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Biomedical subjects

S Suter

Publications and source records attributed to S Suter.

At least 19 recordsLinked to original sources
PubMed1992

High bronchoalveolar levels of tumor necrosis factor and its inhibitors, interleukin-1, interferon, and elastase, in patients with adult respiratory distress syndrome after trauma, shock, or sepsis.

Intrapulmonary activation of leukocytes and release of cellular mediators and enzymes are involved in the pathophysiology of the adult respiratory distress syndrome (ARDS). To investigate a possible role of local cytokines, we measured bronchoalveolar fluid (BALF) and plasma levels of tumor necrosis factor alpha (TNF-alpha) and its soluble inhibitors (sTNF-RI + RII), interleukin-1 beta (IL-1 beta), interferon-alpha (IFN-alpha), and granulocyte elastase in 14 patients at risk for ARDS and in 35 patients developing ARDS after trauma, sepsis, or shock. During clinical development of severe ARDS, BALF cytokines increased markedly: TNF-alpha from 116 +/- 36 to 10,731 +/- 5,048 pg/ml (mean +/- SEM), p = 0.001; sTNF-RI + RII from 3.7 +/- 1.4 to 24.6 +/- 2.6 ng/ml, p less than 0.05; and IL-1 beta from 7,746 +/- 5,551 to 42,255 +/- 19,176 pg/ml, p = 0.01. Plasma cytokines were not increased in most patients, nor were they correlated with the development or severity of ARDS. BALF elastase was higher in patients developing ARDS than in those at risk but not going into pulmonary failure (0.97 +/- 0.26 versus 0.28 +/- 0.13 U/ml, p = 0.026), and the highest values were observed in the early stages of severe ARDS (1.85 +/- 0.39 U/ml). BALF elastase levels correlated with IFN-alpha (r = 0.72, p less than 0.001). In conclusion, local release of TNF-alpha and IL-1 beta, possibly by pulmonary macrophages or other cells, and/or accumulation in the lung is associated with the development of ARDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchoalveolar Lavage Fluid↗
PubMed1992

Secretory leucocyte proteinase inhibitor: inhibition of fibronectin degradation by neutrophil elastase.

Degradation of surface-bound fibronectin of the upper respiratory tract by human leucocyte elastase (HLE) was shown to favour colonization of these mucosal surfaces by Gram-negative bacteria. We investigated the degradation of fibronectin by purified HLE and by enzymes released from stimulated human polymorphonuclear leucocytes (PMNs), in the presence of recombinant secretory leucocyte proteinase inhibitor (rSLPI) and alpha 1-proteinase inhibitor (alpha 1-PI), the two main inhibitors of HLE within the airways. Our results show that HLE degraded fibronectin at concentrations as low as 0.2 nM. To inhibit the degradation of fibronectin by pure HLE in an experimental system in which the enzyme was premixed with inhibitor, a twofold molar excess of rSLPI and an equimolar concentration of alpha 1-PI were required. On the other hand, a fivefold molar excess of rSLPI was necessary to inhibit degradation of fibronectin by enzymes released from stimulated neutrophils. In order to estimate the role of oxidants generated by stimulated PMNs in the activation of the inhibitory capacity of rSLPI by stimulated PMNs, we preincubated PMNs with antioxidants such as superoxide dismutase, methionine, catalase or Na-azide prior to stimulation of the cells. Under these conditions, a threefold molar excess of rSLPI over released HLE was required to inhibit the degradation of fibronectin, raising the possibility that either exogenous or endogenous antioxidants in the lung could be important in improving the efficacy of this therapeutic antiprotease. We conclude that a molar excess of rSLPI to HLE is always necessary to inhibit fibronectin degradation by HLE, and that addition of antioxidants partly prevents the inactivation of rSLPI by oxidants released from stimulated PMNs.

Antioxidants↗
PubMed1991

The chymotrypsin inhibitor carbobenzyloxy-leucine-tyrosine-chloromethylketone interferes with the neutrophil respiratory burst mediated by a signaling pathway independent of PtdInsP2 breakdown and cytosolic free calcium.

The effects of carbobenzyloxy-leucine-tyrosine-chloromethylketone (zLYCK), an inhibitor of chymotrypsin, were investigated on the activation pathways of the human neutrophil respiratory burst. At 10 microM zLYCK, a parallel inhibition was observed of superoxide production stimulated with the chemo-attractant FMLP and of chymotrypsin-like activity of human neutrophils. By contrast, superoxide production induced by PMA was minimally affected by zLYCK. The known transduction pathways triggered by FMLP were analyzed. zLYCK did not affect either the FMLP-induced cytosolic free calcium transient, inositol 1,4,5 trisphosphate formation, nor the PMA-induced phosphorylation of the 47-kDa substrate of protein kinase C. zLYCK did not affect the activity of protein kinase C extracted from neutrophils. In Ca(2+)-depleted cells, in which phosphatidylinositol 4,5-biphosphate breakdown does not occur, zLYCK inhibited the FMLP-induced respiratory burst in cells primed by low doses of PMA. The activity of the NADPH oxidase tested with active membranes from stimulated neutrophils or in a cell-free system was not inhibited by zLYCK. We conclude that: 1) zLYCK inhibits superoxide production through the inhibition of a chymotrypsin-like protease of the neutrophil, 2) zLYCK inhibits FMLP-induced activation of NADPH oxidase through a pathway independent of PtdInsP2 breakdown and cytosolic free calcium, and 3) zLYCK may prove a useful probe for the characterization of its target protease in neutrophil activation.

Amino Acid Chloromethyl Ketones↗
PubMed1991

Osteoarticular infections due to Kingella kingae in children.

By the description of two cases of osteoarticular infections due to Kingella kingae in two young children we wish to draw the attention of clinicians to invasive infections due to this micro-organism. Since its biological characterization in 1976, K. kingae has been increasingly reported as a human pathogen. Most common presentations are endocarditis, bacteraemia, septic arthritis, osteomyelitis and spondylodiscitis. Interestingly, osteorticular involvement is largely predominant in previously healthy children. From the literature, we reviewed 51 cases of K. kingae bone and joint infections, representing 23 cases of septic arthritis, 17 of osteomyelitis and 11 spondylodiscitis. Of the cases 88% occurred in children below 5 years of age and in all cases only one bone or joint was involved. An underlying disorder could be found in only 4 patients. Since these infections have a favourable outcome with intravenous antibiotic treatment, proper isolation and identification of K. kingae is essential.

Arthritis, Infectious↗
PubMed1991

Spatial-frequency-tuned attenuation and enhancement of the steady-state VEP by grating adaptation.

Steady-state visual evoked potentials (VEPs) were recorded from adults using 10% C fast spatial frequency (SF) sweeps of horizontal gratings under two conditions: (a) after exposure to a 40% C grating of 6 or 4 c/deg, and (b) after exposure to a blank screen equalling the adapting gratings in space-averaged luminance. SF adaptation attenuated VEP amplitude near the adapting SF, but maximum attenuation was displaced from the adapting SF for 6 c/deg adaptation. Small displacements in maximum attenuation would be expected if underlying neural subunits are tuned to a small number of different center SFs. In addition, SF adaptation caused amplitude enhancement 1.0-2.0 octaves below the adapting SF, providing electrophysiological evidence in humans for coinhibitory relationships among neural mechanisms that have been postulated on the basis of analogous psychophysical findings. The results are consistent with coinhibition between SF-tuned subunits and between transient and sustained mechanisms.

Adaptation, Ocular↗
PubMed1991

Proteolytic inactivation of alpha 1-proteinase inhibitor in infected bronchial secretions from patients with cystic fibrosis.

The chronic, progressively destructive bronchitis of patients with cystic fibrosis (CF) is characterized by an important imbalance between tissue destroying granulocyte proteases such as granulocyte elastase (GE) and its physiological inhibitors in bronchial secretions. Recent in vitro studies suggest, that proteases derived from bacteria or endogenous proteases may contribute to inactivation of physiological inhibitors of GE. Since only trypsin-unreactive alpha 1-proteinase inhibitor (alpha 1-PI) was detected in CF bronchial secretions, we attempted to identify the mechanism of inactivation of alpha 1-PI. We found a heat stable, serine protease-like enzymatic activity capable of degrading 125I-labelled alpha 1-PI extensively in 22 infected but not in one non-infected CF bronchial secretion. In infected secretions, only degraded alpha 1-PI, which did not migrate like oxidized alpha 1-PI in tandem-crossed immunoelectrophoresis, was detectable. We conclude, that free GE in excess as well as GE bound to bronchial mucosal inhibitor may partly account for the alpha 1-PI-cleaving activity, but that other yet unknown bacterial or host serine proteases also contribute to alpha 1-PI inactivation.

Bacterial Infections↗
PubMed1991

Epidemiology of invasive Haemophilus influenzae type b infections in Geneva, Switzerland, 1976 to 1989.

We report a retrospective study of invasive Haemophilus influenzae type b (Hib) diseases in Geneva from 1976 to 1989. Among the 183 children who fulfilled the case definition, 6 (3.3%) presented with more than one site of infection. The overall incidence rate among children younger than 5 years of age was 60.2/100,000 but it was 92.1/100,000 in 1989. Forty-one percent of patients had meningitis, 37% had epiglottis and 22% had other forms of Hib infections. Fifty-four percent of cases occurred in children younger than 2 years of age. Invasive Hib infections were found more often in boys than in girls (1.6/1). From 1984, 21% of all Hib were beta-lactamase-producing strains. During the study period 2 children (1.1%) died from epiglottitis and 12 children with meningitis (15.8%) developed serious neurologic deficits. These data suggest that administration of a conjugate vaccine against Hib to all infants living in Geneva is justified.

Age Factors↗
PubMed1990

[Paroxysmal non-hereditary angioedema].

Recurrent hypovolaemic shock had been occurring over the last five and four years, respectively, in a 53-year-old woman and a 46-year-old man who had previously been healthy. The attacks were characterized by a tension feeling and sometimes oedema in the limbs, as well as increased thirst. Within a few hours sweating, tachycardia, orthostatic complaints and shock would occur. The woman's systolic blood pressure would fall to 70 mm Hg and the pulse rate rise to 150/min. The man's blood pressure was not measurable by sphygmomanometer during his first attack. Haematocrit rose to 61 and 71.5%, haemoglobin concentration to 20.7 and 21.3 g/dl, respectively. On administration of plasma expanders all abnormal clinical and biochemical changes quickly disappeared, only to recur within weeks or months. The cause of the condition is an increased permeability of the tissue capillaries, while renal, pulmonary and cerebral vessels apparently are unaffected. During ketotifen and tebonin (gingko biloba extract) administration to the man, he required no further hospitalization for nine months, after which he had three severe attacks. The woman had a severe attack of hypovolaemic shock one month on this treatment. The prognosis of capillary leak syndrome is bad.

Angioedema↗
PubMed1990

A comparison of ceftriaxone and cefuroxime for the treatment of bacterial meningitis in children.

To compare ceftriaxone with cefuroxime for the treatment of meningitis, we conducted a study in which 106 children with acute bacterial meningitis were randomly assigned to receive either ceftriaxone (100 mg per kilogram of body weight per day, administered intravenously once daily; n = 53) or cefuroxime (240 mg per kilogram per day, administered intravenously in four equal doses; n = 53). The mean age of the children was 3 years (range, 42 days to 16 years), and the characteristics of the two treatment groups were comparable at admission. Excluded from the study were eight other children who died within 48 hours of admission. After 18 to 36 hours of therapy, cultures of cerebrospinal fluid remained positive for 1 of the 52 children (2 percent) receiving ceftriaxone for whom cultures were available and 6 of 52 (12 percent) receiving cefuroxime (P = 0.11). In both groups the mean duration of antibiotic therapy was 10 days. The clinical responses to therapy were similar in the two treatment groups, and all 106 children were cured. Reversible biliary pseudolithiasis was detected by serial abdominal ultrasonography only in the children treated with ceftriaxone (16 of 35 vs. 0 of 35; P less than 0.001). The treatment of three children was switched from ceftriaxone to alternative antibiotics because these children had upper abdominal pain. Other side effects were infrequent in both groups. At follow-up examination two months later, moderate-to-profound hearing loss was present in two children (4 percent) treated with ceftriaxone and in nine (17 percent) treated with cefuroxime (P = 0.05); other neurologic abnormalities were similar in the two treatment groups. We conclude that ceftriaxone is superior to cefuroxime for the treatment of acute bacterial meningitis in children and that the benefits of milder hearing impairment and more rapid sterilization of the cerebrospinal fluid with ceftriaxone outweigh the problem of reversible biliary pseudolithiasis with this drug.

Adolescent↗
PubMed1990

Three cases of neonatal herpes simplex virus infection presenting as fulminant hepatitis.

We report three cases of neonatal herpes simplex virus (HSV) infection presenting as fulminant hepatitis. None of the patients had clear risk factors for HSV infection and they all died. Antiviral treatment for HSV is currently available but must be administered early in the course of the disease before irreversible liver tissue damage is present. Since the diagnosis may be difficult to establish, we wish to draw the attention of clinicians to the presentation of neonatal HSV infection and suggest that in such cases viral cultures, including culture of liver tissue, should be obtained early and antiviral treatment administered while awaiting the culture results.

Acute Disease↗
PubMed1990

Serum tumour necrosis factor in newborns at risk for infections.

Tumour necrosis factor-alpha (TNF-alpha) is an important mediator in the pathogenesis of Gram-negative shock. In order to assess the role of TNF-alpha as a marker of the severity of infections in the neonates, serum TNF-alpha concentrations were determined at the time of septic work-up in 69 newborns (gestational age: 28-40 weeks). Nine patients had systemic infection (group A), four of them with signs of circulatory failure. Eleven patients had positive cultures of gastric aspiration or placental smears (group B) and 49 patients had completely negative septic work-up. Patients of group A had significantly more elevated serum TNF-alpha levels than patients of group B and C. Within group A, patients with circulatory failure had mean serum TNF-alpha concentration of 2165 +/- 817 pg/ml versus 27 +/- 8 pg/ml in newborns without shock. Serum TNF-alpha concentrations of more than 15 pg/ml detected systemic infections in eight out of nine patients. The specificity was 98% (1 elevated TNF-alpha concentration out of 60 non infected patients). These data indicate that premature neonates and term newborns are able to produce TNF-alpha when they are infected. Highly elevated TNF-alpha concentrations are found in severe systemic infections causing cardiovascular impairment.

Biomarkers↗
PubMed1990

Pregnancy-associated plasma protein-A-induced inhibition of human leukocyte elastase: an artifact.

Pregnancy-associated plasma protein A (PAPP-A), was reported to be an inhibitor in many in vitro systems. Since it was shown that the inhibition of coagulation and complement activity attributed to PAPP-A was in fact due to a contamination by heparin occurring during the purification process, we undertook the present study to see whether the reported PAPP-A-induced inhibition of human leukocyte elastase (HLE) could also be attributed to heparin contamination. PAPP-A was purified from maternal pregnancy EDTA plasma by a method which was previously shown to eliminate contaminating heparin: this preparation was inactive in the HLE assay. But PAPP-A isolated by heparin-Sepharose chromatography, or a PAPP-A-free washing of the heparin-Sepharose column were both inhibitors of HLE. Furthermore the inactive PAPP-A preparation, when incubated with the PAPP-A-free washing of the heparin-Sepharose column, yielded a high molecular weight preparation which inhibited HLE. It is concluded that PAPP-A is not an inhibitor of HLE and that the inhibition of HLE previously attributed to PAPP-A was due to contaminating heparin.

Chromatography, Gel↗
PubMed1989

Effect of cyclic adenosine monophosphate elevations on functional responses of polymorphonuclear leukocytes from patients with cystic fibrosis.

Recently, it has been suggested that the primary metabolic defect of cystic fibrosis (CF) is in the metabolic steps between an elevation of cyclic adenosine monophosphate (cAMP) and the opening of the Cl- ion channel in airway epithelial cells. Results from other studies have indicated that the primary defect may also be present in polymorphonuclear leukocytes (PMNL). In PMNL, cAMP is a potent inhibitor of cell function. We therefore used three compounds (epinephrine, theophylline, and forskolin) known to elevate cAMP in PMNL by three different mechanisms, to study the effect of an elevation of cAMP on various cell functions, such as superoxide production, membrane depolarization, and degranulation of CF patient PMNL and PMNL from healthy individuals. The baseline rates of superoxide production, degranulation, and membrane depolarization were identical for CF and control PMNL. After exposure to epinephrine as well as theophylline plus forskolin, the cell function of CF PMNL was inhibited to the same extent as that of control PMNL. Our results argue against an abnormal response of PMNL from patients with CF to an elevation of cAMP.

Adolescent↗
PubMed1989

Tumour necrosis factor in neonatal listeriosis: a case report.

A newborn with fatal neonatal listeriosis developed septic shock, neutropenia, thrombocytopenia and profound hypoxaemia due to severe pulmonary hypertension. Tumour necrosis factor alpha, interleukin-1-beta and interferon-gamma serum concentrations were markedly elevated, suggesting the participation of these cytokines in the aetiopathogenesis of shock induced by Listeria monocytogenes in the neonate.

Amoxicillin↗
PubMed1989

Permeability and penicillin-binding protein alterations in Salmonella muenchen: stepwise resistance acquired during beta-lactam therapy.

A patient with Salmonella muenchen sepsis was unsuccessfully treated with ampicillin. During therapy, four strains that showed stepwise ampicillin resistance and affected other beta-lactams and unrelated antibiotics were isolated sequentially. Resistance was caused by decreased outer membrane permeability associated with diminished expression of porin OmpF. Furthermore, the most resistant isolate overproduced the PBP 3 target molecule.

Anti-Bacterial Agents↗