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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1067/mtc.2000.106526 Byline: Raymond H. Chen, Alexander Kadner, Richard N. Mitchell, David H. Adams Abstract: Objective: Transplanted porcine hearts are hyperacutely rejected by human immunoglobulin M antibodies against a porcine vascular endothelial molecule, galactose [alpha]-1,3-galactose, with ensuing human complement activation and membrane attack complex deposition. It is unclear, however, whether porcine valve endothelium triggers a similar immune response. We sought to investigate whether fresh porcine valves implanted into primates are rejected. Methods: Wild-type porcine hearts before (n = 6) and after (n = 3) heterotopic transplantation into baboons underwent sectioning and were examined by hematoxylin and eosin staining and immunohistochemistry for galactose [alpha]-1,3-galactose, primate immunoglobulin M, and membrane attack complex. Results: Examination of untransplanted porcine hearts showed that although cardiac microvascular endothelium strongly expressed the galactose [alpha]-1,3-galactose antigen, galactose [alpha]-1,3-galactose was not detected on the endothelium of porcine aortic and pulmonary valves. Porcine hearts transplanted into baboon recipients were hyperacutely rejected 60 to 80 minutes after implantation. Despite dramatic tissue damage associated with extensive immunoglobulin M and membrane attack complex binding on the microvascular endothelium, the aortic and pulmonary valves were entirely spared. Valves remained morphologically intact at explant and showed no signs of immunoglobulin M- and membrane attack complex-mediated damage. Conclusions: The absence of galactose [alpha]-1,3-galactose expression may protect unfixed porcine valves from xenograft rejection in primates. Further investigation of viable porcine valves appears warranted. (J Thorac Cardiovasc Surg 2000;119:1216-20) Author Affiliation: From the Departments of Surgery.sup.a and Pathology,.sup.b Brigham & Women's Hospital, Harvard Medical School, Boston, Mass Article History: Received 8 December 1999; Accepted 14 February 2000 Article Note: (footnote) [star] Dr Chen is an American College of Surgeons Research Scholar 1998-00 and recipient of National Institutes of Health Individual National Research Service Award (NRSA) 1F32HL0996601. This work is supported by a Nextran, Inc, sponsored research grant. Primate quarantine work was supported by the New England Primate Research Center grant P51RR00168-37., [star][star] Address for reprints: David H. Adams, MD, Division of Cardiac Surgery, Brigham & Women's Hospital, 15 Francis St, Boston, MA 02115 (E-mail: dadams@partners.org ).

The amount of lean tissue a pregnant woman has influences her baby's birth weight more than the amount of body fat. This was the conclusion of researchers who measured pre-pregnancy weight, body fat and lean tissue in 200 pregnant women. Body fat had no influence on infant birth weight, but weight and the amount of lean tissue did. Different body compositions may explain why two women of similar weight can produce similar weight babies even though one woman gained much more weight during pregnancy.

Byline: Richard N. Mitchell, Richard A. Jonas, Frederick J. Schoen Abstract: Objective: We sought to determine the morphology, mechanisms of deterioration, cellular viability, extracellular matrix integrity, and the role of immune responses in the dysfunction of cryopreserved aortic and pulmonic valve allografts. Methods: We studied 33 explanted left-sided (n = 20) or right-sided (n = 13) cryopreserved human allograft heart valves explanted several hours to 9 years after operation, 14 nonimplanted allografts, and 16 aortic valves removed from transplanted allograft hearts 2 days to 4 years after operation. Analysis included gross inspection, radiography, light microscopy, electron microscopy, and immunohistochemical studies. Results: Allografts implanted for more than 1 day had progressive collagen hyalinization and loss of normal structural complexity and cellularity, including endothelium and deep connective tissue cells. Inflammatory cells were generally minimal or absent in the allografts. Transmission electron microscopy of long-term cryopreserved allograft valves revealed no viable cells, focal calcification centered around dead cell remnants, and distorted but preserved collagen. In contrast, aortic valves from transplanted hearts showed remarkable structural preservation, including endothelium and abundant deep connective tissue cells; inflammatory infiltrates were generally mild and of no apparent deleterious consequence, including valves from patients who died of fatal rejection. Conclusions: Cryopreserved allografts are morphologically nonviable; their collagen is flattened but largely preserved. They are unlikely to grow, remodel, or exhibit active metabolic functions, and their usual degeneration cannot be attributed to immunologic responses. In contrast, aortic valves of transplanted hearts maintain near-normal overall architecture and cellularity and do not show apparent immunologic injury, even in the setting of fatal myocardial parenchymal rejection or graft arteriosclerosis. (J Thorac Cardiovasc Surg 1998;115:118-27) Article History: Received 6 March 1997; Revised 24 June 1997; Accepted 18 August 1997 Article Note: (footnote) [star] From the Department of Pathology,a Brigham and Women's Hospital, Department of Cardiovascular Surgery,b Children's Hospital, and the Departments of Pathologya and Surgery,b Harvard Medical School, Boston, Mass., [star][star] revisions requested May 13, 1997, a Address for reprints: Frederick J. Schoen, MD, PhD, Department of Pathology, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115., aa 12/1/85526

Public health agencies across the country uniformly retain three core functions, as identified in a 1988 Institute of Medicine report: assessment, assurance, and planning and policy development. The conduct of these functions will influence the ways the Public Health Service recommendations for postexposure prophylaxis are implemented locally. State, territorial, and local health departments play a key role in the monitoring and prevention of occupationally acquired human immunodeficiency virus (HIV) infections. Through assessment, public health agencies often are responsible for investigating healthcare workers who apparently have contracted HIV infection through an occupational exposure. In their function of providing assurance, public health agencies disseminate the national recommendations and may provide expert consultation taking into consideration local conditions. Specific healthcare worker exposure situations may pose complex medical and legal challenges best handled by public health agencies. In their role of providing policy development, public health agencies may convene an expert panel to review local data that affect postexposure prophylaxis, such as antiretroviral drug resistance and drug availability. The recommendations may result in legislative action in the form of mandatory testing of patients or other groups, and public health agencies must be wary of such attempts that are of unproven efficacy. Public health agencies nationwide must see that exposed healthcare workers and the clinicians counseling them are adequately informed about the risks of HIV transmission and the options available for prophylaxis. Am J Med. 1997;102(5B):98-101. [C] 1997 by Excerpta Medica, Inc.

The participation of the U.S. federal government in the progress of the computer software industry is examined covering the period 1955-1990. In particular, the study primarily takes into account government policies that have major impact in the industry. Government participation in computer software is nearly the same as in other existing industries. However, government purchasing and funding are influenced by military interests. And since computer science presents one area that is advantageous to defense operations, it resulted to the development of the software industry.

The finding of a restrictive pulmonary defect may divert clinicians from considering the diagnosis of chronic thromboembolic pulmonary hypertension because lung volumes are usually normal in this disorder. We have, [...]

Background: Inhaled nitric oxide (NO) has been shown to be a selective pulmonary vasodilator in certain patients with primary pulmonary hypertension (PPH). Objectives: The purpose of this study was to [...]

The influence of institutional structures on the technological development and economic growth of firms is analyzed. Results show that existing technological structures do not provide definite solutions to growth. The effectiveness of structures depend on the nature and scope of technological change in the industry as well as the impact of product life-cycle patterns. Governments should also allow firms to develop their own structures to suit their needs.

Byline: Ehud Rudis, Richard N. Gates, Hillel Laks, Davis C. Drinkwater, Abbas Ardehali, Alon Aharon, Paul Chang Abstract: This study documents the gross flow characteristics and capillary distribution of cardioplegic solution delivered retrogradely with the coronary sinus open versus closed. Methods : Five explanted human hearts from transplant recipients were used as experimental models. Hearts served as their own controls and received two doses of warm blood cardioplegic solution, each containing colored microspheres. The first dose was delivered through a retroperfusion catheter with the coronary sinus open and the second dose was delivered with the sinus occluded. Capillary flow was measured at twelve ventricular sites and gross flow was measured by examining coronary sinus regurgitation, thebesian vein drainage, and aortic effluent (nutrient flow). Results : Coronary sinus ostial occlusion allowed for a significant decrease in total cardioplegic flow (1.74 [+ or -] 0.40 ml/gm versus 1.06 [+ or -] 0.32 ml/gm; p < 0.05) to occur while maintaining an identical intracoronary sinus pressure. Ostial occlusion also resulted in an increase in the ratio of nutrient flow/total cardioplegic flow from 32.3% [+ or -] 15.1% to 61.3% [+ or -] 7.9% (p < 0.05). A statistically significant improvement in capillary flow was found at the midventricular level in the posterior intraventricular septum and posterolateral right ventricular free wall. This improvement was also documented for the intraventricular septum and right ventricle at the level of the apex. Conclusion : Coronary sinus occlusion during retrograde cardioplegia significantly improves cardioplegic delivery to the right ventricle and posterior intraventricular septum. Furthermore, the technique affords a significant improvement in nutrient cardioplegic flow while reducing the overall volume of cardioplegic solution administered. (J T HORAC C ARDIOVASC S URG 1995; 109: 941-7) Author Affiliation: Los Angeles, Calif. Article Note: (footnote) [star] From the Division of Cardiothoracic Surgery, Department of Surgery, University of California at Los Angeles Medical Center, Los Angeles, Calif., [star][star] Read at the Twentieth Annual Meeting of The Western Thoracic Surgical Association, Olympic Valley, Calif., June 22-25, 1994., a From the Division of Cardiothoracic Surgery, Department of Surgery, University of California at Los Angeles Medical Center, Los Angeles, Calif., aa Read at the Twentieth Annual Meeting of The Western Thoracic Surgical Association, Olympic Valley, Calif., June 22-25, 1994., acents Read at the Twentieth Annual Meeting of The Western Thoracic Surgical Association, Olympic Valley, Calif., June 22-25, 1994., acentsacents 0022-5223/95 $3.00 + 0, a[bar] 12/6/62472

Intestinal ischemia is associated with changes of the basic electric rhythm (BER) of the small intestine. We hypothesized that these changes can be measured noninvasively using a superconducting quantum interference device (SQUID). After general anesthesia, a laparotomy was performed on 10 animals and the jejunum was placed in a nonmagnetic recording chamber containing Krebs' solution at 38 [degrees]C. Five animals had electrodes placed while five others were Placed under the SQUID. Injection of thrombin into the mesenteric artery decreased blood flow (measured with a laser doppler flow-meter) 95% within 5 minutes. SQUID measurements showed significant decreases (P

Nitric oxide (NO) is a potent dilator of vascular smooth muscle that likely represents an important endothelium-dependent relaxing factor. Recent interest has focused on inhaled NO as a pulmonary vasodilator [...]

Oral dehydroepiandrosterone (DHEA) appears to enhance immune system functioning in postmenopausal women. DHEA is a steroid hormone. DHEA levels decrease with age. Eleven postmenopausal women were randomly assigned to receive either 50 milligrams of DHEA daily for three weeks or a similar-looking placebo. After an additional two weeks of taking no pills, the women then switched treatments. Blood levels of DHEA, DHEA sulfate, testosterone and cortisol were measured before and 24 hours after the last treatment. Testosterone and cortisol are steroid hormones. Blood levels of DHEA, DHEA sulfate and testosterone increased twofold when women received oral DHEA. Natural killer cell toxicity was increased by treatment with DHEA. Natural killer cells are components of the immune system that are thought to play a role in controlling viral infections and malignant transformations. Cortisol levels appeared to be higher in women taking the placebo, but urinary cortisol levels remained normal.

The purpose of this study was to evaluate retrospectively the incidence and severity of heparin-induced thrombocytopenia (HIT)-related complications in patients undergoing cardiopulmonary bypass. We reviewed the records of 1,500 consecutive [...]

Patients with idiopathic dilated cardiomyopathy (IDC) constitute a minority among implantable cardioverter-defibrillator (ICD) recipients; how these patients fare versus those with coronary artery disease (CAD) is not well defined, nor is the mechanism of cardiac arrest recurrence, which may involve a more significant role of bradyarrhythmias. A retrospective multicenter study regarding outcome of ICD therapy was conducted in 224 patients with either IDC (n = 69; 31%) or CAD (n = 155; 69%) presenting exclusively with ventricular fibrillation (VF) unassociated with acute myocardial infarction. Patients with IDC were significantly younger (mean age 57 vs 61 years in patients with CAD, p

The modular system of production offers both demand and supply side benefits. The potential for autonomous innovation, driven by the division of labor which provides the opportunity for rapid trial and error learning, is the supply-side advantage gained from modular systems. Demand-side benefits center on the ability to finetune the product to consumer needs and therefore covers the product space more completely. Innovation in a modular system also leads to vertical and horizontal integration, as firms can best appropriate the rents of innovation by opening their technology to an outside network of competing and cooperating companies.

OBJECTIVE: The null hypothesis of this study is that in an urban, indigent obstetric population at high risk for adverse perinatal outcome, unexplained elevations of maternal serum [Alpha] -fetoprotein are not an additional predictor of adverse perinatal outcome. STUDY DESIGN: Perinatal outcomes of 72 patients from a clinic for indigent patients with unexplained elevated maternal serum [Alpha]-fetoprotein levels were compared with those of matched controls from the same population with normal maternal serum [Alpha]-fetoprotein levels. Subjects and controls were matched for age, race, parity, and presence or absence of Hollister risk factors. The frequency of adverse perinatal outcome in the two groups was subjected to matched-pair [X.sup.2] analysis. RESULTS: Adverse perinatal outcome occurred in 38.9% (28 of 72) of subjects with unexplained elevated maternal serum [Alpha]-fetoprotein levels [is greater than or equal to] 2.5 multiples of the median, compared with 31.9% (23 of 72) of controls with normal maternal serum [Alpha]-fetoprotein levels (p = 0.5). No statistically significant difference in adverse perinatal outcomes was found. CONCLUSIONS: Elevated maternal serum [Alpha]-fetoprotein levels offer little if any additional predictive value for adverse perinatal outcome in populations already at high risk for such outcomes on the basis of obstetric or socioeconomic criteria. (Am J Obstet Gynecol 1992;166:978-82.)

Arrhythmias are irregular heartbeats that may be serious, leading to sudden death in some cases. Implantable cardioverter defibrillators (ICD) have been used during the last 10 years to treat this problem. These devices are implanted in the chests of patients who are at high risk for sudden death. When life-threatening arrhythmias occur, the ICD administers an electrical shock to the heart, converting the abnormal rhythm to a normal rhythm. Early studies reported that the risk for sudden death was greatly decreased in patients who received ICDs. However, these studies were not well controlled; clinical trials of the ICD did not include randomized, controlled testing. Over the past few years, a number of people have questioned whether these devices are effective in preventing sudden death in patients with arrhythmias. In an editorial in the March 1989 issue of PACE, Dr. Seymour Furman offered three arguments challenging the research that found the ICD to be beneficial. His first argument was that many patients who received the device did not need it, thus the survival rates were inflated. Although with the data Dr. Furman had available, this assumption could be generated, further actuarial data have shown that the patients were appropriately chosen. His second argument was that the studies should have separated patients into two groups: those who actually needed shocks from the ICD and those who did not. This implies that patients with less severe heart disease do not benefit from the ICD and that those with severe heart disease, although they may be rescued by the device, are only protected from sudden death. Their survival is not increased. When these two groups are separated, the data clearly show that both groups benefit from the ICD. His third argument was that survival rates should be evaluated from the time the first shock is given. Although such an analysis is unreasonable and has not been conducted for other types of therapies, when it is performed, the ICD shows a 72 percent survival rate 4 years after the first shock. The challenges to the benefit of the ICD have been answered, but they point to the importance of conducting randomized controlled trials when evaluating any therapy. (Consumer Summary produced by Reliance Medical Information, Inc.)

Gestational diabetes is diabetes that occurs during pregnancy. Diabetes can be diagnosed by measuring the amount of glucose (sugar) present in the blood after a meal and by measuring the amount of sugar in the blood after drinking a solution containing large amounts of glucose, the glucose tolerance test (GTT). Those with diabetes will have high levels of sugar in their blood following a meal and following GTT. To determine if the results of glucose testing for diabetes are related to the outcome of the pregnancy, 608 pregnant women were studied. Eighty-eight of the women had abnormally high glucose levels detected by glucose screening. When GTTs were performed, 35 of the women had higher than normal levels of blood glucose (an abnormal GTT), and 48 had normal GTT. The mean infant birth weight and the incidence of infant morbidity and maternal morbidity were the same for those with normal GTTs and those who had abnormal GTTs. There was no relationship between the results of the GTTs and the incidence of birth trauma, cesarean delivery, or fetal macrosomia (oversized body). These findings indicate that the results of glucose testing had little relationship to the outcome of these pregnancies. (Consumer Summary produced by Reliance Medical Information, Inc.)

Testing for elevated maternal levels of alpha-fetoprotein (AFP), a plasma protein produced by the fetus, to determine risk of neural tube (structural beginning of central nervous system) defects of the fetus is a common practice. However, elevated levels are often associated with other situations such as twins, wrong gestational age, or fetal death, rather than with neural tube defects. In many cases, AFP levels are elevated with no known cause. Some reports suggest that in these cases, there may an increase in pregnancy complications such as preeclampsia or poor outcomes such as low-birth-weight infants. However, the research supporting this association is limited, and bias in the way studies have been conducted may be responsible for these findings. To determine if elevated AFP levels during or following the second trimester are related to poorer outcomes, 279 women from an area with a high frequency of obstetric complications were studied. AFP levels rose until 32 weeks of gestation and then progressed at a slower rate. Third trimester levels were more variable, but still useful. Of 279 women, 270 with normal second trimester AFP values had similar third trimester values. Of six women with elevated second trimester values who had singleton pregnancies, none had elevated third trimester values, even though two had poor outcomes. In another group of 24 women who had elevated AFP in the third trimester, two had fetal deaths and others experienced complications. The study suggests that AFP levels in the second and third trimester are not related, but that elevated levels in the third trimester may be somewhat predictive of complications. The study does not recommend rigorous screening of women with unexplained second trimester AFP levels. Addition research with properly designed studies with larger sample sizes are needed before the significance of elevated AFP levels is fully understood. (Consumer Summary produced by Reliance Medical Information, Inc.)

PURPOSE: The metabolic disturbances seen during infection are thought to be due to cytokines, modulators of the immune response. The acquired immunodeficiency syndrome (AIDS) is characterized by a high prevalence of hypertrigelyceridemia and at times depletion of body cell mass (wasting). Elevated circulating levels of cytokines have also been reported in AIDS. Therefore, we determined the relationship between circulating cytokine levels and lipid levels and between circulating cytokine levels and wasting in AIDS and human immunodeficiency virus (HIV) infection. PATIENTS AND METHODS: Serum samples from 45 patients with AIDS, 13 subjects with evidence of HIV infection by presence of antibody but without AIDS (HIV positive), and 17 seronegative cOntrOl subjects who had Previously undergone body composition analysis were analyzed for triglyceride, cholesterol interferon, tumor necrosis factor (TNF), and interleukin-1 levels. Eleven subjects with AIDS or HIV infection had sequential measurements. Interferon was analyzed by bioassay with identification using specific antibodies. TNF and interleukin-1 were assayed by enzyme-linked unmunosorbent assay. Lean body mass was assessed by total body potassium. RESULTS.- Serum interferon-a levels were significantly elevated in patients with AIDS (p [is not greater than]0.001 compared to controls), with detectable levels in 84% of AIDS patients. interferon-[Alpha] was not detectable in serum from controls, while three of 13 EGIV-positive subjects had detectable interferon-[Alpha] levels. There was a significant correlation between interferon-[Alpha] levels and serum triglyceride levels in AIDS and HIV-positive patients (R = 0.446, p [is not greater than]0.002). There was no relationship between interferon-[Alpha] and serum cholesterol levels (R = -0.039, NS). In contrast only 11 % of AIDS patients had detectable circulating TNF levels; the mean value for and the prevalence of detectable serum TNF levels were not significantly different from those of control subjects. Interleukin-1 was not detected in the circulation. There was no correlation between the presence of circulating TNF and serum triglycerides. There was no relationship between circulating interferon-[Alpha] or TNF levels and the presence of wasting as measured by total body potassium. CONCLUSION: These studies suggest that interferon-[Alpha], which has previously been shown to modulate lipid metabolism in vivo and in vitro, may be responsible for the hypertriglyceride found in AIDS., Infections are often complicated by disturbances in metabolism, possibly resulting from the actions of cytokines, which are modulators, or regulators, of the immune system. AIDS is often associated with hypertriglyceridemia, or abnormally high levels of triglycerides, and wasting of tissue. Increased blood levels of cytokines have been detected in AIDS patients. The relation of blood levels of cytokines to lipid levels and wasting was assessed in 45 patients with AIDS, 13 patients infected with human immunodeficiency virus (HIV), and 17 subjects without HIV disease. The levels of triglyceride, cholesterol, and the cytokines interferon, tumor necrosis factor (TNF), and interleukin-1 were measured. Interferon-alpha was detected in 84 percent of AIDS patients and three HIV-infected patients, but in no patients without HIV disease. In addition, interferon-alpha levels were correlated with blood levels of triglycerides in patients with HIV disease, but not with blood cholesterol levels. TNF levels were detectable in only 11 percent of AIDS patients and were similar in prevalence to those of subjects without HIV disease. Interleukin-1 was not detected. TNF levels were not correlated with blood triglyceride levels. Tissue wasting did not appear to be related to levels of interferon-alpha or TNF. These findings suggest that increased levels of interferon-alpha, which regulates lipid (fat) metabolism, may contribute to the development of hypertriglyceridemia associated with AIDS. (Consumer Summary produced by Reliance Medical Information, Inc.)