Blood pressure reference intervals for healthy adult chimpanzees (Pan troglodytes).

BACKGROUND: Cardiovascular disease is the primary cause of morbidity and mortality among captive chimpanzees. But there are no clinical definitions of normotension or hypertension in chimpanzees. METHODS: We analyzed 1 year of blood pressure (BP) data from a population of 261 healthy captive adult chimpanzees using a consistent set of criteria to ascertain health. RESULTS: Systolic BP varied by body weight. Diastolic BP varied by age. Median normotension was 126/63 mmHg, with an upper limit of 147/84 mmHg. We defined categories of pre-hypertension (148/85-153/88 mmHg) and hypertension (≥154/89 mmHg). The prevalence of elevated BP was 15%. The relative risk of mortality was 2.60, compared to normotensive animals. CONCLUSIONS: We used contemporary methods from human laboratory medicine to define reliable reference intervals for chimpanzee BP. Results allow accurate diagnosis of hypertension and pre-hypertension, and demonstrate an effect of elevated BP on mortality.

Anesthesia using microcannula and sharp needle in upper blepharoplasty: A randomized, double-blind clinical trial evaluating pain, bruising, and ecchymoses.

INTRODUCTION: With the emergence of blunt-tipped microcannulas, there is a hypothesis that these could cause less damage and reduce pain as compared to conventional sharp needles in eyelid surgery. The purpose is to determine whether an 18G blunt-tipped cannula can be better than a 26G needle. METHODS: This prospective, observer-blinded, randomized clinical trial was conducted from June 2017 to December 2018. Sixty-eight patients were randomized to receive local anesthesia injections for upper blepharoplasty. Infiltration was performed by using a 26-gauge sharp needle on one side and on the other side, infiltration was performed by using an 18-gauge stainless-steel blunt-tipped microcannula. A numeric rating scale (NRS) from 0 to 10 was used to blindly assess pain in patients receiving anesthesia injections with both needle types. Photographs of the eyelids of each patient were taken in five different periods and used by three blinded observers to identify bruise or ecchymoses. RESULTS: A total of 136 eyelid operations were performed. There was no statistically significant difference when both groups were compared; however, the average score of pain was higher in patients taking the infiltration through the needle (2.85 versus 2.50). Regarding the evaluation of bruising and ecchymoses, the results showed that, in the five periods evaluated, there was no statistical difference in bruising and ecchymosis in the eyelids when taking the infiltration through a sharp needle when compared with that of the eyelids taking infiltration through a (blunt-tipped) microcannula. CONCLUSION: The evaluation of the blunt-tipped microcannula showed a lower pain score mean than that obtained for the sharp needle (2.5 versus 2.85) (p > 0.05). There was no statistically significant difference in the bruising and ecchymosis courses.

Pulmonary tissue engineering using dual-compartment polymer scaffolds with integrated vascular tree.

OBJECTIVES: The persistent shortage of donor organs for lung transplantation illustrates the need for new strategies in organ replacement therapy. Pulmonary tissue engineering aims at developing viable hybrid tissue for patients with chronic respiratory failure. METHODS: Dual-chamber polymer constructs that mimic the characteristics of the pulmonary air-blood interface were fabricated by microfabrication techniques using the biocompatible polymer polydimethylsiloxane. One compartment ("vascular chamber") was designed as a capillary network to mimic the pulmonary microvasculature. The other compartment ("parenchymal chamber") was designed to permit gas exchange. Immortalized mouse lung epithelium cells (MLE-12) were cultured on the surface of polystyrene microcarrier beads. These beads were subsequently injected into the parenchymal chamber of the dual-chamber microsystems. The vascular compartment was perfused with cell culture medium in a bioreactor and the construct was maintained in culture for 1 week. RESULTS: The microcarriers evenly distributed MLE-12 cells on the parenchymal compartment surface. Confluent cell layers were confirmed by fluorescent and electron microscopy. Adequate proliferation of MLE-12 cells within the construct was monitored via the DNA content. Viability of the cells was maintained over 1 week. Finally, cellular specificity and functional capacity in situ were demonstrated by immunostaining for proSP-B and proSP-C (alveolar epithelium), and by using MLE-12 cells transfected to overexpress green fluorescent protein. CONCLUSION: We conclude that functional hybrid microsystems mimicking the basic building plan of alveolar tissue can be engineered in vitro.

Impact of complications on outcomes following aortic and mitral valve replacements in the United States.

AIM: Heart valve replacement surgeries account for 20% of all cardiac procedures. In-hospital mortality rates are approximately 6% for aortic valve replacements and 10% for mitral valve replacements. The objectives of the study are to provide nationally representative estimates of complications following aortic and mitral valve replacements and to quantify the impact of different types of complications on in-hospital outcomes. METHODS: The Nationwide Inpatient Sample was analyzed for years 2000-2003. The effect of complications on in-hospital mortality, length of stay (LOS), and hospital charges were examined using bivariate and multivariable logistic and linear regression analyses. The confounding effects of age, sex, primary diagnosis, type of valve replacement, type of admission, comorbid conditions, and hospital characteristics were adjusted. RESULTS: A total of 43,909 patients underwent aortic valve replacement as the primary procedure during the study period and 16,516 patients underwent mitral valve replacement. Complications occurred in 35.2% of those undergoing aortic valve replacements and in 36.4% of those undergoing mitral valve replacements. Almost half of these are cardiac complications and a quarter involve hemorrhage/hematoma/seroma. Complications were significantly associated with in-hospital mortality, LOS, and hospital charges even after adjusting for patient and hospital characteristics. CONCLUSION: Complications are prevalent and exert a considerable influence on outcomes following aortic and mitral valve replacements. Quality initiatives should focus on minimizing complications and improving processes of care that would enable complications to be better resolved if they occur.

T-cell lineage of a Friend virus-induced lymphatic leukemia in athymic rats.

Athymic (rnu/rnu) and euthymic rats inoculated with the Friend virus-associated lymphatic leukemia virus developed lymphocytic leukemia. Neoplastic cells from these animals were evaluated by means of indirect immunofluorescence and flow cytofluorometry with monoclonal antibodies Ox-1, Ox-7, and W3/25, which react with surface antigens present on normal rat lymphoid cell populations. Lymphoid cells from leukemic animals revealed characteristic alterations in cell surface fluorescence profiles when compared to normal, healthy controls. Athymic and euthymic leukemic rats were similar in that many cells from both the spleen and bone marrow had markers on the cell surface normally found on thymocytes but not on mature peripheral lymphocytes. These studies provided evidence supporting the presence of T-lineage lymphocytes in the athymic rat. Further, this population of early or "pre"-T-lymphocytes included the predominant leukemia cell type induced by the Friend virus-associated lymphatic leukemia virus.

Modulation of agonist-induced inositol phosphate metabolism by cyclic adenosine 3',5'-monophosphate in adrenal glomerulosa cells.

Activation of the cAMP messenger system was found to cause specific changes in angiotensin-II (All)-induced inositol phosphate production and metabolism in bovine adrenal glomerulosa cells. Pretreatment of [3H]inositol-labeled glomerulosa cells with 8-bromo-cAMP (8Br-cAMP) caused both short and long term changes in the inositol phosphate response to stimulation by All. Exposure to 8Br-cAMP initially caused dose-dependent enhancement (ED50 = 0.7 microM) of the stimulatory action of All (50 nM; 10 min) on the formation of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and its immediate metabolites. This effect of 8Br-cAMP was also observed in permeabilized [3H]inositol-labeled glomerulosa cells in which degradation of Ins(1,4,5)P3 was inhibited, consistent with increased activity of phospholipase-C. Continued exposure to 8Br-cAMP for 5-16 h caused selective enhancement of the All-induced increases in D-myo-inositol 1,3,4,6-tetrakisphosphate [Ins(1,3,4,6)P4] and myo-inositol 1,4,5,6-tetrakisphosphate. The long term effect of 8Br-cAMP on the 6-phosphorylated InsP4 isomers, but not the initial enhancement of Ins(1,4,5)P3 formation, was inhibited by cycloheximide. The characteristic biphasic kinetics of All-induced Ins(1,4,5)P3 formation were also changed by prolonged treatment with 8Br-cAMP to a monophasic response in which Ins(1,4,5)P3 increased rapidly and remained elevated during All stimulation. In permeabilized glomerulosa cells treated with 8Br-cAMP for 16 h, the conversion of D-myo-inositol 1,3,4-trisphosphate [Ins(1,3,4)P3] to Ins(1,3,4,6)P4 was consistently increased, whereas dephosphorylation of Ins(1,4,5)P3 to D-myo-inositol 1,4-bisphosphate and of D-myo-inositol 1,3,4,5-tetrakisphosphate to Ins(1,3,4)P3, was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Neutron detection via bubble chambers.

Research investigating the application of pressure-cycled bubble chambers to fast neutron detection is described. Experiments with a Halon-filled chamber showed clear sensitivity to an AmBe neutron source and insensitivity to a (137)Cs gamma source. Bubble formation was documented using high-speed photography, and a ceramic piezo-electric transducer element registered the acoustic signature of bubble formation. In a second set of experiments, the bubble nucleation response of a Freon-134a chamber to an AmBe neutron source was documented with high-speed photography.

Partial purification and characterization of a colony-stimulating factor secreted by a T lymphocyte clone.

The mouse T lymphocyte clone L2 secretes a minimum of 10 lymphokine activities affecting at least 5 different target cells. Large amounts of colony-stimulating factor (CSF) (8.6 X 10(6) U/ml) can be obtained by stimulating L2 cells with concanavalin A. The major CSF activity secreted by L2 cells has been enriched to a specific activity of approximately 2-4 X 10(8) colonies/mg of protein using hydrophobic-interaction, gel-permeation, ion-exchange, and lectin-affinity chromatography. This preparation of CSF contains no detectable interleukin 2, interleukin 3, or interferon. The major L2-cell CSF induces granulocyte/macrophage colonies from bone marrow cells. This GM CSF has an apparent Mr of 22,000 as determined by gel-permeation chromatography. Treatment of L2-cell CSF with proteolytic enzymes abrogates biologic activity.

Regulation of 1,2-diacylglycerol production by angiotensin-II in bovine adrenal glomerulosa cells.

In bovine adrenal glomerulosa cells, angiotensin-II (AII) induced a biphasic increase in 1,2-sn-diacylglycerol (DAG), with an initial peak at 10 sec followed by a transient decrease at 30 sec. The second increase was much higher in magnitude than the first peak and reached its maximum after 1 h of stimulation. Such kinetics of DAG formation resemble those with which AII stimulates the formation of inositol-1,4,5-trisphosphate. The protein synthesis inhibitor cycloheximide, which prevents hormone-induced de novo phospholipid synthesis in adrenal fasciculata cells, had no effect on the DAG response to Aii. The first phase of signal generation of both inositol-1,4,5-trisphosphate and DAG was not affected by incubation in calcium-deficient extracellular medium. However, the second phase of the inositol phosphate response was almost completely inhibited in low calcium medium, while the DAG response was reduced by only one third. Pertussis toxin (150 ng/ml) and the voltage-sensitive calcium channel inhibitors, nifedipine (1 microM) and Ni2+ (100 microM), had no effect on the DAG response to AII. The retention of a substantial DAG response to AII in low calcium medium, with concomitant diminution of the inositol phosphate response, indicates that a major part of the DAG formed during the sustained phase of hormonal stimulation is derived from sources other than phosphoinositides. The DAGs produced from different phospholipids could have distinctive fatty acid compositions and membrane localizations, which, in turn, could result in the differential activation of protein kinase-C. In this way, the increased complexity of the hormonally induced signalling pathway could allow for a greater diversity of responses in hormone-stimulated target cells.

Ribozymes in gene therapy of HIV-1.

Human immunodeficiency virus type 1 (HIV-1) is the primary etiologic agent for Aquired Immune Deficiency Syndrome (AIDS). HIV-1 is a lentivirus, a separate genus of the Retroviridae, which are complex RNA viruses that integrate into the genome of host cells and replicate intracellularly. Ribozymes are catalytic RNA molecules with enzyme-like cleavage properties, that can be designed to target specific RNA sequences within the HIV-1 genome. In addition to the genomic RNA, several RNA intermediates, including splice variants, can be targeted by a single ribozyme. We and others have demonstrated the ability of ribozymes to suppress HIV-1 replication in a variety of cultured cells. Ribozyme gene therapy for HIV-1 infection is a therapeutic approach that offers several potential advantages over conventional therapies in that it can potentially impact on both viral load and restoration of the immune system. Ribozyme gene therapy may be used as an adjunct to chemotherapeutic drugs, effecting viral suppression, and facilitating immune restoration without problems of patient compliance. Currently, an anti-HIV-1 ribozyme is being tested in two separate Phase I Clinical Trials.

An introduction to time-trend analysis.

Healthcare professionals often are presented with data that appear to indicate an upward or downward trend over time. For example, admissions of acquired immunodeficiency syndrome (AIDS) patients appear to be increasing, cesarean section rates appear to be decreasing, or nosocomial pneumonia rates appear to be increasing. Critical decisions sometimes are based on such trends, which often are presented without a statistical analysis. Those responsible for decision making may be left wondering whether these apparent trends represent only chance variation. Graphs showing trends over time generally present one of three kinds of outcome data: counts (eg, three AIDS admissions), proportions (eg, 10 cesarean sections per 100 total deliveries), or person-time data (eg, 13 cases of nosocomial pneumonia per 10,000 patient days). Using familiar examples and a minimum of technical language, we illustrate the analysis of time trends.

The physician's decision to use tube feedings: the role of the family, the living will, and the Cruzan decision.

OBJECTIVE: To determine the relative importance of factors influencing physicians to use tube feedings in patients lacking decision-making capacity. DESIGN: Survey. SETTING AND PARTICIPANTS: Four hundred thirty-nine members of the Missouri Academy of Family Physicians. MEASUREMENTS: Using a mailed questionnaire, physicians were asked for a decision about feeding tube placement in an 89-year-old man who was unable to swallow or communicate after a stroke. Changing the conditions of the scenario, we then evaluated the influence of patient age, duration of disability, a living will, the Cruzan decision, and family preferences on the physician's decision. RESULTS: After reading the initial case history, 47% of physicians opposed tube feedings. Physicians who were told that the patient signed a living will specifically excluding tube feedings were more likely to oppose tube feedings than those who were told that he signed only a standard living will (53% vs 42%; P = 0.02). Forty-two percent of physicians who initially suggested a feeding tube changed their recommendation if the family opposed it. Sixty-six percent of physicians who initially opposed a feeding tube changed their recommendation if the family "pushed" for it. Thirty-three percent of physicians who initially opposed tube feedings under the living will scenario would favor tube feedings if the patient had not signed a living will. Twenty-two percent of physicians who initially opposed tube feedings would change to favor them if the issue had arisen before the Cruzan decision. CONCLUSIONS: Among this group of physicians, there was no consensus on whether tube feedings should be initiated. However, it was found that the family's opinion was the most influential factor affecting the physician's recommendation about tube feedings. Most physicians endorsed family preferences for tube feedings even when this intervention was specifically opposed in the patient's living will.

Community characteristics associated with elder abuse.

OBJECTIVES: To help define the relationship between elder abuse rates and counties' demographics, healthcare resources, and social service characteristics. DESIGN: County-level data from Iowa were analyzed to test the association between county characteristics and rates of elder abuse between 1984 and 1993 using univariate correlation analysis and stagewise linear regression. SETTING: Ninety-nine counties in Iowa. PARTICIPANTS: Iowa residents aged 65 years and older. MEASUREMENTS: County-level population-adjusted numbers of abused elderly, abused children, children in poverty, high school dropouts, physicians and other healthcare providers, hospital beds, social workers and caseworkers in the Department of Human Services (DHS). RESULTS: Community characteristics that had a positive association with rates of reported or substantiated elder abuse at the P < .001 level were population density, children in poverty, and reported child abuse. Lower substantiated elder abuse rates were associated at P < .05 with higher community rates of high school dropouts, number of chiropractors, and number of nurse practitioners. After adjusting for number of DHS caseworkers and reported child abuse rates (a surrogate for workload) a district effect persists for substantiated elder abuse cases (P = .002). CONCLUSION: County demographics are risk factors for reported and substantiated elder abuse. The strongest risk factor for reported elder abuse was reported child abuse. The difference in districts may reflect differences in resources and/or differing characteristics of caseworkers who substantiate elder abuse. The risk factors may reflect conditions that influence the amount of elder abuse or the detection of existing elder abuse.

The association between manual removal of the placenta and postpartum endometritis following vaginal delivery.

OBJECTIVE: To determine whether manual removal of the placenta after vaginal delivery is a risk factor for postpartum endometritis. METHODS: A retrospective cohort study of vaginal deliveries compared 1052 patients who had manual removal of the placenta with 1085 patients whose placentas delivered spontaneously. Subjects were selected randomly from the 25,687 vaginal deliveries at the University of Iowa Hospitals during 1979-1992. The presence of endometritis was determined using information in medical records. The data were analyzed using odds ratios (OR) and multiple logistic regression. RESULTS: After controlling for confounding variables, manual removal of the placenta was associated with postpartum endometritis (adjusted OR 2.9, 95% confidence interval [CI] 1.7-4.9). Other risk factors for endometritis included maternal age less than 17 years (OR 3.3, 95% CI 1.5-7.2), postpartum anemia (OR 2.9, 95% CI 1.9-4.5), and membranes ruptured longer than 24 hours (OR 2.5, 95% CI 1.4-4.3). CONCLUSION: Manual removal of the placenta is a risk factor for postpartum endometritis after vaginal delivery.

Anti-HIV ribozymes.

HIV is an RNA virus that replicates intracellularly through various RNA intermediates. Several of these can be targeted by ribozymes (catalytic RNA molecules), and a number of investigators, including this group, have demonstrated the ability of ribozymes to suppress HIV replication in this way. It is argued that this gene therapy approach may be viewed as an adjunct to chemotherapeutic drugs, which may allow not just viral suppression, but also immune restoration. This can only finally be tested in clinical trials, and several are planned. The basic ribozyme unit, the potential of which was described less than 10 years ago, is about to be tested in an amunable disease state.

Hyperglycemia and reproductive defects in non-diabetic gravidas: a mouse model test of a new theory.

The frequent association of various reproductive anomalies with maternal diabetes is explained by a theory that predicts such defects will occur even in transient moderate hyperglycemia in non-diabetic gravidae. A first test of this hypothesis produced strongly supportive results in a mouse model. Thirteen C57BL/6J dams on a grain (control) diet produced (in the 4th week after first mating) 64 pups, 62 surviving to maturity. In the same time interval on a high sucrose diet, fourteen isogenic dams produced only 5 pups, none surviving 5 days (p much less than .001). Additional ongoing studies of the underlying glucose-ascorbate antagonism and of early vs. perinatal hyperglycemia are described briefly.

Clinical diagnosis and the order of information.

BACKGROUND: Information order can influence judgment. However, it remains unclear whether the order of clinical data affects physicians' interpretations of these data when they are engaged in familiar diagnostic tasks. METHODS: Of 400 randomly selected family physicians who were given a questionnaire involving a brief written scenario about a young woman with acute dysuria, 315 (79%) returned usable responses. The physicians had been randomized into two groups, and both groups had received the same clinical information but in different orders. After learning the patient's chief complaint, physicians received either the patient's history and physical examination results followed by the laboratory data (the H&P-first group) or the laboratory data followed by the history and physical examination results (the H&P-last group). The results of the history and physical examination were supportive of the diagnosis of UTI, while the laboratory data were not. All physicians judged the probability of a urinary tract infection (UTI) after each piece of information. RESULTS: The two groups had similar mean estimates of the probability of a UTI after learning the chief complaint (67.4% vs 67.8%, p = 0.85). At the end of the scenario, the H&P-first group judged UTI to be less likely than did the H&P-last group (50.9% vs 59.1%, p = 0.03) despite having identical information. Comparison of the mean likelihood ratios attributed to the clinical information showed that the H&P-first group gave less weight to the history and physical than did the H&P-last group (p = 0.04). CONCLUSIONS: The order in which clinical information was presented influenced physicians' estimates of the probability of disease. The clinical history and physical examination were given more weight by physicians who received this information last.

A comparison of the classical and modified forms of the continuity equation in the On-X prosthetic heart valve in the aortic position.

BACKGROUND AND AIM OF THE STUDY: The use of echocardiography to determine prosthetic valve hemodynamics has become generally accepted; however, there are still many differing methodologies in use. The continuity equation, which uses the ratio of the subaortic and transaortic velocity-time integrals for determining aortic effective orifice area (EOA), has been established as an accurate method. Another method using the more easily measured peak velocities in ratio has also been employed. These methods were compared to determine if the simpler method gave equivalent results. METHODS: Early postoperative echocardiographic data on prosthetic valves from the MCRI Multicenter Trial were used to compare the two methods of calculating EOA (A2). Results using the two methods were compared by paired t-tests, the Wilcoxon signed rank test, regression and Bland-Altman analysis. RESULTS: Despite a good correlation between the two methods (r = 0.91), results were different when compared by a paired t-test. On average, results by the modified method were 0.2 cm2 lower, but in 28% of cases they were in fact higher than the classical method. CONCLUSION: The modified continuity equation based on the peak velocity ratio does not give the same result as the classical formula based on the velocity-time ratio. The modified method cannot reliably be substituted for the classical method in normally functioning On-X valves.

Early postoperative echocardiographic hemodynamic performance of the On-X prosthetic heart valve: a multicenter study.

BACKGROUND AND AIMS OF THE STUDY: This study aimed to investigate the early postoperative Doppler-derived hemodynamic results from the first patients receiving the On-XR prosthetic heart valve, a new bileaflet, pyrolytic carbon valve. METHODS: Data were derived from 111 patients included in a 10-center international trial between September 1996 and December 1997. RESULTS: The effective orifice area (EOA) for the valve, when implanted in the aortic position, ranged from 1.5 to 2.7 cm2 in 19 mm to 25 mm valves. The corresponding mean pressure gradients ranged from 11.8 to 7.6 mmHg. Mitral EOA was 2.3 cm2 for all sizes, these values being combined because the housing was identical for all mitral valves used in this study. The mitral mean gradient was 4.7 mmHg. CONCLUSIONS: Early results of the study show the good hemodynamic performance of the On-X valve when implanted in the aortic or mitral positions.