Successful Use of Surgically Placed Impella 5.0 and Central Extracorporeal Membrane Oxygenation Circuit in a Patient with Postcardiotomy Shock

The Impella 5.0, a percutaneously inserted left ventricular assist device, has been used to support patients who have severe heart failure or who are undergoing high-risk percutaneous coronary intervention. We report our surgical placement of the Impella 5.0, through a graft sewn to the aorta, to unload the left ventricle of a 59-year-old man who was undergoing venoarterial extracorporeal membrane oxygenation for postcardiotomy shock. The patient underwent successful placement of a long-term left ventricular assist device before his discharge from the hospital. The versatility of the Impella 5.0 is exemplified in this patient who was successfully bridged to long-term support.     

Prevalence of knee abnormalities in patients with osteoarthritis and anterior cruciate ligament injury identified with peripheral magnetic resonance imaging: a pilot study.

OBJECTIVES: 1) To assess, with a peripheral magnetic resonance imaging system (pMRI), the prevalence of bony and soft tissue abnormalities in the knee joints of normal subjects, osteoarthritis (OA) patients, and individuals who have suffered an anterior cruciate ligament (ACL) rupture; and 2) to compare the prevalence among groups. METHODS: Magnetic resonance (MR) images of 28 healthy, 32 OA, and 26 ACL damaged knees were acquired with a 1.0-T pMRI system. Two radiologists graded the presence and severity of 9 MR image features: cartilage degeneration, osteophytes, subchondral cyst, bone marrow edema, meniscal abnormality, ligament integrity, loose bodies, popliteal cysts, and joint effusion. RESULTS: Ten of 28 healthy (35.7%), 24 of 26 ACL (92.3%), and all OA knees (100%) showed prevalent cartilage defects; 5 healthy (17.9%), 20 ACL (76.9%), and all OA knees (100%) had osteophytes; and 9 normal (32.1%), 21 ACL (80.8%), and 29 OA knees (90.6%) had meniscal abnormalities. One-half of the knees in the OA group (16 of 32, 50%) had subchondral cysts, and almost one-half had bone marrow edema (15 of 32, 46.9%). These features were not common in the ACL group (7.7%, and 11.5%, respectively) and were not observed in healthy knees. The OA group had the most severe cartilage defects, osteophytes, bone marrow edema, subchondral cysts, and meniscal abnormalities; the ACL group showed more severe cartilage defects, osteophytes, and meniscal abnormalities than did normal subjects. CONCLUSION: The results suggest that knees that have sustained ACL damage have OA-like reatures; most subjects (19 of 26, 73.1%) could be identified as in the early stage of OA. The prominent abnormalities present in ACL-damaged knees are cartilage defects, osteophytes, and meniscal abnormalities.     

The role of law in reproductive medicine: a new approach.

It is a common feature of debates on the regulation of reproductive medicine to find law portrayed as a crude form of intervention consisting in the imposition of inflexible rules on doctors and medical researchers. This paper argues that this view must be replaced by a more accurate assessment of the law's potential role in the regulation of reproductive medicine. From an analysis of the White Paper on human fertilisation and embryology, and in particular the proposed Statutory Licensing Authority, the author contends that far from being an inflexible method of regulation law can foster discussion and compromise.     

Inhibition of cysteine proteinases by autolytic digestion is mediated by CBP2/Hsp47

CBP2/Hsp47 is a glycoprotein normally limited to the ER-Golgi where it is first associated with procollagen chains at a very early point during translation of nascent chains and later with properly folded procollagen. Although CBP2/Hsp47 is regarded as a molecular chaperone belonging to the serpin superfamily, this protein does not appear to inhibit serine proteinases. Here we demonstrate that CBP2/Hsp47 functions in a manner similar to other serpin superfamily members by cross class inhibiting cysteine proteinases. A CBP2/Hsp47 to cathepsin L inactivation stoichiometery of approximately 1.5 revealed concurrent cleavage of CBP2/Hsp47 with proteinase inactivation. Cleavage of the CBP2/Hsp47 was shown to occur outside the P1-P1' at the P16-P15 and P2'-P3' bonds. In addition, the proteinase bands in SDS/PAGE diminished on reaction of the enzyme with CBP2/Hsp47. These results sustain a mechanism advocated by Bjork et al. (1998), in which cysteine proteinases assault a peptide bond in the reactive site loop of serpins, (CBP2/Hsp47) adjacent to the P1-P1' bonds involved in serine proteinase inhibition. The reaction proceeds with the substrate pathway dominating in the cysteine proteinase reaction. In these complexes the cysteine proteinases, papain and cathepsin L, are rendered more susceptible to proteolysis and are degraded by active enzyme. These properties help explain the mechanism by which CBP2/Hsp47 increases the fidelity of collagen production. Moreover, if CBP2/Hsp47 is shown to involve the multiplexin subclass of collagens, it may further provide a mechanism by which the motogen and angiogenic properties during development and/or neoplasia are regulated.     

In vitro osteogenic differentiation of marrow stromal cells encapsulated in biodegradable hydrogels

Novel hydrogel materials based on oligo(poly(ethylene glycol) fumarate) (OPF) crosslinked with a redox radical initiation system were recently developed in our laboratory as injectable cell carriers for orthopedic tissue engineering applications. The effect of OPF hydrogel material properties on in vitro osteogenic differentiation of encapsulated rat marrow stromal cells (MSCs) with and without the presence of osteogenic supplements (dexamethasone) was investigated. Two OPF formulations that resulted in hydrogels with different swelling properties were used to encapsulate rat MSCs (seeding density approximately 13 million cells/mL, samples 6 mm diameter x 0.5 mm thick before swelling) and osteogenic differentiation in these constructs over 28 days in vitro was determined via histology and biochemical assays for alkaline phosphatase, osteopontin and calcium. Evidence of MSC differentiation was apparent over the culture period for samples without dexamethasone, but there was large variability in calcium production between constructs using cells of the same source. Differentiation was also seen in samples cultured with osteogenic supplements, but calcium deposition varied depending on the source pool of MSCs. By day 28, osteopontin and calcium results suggested that, in the presence of dexamethasone, OPF hydrogels with greater swelling promoted embedded MSC differentiation over those that swelled less (43.7 +/- 16.5 microg calcium/sample and 16.4 +/- 2.8 microg calcium/sample, respectively). In histological sections, mineralized areas were apparent in all sample types many microns away from the cells. These experiments indicate that OPF hydrogels are promising materials for use as injectable MSC carriers and that hydrogel swelling properties can influence osteogenic differentiation of encapsulated progenitor cells.     

An immunocytochemical study of isolated human retinal Müller tells in culture

Background: We report a modified method for the isolation and propagation of adult human Müller cells in culture. Methods: The retina of postmortem human eyes was mechanically dissociated and cultured. Using immunocytochemical techniques, these cells were stained with monoclonal antibodies specific for Müller cells, glial fibrillary acidic protein (GFAP), vimentin, glutamine synthetase (GS) and keratin. Transmission electron microscopy (TEM) was also performed. Results: The dissociated and cultured cells expressed vimentin and GS, but not GFAP. At least 85% of these cells stained with a Müller tell-specific monoclonal antibody. Using TEM, flat cells containing 13-nm intermediate filaments and glycogen were identified. Conclusion: Human retinal Müller cells tan be isolated and propagated in culture. Purified cell cultures are required for controlled studies of the normal physiology and pathologie responses of Müller cells.     

Predictive factors of local-regional recurrences following parotid sparing intensity modulated or 3D conformal radiotherapy for head and neck cancer.

BACKGROUND AND PURPOSE: Predictive factors for local-regional (LR) failures after parotid-sparing, Intensity modulated (IMRT) or 3D conformal radiotherapy for head and neck (HN) cancers were assessed. PATIENTS AND METHODS: One hundred and fifty-eight patients with mostly stages III-IV HN squamous cell carcinoma underwent curative bilateral neck irradiation aimed at sparing the parotid glands. Patient, tumor, and treatment factors were analyzed as predictive factors for LR failure. RESULTS: Twenty-three patients had LR recurrence (19 in-field and four marginal). No differences were found in the doses delivered to the PTVs of patients with or without in-field recurrences. In univariate analysis, tumor site was highly predictive for LR failure in both postoperative and definitive RT patients. In postoperative RT patients, pathologic tumor size, margin status, extracapsular extension (ECE) and number of lymph node metastases, were also significantly predictive. Multivariate analysis showed tumor site (oropharynx vs. other sites) to be a significant predictor in all patients, and involved margins and number of involved lymph nodes in postoperative patients. CONCLUSIONS: Clinical rather than dosimetric factors predicted for LR failures in this series, and were similar to those reported following standard RT. These factors may aid in the selection of patients for studies of treatment intensification using IMRT.     

Osteogenic Differentiation of Marrow Stromal Cells on Random and Aligned Electrospun Poly(l-lactide) Nanofibers

The fibrillar structure and sub-micron diameter of electrospun nanofibers can be used to reproduce the morphology and structure of the natural extracellular matrix (ECM). The objective of this work was to investigate the effect of fiber alignment on osteogenic differentiation of bone marrow stromal (BMS) cells. Random and aligned poly(l-lactide) (PLLA) nanofibers were produced by collecting the spun fibers on a stationary plate and a rotating wheel, respectively, as the ground electrode. Morphology and alignment of the BMS cells seeded on the fibers were characterized by SEM. The effect of fiber orientation on osteogenic differentiation of BMS cells was determined by measuring alkaline phosphatase (ALPase) activity, calcium content, and mRNA expression levels of osteogenic markers. There was a strong correlation between the fiber and cell distributions for the random (p = 0.16) and aligned (p = 0.81) fibers. Percent deviation from ideal randomness (PDIR) values indicated that cells seeded on the random fibers (PDIR = 6.5%) were likely to be distributed randomly in all directions while cells seeded on the aligned fibers (PDIR = 86%) were highly likely to be aligned with the direction of fibers. BMS cell seeded on random and aligned fibers had similar cell count and ALPase activity with incubation time, but the calcium content on aligned fibers was significantly higher after 21 days compared to that of random fibers (p = 0.003). Osteopontin (OP) and osteocalcin (OC) expression levels of BMS cells on fibers increased with incubation time. However, there was no difference between the expression levels of OP and OC on aligned vs. random fibers. The results indicate that BMS cells aligned in the direction of PLLA fibers to form long cell extensions, and fiber orientation affected the extent of mineralization, but it had no effect on cell proliferation or mRNA expression of osteogenic markers.