro generation of differentiated cardiac myofibers on micropatterned laminin surfaces

Cardiac muscle fibers consist of highly aligned cardiomyocytes containing myofibrils oriented parallel to the fiber axis, and successive cardiomyocytes are interconnected at their ends through specialized junctional complexes (intercalated disks). Cell culture studies of cardiac myofibrils and intercalated disks are complicated by the fact that cardiomyocytes become extremely flattened and exhibit disorganized myofibrils and diffuse intercellular junctions with neighboring cells. In this study we sought to direct the organization of cultured cardiomyocytes to more closely resemble that found in vivo. Lanes of laminin 5-50 microm wide were microcontact-printed onto nonadhesive (BSA-coated) surfaces. Adherent cardiomyocytes responded to the spatial constraints by forming elongated, rod-shaped cells whose myofibrils aligned parallel to the laminin lanes. Patterned cardiomyocytes displayed a striking, bipolar localization of the junction molecules N-cadherin and connexin43 that ultrastructurally resembled intercalated disks. When laminin lanes were widely spaced, each lane of cardiomyocytes beat independently, but with narrow-spacing cells bridged between lanes, yielding aligned fields of synchronously beating cardiomyocytes. Similar cardiomyocyte patterns were achieved on the biodegradable polymer PLGA, suggesting that patterned cardiomyocytes could be used in myocardial tissue engineering. Such highly patterned cultures could be used in cell biology and physiology studies, which require accurate reproduction of native myocardial architecture.     

Maintaining Equity and Access: Successful Implementation of a Virtual Kidney Transplantation Evaluation

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Evaluating the Treatment Patterns of Chlormethine/Mechlorethamine Gel in Patients With Stage I-IIA Mycosis Fungoides: By-time Reanalysis of a Randomized Controlled Phase 2 Study

BackgroundThe pivotal 201 Study investigated chlormethine/mechlorethamine gel treatment for patients with early stage disease mycosis fungoides and demonstrated the treatment was not inferior to chlormethine ointment. However, overall response rates do not provide information about response patterns. The study objective was to assess the value of by-time analysis of clinical response data in visualizing response over time.MethodsThis post hoc analysis re-evaluated chlormethine efficacy using a by-time approach that investigated the trend to treatment response and permitted assessment of response, both monthly between 1 and 6 months, and once every 2 months between 7 and 12 months, over the course of 1 year. In addition, very good partial response was redefined as a ≥ 75% response.ResultsBy-time analyses of Composite Assessment of Index Lesion Severity (CAILS) and modified severity-weighted assessment tool (mSWAT) showed response rates at 1 month (respectively, 8.5% and 5.9%) that increased over time to peak at 10 months (78.9% and 54.4%). Early, intermittent, and late response patterns were observed. In total, 32.5% of patients experienced very good partial response over 2 consecutive visits, indicating that ～ 33% of patients could expect to have very good to complete response within 1 year.ConclusionBy-time analysis for clinical response provides complementary information to traditional overall response rate data regarding response peak time and changes over time.     

Inflammatory myofibroblastic tumor of the liver

Inflammatory myofibroblastic tumor is a rare benign entity formerly known as inflammatory pseudotumor. Involvement of the liver is extremely rare. There are controversies about the optimal treatment of this benign entity. Newer reports suggest an association with autoimmune sclerosing pancreatitis and primary sclerosing cholangitis. We present a case of an 18-year-old patient with biliary obstruction from a perihilar mass of the liver requiring hepatic resection. Division of the hepatic bile duct resulted in drainage of yellow, thick, gelatinous material in the presence of benign margins and absence of cholangitis. Histological examination showed a mass with fibroblastic and myofibroblastic cells set in a loose myxoid matrix containing scattered lymphocytes, consistent with an inflammatory myofibroblastic tumor. One-year recovery was uneventful. This report discusses the presentation, diagnosis, and controversies in management of this disease.     

Reorganization of basement membrane matrices by cellular traction promotes the formation of cellular networks in vitro.

Vascular endothelial cells that are cultured on layers of gelled basement membrane matrix organize rapidly into networks of cords or tubelike structures. Although this phenomenon is a potential model for angiogenesis in vivo, we questioned whether basement membrane matrix directs the differentiation of endothelial cells in a specific manner. In this study, we have examined factors that influence the formation of cellular networks in vitro in an attempt to define a basic mechanism for this process. We found that endothelial cells, fibroblasts, smooth muscle cells, and cells of the murine Leydig cell line TM3 formed networks on basement membrane matrix in much the same fashion. Light and electron microscopy, combined with time-lapse videomicroscopy, revealed that cells organized on a tesselated network of aligned basement membrane matrix that was generated by tension forces of cellular traction. Cellular elongation and progressive motility across the surface of the gel were restricted to tracks of aligned matrix and did not occur until the tracks appeared. The formation of cellular networks on basement membrane matrix was inhibited by reducing the thickness of the matrix, by including native type I collagen in the matrix, or by disrupting cytoskeletal microfilaments and microtubules. Cell division was not required for network formation. Bovine aortic endothelial cells that formed networks did not simultaneously transcribe mRNA for type I collagen, a protein synthesized by endothelial cells that form tubes spontaneously in vitro. Moreover, levels of mRNA for fibronectin and SPARC (Secreted Protein that is Acidic and Rich in Cysteine) in network-forming cells were similar to levels seen in endothelial cells that did not form networks. Endothelial cells and TM3 cells that were plated on highly malleable gels of native type I collagen also formed cords and aligned matrix fibers into linear tracks that resembled those generated on basement membrane matrix, although the structures were not as well-defined. Our observations suggest that the mechanochemical properties of extracellular matrices are able to translate the forces of cellular traction into templates that direct the formation of complex cellular patterns.