Biomedical subjects

R Ritz

Publications and source records attributed to R Ritz.

At least 37 records · Page 2Linked to original sources

PubMed1997

Treatment with N-acetylcysteine during acute respiratory distress syndrome: a randomized, double-blind, placebo-controlled clinical study.

PURPOSE: Intravenous N-acetylcysteine (NAC) has been reported to improve systemic oxygenation and reduce the need for ventilatory support in patients with an acute lung injury. In the more serious form, namely established adult respiratory distress syndrome (ARDS) (PaO2/FIO2 < or = 200 mm Hg), we tested the hypothesis that treatment with intravenous NAC may be beneficial. MATERIALS AND METHODS: Respiratory dysfunction was graded daily according to the need for mechanical ventilation and FIO2 and to the evolution of the lung injury score (LIS) and the PaO2/FIO2 ratio in 42 patients with established ARDS receiving either NAC 190 mg/kg/day or placebo as a continuous intravenous infusion over the first 3 days of their clinical course. RESULTS: NAC and placebo groups (22 and 20 patients, respectively) were comparable for demographic characteristics, ARDS categories, severity of illness (simplified acute physiology score [SAPS II]) LIS and PaO2/FIO2 ratio. Mortality rate was 32% for the NAC and 25% for the placebo group (difference not significant). At admission (day 1), 91% of patients in the NAC and 95% in the placebo group required ventilatory support; at days 2, 3, 5, and 7 after admission, the percentage of patients receiving ventilatory support was not significantly reduced for both groups in comparison with day 1. Moreover, there were no differences between the two groups at the same observation days. In both groups, the FIO2 was significantly lower and the PaO2/FIO2 ratio was significantly higher than the initial values during the evolution (FiO2 at day 3, P < .01 for NAC and P < .05 for placebo; PaO2/FIO2 at day 3: P < .01 for NAC and P < .02 for placebo), but this improvement was similar for both groups and, moreover, the between-group comparison was never significantly different at the various collection days. The LIS decreased significantly in NAC group between days 1 and 3 (2.23 +/- 0.62 v 1.76 +/- 0.17; P < .05), whereas no changes were observed in the placebo group; at day 5, there was a significant difference between the two groups (1.53 +/- 0.21 for the NAC v 2.15 +/- 0.19 for the placebo group; P < .05). In the prevalent sepsis category (10 patients in the NAC and 9 in the placebo group), the mortality rate, the need of ventilatory support, the intensive care unit stay, and the PaO2/FIO2 evolution did not differ significantly in both subgroups. CONCLUSIONS: In this relatively small group of patients presenting with an established ARDS subsequent to a variety of underlying diseases, intravenous NAC treatment during 72 hours neither improved systemic oxygenation nor reduced the need for ventilatory support.

Acetylcysteine↗

PubMed1997

Synchronous oscillatory activity in sensory systems: new vistas on mechanisms.

The origin and nature, as well as the functional role, of synchronous oscillatory activity in the cortex are among the major unresolved issues in systems neurobiology. Recent advances in understanding the mechanisms underlying oscillations include the description of intrinsically bursting pyramidal cells in striate cortex in vivo and the discovery of inhibitory interneurons that fire spike doublets to induce synchrony. The behavioral consequences of coordinated activity in cortical neurons remain poorly understood.

Animals↗

PubMed1997

Assessment of errors when expiratory condensate PCO2 is used as a proxy for mixed expired PCO2 during mechanical ventilation.

OBJECTIVES: We designed a series of experiments to determine whether expiratory water condensate (PconCO2) can be used as a proxy for mixed expired gas collection. METHODS: In 18 adult mechanically ventilated patients with ARDS (40 samples), simultaneous collections of arterial blood, expiratory water trap condensate, mixed expired gas, and minute ventilation were used to calculate VCO2 and VD/VT. To assess the effect of temperature, a constant gas flow (PCO2 10-30 mm Hg) was bubbled through water at temperatures of 19.5-37 degrees C. Gas and water samples were collected, immediately analyzed for PCO2, and a temperature correction factor was calculated. A lung model was constructed using a 5 L anesthesia bag connected to a mechanical ventilator with a heated humidifier. Temperature at the Y-piece was set to approximately 37 degrees C and CO2 was injected into the bag to establish an end-tidal PCO2 of 20-70 mm Hg. After equilibration, condensate was collected, PCO2 was measured, and the temperature-corrected PCO2 was compared to PECO2. The capnogram at points along the expiratory limb circuit was used to evaluate gas mixing. RESULTS: There was an over-estimation of PECO2 by PconCO2 (p < 0.001) for the patient data, resulting in an underestimation of VD/VT (p < 0.001) and an overestimation of VCO2 (p < 0.001). The temperature correction factor for PCO2 in water was -0.010 (about half of the factor used for whole blood). The bias between temperature-corrected PconCO2 and PECO2 was 0.3 +/- 3.2 mm Hg in the lung model. Mixing in the expiratory limb was poor, as evaluated by the capnogram. CONCLUSIONS: Even with temperature correction, we failed to precisely predict PECO2 from PconCO2. For measurement of VD/VT and VCO2, we do not recommend methods that use PconCO2.

Adult↗

PubMed1997

Delivery systems for inhaled nitric oxide.

From a practical standpoint, technical issues related to NO delivery are as important as therapeutic issues. The benefits can be appreciated only if a reliable delivery system is used. Further, hazards and toxicity may be more problematic with an unreliable delivery system. It is incumbent on clinicians using inhaled NO to ensure that the delivery system is safe and reliable.

Administration, Inhalation↗

PubMed1996

[Clinico-pharmacological case (4). Epileptic seizure as an unwanted drug effect on theophylline poisoning].

In spite of the better understanding of the pharmacokinetics and optimized galenics of oral theophylline formulations, therapy with this bronchodilator still bears risks because of its narrow therapeutic window combined with substantial inter- and intra-individual variability of theophylline metabolism. In particular, the comedication with a variety of drugs inhibiting theophylline metabolism requires consideration as a potential source of toxicity. Besides mild, self-limited adverse effects, potentially life-threatening toxic manifestations such as ventricular tachyarrhythmias, shock, and seizures can occur especially with high plasma concentrations. We report the case of a 72-year-old patient with chronic obstructive pulmonary disease who was admitted for surgical treatment of an ulcer of the foot. During combined therapy with theophylline and ciprofloxacin he developed signs of theophylline toxicity with a single episode of partial seizures. These symptoms rapidly improved with repetitive application of activated charcoal and sorbitol. Clinically relevant drug-drug interactions with theophylline and the role and mechanism of action of activated charcoal in intoxicated patients are discussed.

Aged↗

PubMed1996

[Heparin-induced thrombopenia and thrombosis].

Heparin-induced thrombocytopenia (HIT) with thrombosis is a rare, but important complication of heparin therapy. We describe the case of a 53-year-old patient hospitalized with complicated pelvic fracture. Intravenous infusion of unfractionated heparin (15'000 IU/24 h) was given for thrombosis prevention. After 11 days' treatment the patient developed deep venous thrombosis of the left calf, complicated 2 days later by massive bilateral pulmonary embolism. Simultaneous with these thromboembolic events, thrombocytopenia, signs of activated coagulation, and antibodies to heparin occurred. In the context of this case the diagnostic and therapeutic possibilities of HIT, and in particular treatment with the heparinoid danaproid (Orgaran), are discussed.

Chondroitin Sulfates↗

PubMed1996

Vertical signal flow and oscillations in a three-layer model of the cortex.

A model of vertical signal flow across a layered cortical structure is presented and analyzed. Neurons communicate through spikes, which evoke an excitatory or inhibitory postsynaptic potential (spike response model). The layers incorporate two anatomical features-dendritic and axonal arborization patterns and distance-dependent time delays. The vertical signal flow through the network is discussed for various stimulus conditions using two different, but typical, axonal arborization patterns. We find stationary as well as oscillatory response, but the oscillatory response may be restricted to a single layer. Confronted with conflicting stimuli the network separates the patterns through phase-shifted oscillations. We also discuss two hypothetical animals, to be called "cat" and "mouse." These have different axonal arborizations, which give rise to a different oscillatory response (if any) of the various layers.

Axons↗

PubMed1996

Assessment of depth of midazolam sedation using objective parameters.

OBJECTIVE: To determine the relationship between the clinically evaluated depth of midazolam-induced sedation and the cardiac beat-to-beat variability (RR variability) in ICU patients in the intensive care unit (ICU). DESIGN: Prospective study. SETTING: ICU of a university hospital. PATIENTS: 20 consecutive patients studied during weaning from mechanical ventilation and withdrawal of midazolam-induced sedation. MEASUREMENTS AND RESULTS: After clinical evaluation of depth of sedation according to the Ramsay sedation score, the RR variability over 512 RR intervals and predominant respiratory rate were measured. The power spectrum of RR variability was calculated by a fast Fourier transformation and the resulting total frequency band (0.016-0.35 Hz) was subdivided into a very low, a low, and a high frequency band. Stepwise multiple regression analysis in the first 10 patients (group 1) showed a significant relationship between depth of sedation and measures of RR variability combined with respiratory rate (r2 = 0.59; F = 12.1; p < 0.001). The more effective sedation was, the more depressed were both RR variability and predominant respiratory rate. Mean heart rate, mean respiratory rate, median deviation of RR intervals from the mean, and the ratio between spectral power density in the high and the low frequency bands proved to be the most important predictors of the Ramsay score (+/-1 level accuracy: 87%, p < 0.001). Using this regression equation, the Ramsay score was predicted in the remaining 10 patients (group 2) with a +/-1 level of accuracy of 81% (p < 0.001). CONCLUSION: In ICU patients, a significant correlation is found between the depth of midazolam-induced sedation as assessed by the Ramsay sedation score and RR variability, with a clinically sufficient prediction accuracy. RR variability can serve as an objective, continuously available, and non-invasive measurement to monitor midazolam-induced sedation in intubated and mechanically ventilated patients.

Adult↗

PubMed1996

Vigabatrin dosing during haemodialysis.

The antiepileptic drug vigabatrin has shown efficacy in the treatment of patients with refractory epilepsy. Unlike many other antiepileptics it is not bound to plasma protein and mainly eliminated by the kidney. Although the therapeutic and toxic serum concentration range is not clearly defined and efficacy and toxicity are not closely correlated with the dose, factors decreasing vigabatrin elimination such as advanced age or renal failure may pose risk of untoward effects. Thus far there are no dose recommendations available for patients on haemodialysis. We report on an epileptic patient who experienced severe, partially reversible renal failure as a consequence of near-drowning. In this patient serum concentrations of vigabatrin were measured repeatedly both during haemodialysis and after partial recovery of renal function. The terminal elimination half-life in this patient was 41 hours during the period of severe renal failure (creatinine clearance < 5 ml/min). As about 60% of vigabatrin was removed from the blood pool by haemodialysis in these patients the antiepileptic should be administered after dialysis. To maintain serum concentrations in the usual range and to control seizure activity only 500 mg vigabatrin every 3 days were necessary.

Anticonvulsants↗

PubMed1996

Low whole-blood S-adenosylmethionine and correlation between 5-methyltetrahydrofolate and homocysteine in coronary artery disease.

Mild elevation of plasma homocysteine is an independent risk factor for vascular disease. We studied the role of 5-methyltetrahydrofolate (5-MTHF), the folate form directly involved in homocysteine metabolism, in contrast to previous studies, which used total folate measurements, in 70 coronary artery disease (CAD) patients and control subjects. We also measured S-adenosylmethionine (SAM), which controls the activity of critical enzymes of homocysteine metabolism. Fasting plasma total homocysteine was elevated (> 12.4 mumol/L for women, > 13.3 mumol/L for men) in 17% of patients, in accordance with earlier studies. These patients showed lower 5-MTHF (12.4 +/- 1.0 mumol/L, mean +/- SD) than control subjects (24.2 +/- 15.0, P < .001), and there was a clear correlation (multiple linear regression analysis: P = .002) of this relevant form of folate with homocysteine. However, 37% of the normohomocysteinemic patients also revealed similarly low 5-MTHF levels, suggesting that a decrease of 5-MTHF does not necessarily cause hyperhomocysteinemia. SAM was significantly decreased in patients (1.4 +/- 0.4 mumol/L) compared with control subjects (1.8 +/- 0.3, P < .001) but was not correlated to homocysteine or 5-MTHF. The correlation between homocysteine and 5-MTHF that was found in CAD patients but not in control subjects confirms the direct relationship between these compounds in vivo. The new finding of low SAM in patients demands further studies, since it might indicate that low levels pose risk and that SAM might be a protective factor against the development of CAD.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

PubMed1996

Tracheal gas insufflation-pressure control versus volume control ventilation. A lung model study.

Tracheal gas insufflation (TGI) has been recommended as an adjunct to mechanical ventilation in the presence of elevated Pa CO2. Based on our initial clinical experience with continuous flow TGI and pressure control ventilation (PCV), we were concerned about elevation in peak airway pressure as TGI was applied. In a lung model, we evaluated the effects of continuous flow TGI during both PCV and volume control ventilation (VCV). A single compartment lung model was configured with an artificial trachea into which an 8-mm endotracheal tube was positioned. TGI was established with a 16-G catheter positioned 2 cm beyond the tip of the endotracheal tube. Ventilation was provided by a Puritan-Bennett 7200ae ventilator with PCV 20 cm H2O or VCV with a tidal volume (VTt) similar to that with PCV. A rate of 15 breaths/min and PEEP of 10 cm H2O were used throughout. Inspiratory times (TI) of 1.0, 1.5, 2.0, and 2.5 s were used with TGI of 0, 4, 8, and 12 L/min. Lung model compliance (ml/cm H2O) and resistance (cm H2O/L/s) combinations of 20/20, 20/5, and 50/20 were used. Auto-PEEP, VT, and peak alveolar and airway opening pressures increased as TGI and Ti increased, regardless of lung mechanics settings (p<0.01). All increases were greater with VCV than PCV (p<0.05). Continuous flow TGI with both PCV and VT-uncorrected VCV may result in marked increases in Vt and system pressures, especially at long TI.

Airway Resistance↗

PubMed1996

[Mesenteric venous thrombosis (MVT): a problem in diagnosis and management].

The mesenterial venous thrombosis is a rare and independent cause of intestinal ischemia. 5 to 15% of all intestinal ischemias are due to venous problems. The lack of specific clinical symptoms and laboratory data often leads to a delayed diagnosis with irreversible intestinal infarction. Only by thorough searching by means of modern diagnostic devices is it possible to make an early diagnosis and treat the ischemic situation timely. Several therapeutical options are at hand. A timely and adequate application of these aids mostly depends on the clinical experience of the medical team as well as on an optimal interdisciplinary collaboration (radiology, hematology, angiology, gastroenterology, surgery). We want to analyze the problems related to diagnostics and management on the basis of 2 cases with different manifestations of a mesenterial venous thrombosis. We ascertain that: (1) the enhanced-CT analysis and/or the duplex-sonography mostly lead to a diagnosis, (2) the prognosis benefits from an immediate heparinization, (3) the request for large-scale intestinal resection, keeping a safety-space, has been replaced by the technique of limited resection, followed by earlier second-look-operations.

Adult↗

PubMed1995

Prolonged sedation due to accumulation of conjugated metabolites of midazolam.

Midazolam is a short-acting benzodiazepine routinely used in intensive-care medicine. Conjugates of its main metabolite, alpha-hydroxymidazolam, have been shown to accumulate in renal failure but have not previously been related to the prolonged sedative effects commonly observed in critically ill patients. We report five patients with severe renal failure who had prolonged sedation after administration of midazolam. In all five patients, the comatose state was immediately reversed by the benzodiazepine-receptor antagonist flumazenil. Serum concentration monitoring showed high concentrations of conjugated alpha-hydroxymidazolam when concentrations of the unconjugated metabolite and the parent drug were below the therapeutic range. In-vitro binding studies showed that the affinity of binding to the cerebral benzodiazepine receptor of glucuronidated alpha-hydroxymidazolam was only about ten times weaker (affinity constant 16 nmol/L) than that of midazolam (1.4 nmol/L) or unconjugated alpha-hydroxymidazolam (2.2 nmol/L). Conjugated metabolites of midazolam have substantial pharmacological activity. Physicians should be aware that these metabolites can accumulate in patients with renal failure.

Aged↗

PubMed1995

[Diagnostic and therapeutic consequences of pulmonary artery catheters. Prospective evaluation in an intensive care unit].

BACKGROUND: The diagnostic value and the therapeutic impact of pulmonary artery catheters have been repeatedly challenged. As part of a quality assurance project we compared clinical assessment with invasive measurements of hemodynamic parameters in critically ill patients and assessed changes in therapy following catheter insertion. METHODS: In 47 consecutive patients (age 31-79 years; mean APACHE-II score 19 +/- 8) of a medical intensive care unit both physicians and intensive care nurses independently estimated mean pulmonary arterial pressure (PAPm), pulmonary capillary wedge pressure (PCWP), and cardiac output (CO) prior to pulmonary artery catheterization based on available clinical and radiological information. The physician-in-charge had to specify a presumptive treatment strategy in case hemodynamic measurements were not available. RESULTS: In 19% minor complications due to catheter insertion occurred, only one requiring intervention (intravenous adenosine). Overall, PAPm was correctly predicted in 56%, PCWP in 51% and CO in 50% of the patients (Z > 2.6; p < 0.01 for all 3 parameters). There was no statistically significant difference in the percentage of correct predictions between physicians of different training levels or between physicians and nurses. In patients with sepsis the clinical prediction of PAPm (37% correct) and of PCWP (37%) was probably not better than by chance alone (Z = 1.53; p = 0.06). In 21% there was a major change in treatment after obtaining the invasive hemodynamic values compared to the preinsertion plan. CONCLUSIONS: Although randomized trials have not yet shown pulmonary artery catheterization to decrease mortality in critically ill patients, possible useful effects on intermediate outcomes cannot be excluded in view of the high numbers of misjudgements based on clinical information alone and the considerable number of changes in therapy following catheter insertion. Reducing uncertainty in clinical judgement may not in every case lead to a beneficial strategy, but it may prevent potentially harmful decisions.

APACHE↗

PubMed1995

Influence of carbon monoxide (CO) on the early course of acute myocardial infarction.

OBJECTIVE: To clarify the influence of an elevated carboxyhemoglobin (COHb) blood level on the course of acute myocardial infarction and to evaluate the administration of supplemental oxygen on the COHb level and the incidence of complications. DESIGN: Prospective clinical study with randomized, unblinded intervention. SETTING: Coronary Care Unit of a university hospital. PATIENTS: 78 consecutive patients with acute myocardial infarction. Excluded were patients with severe dyspnea, pulmonary edema or any other medical indication for supplemental oxygen therapy. INTERVENTIONS: Randomized therapy with 41/min oxygen in 35 patients. MEASUREMENTS AND RESULTS: COHb was measured at admission and 4 h later. The incidence of serious arrhythmias and the maximal creatine kinase (CK) values were recorded. In patients with initial COHb > or = 5%, there were significantly more arrhythmias and significantly higher maximal CK values than in those with normal COHb admission (89 vs 33%, p < 0.001; and 1897 +/- 1602 u/l vs 960 +/- 1097 u/l, p=0.05). This effect was seen only in patients with Q-wave infarction, not in those with non-Q-wave infarction. Supplemental oxygen had no effect on the incidence of arrhythmias. CONCLUSIONS: We conclude that myocardial infarction patients with acute Q-wave infarction and increased COHb levels at admission suffer a more severe course of the disease. This outcome was not influenced by oxygen therapy. Whether this finding indicates a casual relationship and whether higher oxygen concentrations would favorably alter the course of acute myocardial infarction remains to be determined.

Aged↗

PubMed1995

Nitrogen dioxide production during mechanical ventilation with nitric oxide in adults. Effects of ventilator internal volume, air versus nitrogen dilution, minute ventilation, and inspired oxygen fraction.

BACKGROUND: Inhaled nitric oxide (NO) may be useful in the treatment of adult respiratory distress syndrome and other diseases characterized by pulmonary hypertension and hypoxemia. NO is rapidly converted to nitrogen dioxide (NO2) in oxygen (O2) environments. We hypothesized that in patients whose lungs are mechanically ventilated and in those with a long residence time for NO in the lungs, a clinically important [NO2] may be present. We therefore determined the rate constants for NO conversion in adult mechanical ventilators and in a test lung simulating prolonged intrapulmonary residence of NO. METHODS: NO (800 ppm) was blended with nitrogen (N2), delivered to the high-pressure air inlet of a Puritan-Bennett 7200ae or Siemens Servo 900C ventilator, and used to ventilate a test lung. The ventilator settings were varied: minute ventilation (VE) from 5 to 25 l/min, inspired O2 fraction (FIO2) from 0.24 to 0.87, and [NO] from 10 to 80 ppm. The experiment was then repeated with air instead of N2 as the dilution gas. The effect of pulmonary residence time on NO2 production was examined at test lung volumes of 0.5-4.0 l, VE of 5-25 l/min, FIO2 of 0.24-0.87, and [NO] of 10-80 ppm. The inspiratory gas mixture was sampled 20 cm from the Y-piece and from within the test lung. NO and NO2 were measured by chemiluminescence. The rate constant (k) for the conversion of NO to NO2 was determined from the relation 1/[NO]t-1/[NO]o = k x [O2] x t, where t = residence time. RESULTS: No NO2 was detected during any trial with VE 20 or 25 l/min. With N2 dilution and the Puritan-Bennett 7200ae, NO2 (< or = 1 ppm) was detected only at a VE of 5 l/min with an FIO2 of 0.87 and [NO] > or = 70 ppm. In contrast, [NO2] values were greater with the Servo 900C ventilator than with the Puritan-Bennett 7200ae at similar settings. When NO was diluted with air, clinically important [NO2] values were measured with both ventilators at high [NO] and FIO2. Rate constants were 1.46 x 10(-9) ppm-2.min-1 when NO was mixed with N2, 1.17 x 10(-8) ppm-2.min-1 when NO was blended with air, and 1.44 x 10(-9) ppm-2.min-1 in the test lung. CONCLUSIONS: [NO2] increased with increased FIO2 and [NO], decreased VE, blending with air, and increased lung volumes. Higher [NO2] was produced with the Servo 900C ventilator than the Puritan-Bennett 7200ae because of the greater residence time. With long intrapulmonary residence times for NO, there is a potential for NO2 production within the lungs. The rate constants determined can be used to estimate [NO2] in adult mechanical ventilation systems.

Adult↗

PubMed1995

Intracellular Ca2+ stores can account for the time course of LTP induction: a model of Ca2+ dynamics in dendritic spines.

1. A model of Ca2+ dynamics in spines of CA1 hippocampal neurons is presented. In contrast to traditional models, which concentrate on the effects of Ca2+ influx, diffusion, buffering, and extrusion, we also consider the additional effect of intracellular Ca2+ stores. 2. It is shown that traditional models without Ca2+ stores cannot account for the time course of long-term potentiation (LTP) induction as found in recent experiments. Experimental data suggest that the intracellular Ca2+ concentration should be elevated for up to 2 s, whereas the Ca2+ concentration in standard models of Ca2+ dynamics decays much faster. 3. When intracellular Ca2+ stores are taken into account, a much slower decay is found. In particular, a model simulation with a stimulation paradigm consisting of two bursts of four impulses at 100 Hz each and variable interburst intervals can reproduce experimental results found for primed or theta-burst stimulation. 4. In our model, Ca2+ release from the store has a nonlinear, bell-shaped dependence on the intracellular Ca2+ concentration, similar to the one found for inositoltrisphosphate and ryanodine receptors. These receptors are known to control calcium release from intracellular stores. 5. Our model suggests an important role of intracellular calcium stores in the induction of LTP. The stores serve as a long-term calcium source that can sustain an intracellular Ca2+ concentration above the resting level for 1-2 s.

Animals↗

PubMed1995

Spontaneous excitations in the visual cortex: stripes, spirals, rings, and collective bursts.

As a simple model of the cortical sheet, we study a locally connected net of spiking neurons. Refractoriness, noise, axonal delays, and the time course of excitatory and inhibitory postsynaptic potentials are taken into account explicitly. In addition to a low-activity state and depending on the synaptic efficacy, four different scenarios evolve spontaneously, viz., stripes, spirals, rings, and collective bursts. Our results can be related to experimental observations of drug-induced epilepsy and hallucinations.

Action Potentials↗