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PubMed2006

Effects of increased intra-abdominal pressure on central circulation.

BACKGROUND: In an experimental model we investigated the effects of a gradual increase in intra-abdominal pressure (IAP) on the central circulation. METHODS: Seven pigs were anaesthetized, mechanically ventilated and instrumented. IAP was gradually increased by 5 mm Hg up to 30 mm Hg by abdominal banding in normovolaemic animals, and then they were made hypovolaemic after blood withdrawal. Right atrial pressure (RAP) and left ventricular end-diastolic pressure (LVEDP) at each step and aortic, femoral and inferior vena cava blood flows were measured. Left ventricular end-diastolic area (LVEDA) was determined using epicardial echocardiography. RESULTS: Cardiac output maintained at mild IAP was reduced to 76 (24)% of the initial value at 30 mm Hg IAP [mean (sd)] in normovolaemic animals, and 72 (22)% (P<0.001) in hypovolaemic animals. In normovolaemic animals the LVEDA and LVEDP were significantly increased at an IAP of 10 and 15 mm Hg by 26 (24)% and 38 (23)%, respectively. At these IAP values, the difference between the RAP and IAP was positive. When this gradient became negative, that is beyond 15 mm Hg in normovolaemia and for all IAP values in hypovolaemic animals, the LVEDA declined, reaching 78 (16)% and 62 (22)% (P<0.05) of the initial values in normovolaemic and hypovolaemic groups at the highest IAP value. CONCLUSIONS: These results showed that a gradual increase in IAP led to a redistribution of abdominal blood volume towards the thoracic compartment, at IAP lower than 15 mm Hg in normovolaemia, and at its expense at higher values of IAP. In hypovolaemia there was no thoracic compartment gain. Whereas the absolute or transmural RAPs were not informative of the direction of this blood shift, an RAP greater than IAP was associated with an intrathoracic compartment gain.

Abdomen↗

PubMed2000

Ras mediates the cAMP-dependent activation of extracellular signal-regulated kinases (ERKs) in melanocytes.

In melanocytes and melanoma cells, cAMP activates extracellular signal-regulated kinases (ERKs) and MEK-1 by an unknown mechanism. We demonstrate that B-Raf is activated by cAMP in melanocytes. A dominant-negative mutant of B-Raf, but not of Raf-1, blocked the cAMP-induced activation of ERK, indicating that B-Raf is the MEK-1 upstream regulator mediating this cAMP effect. Studies using Clostridium sordelii lethal toxin and Clostridium difficile toxin B have suggested that Rap-1 or Ras might transduce cAMP action. We show that Ras, but not Rap-1, is activated cell-specifically and mediates the cAMP-dependent activation of ERKs, while Rap-1 is not involved in this process in melanocytes. Our results suggest a novel, cell-specific mechanism involving Ras small GTPase and B-Raf kinase as mediators of ERK activation by cAMP. Also, in melanocytes, Ras or ERK activation by cAMP is not mediated through protein kinase A activation. Neither the Ras exchange factor, Son of sevenless (SOS), nor the cAMP-responsive Rap-1 exchange factor, Epac, participate in the cAMP-dependent activation of Ras. These findings suggest the existence of a melanocyte-specific Ras exchange factor directly regulated by cAMP.

Animals↗

PubMed1992

A comparison of the effects of hard rock and easy listening on the frequency of observed inappropriate behaviors: control of environmental antecedents in a large public area.

Observation of clients at a state mental health hospital by direct care staff indicated that they appeared to act in more inappropriate ways when "hard rock" or "rap" music was played in an open courtyard than when "easy listening" or "country" music was played. A study was conducted to compare the inappropriate behavior of clients when hard rock and rap music were played (21 days), followed by easy listening and country and western music (21 days). This comparison was followed by a reversal phase in which hard rock and rap music were again played (18 days). The behaviors of the clients were observed and recorded via a controlled methodology. The results demonstrated that more inappropriate behavior was observed under conditions in which hard rock and rap music were played than when easy listening and country western music were played. The implications of these findings are discussed.

Adult↗

PubMed1989

Children with recurrent abdominal pain and their parents: more somatic complaints, anxiety, and depression than other patient families?

Patients presenting with abdominal pain were classified into two groups: the recurrent abdominal pain (RAP) group (n = 41), consisting of patients without identifiable organic etiology for abdominal pain, and the organic group (n = 28), consisting of patients with organic findings (primarily ulcer-related conditions). A control group of well patients (n = 41) also participated. RAP and organic patients had higher anxiety, depression, and somatic complaints than well patients, but did not differ from each other. Anxiety, depression, and somatization were greater in RAP mothers than well mothers. Father symptomatology did not differ for the groups. Results suggest that psychological distress does not discriminate between patients with and without identifiable organic etiology for abdominal pain. The high levels of anxiety and depression in RAP and organic patients suggest that they should be targeted in efforts to address "the new hidden morbidity" in pediatrics.

Abdomen↗

PubMed1991

Negative life events and symptom resolution in pediatric abdominal pain patients.

Investigated relation of negative life events (NLE) to initial symptom severity and symptom resolution at 3 months in 2 patient groups: (a) recurrent abdominal pain (RAP) without identifiable organic etiology, (b) abdominal pain with organic diagnosis. Symptoms assessed were abdominal pain, somatization symptoms, anxiety, depression. Number of NLE was positively correlated with anxiety and depression in both groups at clinic visit. NLE predicted resolution of abdominal pain for RAP patients only; RAP patients with more NLE prior to or following the clinic visit were more likely to maintain their abdominal pain. More NLE following clinic visit was associated with maintenance of anxiety and somatization symptoms at follow-up in RAP patients. Results suggest a measure of NLE is not useful in differential diagnosis of patients with and without organic findings, but is useful in predicting outcome in patients without organic findings.

Abdominal Pain↗

PubMed1994

Survey of pediatricians' management practices for recurrent abdominal pain.

Surveyed general pediatricians (N = 116) regarding six content areas: (a) diagnostic procedures utilized during the initial evaluation sequence of a child with recurrent abdominal pain (RAP); (b) factors that influence decisions to order additional evaluations; (c) management practices following negative evaluation results; (d) factors influencing decisions about consultation with or referral to a mental health professional; (e) attitudes about the etiology of RAP; and (f) the frequency in which pediatricians encountered children with RAP and referred them to mental health services. Results of this survey are presented and discussed from a biopsychosocial perspective. Limitations of the survey, implications of the results for integrating mental health professionals into the evaluation and treatment process of RAP patients, and directions for future research are discussed.

Abdominal Pain↗

PubMed1995

Long-term health outcomes in patients with recurrent abdominal pain.

Investigated somatic and emotional symptoms, functional disability, and health service utilization in 31 former RAP patients and 31 former well patients who had originally been interviewed 5 to 6 years earlier. Both former patients and their mothers were interviewed for this follow-up study. Medical records were obtained for those patients who reported receiving new diagnoses for abdominal pain since their initial assessment. Results indicated that only one of the former RAP patients was later diagnosed with organic disease that clearly accounted for his earlier abdominal pain. Nonetheless, at follow-up former RAP patients reported significantly higher levels of abdominal pain, other somatic symptoms, and functional disability (including school/work absence) than did former well patients. Mothers reported higher levels of internalizing emotional symptoms in former RAP patients than in former well patients.

Abdominal Pain↗

PubMed2005

Attentional biases to pain and social threat in children with recurrent abdominal pain.

OBJECTIVES: To test whether children with recurrent abdominal pain (RAP) exhibit subliminal (nonconscious) and supraliminal (conscious) attentional biases to pain-related words, and to determine correlates of these biases. Previous research indicates that individuals attend to disorder-relevant threat words, and in this study, attentional biases to disorder-relevant threat (pain), alternative threat (social threat), and neutral words were compared. METHODS: Participants were 59 children with RAP who completed a computer-based attentional bias task. Participants and their parents also completed questionnaires measuring pain, somatic complaints, anxiety/depression, and body vigilance. RESULTS: Children with RAP showed attentional biases toward subliminal pain-related words and attentional biases away from supraliminal pain-related words. Participants' attentional biases to social threat-related words were marginally significant and also reflected subliminal attention and supraliminal avoidance. Attentional biases were related to parent and child reports of pain, body vigilance, and anxiety/depression. CONCLUSIONS: Children with RAP show nonconscious attention to and conscious avoidance of threat-related words. Their attentional biases relate to individual differences in symptom severity. Implications for models of pediatric pain and future studies are discussed.

Abdominal Pain↗

PubMed2000

Differential expression of the alpha(2)-macroglobulin receptor and the receptor associated protein in normal human endometrium and endometrial carcinoma.

Extracellular matrix degradation, mediated by the activation of receptor-bound proteolytic enzymes, is essential to the process of cellular invasion. Many normal physiological functions such as endometrial remodelling are reliant on the activation of these surface associated proteolytic enzymes, as are pathological functions such as cancer-cell invasion. The internalization of proteolytic complexes is mediated by the multi-functional clearance receptor, alpha(2)-macroglobulin receptor/LRP. The role of LRP and its ligand binding inhibitor, the receptor-associated protein (RAP), in the advancement of invasive endometrial carcinoma is unknown. The aim of this study was to compare the expression of LRP and RAP mRNA in normal endometrium (n = 14) and endometrial carcinoma (n = 33) by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Expression of LRP mRNA in normal endometrium was significantly increased in the secretory phase when compared with proliferative phase endometrium (P: < 0.05). The expression of LRP in all carcinomas examined was significantly reduced to about 20% of the amount in normal endometrium (P: < 0.05), whereas RAP expression was not significantly different between endometrium and carcinoma. No significant difference in the level of LRP or RAP expression was observed between carcinoma grades or stages. In conclusion, we have shown that LRP expression is differentially regulated in the normal endometrium during the menstrual cycle and is decreased in invasive endometrial carcinomas.

Adenocarcinoma↗

PubMedDate not supplied

Estimation of timing errors for the intraaortic balloon pump use in pediatric patients.

The use of the intraaortic balloon pump (IABP) for managing acute left ventricular failure in pediatric patients is less successful than in adults. It is often reported that rapid pediatric heart rates make accurate timing difficult to achieve. Traditional IABP theory requires that the balloon inflate during diastole (after aortic valve closure), for optimum coronary pressure and flow augmentation, and deflate just before the next systole for optimal ventricular afterload reduction. Errors in timing balloon inflation and deflation may result in the reduced IABP efficacy seen in children. To investigate timing errors when using the traditional IABP inflation and deflation markers in pediatric patients, six patients (age, 2.2+/-1.4 years; weight, 11.5+/-3.9 kg) were studied intraoperatively. Radial artery pressure (RAP) waveforms from a standard, fluid-filled pressure monitoring system were recorded on an FM data tape recorder simultaneously with high-fidelity, aortic root pressure waveforms, aortic root flow waveforms, and M-mode echocardiography. For each patient, a sequence of five recorded waveforms was analyzed. The mean +/- standard deviation of the time delay between aortic root and RAP markers and percentage delay of the corresponding part of the cardiac cycle were determined. When compared with aortic root waveforms, the RAP waveform consistently showed a delay in the IABP timing markers. A 107+/-23 msec (53+/-11%) delay in diastolic inflation and a 92+/-11 msec (40+/-4%) delay in presystolic deflation was found. If IABP timing to the RAP markers were to be used, the delay in IABP inflation would result in reduced diastolic augmentation, and the delay in IABP deflation into the systolic period would increase afterload. M-mode echocardiography provided timing markers that were identical to those provided by high-fidelity aortic root pressure waveforms. The combined effect of these delays on IABP function could substantially reduce the efficacy of the IABP in pediatric patients, indicating the need for more accurate indices for IABP timing in this patient group.

Aorta↗

PubMed1989

Mediastinal, left, and right atrial pressure variations with different modes of mechanical and spontaneous ventilation.

Variations in mediastinal, left, and right atrial pressures (MedP, LAP, RAP, respectively) were measured by means of catheters and tubes positioned in ten patients with nonvalvular cardiac surgery. For each pressure, a maximum, minimum, and mean value was determined in relation to its oscillations during the respiratory cycle. Thus, we compared the variations in MedP, LAP, and RAP in controlled mechanical ventilation (CMV), CMV with 5 cm H2O PEEP, synchronous intermittent mandatory ventilation (SIMV), SIMV with 5 cm H2O PEEP, continuous positive airway pressure (CPAP), and spontaneous respiration (SR). We built an experimental model to compare the measurements obtained by air-filled tubes inserted at surgery with those obtained by esophageal balloons filled with water. The maximum MedP did not vary significantly in these patients except when SIMV and SR were compared; however, the minimum MedP diminished significantly (p less than .001) in SIMV, SIMV-PEEP, CPAP, and SR, with negative inspiratory values reaching significant proportions. The mean values of MedP, LAP, and RAP showed a similar tendency although to a lesser degree. The experimental model revealed a strong linear relation between the values obtained with air-filled tubes and those obtained with water-filled esophageal balloons (r = .99, p less than .001). These results suggest that the mean values of MedP, LAP, and RAP do not reflect the dynamic variations in ventricular filling pressure accurately, nor the important negative inspiratory peaks that appear in different types of ventilation using spontaneous cycles with and without PEEP. These inspiratory peaks can overload the left ventricle by hydrostatic gradients, and lead to pulmonary edema in susceptible patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2004

A randomized placebo-controlled trial of a school-based depression prevention program.

OBJECTIVE: To conduct a placebo-controlled study of the effectiveness of a universal school-based depression prevention program. METHOD: Three hundred ninety-two students age 13 to 15 from two schools were randomized to intervention (RAP-Kiwi) and placebo programs run by teachers. RAP-Kiwi was an 11-session manual-based program derived from cognitive-behavioral therapy. The placebo was similar but with cognitive components removed. Outcomes were self-rated depression scales, the Reynolds Adolescent Depression Scale (RADS), and the Beck Depression Inventory II (BDI-II). Follow-up was to 18 months. Analysis was done on an intent-to-treat basis. RESULTS: Immediately after the intervention, depression scores were reduced significantly more by RAP-Kiwi than by placebo, with a mean difference in change from baseline between groups of 1.5 on BDI-II (CI > 0.38, p =.01) and 2.24 on RADS (CI > 0.22, p =.04). Categorical analysis confirmed significant clinical benefit with an absolute risk reduction of 3% (95% CI, 1-11%, McNemar chi, p =.03), with the "number needed to treat" for short-term benefit of 33. Group differences in depression scores averaged across time to 18 months were significant on RADS but not on BDI-II. Retention rates were 91% at 6 months and 72% at 18 months. CONCLUSIONS: The RAP-Kiwi program is a potentially effective public health measure. Confirmation of effectiveness measuring episodes of depressive illness and broader measures of adjustment is warranted.

Adolescent↗

PubMed1980

Gastric acid secretion and serum gastrin levels in children with recurrent abdominal pain, gastric and duodenal ulcers.

Basal and histalog-stimulated gastric acid secretion and serum gastrin levels before and after a standard protein meal were compared in eight children with active duodenal ulcer (DU), four with active gastric ulcer (GU), and in seven children with recurrent abdominal pain (RAP) of undetermined etiology. There was no discernible difference in the pattern of abdominal pain in DU, GU, and RAP. Basal acid output, peak and maximal acid output, whether expressed as milliequivalents per hour or as milliequivalents per kilogram per hour, were comparable in children with DU, GU, and RAP. In contrast, serum gastrin levels, 1 and 2 hours after standard protein meal, were significantly higher in the DU children than in the GU or RAP group. These studies have suggested that hypersecretion of gastric acid may not be associated with duodenal ulcer or gastric ulcer disease in children, and that increased gastrin secretion and possible reduced acid responsiveness coexist in children with duodenal ulcers.

Abdomen↗

PubMed1988

Pressure natriuresis and control of arterial pressure during chronic norepinephrine infusion.

The goal of this study was to quantitate changes in mean arterial pressure (MAP) and renal function during chronic increases in plasma levels of norepinephrine, and to determine the role of the renal pressure natriuresis mechanism in controlling sodium balance in norepinephrine hypertension. In six conscious dogs in which renal artery pressure (RAP) was allowed to increase during 7 days of norepinephrine infusion (0.2 micrograms/kg per min), sodium excretion (UNaV) rose from 66 +/- 3 to 112 +/- 15 mmol/day and MAP increased from 100 +/- 3 to 109 +/- 3 mmHg on the first day. On days 2-7, UNaV returned toward the control level while MAP averaged 108 +/- 2 mmHg. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) did not change significantly, averaging 85.9 +/- 4.0 and 235 +/- 17 ml/min, respectively, during 7 days of norepinephrine, compared to controls of 84.1 +/- 3.9 and 252 +/- 20 ml/min. When RAP was servo-controlled for 7 days during norepinephrine infusion, the natriuresis was abolished; UNaV averaged 76 +/- 8 during control, 77 +/- 13 during the first day of norepinephrine and 65 +/- 4 mmol/day during 7 days of norepinephrine. GFR and ERPF did not change significantly during norepinephrine infusion with RAP held constant. MAP did not reach a plateau but continued to rise from 102 +/- 3 to 137 +/- 3 mmHg after 7 days of norepinephrine and servo-control of RAP.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

PubMed1999

Hemodynamic and hormonal responses to nicorandil in a canine model of acute ischemic heart failure: a comparison with cromakalim and nitroglycerin.

The pharmacologic profiles of nicorandil in the cardiovascular system have been characterized by K-channel opening and nitrate activities. However, the effects of nicorandil on acute heart failure have yet to be elucidated. To investigate the effects of nicorandil under such pathophysiologic conditions, we administered nicorandil intravenously to dogs with acute ischemic heart failure induced by coronary embolization and compared the results with those induced by cromakalim and nitroglycerin. The heart failure in this experiment was demonstrated by a reduction of mean blood pressure (MBP) from 143+/-3 to 129+/-2 mm Hg (p < 0.01); cardiac output (CO) from 2.18+/-0.10 to 1.06+/-0.05 L/min (p < 0.01); stroke volume (SV) from 12.7+/-0.6 to 6.8+/-0.3 ml/min (p < 0.01); Vmax, an index of the contractility of the left ventricle, from 105.5+/-4.4 to 49.9+/-1.8 1/s (p < 0.01), and an increase in right atrial pressure (RAP) from 2.9+/-0.3 to 5.3+/-0.3 mm Hg (p < 0.01); left ventricular end-diastolic pressure (LVEDP) from 2.5+/-0.4 to 26.0+/-1.4 mm Hg (p < 0.01); and T, time constant of left ventricular relaxation, from 38.3+/-0.8 to 62.4+/-2.8 ms (p < 0.01). Furthermore, plasma renin activity (PRA) and plasma atrial natriuretic peptide (ANP) increased (from 1.72+/-0.29 to 5.03+/-0.68 ng AngI/ml/h, p < 0.01; from 103.9+/-5.8 to 411.5+/-29.4 pg/ml, p < 0.01, respectively), whereas brain natriuretic peptide (BNP) remained unchanged (from 23.1+/-2.2 to 26.9+/-1.4 pg/ml). Nicorandil (10-40 microg/kg/min, i.v. infusion for 20 min for each dosing) or cromakalim (0.25-1 microg/kg/min) decreased MBP, systemic vascular resistance (SVR), RAP, and LVEDP, and increased CO, SV, and Vmax. However, the reduction of RAP in cromakalim was significantly smaller than those of nicorandil and nitroglycerin in comparison at similar hypotensive doses. Nitroglycerin (2.5-10 microg/kg/min) decreased MBP, RAP, and LVEDP, and increased Vmax but did not change CO or SV. Increased plasma ANP levels, an index of cardiac filling pressure after induction of acute ischemic heart failure, were decreased significantly by cromakalim and tended to decrease by nicorandil or nitroglycerin. Plasma BNP levels and PRA were not influenced by any of these drugs. These results suggest that nicorandil produces the reduction of both preload and afterload followed by an improvement of cardiac contractility in this model. The increase in CO may be mediated mainly by the drug's K-channel opening activities and the reduction of venous tone by its nitrate properties. Nicorandil may prove to be useful in the treatment of acute ischemic heart failure.

Acute Disease↗

PubMed2000

Association of glucocorticoids and cyclosporin A or rapamycin prevents E-selectin and IL-8 expression during LPS- and TNFalpha-mediated endothelial cell activation.

BACKGROUND: Endothelial cell (EC) activation plays an important role in inflammation, hemostasis, and organ rejection of allogeneic and xenogeneic transplantation. These processes leads to rapid and transient up-regulation of proinflammatory molecules, such as the adhesion molecule E-selectin and the chemotactic cytokine IL-8. The purpose of this study was to investigate the specific effects of several major and potentially synergistic immunosuppressive drugs-cyclosporin A (CsA), rapamycin (Rap), and glucocorticoids (GC)-on lipopolysaccharide (LPS)- or tumor necrosis factor (TNF)alpha-induced EC activation METHODS: The ability of immunosuppressive drugs, used alone or in combination, to prevent in vitro TNFalpha- and LPS-induced expression of E-selectin and interleukin 8 on porcine ECs, as well as their effect on leukocyte-EC interaction, were investigated. In addition, we studied the in vivo effect of these drugs after i.v. administration of recombinant TNFalpha to rats. RESULTS: At high concentrations, which correspond to the acceptable experimental levels in primate xenograft recipients, CsA, Rap, and GC individually inhibited E-selectin protein induction in a dose-dependent manner in cultured porcine ECs treated with LPS with an additive effect when the drugs were associated. The pattern of drug-mediated inhibition was related to the stimulus used to activate ECs (i.e., LPS vs. TNFalpha). Reduced expression of E-selectin on ECs activated in the presence of the tested immunosuppressive drugs correlated with a weaker adhesion of human U937 cells to ECs. Messenger RNA analysis demonstrated that the presence of CsA, Rap, and GC during EC activation inhibited E-selectin and interleukin 8 at the gene expression level. LPS-mediated induction of IbetaBalpha expression was not observed in ECs treated with CsA, whereas GC reduced its transcripts by approximately 50%. It is interesting that in vivo studies confirmed that CsA and GC inhibited EC activation at therapeutic doses (1 mg/kg and 10 mg/kg for GC and CsA, respectively) and showed that the combination of CsA and GC efficiently prevents TNFalpha-mediated induction of E-selectin on cardiac ECs. CONCLUSION: Our data show that, besides their specific immunosuppressive effects on T cells, CsA, Rap, and GC can efficiently contribute to the attenuation of EC activation in vivo and the resulting inhibition is enhanced by the association of CsA with GC.

Animals↗

PubMed2001

Decision rules, energy metabolism and vigour of hermit-crab fights.

Aggressive interactions between animals are often settled by the use of repeated signals that reduce the risk of injury from combat but are expected to be costly. The accumulation of lactic acid and the depletion of energy stores may constrain activity rates during and after fights and thus represent significant costs of signalling. We tested this by analysing the concentrations of lactate and glucose in the haemolymph of hermit crabs following agonistic interactions over the ownership of the gastropod shells that they inhabit. Attackers and defenders play distinct roles of sender and receiver that are fixed for the course of the encounter. Attackers perform bouts of 'shell rapping', which vary in vigour between attackers and during the course of the encounter, and are a key predictor of victory. In contrast to the agonistic behaviour of other species, we can quantify the vigour of fighting. We demonstrate, to our knowledge for the first time, an association between the vigour of aggressive activity and a proximate cost of signalling. We show that the lactate concentration in attackers increases with the amount of shell rapping, and that this appears to constrain the vigour of subsequent rapping. Furthermore, attackers, but not defenders, give up when the concentration of lactate is high. Glucose levels in attackers also increase with the amount of rapping they perform, but do not appear to influence their decision to give up. Defenders are more likely to lose when they have particularly low levels of glucose. We conclude that the two roles use different decision rules during these encounters.

Aggression↗

PubMed2004

Resonant activation in discrete systems.

The resonant activation phenomenon (RAP) in a discrete system is studied using the master equation formalism. We show that the RAP corresponds to a nonmonotonic behavior of the frequency dependent first passage time probability density function (PDF). An analytical expression for the resonant frequency is introduced, which, together with numerical results, helps understand the RAP behavior in the space spanned by the transition rates for the case of reflecting and absorbing boundary conditions. The limited range of system parameters for which the RAP occurs is discussed. We show that a minimum and a maximum in the mean first passage time can be obtained when both boundaries are absorbing. Relationships to some biological systems are suggested.

Algorithms↗