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PubMed2002

Ventricular reconstruction results in improved left ventricular function and amelioration of mitral insufficiency.

INTRODUCTION: Surgical restoration of the left ventricular wall (Dor procedure) has been advocated as a therapy for left ventricular dysfunction due to ischemic cardiomyopathy. This procedure involves placement of an endoventricular patch through a ventriculotomy. METHODS: We reviewed our series of patients that underwent the Dor procedure within the past 4 years and examined their pre and postoperative ventricular function and mitral valve function. Pre and postoperative ejection fraction and degree of mitral regurgitation were analyzed using the paired Student t-test. We hypothesized that this procedure would result in improved ventricular function and that it would also help improve mitral valve function. RESULTS: Thirty-four patients underwent this procedure, with one death. Of these, 30 patients underwent concomitant coronary artery bypass grafting and 8 patients had mitral intervention (seven had an Alfieri repair of the mitral valve, and one had mitral valve annuloplasty). The average preoperative ejection fraction among these patients was 26.8% (range 10-45%). The postoperative ejection fraction was significantly higher at 35.4% (range 25-52%) (P <.001). We noted an improvement in ejection fraction in 27 patients (82%). We also noted that 21 of 33 patients (64%) had improvement in the degree of mitral regurgitation based on echocardiography data (P <.001). CONCLUSIONS: We conclude that the Dor procedure results in improvement in the left ventricular function. Furthermore, we also note that this procedure ameliorates mitral regurgitation in a majority of these patients even in the absence of associated mitral valve procedures, probably due to reduction in the size of the ventricle and improved orientation of the papillary muscles.

Cardiac Surgical Procedures↗
PubMed1994

Flow cytometric DNA content analysis of paraffin-embedded tissue derived from cervical carcinoma.

PURPOSE: Flow cytometric deoxyribonucleic acid (DNA) content analysis has been shown to be of prognostic importance in some cancers. There have been recent reports of a prognostic importance for DNA content analysis in cervical carcinoma. METHODS AND MATERIALS: We retrospectively reviewed the hospital and radiation oncology records of cervical carcinoma patients who presented between 1984-1990. RESULTS: A total of 101 archival paraffin-embedded blocks were processed, of which 77 were of technical quality for analysis. Thirty-five percent were found to be DNA content aneuploid (DNA-A) and 65% DNA content diploid (DNA-D). No statistical difference was found between the two groups in age at diagnosis, % S-phase, coefficient of variation (CV), or proliferative index (PI). A statistical difference was noted in the G2M phase between the two groups (p = 0.004). The median % S-phase was 8.4% in the DNA-D group. A statistical difference (p = 0.017) in survival was noted between the low and high % S-phase DNA-D groups. In patients who received radiation alone, high-PI patients had improved survival compared to low-PI patients. No statistical difference in survival was noted in the high % S-phase DNA-D group and DNA-A group (p = 0.28). Proportional Hazard (Cox) Regression found clinical stage the only independent prognostic indicator for survival. CONCLUSION: Flow cytometric DNA content analysis is being used more frequently in the management of different malignant tumors. Our study shows that DNA content analysis is useful in determining the prognosis and survival outcomes in cervical carcinomas and may aid in predicting outcome to certain types of treatment regimens.

Aneuploidy↗
PubMed2004

Tumor necrosis factor-alpha from resident lung cells is a key initiating factor in pulmonary ischemia-reperfusion injury.

OBJECTIVE: A central role of macrophages in initiating lung ischemia-reperfusion injury is emerging. Tumor necrosis factor-alpha is a proinflammatory cytokine secreted mainly by macrophages under various conditions. We hypothesized that tumor necrosis factor-alpha from resident lung cells is a key initiating factor in pulmonary ischemia-reperfusion injury. METHODS: We used an isolated, buffer-perfused lung system to explore the role of tumor necrosis factor-alpha production by resident lung cells in pulmonary ischemia-reperfusion injury. Lungs from wild-type mice and tumor necrosis factor-alpha-deficient mice were subjected to 60 minutes of ischemia followed by 60 minutes of reperfusion. Histologic injury scores and measurements of lung compliance, airway resistance, mean pulmonary artery pressure, vascular reactivity, and wet lung weight index were obtained and compared using repeated-measures analysis of variance. RESULTS: Lungs from tumor necrosis factor-alpha-deficient mice showed significantly less injury in all physiologic parameters throughout the entire 60 minutes of reperfusion compared with lungs from wild-type mice (P <.001). The most notable effects were observed in pulmonary artery pressure and airway resistance. Vascular reactivity (acute vasoconstrictive episodes per 60 minutes) was also blunted in the lungs from tumor necrosis factor-alpha-deficient mice compared with the lungs from wild-type mice (5.8 responses/hour vs 1.2 responses). Histologic injury scores and wet lung weight index were significantly reduced in lungs from tumor necrosis factor-alpha-deficient mice. CONCLUSIONS: By using the advantages of a nonblood-perfused system, we have focused our investigation on resident lung cells. Our results demonstrate that resident cell-produced tumor necrosis factor-alpha is a key initiating factor in acute lung ischemia-reperfusion injury.

Airway Resistance↗
PubMed2004

Sequence-based identification of aerobic actinomycetes.

We investigated the utility of 500-bp 16S rRNA gene sequencing for identifying clinically significant species of aerobic actinomycetes. A total of 28 reference strains and 71 clinical isolates that included members of the genera Streptomyces, Gordonia, and Tsukamurella and 10 taxa of Nocardia were studied. Methods of nonsequencing analyses included growth and biochemical analysis, PCR-restriction enzyme analysis of the 439-bp Telenti fragment of the 65 hsp gene, susceptibility testing, and, for selected isolates, high-performance liquid chromatography. Many of the isolates were included in prior taxonomic studies. Sequencing of Nocardia species revealed that members of the group were generally most closely related to the American Type Culture Collection (ATCC) type strains. However, the sequences of Nocardia transvalensis, N. otitidiscaviarum, and N. nova isolates were highly variable; and it is likely that each of these species contains multiple species. We propose that these three species be designated complexes until they are more taxonomically defined. The sequences of several taxa did not match any recognized species. Among other aerobic actinomycetes, each group most closely resembled the associated reference strain, but with some divergence. The study demonstrates the ability of partial 16S rRNA gene sequencing to identify members of the aerobic actinomycetes, but the study also shows that a high degree of sequence divergence exists within many species and that many taxa within the Nocardia spp. are unnamed at present. A major unresolved issue is the type strain of N. asteroides, as the present one (ATCC 19247), chosen before the availability of molecular analysis, does not represent any of the common taxa associated with clinical nocardiosis.

Actinobacteria↗
PubMed2001

Assessment of white matter injury following prolonged focal cerebral ischaemia in the rat.

The ability of putative neuroprotective compounds to protect against white matter injury remains poorly investigated due to the lack of suitable methods for assessing white matter injury. This study was therefore designed to investigate the utility of Tau 1 (oligodendrocytes/axons), myelin basic protein (MBP; myelin) and amyloid precursor protein (APP; axons) immunohistochemistry in assessing white matter injury at various times following middle cerebral artery occlusion (MCAO) in the rat. Focal cerebral, ischaemia was induced in halothane-anaesthetised rats using an intraluminal thread model. At 24 h, 1 and 2 weeks following MCAO, white matter injury was assessed using Tau 1, APP, MBP and Luxol-fast blue staining and neuronal injury with cresyl fast violet (CFV). In histologically normal tissue MBP immunoreactivity was detected in myelinated fibre tracts, while Tau 1 and APP were axonally located. At 24 h following permanent MCAO, MBP, and Tau 1 staining remained relatively unchanged within the myelin and axonal compartments of the ischaemic region. In contrast, increased Tau 1 staining was apparent in oligodendrocytes within ischaemic tissue, while APP accumulated in axons surrounding the lesion. At 1 and 2 weeks following transient MCAO, Tau 1 and APP staining was markedly decreased within ischaemic tissue. Marked reduction in MBP levels within ischaemic tissue were not detected until 2 weeks following MCAO. The area of axonal injury as assessed by reduced Tau 1 or APP staining correlated with the area of neuronal damage as assessed by CFV staining. This study shows that MBP, Tau 1 and APP immunohistochemistry can be utilised to assess myelin and axonal integrity following sustained ischaemia using standard image analysis techniques.

Amyloid beta-Protein Precursor↗
PubMed2002

Clinical impact of endoscopic ultrasound-guided fine needle aspiration of celiac axis lymph nodes (M1a disease) in esophageal cancer.

BACKGROUND: The purpose of this study was to determine how endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) with a histology confirmed biopsy protocol impacted on staging and managing esophageal carcinoma in terms of resectability and neoadjuvant therapy (chemotherapy and radiation therapy). METHODS: The records of 40 consecutive patients diagnosed with esophageal cancer referred for EUS staging were reviewed. Computed tomography (CT) scan then EUS imaging and EUS-guided FNA staging, including involvement of celiac node (M1a stage), surgical pathology, and subsequent treatment were correlated. Through-the-scope balloons were used for dilatation when needed to examine the celiac nodes. RESULTS: All 40 patients followed the protocol and were successfully imaged by EUS. Sixteen of the 40 required esophageal dilatation using the through-the-scope balloon. No complications were observed from esophageal dilatation for EUS. Twenty-three (58%) met the criteria for EUS-guided FNA biopsy from a total of 40 EUS imaging procedures. Twenty (87%) of the 23 EUS-guided FNA were directed toward the celiac nodes; 18 (90%) of the 20 were positive for malignancy and were treated by chemoradiation therapy and 2 (10%) FNA were negative for malignancy and were treated by surgical resection. The CT scan was able to detect only 6 (30%) of 20 cases of suspicious celiac lymph nodes, of which 5 (83%) were positive for malignancy by FNA. CONCLUSIONS: EUS-guided FNA of celiac nodes (20 patients) directed management in all patients biopsied. EUS-guided FNA is superior to CT scan for diagnosing M1a disease. Protocol-directed EUS-guided FNA is a pivotal study when used in conjunction with stage-oriented treatment protocols for esophageal carcinoma.

Adult↗
PubMed2006

Toward an optimum system for intervertebral disc organ culture: TGF-beta 3 enhances nucleus pulposus and anulus fibrosus survival and function through modulation of TGF-beta-R expression and ERK signaling.

STUDY DESIGN: Rat lumbar discs comprising nucleus pulposus, annulus fibrosus, and cartilaginous endplates were cultured for 1 week in a specialized media containing either TGF-beta1 or TGF-beta3. Role of TGF-beta isoforms on cell function was evaluated. OBJECTIVE: To develop an in vitro organ culture of rat intervertebral disc and evaluate effects of TGF-beta3 on disc cell function. SUMMARY OF BACKGROUND DATA: An in vitro model system is of considerable value in understanding the cell biology of the intervertebral disc. Development of a useful organ culture model would enhance understanding of disc function in health and disease. MATERIALS AND METHODS: Rat lumbar intervertebral discs were maintained in organ culture in media supplemented with TGF-beta3 or TGF-beta1 for 1 week. Tissue morphology was studied using routine histologic, histochemical and immunohistochemical techniques. Cell function was assessed by gene expression, sulfate incorporation, and Western blot analysis. RESULTS: After 1 week in culture with TGF-beta3 and TGF-beta1, the gross morphology and tissue architecture of the disc were preserved. TUNEL analysis indicated that there was no evidence of cell death in the nucleus pulposus or the anulus fibrosus. The level of Alcian blue staining in the nucleus pulposus was similar to that of the freshly isolated disc. However, when compared with TGF-beta1, TGF-beta3 elevated the expression of critical matrix genes, enhanced [S] incorporation into proteoglycans, preserved the expression of TGF-beta receptors, and decreased aggrecan turnover. There was also increased activation (phosphorylation) of ERK, a critical signaling protein. Moreover, inhibition of ERK activity, in the presence TGF-beta3, resulted in suppression of collagen Type II, aggrecan, TGF-beta-RI, TGF-beta-RII and TGF-beta-RIII mRNA expression. CONCLUSIONS: TGF-beta3 maintains the phenotype of disc cells in organ culture. It exerts this effect, in part, by elevating the levels of activated ERK1/2, which in turn regulates the expression of TGF-beta-RI and TGF-beta-RII.

Activin Receptors, Type I↗
PubMed1995

Fetal pelvi-ureteric junction obstruction: predictors of outcome.

OBJECTIVE: To examine the relationship between pre-natal ultrasonographic findings typical of pelvi-ureteric junction (PUJ) obstruction and post-natal renal function in the affected kidney. PATIENTS AND METHODS: This retrospective study comprised 35 infants in whom pre-natal ultrasonography had identified a unilateral pattern of dilatation of the renal pelvis and calices typical of PUJ obstruction. In each case, the presence of unilateral hydronephrosis had been confirmed post-natally by ultrasonography, and differential function and drainage evaluated by isotope renography. The results of isotope renography were compared with the severity and timing of onset of the fetal hydronephrosis. RESULTS: Eleven kidneys (31%) appeared normal in the second trimester and dilatation only became apparent during the third trimester. Mean differential function in these kidneys was 48%. However, mean differential function was reduced (mean 38%) in those kidneys noted to be dilated between 16 and 24 weeks gestation. Differential function was loosely correlated with the severity of dilatation in early onset cases, i.e. the mean differential function was 42% for mild, 37% for moderate and 27% for severe dilatation. A considerable variation in differential function values was present in each group except for those with severe dilatation, which was a significant predictor of poor functional outcome when compared with mild and moderate dilatation combined (P < 0.01). CONCLUSION: Fetal PUJ obstruction is a heterogeneous condition permitting only broad predictions of functional outcome. Severe dilatation detected on second trimester imaging predicted significant loss of function. Mild and moderate degrees of dilatation were associated with a one in three risk of functional impairment in the obstructed kidney.

Dilatation, Pathologic↗
PubMed2005

Using a miniaturized circuit and an asanguineous prime to reduce neutrophil-mediated organ dysfunction following infant cardiopulmonary bypass.

BACKGROUND: Contemporary infant cardiopulmonary bypass circuits require a blood prime. Blood, especially when stored, generates an inflammatory response, and may contribute to organ dysfunction following cardiopulmonary bypass. We determined whether using a miniaturized circuit and an asanguineous prime attenuated the post-bypass inflammatory response, and improved right ventricular and pulmonary function. METHODS: Sixteen infant piglets were placed into 3 groups based on prime components: group I (fresh blood), group II (stored blood), and group III (miniaturized circuit and asanguineous prime). Piglets were placed on cardiopulmonary bypass (100 mL.kg(-1).min(-1)), cooled to 18 degrees C, and underwent continuous perfusion (50 mL.kg(-1).min(-1)) for 30 minutes. They were rewarmed and separated from bypass. Serum tumor necrosis factor-alpha, right ventricular function, and pulmonary function were measured before and 30 minutes after bypass. Neutrophil priming activity in fresh and stored donor blood was also assessed. RESULTS: Animals in group III had significantly improved cardiopulmonary function than the groups receiving blood (right ventricular cardiac index [mL.kg(-1).min(-1)]: group I [18.8 +/- 4.8], group II [21.5 +/- 6.2], and group III [81.2 +/- 11.4], p < 0.001; and pulmonary vascular resistance index [dynes.mL(-1).kg(-1)]: group I [1169 +/- 409], group II [1610 +/- 486], and group III [214 +/- 63], p = 0.03). Tumor necrosis factor-alpha (pg.mL(-1)) was lower in group III (1465 +/- 39) than in the groups receiving blood (3940 +/- 777), p = 0.002. Neutrophil priming activity (nmol.min(-1)) was also higher in stored blood (3.7 +/- 6) than in fresh blood (1.9 +/- 0.2), p = 0.02. CONCLUSIONS: We have devised a unique miniaturized circuit that allows an asanguineous prime without hemodilution in an infant swine model. The employment of this circuit attenuates the post-bypass inflammatory response and has salutary effects on cardiopulmonary function.

Animals↗
PubMed2005

Extracorporeal life support in neonates, infants, and children after repair of congenital heart disease: modern era results in a single institution.

BACKGROUND: Extracorporeal life support has assumed a very effective role in the support of patients with refractory heart failure after repair of congenital heart disease, with hospital survival between 37% and 42%. We reviewed our results of different applications of extracorporeal life support in the last 2 years. METHODS: Between January 2001 and October 2003, 671 patients underwent surgery for congenital heart disease at our institution. We retrospectively reviewed the hospital and clinic charts of the patients who required extracorporeal life support postoperatively, and studied the factors associated with survival. RESULTS: Thirty-six patients (5.36%) received extracorporeal life support after surgery, between 1 day and 8 years of age (age < 30 days, n = 34). We divided the patients into four groups. Group 1 consisted of 13 patients who were electively placed on ventricular support without an oxygenator (univentricular assist device) after repair of single-ventricle disease. Group 2 consisted of 16 patients who required extracorporeal membrane oxygenation after surgery for failed hemodynamics. Group 3 consisted of 2 patients who required left ventricle support (left ventricular assist device) after surgery for two-ventricle disease but who did not require biventricular (extracorporeal membrane oxygenation) support. Group 4 consisted of 5 patients who required conversion from ventricular assist device to extracorporeal membrane oxygenation. Overall, 28 patients were weaned successfully (78%), and 24 survived to discharge (67%). Hospital survival in groups 1, 2, 3, and 4 was 100%, 50%, 100%, and 20%, respectively. Univariate factors associated with survival were age, weight, ventricular assist device type, duration, single-ventricle disease, reexploration, number of complications, and specific complications such as sepsis, renal failure, and pulmonary failure. CONCLUSIONS: Extracorporeal life support utilization was expanded to include different applications with different outcomes. The extracorporeal life support registry should be altered to reflect those changes.

Assisted Circulation↗
PubMed2004

Coronary artery bypass with ventricular restoration is superior to coronary artery bypass alone in patients with ischemic cardiomyopathy.

BACKGROUND: Coronary artery bypass is an acceptable therapy in patients with ischemic cardiomyopathy. However, it has been demonstrated that patients with increased left ventricular volume have a worse outcome than patients with normal ventricular volume. Our hypothesis was that ventricular restoration plus coronary artery bypass provides improved outcome compared with coronary artery bypass alone in ischemic cardiomyopathy with ventricular enlargement. METHODS: A retrospective analysis was performed of patients with ischemic cardiomyopathy (ejection fraction <30%) who underwent operation between 1998 and 2002. Patients with enlarged ventricles (end-diastolic dimension > or =6.0 cm) who underwent either coronary artery bypass alone or coronary artery bypass with ventricular restoration were compared. Preoperative and postoperative ejection fraction, morbidity, mortality, and freedom from heart failure (hospitalization secondary to heart failure) were assessed. RESULTS: Ninety-five patients were included in the study. Thirty-nine patients had coronary artery bypass alone, whereas 56 patients had ventricular restoration with coronary artery bypass. Both groups demonstrated an improved postoperative ejection fraction; however, the improvement was significantly greater in the ventricular restoration plus coronary artery bypass group (P <.01). There were no hospital deaths in either group; however, late mortality was higher in the coronary artery bypass group. Freedom from heart failure was achieved in all but 2 of the ventricular restoration plus coronary artery bypass patients (2/56, or 3.6%) versus 7 in the coronary artery bypass group (7/39, or 18%). The combined outcomes of freedom from failure and late mortality were significantly improved in the ventricular restoration plus coronary artery bypass group (P <.05). CONCLUSIONS: Ventricular restoration affords significant improvement in ejection fraction compared with coronary artery bypass alone, without added mortality. Most importantly, left ventricular restoration reduces late morbidity and mortality compared with coronary artery bypass alone in patients with large ventricles.

Aged↗
PubMed2002

Steroid use among adolescents: findings from Project EAT.

PURPOSE: To explore the prevalence and correlates of using steroids for the purpose of gaining muscle among adolescent males and females. More specifically, the study objectives were to: (a) assess the prevalence of anabolic steroid use in a large population-based sample of adolescent males and females; and (b) identify personal, socio-environmental, and behavioral factors related to the health of adolescents that use anabolic steroids. METHODS: The study population included 4746 middle and high school students from St. Paul/Minneapolis public schools who completed surveys and anthropometric measurements as part of a population-based study of eating patterns and weight concerns among teenagers (Project EAT: Eating Among Teens). Steroid use and a range of socio-environmental, personal, and behavioral factors hypothesized to be correlates of steroid use were assessed. Associations were examined separately among males and females through comparisons of means (unadjusted and adjusted for grade-level and race) for continuous variables, and percentages, and odds ratios for dichotomized variables. RESULTS: Steroid use was more common in males (5.4%, vs. 2.9% of females), non-Caucasians (especially Hmong, a subset of the Asian-American population), and in middle school students (as compared to high school). In males, steroid use was associated with poorer self-esteem and higher rates of depressed mood and attempted suicide, poorer knowledge and attitudes about health, greater participation in sports that emphasize weight and shape, greater parental concern about weight, and higher rates of disordered eating and substance use. Among females, steroid use was less consistent in its associations with other variables, although overall, a similar pattern of results emerged. CONCLUSIONS: Anabolic steroid use in adolescence is associated with poorer health-related attitudes and behaviors and exposure to socio-environmental influences encouraging weight preoccupation. Attention needs to be directed toward youth who may be at increased risk for steroid use within clinical and community-based settings

Adolescent↗
PubMed2006

Reemergence of gram-negative health care-associated bloodstream infections.

BACKGROUND: Primary health care-associated bloodstream infections (PHA-BSIs) affect as many as 350 000 patients in the United States annually. Whereas gram-negative organisms were the leading cause before the 1970s, gram-positive organisms have been the predominant microbial isolates since then. METHODS: We identified all PHA-BSIs among adult inpatients in a 625-bed quaternary care hospital from January 1, 1996, through December 31, 2003, and evaluated trends in the microbial etiology, geographic distribution within the institution, and antimicrobial susceptibilities. RESULTS: A total of 3662 PHA-BSIs caused by 4349 bacterial and fungal isolates were identified. From 1999 to 2003, the proportion of PHA-BSIs due to gram-negative organisms increased from 15.9% to 24.1% (P<.001 for trend). This trend was not significantly different across various units of the hospital, and no specific gram-negative species contributed disproportionately to the increase. With few exceptions, there were no significant increases in antimicrobial resistance. The increase in gram-negative organisms was accompanied by a decline in the proportion of PHA-BSIs from coagulase-negative staphylococci (from 33.5% in 1999 to 29.9% in 2003, P = .007) and from Staphylococcus aureus (from 18.8% in 1999 to 11.8% in 2003, P = .004). The proportion of PHA-BSIs from Candida species almost doubled from 5.8% in 1999 to 11.3% in 2003 (P = .002). CONCLUSIONS: To our knowledge, this is the first US study to report a reemergence of gram-negative organisms as a cause of PHA-BSIs. This finding does not seem to be related to changes in specific gram-negative organisms or to antimicrobial resistance. If this trend continues, it will have important implications for the management of bloodstream infections.

Adult↗
PubMed2005

Expression of Ras GTPase isoforms in normal and diseased pancreas.

BACKGROUND: Ki-Ras is well studied in its oncogenic form in relation to pancreatic pathologies. However, the individual contribution of each of the wild-type Ras isoforms (Ha-, Ki-, and N-) in pancreatic cells in health and disease is unknown. METHODS: Archival formalin-fixed, paraffin-embedded specimens of normal (n = 6) and malignant pancreas (n = 35) were used for immuno-histochemical detection of Ras isoforms using a modified polymer system. In addition, immunogold labelling for Ras isoforms was done for subcellular localisation under electron microscopy. RESULTS: Pancreatic ductal cells expressed Ha-Ras in the cytoplasm, with Ki-Ras in the apical region and N-Ras (50% of cases) in a supranuclear distribution. Pancreatic acinar cells express all three isoforms with some nuclear expression of Ki-Ras and supranuclear expression of N-Ras. Islets show Ki- and Ha-Ras mainly with differential expression of Ha-Ras (beta cells showing less Ha-Ras and more Ki-Ras than alpha cells). Electron microscopy shows that Ha-Ras is mainly localised in the endoplasmic reticulum and Golgi apparatus of the acinar cells with some plasma membrane localisation of Ki-Ras in the ductal cells. There was no change in any of the Ras isoform expression in the ductal or acinar cells in various malignancies studied (Mann-Whitney U test, p > 0.1). CONCLUSIONS: Ras isoforms have distinct and separate cellular and subcellular distribution that may persist even in the malignantly transformed state. Understanding this distinct functional distribution patterns in detail is an essential step if mutant Ki-Ras is to be targeted in the pancreas by genetic or molecular therapeutic tools.

Genes, ras↗
PubMed2004

Impaired functional recovery after stroke in the stroke-prone spontaneously hypertensive rat.

BACKGROUND AND PURPOSE: To identify if the stroke-prone spontaneously hypertensive rat (SHRSP) exhibits impaired functional recovery after stroke compared with its normotensive reference strain, the Wistar Kyoto rat (WKY). METHODS: In study 1, a 2-mm distal middle cerebral artery occlusion (middle cerebral artery occlusion) was performed in both strains and recovery assessed using a 33-point neurological score. Because SHRSPs displayed much larger infarcts than WKYs, study 2 and study 3 involved extending the length of middle cerebral artery (MCA) occlusion in the WKY to increase the volume and distribution of infarction to comparable levels with SHRSP. Animals were assessed with the neurological score, tapered beam walk, and cylinder tests. RESULTS: In study 1, infarct volume (expressed as a percent of contralateral hemisphere) was WKY 13.1+/-3% and SHRSP 19.8+/-1%. Initial neurological deficit was greater (WKY 25+/-1, SHRSP 22+/-1, out of a possible 33) and subsequent recovery was poorer in SHRSP. In studies 2 and 3, infarct volume and distribution (study 2, WKY 21.8+/-1.3%, SHRSP 22.9+/-3%; study 3, WKY 17.2+/-2%, SHRSP 16.5+/-3%) and initial neurological deficit at 2 hours after middle cerebral artery occlusion (study 2 WKY 23+/-1, SHRSP 22+/-2; study 3 WKY 25+/-1 and SHRSP 23+/-1; mean+/-SEM) were comparable between strains. However, whereas WKY recovered toward normal scores, SHRSP scored significantly lower 2 weeks (study 2) and 4 weeks (study 3) after middle cerebral artery occlusion. Beam walk data revealed long-term impairment in SHRSP contralateral limb use, compared with WKY, at days 3, 7, and 28 (P<0.05). CONCLUSIONS: SHRSP exhibit impaired functional recovery after stroke compared with WKY.

Animals↗
PubMed2006

Hypothermic low-flow cardiopulmonary bypass impairs pulmonary and right ventricular function more than circulatory arrest.

BACKGROUND: Hypothermic circulatory arrest (HCA) is used during surgical treatment of certain congenital heart defects. The possibility of ischemic neurologic injury associated with HCA has led some surgeons to use low-flow cardiopulmonary bypass (CPB) during the hypothermic interval (hypothermic low flow [HLF]). This study investigates the inflammatory response to HCA and HLF, and reports the consequences of this response on pulmonary and right ventricular function. METHODS: Piglets (3.1 to 6.6 kg) were cooled to 16 degrees to 18 degrees C using CPB, and randomized: HCA for 60 minutes (n = 7), or HLF (50 cc.kg(-1).min(-1)) for 60 minutes (n = 6). The piglets were rewarmed to 36 degrees C and weaned from CPB. Serum tumor necrosis factor-alpha (TNF-alpha) concentration, percent lung water, and pulmonary and cardiac function were measured before and after CPB. RESULTS: Tumor necrosis factor-alpha was higher after HLF (2,990.5 +/- 884.5 pg/mL), compared with HCA (347.6 +/- 89.2 pg/mL; p = 0.03). The percent lung water was higher after HLF (84.8% +/- 0.3%) than HCA (82.0% +/- 0.4%; p < 0.001). The alveolar to arterial oxygen gradient was worse after HLF (457 +/- 42 mm Hg) than HCA (285.8 +/- 45 mm Hg; p = 0.02). Pulmonary vascular resistance was greater after HLF (36.08 +/- 8.28 mm Hg.mL(-1).m(-2).min(-1)) than HCA (14.55 +/- 3.46 mm Hg. mL(-1).m(-2).min(-1); p = 0.049). The right ventricular pressure waveform peak derivative, corrected for systolic pulmonary artery pressure, was lower after HLF (14.1 +/- 1.4 sec(-1)), than HCA (23.8 +/- 2.7 sec(-1); p = 0.01). CONCLUSIONS: Hypothermic low flow extends exposure to CPB, and is associated with an increased inflammatory response compared with HCA. The greater inflammatory response after HLF may result in substantial nonneurologic morbidity in the postoperative period, demonstrated by pulmonary and right ventricular dysfunction. Interventions that attenuate the inflammatory response to CPB may prevent pulmonary and right ventricular dysfunction after HLF.

Animals↗
PubMed1994

Surface modification of poly(lactide-co-glycolide) nanospheres by biodegradable poly(lactide)-poly(ethylene glycol) copolymers.

The modification of surface properties of biodegradable poly(lactide-co- glycolide) (PLGA) and model polystyrene nanospheres by poly(lactide)-poly(ethylene glycol) (PLA:PEG) copolymers has been assessed using a range of in vitro characterization methods followed by in vivo studies of the nanospheres biodistribution after intravenous injection into rats. Coating polymers with PLA:PEG ratio of 2:5 and 3:4 (PEG chains of 5000 and 2000 Da. respectively) were studied. The results reveal the formation of a PLA:PEG coating layer on the particle surface resulting in an increase in the surface hydrophilicity and decrease in the surface charge of the nanospheres. The effects of addition of electrolyte and changes in pH on stability of the nanosphere dispersions confirm that uncoated particles are electrostatically stabilized, while in the presence of the copolymers, steric repulsions are responsible for the stability. The PLA:PEG coating also prevented albumin adsorption onto the colloid surface. The evidence that this effect was observed for the PLA:PEG 3:4 coated nanospheres may indicate that a poly(ethylene glycol) chain of 2000 Da can provide an effective repulsive barrier to albumin adsorption. The in vivo results reveal that coating of PLGA nanospheres with PLA:PEG copolymers can alter the biodistribution in comparison to uncoated PLGA nanospheres. Coating of the model polystyrene nanospheres with PLA:PEG copolymers resulted in an initial high circulation level, but after 3 hours the organ deposition data showed values similar to uncoated polystyrene spheres. The difference in the biological behaviour of coated PLGA and polystyrene nanospheres may suggest a different stability of the adsorbed layers on these two systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Somatostatin and octreotide in the prevention of postoperative pancreatic complications and the treatment of enterocutaneous pancreatic fistulas: a systematic review of randomized controlled trials.

BACKGROUND: The aim of this study was to evaluate, through systematic review, the effectiveness of somatostatin and octreotide in the prevention of postoperative pancreatic complications and the treatment of established enterocutaneous pancreatic fistulas. METHODS: Electronic databases, including Medline and EMBASE, were searched systematically by using keywords including 'somatostatin', 'octreotide', 'fistula' and 'randomiz(s)ed controlled trial'. In addition, citations of relevant primary and review articles were examined. Particular authors were contacted when necessary. Data on patient recruitment, intervention and outcome were extracted from the included trials and analysed. RESULTS: Use of somatostatin or octreotide for the prevention of postpancreatectomy complications, including pancreatic fistulas, was identified in 14 randomized controlled trials, including one abstract and one conference proceeding, involving a total of 1686 patients. Use of somatostatin or octreotide for the treatment of established enterocutaneous pancreatic fistulas was identified in ten trials involving a total of 301 patients. Significant heterogeneity was found among the identified trials with regard to the definition of fistula, dosage of octreotide, starting time and duration of the treatment, among other factors. CONCLUSION: There was major disagreement between the studies on whether use of the drugs in question is of value in preventing postoperative complications. This analysis suggests that, in units where the postoperative fistula rate following pancreaticoduodenectomy for neoplasia and other pancreatic conditions exceeds 10 per cent, somatostatin or octreotide administered before operation may significantly reduce the rate of major postoperative complications, particularly pancreatic fistulas. The identified evidence also suggests that there may be a limited role for such drugs in the treatment of established postoperative enterocutaneous pancreatic fistulas. A major conclusion is that further clarification of the roles of these drugs is still required through large, high-quality, randomized trials.

Cutaneous Fistula↗