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C Metz

Publications and source records attributed to C Metz.

At least 73 records · Page 4Linked to original sources

TNF-alpha up-regulates renal MIF expression in rat crescentic glomerulonephritis.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a potent proinflammatory mediator that participates in the pathogenesis of endotoxemia and experimental crescentic glomerulonephritis. However, very little is known about how MIF production is regulated in disease. We therefore examined whether tumor necrosis factor alpha (TNF-alpha), a known inducer of MIF expression by macrophages in vitro, up-regulates local and systemic MIF expression in a macrophage-mediated rat model of crescentic glomerulonephritis. MATERIALS AND METHODS: Anti-glomerular basement membrane (GBM) glomerulonephritis was induced in groups of six primed rats. Animals were treated with 1 mg/kg soluble TNF-alpha receptor (TNFbp) or saline from the time of disease induction until they were killed on Days 1, 7, or 14. Renal MIF expression was assessed by in situ hybridization, immunohistochemistry, and ELISA, and compared with macrophage accumulation and indices of renal damage. RESULTS: Although TNFbp treatment on Day 1 of the disease had only a partial effect upon the up-regulation of glomerular MIF expression, on Days 7 to 14 it almost completely abrogated the increase in glomerular and interstitial MIF mRNA and protein expression. In addition, TNFbp treatment significantly inhibited MIF secretion by cultured glomeruli and reduced serum MIF levels. The inhibition of renal MIF expression was paralleled by a significant inhibition of glomerular and interstitial macrophage infiltration (p < 0.001 versus saline treated), a significant suppression of renal injury (proteinuria and serum creatinine), and a marked reduction in histologic damage (glomerular hypercellularity, crescent formation, and interstitial fibrosis; all p < 0.01 versus saline treated). CONCLUSIONS: This study demonstrates for the first time that TNF-alpha up-regulates local MIF expression by both infiltrating macrophages and resident kidney cells in rat crescentic glomerulonephritis. In addition, TNF-alpha regulates systemic MIF production. Thus, TNF-alpha, together with MIF, may play a pathological role in immunologically induced renal disease.

Animals↗

Effects of extreme lateral posture on hemodynamics and plasma atrial natriuretic peptide levels in critically ill patients.

OBJECTIVE: To quantify the hemodynamic effects of turning critically ill, mechanically ventilated patients to the extreme left and right lateral postures. DESIGN: Prospective investigation. SETTING: Eight-bed intensive care unit in a university hospital. PATIENTS: Twelve consecutive patients presenting with severe respiratory failure and requiring continuous positive inotropic support. INTERVENTIONS: All patients were mechanically ventilated and placed in a kinetic treatment system. They were positioned in the supine, left dependent, and right dependent postures, resting for 15 min in each position. MEASUREMENTS AND RESULTS: Hemodynamic measurements, assessments of right ventricular function, and determinations of intrathoracic blood volume were performed in three different positions. Concentrations of atrial natriuretic peptide in plasma were quantified. In three patients, the findings were controlled by transesophageal echocardiography. Cardiac index [median (range) 5.5 (3.2-8.1) vs 4.3 (3.2-7.5) l/min per m2, p < 0.01], intrathoracic blood volume [1125 (820-1394) vs 1037 (821-1267) ml/m2, p < 0.01], and right ventricular end-diastolic volume [130 (83-159) vs 114 (79-155) ml/m2, p < 0.05] increased significantly in the left dependent position compared to supine. Mean arterial pressure did not change. Atrial natriuretic peptide levels rose from 140 to 203 pg/ml. In the right dependent position, we found a marked decrease in the mean arterial pressure [85 mmHg (supine) to 72 mmHg (right dependent), p < 0.01]. Cardiac index and intrathoracic blood volume were unchanged, but right ventricular end-diastolic volume decreased from 114 to 102 ml/m2 (p < 0.05). Additionally, atrial natriuretic peptide levels decreased significantly (median delta value: 37 pg/ml). In echocardiographic controls we found an increase in right ventricular end-diastolic diameters in the left dependent position and shortened diameters in the right dependent position. CONCLUSIONS: Extreme lateral posture affects the cardiovascular system in critically ill, mechanically ventilated patients: in the left dependent position a "hyperdynamic state" is reinforced, while the right decubitus position impairs right ventricular preload and predisposes to hypotension. Echocardiography and changes in plasma atrial natriuretic peptide values indicate that these findings are due to altered distensibility of the right ventricle caused by regional intrathoracic gravitational changes. We conclude that the duration and the angle of lateral posture should be restricted in hemodynamically unstable patients.

Acute Disease↗

[Ventilation-perfusion ratio in patients with acute respiratory insufficiency].

UNLABELLED: Acute respiratory failure is characterised by mismatch of ventilation with perfusion (VA/Q). The multiple inert gas elimination technique (MIGET) is a complex method which allows the description of a virtually continuous distribution of VA/Q ratios. We investigated VA/Q relationships in patients admitted to the intensive care unit due to acute respiratory failure and thus requiring for mechanical ventilation. METHOD: Eight patients (mean APACHE 11 = 22 +/- 4) who suffered from acute pneumonia (n = 4), traumatic lung contusion (2), toxic lung failure (1) or massive bilateral atelectasis (1) were investigated by MIGET within 3 days after the begin of mechanical ventilation. A mixture of six inert gases, dissolved in isotonic saline, was infused continuously. Arterial and mixed venous blood samples and expired gas samples were obtained and analysed by gas chromatography. Blood-gas partition coefficients were determined, and the ratios of retention and excretion were calculated. The data were transformed in a 50-compartment model of blood flow and ventilation against VA/Q ratio. We assessed the amount of intrapulmonary shunt (VA/Q = 0), low VA/Q regions (VA/Q = 0.005-0.1), normal VA/Q regions (VA/Q = 0.11-10), high VA/Q regions (VA/Q = 11-100) and dead space ventilation (VA/Q > 100). Furthermore, we calculated the logarithmic standard deviation of pulmonary perfusion distribution (logSDQ). RESULTS: In all patients we found moderate to severe intrapulmonary shunt and VA/Q mismatching. The data are expressed as median values and ranges. Inert-gas-measured shunt was 21% (3-45.5%), whereas low VA/Q regions were little affected. Normal VA/Q regions ranged from 41.5% to 96.0% (median 76.8%). The amount of alveolar dead space ventilation was 28% (19.7-41.8%). Median logSDQ (normal range 0.3-0.6) was calculated to be 0.855 (0.540-1.490). In patients presenting with moderate lung injury (Murray score < 3), a moderate increase in shunt and a moderate VA/Q mismatch were observed. In contrast, patients with severe lung failure and critically decreased oxygenation (Murray score > 3) were characterised by massive shunting and VA/Q mismatching. Additionally, low VA/Q and high VA/Q compartments and an increase in dead space ventilation was found in these patients. CONCLUSIONS: The impairment of oxygenation in patients with acute respiratory failure is due to several pathophysiological mechanisms: increase in intrapulmonary shunt, VA/Q-mismatching and dead space ventilation, according to the severity of lung failure. We conclude from our results that the prevention and/or reduction of non-ventilated lung areas (atelectasis) is an outstanding therapeutic strategy in the treatment of patients with acute respiratory failure. From this point of view, several techniques of systemic changes in body position should be integrated as supportive therapeutic strategies.

APACHE↗

[Neonatal diabetes mellitus associated with an autoimmune disease].

BACKGROUND: Insulin-dependent diabetes mellitus can be associated to an auto-immune disease. A similar association may be seen in the neonate. CASE REPORT: A one-day-old boy was admitted for ketoacidosis due to diabetes mellitus. Investigation showed that he also suffered from an auto-immune enteropathy with several types of autoantibodies, particularly anti-enterocytes antibodies. Immunotherapy was ineffective. Multi-organ lesions developed subsequently, particularly a pulmonary disease responsible for the death at the age of 2 years. CONCLUSION: Physiopathology of this association remains unclear and the report of further cases should help improve our knowledge.

Autoimmune Diseases↗

Cardiovascular and pulmonary effects of aerosolized prostacyclin administration in severe respiratory failure using a ventilator nebulization system.

We investigated the effects of aerosolized prostacyclin (PGI2) administration on hemodynamics and pulmonary gas exchange in 8 patients with severe respiratory failure and acute pulmonary hypertension. Nebulization of epoprostenol (5 ng/kg body weight for 15 min) decreased mean pulmonary blood pressure from 41.2 +/- 6.7 mm Hg (mean +/- SD, before administration) to 36.1 +/- 6 mm Hg < or = 15 min (p < 0.05). The effect was reversed 10 min after discontinuation of PGI2 (40.9 +/- 6.3 mm Hg). Pulmonary vascular resistance index (339 +/- 138 dynes.s.cm-5.m2, before administration) was significantly (p < 0.05) reduced < or = 15 min (260 +/- 89 dynes.s.cm-5.m2) and increased again after discontinuation of PGI2 (341 +/- 142 dynes.s.cm-5.m2). The ratio of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) increased from 119 +/- 34 mm Hg (before administration) to 163 +/- 76 mm Hg (15 min after initiation of administration p < 0.05) and was reduced after PGI2 discontinuation (116 +/- 35 mm Hg). Heart rate, mean blood pressure, central venous pressure, and pulmonary arterial wedge pressure remained unchanged, whereas cardiac index was slightly reduced. We assume that PGI2 aerosolization is a beneficial technique, applied with a ventilator nebulization system. The beneficial effect might be caused by selective pulmonary vasodilatation in well-ventilated areas of the lung.

Aerosols↗

Moderate hypothermia in patients with severe head injury: cerebral and extracerebral effects.

Cerebral and extracerebral effects of moderate hypothermia (core temperature 32.5 degrees C-33.0 degrees C) were prospectively studied in 10 patients with severe closed head injury (Glasgow Coma Scale score < 7) in the intensive care unit of a university hospital. Hypothermia was induced by cooling the patient's body surface with water-circulating blankets. Before cooling, a conventional intracranial pressure (ICP) reduction therapy was applied, which remained unchanged throughout the study. Cerebral blood flow (CBF), cerebral metabolic rates for oxygen (CMRO2) and lactate (CMRL), and ICP were simultaneously measured prior to inducing hypothermia, after obtaining hypothermia, after 24 hours of hypothermia, and after rewarming. With respect to extracerebral effects, supplemental investigations were conducted 24 and 72 hours after rewarming. The median delay between injury and induction of hypothermia was 16 hours. Hypothermia reduced CMRO2 by 45% (p < 0.01), whereas CBF did not change significantly. Before cooling, six patients had elevated CMRL indicating cerebral ischemia. Cooling normalized CMRL in all patients (p < 0.01). The intracranial hypertension present prior to cooling declined markedly during hypothermia (p < 0.01) without significant rebound effects after rewarming. Cardiac index decreased by 18% after hypothermia was reached (p < 0.05), recovered at 24 hours of hypothermia, and surpassed baseline values after rewarming. Platelet counts dropped continuously up to 24 hours after rewarming (p < 0.01). Plasma coagulation tests did not show significant worsening. Creatinine clearance decreased during cooling (p < 0.01) and recovered by 24 hours after rewarming. Twenty-four hours after cooling had begun, eight patients had elevated serum lipase activity (p < 0.01) and four of them acquired pancreatitis. Rewarming normalized both pancreatic alterations. Seven patients made a good recovery; one survived severely disabled; and two patients died. Moderate hypothermia is effective in preventing secondary brain damage while reducing cerebral ischemia. However, there are potentially hazardous side effects that require additional monitoring.

Adolescent↗

[Comparison of APACHE-II AND APACHE-III for classification of disease severity of intensive care patients].

The Acute Physiology and Chronic Health Evaluation model (APACHE II, APACHE III) is used to describe the severity of illness and predict the outcome in critically ill patients. APACHE III, introduced in 1991, has not yet been validated in Europe. We calculated APACHE II and APACHE III scores in patients after admission to the intensive care unit (ICU) and compared the prognostic value on hospital mortality. METHOD. One hundred fifty patients with stay of over 24 h were enrolled in the study and prospectively and consecutively investigated. APACHE II and III scores were calculated as described by the authors. The mean and median values of the survivors were compared with the non-surviving group (Mann-Whitney U test). Receiver operating characteristics (ROC analysis) and the areas under the ROC curves were plotted. RESULTS. Of the 150 patients, 34 died during their hospital stay (22.7%). The mean and median APACHE II and III scores were significantly higher (P < 0.001) in the non-surviving group. The area under the ROC curve was higher for APACHE III (0.899) compared to APACHE II (0.847). CONCLUSIONS. APACHE II and APACHE III were both found to have good prognostic value in general ICU patients. Our results suggest that the APACHE III version includes a more precise prediction of hospital mortality than APACHE II. A new aspect of APACHE III is an expanded modification of the Glasgow Coma Scale to assess neurologic derangements.

APACHE↗

[Severe legionellosis after abuse of anti-inflammatory drugs--diagnostic and intensive care aspects based on a case report].

Legionella infections are getting increasingly important as causes of severe pneumonias or of acute respiratory insufficiency. Consumptive or immunosuppressive underlying diseases such as diabetes mellitus, cardiac insufficiency, alcohol-induced liver damage, malignant tumours or drug-induced immunosuppression after organ transplantation, are among the risk factors. Diagnosis is based on direct identification of the pathogen from body secretions by means of direct immunofluorescence. The serological immunoresponse often takes place long after outbreak of the disease or fails entirely to appear and is therefore only suitable for retrospective confirmation. Therapy of choice is an intravenous administration of erythromycin. There are now increasing pointers to the efficiency of fluoroquinolone antibiotics, such as ciprofloxacin. We report on the course of a severe case of legionnaire's disease with multiple organ failure occurring in a patient after bone marrow depression induced by anti-inflammatory drugs. Treatment erythromycin resulted in a marked cholestasis, so that antibiotic treatment was changed to ciprofloxacin. This therapy as well as the supportive intensive-care treatment eventually led to the patient's complete recovery. Based on the case report, fundamental aspects of diagnostics, antibiotic treatment, intensive-care treatment and prognosis of severe cases of legionellosis are discussed.

Anti-Inflammatory Agents, Non-Steroidal↗

[Exposure of intensive care personnel to isoflurane in long-term sedation].

OBJECTIVE: Isoflurane is a suitable agent to produce sedation in the intensive care unit (ICU). However, data concerning occupational exposure to isoflurane during long-term sedation are not yet available. The purpose of this study was to evaluate occupational exposure to isoflurane in the ICU. DESIGN: Trace concentrations of isoflurane were measured directly by means of photoacustic infrared spectrometry during isoflurane sedation in ten cases over a period of 24 hours. Values were obtained at four personnel-related and two leakage-related locations in an ICU chamber. RESULTS: All measured values were low, the majority under 3 ppm isoflurane at the personnel-related points. Peak concentrations up to 40 ppm were recorded for several minutes during nursing interventions. At measurement point "nearby patient's mouth" values up to 5 ppm were recorded, at location "anaesthesia machine" values ranged from 2 to 69 ppm isoflurane. CONCLUSION: We conclude that an effective high flow scavenging system, a low-leakage anaesthesia machine and an airconditioning equipment without recirculation could keep occupational exposure low. The majority of the measured values was below the NIOSH recommendation (2 ppm). All values was lower than a national state recommendation (10 ppm). Under other circumstances (e.g. without scavenging system) air pollution will be higher and therefore measurements at the working place are needed.

Air Pollutants, Occupational↗

Is the transfusion requirement predictable in critically ill patients after admission to the intensive care unit?

OBJECTIVE: In intensive care medicine the clinical decision to order and transfuse red blood cells (RBC) is usually based on hematocrit or hemoglobin levels. The intention of this study was to investigate whether clinical or laboratory variables, taken after the admission of patients to the intensive care unit (ICU), are able to predict the transfusion requirement of the following 72 h. DESIGN: The values of initially measured systolic blood pressure, hematocrit level, and the values of 2 scores of severity of disease (Acute Physiology And Chronic Health Evaluation [APACHE-II], Mortality Prediction Model [MPM]) were calculated after the admission of patients to the ICU. The decision for transfusion was based on specific criteria. The median values of the scores, those of the variables, and the median number of transfused RBC units of the surviving group were compared to the values of the group of patients who died during hospital stay. The quantity of RBC transfusions was compared to the variables and score values by linear regression analysis. Additionally, the values of the patients who did not receive blood transfusion were compared to those of patients who required RBC. Furthermore, the patient group with neurosurgical diseases was compared to the group without neurosurgical diseases. PATIENTS: 117 patients were prospectively and consecutively investigated in an 8-bed ICU of a university hospital. RESULTS: Nonsurvivors required significantly more units of RBC during the first 72 h (p < 0.05). Patients who did not require transfusion had a higher hematocrit and a lower APACHE-II value at admission (p < 0.001). In the MPM values no differences were found. Patients with neurosurgical diseases had a higher initial hematocrit value, and they required less units of RBC in comparison to patients without neurosurgical diseases. In the analysis of linear regression neither in the initially measured systolic blood pressure nor in the APACHE-II and MPM we found a strong linear correlation to the quantity of blood transfusion. CONCLUSIONS: A hematocrit value < or = 20% and a APACHE-II score > or = 20 at the time of admission to the ICU referred to a demand for blood transfusion. We believe that these parameters are useful as predictive instruments. The initially measured systolic blood pressure had no prognostic capacity. In the individual patient a number of factors should be taken into account to decide whether to transfuse or not.

APACHE↗

Right ventricular function and plasma atrial natriuretic peptide levels during fiberbronchoscopic alveolar lavage in critically ill, mechanically ventilated patients.

STUDY OBJECTIVE: To assess the influence of fiberbronchoscopic alveolar lavage on hemodynamics, right ventricular function, and plasma atrial natriuretic peptide (ANP) concentrations in critically ill, mechanically ventilated patients. DESIGN: Prospective investigation. SETTING: Eight-bed ICU of a university hospital. PATIENTS: Fourteen patients with cardiovascular instability due to a systemic inflammatory response syndrome who were mechanically ventilated. INTERVENTIONS: Fiberbronchoscopic alveolar lavage after fluid replacement, deep sedation, and paralyzation. Intervention time: 10 min. After inspection of the endobronchial system, one lavage of 40 mL sterile saline solution was instilled in each lung and recovered. MEASUREMENTS AND RESULTS: The fiberbronchoscopic procedure induced a prompt increase in mean pulmonary arterial pressure after 3 min (median[range]: 25 [13 to 39] to 30 [19 to 45] mm Hg, p < 0.05), which increased further after 6 min (34 [17 to 46] mm Hg, p < 0.01). Cardiac index increased simultaneously (4.25 [3.1 to 5.7] to 4.85 [4.3 to 6.9] L/min.m2 after 6 min, p < 0.01), whereas mean arterial pressure and heart rate remained unchanged. Central venous pressure rose from 12 (3 to 18) mm Hg before procedure to 14 (4 to 20) mm Hg after 6 min (p < 0.01). The right ventricular function was measured using a "fast response" ejection fraction thermodilution catheter: end-diastolic volume increased (238 [137 to 358] to 280 [150 to 4ll] mL after 9 min, p < 0.05), as well as stroke volume (88 [54 to 113] to 103 [67 to 153] mL after 9 min, p < 0.01). Right ventricular ejection fraction (37 [25 to 50] %) did not change significantly during the procedure, but the stroke work index was reinforced (8.2 [4.7 to 15.7] to 13.3 [2.4 to 41.3] gm.M/M2 after 6 min, p < 0.01). Plasma c-ANP concentration rose from 135 (24 to 350) to 196.5 (44 to 830 pg/ml after 20 min (p < 0.05). Systemic vascular resistance decreased from 533 (390 to 1,042) to 429 (281 to 684) dynes.s/cm5 after removal of the bronchoscope (p < 0.01). CONCLUSIONS: Although acute pulmonary hypertension was observed during the fiberbronchoscopic procedure, the right ventricular performance did not deteriorate in hemodynamically unstable patients. To maintain a "hyperdynamic cardiovascular state," the right ventricular stroke work was reinforced, presumably by the "Frank-Starling mechanism." We assume that the acute distention of the right side of the heart resulted in elevated ANP concentrations. The marked decrease in systemic vascular resistance might be due to high ANP levels.

Adult↗

[Acute pulmonary and cardiovascular effects of continuous axial rotation (kinetic therapy) in respiratory failure].

AIM: Continuous lateral rotational therapy (kinetic therapy) is advocated to improve pulmonary gas exchange in patients with severe respiratory failure, by promoting mobilization of secretions and reducing mismatch of ventilation and perfusion. We analyzed the acute pulmonary and hemodynamic changes before and after beginning kinetic therapy in critically ill patients with inotropic support. PATIENTS AND METHODS: Due to severe respiratory failure, 18 patients with "systemic inflammatory response syndrome" had been placed in a kinetic bed (Rotorest, KCI Mediscus). Retrospective analysis included several indices of arterial oxygenation, intrapulmonary "shunt fraction", cardiac index, arterial and pulmonary arterial pressure, systemic vascular resistance and systemic oxygen consumption. RESULTS: After the start of kinetic therapy, we found a statistically significant improvement of pulmonary gas exchange and a reduction of shunt fraction 12 hours later. Cardiac index and arterial and pulmonary arterial pressure remained unchanged. Systemic oxygen consumption was increased. CONCLUSION: The continuous axial rotation of patients with severe respiratory failure results in a prompt improvement of arterial oxygenation. Even in hemodynamically unstable patients we did not observe harmful effects.

Adult↗

Characterization of human peroxisomal membrane proteins.

The peroxisomal membrane appears to play a crucial role in transporting proteins into the organelle. Some human genetic disorders involving peroxisome biogenesis, such as Zellweger syndrome, may be caused by genetic defects of the import machinery located in the peroxisomal membrane. In order to characterize the proteins of the human peroxisomal membrane, we isolated peroxisomes from human liver. We obtained their membranes using various procedures and analyzed their proteins by SDS-polyacrylamide gel electrophoresis and silver staining. We compared the protein composition of peroxisomal membranes with membranes derived from mitochondria and microsomes. The main peroxisomal membrane proteins (PMPs) have apparent molecular masses of 147, 112, 95, 87, 81, 79, 74, 69(70), 53-52 (double band), 47, 45, 43, 37, 31, 28, 22, and 17 kDa. The following PMPs of 147, 112, 79, 69(70), 53-52 (double band), 47, 43, 31, 28, 22, and 17 kDa fit the criteria for integral membrane proteins. We then produced rabbit polyclonal and mouse monoclonal antibodies that recognized some human PMPs. One of these antibodies detected mainly PMP43. We used this antiserum to evaluate the presence and subcellular distribution of the PMP43 in fibroblasts derived from patients affected by Zellweger syndrome. These results represent new information about the protein composition of the human peroxisomal membrane and provide biological tools for further characterization of the human PMPs and their genes in normal and pathological conditions.

Animals↗

[Fictional film and the audience. A metapsychological study].

Comparing and contrasting dreams and films we find a complex behind of affinities and distinctions between the dream state and the film state. The author classifies the totality of these partial distinctions and similarities in terms of three factors deriving from the discrepancy between sleep and the waking state: first, the inconsistent knowledge of the subject with regard to what he is doing; second, the presence or absence of real perceptual material; and third, the qualitative difference between dream text and film text. Metz shows that, unlike dreams, which obey primary events, films have much greater affinities with secondary events and the pre-conscious figments of daydreaming. Dreams, the author contends, belong to childhood and night, while films and daydreams are more adult and belong to the day and the evening.

Adult↗

Renal and single-nephron function is comparable in thiobutabarbitone- and thiopentone-anaesthetised rats.

The thiobutabarbitone(TB, Inactin)-anaesthetised rat is an extremely widely used preparation for the study of renal function at the whole-organ and nephron levels. The recent withdrawal of TB from the market has made it essential to find an anaesthetic producing experimental conditions as similar as possible to TB to allow comparison of past and future data. Blood gas analysis, clearance and micropuncture studies were therefore performed in rats anaesthetised with TB or the related thiobarbiturate thiopentone (TP) (both 100 mg/kg body weight) to establish whether the latter meets this requirement. Both barbiturates caused similar transient respiratory depression and acidosis. Mean values (TP versus TB) over the total 8-h observation period for glomerular filtration rate (0.94 versus 1.05 ml/min), urine flow (3.8 versus 4.4 microliters/min) and K+ excretion (0.98 versus 1.18 mumol/min) were slightly lower (P < 0.05) in TP rats, whereas renal blood flow (6.26 versus 6.24 ml/min), filtration fraction (0.31 versus 0.34) and Na+ excretion (0.11 versus 0.098 mumol/min) did not differ. The single-nephron filtration rate (SNGFR) (42.1 versus 41.1 nl/min) and fractional reabsorption (42% versus 47%), both measured in the proximal tubule, did not differ, although in the TP group SNGFR rose with time (4.4%/h) whereas the fractional reabsorption did not change significantly; in the TB group SNGFR was constant but fractional reabsorption declined with time (1.5%/h). Fractional reabsorption up to the distal convoluted tubule declined with time, this was more pronounced in the TP group. SNGFR measured at this site did not differ between TP and TB (30.3 versus 30.1 nl/min) but increased with time with TP (2.7%/h).(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

Gastric acid suppression is greater during intravenous ranitidine infusion versus bolus injections of famotidine.

It has been proposed that famotidine may be effective in maintaining intragastric pH > or = 4 for up to 12 h with a single i.v. 20 mg bolus injection and thereby prevent acute stress-related mucosal haemorrhage. The present study was designed to compare a ranitidine continuous i.v. infusion (6.25 mg/h) vs. famotidine bolus injection (20 mg every 12 h) on 24-h intragastric pH and gastric acid secretion. Twenty-eight healthy volunteers (15 males, 13 females; 20-56 years) participated in two 24-h treatment periods; each test was in random order separated by 7-10 days. After an overnight fast, subjects were intubated and gastric pH and acid secretion measured hourly. Whereas ranitidine maintained gastric pH above 4 for the entire 24-h period, mean pH steadily decreased to a nadir of 2.9 and 3.7, respectively, 12 h after each famotidine injection (P < 0.01 vs. ranitidine). Furthermore, gastric acid secretion increased to 4.4 +/- 1.2 mmol/h 12 h after famotidine injection compared to 1.1 +/- 0.3 mmol/h with ranitidine (P < 0.01). We conclude that ranitidine delivered as a continuous i.v. infusion (6.25 mg/h) is superior to bolus famotidine injections (20 mg) at 12-h intervals in suppressing gastric acid secretion and maintaining an intragastric pH > or = 4. More frequent famotidine dosing, or delivery by continuous i.v. infusion, may be required to provide prolonged acid suppression.

Adult↗