Use of cardiopulmonary bypass to salvage patients with multiple-chamber heart wounds

BACKGROUND: The need for cardiopulmonary bypass in the treatment of penetrating heart injuries is debated. OBJECTIVES: To review our experience with penetrating heart injuries and determine the indications and outcome for cardiopulmonary bypass. DESIGN: Retrospective review. SETTING: A university-based, level I trauma center. PATIENTS: All victims of penetrating heart injury presenting between July 1, 1989, and December 31, 1995. METHODS: Medical records were reviewed for demographic and physiological data, operative findings, and outcome. RESULTS: Overall survival for 106 patients with penetrating heart injury was 55%. In an effort to resuscitate the heart, 4 patients with unresponsive cardiogenic shock were placed on cardiopulmonary bypass; none survived. Of 30 patients with multiple-chamber injuries, 11 presented with signs of life and 7 survived. Cardiopulmonary bypass was essential to repair complex injuries in 2 of the 7 survivors. CONCLUSION: Cardiopulmonary bypass was ineffective in salvaging patients with cardiogenic shock but was essential in some patients with complex multiple-chamber cardiac injuries that could not be exposed and repaired by other means.     

Prospects of glutamate antagonists in the therapy of Parkinson''s disease

BACKGROUND AND AIMS OF THE STUDY: Several different biological, bioprosthetic and mechanical devices are available for heart valve replacement. We present a quantitative methodology to estimate the (event-free) life-expectancy and lifetime risk of valve-related events for individual patients after implantation of any one of these valve types. METHODS: We modelled the age-dependent prognosis of a patient after aortic valve replacement with a discrete-time Markov model and Monte-Carlo simulation to estimate (event-free) life-expectancy and life-time risk of valve-related events, respectively. Quantitative estimates to parameterize these models used hypothetical devices and presumed data were based on a limited review of published literature. RESULTS: This decision-analytical approach allowed an estimation of the overall and event-free life-expectancy as well as the lifetime risk of valve-related events after implantation of different types of prosthetic heart valve in the aortic position. In the current, hypothetical model, one valve type excelled for all age groups in terms of life expectancy and life-time risk of valve-related events. The choice of the second-best alternative varied according to patient age and comorbidity. Sensitivity analyses showed results to be especially dependent on the durability of the replacement valve and surgical risk. CONCLUSIONS: This methodological approach is very flexible, and its quantitative results may guide decision making, if increasing quantitative information on heart valve prosthesis performance becomes available in future. Markov models and Monte Carlo simulation may be used to obtain a better understanding of the effect that different types of prosthetic heart valves have on patient prognosis, while quantitative results may help cardiologists and cardiac surgeons to choose a specific valve type for an individual patient.     

Effects of interleukin-1 receptor antagonist in a slow-release hylan vehicle on rat type II collagen arthritis

PURPOSE: To determine the effect of hylan fluid (HA), a model slow release vehicle on the pharmacokinetic profile and efficacy of interleukin-1 receptor antagonist (IL-1ra) in rats with established type II collagen arthritis. METHODS: Female Lewis rats with type II collagen arthritis were treated daily, every other day or every third day with single subcutaneous (sc) injections of IL-1ra formulated in HA and the effects on arthritis determined. Results were compared to those obtained with IL-1ra in citrate buffered saline with EDTA and polysorbate (CSEP). Sequential blood levels were determined in rats injected sc with IL-1ra in CSEP or HA. RESULTS: Incorporation into HA led to slower release of IL-1ra into the bloodstream and maintained therapeutic blood levels of IL-1ra for a longer time compared to the IL-1ra/CSEP formulation. Single daily sc doses of 100 mg/kg IL-1ra in CSEP were ineffective in type II collagen arthritis. By contrast, once per day dosing of 100 mg/kg IL-1ra in HA provided 78% inhibition of paw swelling. Every other day dosing with 100 mg/kg IL-1ra in HA resulted in 62% inhibition. IL-1ra (100 mg/ kg in HA) given every third day provided 19% inhibition of arthritis. Improved efficacy correlated with improved pharmacokinetics. CONCLUSIONS: Administration of IL-1ra in the slow release vehicle HA improves pharmacokinetics and efficacy in rat type II collagen arthritis.     

Menin, the product of the MEN1 gene, is a nuclear protein

The MEN1 gene, mutations in which are responsible for multiple endocrine neoplasia type 1 (MEN1), encodes a 610-amino acid protein, denoted menin. The amino acid sequence of this putative tumor suppressor offers no clue to the function or subcellular location of the protein. We report herein, based on immunofluorescence, Western blotting of subcellular fractions, and epitope tagging with enhanced green fluorescent protein, that menin is located primarily in the nucleus. Enhanced green fluorescent protein-tagged menin deletion constructs identify at least two independent nuclear localization signals (NLS), both located in the C-terminal fourth of the protein. Among the 68 known independent disease-associated mutations, none of the 22 missense and 3 in-frame deletions affect either of the putative NLS sequences. However, if expressed, none of the truncated menin proteins resulting from the 43 known frameshift/nonsense mutations would retain both the NLSs. The precise role(s) of menin in the nucleus remain to be understood.     

Histopathology of coronary lesions with early loss of minimal luminal diameter after successful percutaneous transluminal coronary angioplasty: is thrombus a significant contributor?

BACKGROUND: Early loss of minimal luminal diameter of >0.3 mm after successful percutaneous transluminal coronary angioplasty (PTCA) is associated with a higher incidence of restenosis. The underlying mechanism of this early loss is unknown and thrombus may be a contributing factor. METHODS: We performed a prospective study using quantitative computerized planimetry on coronary tissue specimens obtained by directional coronary atherectomy of 24 lesions in which early loss occurred 22+/-9 minutes after successful PTCA. RESULTS: Thrombus was present in 9 (37%) of 24 coronary specimens. Segmental areas (mm2) and percentage of total area were distributed as follows: sclerotic tissue, 4.07+/-0.7 mm2 (63%+/-6%); fibrocellular tissue, 0.97+/-0.27 mm2 (16%+/-4%); hypercellular tissue, 0.99+/-0.29 mm2 (12%+/-3%); atheromatous gruel, 0.18+/-0.07 mm2 (3%+/-0.1%); and thrombus, 0.24+/-0.15 mm2 (6%+/-0.4%). There was no difference in the relative early loss index between lesions with or without thrombus (35%+/-7% vs 26%+/-2%, respectively; P= .87). Multiple stepwise regression analysis did not identify any histologic predictors of relative early loss index. CONCLUSION: Histopathologic analysis of coronary lesions with early loss after successful PTCA suggests that thrombus may not play a significant role in this angiographic phenomenon.     

Analysis of the botulinum neurotoxin type F gene clusters in proteolytic and nonproteolytic Clostridium botulinum and Clostridium barati

The purpose of this in vitro study was to compare both apical and coronal dye penetration when Ketac-Endo and AH-26 sealers were used with laterally condensed gutta percha. Crowns were removed from 28 teeth and the root canals were biomechanically prepared. The teeth were divided into two groups of 12-teeth each and a control group of 4 teeth. Root canals in the two experimental groups were filled with laterally condensed gutta percha and either Ketac-Endo or AH-26 sealer. The Ketac-Endo group had the coronal 3 mm of gutta percha and sealer removed and the resultant cavity was filled with Ketac-Endo alone. After the sealers had set, the root surfaces were coated with nail varnish except at the apex and at the coronal end. Positive controls had no root fillings and were coated with nail varnish in the same manner while the negative controls were sealed apically and coronally with Cavit prior to sealing the entire external root surface with nail varnish. Specimens were placed in 2% methylene blue dye in a vacuum of 660 mm of mercury for five minutes and then left immersed for a further two days. The roots were vertically sectioned to determine the following mean levels of dye penetration: Ketac-Endo, 1.08 mm apically and 6.29 mm coronally; AH-26, 0.75 mm apically and 6.67 mm coronally. Positive controls had total leakage and negative controls had no leakage. This study demonstrated that the apical and coronal seals obtained with Ketac-Endo and AH-26 were not significantly different although the apical seal obtained with each material was significantly better than the corresponding coronal seal.     

Catalytic activities, protein- and mRNA-expression of cytochrome P450 isoenzymes in intestinal cell lines

1. Certain chemicals and drugs in addition to metabolically activated carcinogens are substrates for intestinal cytochrome P450s (CYPs) and a number of cell lines are available which could be used in metabolism studies. These include the rat duodenal cell line IEC 6, rat ileal IEC 18, foetal human HuTu 80, foetal human small intestinal FHS 74, human duodenal HCT 8 and human colon CaCo-2 cells, but they lack thorough biochemical characterization. 2. The aim of the present study was therefore to investigate the mRNA and protein expression of CYP1A1, CYP1A2, CYP2C9/10, CYP2E1 and CYP3A. In addition, the metabolism of the immunosuppressant drug tacrolimus and of the procarcinogen 7,12-dimethyl-benz[a]anthracene (DMBA) was studied to obtain information on the functional activity on these cell lines. 3. Of all the cell lines tested only CaCo-2 cells expressed CYP1A1 at the protein and mRNA level, but the CYP2E1 and CYP3A protein was also detected in CaCo-2 and FHS 74 cells. It is of considerable interest that none of the other cell lines expressed CYP1A1, CYP1A2, CYP2C9/10 or CYP3A4 at the protein and mRNA level. 4. When the metabolism of DMBA (a model carcinogen) was studied, CaCo-2 cells produced the following metabolites: 7,12-dihydroxymethylbenz[a]anthracene, 7,12-dimethylbenz-[a]anthracene-di-hydrodiol, 7-methyl-12-hydroxymethylbenz[a]anthracene, 7-hydroxy-methyl-12-benz[a]anthracene and possibly the dihydrated product of the latter two derivatives. 5. CaCo-2 cells also catalysed the metabolism of the immunosuppressant drug tacrolimus resulting in the formation of 13-O-demethyl-tacrolimus bisdemethyl-hydroxy-tacrolimus and demethyl-dihydroxy-tacrolimus. Neither the foetal human small intestinal FHS 74 cell line nor any of the other cell lines were able to catalyse the biotransformation of tacrolimus. 6. In conclusion, only CaCo-2 cells were able to produce metabolites similar to those observed in in vivo metabolism studies, whereas all other cell lines were metabolically incompetent. Therefore, this cell line may be used in studies of intestinal biotransformation.