Lactate and glucose concentrations in brain interstitial fluid, cerebrospinal fluid, and serum during experimental pneumococcal meningitis

Metabolic abnormalities during bacterial meningitis include hypoglycorrhachia and cerebrospinal fluid (CSF) lactate accumulation. The mechanisms by which these alterations occur within the central nervous system (CNS) are still incompletely delineated. To determine the evolution of these changes and establish the locus of abnormal metabolism during meningitis, glucose and lactate concentrations in brain interstitial fluid, CSF, and serum were measured simultaneously and sequentially during experimental pneumococcal meningitis in rabbits. Interstitial fluid samples were obtained from the frontal cortex and hippocampus by using in situ brain microdialysis, and serum and CSF were directly sampled. There was an increase of CSF lactate concentration, accompanied by increased local production of lactate in the brain, and a decrease of CSF-to-serum glucose ratio that was paralleled by a decrease in cortical glucose concentration. Brain microdialysate lactate concentration was not affected by either systemic lactic acidosis or artificially elevated CSF lactate concentration. These data support the hypothesis that the brain is a locus for anaerobic glycolysis during meningitis, resulting in increased lactate production and perhaps contributing to decreased tissue glucose concentration.

Use of ampicillin-sulbactam for treatment of experimental meningitis caused by a beta-lactamase-producing strain of Escherichia coli K-1

We evaluated the pharmacokinetics and therapeutic efficacy of ampicillin combined with sulbactam in a rabbit model of meningitis due to a beta-lactamase-producing strain of Escherichia coli K-1. Ceftriaxone was used as a comparison drug. The MIC and MBC were 32 and greater than 64 micrograms/ml (ampicillin), greater than 256 and greater than 256 micrograms/ml (sulbactam), 2.0 and 4.0 micrograms/ml (ampicillin-sulbactam [2:1 ratio, ampicillin concentration]) and 0.125 and 0.25 micrograms/ml (ceftriaxone). All antibiotics were given by intravenous bolus injection in a number of dosing regimens. Ampicillin and sulbactam achieved high concentrations in cerebrospinal fluid (CSF) with higher dose regimens, but only moderate bactericidal activity compared with that of ceftriaxone was obtained. CSF bacterial titers were reduced by 0.6 +/- 0.3 log10 CFU/ml/h with the highest ampicillin-sulbactam dose used (500 and 500 mg/kg of body weight, two doses). This was similar to the bactericidal activity achieved by low-dose ceftriaxone (10 mg/kg), while a higher ceftriaxone dose (100 mg/kg) produced a significant increase in bactericidal activity (1.1 +/- 0.4 log10 CFU/ml/h). It appears that ampicillin-sulbactam, despite favorable CSF pharmacokinetics in animals with meningitis, may be of limited value in the treatment of difficult-to-treat beta-lactamase-producing bacteria, against which the combination shows only moderate in vitro activity.

Experimental models of CNS infections. Contributions to concepts of disease and treatment

Lessons learned from studies of experimental meningitis and brain abscess in animal models of infection represent major, highly significant contributions to our understanding of the pathogenesis and antimicrobial chemotherapy of these infections. For example, studies of experimental meningitis in rabbits demonstrated that the subarachnoid space is deficient in local host defenses, a finding that explains why only bactericidal antibiotic regimens are effective in treating this disease; studies of the efficacy of corticosteroids as adjunctive therapy for meningitis yielded data indicating that both beneficial and detrimental effects on the host are imparted by these compounds. These and a number of other key investigations of experimental meningitis and brain abscess, the results of these investigations, and the clinical significance of these results are presented in this article.

Prevalence study of Staphylococcus aureus in quarter milk samples of dairy cows in the Canton of Bern, Switzerland

In the present study, the prevalence of S. aureus in mammary gland quarters of dairy cows in Switzerland was estimated and a risk factor analysis was carried out. Dairy cows were selected by one-step-cluster sampling with stratification by herd size. Forty-seven of 50 randomly chosen farms participated in the study, resulting in 603 cows and 2388 quarter samples. Milk samples were collected in all herds on two occasions two weeks apart. In 6% of cows (95% CI: 2.7-9.3%) at least one milk sample was positive for S. aureus and from 2% (0.8-3.2%) of all quarters, S. aureus was cultured at least once. In four quarters a latent S. aureus infection (agent detected and somatic cell count (SCC) <100,000cell/ml) was diagnosed. Multivariable hierarchic logistical regression analysis yielded five significant risk factors for observing S. aureus in a milk sample: high SCC, a S. aureus-positive neighbouring quarter, a palpable induration in the quarter, and a wound, scar tissue or crush injury affecting the teat. The type of housing (P=0.1596) was also a factor that remained in the model. The mentioned risk factors must be considered during the evaluation of herds with S. aureus problems. The occurrence of latent S. aureus infections emphasises that not only quarters with a high SCC but all quarters of all cows must be cultured for control measures to be effective.

Mastitis-related subtypes of bovine Staphylococcus aureus are characterized by different clinical properties

Based on a former study from our group, one subtype of Staphylococcus aureus was associated with high within-herd prevalence of mastitis, whereas the other subtypes were associated with a low prevalence (sporadic intramammary infection). To confirm this hypothesis, a prospective study was done in 29 Swiss dairy herds. In particular, milk samples were collected from 10 herds with Staph. aureus herd problems (cases) and compared with samples from 19 herds with only sporadic cases of with Staph. aureus intramammary infection (controls). The isolates were tested for their virulence gene pattern and genotyped by PCR amplification of the 16S-23S rRNA intergenic spacer. The patterns and genotypes were then associated and compared with epidemiological and clinical data. Confirming the hypothesis, one particular subtype (genotype B) was associated with high within-herd and within-cow prevalence of intramammary infection, whereas the other subtypes were associated with low within-herd prevalence and infected single quarters. The gene patterns and genotypes were highly related, demonstrating the genetic diversity of the genotypes. The somatic cell counts were clearly increased in herds with a genotype B problem compared with herds with infections of other genotypes. Based on the different clinical properties and treatment consequences associated with these different genotypes found in Switzerland, we recommend subtyping Staph. aureus in other countries to determine if this finding is universally applicable.

Bovine Staphylococcus aureus: association of virulence genes, genotypes and clinical outcome

Based on our clinical experience on bovine mastitis, we hypothesized that subtypes of Staphylococcus aureus (S. aureus) exist which differ in their contagious and pathogenic properties. In order to investigate this hypothesis, we analyzed strains of S. aureus isolated from spontaneous intramammary infection (IMI) with their virulence gene patterns and genotypes obtained by PCR amplification of the 16S-23S rRNA intergenic spacer (RS-PCR). The genotypes were then associated with epidemiological and clinical data including 26 herds. The results demonstrated a high association between genotypes and virulence gene patterns as well as between epidemiological and pathogenic properties of S. aureus. In particular, genotype B was related to high contagiosity and increased pathogenicity whereas the other types (C, OG) were found with infection of single cows. Because of the high clinical relevance, our results indicate the need to subtype the IMI-associated strains of S. aureus in the future.

Diagnostic delay in Crohn's disease is associated with a complicated disease course and increased operation rate

OBJECTIVES The impact of diagnostic delay (a period from appearance of first symptoms to diagnosis) on the clinical course of Crohn's disease (CD) is unknown. We examined whether length of diagnostic delay affects disease outcomes. METHODS Data from the Swiss IBD cohort study were analyzed. Patients were recruited from university centers (68%), regional hospitals (14%), and private practices (18%). The frequencies of occurrence of bowel stenoses, internal fistulas, perianal fistulas, and CD-related surgery (intestinal and perianal) were analyzed. RESULTS A total of 905 CD patients (53.4% female, median age at diagnosis 26 (20-36) years) were stratified into four groups according to the quartiles of diagnostic delay (0-3, 4-9, 10-24, and ≥25 months, respectively). Median diagnostic delay was 9 (3-24) months. The frequency of immunomodulator and/or antitumor necrosis factor drug use did not differ among the four groups. The length of diagnostic delay was positively correlated with the occurrence of bowel stenosis (odds ratio (OR) 1.76, P=0.011 for delay of ≥25 months) and intestinal surgery (OR 1.76, P=0.014 for delay of 10-24 months and OR 2.03, P=0.003 for delay of ≥25 months). Disease duration was positively associated and non-ileal disease location was negatively associated with bowel stenosis (OR 1.07, P<0.001, and OR 0.41, P=0.005, respectively) and intestinal surgery (OR 1.14, P<0.001, and OR 0.23, P<0.001, respectively). CONCLUSIONS The length of diagnostic delay is correlated with an increased risk of bowel stenosis and CD-related intestinal surgery. Efforts should be undertaken to shorten the diagnostic delay.

Proceedings of the Ninth Annual Biochemical Engineering Symposium

This report presents the proceedings of the Biochemical Engineering Symposium held at Kansas State University, April 28, 1979. Since a number of the contributions will be published in detail elsewhere, only brief reports of each contribution are included here. Requests for further information on work at Iowa State University should be directed to Dr. Peter J. Reilly; at Colorado State University to Drs. V. G. Murphy and A. R. Moreira, and at Kansas State University to Drs. L. T. Fan and L. E. Erickson. ContentProperties of a Homogeneous Xylobiohydrolase from Aspergillus niger, Mary M. Frederick, Iowa State University Kinetic Studies on the Enzymatic Hydrolysis of Cellulose–Absorption and Desorption of Cellulase onto Cellulose and the Behavior of Absorbed Cellulase, Yong-Hyun Lee and L. T. Fan, Kansas State University Properties of a Homogeneous Endo-Xylanase from Aspergillus niger, Ricardo Fournier A., Iowa State University Solid State Fermentation of Manure Fibers, D. C. Ulmer, Colorado State University Analysis and Consistency of Experimental Data for Microbial Growth on Renewable Resources, B. 0. Solomon, Kansas State University Biochemical Mechanisms of Enzyme Regulation, Frederick A. Blum, Colorado State University An Evaluation of Cellulose Pretreatments for Enzymatic Hydrolysis, David H. Beardmore, Kansas State University Use of Immobilized 8-Amylase/Glucoamylase Mixtures to Produce High Maltose Syrups, Carol G. Bohnenkamp, Iowa State University Effect of Viscosity on Bubble Behavior in an Airlift Fermentor, Vasanti Deshpande, Kansas State University

Proceedings of the Eighth Annual Biochemical Engineering Symposium

Contents"Effects of Swell-Shear Treatment on the Digestibility of Cellulosics", Dou-Houng Hwang, UMC "Application of Material and Energy Balance Regularities to Biomass Production from Cellulosic Substrates", Y.H. Lee, KSU "Immobilization of Aspergillus niger beta-Xylosidase", Gbekeloluwa B. Oguntimein, ISU "The Effect of the Major Structural Parameters of Cellulose on Enzymatic Hydrolysis", David H. Beardmore, Y.H. Lee, and L.T. Fan, KSU "Purification of a High Molecular Weight Hemicellulase", Ricardo A. Fournier, ISU "Aerobic Fermentation of Banana Pulp by Aspergillus Fumigatus", Stephen Lorbert, UMC "Purification and Properties of Two Very Small Xylanases", Chih-hen Kiang, ISU "Testing Theoretical Models for Cellulose Enzymatic Hydrolysis", Lin-Chang Chiang, UMC "Utilization of Material and Energy Balances in Hydrocarbon Fermentation", Alexis Ferrer, KSU "Purification of a Series of Closely Related Xylanases", Mary M. Frederick, ISU

Penetrating or stricturing diseases are the major determinants of time to first and repeat resection surgery in Crohn's disease

BACKGROUND About 80% of patients with Crohn's disease (CD) require bowel resection and up to 65% will undergo a second resection within 10 years. This study reports clinical risk factors for resection surgery (RS) and repeat RS. METHODS Retrospective cohort study, using data from patients included in the Swiss Inflammatory Bowel Disease Cohort. Cox regression analyses were performed to estimate rates of initial and repeated RS. RESULTS Out of 1,138 CD cohort patients, 417 (36.6%) had already undergone RS at the time of inclusion. Kaplan-Meier curves showed that the probability of being free of RS was 65% after 10 years, 42% after 20 years, and 23% after 40 years. Perianal involvement (PA) did not modify this probability to a significant extent. The main adjusted risk factors for RS were smoking at diagnosis (hazard ratio (HR) = 1.33; p = 0.006), stricturing with vs. without PA (HR = 4.91 vs. 4.11; p < 0.001) or penetrating disease with vs. without PA (HR = 3.53 vs. 4.58; p < 0.001). The risk factor for repeat RS was penetrating disease with vs. without PA (HR = 3.17 vs. 2.24; p < 0.05). CONCLUSION The risk of RS was confirmed to be very high for CD in our cohort. Smoking status at diagnosis, but mostly penetrating and stricturing diseases increase the risk of RS.

La figure de la sorcière dans la littérature du XIXe siècle (Jules Michelet, George Sand, Eliza Orzeszkowa)

The nineteenth century uncovered and analysed the tragic episodes of witch-hunting and ‘witch’ trials common in Renaissance Europe. Fascinating not only to historians, this subject also inspired men of letters who popularized the image of the witch as an old, ugly and evil person, who thus deserved her lot. Jules Michelet’s La sorcière of 1862 takes a very different approach. Simultaneously a literary and historical work, the book proved scandalous as it rehabilitated the figure of the witch, shedding favourable light on her image: it was the witch who was able to save a last spark of humanity in moments of despair; it was she who acted as comforter and healer to the people. In the context of nineteenth-century literature, certain works by female authors that focused on ‘witches,’ stand out. Whilst certain male authors (Michelet included) presented the witch as a figure from the past, who had finally perished in the 17th century, texts such as George Sand’s La petite Fadette (1848) or Eliza Orzeszkowa’s Dziurdziowie (1885), suggest that the end of witch trials did not imply an end to accusations, persecutions, and even executions of ‘witches’ – and, that in terms of culture, witchcraft or sorcery had not disappeared from the societies they knew.

Wieczna kobiecość i emancypacja kobiet: obraz kobiecości w twórczości Karoliny Světlej

To nie przypadek, że wyrażenie „wieczna kobiecość" ukute przez Goethego zbiega się w czasie z pierwszymi zachodnimi próbami emancypacji kobiet. W chwili, kiedy model kobiety istniejącej tylko w zależności od mężczyzny zaczyna być kwestionowany, kategoria wiecznej kobiecości pozwala ponownie potwierdzić ten model, wypełniając go pozytywnymi wartościami. Naturą kobiety jest być uległą i oddaną, a te cechy sprawiają, że kobieta jest depozytariuszem wszelkiej potencjalnej zbawczej łaski. Tak w Fauście Goethego, przypada Małgorzacie, dziewczynie naiwniej, niewinnej, niewykształconej i bez własnej woli, wykupić Fausta siłą swojej miłości. Wszystko dzieje się tak, jakby pozytywna kodyfikacja właściwości kobiet dzięki kategorii wiecznej kobiecości służyła tylko lepszemu ukryciu rzeczywistości ich ucisku; feministki jednak nie dają się zwieść: ideały popierane przez kategorię wiecznej kobiecości są a priori niezgodne z emancypacją kobiet. Karolina Světlá, jedna z najważniejszych postaci w walce o zrównanie praw między mężczyznami i kobietami w Czechach w XIX wieku, wykorzystywała przecież intensywnie w swojej literackiej twórczości ten model kobiety, która poświęca się dla kochanego mężczyzny i tym samym udaje się jej go "podciągnąć do góry" ("hinan zu ziehen", Goethe) oraz dać mu dostęp do "nieskończoności", "nieśmiertelności" i "wieczności". Czy jej teoretyczne pisma i jej działalność na rzecz emancypacji kobiet zaprzeczałyby jej tekstom literackim, na pierwszy rzut oka tak konwencjonalnym? W tym wykładzie podejmuję próbę odpowiedzi na to pytanie uważną lekturą jednego z jej najbardziej faustowskich opowiadań, mianowice "Czarna dziewanna".