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Biomedical subjects

G Regel

Publications and source records attributed to G Regel.

102 records · Page 6Linked to original sources

Pharmacokinetics and pharmacodynamics of oral nizatidine.

Nizatidine was studied in six high-acid-secretor (basal secretion, greater than or equal to 5 mEq/hr) male volunteers in a randomized, double-blind, nonbalanced, cross-over, placebo and standard drug-controlled study. Doses of 75 mg, 150 mg, and 300 mg bid were compared with placebo and cimetidine 300 mg qid. Nocturnal acid output was significantly reduced (P less than .01) by all doses of nizatidine (36 +/- 22, 36 +/- 31, and 26 +/- 20 mEq) with 75 mg, 150 mg and 300 mg, respectively, and also by cimetidine (43 +/- 39 mEq) as compared with placebo (101 +/- 61 mEq). Nizatidine also significantly reduced meal-stimulated acid secretion at breakfast (14 +/- 9, 9 +/- 7, and 5 +/- 6 mEq/2 hours with 75 mg, 150 mg, and 300 mg, respectively, P less than .01), at lunch (50 +/- 22, 57 +/- 22 and 50 +/- 35 mEq/2 hours, P less than .05) but did not have any effect at dinner (65 +/- 16, 78 +/- 24, and 71 +/- 17 mEq/2 hours) whereas cimetidine, given every 6 hours, significantly (P less than .01) reduced meal-stimulated acid secretion (25 +/- 16, 27 +/- 20 and 31 +/- 15 mEq/2 hours, breakfast, lunch, and dinner, respectively) as compared with placebo (81 +/- 30, 76 +/- 25, and 66 +/- 16 mEq/2 hours, breakfast, lunch, and dinner, respectively). Both drugs have a similar pharmacokinetic profile. Nizatidine seems to be a promising H2 antagonist, more potent than cimetidine (on an mg/mg basis), and efficacy studies on gastric acid disorders should be performed.

Administration, Oral↗

Paranasal sinusitis and sepsis in ICU patients with nasotracheal intubation.

During a 1-year period 4 out of 171 nasotracheally intubated patients (2.3%) developed sepsis due to purulent sinusitis. 98 (57%) of the patients received mechanical ventilation for more than 10 days. In all cases of sinusitis the diagnosis could be confirmed by conventional X-ray examination. Sepsis resolved 1 to 3 days after initiation of a therapy protocol consisting of tracheostomy, surgical drainage and lavage. Pseudomonas aeruginosa was involved as pathogenic organism in 3 of 4 patients. We conclude that purulent sinusitis represents a serious and often occult problem in already critically ill patients with multiple potential sources of sepsis. Most important for diagnosis is a high level of suspicion particularly in patients with risk factors for infection. Prompt and successful treatment can be achieved by an aggressive surgical approach.

Adult↗

[Significance of lung contusion in mortality following polytrauma. Possibilities for therapeutic influence].

Multiple trauma is often associated with blunt thoracic injuries. Especially lung contusion can result in respiratory insufficiency and therefore a higher mortality rate. In our prospective study comparing 8 multiple trauma patients with and without associated lung contusion, we found that respiratory function was already significantly disturbed (decrease of paO2/FiO2 and increase of AaDO2, a rise in extravascular lung water (EVLW) both early after trauma and also with a second peak following the 4th day. This group (LK) developed significantly more cases of respiratory distress (ARDS). The disturbance of respiratory function seen initially was interpreted as a consequence of the direct mechanical impact, leading to the formation of interstitial fluid and hematoma. The frequent development of ARDS in the LK-group probably results from a pronounced activation of cellular and humoral mechanisms and therefore an enforced injury of the pulmonary capillary bed. A significant increase of pulmonary infections or the development of sepsis was not seen in the LK-group and is probably not responsible for the higher ARDS-rate in this group.

Adolescent↗

[Prognostic significance of early management as exemplified by the accident patient].

Progress in the therapeutic management of multiple trauma patients has led to a decline in mortality (now 20%). The main cause for death is still the multiple organ failure (MOF), which is initiated in an early phase after trauma by shock and tissue damage, and manifests in a late phase during posttraumatic sepsis. Humoral and cellular changes accelerate the capillary damage, which provokes the failure of the organ systems. For this reason all therapeutic efforts should aim to minimize these influences. Next to infusion and ventilation therapy, early definite reduction of bleeding and tissue damage (debridement) and early osteosynthesis in multiple trauma patients seems reasonable.

Combined Modality Therapy↗

Phagocytic function of polymorphonuclear leukocytes and the RES in endotoxemia.

The reticuloendothelial system (RES) and the polymorphonuclear leukocytes (PMNs) are thought to play a major role in defense against sepsis. Disturbances in the function of these two phagocytic systems during a septic event is associated with the development of lung capillary injury. Endotoxemia is said to lead to similar changes. Our study examined the function of the RES and PMNs after bolus injection of endotoxin (2 micrograms/kg BW) in a standardized sheep model. For up to 24 hr after endotoxin, blood samples were drawn and PMN function was followed by chemiluminescence, chemotaxis, and adherence as well as the phagocytosis and killing of bacteria. RES function was determined by the blood clearance of a labeled Tc99 colloid. We found an increase of RES clearance directly after endotoxin. Chemotaxis, phagocytosis, and killing were reduced. Adherence was increased. Chemiluminescence peak maximum (CLPM), representing the metabolic activity of the PMNs, was initially increased but shortly thereafter showed a significant decline (at 1 hr: 0.52 +/- 0.13 X 10(6) cpm with P less than 0.05 compared to baseline). The chemiluminescence peak time (CLPT), a measure of membrane receptor function, was significantly reduced (10.0 +/- 2.2 min with P less than 0.001 compared to baseline). Endotoxin led to a reduction of intracellular PMN functions (phagocytosis, killing, CLPM) within 1 hr. Membrane localized functions (adherence, CLPT) were increased. The changes in PMN function might be the reason for the development of lung capillary injury, in spite of undisturbed RES clearance.

Animals↗

Bronchoalveolar lavage fluid and plasma proteins, chemiluminescence response and protein contents of polymorphonuclear leukocytes from blood and lavage fluid in traumatized patients.

The technique of bronchoalveolar lavage was used to obtain serial samples of lavage every two days from non-contused lung areas of seven traumatized patients and four normals; blood was drawn simultaneously. Urea, total protein, albumin, alpha 1-proteinase inhibitor, alpha 2-macroglobulin, lactate dehydrogenase, beta-N-acetyl-glucosaminidase, myeloperoxidase, and elastase enzyme activity, as well as complexed and total elastase concentrations were determined in bronchoalveolar lavage fluids and plasma samples. Lavage fluid cell pattern was counted. Polymorphonuclear leukocytes were isolated from lavage fluids and blood samples. Granulocyte contents of elastase enzyme activity, complexed and total elastase concentrations, and myeloperoxidase and lactate dehydrogenase activity were determined. Polymorphonuclear leukocyte stimulatory functions were measured by luminol-enhanced chemiluminescence. The following results were obtained for the patient group: Patterns of lavage fluid cells were shifted in favour of polymorphonuclear leukocytes and lymphocytes. The protein determinations of bronchoalveolar lavage fluids and plasma samples gave information about the extent of alterations of permeability of the capillary-interstitial-alveolar space (albumin/urea and alpha 1-proteinase inhibitor/urea ratios) as well as about the amounts of cytoplasmic and lysosomal enzymes released by phagocytes (lactate dehydrogenase/urea, beta-N-acetylglucosaminidase/urea, elastase/urea ratios). Polymorphonuclear leukocytes isolated from bronchoalveolar lavage fluids contained a decreased content of myeloperoxidase and elastase enzyme activities and total elastase concentration; the content of complexed elastase was found to be increased more than 100 fold. From chemiluminescence measurements there was evidence for decreased zymosan-induced stimulatory function, while the photon emission rate of polymorphonuclear leukocytes after passage into the alveolar space was increased.

Blood Proteins↗