Minimally Invasive Versus Conventional Aortic Valve Replacement: A Propensity-Matched Study From the UK National Data.

OBJECTIVE: Minimally invasive aortic valve replacement (MIAVR) has been demonstrated as a safe and effective option but remains underused. We aimed to evaluate outcomes of isolated MIAVR compared with conventional aortic valve replacement (CAVR). METHODS: Data from The National Institute for Cardiovascular Outcomes Research (NICOR) were analyzed at seven volunteer centers (2006-2012). Primary outcomes were in-hospital mortality and midterm survival. Secondary outcomes were postoperative length of stay as well as cumulative bypass and cross-clamp times. Propensity modeling with matched cohort analysis was used. RESULTS: Of 307 consecutive MIAVR patients, 151 (49%) were performed during the last 2 years of study with a continued increase in numbers. The 307 MIAVR patients were matched on a 1:1 ratio. In the matched CAVR group, there was no statistically significant difference in in-hospital mortality [MIAVR, 4/307,(1.3%); 95% confidence interval (CI), 0.4%-3.4% vs CAVR, 6/307 (2.0%); 95% CI, 0.8%-4.3%; P = 0.752]. One-year survival rates in the MIAVR and CAVR groups were 94.4% and 94.6%, respectively. There was no statistically significant difference in midterm survival (P = 0.677; hazard ratio, 0.90; 95% CI, 0.56-1.46). Median postoperative length of stay was lower in the MIAVR patients by 1 day (P = 0.009). The mean cumulative bypass time (94.8 vs 91.3 minutes; P = 0.333) and cross-clamp time (74.6 vs 68.4 minutes; P = 0.006) were longer in the MIAVR group; however, this was significant only in the cross-clamp time comparison. CONCLUSIONS: Minimally invasive aortic valve replacement is a safe alternative to CAVR with respect to operative and 1-year mortality and is associated with a shorter postoperative stay. Further studies are required in high-risk (logistic EuroSCORE > 10) patients to define the role of MIAVR.

The role of adrenal medullary catecholamine release in the response to a cold pressor test.

We studied the effects of a cold pressor test on the plasma catecholamine levels of ten patients undergoing coronary angiography, to determine whether the pressor changes were related to adrenergic activity. To investigate the relative contribution of adrenal medullary catecholamine release, we subjected two adrenalectomised volunteers to the same test. Arterial blood was assayed for dopamine (DA), adrenaline (A) and noradrenaline (NA). We found significant rises in the levels of all three catecholamines in the angiography patients, accompanied by a significant elevation in arterial blood pressure. In both the adrenalectomised patients a rise in blood pressure was seen but no significant rise in plasma catecholamines could be demonstrated. We postulate that although adrenal medullary catecholamine release occurs in response to the cold pressor test, the blood pressure elevation is independent of such adrenal activity. Sampling radial arterial blood may not reflect changes in plasma levels of peripherally released NA.

Cardioprotection by Cu,Zn-superoxide dismutase is lost at high doses in the reoxygenated heart.

Limited dose-response curves for superoxide dismutase (SOD) were assessed in isolated and in vivo hearts. SOD at 2.3, 7, 20, or 50 mg/L suppressed CK release in Langendorff rat hearts by 61%, 63%, 72%, and 30%, respectively. SOD at 0.5, 1, 5, and 50 mg/L suppressed LDH release in Langendorff rabbit hearts by 32%, 48%, 54%, and -12%, respectively. In rabbit hearts subjected to coronary artery ligation and reperfusion in vivo, SOD at 2, 5, or 15 mg/kg reduced infarct size by 10%, 30% or 19%, respectively, while 50 mg/kg increased infarct size by 28%. In conclusion, while SOD was protective at low doses in all models, protection was lost at higher doses in the isolated rat and rabbit hearts, and exacerbation of damage was seen in the in vivo rabbit hearts.

Transforming growth factor beta within fibrotic scleroderma lungs.

PURPOSE, PATIENTS, AND METHODS: Since transforming growth factor beta (TGF beta) has been implicated as an important mediator of pulmonary fibrosis, we measured TGF beta protein and gene expression in alveolar epithelial lining fluid (ELF) of fibrotic scleroderma lungs sampled by bronchoalveolar lavage (BAL). TGF beta protein was qualitatively examined by Western blot analysis, and quantitatively by radioreceptor assays. Gene expression was evaluated in BAL mononuclear cells by Northern blot analysis with quantification of relative gene expression by densitometric analysis of the autoradiograms. RESULTS: Normal and scleroderma subjects had a 24-kd protein that comigrated with defined human TGF beta 1 and immunoreacted with anti-TGF beta antibody. The normal population had a significantly higher average TGF beta concentration (705 pM) compared with the scleroderma subjects (177 pM). The TGF beta 1 gene was expressed in amounts that did not significantly differ between the scleroderma and normal groups. On an individual subject basis, the TGF beta concentration variability did not correlate with variations in BAL cellularity or TGF beta 1 gene expression within the recovered mononuclear cells. CONCLUSIONS: It is concluded that both normal and fibrotic lungs have TGF beta 1 present at the alveolar epithelial surface. However, in the fibrotic scleroderma lungs, TGF beta protein content and gene expression were not increased at the alveolar epithelial surface. The simultaneous analysis of TGF beta protein content, gene expression, and cellular constituents within individual ELF specimens showed that the cellular components of the ELF do not appear to be major determinants of TGF beta protein concentration at the alveolar epithelial surface.

The incidence of thoracic vertebral fractures in a Japanese population, Hiroshima and Nagasaki, 1958-86.

The incidence of thoracic vertebral fractures (TVF) in a Japanese population of 14,607 individuals from Hiroshima and Nagasaki was determined by sex, age, birth cohort, and exposure to atomic bomb radiation. The diagnosis of TVF was based on lateral chest radiographs made from 1 July 1958 to 28 February 1986. The subjects, who were born between 1880 through 1939, were categorized by sex into 10-year birth cohorts. TVF incidence increased by a factor of 1.7 in all birth cohorts with each 10-year increase in age in females, but did not increase with age in males. The incidence was significantly lower in the younger birth cohorts in both sexes. The incidence declined by a factor of 0.5 in males and 0.6 in females for each 10-year decrease in the year of birth. TVF incidence did not differ between the cities, and no correlation with atomic bomb radiation exposure was demonstrated.

Radiation therapy among atomic bomb survivors, Hiroshima and Nagasaki.

As a follow-up to the two previous surveys of radiation therapy among the atomic bomb survivors, a large-scale survey was performed to document (1) the number of radiation therapy treatments received by the atomic bomb survivors and (2) the types of radiation treatments conducted in Hiroshima and Nagasaki. The previous two surveys covered the radiation treatments among the Radiation Effects Research Foundation Adult Health Study (AHS) population, which is composed of 20,000 persons. In the present survey, the population was expanded to include the Life Span Study (LSS), including 93,611 atomic bomb survivors and 26,517 Hiroshima and Nagasaki citizens who were not in the cities at the times of the bombings. The LSS population includes the AHS population. The survey was conducted from 1981 to 1984. The survey teams reviewed all the medical records for radiation treatments of 24,266 patients at 11 large hospitals in Hiroshima and Nagasaki. Among them, the medical records for radiation treatments of 1556 LSS members were reviewed in detail. By analyzing the data obtained in the present and previous surveys, the number of patients receiving radiation therapy was estimated to be 4501 (3.7%) in the LSS population and 1026 (5.1%) in the AHS population between 1945-1980. During 1945-1965, 98% of radiation treatments used medium-voltage X rays, and 66% of the treatments were for benign diseases. During 1966-1980, 94% of the radiation treatments were for malignant neoplasms. During this period, 60Co gamma-ray exposure apparatus and high-energy electron accelerators were the prevalent mode of treatment in Hiroshima and in Nagasaki, respectively. The mean frequency of radiation therapy among the LSS population was estimated to have been 158 courses/year during 1945-1965 and 110 courses/year during 1966-1980. The present survey revealed that 377 AHS members received radiation therapy. The number was approximately twice the total number of cases found in the previous two surveys. Thus the data on radiation therapy in the AHS members have been updated well by this survey, and will provide information for more precise dose-response analyses of radiation effects in the AHS population. The information extracted from the medical records of the hospitals consisted of hospital names, treatment periods, body sites treated, diagnoses, treatment doses, radiation sources, the field sizes of the exposures and the data for identification of the patients. These data will be essential in estimating the organ doses from scattered radiation and in evaluating the effects of therapeutic radiation.

In vitro modulation of AL-amyloid formation by human mesangial cells exposed to amyloidogenic light chains.

We have shown in vitro AL-amyloid formation by human mesangial cells (HMCs). AL-amyloid formation may require lysosomal processing of the light chains (LCs) by HMCs for amyloidogenesis to occur. Chloroquine inhibits lysosomal activity. TGF-beta mediates extracellular matrix formation in many glomerulopathies. Thrombospondin (TSP) has been proposed as a mediator of cell proliferation and a marker of early fibrosis. We investigated amyloid formation by HMCs exposed to AL-LCs in the absence of amyloid enhancing factor (AEF). The effects of TGF-beta, TSP and chloroquine on in vitro amyloid formation were studied. HMCs were incubated with two AL-LCs, a light chain deposition disease (LCDD)-LC, or one of two tubulopathic LCs (T-LCs). Additional cells were treated with an AL-LC and chloroquine, TGF-beta, or TSP. Amyloid formation was evaluated microscopically using hematoxylin and eosin, Congo red and Thioflavin-T stains, as well as ultrastructurally. Amyloid was formed only when HMCs were incubated with AL-LCs. Addition of TSP significantly enhanced amyloid formation. In contrast, exogenous TGF-beta and chloroquine significantly attenuated amyloid formation. These findings show that some AL-LCs do not require AEF for amyloidogenesis to occur, and that chloroquine, TGF-beta and sTSP modulate in vitro AL-amyloidosis.

Human papovavirus in Papanicolaou smears of urinary sediment detected by transmission electron microscopy.

A technique is described whereby inclusion-bearing cells identified by light microscopy in stained smears of urinary sediment were reprocessed for examination in the electron microscope. The nuclei of the abnormal cells were found to contain numerous virus particles, 35 nm in diameter, which morphologically resembled papovaviruses. The technique was applied in this case to identify further the virus producing the cytopathic changes in the Papanicolaou smear. It could be particularly valuable for retrospective studies of mounted cytological or histological material when suitable specimens are no longer available for virological investigation.

Human polyomavirus (BK) infection and ureteric stenosis in renal allograft recipients.

Human polyomavirus (BK) was detected in two renal allograft recipients as a result of routine examination of Papanicolaou-stained smears of urinary sediment in the light microscope. Infection with this recently identified virus was confirmed by virus isolation and electron microscopy. The cytological, histological, and ultrastructural changes due to the virus are described, and virus excretion is correlated with the clinical progress of the patients and the pathological findings. The transplant ureters in both patients were found to be ulcerated and stenosed, and virus-infected cells were observed in the ureteric epithelium. We suggest that the administration of high-dose steroids in transplantation may permit active infection with human polyomavirus to occur in ureteric epithelium which has been damaged by ischaemia or inflammation.

Endogenous and exogenous catalase in reoxygenation lung injury.

Reexpansion pulmonary edema parallels reperfusion (reoxygenation) injuries in other organs in that hypoxic and hypoperfused lung tissue develops increased vascular permeability and neutrophil infiltration after reexpansion. This study investigated endogenous lung catalase activity and H2O2 production during hypoxia (produced by lung collapse) and after reoxygenation (resulting from reexpansion), in addition to assessing the effects of exogenous catalase infusion on the development of unilateral pulmonary edema after reexpansion. Lung collapse resulted in a progressive increase in endogenous catalase activity after 3 (14%) and 7 days (23%), while activities in contralateral left lungs did not change (normal left lungs averaged 180 +/- 11 units/mg DNA). Tissue from control left lungs released H2O2 into the extracellular medium at a rate calculated to be 242 +/- 34 nmol.h-1.lung-1. No significant change in extracellular release of H2O2 occurred after 7 days of right lung collapse. However, after reexpansion of the previously collapsed right lungs for 2 h, H2O2 release from both reexpanded right and contralateral left lungs significantly increased (88 and 60%, respectively) compared with controls. Infusion of exogenous catalase significantly increased plasma and lung catalase activities. Exogenous catalase infusion prevented neither the increase in lung permeability nor the infiltration with neutrophils that typically occurs in reexpanded lungs. These data indicate that lung hypoxia/reoxygenation, induced by sequential collapse and reexpansion, has specific effects on endogenous lung catalase activity and H2O2 release. However, exogenous catalase does not prevent reexpansion pulmonary edema, eliminating extracellular (but not intracellular) H2O2 as an important mediator of unilateral lung injury in this model.

Destruction of ristocetin cofactor by coagulation at 4 degrees C.

Ristocetin cofactor (VIIIR:RCo) and factor VIII-related antigen (VIIIR:Ag) were measured in anticoagulated and non-anticoagulated blood incubated at 4 degrees C, room temperature (RT) or 37 degrees C for 24 hours. A marked decrease in VIIIR:RCo, to almost undetectable levels, and a smaller decrease in VIIIR:Ag occurred when whole blood clotted at 4 degrees C. These changes were slight or absent when blood clotted at RT or 37 degrees C. VIIIR:RCo lost at 4 degrees C was not recoverable by further incubation at 37 degrees C but the less-marked loss of VIIIR:Ag was partially recovered. In blood which had clotted at 4 degrees C there was a change in the electrophoretic profile of VIIIR:Ag on crossed immunoelectrophoresis: there was more anodal migration of the VIIIR:Ag peak, consistent with a decrease in the mean molecular size. Further experiments showed that the decrease in VIIIR:RCo during coagulation at 4 degrees C preceded the decrease in fibrinogen levels. In cell-free plasma VIIIR:RCo also decreased markedly when coagulation occurred at 4 degrees C. The results show that loss of VIIIR:RCo occurs when blood is allowed to clot at 4 degrees C: this is not due to cryoprecipitation and does not require the presence of blood cells. The data suggest that it is probably caused by plasma proteases activated early in the coagulation pathway.

Calibration of Mg2SiO4(Tb) thermoluminescent dosimeters for use in determining diagnostic x-ray doses to adult health study participants.

Characteristics of Mg2SiO4(Tb) thermoluminescent dosimeters (TLD) were ascertained preparatory to measuring doses from diagnostic x-ray examinations received by Adult Health Study participants. These detectors are small, relatively sensitive to low-dose x-rays, and are appropriate for precise dosimetry. Extensive calibration is necessary for precisely determining doses according to their thermoluminescent intensities. Their sensitivities were investigated by dose, according to x-ray tube voltage, and by exposure direction, to obtain directional dependence. Dosimeter sensitivity lessened due to the fading effect and diminution of the planchet. However, these adverse effects can be avoided by storing the dosimeters at least 1.5 h and by using fresh silver-plated planchets. Thus the TLDs, for which sensitivities were determined in this study, will be useful in subsequent diagnostic x-ray dosimetry.

Soft X-ray dosimetry and RBE for survival of Chinese hamster V79 cells.

Dosimetry and biological effects of 40 and 50 keV low-energy X-rays generated by a SOFTEX Model CMBW-2 apparatus were studied. Doses were measured using a thin-window parallel-plate ionization chamber; beam quality was assessed using aluminum absorbers; exposure rates per unit current were determined according to the X-ray tube current and exposure times; and thermoluminescent (BeO chip) dosimeters were used to ascertain dose distributions in the irradiation field. The average correction factors for nonuniformity were calculated from the measured dose distributions. The means for ascertaining accurate exposures and doses using these methods are discussed. The dose-survival relationship of Chinese hamster V79 cells were assessed by irradiating them with 40 and 50 kV soft X-rays, 180 kV X-rays, and 60 Co gamma rays. Soft X-rays with three distinct effective energies were tested by changing the tube voltage kV and aluminium filter thicknesses; namely (1) 40 kV without filter, (2) 40 kV with a 0.2 mm thick aluminium filter and (3) 50 kV with a 0.7 mm thick aluminium filter. The effective energies obtained according to attenuation measurements using aluminium for these soft X-rays were 8.1, 11.7 and 18.5 kV, respectively. In this study the relative biological effectiveness (RBE) at 10 per cent survival compared with 60Co gamma rays ranged from 1.5 to 1.6. The RBE of 180 kV X-rays relative to 60Co gamma rays was 1.29. This study provided experimental data for the RBE of V79 cells in the intermediate energy range between hard and ultrasoft X-rays, data for which were previously reported by Goodhead and co-workers (1977, 1979, 1981).

Organ doses received by atomic bomb survivors during radiological examinations at the Radiation Effects Research Foundation.

When evaluating the risks of oncogenesis and cancer mortality following exposure to the radiations of the atomic bombs (A-bombs), the medical X-ray doses received by the A-bomb survivors must also be estimated and considered. Using a human phantom, dosimetry was performed to estimate the X-ray doses received by A-bomb survivors during medical examinations at the Radiation Effects Research Foundation (RERF) as part of the long-term follow-up on the Adult Health Study (AHS). These examinations have been estimated to represent nearly 45% of the survivors' cumulative medical irradiation dose. Doses to the salivary glands, thyroid gland, lung, breast, stomach and colon were measured using thermoluminescent dosimeters. The results, which are reported here, will aid in estimating organ doses received by individual AHS participants.

Organ doses to atomic bomb survivors during photofluorography, fluoroscopy and computed tomography.

Doses to the salivary glands, thyroid gland, breast, lung, stomach and colon during mass radiological gastric screening, mass radiographic chest screening, upper gastrointestinal series and computed tomography were determined by exposing a female human phantom to simulated radiological X-ray examinations as performed in community hospitals. The doses were measured using thermoluminescent dosimeters, and the results will be used to document organ doses received by participants in the Atomic Bomb Casualty Commission/Radiation Effects Research Foundation Adult Health Study.

Hydrogen peroxide release by mitochondria from normal and hypoxic lungs.

Ischemia/reperfusion mechanisms contribute to lung injury after transplantation, pulmonary embolism, and resolution of atelectasis. Alveolar tissue becomes hypoxic and deprived of substrate only when both ventilation and perfusion are interrupted, a situation modeled in vivo by complete, unilateral lung collapse. Because previously hypoxic mitochondria may be an important intracellular source of superoxide and hydrogen peroxide (H2O2) during reperfusion and re-oxygenation, the authors, in this study, investigated whether mitochondrial H2O2 release changed as a result of lung hypoxia/hypoperfusion resulting from collapse. Mitochondria were isolated from hypoxic (previously collapsed) right or contralateral left rabbits' lungs and from control rabbits' lungs. Mitochondrial H2O2 release, a marker of superoxide production, was measured fluorometrically after incubation with or without 1 mmol/L cyanide and 0.1 mmol/L nicotinamide adenine dinucleotide. Mitochondrial recovery was determined by assaying succinate dehydrogenase activity in mitochondrial preparations and lung homogenates. Lung succinate dehydrogenase activity and mitochondrial recovery were comparable among groups. Calculated lung mitochondrial content did not change (control subjects: left 7.9 +/- 0.5, right 13.8 +/- 1.7; hypoxic: left 10.3 +/- 1.3, right 10.5 +/- 2.4, all mg mitochondrial protein/lung). Mitochondria released hydrogen peroxide at approximately 5.6 nmol/h/mg pro in buffer alone and 14.8 nmol/h/mg pro in buffer with cyanide and nicotinamide adenine dinucleotide. However, lung collapse and resulting hypoxia caused no change in mitochondrial number or capacity to release H2O2 in vitro. Based on these findings, it is suggested that other sources of reactive oxygen metabolites, including xanthine oxidase and activated neutrophils, contribute to the oxidant injury observed in this model.

The determination of absorption coefficients for measurement of carboxy-hemoglobin, oxy-hemoglobin, reduced hemoglobin, and met-hemoglobin in sheep using the IL482 CO-Oximeter.

The IL482 CO-Oximeter uses four wavelengths of visible light to analyze blood samples for the relative percentages of oxy-, carboxy-, reduced, and met-hemoglobin. In the analysis, the absorption at each of the wavelengths is multiplied by a matrix of four coefficients to derive the quantities of the four hemoglobin types. The normal settings of the CO-Oximeter coefficients are those for adult human hemoglobin. However, animal blood can be measured provided that the appropriate matrix of coefficients is available. Instrumentation Laboratory has provided sets of coefficients for several animal species. The company has also published a protocol for determining coefficients for other animal species. This protocol was examined using sheep hemoglobin-A blood and found to be inaccurate. The IL482 protocol is unsatisfactory because, if the initial error is large, successive iterations to determine the coefficient matrix through revision of the estimates of residual hemoglobin types do not converge. With sheep type-A hemoglobin, the use of human coefficients for the initial estimate gave a value of 6%, whereas, by chromatography, the carboxyhemoglobin (COHb) was 0.12% (i.e., a better initial estimate would be zero). When this was done, the final COHb estimate on "as-drawn" blood was within 1% of the COHb measured independently by gas chromatography. Revision of the protocol gave a markedly better accuracy, within 2% for COHb over the whole range when tested against mixtures of CO and O2 tonometered blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic and immunologic consequences of laparoscopy with helium or carbon dioxide insufflation: a randomized clinical study.

BACKGROUND: Previous studies using animal models have demonstrated that carbon dioxide (CO2) pneumoperitoneum during laparoscopy is associated with adverse physiological, metabolic, immunological and oncological effects, and many of these problems can be avoided by the use of helium insufflation. The present study was performed in patients to compare the effect of helium and CO2 insufflation on intraperitoneal markers of immunological and metabolic function. METHODS: Eighteen patients undergoing elective upper gastrointestinal laparoscopic surgery were randomized to have insufflation achieved by using either helium (n = 8) or CO2 (n = 10) gas. Intraperitoneal pH was monitored continuously during surgery, and peritoneal macrophage function was determined by harvesting peritoneal macrophages at 5 min and 30 min after commencing laparoscopy, and then assessing their ability to produce tumour necrosis factor-alpha (TNF-alpha), and their phagocytic function. RESULTS: Carbon dioxide laparoscopy was associated with a lower intraperitoneal pH at the commencement of laparoscopy, although this difference disappeared as surgery progressed. The production of TNF-alpha was better preserved by CO2 laparoscopy, but the insufflation gas used did not affect macrophage phagocytosis. Patients undergoing helium laparoscopy required less postoperative analgesia. CONCLUSION: The choice of insufflation gas can affect intraperitoneal macrophage function in the clinical setting, and possibly acid-base balance. The present study suggested no immunological advantages for the clinical use of helium as an insufflation gas. The outcomes of the present study, however, are different to those obtained from previous laboratory studies and further research is needed to confirm this outcome.

Aging factors and cardiovascular dimensions: a longitudinal study.

The effects of selected aging factors including body weight, blood pressure, and radiation dose on the cardiac and aortic arch transverse diameters, based on posteroanterior and lateral radiographs obtained 17 to 22 years apart were evaluated for 200 normal subjects. Increases in body weight and blood pressure caused increases in transverse cardiac diameter of 26% and 2%, respectively, but no appreciable effect on aortic arch transverse diameter. Radiation dose caused no significant effects. Effects of increases in body weight and blood pressure on cardiac and aortic arch transverse diameters with age ought not be overestimated in healthy adults.