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Biomedical subjects

D Inthorn

Publications and source records attributed to D Inthorn.

At least 19 recordsLinked to original sources

Comparison of pump-driven and spontaneous continuous haemofiltration in postoperative acute renal failure.

In a comparison of spontaneous continuous arteriovenous haemofiltration (CAVH) and pump-driven haemofiltration (PDHF) for acute renal failure after surgery, 116 patients admitted to a surgical intensive care unit were assigned CAVH (48) or PDHF (68). The method of assignment was that a patient was treated by PDHF if he or she was the only patient requiring treatment at that time (only one pump was available); any other patient coming to the unit would be treated by CAVH. The groups were slightly unbalanced because there were fewer simultaneous cases than expected. The main endpoints were survival rate, control of uraemia, and additional application of haemodialysis. There were no differences between the patient groups in age, duration of treatment, severity of illness, serum creatinine concentration at the start of treatment, or cause of acute renal failure. Both treatments adequately controlled uraemia and fluid overload. However, the survival rate was significantly higher with PDHF than with CAVH (6 [12.5%] vs 20 [29.4%]; p less than 0.05). The daily ultrafiltrate volume was significantly higher with PDHF than with CAVH (15.7 [95% confidence interval 13.6-17.8] vs 7.0 [6.6-7.4] l/day; p less than 0.05). The volume of ultrafiltrate in patients with ischaemic or sepsis-induced acute renal failure was correlated with the survival rate. This finding suggests that the better survival rate in the PDHF group was due to faster elimination of toxic mediators (of molecular weight 800-1000 daltons) through the filter membrane by high-volume haemofiltration.

Acute Kidney Injury

[Improved survival rate of postoperative renal failure caused by high volume hemofiltration].

Continuous arteriovenous hemofiltration is the treatment of choice for postoperative acute renal failure (ARF). The clinical value of two different treatment modalities (spontaneous vs. pump-driven hemofiltration PDHF) were compared in two groups of patients with postoperative ARF. There were no differences in both groups regarding age, duration of treatment, severity of illness or cause of renal failure. The survival rate of patients treated with PDHF was significantly higher (29.4 vs. 12.5%). PDHF also led to a significantly larger daily ultrafiltrate volume (15.6 +/- 1.9 vs. 7.0 +/- 0.4 l/d, p less than 0.05). The accelerated elimination of toxic mediators through the filtration membrane in high-volume filtration using a pump system (PDHF) may have been responsible for the improved survival rate.

Acute Kidney Injury

Immunoprotective effects of cyclooxygenase inhibition in patients with major surgical trauma.

Dysfunctional monocytes (M phi), exerting their inhibitory functions via prostaglandin E2 (PGE2), have been implicated in the depression of immune responses following major surgical, accidental, and burn trauma. A randomized prospective study of the PG-synthetase inhibitor indomethacin (Indo) was performed in 43 patients undergoing major surgical procedures, to evaluate its efficacy in correcting postoperative abnormalities of the cell-mediated immune system (CMI) and preventing infectious morbidity and mortality. Patients, following gastrectomy (GX) or reconstruction of the abdominal aorta (AG), in the treated group (PIndo), received 100 mg IV of Indo 6 hours postoperatively and 3 x 50 mg IV Indo over 24 hours on postoperative days (D) 1,2,3,4. The rate of infectious complications was recorded. Parameters of CMI evaluated preoperatively (D0) and on D1,D3,D5,D7 were: Delayed type hypersensitivity (DTH) response to recall antigens, mitogen-induced lymphocyte proliferation (LP), interleukin 2 (IL-2) synthesis, and phenotyping of mononuclear blood leukocytes (PBMC's) with the monoclonal antibodies for CD3+, CD4+, IL-2 receptor (IL-2R)+ and LeuM3+ receptor sites. In contrast to the group of untreated patients (Pc), PIndo did not show a depression of their preoperative DTH responses, and they also showed a lower rate of early opportunistic infections. The in vitro test of CMI revealed that there was a higher LP capacity in PBMC's of PIndo (p less than 0.05); the postoperative profile of IL-2 synthesis was not statistically different between the groups. Indomethacin administration resulted in a considerable alleviation of postoperative monocytosis (p less than 0.05) and in a protective effect on lymphocyte receptor expression of CD3+, CD4+, and IL-2R+ cells. From these data it is concluded that in vivo cyclooxygenase inhibition may be useful to prevent impairment of CMI, a crucial predisposing factor of the high susceptibility to postoperative infection.

Aged

[Diagnosis and monitoring of postoperative pulmonary complications].

There is no distinct difference between regular postoperative pulmonary changes and postoperative pulmonary complications (PPC). Beside the "classic" PPC, atelectases and bronchopneumonia, adult respiratory distress syndrome (ARDS) and barotraumas are becoming of increasing importance. A single examination allows the diagnosis of up to 60% of PPC. Only in 63% of cases of bronchopneumonia does the X-ray diagnosis agree with the necropsy results. The varieties of germs found in bronchial secretions and lung parenchyma, however, are not considerably different. CAT scan seems to be the best diagnostic imaging tool for the follow-up of ARDS and barotrauma.

Bronchopneumonia

Ticarcillin/clavulanate in the treatment of severe peritonitis.

A prospective study was performed on 50 consecutive patients with secondary peritonitis. All patients received ticarcillin/clavulanate 5.2 g three times daily as initial antibiotic therapy. In 30 patients a primary perforation was found in the gastro-intestinal tract and 20 had post-operative peritonitis. In two thirds of the patients a diffuse peritonitis was found which affected the whole abdomen. Thirty-six patients underwent one or two laparotomies and 11 patients had more than three laparotomies. Subsequently, 17 patients died. The cause of death was a therapeutic failure as a result of the surgical procedure in ten patients (nine patients with persisting intestinal fistulae, one patient with bleeding), whereas in seven cases antibiotic therapy failed. Micro-organisms found in the latter patients were producers of type 1 beta-lactamase (Pseudomonas aeruginosa, Enterobacter sp., Citrobacter sp., Serratia marcescens) and enterococci. Ticarcillin/clavulanate is characterized by its broad antimicrobial spectrum against anaerobic and aerobic bacteria and seems, therefore, to be well suited for initial chemotherapy in patients with diffuse peritonitis.

Adult

Enzymatically active cathepsin B dissociating from its inhibitor complexes is elevated in blood plasma of patients with septic shock and some malignant tumors.

Using fluorogenic substrates and the specific inhibitor E-64, cysteine proteinase (CP) activity was measured in blood plasma of healthy controls (mean = 35.0 mU/l) and patients with cancer and severe septic shock. Whereas moderately elevated activity was observed in some kinds of cancer (mean = 63.9 mU/l), 10-fold increased CP activity was found in septic shock. The plasma CP activity of sepsis patients paralleled the immunologically determined concentration of elastase-alpha 1-proteinase inhibitor complex. On the basis of its substrate specificity and its Michaelis constant for Z-Phe-Arg-NMec the plasma CP was identified as cathepsin B or a cathepsin B-like proteinase (CBP). Kinetic studies revealed that dilution and competition with substrate effects reversible dissociation of CBP from complexes with plasma inhibitors that are most probably the kininogens. The dissociation of CBP was confirmed by gel chromatographic fractionation of the plasma proteins. The results suggest that active CBP can easily dissociate from its plasma inhibitor complexes in vivo and may be involved in pathogenetic extracellular proteolysis.

Cathepsin B

Reactive hyperemia in patients with septic conditions.

In a prospective study microvascular reactivity was examined in 12 patients with septic conditions by means of the provocation of reactive hyperemia (RH) for evaluation of microcirculatory function. Data were compared with data from 10 nonseptic, postsurgical patients. At the time of the initial measurement, an adequate hyperemic response could be produced in all patients. In the further course of the disease, in nine of the 12 patients severe multiple organ failure developed. In spite of sufficient values for arterial blood pressure, oxygenation, and the clotting system, RH was absent in these patients (8 +/- 2 days after the initial measurement). Subsequently, seven of these nine patients died (4 +/- 2 days after the onset of microvascular nonreactivity). Until death, RH was absent in each patient, and at this time therapy-resistant hypoxemia, hypotension, and severe disturbances of the clotting system were present. In the two surviving patients RH was restored completely. These results indicate that (1) the septic state per se is not necessarily combined with impaired microvascular reactivity (rather, the absence of RH may be a sign of generally poor clinical conditions); (2) the absence of RH is not related to therapy-resistant hypotension, hypoxia, and severe clotting disorders but precedes these changes; and (3) provocation of RH may be of clinical use for early detection of microcirculatory malfunction in high-risk patients.

Age Factors

D-erythro-neopterin plasma levels in intensive care patients with and without septic complications.

The activation of macrophages is accompanied by release of 2-amino-4-oxo-6(D-erythro-1',2',3'-trihydroxypropyl)-dihydropterid ine (D-erythro-neopterin). The neopterin levels of 21 patients were measured with radioimmunoassay. The patients were classified according to the clinical course and outcome. We found highly significant differences between survivors and nonsurvivors for each of the evaluated days of the observation period. In addition to a sustained increase, patients with fatal outcome always showed a higher percentage of neopterin levels (88.2 +/- 28 [SD]%) exceeding the upper confidence limit (27.4 nmol/L) than survivors (31.8 +/- 29.9%). We conclude that the assessment of D-erythro-neopterin might be an easily available aid for an early evaluation of the immunologic status of a patient at risk for septic complications.

Adult

Pathobiochemistry of sepsis: role of proteinases, proteinase inhibitors and oxidizing agents.

Degradation of structural elements and excessive consumption of humoral factors, especially of plasma proteinase inhibitors, by proteolysis and/or oxidation is a major cause of multiple organ failure in sepsis or septic shock. Such pathobiochemical reactions seem to be induced primarily by extracellularly liberated lysosomal proteins from PMN granulocytes (e.g. elastase, cathepsin G, myeloperoxidase, lactoferrin) as well as oxygen radicals produced during extensive phagocytosis. In clinical studies on septicemia and septic shock the consumption of plasma proteins including proteinase inhibitors was inversely correlated to the liberation of lysosomal factors, especially the granulocytic elastase. Administration of relatively specific elastase-cathepsin G-inhibitors (Bowman-Birk inhibitor, eglin) in experimental septicemia proved to be a promising therapeutic approach to reduce consumption of plasma proteinase inhibitors and development of interstitial lung edema in severe inflammation.

Animals

[Comparison between cimetidine-pirenzepine and antacids for the prevention of stress hemorrhage in intensive care patients. A controlled clinical study on 125 patients].

In a controlled clinical trial, the efficacy of an intravenous combination of cimetidine and pirenzepine (group A: 62 patients) was compared with that of an intragastric administration of a magnesium-aluminium-hydroxide concentrate (group B: 58 patients) in preventing visible and occult upper gastrointestinal tract bleeding in intensive-care patients. It was found that both forms of therapy had the same favourable effect on the extent and incidence rate of visible and occult gastric bleeding. The antacid was more effective than the cimetidine-pirenzepine combination in raising the pH level to 4 or higher (P less than 0.05). Intensive-care patients should, therefore, be treated with the antacid whenever possible, since it is equally effective as the cimetidine-pirenzepine combination in preventing bleeding from the upper gastrointestinal tract, whereas it is superior in elevating the gastric pH. Besides, the use of the antacid is also less costly.

Adult