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Biomedical subjects

N Keller

Publications and source records attributed to N Keller.

At least 109 records · Page 6Linked to original sources

Atrial natriuretic factor and central venous pressure during intermittent and continuous lower-body positive pressure in healthy humans.

In eight healthy volunteers undergoing 16 experiments in a cross-over design central venous pressure (CVP) and atrial natriuretic factor (ANF) in central venous plasma were measured during a 30 min control period followed by three separated periods of 10 min lower-body positive pressure (LBPP) or 90 min continuous LBPP induced by inflation of a military anti-G suit to evaluate the effect of short repeated and of extended increases in right atrial pressure on plasma ANF levels. CVP increased significantly during each of three separate periods of intermittent LBPP, and 15 min after application of continuous LBPP (P less than 0.025 for all). Blood pressure and heart rate did not change. During intermittent LBPP plasma ANF levels increased 10 min after the first inflation of the MAGT-suit (P = 0.013), but not after the second or third inflation. During continuous LBPP plasma ANF remained unchanged until 90 min after application of LBPP where a significant rise was observed (P = 0.023). The data demonstrate that the ANF response to short-term increases in right atrial pressure, as small as 2.5 mmHg, is maximal within 10 min and that repeated pressure stimuli may decrease ANF release. Sustained increases in right atrial pressure are not associated with increases in plasma ANF until long after initiation of the pressure stimulus suggesting rapid receptor-binding of ANF and that the ANF receptors might be saturated during continuously elevated ANF levels.

Adult↗

Enhanced phagocytosis of encapsulated Escherichia coli strains after exposure to sub-MICs of antibiotics is correlated to changes of the bacterial cell surface.

The influence of five antibiotics (netilmicin, ceftriaxone, cefepime, fleroxacin, and ciprofloxacin) on capsular polysaccharide distribution and on opsonophagocytosis by human polymorphonuclear leukocytes of unencapsulated and encapsulated Escherichia coli strains was studied. Unencapsulated E. coli strains were readily opsonized in serum and easily ingested by polymorphonuclear leukocytes, and antibiotics did not further enhance the phagocytosis rates. In contrast, encapsulated bacteria were poorly opsonized in human serum, and phagocytosis was enhanced after overnight exposure to 0.5x the MICs of the antibiotics, with the exception of cefepime. Incubation of unencapsulated as well as encapsulated bacteria in complement-inactivated serum markedly reduced the bacterial uptake by polymorphonuclear leukocytes regardless of the presence of antibiotics. Slide agglutination assays, performed either with a monoclonal antibody for capsular polysaccharide or with an antiserum raised against the stable unencapsulated mutant E. coli O7:K-, showed reduction but not lack of the capsular polysaccharide of encapsulated E. coli O7:K1, and better exposure of subcapsular epitopes, after incubation with 0.5x the MICs of antibiotics. Flow cytometric analysis of encapsulated E. coli exposed to netilmicin, ciprofloxacin, and fleroxacin revealed that the reduction in capsular material was homogeneous among the bacterial population. Treatment with cefepime and ceftriaxone induced two populations of bacteria that differed in the amount of K antigen present. These results indicate that sub-MICs of netilmicin, ceftriaxone, fleroxacin, and ciprofloxacin influenced complement-mediated opsonization, probably due to changes in the capsular polysaccharide structure.

Agglutination Tests↗

Double-blind comparison of tiapamil and atenolol in patients with mild to moderate hypertension: a multicenter trial.

The efficacy and safety of tiapamil, a new calcium-channel blocker, was compared with the cardio-selective beta-blocker atenolol in a 16-week double-blind, multicenter trial with an initial 4-week placebo run-in period. Eighty-one outpatients with WHO stage I or II hypertension, 55 men and 26 women, entered the study. There was a total of nine drop-outs, six in the tiapamil group and three in the atenolol group. Five were due to side effects (four in the tiapamil group and one in the atenolol group). Sixty-one patients performed a graded exercise test sitting on a ergometer bicycle before and after completion of the therapy. Patients eligible for the study after the placebo period received either tiapamil 450 mg b.i.d. or atenolol 100 mg daily. Both drugs lowered systolic and diastolic blood pressure significantly. After 12 weeks of therapy, supine blood pressure in the tiapamil group fell from 167/104 mmHg to 154/91 mmHg (p less than 0.005), and in the atenolol group from 166/102 mmHg to 151/89 mmHg (p less than 0.005). A satisfactory reduction in diastolic blood pressure, defined as a reduction of more than 10 mmHg and/or values below or equal to 90 mmHg at the end of the study, was achieved in 29 of 35 patients in the tiapamil group and in 27 of 37 in the atenolol group. No changes in heart rate were observed in the tiapamil group, whereas there was a significant fall in heart rate in the atenolol group. The maximal exercise workload tolerated increased equally in both groups, from 135 to 147 watts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Characterized and predictable rabbit uveitis model for antiinflammatory drug screening.

A model has been developed for the screening of antiinflammatory ophthalmic drugs in rabbits. This simple and rapid method is reproducible and uses fewer animals than do some other methods. Rabbits are sensitized to bovine serum proteins, then challenged intravitreally to induce a uveitis. The basis of the inflammatory response is shown to be due primarily to an immunologic mechanism. At 24 hr postchallenge, animals are sorted into treatment groups of approximately equal "titer" as defined by the slit lamp examination iris score which measures the magnitude of the immunologic response. Topical ocular treatment (control or drug) is then initiated and continued for a total of four days. Iris inflammation is evaluated by daily slit lamp exams. Results indicate that this model has statistically narrower frequency distribution of iris ratings than another published method, and is faster than other equally accurate and precise methods that depend upon blood antibody titer to sort animals.

Administration, Topical↗

The influence of subminimal inhibitory concentrations of netilmicin and ceftriaxone on the interaction of Escherichia coli with host defences.

The effect of sub-MICs of netilmicin and ceftriaxone on the interaction between encapsulated and unencapsulated strains of Escherichia coli and certain host defence mechanisms, i.e. complement activation, opsonization, phagocytosis by human polymorphonuclear leucocytes (PMN), and serum bactericidal activity have been studied. Experiments were carried out testing antibiotics either alone or in combination. Non-capsulated strains of E. coli activated complement rapidly and were easily phagocytosed and killed after opsonization in human pooled serum. Pretreatment of these strains with sub-MICs of antibiotics did not change the rate of opsonization or the degree of uptake by PMN, but did enhance serum sensitivity. Capsulated strains of E. coli were both poorly opsonized and resistant to serum bactericidal activity. Treatment of these strains with sub-MICs of antibiotics enhanced complement consumption as well as phagocytosis by PMN, but did not affect serum-resistance.

Blood Bactericidal Activity↗

Determinants of atrial natriuretic factor levels in coronary heart disease: significance of central pressures, heart chamber volumes and left ventricular mass.

Atrial natriuretic factor (ANF) was determined in pulmonary and systemic arterial plasma during diagnostic left and right heart catheterization in twenty-three patients. In twenty of these patients ANF was subsequently measured in systemic arterial plasma during nuclear magnetic resonance (NMR) imaging of the heart with computation of left heart chamber volumes and left ventricular mass. Left ventricular end-diastolic pressure was the strongest independent predictor of pulmonary arterial plasma ANF, whereas cardiac index best predicted aortic plasma ANF. Both pulmonary and aortic plasma ANF correlated with systolic and diastolic pulmonary arterial pressure, left ventricular end-diastolic pressure and cardiac index. Left atrial volume index and left ventricular mass index did not correlate with systemic arterial plasma ANF whereas a positive linear correlation between left ventricular end-diastolic volume index and ANF could be demonstrated (r = 0.61, P less than 0.01). Left ventricular end-diastolic volume index was the most important independent predictor of systemic arterial plasma ANF. Systemic arterial plasma ANF might be a simple marker of left ventricular dilatation in patients with heart disease.

Adult↗

Atrial natriuretic factor during exercise in male endurance athletes: effect of training.

Nine male endurance runners were evaluated with bicycle exercise testing before a training break of 3 weeks duration, and 0, 2 and 4 weeks after resumption of training to assess the effects of training on resting and exercise plasma atrial natriuretic factor (ANF) measured at 50% and 100% of predetermined maximal workload. Maximal oxygen uptake and lean body mass (LBM) were calculated at each time point. Maximal oxygen uptake decreased during training break, but rose 4 weeks after resumption of training (P less than 0.01). LBM was unchanged after inactivity, but rose after resumption of training (P less than 0.01). Plasma ANF at rest did not change throughout the experiment. ANF levels rose after training break at maximal workload (P less than 0.05), and decreased 4 weeks after resumption of training, but only at submaximal workload (P less than 0.05). No correlations between systolic blood pressure, mean blood pressure or heart rate and ANF could be demonstrated. These results indicate that the haemodynamic changes associated with endurance training are reflected in plasma ANF levels during exercise, but not at rest. The full adaptation of ANF release to training probably requires more time than the 4 weeks reported for the haemodynamic adjustments.

Adult↗

The influence of cefepime on opsonophagocytosis of bacteria.

The effect of subminimal inhibitory concentrations (sub-MICs) of a semi-synthetic beta-lactam antibiotic, cefepime (BMY 28142), was studied on the opsonophagocytosis by human polymorphonuclear leukocytes (PNMs) of strains of Escherichia coli, Klebsiella oxytoca and Staphylococcus aureus. Cefepime-treated Gram-negative bacteria were not better phagocytosed by PMNs; however the uptake of one of three S. aureus strains was enhanced. The effect of cefepime on the uptake of strains of E. coli was compared to that of two other beta-lactam antibiotics, mecillinam and ceftriaxone. Exposure of E. coli to sub-MICs of mecillinam and ceftriaxone enhanced phagocytosis by PMNs.

Amdinocillin↗

Atrial natriuretic peptide during exercise in patients with coronary heart disease before and after single dose atenolol and acebutolol.

Plasma atrial natriuretic peptide (ANP) was measured during dynamic exercise in 10 patients with coronary heart disease before and after single dose atenolol 50 mg and acebutolol 200 mg, respectively. Systolic blood pressure, heart rate and the rate-pressure product increased during exercise before and after beta-blockade, but levels were lower after beta-blockade. Plasma ANP levels at rest were unchanged after atenolol, but rose after acebutolol (p less than 0.01). During exercise plasma ANP increased significantly both before and after beta-blockade, but plasma ANP levels were higher after acebutolol at all workloads (p less than 0.05), whereas plasma ANP levels after atenolol were higher at 125 W exclusively (p less than 0.05). The augmented ANP levels during exercise after beta-blockade probably reflect catecholamine-stimulated ANP release, whereas the elevated plasma ANP levels after acebutolol at rest might be a beta-adrenoceptor-mediated ANP release due to the intrinsic sympathomimetic effect of acebutolol.

Acebutolol↗

Changes in atrial natriuretic factor during preload reduction with nitroglycerin in patients with congestive heart failure.

Nine patients with congestive heart failure, New York Heart Association class II-III, were evaluated with right heart catheterization. Plasma atrial natriuretic factor (ANF) was determined in blood samples from the pulmonary artery simultaneously with recordings of right atrial, pulmonary arterial, pulmonary capillary wedge and systemic arterial pressures and heart rate during preload reduction with 0.5 mg nitroglycerin sublingually. Basal plasma ANF levels were higher in patients with congestive heart failure compared to normal controls, and correlated to right atrial, pulmonary arterial, and pulmonary capillary wedge pressures. After nitroglycerin all patients had reductions in right atrial, pulmonary arterial, and pulmonary capillary wedge pressures and a simultaneous decrease in plasma ANF concentrations, reaching lowest values after 10 min. Central pressures and plasma ANF rose to baseline values within 30 min. After nitroglycerin plasma ANF concentrations correlated to pulmonary arterial and pulmonary capillary wedge pressures, while changes in plasma ANF correlated to changes in right atrial and pulmonary arterial pressures. These results provide further evidence that ANF is released by a pressure-sensitive mechanism and demonstrates that ANF secretion in relation to central pressure variations is preserved in patients with congestive heart failure and that the response is rapid.

Adult↗

Atrial natriuretic factor during exercise in patients with congestive heart failure.

In order to evaluate the potential relationship between atrial pressure development and release of atrial natriuretic factor (ANF), 33 patients with congestive heart failure were investigated with right-sided heart catheterization during supine graded bicycle exercise. Resting plasma ANF levels were higher in patients with heart failure as compared with normal controls, 75.1 +/- 45.6 pmol/l vs 12.3 +/- 6.2 pmol/l (mean +/- SD, N = 33 and N = 42, respectively) and correlated with right atrial, pulmonary arterial and pulmonary capillary wedge pressures. During exercise, central pressures rose steeply with a simultaneous increase in plasma ANF in all patients. Plasma ANF levels correlated with heart rate at a workload of 25 w, to pulmonary arterial and pulmonary capillary wedge pressure at 50 w, and to pulmonary capillary wedge pressure at 75 w. The increments in ANF levels between the different workloads during exercise did not correlate with the corresponding increments in pressure values. In congestive heart failure, the capability of ANF secretion in consequence to pressure stimuli is preserved, and left atrial pressure seems to be the major stimulus for ANF release during exercise.

Adult↗

[Tissue colonization of expanded polytetrafluoroethylene in healthy cornea in the view of its use as a support in keratoprosthesis].

The biocompatibility of polytetrafluoroethylene (E. PTFE) keratoprosthetic skirts was studied for periods of observation from 4 to 14 weeks. In a first experimental study, the authors showed that E. PTFE was well tolerated but without fibrovascular ingrowth. In this study, eight perforating keratoplasties were performed and a disk of E. PTFE with a diameter of 4.5 mm was sutured in and covered with a conjunctival flap. The results show that E. PTFE allows fibrovascular ingrowth without a significant foreign body response or encapsulation. Coverage of E. PTFE with conjunctival was essential for fibrovascular ingrowth and to prevent extrusion and rejection.

Animals↗

Enzyme-linked immunosorbent assay of CA-125 in serum of patients with endometriosis: efficacy in diagnosis.

We used an enzyme-linked immunosorbent assay to quantify CA-125, a cancer antigen, in serum of patients with endometriosis. Concentrations of CA-125 in 103 patients with untreated endometriosis significantly (P less than 0.005) exceeded those for 31 controls with no evidence of disease: 9.1 (SD 12.3) vs 2.2 (SD 3.2) arb. units/mL. Values for patients with treated endometriosis were lower (2.3, SD 2.6, arb. units/mL, n = 9) than those for patients with untreated endometriosis. The mean concentrations of CA-125 in different stages of untreated endometriosis were 4.8 (SD 4.5), 7.1 (SD 9.9), 9.8 (SD 13.2), and 10.8 (SD 13.0) arb. units/mL for Stages I, II, III, and IV, respectively. The differences between controls and each stage were statistically significant (for all stages: P less than 0.05). We also assayed serum sampled from controls and patients with untreated endometriosis during menstruation (Group A) and during nonmenstruation (Group B). The efficacy of the present assay for concentrations of CA-125 in serum of patients with endometriosis was greater for Group B than for Group A. Evidently, determination of CA-125 in serum by the present assay may assist in such diagnosis.

Adult↗