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The development of resistance by infective bacterial species is an incentive to reconsider the indications and administration of available antibiotics. Correct recognition of the indications and duration of therapy are particularly important for the use of highly potent substances in the intensive care situation. There has as yet been no clinical chemical parameter which is capable of specifically distinguishing a bacterial infection from a viral or non-infectious inflammatory reaction, but it now appears that procalcitonin (PCT) offers this possibility. The present study was intended to clarify whether PCT can be used to guide antibiotic therapy in surgical intensive care patients. A total of 110 patients in a surgical intensive care ward receiving antibiotic therapy after confirmed infection or a high grade suspicion of infection were enrolled in this study. In 57 of these patients a new decision was reached each day as to whether the antibiotic therapy should be continued after daily PCT determination and clinical assessment. The control group consisted of 53 patients with a standardized duration of antibiotic therapy over 8 days. Demographic and clinical data were comparable in both groups. However, in the PCT group the duration of antibiotic therapy was significantly shorter compared to controls (5.9+/-1.7 vs. 7.9+/-0.5 days, p

Adequate indication and duration of administration are central issues of modern antibiotic treatment in intensive care medicine. The biochemical variable procalcitonin (PCT) is known to indicate systemically relevant bacterial infections with high accuracy. In the present study, we aimed to investigate the clinical usefulness of PCT for guiding antibiotic treatment in surgical intensive care patients with severe sepsis. Patients were randomly assigned to a PCT-guided or a control group requiring antibiotic treatment. All patients received a calculated antibiotic regimen according to the presumed microbiological spectrum. In the PCT-guided group, antibiotic treatment was discontinued if clinical signs of infection improved and the PCT value was either

The development of resistance by infective bacterial species is an incentive to reconsider the indications and administration of available antibiotics. Correct recognition of the indications and duration of therapy are particularly important for the use of highly potent substances in the intensive care situation. There has as yet been no clinical chemical parameter which is capable of specifically distinguishing a bacterial infection from a viral or non-infectious inflammatory reaction, but it now appears that procalcitonin (PCT) offers this possibility. The present study was intended to clarify whether PCT can be used to guide antibiotic therapy in surgical intensive care patients. A total of 110 patients in a surgical intensive care ward receiving antibiotic therapy after confirmed infection or a high grade suspicion of infection were enrolled in this study. In 57 of these patients a new decision was reached each day as to whether the antibiotic therapy should be continued after daily PCT determination and clinical assessment. The control group consisted of 53 patients with a standardized duration of antibiotic therapy over 8 days. Demographic and clinical data were comparable in both groups. However, in the PCT group the duration of antibiotic therapy was significantly shorter compared to controls (5.9+/-1.7 vs. 7.9+/-0.5 days, p0.001) without unfavorable effects on clinical outcome.

We investigated the formation of a "nonthyroidal illness" (NTI) in pigs undergoing ventricular fibrillation (VF) and resuscitation. Seven minutes after VF twenty-one pigs received either Epinephrine (E: 45 micrograms/kg B.W.; n = 7), Norepinephrine (NE: 45 micrograms/kg B.W.; n = 7), or Vasopressin (VP: 0.8 U/kg B.W.; n = 7). We determined the serum concentrations (sc) of total T4 (TT4), FT4, total T3 (TT3) and rT3 120 min before, during (t0), and 5, 15, 60 and 120 min after VF. At the end of the observation period we figured out the in-vitro T3-generation (kM, Vmax), the in-vitro rT3-generation, the in-vitro rT3-decomposition (kM, Vmax) and the content of cytosolic sulfhydryls (total sulfhydryls, non-protein bound sulfhydryls) in liver and kidney specimen. Animals not undergoing VF served as controls (C) for parameters measured in the intracellular compartment. TT4- and TT3-sc decreased to 3.3 +/- 0.6 micrograms/dl (p < 0.05, vs. t0) and 15.2 +/- 4.1 ng/dl (p < 0.05, vs t0), resp. FT4-sc remained stable for five minutes (2.63 +/- 0.41 ng/dl) before declining to 1.8 +/- 0.39 ng/dl (p < 0.05, vs. t0). The rT3-sc raised finally to 46.9 +/- 7.3 ng/dl (p < 0.05, vs t0). Iodothyronine sc did not exhibit differences between E-, NE- and VP-treatment. Neither in-vitro T3-generation, nor in-vitro rT3-generation, nor in-vitro rT3-decomposition nor intracellular sulfhydryl content were affected by the events of VF and resuscitation as compared to the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

The microdialysis technique was used for following the glucose content of the extracellular subcutaneous (SC) fluid under varying blood glucose levels in rats. The glucose content in the microdialysis perfusion fluid was continuously analyzed by means of the measuring flow chamber of an ex vivo glucose monitor. In six ChBB rats blood glucose levels were varied between 40 mg/dl and 575 mg/dl by intravenous (IV) infusion of glucose and by SC injections of insulin, respectively. After a running-in period of about half an hour, the glucose content in the perfusion fluid was closely related to the blood glucose concentration (r0.92) up to a time period of 6 hrs. The "relative recovery" rate of glucose by the microdialysis probe in the SC tissue varied within the 6 experimental sessions. The relative recovery rate could be shown to be not dependent on the absolute blood glucose levels in the individual rat within the glucose concentration range tested.

The intracellular 5'deiodination (5'D) of T4 and rT3 has been investigated in human adipose tissue. We studied 5'D in intact adipose tissue, its morphological components and in 3T3-L1-cells. 5'D as assessed by T3-production out of T4 and by rT3-decomposition was not inhibited by propylthiouracil (PTU), but by iopodate (IOP). The apparent Michaelis constants were kM = 3 nM for rT3 and kM = 1 microM for T4. The rT3-degradation was linear over 25 h (115 pg/h.mg (prot.)) both at 37 degrees C and at 4 degrees C. The same type of 5'D was observed in adipocytes, stromal-vascular cells and in 3T3-L1-cells regarding T4 to T3 degradation (244 +/- 30, 181 +/- 27, 227 +/- 37 pg T3/mg.min), resp.; PTU did not exert any influence upon 5'D in the cells investigated. We conclude, that i. the intracellular generation of T3 in adipose tissue does not derive from type I deiodination; ii. 5'D in adipocyte precursors and differentiated adipocytes is identical and iii. there is no difference between human cells and 3T3-L1-cells regarding 5'D.

The effects of 16 days of oral treatment with thyrotropin-releasing hormone (TRH, 1 mg/24 h) on serum levels of thyrotropin (TSH), thyroxine (T4) and triiodothyronine (T3) and the kinetics of TRH in the blood were studied in normal rats. A second group of animals served as controls. TRH was dissolved by sonification (10 mg/l) and was stable in tap water. TRH was measured by a radioimmunoassay procedure (normal range: 20-80 pmol/l, antiserum K2B9 1:120,000 final dilution). An increase in basal TSH (7,200 +/- 440 ng/l, mean +/- SD) was found after 2 days of treatment (11,420 +/- 810 ng/l), but a significant increase was observed after 5 days of treatment (12,530 +/- 640 ng/l, p less than 0.001). T4 serum concentrations remained in the normal range during the entire period of study, whereas T3 serum concentrations (0.76 +/- 0.1 micrograms/l) were increased to 1.22 +/- 0.2 micrograms/l on day 5 (p less than 0.001). A subsequent decline of TSH, T4 and T3 up to the end of the study was observed. TRHmax concentrations were registered on day 5 (790 +/- 24 pmol/l). The mean value of TRHmax was 723 +/- 34 pmol/l. To improve the stability of TRH in tap water, 1-ml samples of drinking water with dissolved TRH were measured. The mean TRH concentration in drinking water was 73 +/- 1.5% (SD). No significant correlations were found between the area under the curve of TSH (184,340 ng.l-1.24 h) and that of TRH (14,954 pmol.l-1.24 h).(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of a series of sympathomimetic agents on the liver content of non protein bound thiol groups (NP-SH), mainly representing glutathione, has been assessed in the male rat. The rats were intravenously and/or subcutaneously infused over 6 h at different dosages either with dopamine, dobutamine, epinephrine, terbutaline, or phentolamine, or simultaneously with dopamine and phentolamine, or with epinephrine and phentolamine. Besides NP-SH, total sulfhydryl group content was measured in liver cytosol, while glucose and insulin concentrations were determined in the serum. Liver NP-SH content was significantly decreased by epinephrine. This decrease was abolished and even inverted to an increase, when appropriate doses of phentolamine were infused simultaneously. Dopamine caused a rise in NP-SH content at a dose rate of 7.5 micrograms/kg.min, while lower and higher dose rates of dopamine exerted not any influence on liver NP-SH. When phentolamine was concomitantly infused with 15 micrograms/kg.min of dopamine, NP-SH was significantly elevated. Phentolamine, when infused exclusively, increased NP-SH as well, while it was not influenced, however, by terbutaline or dobutamine at any dosage. Cytosolic total sulfhydryls were found to be unaltered across all experimental groups. When the NP-SH values are related to the corresponding serum insulin levels, a close and linear relationship becomes evident. The study demonstrates, that some sympathomimetic agents can exert a considerable influence on hepatic non protein bound thiol content. The data suggest, that the varying liver NP-SH content under adrenergic drugs is primarily related to changes in serum insulin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of varying glucoregulatory states as induced by fasting, feeding and intravenous glucose infusion on liver thiol content has been assessed in the male rat. As expected, increasing the serum glucose levels from 131 +/- 7 mg/dl to 343 +/- 12 mg/dl (mean +/- S.E.) caused a corresponding increase in serum insulin responses. Rising from 3.2 +/- 0.4 mumol/g w.w. in the fasted group to a peak value of 6.3 +/- 0.4 mumol/g (P less than 0.01) in the group infused by 10% glucose solution, hepatic non protein bound sulphydryl groups (NP-SH) were closely related to serum glucose levels up to 244 +/- 11 mg/dl. When higher glucose doses were infused. NP-SH values fell steadily, they even inclined below the level of the fasted rats after infusion of 30% and 40% glucose solutions (1.3 +/- 0.4 mumol/g w.w., P less than 0.05 and 0.7 +/- 0.3, P less than 0.01, resp.), mean serum glucose levels being 291 +/- 12 and 343 +/- 13 mg/dl, resp. Hepatic protein bound thiols were not affected by any of the glucoregulatory states experimentally induced. The data demonstrate that the glucoregulatory state influences hepatic NP-SH content divergently. The study suggests that under physiological conditions liver NP-SH content covariates positively with serum insulin and glucose levels.

The influence of the beta-adrenoreceptor stimulating agents dobutamine and terbutaline as compared to epinephrine on insulin and glucose levels has been assessed in the male rat. All agents were infused either intravenously or subcutaneously over 6 h at varying dosages. In addition, epinephrine was given concomitantly with the alpha-adrenoreceptor blocker phentolamine. The heart frequency as an estimate of the effects of the adrenergic agents beyond the glucoregulatory system was accelerated in a dose-dependent manner. Serum insulin concentrations were significantly increased by phentolamine and significantly depressed by epinephrine, while they were virtually unchanged at any dosages of dobutamine, terbutaline, or epinephrine, when simultaneously applicated with phentolamine. As for serum glucose levels, these agents, again, did not exert any influence, while glucose levels were significantly depressed under phentolamine and significantly increased under epinephrine application. The data demonstrate, that dobutamine and terbutaline at pharmacologically common dosages do not affect glucose homoeostasis. The study does not support a major effect of beta-adrenergic stimulation on the pancreatic B cell in the male rat.

Blood concentrations of thyrotropin-releasing hormone (TRH, Protirelin) were measured by a specific radioimmunoassay in 16 euthyroid subjects after intravenous (200 micrograms), nasal (2 mg) or oral (40 mg) administration of TRH. TRH blood levels peaked 2 min after i.v. administration (13,400 +/- 1,020 fmol/ml), 10 min after nasal (5,000 +/- 1,800 fmol/ml) and 150 min after oral (2,650 +/- 1,080 fmol/ml) administration. The degradation of TRH followed an exponential curve, giving a half-life of 6.5 min. The disappearance rate gave a "half-life" of 22 min in the nasal application group and of 31 min in the oral group. Maximal concentration of stimulated thyrotropin-stimulating hormone (TSH) always occurred 30 min after the peak TRH concentration without any correlation with the TRH concentration time integrals, suggesting that TSH secretion is dependent on a continually rising TRH blood level.

Radioactivities of endogenously labelled thyroid hormones following in vivo application of 131 I and extraction from serial blood samples, show that T4 secretion is enhanced in T3-hyperthyroidism as it is in T4-T3-hyperthyroidism. In an extreme case of T3-hyperthyroidism with serum concentrations (SC) of T3 nearly equal to T4 (1000 ng/dl and 1800 ng/dl, respectively) tracer studies revealed a very short half life of T4 when compared to T3 (21.8 and 20.2 hrs., respectively). In 110 cases with both types of hyperthyroidism, regression analysis showed that T3/T4 ratio as an indicator of T4 conversion, as well as T3/rT3 ratio as an indicator of the direction of the conversion, are related to T4SC (r = -0.84 and -0.72, respectively, p less than 0.001). T3-hyperthyroidism is described by high values of these ratios. For the definition of T3-hyperthyroidism it is suggested that both T4 and rT3SC are within the normal range (T4 less than or equal to 11.5 micrograms/dl, rT3 less than or equal to 43.0 ng/dl) and according to this definition, T3/rT3 is higher than in T4-T3-hyperthyroidism and in an undefined group (24.8 +/- 4.5 vs. 6.3 +/- 0.4 or 7.5 +/- 0.4, respectively). By means of the ratios the undefined group may be allocated to T4-T3-hyperthyroidism. The T3/rT3 ratio is value of greater than 10 has a frequency of 88% in thus defined T3-hyperthyroidism and a ratio of less than or equal to 10 is found in 90% of the other cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Rats were treated with insulin infusion over 12 h with or without addition of cycloheximide and compared with controls. T4 to T3 deiodination in microsomal liver fraction was measured. Insulin treatment led to an increase in T3 production, whereas this effect was blunted by the inhibition of protein synthesis by cycloheximide. Neither serum concentrations of T4 nor the liver content of non-protein-bound sulph-hydryl groups explained the alterations in T3 production. It is strongly suggested that insulin directly acts on T4-5'-monodeiodination by stimulating de novo synthesis of protein.

Manometric investigation of the gastro-esophageal closure mechanism is an important tool for the classification and adequate therapy of functional disorders in this region. Because of the relatively low pressure differences the reliability of a measuring procedure has to meet all requirements. Manometry by continuously perfused and withdrawn catheters being the most frequently applied measuring procedure got some criticism regarding its reliability and reproducibility. The theoretical basis of this criticism is examined closely. The reproducibility of the recorded pressure curves is studied and quantified in 36 dogs and 122 persons (32 controls, 63 patients with hiatal hernia, 27 patients with achalasia of the cardia). On experimental condition, lower esophagel sphincter pressure shows a high degree of reproducibility (retest reliability r = .98, p less than 0.001), in clinical investigations it is significantly lower (r = .81). There are no statistically significant differences between the patient groups and the controls. The importance of the findings for the reliability and the interpretation of clinical manometric data is discussed.