Biomedical subjects
Publications and source records attributed to W Graninger.
The response to pirenzepin, a new acetylcholine receptor blocking agent, was assessed and compared to placebo in patients with reversible bronchoconstriction. A single intravenous injection of 20 mg of pirenzepin induced a significant reduction of airway resistance compared to placebo (p less than 0.05). The anticholinergic substance pirenzepin appears to be useful in the treatment of bronchospasm.
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Antithrombin III activity and plasma fibronectin levels were determined in patients with preeclampsia. In several cases low antithrombin III and high plasma fibronectin concentrations could be related to proteinuria. Altered plasma fibronectin and antithrombin III concentrations might contribute to a hypercoaguable state in patients with preeclampsia.
Plasma concentrations of fibronectin, albumin, total protein and IgM were measured in 14 male patients undergoing aorto-coronary bypass operations. Fibronectin and IgM concentrations fell to 55% of the preoperative values 5 minutes after start of the extracorporeal circulation, and the same percentages were encountered 5 minutes after the termination of bypass. The concentrations had recovered to 75% of the preoperative values by the end of the operation. The plasma concentration of albumin was 68 +/- 9% of the preoperative value after 5 minutes of bypass, 66 +/- 7% at the end of bypass, and 83 +/- 9% of the end of operation (significantly different from fibronectin and IgM, p less than 0.05; Wilcoxon's test for paired differences). No correlation was found between the duration of extracorporeal circulation and the post-bypass concentrations of any protein (Kendall correlation). It is concluded that the fall of fibronectin concentrations during cardiopulmonary bypass can be sufficiently explained by dilution, and that a specific consumption of fibronectin does not occur. The less marked decreases of albumin and total protein were probably due to infusion of plasma-protein solution, which is poor in fibronectin and IgM.
12 patients with severe chronic idiopathic thrombocytopenic purpura (ITP) were treated with i.v. polyvalent intact immunoglobulin (0.14-0.4 g/kg body weight for 5 d) because of various bleeding episodes or prior to surgery. In 9 patients a significant rise in platelet counts was noted, starting on d 2 and reaching its maximum between d 4 and 11. Thereafter, platelet counts decreased slowly, approaching pre-treatment values after 20 d in most cases. Response to immunoglobulin was reproducible, when infusions were repeated. Response to high-dose immunoglobulin was independent of age of patients and duration of disease. Platelet-associated IgG decreased in all patients tested. A pepsin-treated immunoglobulin preparation was ineffective in 3 patients.
Plasma fibronectin concentrations up to 85 mg/100 ml were found in hyperthyroid patients. There was a significant correlation between free thyroxine index and plasma fibronectin values. Hypothyroid patients had low to normal fibronectin concentrations. Parallel decreases of thyroid hormones and plasma fibronectin concentrations were noted during treatment with thiamazole. A direct effect of thyroid hormones on fibronectin synthesis seems probable.
14 patients with hemophilia were studied for the distribution of T cell subsets, the presence of antibody to lymphadenopathy-associated or human T lymphotropic virus type III (LAV/HTLV-III), and their responsiveness in autologous mixed lymphocyte reactions. In addition, mitogen and alloantigen responsiveness and Interleukin-2 production were investigated. Seven patients were found to have low Leu 3a/Leu 2a (T4/T8) ratios; eight patients had antibody to LAV/HTLV-III; and an additional patient had acquired immunodeficiency syndrome. Responsiveness to mitogens and alloantigens as well as Interleukin-2 production were comparable with those of healthy individuals. However, patients with low ratio, many of whom had antibodies to LAV/HTLV-III, had a highly deficient autologous mixed lymphocyte reaction. This reduced response of T cells to autologous non-T cells could not be corrected by elimination of Leu 2a/T8 cells, which indicated that there was a preferential loss of the Leu 3a cell subset(s) which responded to autologous non-T cells. Thus, these patients have a deficiency of intercellular communication within their immune system.
Approximately 25% of blood was replaced by either hydroxyethyl starch (mol. wt 450,000), dextran (mol. wt 60,000), or 5% plasma protein solution, 24 h prior to a surgical intervention. Twenty-four adult patients were studied and haematocrit, total protein, plasma albumin, alpha-1-antitrypsin, IgG, IgM, antithrombin III, fibronectin and alpha-2-macroglobulin were determined. The resulting blood concentrations suggest that the various replacement solutions exert only a dilutional effect upon the proteins studied. Furthermore, there is no difference regarding the course of the various infection-related proteins whether plasma protein solution or synthetic colloids are used for blood replacement. The decrease of the studied proteins during the study period does not exceed 35% of the control value. This is not considered to be a clinically significant reduction and levels of infection-related proteins were not dangerously low.
The in vitro activity of fosfomycin against 90 strains of methicillin- and gentamicin-resistant Staphylococcus aureus was studied in an in vitro microtitre system using Mueller-Hinton broth supplemented with glucose-6-phosphate. In parallel the antistaphylococcal activity of cefamandole, N-formimidoyl-thienamycin, clindamycin, fusidic acid and vancomycin was determined with the same organisms. The following MIC50 (MIC95) values were obtained: fosfomycin 8 (128) mg/l, cefamandole 8 (greater than 64) mg/l, clindamycin 0.25 (16) mg/l, fusidic acid less than 0.25 (less than 0.25) mg/l, vancomycin 1 (2) mg/l and N-formimidoyl-thienamycin 4 (16) mg/l. A high MIC/MBC ratio was noted for cefamandole, in contrast to fosfomycin.
In 18 adult patients, in a randomized way, 15 ml/kg of blood were replaced either by gelatin 5.5 pc or serum protein solution. 0,5, 4 and 24 h later there was only a significant difference between the two groups in total protein and serum albumin. The low molecular weight infection related proteins alpha-1-antitrypsin, immunoglobulin G and antithrombin III, as well as the high molecular weight proteins immunoglobulin M, plasma fibronectin and alpha-2-macroglobulin were at no time significantly different between the two groups. It is concluded that gelatin as a plasma substitute does not impair the opsonising effect of plasma fibronectin upon the reticuloendothelial system.
Nosocomial pneumonia is a major risk for long term ventilated ICU patients. The infection route may be hematogenic or via inhalation or aspiration of microorganisms. The source of aspiration is the oropharynx. This prospective study intended to study the role of the stomach as a reservoir of bacteria in ICU patients treated with cimetidine. Gastric juice and bronchial secretion from 34 patients ventilated for more than 4 days were examined bacteriologically. 72,8% of the gastric (G) and 79,1% of the bronchial aspirates (B) revealed significant bacterial growth (more than 10(4) microorganism/ml). Pseudomonas, Klebsiella, and Candida spp. were found in 56,7% (B) and 51,8% (G) of the positive cultures as an effect of selection caused by antibiotics. Organisms of intestinal origin were found in 17,8% (B) und 15,5% (G), respectively. In 32,5%, identical organisms or patterns of organisms were found in the gastric and bronchial aspirates. 7 of the 34 patients (20,6%) developed pneumonia; in 6 of these 7 cases, the same organisms could be identified at the same and/or at the last examination before developing pneumonia in gastric content and bronchial secretion. The pH-value of the sterile aspirates was lower than of the colonized aspirates (5,39 vs 5,99). During enteral nutrition, 31,4% of the aspirates were sterile, whereas during parenteral nutrition only 24,3% of the gastric aspirates were sterile. Therefore, enteral nutrition should be started as soon as possible, the pH-value should be checked frequently and should not exceed 4 in order to reduce bacterial overgrowth in the stomach. A further consequence is to use as few antibiotics as possible.
The intestinal flora under normal conditions prevents colonisation of the intestinal mucosa with pathogenic bacteria. Various diseases as well as antibiotics may disturb the host/bacteria balance. If patients are in addition immunocompromised, otherwise commensal bacteria may cause life threatening infections. Treatment of intensive care patients with antibiotics thus should account for preservation of resistance against colonization. Antibiotics active against anaerobes or poorly absorbed from the gastrointestinal tract, or excreted in the bile should be avoided. In patients with colitis induced by antibiotics the number of clostridium difficile with subsequent toxin production are greatly increased as a consequence of the killing of the normal anaerobic colon bacterial flora; in these patients vancomycin has to be applied. Mostly "dysbiosis" caused by antibiotics does not need any treatment. Therapeutic adjuncts like the administration of bacterial preparations e.g. lactobacilli are of no value.
A method for investigating the cellular response of polymorphonuclear leukocytes to various stimuli was introduced using simultaneously native (luminol-independent) and luminol dependent luminescence as an indicator for myeloperoxidase (MPO)-H2O2-halide and O2- mediated reactions. In experimental systems containing low concentrations of luminol the total light emission was separated into contributions of native and luminol-dependent luminescence by making use of the different spectral behaviour of the two kinds of luminescence. Consequently the MPO-H2O2-halide system could be distinguished from the O2- dependent system by interpreting the recorded temporal traces of the emitted light.
An assessment was undertaken of the value of plasmapheresis in patients with circulating immune complexes and/or extraintestinal manifestations of Crohn's disease (arthritis, iridocyclitis, erythema nodosum, pyoderma gangrenosum, stomatitis, fever). In 17 patients aged 20 to 50 years (median 34 years) 46 plasmaphereses were performed using a continuous flow-cell separator. Before and after plasmaphereses the concentrations of circulating immune complexes, of complement C4, of the immunoglobulins IgG and IgM and of the proteins alpha-1-antitrypsin, CRP, prealbumin and beta-lipoprotein were determined. 71% of patients given plasmaphereses showed clinical remission of the extraintestinal manifestations and 85% demonstrated a reduction of circulating immune complexes. Clinical follow-up of the patients was documented by the Crohn's Disease Activity Index (CDAI), which was reduced by plasmaphereses to a highly significant degree (p less than 0.005). For patients displaying an acute phase of Crohn's disease with extraintestinal manifestations and/or circulating immune complexes plasmapheresis represents an effective mode of therapy, which, moreover, lacks serious side effects.
In nine patients with nephrotic syndrome the behaviour of plasma fibronectin was studied. Of nine patients seven showed elevated plasma fibronectin levels while the plasma fibrinogen level was increased in eight of the nine investigated patients. A positive correlation was found between plasma fibronectin levels and fibrinogen (P less than 0.01), cholesterol (P less than 0.01) and proteinuria (P less than 0.05). The results indicate that elevated plasma fibronectin levels could be an additional factor responsible for hypercoagulability in nephrotic syndrome.
Activity of Poly (C) avid ribonuclease was estimated in sera of 129 patients with different malignancies. All patients had histologically verified carcinomas, normal renal function, and no signs of acute catabolic condition. Activity values were compared with those of normal subjects (U-test, Mann and Whitney) separately for each age decade and type of carcinoma. Patients with ovarian and bronchus carcinoma had statistically elevated activity values throughout all age groups. Colon carcinoma patients showed elevated values in most instances. In patients with pancreatic carcinoma a difference could be detected in only one age group (51-60 years of age). No significant elevation of enzyme activity was detected in carcinoma of the stomach and of the prostate. It is concluded that there are carcinomas leading to elevated ribonuclease activity, although the biological basis of this phenomenon is not understood. No special sensitivity nor specificity of ribonuclease elevation could be demonstrated in pancreatic carcinoma patients. Up to now the usefulness of ribonuclease estimation in prospective carcinoma detection remains questionable.
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Antibiotic prophylaxis with 2 g Cefamandole at induction of anaesthesia was performed in 12 male patients undergoing aortocoronary bypass surgery. Caused by hemodilution, there was a marked decrease of serum concentration at the beginning of extracorporeal circulation, from 110.96 +/- 40.29 mcg/ml to 70.89 +/- 34.65 mcg/ml within 10 min. During extracorporeal circulation, elimination was as fast as before and after perfusion. 240 min after application, mean serum concentrations of 16.80 +/- 9.32 mcg/ml were measured. Failure of antibiotic prophylaxis in operations exceeding 4 h might be due to unadaequate antibiotic concentrations, beyond the minimal inhibitory concentration for the pathogens, reported to cause infections after cardiac operations.