[Carl Gillmeister: the first Doctor of veterinary medicine in Mecklenburg--and in Germany (1834)]. / Carl Gillmeister: der erste Doctor medicinae veterinariae in Mecklenburg--und in Deutschland (1834).

German schools and faculties of veterinary medicine did not receive the sovereign right to award the degree "Doctor medicinae veterinarae" until the early twentieth century. Until then, in the nineteenth century there were two possibilities for veterinarians to earn a doctoral degree, usually referred to as the title of "Doctor": 1. On the basis of an exceptionally excellent dissertation and after very stringent examination a candidate could be awarded the degree "Dr. med." by the faculty of a medical school, or, if the candidate had studied at a philosophical faculty, the degree "Dr. phil." 2. A doctoral degree specifically in veterinary medicine could be earned only at a medical faculty. The Medical Faculty of the University of Giessen awarded the degree "Doctor in arte veterinaria" for the first time in 1832. In this study we prove that Giessen was not the first German university to award a doctorate in veterinary medicine, a priority which has never been questioned in the literature. As early as 1829, veterinarians could earn the degree "Doctor artis veterinariae" at the Medical Faculty of the University of Rostock, where three such awards are documented between 1829 and 1831. The designation "medicina" was also intially avoided in Rostock. Therefore, of particular significance is the discovery of a fourth such document from the Rostock University Archives, the doctoral diploma of Carl Jacob Friedrich Gillmeister, who at the age of 22 was awarded the degree "Doctor medicinae veterinariae" in Rostock after a successful defense. This is the earliest, but also the last archival record of the German doctoral degree in veterinary medicine in the modern sense, because after Gillmeister no veterinarian could earn a doctoral degree in Rostock further more. Gillmeisters vita sheds light on the times and the difficulties of the veterinary profession in the poor agricultural area of Mecklenburg.

Ventilatory sensitivity to changes in inspired and arterial carbon dioxide partial pressures in the chicken.

To determine if intrapulmonary chemoreceptors could be the sole peripheral chemoreceptors responsible for ventilatory responses to inhaled CO2, we studied the relationships of minute ventilation, tidal volume, and respiratory frequency to inspired and arterial partial pressure of CO2 (P(I)CO2 and PaCO2) in decerebrate upright chickens when the birds inspired gases containing four low partial pressures of CO2 (0.02, 5.0, 8.2, and 11.4 torr). Because of variability in the measured variables from time to time in the same birds, as well as between birds, and because of the limited precision in measuring PaCO2, a 4 x 4 Latin square design and four statistical methods of data analyses (modified reduced major axis estimator, maximum likelihood estimator, average slope method, and summary slope method) were used. Tidal volume, minute ventilation, and PaCO2 increased, but respiratory frequency remained unchanged, as gases containing increased partial pressures of CO2 were inhaled. The results indicate that intrapulmonary chemoreceptors are not the sole receptors stimulated by inhaling gas containing even low partial pressures of CO2 and that stimulation of arterial and central chemoreceptors also occurs. Stimulation of these latter chemoreceptors may account for the increase in ventilation. Further, the results demonstrate the importance of maintaining a low level of environmental CO2 in poultry houses to minimize its influence on ventilation.

Alterations of cell-mediated immunity following cardiac operations: clinical implications and open questions.

Cardiac surgery with cardiopulmonary bypass (CPB) is known to induce an immune response whose nature has been increasingly elucidated during the recent decade. Clinically, patients usually show two to three of the four symptoms, which define the so-called systemic inflammatory response syndrome (SIRS). In addition, all parameters of the innate, nonspecific immune system, e.g., polymorphonuclear cells, elastase, and complement, are activated. This also applies to the proinflammatory mediators interleukin (IL)-1beta, -6, and -8, and tumor necrosis factor (TNF)-alpha. Within the adaptive, specific immune system, a decrease of T lymphocytes and T helper (TH) cells is observed, whereas suppressor/ cytotoxic T cells and B cells appear to be nearly unaffected. Cytokine measurements provide more detailed information: IL-2 and IL-12, which are important for the activation of the type-1 TH-cell (TH1)-mediated immune response, are depressed following cardiac operation. In contrast, IL-10 and transforming growth factor-beta essential to TH2-mediated humoral or anti-inflammatory immune response, are upregulated. In vivo tests, e.g., delayed type hypersensitivity skin reaction and tetanus antibody production, confirm the polarization of the adaptive immune response towards the TH2 pathway. However, all these alterations usually do not result in clinical adverse events. Therefore, more information is needed about the immune response of patients at high preoperative risk or with serious perioperative complications to find out whether clinically relevant events are correlated to alterations of immune response. For this purpose, more readily available, standardized methods for immunologic monitoring appear highly desirable.

Leukocyte depletion of red cell components prevents exposure of transfusion recipients to neutrophil elastase.

BACKGROUND: Polymorphonuclear leukocytes contain a large number of enzymes and bactericidal proteins stored in granules. Neutrophil activation induces degranulation and immediate release of these bioactive substances, including human neutrophil elastase (HNE) also known as elastase-2 (ELA2), which may contaminate whole blood units and blood components. MATERIALS AND METHODS: The HNE concentration was determined in the supernatants of blood components with a commercial enzyme-linked immunosorbent assay (ELISA). The effect of leukocyte depletion and storage was evaluated by testing whole blood, buffy-coat-reduced, and leukocyte-depleted red cell units. Buffy-coat-derived platelets and plasma were also tested. RESULTS: HNE concentrations at day 1 were about 50 microg/l in all types of red cell components with the exception of leukocyte-depleted red cells (<0.26 microg/l). In leukocyte-depleted red cells, platelets and plasma, no significant increase was observed during storage. In whole-blood units and buffy-coat-reduced red cells, the HNE concentrations increased steadily and often exceeded 1,000 microg/l when the units expired. CONCLUSION: Leukocyte depletion may limit the inadvertent infusion of bioactive substances derived from polymorphonuclear leukocytes, of which HNE is but one example. The accumulation of HNE in buffy-coat-reduced red cells may be greater than that of whole blood units. HNE accumulates during storage and its quantity may have pathophysiologic significance. Platelets and plasma derived from buffy coats contain some HNE, but leukocyte-depleted red cells virtually none. However, we consider the accumulation of HNE in these components not to be clinically important. The quantities, kinetics, and occurrence in various blood components of HNE contamination differ from those observed with cytokines.

Detection of acute phase response and infection. The role of procalcitonin and C-reactive protein.

OBJECTIVE: Established parameters, e.g. C-reactive protein (CRP), do not differentiate specifically enough between patients developing an infection and those exhibiting an acute phase response following cardiac surgery. The objective of this prospective study was to investigate if procalcitonin (PCT) is more helpful than CRP. METHODS: During a 1-year period, seven out of 563 patients (1.2%) developed systemic infections (group A) after cardiac operations with cardiopulmonary bypass (CPB), and additional eight patients (1.4%) had local wound infections requiring surgical therapy (group B). Blood samples for PCT and CRP measurements were taken preoperatively, at the onset of infection (d1), as well as on the third day (d3), fifth day (d5), and seventh day (d7) following diagnosis of infection. Forty-four randomly selected patients undergoing cardiac surgery with CPB without clinical signs of infection, additional intensive care unit (ICU) management or additional antibiotic treatment served as control (group C) to assess the PCT and CRP contribution to acute phase response. PCT and CRP levels were measured preoperatively, on the first (d1), third (d3) and fifth day (d5) after operation. RESULTS: At the onset of infection, PCT levels (median interquartile range 25%-75%) increased significantly in group A as compared to baseline values (10.86 (3.28-15.13) ng/ml vs. 0.12 (0.08-0.21) ng/ml), and decreased during treatment to still significantly elevated values on d5 (0.56 (0.51-0.85) ng/ml). CRP levels were significantly elevated on all days investigated with no trend towards normalisation (d1: 164.5 (137-223) mg/l) vs. 1.95 (1.1-2.8) mg/l preoperatively, d5: 181.1 (134-189.6) mg/l. In group B, no increase in PCT levels, but a significant increase of CRP from d1 (165.9 (96.6-181.6) mg/l) vs. 3.7 (2-4.3) mg/l preoperatively) until d5 98 (92.8-226.2) mg/l was detected. In group C, postoperative PCT levels increased slightly but significantly in the absence of infection on d1 (0.46 (0.26-0.77) ng/ml vs. 0.13 (0.08-0.19) ng/ml preoperatively), and d3 (0.37 (0.2-0.65) ng/ml and reached baseline on d5 (0.24 (0.11-0.51) ng/ml)). CRP levels were significantly elevated as compared to baseline on all postoperative days investigated (baseline: 1.75 (0.6-2.9) mg/l, d1: 97.5 (74.5-120) mg/l), d3: 114 (83.05-168.5) mg/l, d5: 51.4 (27.4-99.8) mg/l)). PCT showed a significant correlation to CRP in group A (r =0.48, p < 0.001), a weak correlation in group C (r=0.27, p=0.002) and no correlation in group B. Intergroup comparison revealed a significant difference for PCT between all groups (A>C>B) and significantly higher CRP levels in group A vs. C and in group B vs. C. Thus, the pattern high PCT/high CRP appears to indicate a systemic infection, while low PCT/high CRP indicates either acute phase response or local wound problems, but no systemic infection. The cost for PCT measurements was 5.6-fold higher as compared to CRP. CONCLUSION: Due to the significant differences in the degree of increase, PCT appears to be useful in discriminating between acute phase response following cardiac surgery with CPB or local problems and systemic infections, with additional CRP-measurement increasing the specificity.

Cognitive performance during respirator wear in the absence of other stressors.

Reaction time, decision-making speed, and response accuracy were measured in 12 male and 5 female subjects performing computer-controlled tasks under nonexercise conditions during two 3.5-hour days, one with and one without (control) wearing a respirator, to assess the effects of respirator wear alone on cognitive performance. Tasks included measures of simple and choice reaction time (CRT), serial pattern matching, lexical discrimination (LD), visual selective attention, rapid visual scanning, and form discrimination (FD). Anxiety levels were assessed along with reaction time measures obtained at the start of each test day and after 1, 2, and 3 hours of testing. Reaction time and response accuracy did not differ significantly between respirator and control trials and were not changed over time. However, mean decision-making times were significantly faster during respirator wear compared to control for the LD (0.17 +/- 0.04 versus 0.19 +/- 0.05 sec) and FD (0.32 +/- 0.10 versus 0.36 +/- 0.12 sec) CRT tasks. Females exhibited significantly faster reaction times than males, but no differences within sex groups were observed between control and respirator trials. Response accuracy and decision-making speed did not differ within and between male and female groups for any reaction time tasks during respirator wear. The improvements in decision-making time observed during respirator wear probably reflect the effect of the respirator to increase arousal and improve focusing of attention by excluding peripheral visual stimuli. Furthermore, the results suggest that respirator wear over a relatively short period in the absence of other stressors should not inhibit cognitive function.

An outbreak due to enterohaemorrhagic Escherichia coli O157:H7 in a children day care centre characterized by person-to-person transmission and environmental contamination.

An outbreak of gastrointestinal disease and haemolytic uraemic syndrome caused by Escherichia coli O157:H7 was investigated. The outbreak occurred in a day care centre located in northern Germany in August 1992 and involved 39 children and two adults. Furthermore, four asymptomatic infections were detected among the staff. Initial and secondary cases were reported over a 30-day interval, with cases occurring in three waves. Person-to-person contact and environmental contamination were assumed to be the main mode of transmission. The source of the outbreak has remained unknown but it is likely that primary or secondary contamination of the day care centre's kitchen, too, played a role in the spread of infections. The organisms were isolated from two open packs of deep-frozen stuffed cabbage rolls and turkey scallops in batter, and furthermore from swabs from two kitchen utensils. Of the 39 cases with diarrhoea, three developed a haemolytic uraemic syndrome; one of the latter patients died. In 8 of the cases as well as in four healthy adult employees, E. coli O157:H7 was isolated from stool samples, and in two stool culture-negative cases the presence of IgM antibody to O157 LPS indicated recent infection. The E. coli O157:H7 isolates from the cases and the kitchen were of identical phage type and yielded identical biochemical reactions. All E. coli O157:H7 isolates harboured stable slt-II genes. However, slt-I genes could only be demonstrated in the primary cultures and were lost during subcultivation. This is the largest outbreak caused by enterohaemorrhagic E. coli O157:H7 that has been documented in Germany so far. The high infectivity of the organism which was demonstrated by person-to-person transmission and propagation within certain groups of children stresses the need for strict hygienic measures and early case reporting when such infections occur in susceptible settings like day care centres, nursing homes, or hospitals.

Reliability of respiratory inductive plethysmography for measuring tidal volume during exercise.

This study was designed to determine the reliability of measurements of respiratory volumes obtained with a respiratory inductive plethysmograph (RIP) during exercise. Tidal volumes (VT) from the RIP were compared with simultaneous flowmeter volumes in 8 healthy subjects at 5 incremental work rates of 60, 90, 120, 150, and 180 W during cycling and treadmill exercise. During cycling, average RIP and flowmeter values did not differ significantly at work rates below 180 W for 63% of the subjects. Average RIP and flowmeter VT were similar at work rates below 180 W for 50% of the subjects, and for 83% of the subjects at intensities below 150 W. The variability in these results may be attributed to several factors including RIP calibration errors and slippage of the RIP elastic bands containing the inductive coils. Correlations of breath-by-breath flowmeter and RIP VT were significant for subjects during cycling (R = 0.73, P < 0.05) and treadmill exercise (R = 0.78, P < 0.05). These findings suggest that the RIP should be considered a semi-quantitative method for measurements of tidal volume during exercise with and without respirator wear.

Knowledge-based approach to clinical decision-support system, with an application in tetanus serology.

In tetanus immunization, the need for a booster vaccination can be easily determined by a serological analysis of tetanus antitoxin. Vaccination without knowledge of the immune status carries a high risk of postvaccinal complications. We have used the Pro. M.D. expert system shell to produce the knowledge base TETANUS, to improve the diagnostic interpretation of tetanus antitoxin findings. This knowledge base is comprehensive, runnable, useful, and modifiable by anyone who works with Pro.M.D. and is able to provide medical knowledge in this field.

[Preventive tetanus immunization and avoidance of side effects of booster immunization]. / Tetanusimpfschutz und Vermeidung von Nebenreaktionen bei Auffrischimpfungen.

Prevalence of antibodies against tetanus toxoid (tetanus antitoxin titre) was measured in 5,235 males aged 17-60 years, 3,069 (59%) aged 20-22 years. Taking as criterion a threshold value of 0.1 IU/ml, 5,071 (97%) had adequate tetanus immunity. 1,301 of 4,355 aged 21-30 years (30%) actually had antibody concentrations above 6.3 IU/ml. Booster injections are especially contraindicated in this latter group because of the danger of side effects with further toxoid doses. Thoughtless routine booster immunization should therefore be avoided.

Detection of tetanus antitoxin using Eu(3+)-labeled anti-human immunoglobulin G monoclonal antibodies in a time-resolved fluorescence immunoassay.

Tetanus antitoxin in human sera was detected with solid-phase immunoassays in microtitration modules coated with tetanus toxoid by using Eu(3+)-labeled anti-human monoclonal antibodies on the basis of an exactly calibrated antibody standard. The use of a time-resolved fluorescence immunoassay (TR-FIA) significantly improved the quantitative detection of tetanus antitoxin over that of the enzyme-linked immunosorbent assay (ELISA) technique because of its high sensitivity and its wide measurement range, detecting antibody levels between 0.001 and 12.5 IU/ml with a single serum dilution of 1:100. For the same purpose, two different serum dilutions (1:100 and 1:1,000) were needed in the ELISA technique. TR-FIA is reproducible and can be performed in 3.5 h. A study of 2,630 serum samples was undertaken to examine the age-dependent distribution of titer levels, indicating the decline of sufficient protection in patients older than 60 years. The wide measurement range of TR-FIA enabled fast examination of large numbers of serum samples without the need for repetition, with further sample dilution, as was often necessary in the ELISA procedure.

[Tetanus immunity in men and women in the Federal Republic of Germany]. / Tetanusimmunität bei Männern und Frauen in der Bundesrepublik Deutschland.

Tetanus antitoxin was measured by solid-phase enzyme-immunoassay in sera of 4187 men and 408 women in the age of 19 to 90 years. When 0.1 IE/ml antitoxin antibodies were supposed to be protective, then vaccination proved sufficient in 96% of men and 71% of women. Immunity to tetanus was at a higher level in the younger persons than in the older ones. Between the age of 60 and 70, a rapid loss of immunity was stated in both men and women. Need of vaccination is easily supported by quantitative measurement of the respective antibodies in sera. Moreover, serological screening of tetanus antitoxin antibodies is recommended in doubtful cases in order to avoid hyperimmune reactions in sufficiently immunized persons. The employed method of quantitation is easily performed under routine conditions.

[The detection of Vibrio parahaemolyticus and Vibrio alginolyticus using modified culture media]. / Versuche zum Nachweis von Vibrio parahaemolyticus und Vibrio alginolyticus mit Hilfe modifizierter Nährmedien.

Studies have been completed for the detection of Vibrio(V.) parahaemolyticus and V. alginolyticus in Baltic Sea fish. The author had prepared for that purpose a liquid culturing medium and a solid substrate. The percentage of positive findings is remarkable. The results so far recorded should be a good reason for further studies.

Optimization of a membrane oxygenation system for cell culture in stirred tank reactors.

Bubble free aeration of animal cell cultures in conventional stirred tank reactors is performed with a silicone tubing oxygenation system. This system is characterized for the laboratory fermenter BIOSTAT M with 1.5 l working volume in respect to oxygen transfer and mixing performance.

Expression and inducibility of drug-metabolizing enzymes in preneoplastic and neoplastic lesions of rat liver during nitrosamine-induced hepatocarcinogenesis.

The expression, inducibility, and regulation of four different cytochrome (cyt.) P-450 isoenzymes (PB1, PB2, MC1, and MC2) NADPH-cytochrome P-450 reductase, the glutathione transferases (GSTs) B and C and microsomal epoxide hydrolase (mEHb) have been studied during nitrosamine-induced hepatocarcinogenesis using immunohistochemical techniques. The investigations revealed basic differences in the expression of the individual drug metabolizing enzymes in the course of neoplastic development. While the two GSTs and mEHb were increased in all preneoplastic and benign neoplastic lesions, the levels of the distinct cyt. P-450 isoenzymes were characteristically different from each other. Following initial changes in the expression of these enzymes in early preneoplastic lesions (i.e., increase of cyt. P-450 PB1 versus slight decrease of the other cyt. P-450 isoenzymes), a continuous reduction of all cyt. P-450 isoenzymes was observed during the further course of hepatocarcinogenesis. In progressed neoplastic nodules, all cyt. P-450-isoenzymes and NADPH cyt. P-450 reductase were decreased to varying extents. Treatment of animals with inducers of the monooxygenase system, such as phenobarbital, 3-methylcholanthrene and polychlorinated biphenyls, led to a rather heterogenous pattern of enzyme alterations in preneoplastic and neoplastic lesions. Following administration of phenobarbital, some islets responded to the same degree as the surrounding tissue, others were less or not at all inducible and a few of the lesions showed a prominent increase in cyt. P-450 PB2 and NADPH-cyt. P-450 reductase levels. The interesting finding that these two enzymes always showed concurrent changes may be indicative of a common regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose oxidase as label in histological immunoassays with enzyme-amplification in a two-step technique: coimmobilized horseradish peroxidase as secondary system enzyme for chromogen oxidation.

A sensitive staining procedure for glucose oxidase (GOD) as marker in immunohistology is described. The cytochemical procedure involves a two-step enzyme method in which GOD and horseradish peroxidase (HRP) are coimmobilized onto the same cellular sites by immunological bridging or by the principle of avidin-biotin interaction. In this coupled enzyme technique, H2O2 generated during GOD reaction is the substrate for HRP and is utilized for the oxidation of chromogens such as 3,3'-diaminobenzidine or 3-amino-9-ethylcarbazole. Due to the immobilization of the capture enzyme HRP in close proximity to the marker enzyme (GOD), more intense and specific staining is produced than can be obtained with soluble HRP as coupling enzyme in the substrate medium. Indirect antibody labelled and antibody bridge techniques including the avidin (streptavidin)-biotin principle have proven the usefulness of this GOD labelling procedure for antigen localization in paraffin sections. Antigens such as IgA in tonsil, alpha-fetoprotein in liver and tissue polypeptide antigen in mammary gland served as models. The immobilized two-step enzyme procedures have the same order of sensitivity and specificity as comparable immunoperoxidase methods. The coupled GOD-HRP principle can be superior to conventional immunoperoxidase labelling for the localization of biomolecules in tissue preparations rich in endogenous peroxidase activities.

Effect of ruminal CO2 on gas exchange and ventilation in the Hereford calf.

The contribution of ruminal CO2 to gas exchange measurements and ventilation was determined in four rumen-fistulated Hereford steers at rest and during exercise. The calves were exercised at 1.4 and 2.2m X s-1 under three treatments: 1)full rumen with fistula sealed, 2) full rumen with fistula open, and 3) empty rumen. Measurements also were made at rest while flushing the empty rumen with either 100% N2 or a mixture of 50% CO2-50% N2. O2 consumption, CO2 production (Mco2), and ventilation were measured by collecting the expired gas. Absorption across the ruminal epithelium during rest increased Mco2 by 3%, whereas absorption and eructation together increased Mco2 by 15%. The respiratory exchange ratio (R) was significantly different among the three treatments at rest, but no differences were observed in R among the treatments during exercise. No changes were observed in minute ventilation among the three conditions, but a decrease in respiratory frequency and an increase in tidal volume occurred when the rumen was empty. These changes in ventilatory pattern may have been due to a decrease in body temperature when the rumen was empty. When the empty rumen was flushed with 50% CO2, Mco2 was increased 21% over the value observed when flushing with 100% N2. CO2 of fermentation origin is added to the expired gas by both eructation and absorption and has a significant effect on R in the resting animal, but no effect on R during exercise.