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Biomedical subjects

R L Johnson

Publications and source records attributed to R L Johnson.

At least 127 records · Page 7Linked to original sources

Effect of extracorporeal membrane oxygenation flow on pulmonary capillary blood flow.

OBJECTIVE: To validate a new application of the modified acetylene rebreathing method for pulmonary capillary blood flow in a swine extracorporeal membrane oxygenation (ECMO) model. DESIGN: Prospective, sequential measurements of pulmonary capillary blood flow, using a rebreathing technique, as affected by different flows through the ECMO circuit. SETTING: A cardiovascular hemodynamic research laboratory at a university medical center. SUBJECTS: Fifteen young mature farm swine (48 to 52 kg). INTERVENTIONS: Pulmonary capillary blood flow was measured using a modified rebreathing technique, and this measurement repeated at different flow rates through the extracorporeal membrane oxygenation circuit. Pulmonary artery flow rates were measured using both thermodilution and echo-Doppler techniques for comparison purposes. MEASUREMENTS AND MAIN RESULTS: Pulmonary capillary blood flow measurements, as assessed by modified acetylene rebreathing, compared well with both the thermodilution cardiac output measurement during normal circulation and the pulmonary artery flow probe measurement while the subjects received ECMO. Mean pulmonary capillary blood flow measured by acetylene rebreathing decreased from 89.72 +/- 6.97 (baseline) to 43.59 +/- 5.66 mL/kg/min as ECMO flow was maximized to 56.22 +/- 3.62 mL/kg/min. Decreasing the ECMO flow rate by half (to 28.23 +/- 3.45 mL/kg/min) caused an increase in mean pulmonary capillary blood flow to 53.79 +/- 6.16 mL/kg/min. When ECMO flow was discontinued, pulmonary capillary blood flow returned to a near baseline value of 71.68 +/- 7.05 mL/kg/min (mean values of pooled data for both closed- and open-chest animals [n = 15]). These measurements correlated well with both thermodilution cardiac output and pulmonary artery ultrasonic flow probe measurements. CONCLUSIONS: The modified acetylene rebreathing method is a valid and accurate method for the measurement of pulmonary capillary blood flow in the presence of ECMO flows. Pulmonary blood flow decreases as ECMO flow is increased, and the extent of decrease is directly proportional to the amount of flow through the extracorporeal circulation.

Animals↗

Hospital governance in a competitive environment.

The modern hospital has evolved through three phases since 1900. Between 1900 and 1950, hospitals were in a charitable era and from 1950 to 1990, they were in a technological era developing a comprehensive range of clinical services. From 1990 to well into the 21st century, hospitals will be in an economic era where decision making will shift from the boardroom to the administrative suite. Clinical and management viewpoints will be blended in order to successfully compete in the new environment.

Capitation Fee↗

Pregnancy-induced alterations of neurogenic constriction and dilation of human uterine artery.

The responses to electrical field stimulation (EFS) of perivascular nerves in human uterine arteries were characterized. The arteries were removed from pregnant and nonpregnant patients undergoing hysterectomy. Tetrodotoxin, guanethidine, and phentolamine blocked EFS (2 min, 80 V, 0.1-ms duration)-induced constriction. The constrictions and the endogenous norepinephrine levels were lower (P < 0.01) in uterine arteries from pregnant than from nonpregnant patients. When arterial rings were precontracted, the response to EFS was biphasic, consisting of an initial constriction followed by a postconstriction relaxation. The EFS-induced relaxation was endothelium independent and was greater (P < 0.01) in uterine arteries from pregnant than from nonpregnant patients. The relaxation was enhanced by guanethidine and superoxide dismutase, inhibited by nitric oxide synthase inhibitors, blocked by tetrodotoxin, and unaffected by atropine, propranolol, or indomethacin. The results demonstrate that human uterine arteries respond to EFS with contraction and relaxation and that these responses may be mediated, respectively, by norepinephrine and, in part, by nitric oxide released from periarterial nerves. The decrease in neuronally mediated uterine arterial constriction and the increase in dilation could be physiological mechanisms for ensuring appropriate uteroplacental perfusion.

Adult↗

Cardiac output during exercise measured by acetylene rebreathing, thermodilution, and Fick techniques.

In dogs during exercise, respiratory rate can reach 200 breaths/min, blood temperature can exceed 42 degrees C, and hematocrit can approach 60%. To determine whether these changes significantly affect the measurement of cardiac output by the acetylene rebreathing method (QcRB), we compared estimates of QcRB with those measured by thermodilution and Fick (QcFI) techniques in nine dogs at rest and during steady-state exercise on a treadmill up to near-maximal workloads. Solubility of acetylene in blood was corrected to the simultaneously measured blood temperature and hematocrit. Results were also adjusted for mixing efficiency. Up to a QcFI of 20 l/min, QcRB was not significantly different from QcFI (P > 0.05). However, cardiac output measured by thermodilution was consistently higher than those measured by the other techniques (P < 0.0001). We conclude that the overall agreement between QcRB and QcFI estimates supports the validity of the rebreathing technique under exercise conditions where body temperature and hematocrit are changing rapidly and the breathing pattern is unrestrained. Systematic error by the thermodilution technique may be related to a variety of methodological issues as well as possible dissipation of cooling into the myocardial tissue and subsequent incomplete washout.

Acetylene↗

Critique of conceptual basis of diffusing capacity estimates: a finite element analysis.

We present a simple geometric model of a pulmonary capillary segment containing a variable number of red blood cells. The pattern of CO transfer from alveolar air to capillary red blood cells in this model is accurately computed by a finite element method and used to explore conceptual flaws in the Roughton-Forster (RF) and morphometric methods of estimating pulmonary diffusing capacity for CO. The CO uptakes calculated by the finite element method at two alveolar O2 tensions are introduced into the RF model to determine whether the anatomically defined membrane component of diffusing capacity for CO (DmCO) and pulmonary capillary blood volume (Vc) are recovered. The same capillary model is also subjected to standard morphometric analysis. Results are compared at different levels of capillary hematocrit (Hct). The RF method accurately recovers DmCO and Vc at a low Hct but modestly overestimates DmCO and underestimates Vc at higher Hct; errors arise because conductance of the tissue-plasma membrane for CO varies with alveolar O2 tension. The morphometric method seriously overestimates DmCO because the true tissue-plasma resistance to diffusion is underestimated and the effective membrane utilized for diffusion is overestimated; these errors are accentuated by a low Hct.

Animals↗

Sonic hedgehog is an endodermal signal inducing Bmp-4 and Hox genes during induction and regionalization of the chick hindgut.

Reciprocal inductive signals between the endoderm and mesoderm are critical to vertebrate gut development. Sonic hedgehog encodes a secreted protein known to act as an inductive signal in several regions of the developing embryo. In this report, we provide evidence to support the role of Sonic hedgehog and its target genes Bmp-4 and the Abd-B-related Hox genes in the induction and patterning the chick hindgut. Sonic is expressed in the definitive endoderm at the earliest stage of chick gut formation. Immediately subjacent to Sonic expression in the caudal endoderm is undifferentiated mesoderm, later to become the visceral mesoderm of the hindgut. Genes expressed within this tissue include Bmp-4 (a TGF-beta relative implicated in proper growth of visceral mesoderm) and members of the Abd-B class of Hox genes (known regulators of pattern in many aspects of development). Using virally mediated misexpression, we show that Sonic hedgehog is sufficient to induce ectopic expression of Bmp-4 and specific Hoxd genes within the mesoderm. Sonic therefore appears to act as a signal in an epithelial-mesenchymal interaction in the earliest stages of chick hindgut formation. Gut pattern is evidenced later in gut morphogenesis with the presence of anatomic boundaries reflecting phenotypically and physiologically distinct regions. The expression pattern of the Abd-b-like Hox genes remains restricted in the hindgut and these Hox expression domains reflect gut morphologic boundaries. This finding strongly supports a role for these genes in determining the adult gut phenotype. Our results provide the basis for a model to describe molecular controls of early vertebrate hindgut development and patterning. Expression of homologous genes in Drosophila suggest that aspects of gut morphogenesis may be regulated by similar inductive networks in the two organisms.

Animals↗

patched overexpression alters wing disc size and pattern: transcriptional and post-transcriptional effects on hedgehog targets.

The membrane protein, Patched, plays a critical role in patterning embryonic and imaginal tissues in Drosophila. patched constitutively inactivates the transcription of target genes such as wingless, decapentaplegic, and patched itself. The secreted protein, Hedgehog, induces transcription of target genes by opposing the Patched signaling pathway. Using the Gal4 UAS system we have overexpressed patched in wing imaginal discs and found that high Patched levels, expressed in either normal or ectopic patterns, result in loss of wing vein patterning in both compartments centering at the anterior/posterior border. In addition, patched inhibits the formation of the mechanosensory neurons, the campaniform sensilla, in the wing blade. The patched wing vein phenotype is modulated by mutations in hedgehog and cubitus interruptus (ci). Patched overexpression inhibits transcription of patched and decapentaplegic and post-transcriptionally decreases the amount of Ci protein at the anterior/posterior boundary. In hedgehogMrt wing discs, which express ectopic hedgehog, Ci levels are correspondingly elevated, suggesting that hedgehog relieves patched repression of Ci accumulation. Protein kinase A also regulates Ci; protein kinase A mutant clones in the anterior compartment have increased levels of Ci protein. Thus patched influences wing disc patterning by decreasing Ci protein levels and inactivating hedgehog target genes in the anterior compartment.

Animals↗

Ageing, infecundity and reproductive senescence in free-ranging female rhesus monkeys.

The reproductive performance of 760 free-ranging female rhesus monkeys (Macaca mulatta), 168 of whom were 20 years of age and older at the time observations were begun, was assessed. The monkeys were resident on Raccoon Key or Key Lois, two islands located in the Florida Keys, USA. During 1992 and 1993, live birth rates generally declined with age among the Raccoon and Lois females aged eight years and older. This age-related deterioration of female fertility was the result of proportionately more younger females bearing live young during successive birth seasons, and proportionately more older females experiencing an inability to bear live offspring even after a barren year. It is suggested that (1) older females may be more strongly inhibited by the suckling stimulus than are their younger peers, and (2) the risk of a permanent loss of fecundity increases with each additional year of life or parturition. The live birth rates of females aged 16-24 years were greater on Raccoon Key than they were on Key Lois, because the Raccoon females within this age range were more successful at bearing live offspring during successive birth seasons; the reason for this difference could not be determined. Inter-population differences in both the body condition of the females and the severity of female-female competition for access to males were not considered to be plausible explanations. It is possible that the difference in female fertility between the islands is the result of the greater age of the adult males on Key Lois, or the phytochemicals eaten by the females on Raccoon Key.

Aging↗

Drug abuse.

The wide array of therapeutic responses to substance use/abuse suggests that there is not one best approach to solve the problems of any one adolescent or young adult. Indeed, most young people require a variety of therapeutic interventions, which may include inpatient treatment, ambulatory therapeutic groups, and individual counseling, as well as self-help groups. In choosing a therapeutic program, the physician must be circumspect when interpreting the reported success or "cure" rates of any of these modalities. Such citations often are misleading because frequently they fail to reflect accurately the therapeutic influence of several important patient population variables that distinguish the programs. For example, an outpatient program may report better "cure" rates than an inpatient program because the ambulatory program may have enrolled clients who have more limited substance use patterns and who are more committed to abstinence. Furthermore, there is no standard methodology for reporting "rates of success." Some programs simply report a compliance rate for clients who attend meetings or scheduled therapeutic sessions, some report the numbers of clients who complete the program without any reference to recidivism, and some report the numbers of clients who are "drug-free" after 1 year. Given these caveats, the experience of most clinicians suggests that many adolescents who experiment with the traditional "gateway" drugs (eg, tobacco, alcohol, marijuana) respond well to outpatient group and individual therapy, those adolescents committed to a substance use/abuse pattern respond best to inpatient or residential programs, and adolescents who have a psychiatric/behavioral problem complicated by substance use/abuse require formal psychiatric treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Facilitating changes in exercise behavior: effect of structured statements of intention on perceived barriers to action.

Two groups of worksite employees (58 in a control, 53 in an experimental group) underwent three 90-min. educational sessions designed to increase participation in exercise. At the end of the third session, experimental subjects were asked to complete a structured statement of exercise intention which addressed the major barrier to exercise. Two weeks following the program, chi-squared analysis showed that the two groups were proportionately different in changes in frequency and intensity of exercise such that the experimental group in both cases showed greater changes than the control. Experimental subjects showed a twofold increase in frequency and intensity of exercise over the control group. Pearson r indicated a statistically significant association between the completeness of structured statements of intention and an increase in frequency of exercise. We conclude that structured statements of intention are useful for distinguishing between contrived barriers to exercise (excuses) and actual barriers that require practical solutions.

Adult↗

Serving time: psychiatric mental health nursing in corrections.

1. The opposing philosophies of custody and caring result in direct implications for nurses working in the correctional environment. Nurses constantly "walk in line" between the requirement of security, health care, and client advocacy. 2. Deinstitutionalization, increased rates of incarceration for interpersonal violence, and substance abuse related crimes have resulted in a rapidly expanding prison population. Of all offenders, 10% to 15% have a major mental illness, leading to many treatment challenges for the nurse. 3. Therapy issues with this population are complicated. Correctional nurses must have a good understanding of the therapeutic nurse-client relationship, with particular attention to therapeutic impasses, transference, and countertransference. 4. Historically, role development for nurses working in corrections has been particularly difficult. Correctional nurses must grapple with issues surrounding professional identity, professional isolation, and territoriality.

Criminal Law↗

America's most computer advanced healthcare facilities.

Healthcare Informatics polled industry experts for nominations for this listing of "America's Most Computer Advanced Healthcare Organizations." Survey responses from organizations nominated were reviewed by Ronald L. Johnson, founder and president of R.L. Johnson & Associates, Danville, Calif. The results of his evaluations follow.

Diffusion of Innovation↗

Type 4a metabotropic glutamate receptor: identification of new potent agonists and differentiation from the L-(+)-2-amino-4-phosphonobutanoic acid-sensitive receptor in the lateral perforant pathway in rats.

Before the discovery of the metabotropic glutamate receptors (mGluRs), the glutamate analogue L-2-amino-4-phosphonobutanoic acid (L-AP4) was identified as a potent presynaptic inhibitor of evoked synaptic transmission in the lateral perforant pathway in rats. The localization and L-AP4 sensitivity of the mGluR4a subtype of mGluRs were consistent with the hypothesis that this receptor mediates the synaptic depressant effects of L-AP4 in the lateral perforant pathway. In the present study, the pharmacology of mGluR4a expressed in baby hamster kidney 570 cells was characterized and compared with that previously reported for the lateral perforant pathway responses. The endogenous excitatory amino acid L-aspartate was inactive at mGluR4a, whereas L-homocysteic acid was only 5-fold less potent than L-glutamate. These data suggest that L-homocysteic acid may be an endogenous agonist at mGluR4a. Of the 30 L-AP4 analogues examined, several compounds were identified as agonists at mGluR4a. The cyclopropyl-AP4 analogue (Z)-(+/-)-2-amino-2,3-methano-4-phosphonobutanoic acid inhibited forskolin-stimulated cAMP production with an EC50 of 0.58 microM, which is comparable to that of L-AP4 (EC50 = 0.43 microM). Two other cyclic analogues of L-AP4 were approximately 10-fold less potent as agonists at mGluR4a, i.e., (+/-)-1-amino-3-(phosphonomethylene)cyclobutanecarboxylic acid (EC50 = 4.4 microM) and (E)-(+/-)-2-amino-2,3-methano-4-phosphonobutanoic acid (EC50 = 7.9 microM). Comparison of the potencies of the compounds for activation of mGluR4a with their potencies for inhibition of lateral perforant pathway responses demonstrates that some compounds have comparable activities in the two systems, whereas several compounds are at least 10-fold more potent in one of the systems. In addition, although the mGluR antagonist (+)-alpha-methyl-4-carboxyphenylglycine blocked the effects of L-AP4 in the lateral perforant pathway, it did not block the effects of L-AP4 at the cloned receptor. These data provide evidence that mGluR4a does not mediate the effects of L-AP4 in the lateral perforant pathway, they provide new tools to identify the function of these receptors in the mammalian central nervous system, and they indicate that the effects of L-AP4 in the lateral perforant pathway are mediated by a (+)-alpha-methyl-4-carboxyphenylglycine-sensitive receptor.

Aminobutyrates↗

Fetal acoustic stimulation as an adjunct to external cephalic version.

OBJECTIVE: To evaluate fetal acoustic stimulation (FAS) as an adjunct to external cephalic version in a midline fetal spine presentation. STUDY DESIGN: Breech presentation in a woman presenting for attempted version at 37 weeks' gestation with a fetus in a midline position and the spine anterior is difficult to convert to a vertex. An evaluation of FAS to assist in repositioning the fetus in a more spine lateral position was carried out. Patients with a failed version attempt and a midline breech presentation were enrolled in the study. The patient served as her own control. If that attempt failed, an electrolarynx device was used to produce a one- to three-second stimulus, and then another version attempt was made. RESULTS: Sixteen patients were enrolled. Prior to FAS, 0/16 fetuses were successfully turned. FAS altered the position in 100% of patients from spine midline to lateral. After FAS, 15/16 (94%) were successfully converted to vertex presentation. The one patient whose fetus failed to convert also failed her second version attempt (P < .0005). CONCLUSION: FAS may improve the opportunity for successful external cephalic version in the properly selected candidate with a fetus in a midline position with the spine anterior.

Acoustic Stimulation↗

Ectopic expression of Sonic hedgehog alters dorsal-ventral patterning of somites.

Differentiation of somites into sclerotome, dermatome, and myotome is controlled by a complex set of inductive interactions. The ability of axial midline tissues, the notochord and floor plate, to induce sclerotome has been well documented and has led to models in which ventral somite identity is specified by signals derived from the notochord and floor plate. Herein, we provide evidence that Sonic hedgehog, a vertebrate homolog of the Drosophila segment polarity gene hedgehog, is a signal produced by the notochord and floor plate that directs ventral somite differentiation. Sonic hedgehog is expressed in ventral midline tissues at critical times during somite specification and has the ability, when ectopically expressed, to enhance the formation of sclerotome and antagonize the development of dermatome.

Amino Acid Sequence↗

Sonic hedgehog and Fgf-4 act through a signaling cascade and feedback loop to integrate growth and patterning of the developing limb bud.

Proper limb growth and patterning requires signals from the zone of polarizing activity in the posterior mesoderm and from the overlying apical ectodermal ridge (AER). Sonic hedgehog and Fgf-4, respectively, have recently been identified as candidates for these signals. We have dissected the roles of these secreted proteins in early limb development by ectopically regulating their activities in a number of surgical contexts. Our results indicate that Sonic hedgehog initiates expression of secondary signaling molecules, including Bmp-2 in the mesoderm and Fgf-4 in the ectoderm. The mesoderm requires ectodermally derived competence factors, which include Fgf-4, to activate target gene expression in response to Sonic hedgehog. The expression of Sonic hedgehog and Fgf-4 is coordinately regulated by a positive feedback loop operating between the posterior mesoderm and the overlying AER. Taken together, these data provide a basis for understanding the integration of growth and patterning in the developing limb.

Animals↗

Synthesis of oxadiazolidinedione derivatives as quisqualic acid analogues and their evaluation at a quisqualate-sensitized site in the rat hippocampus.

The ability of quisqualic acid (1) to sensitize neurons to depolarization by omega-phosphono alpha-amino acid analogues of excitatory amino acids is a highly specific phenomenon and is termed the QUIS effect. In an attempt to elucidate the structure-activity relationships for this sensitization, analogues 2-6 of quisqualic acid have been synthesized. Compounds 4, 5, and 6 showed no quisqualate sensitization with respect to L-2-amino-6-phosphonohexanoic acid (L-AP6), while compounds 2 and 3 were 1/10 and 1/1000, respectively, as active as quisqualic acid in sensitizing neurons toward L-AP6.

Animals↗