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PubMed1992

[The effect of intravenous furosemide on the hemodynamic parameters and colloid osmotic pressure in patients with pulmonary edema].

PURPOSE: To evaluate the effects of intravenous furosemide over hemodynamics variables and colloid osmotic pressure in patients with pulmonary edema. METHODS: Eight patients with pulmonary edema, mean age of 58.3 +/- 7.5 years, 6 men, were evaluated. Hemodynamic monitoring was performed by Swan-Ganz catheter in pulmonary artery to obtain RAP and PAWP, in mmHg, and HR, in bpm. Cardiac output (CO) was obtained by thermodilution method. Cardiac index (CI) in L/min/m2, and systolic index, in ml, arose from variables above. Mean arterial pressure (MAP), in mmHg, was obtained through catheterization of radial artery. patients were treated with 20 mg of intravenous furosemide, and hemodynamic variables were measured before and after 5, 15, 30, 60 and 120 minutes. COP was measured in Weil oncometer (IL 196) at same intervals. RESULTS: A significant reduction of RAP (p = 0.002) and PAWP (p < 0.0001), HR (p = 0.02), COP (p < 0.0001) and gradient between PAWP-COP (p < 0.0001) were observed. RAP and PAWP reduction was greater in the first five minutes and, otherwise, COP reduction was gradual in 120 min. PAWP-COP gradient initially positive, stayed negative during all study. MAP, CI, SI and SVR did not show statistical differences. CONCLUSION: Furosemide administration reduced RAP, PAWP, HR, COP and PAWP-COP gradient, probably by a redistribution of fluid excess in the interstitial to intravascular space, through changes in driving fluid forces, with predominance in colloid osmotic pressure, which reverse fluid from intravascular to interstitial observed in pulmonary edema.

Acute Disease↗

PubMed2004

[Basic research and clinical application of cartilage-derived retinoic acid-sensitive protein].

OBJECTIVE: To know the basic research and the clinical application of cartilage-derived retinoic acid-sensitive protein (CD-RAP) in orthopedic and in other clinical fields. METHODS: The literature related to CD-RAP in basic research and clinical application were extensively reviewed. RESULTS: CD-RAP, as a protein, which is cartilage-specific, could be a marker of the joint diseases. It also can be used to monitor metastasis of melanoma. CONCLUSION: CD-RAP test provides a new way to study repair of cartilage and metastasis of melanoma.

Biomarkers↗

PubMedDate not supplied

[Efficacy of two Helicobacter pylori eradication treatments in children with recurrent abdominal pain].

OBJECTIVE: To compare clinical and bacteriologic efficacy of two therapeutic trials to eradicate Helicobacter pylori (H. pylori) in two series of pediatric patients with recurrent abdominal pain (RAP). MATERIALS AND METHODS: n = 36 children with RAP-associated H. pylori infection. Age 9.8 +/- 3.1 years, 19 boys and 17 girls. Clinical and bacteriologic efficacy of two therapeutic trials was compared: Group A (1996-1997), n = 9, amoxicillin, bismuth subsalicilate, and metronidazol, and group B (1991-1993), n = 27, omeprazol, amoxicillin, and clarithromycin. Initially and post-treatment, H. pylori evaluation was carried out with upper endoscopy and gastric biopsies. For statistics, we used Student t test, chi2, Fisher test, and Kruskal-Wallis analysis of variance (alpha = 0.05). RESULTS: We found that 33/36 cases had gastritis at endoscopy, two with duodenal ulcer; nodular gastritis was observed in more than one half of total cases. All cases fulfilled histologic criteria of gastritis according to Sydney Score. In group A eradication was achieved in 28.6%, while in group B eradication rose to 77.8% (p < 0.05). In group A, 8/9 and in group B 15/27 persisted with RAP (p = 0.113). CONCLUSIONS: High frequency of abnormal and histologic findings was observed in the series presented on children with RAP and H. pylori. Eradication efficacy in the omeprazol/amoxicillin/clarithromycin group was higher when compared with bismuth subsalicilate/amoxicillin/metronidazol trial. This efficacy is comparable to pediatric series treated with the same therapeutic trial.

Abdominal Pain↗

PubMed2005

[Correlation between B-natriuretic peptide and hemodynamics in patients with decompensated heart failure and clinical significance].

OBJECTIVE: To determine the correlation between the serum level of B-natriuretic peptide (BNP) and hemodynamic variables and to evaluate the diagnostic value of BNP in patients with decompensated heart failure (HF). METHODS: BNP levels (TRIAGE BIOSITE Diagnostics, San Diego, USA) were obtained by a rapid immunofluorescence assay in 117 patients with dyspnea including cardiogenic group (75 patients) and lung disease (42 patients). Hemodynamic parameters of 53 patients [male 28, female 25, mean age (71.6 +/- 9.8) years] with HF were determined and left ventricular end-diastolic diameter (LVEDD) of all patients were measured by echocardiogram. RESULTS: Pulmonary capillary wedge pressure (PCWP, mm Hg), mean pulmonary arterial pressure (MPAP, mm Hg), right atrial pressure (RAP, mm Hg) and BNP (ng/L) levels according to New York Heart Association (NYHA) class were: 16.10 +/- 3.50, 22.50 +/- 4.68, 3.11 +/- 1.90, 271.25 +/- 159.29 in NYHA class II, respectively; 21.50 +/- 4.42, 28.60 +/- 9.35, 8.95 +/- 3.86, 619.58 +/- 237.48 in NYHA class III; 29.28 +/- 8.61, 36.50 +/- 12.32, 15.27 +/- 4.96, 1519.28 +/- 618.62 in NYHA class IV (P < 0.01-0.05), respectively. PCWP, MPAP, RAP and plasma BNP levels were directly proportional to cardiac function. The plasma BNP levels had also significant positive correlations with PCWP, MPAP, RAP, (r = 0.59, 0.50, 0.32, P < 0.05-0.01). BNP level [(918.48 +/- 453.25) ng/L] of the group with LVEDD (n = 24) > or = 60 mm was much higher than that of the group with LVEDD (n = 29) < 60 mm [(298.58 +/- 167.51) ng/L]. However, the latter was significantly higher than that in pulmonary dyspnea group with a normal left and right ventricular end-diastolic diameter [(35.4 +/- 26.4) ng/L, P < 0.01]. There was a great difference of BNP between cardiogenic dyspnea group [(761.30 +/- 480.47) ng/L]and lung dyspnea group [(35.4 +/- 26.4) ng/L], P < 0.01. CONCLUSIONS: The plasma BNP levels had significant positive correlations with PCWP, MPAP, RAP. BNP is a cardiac neurohormone secreted from cardiac ventricles as a response to ventricular volume expansion and pressure overload. Rapid testing BNP should be of help to differentiate pulmonary dyspnea from cardiac etiologies.

Aged↗

PubMedDate not supplied

Quantification of ovine bone adaptation to altered load: morphometry, density, and surface strain.

Mechanical loading in the sheep proximal radius was increased by ulnar osteotomy (Group O), decreased by Steinmann pinning (Group P) and unaltered in sham operated controls (Group C). A series of intravenous fluochromes was given to label bone formation and the adaptive response was measured at intervals up to 24 weeks. Surface strains, measured in an in vitro rig, were reduced in Group P and increased significantly in Group O. Cross-sectional area (CSA) peaked in all groups at 6 weeks consistent with a regional acceleratory phenomenon (RAP) and the formation of fibrolamellar bone of low density. In Groups C and P the extent of the RAP was related to the degree of operative trauma and the newly-formed bone was subsequently resorbed. In Group P, CSA fell below control levels suggesting negative adaptation. The increase in area was sustained in Group O and bone density increased due to mineralisation and infilling. Periosteal labelling of the scaffold of parallel-fibred bone peaked at 10 weeks, followed by labelling of lamellar bone filling the gaps in the structure. This adaptive response reduced surface strains to near normal levels by 24 weeks in Group O. Positive adaptation was distinguished from the non-specific RAP due to surgical trauma. The adaptive response is both 'intelligent', in that it utilises and adds to the RAP, and accurate, as no further increase in cross-sectional area was required after 6 weeks.

Animals↗

PubMed1991

FK-506, a potent novel inhibitor of the release of proinflammatory mediators from human Fc epsilon RI+ cells.

FK-506, a macrolide that binds with high affinity to a specific binding protein, and the structurally related macrolide rapamycin (RAP) were compared to cyclosporin A (CsA) for their effects on the release of preformed (histamine) and de novo synthesized (peptide leukotriene C4) inflammatory mediators from human basophils. FK-506 (1 to 300 nM) concentration dependently inhibited histamine release from basophils activated by Der p I Ag, anti-IgE, or compound A23187. FK-506 was more potent than CsA when basophils were challenged with Ag (IC50 = 25.5 +/- 9.5 vs 834.3 +/- 79.8 nM; p less than 0.001), anti-IgE (IC50 = 9.4 +/- 1.7 vs 441.3 +/- 106.7 nM; p less than 0.001), and A23187 (IC50 = 4.1 +/- 0.9 vs 36.7 +/- 3.8 nM; p less than 0.001). The maximal inhibitory effect of FK-506 was higher than that caused by CsA when basophils were activated by Der p I (80.0 +/- 3.6 vs 49.5 +/- 4.7%; p less than 0.001) and anti-IgE (90.4 +/- 1.8 vs 62.3 +/- 2.9%; p less than 0.001). FK-506 had little or no effect on the release of histamine caused by f-met peptide, phorbol myristate (12-tetradecanoyloxy-13-acetoxy-phorbol), and bryostatin 1. RAP (30 to 1000 nM) selectively inhibited only IgE-mediated histamine release from basophils, although it had no effect on mediator release caused by f-met peptide, A23187, 12-tetradecanoyloxy-13-acetoxy-phorbol, and bryostatin 1. FK-506 also inhibited the de novo synthesis of sulfidopeptide leukotriene C4 from basophils challenged with anti-IgE. Low concentrations of FK-506 and CsA synergistically inhibited the release of mediators from basophils induced by anti-IgE or compound A23187. IL-3 (3 and 10 ng/ml), but not IL-1 beta (10 and 100 ng/ml), reversed the inhibitory effect of both FK-506 and CsA on basophils challenged with anti-IgE or A23187. RAP was a competitive antagonist of the inhibitory effect of FK-506 on A23187-induced histamine release from basophils with a dissociation constant of about 30 nM. In contrast, RAP did not modify the inhibitory effect of CsA on A23187-induced histamine release. These data indicate that FK-506 is a potent antiinflammatory agent that acts on human basophils presumably by binding to a receptor site (i.e., FK-506 binding protein).

Anti-Bacterial Agents↗

PubMed1990

[The effects of incremental PEEP on atrial natriuretic peptide, right atrial pressure and the size of the right atrium in anesthetized patients].

8 ASA class II-III patients (50-67 years) undergoing traumatic-surgical procedures were studied. Since the release of atrial natriuretic peptide (ANP) is stimulated by volume loading and increased right atrial pressure (RAP), the effects of incremental positive end-expiratory pressure (PEEP) on ANP-concentration, RAP and right atrial dimensions were investigated. Anaesthesia was induced with intravenous etomidate and vecuronium and maintained after endotracheal intubation with 66% N2O in O2 and ethrane (0.4-0.6 Vol.-%). A catheter was inserted into the A. radialis for blood sampling and determination of mean arterial pressure (MAP). For determining endsystolic (RAESA) and end-diastolic (RAEDA) areas of the right atrium a 5 MHz transoesophageal echocardiographic (TEE)-probe was positioned at the level of the foramen ovale. Under TEE-control a catheter was placed into the right atrium for measurement of RAP. The method for ANP determination was based on a direct radioimmunoassay that is specific for human ANP (ANP-J125). PEEP was incrementally raised from 0 to 16 mbar in 4 mbar steps each for 5 min and thereafter reduced to 0 mbar. During the investigation no significant differences were detectable for MAP, heart rate, end-expiratory CO2 partial pressure and the arterial O2 saturation. However, 16 mbar PEEP ventilation increased plasma ANP concentrations (from 44.3 +/- 9.7 to 58.1 +/- 8.7 pg/ml) and RAP (from 4.4 +/- 0.9 to 10.7 +/- 0.9 mmHg) whereas the right atrial dimensions RAESA (from 9.4 +/- 1.0 to 4.6 +/- 0.6 cm2) and RAEDA (from 5.9 +/- 1.2 to 3.2 +/- 0.4 cm2) decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1990

[Hemodynamic impact of pressotherapy].

We study the hemodynamic effects of pressotherapy in 11 patients (mean age : 68 +/- 10 years) with uncomplicated acute myocardial infarction (n = 6) or with chronic ischemic heart failure (n = 5). We measure the right auricular pressure (RAP), the mean pulmonary arterial pressure (MPAP) and the pulmonary wedge pressure (PWP), before, during pressotherapy (MPAP) and the pulmonary wedge pressure (PWP), before, during pressotherapy (T 20 min) and 30 minutes after the end of pressotherapy (T 30 min). We use five-chambered leg garments with 80 mm Hg pressure during 20 minutes. The wavelike action (from the bottom to the top) is intermittent: the compression time is 10 second (sec); compression is maintained during 60 sec; deflation time is 15 sec. After 20 minutes pressotherapy (t 20) the 3 variables increase: RAP: from 3.6 +/- 5 to 7 +/- 7 mm Hg (P less than 0.001), MPAP: from 25 +/- 14 to 29 +/- 17 mm Hg (p less than 0.01) and the PWP from 10 +/- 8 to 17 +/- 11 Hg (p less than 0.01). This rise is particularly important in heart failure patients: from 18 +/- 8 to 29 +/- 8 mm Hg for the PWP, with cough in one patient. At T 30 these 3 variables decrease and return nearly to initial values: respectively 2.7 +/- 4.7 (RAP), 24 +/- 14 (MPAP), 12 +/- 8 mm Hg (PWP). In conclusion pressotherapy increases RAP and pulmonary pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1989

Comparative immunohistochemical reactivity of monoclonal and polyclonal antibodies to H-ras p21 in normal and neoplastic tissues of rodents and humans.

Five mouse monoclonal antibodies (mES 2, 4, 8, 13 and 20) produced against bacterially expressed BALB ras p21 and five other monoclonal or polyclonal antibodies (Cetus rabbit or mouse pan p21, RAP-5, Triton Ha-ras, Y13-259) to H-ras p21 were used for comparative immunohistochemical detection of H-ras p21 by the avidin biotin peroxidase-complex technique in selected normal fixed tissues and tumors from rats, mice, and humans. Nine of these antibodies were immunoreactive with cell membranes and cytoplasm of harvey sarcoma virus-induced sarcoma cells, but usually only with Bouin's fixed tumors. A few normal tissues were immunoreactive with some of the antibodies except for many immunoreactive tissues found with mES 13. Although mES 13 stained sarcoma cells on the cell membrane, a prominent granular staining, which appeared to be mitochondrial or lysosomal, was seen in many normal and neoplastic rodent tissues and in normal human colon, colon polyps, and carcinomas. Interpretation of positive immunoreactivity with any antibody was sometimes difficult due to nonspecific (background) staining. The cellular pattern of specific reactivity (membrane or granular) and inhibition of immunoreactivity by absorption of the antisera with H-ras p21 was therefore important. Western blots with BALB transforming (Lys 12) p21 expressed in E. coli revealed reactivity of all antibodies except for RAP-5. In addition, immunoblots of solubilized proteins from the EJ cell line with RAP-5 indicated reactivity of this monoclonal antibody with proteins of several different molecular weights. RAP-5 also never specifically immunoreacted with cell membranes of normal or malignant cells including EJ cells. Interpretation of these findings in comparison with those in published reports of H-ras p21 localization in fixed tissue sections is discussed, including the importance of fixative, specific antibody and controls.

Animals↗

PubMed1983

Rhythmic afterpotentials in relation to pre-stimulus barbiturate spindle-like activity. Macro- and microelectrode investigations.

It was proposed that the two types of rhythmic afterreactions (RARs) in the somatosensory cortex following forepaw electrical stimulation, i.e. the classical rhythmic afterpotential (RAP) with monophasic waves progressively decreasing in amplitude and the spindle-like afterpotential (SRAP) composed of waxing and waning phase like the spontaneous spindle (SS) were different electrocortical evoked rhythms. The hypothesis that not the RAP, but the SRAP is a SS elicited by stimulation was tested in the present study investigating the relationships between the SS and the two types of RAR by means of macro- and microelectrode recordings. It was shown that the RAP appeared during the SS, while the development of the SRAP was prevented by the SS. The data obtained from the microelectrodes experiments showed that the larger part of the neurons studied discharged in phase both with the waves of the SS and of SRAP (but not of RAP) having an almost one and the same rhythm, supported also the hypothesis for a common pacemaker of the rhythms of the SS and the SRAP.

Animals↗

PubMed1994

Quantitative and temporal analysis of the cellular interaction of FK-506 and rapamycin in T-lymphocytes.

The structurally related immunosuppressive macrolides FK-506 and rapamycin (RAP) exert distinct biological effects: inhibition of interleukin-2 production and inhibition of interleukin-2-induced proliferation, respectively, through binding to intracellular receptors, termed FKBPs. Although the interaction of these drugs with purified FKBPs in vitro has been well characterized, little is known about their interaction with FKBPs in living cells. Here, we used [3H]-dihydro-FK-506 as a probe to examine the binding of these macrolides in both normal mouse splenic T-cells and the human Jurkat T-cell lymphoma. These cells were found to accumulate the radioligand, predominantly in the cytosol, to a saturable level corresponding to an estimated concentration of 6 to 7 microM. Half-maximal suppression of T-cell activation was shown to require radioligand occupancy of only 3 to 5% of the pool of available intracellular binding sites (FKBPs). Moreover, the binding and immunosuppressive effect of the radioligand could not be removed by extensive washing and remained stable for at least 6 hr upon incubation of the cells at 37 degrees C. However, a molar excess of either FK-506 or RAP was found to rapidly displace [3H]-dihydro-FK-506 from its cellular binding sites. Consistently, FK-506 and RAP were able to antagonize mutually their immunosuppressive activities even when added several hr after each other to T-cell cultures. We took advantage of the reciprocal antagonism of FK-506 and RAP to define their apparent affinities for the functionally relevant cellular receptors by Schild analysis. This indicated that the drugs compete for a single cellular receptor with similar KdS and, therefore, may mediate their immunosuppressive action upon interaction with similar or highly related FKBPs.

Animals↗

PubMed1994

[Hemodynamic evaluation during isotonic exercise of patients with orthotopic heart transplantation].

PURPOSE: To evaluate the hemodynamic response of patients submitted to orthotopic heart transplantation during progressive isotonic exercise. METHODS: Eight patients who underwent orthotopic heart transplantation have been evaluated through invasive hemodynamic study during isotonic exercise. The mean right atrial pressure (RAP), pulmonary artery pressure (PAP), pulmonary artery wedge pressure (PAWP), arterial blood pressure (ABP), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), heart rate (HR) and cardiac output (CO) have been determined in three distinct situations: at rest in the supine position (R), at rest with the legs up (RU) and during progressive isotonic exercise (E). The hemodynamic results at rest have been compared to the ones before transplantation. Phase RU and E results have been compared with each other. RESULTS: Comparing to the phase before transplantation at the R phase we found normalization of mean PAP (34.9 +/- 14.0 to 17.0 +/- 3.5 mmHg), RAP (7.3 +/- 4.3 to 2.9 +/- 1.9 mmHg) and CO (2.9 +/- 0.98 to 5.7 +/- 0.99 l/min), otherwise there was an increase in HR (89 +/- 15 to 94 +/- 13 bpm) mean ABP (84 +/- 25 to 115 +/- 12 mmH) and SVR (30 +/- 15 to 22 +/- 7 units Wood), (p < 0.05). Comparing phase E to phase RU, there was a significant increase in RAP (3.1 +/- 1.8 to 9.4 +/- 3.9 mmHg), mean PAP (21.0 +/- 2.8 to 37.0 +/- 10.0 mmHg), PAWP (8.1 +/- 2.1 to 15.0 +/- 5.8 mmHg), CO (5.8 +/- 0.8 to 9.9 +/- 2.4 l/min), HR (93 +/- 8 to 116 +/- 18 bpm) and a decrease in SVR (22.0 +/- 3.0 to 13.3 +/- 3.8 units Wood), (p < 0.05), otherwise there was no statistically significant modifications in PVR (2.2 +/- 0.7 to 2.3 +/- 1.2 units Wood) and mean ABP (129 +/- 12 to 129 +/- 15 mmHg), (p = NS). CONCLUSION: Patients submitted to heart transplantation may improve cardiac output mainly from increasing in stroke volume, associated with an increase in RAP and PAP. Nevertheless, the improvement increase in CO is compatible to exercise capacity after heart transplantation.

Adult↗

PubMed1993

Characterization of a third ras gene, rasB, that is expressed throughout the growth and development of Dictyostelium discoideum.

Previous reports have indicated that the cellular slime mold Dictyostelium discoideum possesses two ras genes (rasG and rasD) and one rap gene (rap1). All three genes are developmentally regulated, with each showing a different pattern of transcription during the Dictyostelium life cycle. To establish whether there are additional ras or rap genes in Dictyostelium, we used degenerate oligonucleotide primers to the highly conserved GTP-binding domains and both ras- and rap-unique sequences to amplify products from cDNA using the polymerase chain reaction (PCR). No additional rap genes were amplified, but a fragment whose nucleotide sequence predicted a novel ras gene was isolated. Using this PCR product as a probe, a full-length cDNA clone was isolated and sequenced. Its deduced amino acid sequence predicted a 197 amino acid protein that is 71% and 68% identical to RasG and RasD respectively. The new ras gene contains the conserved Ras-specific effector domain, the conserved binding site for the Ras-specific Y13-259 monoclonal antibody, and shows greater sequence similarity to the human H-Ras protein than to any other mammalian Ras protein. In view of this high level of identity to the ras gene subfamily, we have designated this gene rasB. Northern blot analysis has shown that rasB is developmentally regulated with maximum levels of a single 950-bp message detected during vegetative growth and the first 8 h of development.

Amino Acid Sequence↗

PubMed1996

Induction of Heymann nephritis with a gp330/megalin fusion protein.

There is considerable evidence that glomerular deposits in Heymann nephritis, a rat model of membranous nephritis, result from shedding of immune complexes formed on podocytes and that the principal antigen is part of the extracellular domain of a cell surface glycoprotein receptor called gp330 or megalin. It has also been reported that the immunogen that induces Heymann nephritis is a complex formed between gp330 and the receptor-associated protein RAP. The recent elucidation of the primary structure of gp330 makes it possible to investigate the ability of defined portions of gp330, devoid of RAP, to induce Heymann nephritis. In the present study we show that a gp330-glutathione-S-transferase fusion protein, containing 137 amino acid residues (1114 to 1250) of the ectodomain, induces active Heymann nephritis and that heterologous antibodies against this fusion protein produce passive Heymann nephritis. By immunofluorescence, typical glomerular immunoglobulin deposits were found, but complement components were lacking and the rats did not develop proteinuria. In the active model, we obtained evidence indicating that the deposits contained portions of the ectodomain of gp330, including regions other than those of the fusion protein. Thus, the deposits were stained by polyclonal antibodies to gp330 and to the gp330 fusion protein, as well as by two monoclonal antibodies reactive with portions of the ectodomain of gp330, only one of which reacted with the fusion protein in vitro. Antibodies against the cytoplasmic domain of gp330 did not stain. Furthermore, we found that RAP was able to bind to gp330 in the glomerular deposits but not to the gp330 fusion protein in vitro. The results show that the region of gp330 spanning amino acid residues 1114 to 1250 contains peptides capable of inducing pathogenic antibodies of Heymann nephritis without a contributory role of RAP.

Amino Acids↗

PubMed1997

Perioperative morbidity and mortality in combined aortic and mitral valve surgery.

BACKGROUND AND AIMS OF THE STUDY: Despite many significant improvements in cardiac surgical technique, the operative risk for combined aortic and mitral valve surgery remains between 5% and 12%. Identification of high-risk patients will allow surgeons to develop strategies to improve these results. METHODS: The 30-day postoperative mortality and complication rates were analyzed in a group of 206 patients operated on over a 16-year period with cold crystalloid cardioplegia. Thirty-three possible risk factors for death and low output syndrome (LOS) were entered into univariate and multivariate logistic regression analysis. RESULTS: There were 10 perioperative deaths (4.9%). Major complications occurred in 38 patients (18.4%), 19 with LOS. On univariate analysis, right atrial pressure (RAP) > or = 8 mmHg (p = 0.001), aortic stenosis (p = 0.009) and systolic pulmonary artery pressure > or = 60 mmHg (p = 0.095) were found to be risk factors for death, as were RAP > or = 8 mmHg (p = 0.001), previous heart surgery (p = 0.007), serum creatinine > or = 120 mumol/l (p = 0.03), tricuspid valve disease (p = 0.038) and aortic stenosis (p = 0.09) for LOS. On multivariate analysis, RAP > or = 8 mmHg (p < 0.001) and aortic stenosis (p = 0.002) were identified as independent risk factors for death, as were RAP > or = 8 mmHg (p = 0.001) and previous heart surgery (p = 0.008) for LOS. CONCLUSIONS: Mitro-aortic valve surgery involves complex procedures with substantial mortality and morbidity. The risk factors point toward the importance of operating before the stage of advanced heart failure and toward the key role of better myocardial protection techniques in these compromised hearts with limited reserves.

Adolescent↗

PubMed1997

LDL receptor family-dependent and -independent pathways for the internalization and digestion of lipoprotein lipase-associated beta-VLDL by rat vascular smooth muscle cells.

Lipoprotein lipase (LPL) promotes the binding and internalization of beta-VLDL (very low density lipoprotein) by many cell types. We examined the function of receptors in the LDL receptor family (LRF) and heparan sulfate proteoglycans (HSPG) in the metabolism of LPL-associated beta-VLDLa by rat vascular smooth muscle cells (VSMCs) in culture. These cells express LDL receptor-related protein and the VLDL receptor, but not the LDL receptor. LPL greatly increased the binding of 125I-labeled beta-VLDL to VSMCs at 4 degrees C. Binding was almost entirely inhibited by heparin, but essentially unaffected by the potent LRF-antagonist, receptor-associated protein (RAP), indicating that LRFs do not contribute significantly to the VSMC binding capacity for LPL-associated beta-VLDL. At 37 degrees C, RAP inhibited the rapid internalization of LPL-associated 125I-labeled beta-VLDL and the digestion of the beta-VLDL into trichloroacetic acid soluble radioactivity; these processes still occurred, but at a decreased rate. RAP did not inhibit the ability of beta-VLDL-LPL complex to stimulate VSMC ACAT activity. Furthermore, in Oil red-O histochemistry experiments, which model foam cell transformation in vitro, RAP paradoxically increased cholesteryl ester storage in VSMCs treated with beta-VLDL and LPL under specific cell culture conditions. These results support a model in which the internalization of LPL-associated beta-VLDL by VSMCs is mediated by two pathways, one involving LRFs and a second that is independent of LRFs, probably involving direct uptake by HSPG. The LRF-dependent pathway leads to less cellular storage of cholesteryl ester and thus may be antiatherogenic under certain conditions.

Animals↗

PubMedDate not supplied

Twenty years of consulting for excellence: the Residency Assistance Program.

BACKGROUND AND OBJECTIVES: The Residency Assistance Program (RAP) in family practice was established in 1975 to provide consultative assistance to family practice residency program directors interested in enhancing the quality of their training programs. Since its inception, RAP activities have been monitored and policies approved by a project board, with representation from all the national family medicine/practice organizations. The voluntary, confidential, nonpunitive, collaborative problem-solving process has provided more than 800 RAP consultations in RAP's 20 years of operation. This paper reviews the historical development, current status, and future directions of the program.

Consultants↗

PubMed1996

Ras/Rap effector specificity determined by charge reversal.

Members of the Ras subfamily of small GTP-binding proteins have been shown to be promiscuous towards a variety of putative effector molecules such as the protein kinase c-Raf and the Ral-specific guanine nucleotide exchange factor (Ral-GEF). To address the question of specificity of interactions we have introduced the mutations E30D and K31E into Rap and show biochemically, by X-ray structure analysis and by transfection in vivo that the identical core effector region of Ras and Rap (residues 32-40) is responsible for molecular recognition, but that residues outside this region are responsible for the specificity of the interaction. The major determinant for the switch in specificity is the opposite charge of residue 31--Lys in Rap, Glu in Ras--which creates a favourable complementary interface for the Ras-Raf interaction.

Amino Acid Sequence↗