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Biomedical subjects

H Keller

Publications and source records attributed to H Keller.

At least 19 recordsLinked to original sources

Risk factors for the reinfection of specific pathogen-free pig breeding herds with enzootic pneumonia.

A case control study was designed to determine the risk factors for the reinfection of Swiss specific pathogen-free (SPF) pig herds with enzootic pneumonia. Detailed housing, management and environmental data were collected from 42 case farms and 50 control farms by means of a questionnaire. Factors with a significantly asymmetrical frequency distribution among the two groups were considered to be possibly associated with reinfection; they included the distance to the nearest non-SPF pig herd, the size of that herd, the density of the pig population in the area, the distance to the next road regularly carrying pig transporters and differences in topography. The results tended to support the hypothesis of the airborne transmission of enzootic pneumonia. Using a formula considering the main risk factors, it was possible to classify farms as high or low risk with an 84 per cent specificity and 74 per cent sensitivity.

Air Pollution

Protein phosphatase inhibitors okadaic acid and calyculin A alter cell shape and F-actin distribution and inhibit stimulus-dependent increases in cytoskeletal actin of human neutrophils.

The phosphatase inhibitors okadaic acid and calyculin A were found to elicit or to modify several neutrophil responses, suggesting that dephosphorylation plays a regulatory role. The concentrations of okadaic acid (> or = 1 mumol/L) that were effective on neutrophil functions (shape changes and marginal stimulation of pinocytosis) were shown to stimulate the incorporation of 32PO4 into many neutrophil proteins several-fold. Calyculin A was effective at 50-fold lower concentrations. In the presence of the inhibitors, the cells exhibited a nonpolar shape and the polarization response induced by chemotactic peptide was inhibited. Both phosphatase inhibitors also induced the association of F-actin with the cell membrane. A steady-state phosphatase activity is thus involved in maintaining shape and F-actin localization of resting cells. Inhibitors alone had no significant effect on the amount of cytoskeleton-associated actin. The increase in cytoskeletal actin observed at 30 minutes of stimulation with phorbol ester or 5 to 30 minutes of stimulation with chemotactic peptide, however, was abolished by okadaic acid or calyculin A, suggesting an important role of a phosphatase. In contrast, the early increase in cytoskeleton-associated actin observed at 1 minute of stimulation with peptide was not affected. This finding indicates that the increased association of actin with the cytoskeleton in the early and the later stages of neutrophil activation may be mediated by different signalling pathways.

Actins

[Spondylitis due to Citrobacter diversus. Case report and review of Citrobacter diversus infections].

Citrobacter diversus (C.d.) is an unusual human pathogen. Its pathogenic potency is small or nil, and in most cases it is isolated in combination with other organisms. Most isolates are of indeterminate clinical significance. Occasionally C.d. may cause opportunistic infections, especially in subjects with primary or secondary conditions of poor host defense, immunosuppressed patients or neonates. We report a case of C.d. vertebral osteomyelitis following C.d. pneumonia. The osteomyelitis was cured by surgery and chemotherapy. This case is interesting since it involves an otherwise healthy subject with no underlying disease. C.d. was isolated in blood during the episode of pneumonia and in bone four weeks later. No other case of Citrobacter diversus vertebral osteomyelitis has hitherto been described.

Aged

Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors.

Three novel members of the Xenopus nuclear hormone receptor superfamily have been cloned. They are related to each other and similar to the group of receptors that includes those for thyroid hormones, retinoids, and vitamin D3. Their transcriptional activity is regulated by agents causing peroxisome proliferation and carcinogenesis in rodent liver. All three Xenopus receptors activate the promoter of the acyl coenzyme A oxidase gene, which encodes the key enzyme of peroxisomal fatty acid beta-oxidation, via a cognate response element that has been identified. Therefore, peroxisome proliferators may exert their hypolipidemic effects through these receptors, which stimulate the peroxisomal degradation of fatty acids. Finally, the multiplicity of these receptors suggests the existence of hitherto unknown cellular signaling pathways for xenobiotics and putative endogenous ligands.

Acyl-CoA Oxidase

Effects of staurosporine, K 252a and other structurally related protein kinase inhibitors on shape and locomotion of Walker carcinosarcoma cells.

The structure/activity relationship of the protein kinase inhibitors, staurosporine and K 252a and their analogues on motility of Walker carcinosarcoma cells has been studied in vitro. Staurosporine and K 252a, similar to phorbol myristate acetate (PMA) and diacylglycerols, suppress cell polarity and locomotor activity of Walker carcinosarcoma cells. Staurosporine inhibits spontaneous and colchicine-induced front-tail polarity (ID50 of about 6.0 x 10(-8) M) as well as spontaneous and colchicine-stimulated locomotion at 10(-7) M. K 252a suppresses cell polarity (ID50 of about 4.5 x 10(-6) M) and inhibits spontaneous and colchicine-stimulated locomotion at 10(-5) M, but suppression of locomotor activity is not complete in the presence of colchicine. CGP 41251, a staurosporine derivative with a much higher specificity for protein kinase C (PKC) than staurosporine, induces a dose-dependent increase in the proportion of polarised cells, and stimulates cell locomotion. Two K252a analogues, KT 5720 and KT 5822, which act preferentially on cyclic nucleotide-dependent protein kinases, and CGP 42700, an inactive staurosporine analogue, had no effect on cell polarity and locomotion. The findings suggest that protein kinase inhibitors acting preferentially on PKC may be of interest in pharmacological regulation of tumour cell locomotion.

Alkaloids

[The gamma-nail as a resilient alternative to the dynamic hip screw in unstable proximal femoral fractures in the elderly].

In a prospective randomised trial between September 1989 and June 1990 one hundred patients with per- and subtrochanteric fractures were consecutively treated by gamma-nail or DHS. The average age of both groups was about 80 years. The operation time for gamma-nailing was longer than for DHS implantation and also the postoperative blood loss was higher in the gamma-nail group. We found no difference of intraoperative blood loss, of perioperative lethality and in duration of hospital care. 90% of gamma-nail patients and 80% of DHS patients were successfully able to walk four days after operation with full weight bearing on the operated limb. Three patients in the DHS group with unstable fractures got cranial perforation of the cephalic screw mobilisation. Five patients of the gamma-nail group were reoperated, one case because of missed distal locking, one because of cranial perforation of the cephalic screw after varus dislocation of the proximal fragment. One patient suffered intraoperatively a proximal femur shaft fracture which was corrected during operation. In one case a wound hematoma was evacuated, an other patient needed secondary wound closure. Despite technical imperfection of implant and instruments, we conclude that the gamma-nail allows a very high percentage early and full weight bearing immediately after operation. So we consider that in the treatment of unstable pertrochanteric fractures of geriatric patients, the gamma-nail has proven to be more efficient than the DHS.

Aged

[The use of laboratory data].

Medical laboratory data are gained by scientific methods. The method-inherent uncertainties always produce an "inexactitude" of varying degree. The physician who uses these data as a support for his decisions should therefore be able to estimate the reliability of the laboratory data; this can be assessed by statistical methods. The most fundamental characteristics of all analytical methods are analytical inaccuracy and analytical imprecision. The limit of detection and the limits of the measuring interval are functions of these figures. A number of illustrations demonstrate the interdependence of analytical performance and of medical significance of laboratory data. Laboratory data, on the other hand, are--to put it simply--used to distinguish diseased from NON-diseased individuals. The "diagnostic validity" of a certain test for a certain medical problem is determined by comparing appropriate collectives. The selection of these collectives and the choice of the cut-off value determine diagnostic sensitivity and specificity respectively. From these figures and prevalence (or "pre-test probability"), the predictive values of a positive (or negative) result can be calculated. The significance of the position of the cut-off value and of prevalence is demonstrated by a number of examples. If the results are not given in a binary form (positive/negative) but in different grades (slightly, moderately, strongly elevated/depressed), and if the results of several tests must be judged in a multivariate manner, the number of theoretically possible patterns can become extremely large. Various approaches designed to overcome these problems are discussed.

Clinical Laboratory Techniques

[Postanesthetic complications in the horse. Evaluation of anesthesia in the last 28 years (1962-1989)].

The anesthesia routine in the horse is briefly explained. 35 postanesthetic complications resulted from the total of 4364 cases of anesthesia. They are evaluated by means of the duration of anesthesia, the time of paresis, the exemplary courses of enzymes as well as the distribution of race and sex and their ratio towards all cases of anesthesia. Finally a list of demands concerning the operative and postoperative phases is compiled to minimize postoperative myositis (PAM) and lameness (PAL).

Anesthesia

On the role of protein kinases in regulating neutrophil actin association with the cytoskeleton.

We have investigated the effect of staurosporine-type protein kinase inhibitors, displaying different enzyme specificity, on the association of actin with the neutrophil cytoskeleton. In resting cells, nanomolar concentrations of staurosporine induced a rapid increase in cytoskeleton-associated actin. Other inhibitors, more specific for protein kinase C (PKC) or kinases dependent on cyclic nucleotides, induced a much smaller response, indicating that inhibition of these enzymes is not involved in the staurosporine-dependent rise. Therefore, inhibition of an unknown staurosporine-sensitive enzyme, not identical with PKC or one of the cyclic nucleotide-dependent kinases, can trigger an increase in cytoskeletal actin. It is well known that chemotactic peptide induces a rapid rise in cytoskeletal actin, followed by a decrease at later times after the onset of activation. Preincubation with CGP 41,251, a relatively specific inhibitor for PKC, did not affect these two events at concentrations of the drug which, in separate experiments, inhibited markedly phorbol ester induced protein phosphorylation in intact neutrophils. Thus the chemotactic peptide-induced changes in the level of cytoskeletal actin appear to be independent of PKC activation.

Actins

New method for the determination of pancreatic amylase evaluated.

We have carried out a multicenter evaluation of a new reagent carrier for Reflotron, specific for pancreatic amylase where the salivary isoenzyme is inhibited by two specific monoclonal antibodies. This new procedure combines easy handling with low imprecision (median CV less than 3%) in control material, serum, heparinized blood, and plasma) and close correlation (r = 0.991 to 0.999) with established manual and automated methods. The same close correlation was found with values obtained from either venous or capillary finger-stick blood. Salivary amylase up to 54 kU/L (37 degrees C) was inhibited to about 97%. Endogenous interference by hemoglobin, bilirubin, triglycerides, cholesterol, or hematocrit was found to be negligible within a wide range of interferent concentrations. Out of a panel of 28 commonly used drugs it was shown that only two (ascorbic acid and paracetamol), and then only at toxic concentrations, caused a deviation in amylase activity of greater than 10%. From the results of this study we conclude that this new method is suitable for highly precise and accurate measurements of pancreatic amylase in emergency and routine laboratories.

Amylases

Diversity in motile responses of human neutrophil granulocytes: functional meaning and cytoskeletal basis.

Different agonists induce motility and shape changes, but only a specific polarized shape is correlated with directed migration. An intact and dynamic actin network appears to be important for motility and migration. Motility is usually associated with an increased level of F-actin, and a specific location of F-actin into surface protrusions. For locomotion, a specific location of F-actin, rather than a large net increase in F-actin appears to be of importance. Three major groups of responses can be distinguished on the basis of the type of shape changes, functional activity and organization of F-actin. 1. Agents capable of polarizing cells, such as chemotactic peptides, and microtubule-disassembling agents elicit, at appropriate concentrations, a marked chemokinetic response, but little if any fluid pinocytosis. F-actin shows a polar location, being concentrated mainly in the protrusions at the leading front. Chemotactic peptide also induces an increase in the level of F-actin and cytoskeleton-associated actin. It is, however, not clear if front-tail polarity and locomotion, induced by chemotactic peptide after longer time of stimulation, correlate with an actual increase in the level of cytoskeleton-associated actin. 2. Activators of protein kinase C such as PMA and diacylglycerols, induce nonpolar cells with surface projections. PMA and diacylglycerols stimulate pinocytosis substantially. All three agents tend to inhibit locomotion or chemotaxis as an immediate response. They also increase the percentage of cytoskeletal actin, and induce an enrichment of F-actin in surface projections. 3. Circus movement may occur in response to D20. These cells show little or no stimulation of locomotion or pinocytosis. Thus the functional significance of this motor response remains to be elucidated. We conclude that different agonists can induce motility and shape changes, but not necessarily chemotaxis. Only a polarized shape is correlated with directed locomotion. An intact and dynamic actin network appears to be important for motility including locomotion. Motility is usually associated with an increased level of F-actin, and a specific location of F-actin into surface protrusions. The actin-associated proteins alpha-Actinin, myosin and actin-binding protein appear also to be important for pseudopod formation. For locomotion, a specific location of F-actin, rather than a large net increase in F-actin may be of importance.

Actins

[Comparison of the adverse effect profile of different substances such as penicillins, tetracyclines, sulfonamides and quinolones].

The penicillins, the tetracyclines and the sulfonamides have often been used in the last few decades in spite of their well-known side effects. Hypersensitivity reactions to penicillins are among the most important adverse reactions in these antibiotics; in every case a careful medical history has to be taken before a new course of penicillin treatment. The use of tetracyclines in women during the last six months of pregnancy or in children under the age of eight years is contraindicated. Patients with severe blood, kidney or liver disease should not be treated with sulfonamides. Toxic reactions to penicillin even with convulsions may occur in patients with renal insufficiency if the dosage is not adapted. The fluoroquinolones do not seem to have greater risks regarding adverse reactions than the historical compounds mentioned. Neurotoxicity is an important problem. Mild reactions are reported with incidences under 2%; severe neurotoxic side effects that require interruption of therapy are rare. Psychotic reactions, hallucinations, depressions and grand mal convulsions also belong to this category. Other side effects (skin, GI-tract) are no more frequent than with the classical antibiotics. In patients with renal insufficiency the dosage of ofloxacin has to be adapted. The cartilage lesions which are seen in juvenile rats and dogs raise the question whether or not the cases of arthralgia during therapy with older quinolones as well as under treatment with fluoroquinolones have a causal relationship. Up to date quinolones should not be prescribed in children and young adults except in cases with cystic fibrosis. The development of resistance has not been a significant problem so far.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Quinolones

Management of perioperative hypertension using intravenous isradipine.

The antihypertensive action of acute intravenous isradipine was investigated during fentanyl/pancuronium/nitrous oxide anesthesia for noncardiac surgery. An intravenous (iv) infusion of 0.5 mg isradipine (n = 10) or placebo (n = 11) was administered double-blind over 5 min if mean arterial pressure (MAP) was greater than 110 mm Hg. The number of patients with a favorable blood pressure reduction (delta MAP greater than or equal to 10% with MAP less than or equal to 110 mm Hg) was 80% with isradipine and 20% with placebo (P less than .05), and the mean MAP reduction from baseline was 26 +/- 12 and 2 +/- 16 mm Hg, respectively (P less than .001). Due to reflex activation of the sympathetic nervous system, the heart rate increased by 14 +/- 12 beats/min with acute iv isradipine. The antihypertensive effect was sustained for 45 min. Isradipine was also well tolerated. It is concluded that intravenous isradipine is an effective antihypertensive agent for the treatment of perioperative hypertension during noncardiac surgery.

Adolescent

[The Gamma Nail in per- and intertrochanteric femoral fractures--alternative or supplement to the dynamic hip screw? A prospective randomized study of 100 patients with per- and intertrochanteric femoral fractures in the surgical clinic of the City Hospital of Triemli, Zurich, September 1989 - June 1990].

In a prospective randomised trial between September 89 and June 90 one hundred patients with per- and subtrochanteric fractures were consecutively treated by Gamma-nail or DHS. The average age of both groups was about 80 years. The operation time for Gamma-nailing was longer than for DHS-implantation and also the postoperative blood loss was higher in the Gamma-nail-group. We found no difference of intraoperative blood loss, of perioperative letality and in duration of hospital care. 90% of Gamma-nail-patients and 80% of DHS-patients were successfully able to walk four days after operation with full weight bearing on the operated limb. Six patients (12%) with DHS had to be reoperated within 6 weeks. Three patients with unstable fractures got cranial perforation of the cephalic screw after mobilisation. The other three patients had soft tissue complications. Five patients (10%) of the Gamma-nail-group were reoperated, one case because of missed distal locking, one because of cranial perforation of the cephalic screw after varus dislocation of the proximal fragment. One patient suffered intraoperatively a proximal femur shaft fracture which was corrected during operation. In one case a wound hematoma was evacuated, an other patient needed secondary wound closure. Despite technical imperfection of implant and instruments, we conclude that the Gamma-nail allows a very high percentage early and full weight bearing immediately after operation. So we consider that in the treatment of unstable pertrochanteric fractures of geriatric patients, the Gamma-nail has proven to be more efficient than the DHS.

Adult