Effect of nitrous oxide on cerebral blood flow velocity after induction of hypocapnia

Triphasic waves (TWs) can be recorded on EEG in the course of several metabolic disorders, mainly hepatic encephalopathy. A case of acute encephalopathy due to naproxen intoxication is reported, in the course of which diffuse, bilateral and symmetrical TWs were recorded. Biochemical mechanisms that might determine both a complex encephalopathy and TWs are discussed.     

The clinical relevance of the Waterlow pressure sore risk scale in the ICU

OBJECTIVE: To evaluate whether the Waterlow pressure sore risk (PSR) scale has prognostic significance for intensive care patients. DESIGN: A prospective study. SETTING: The surgical intensive care unit (ICU) of the University Hospital Rotterdam. PATIENTS: Data were evaluated from 594 patients who had been admitted to the ICU during the year 1994. METHODS AND RESULTS: Each patient was assessed daily with respect to their Waterlow PSR score and the development of pressure sores in the sacral region. Actuarial statistical methods were used to analyse the predictive value of the risk score. When a patient had a Waterlow PSR score > 25 on admission, the risk of developing a pressure sore was significantly increased compared to patients with a PSR score < 25. After admission, the daily Waterlow PSR scores obtained were significantly associated with the risk of developing a pressure sore. For each additional point this risk increased by 23% (95% confidence interval 17 to 28%). CONCLUSIONS: The Waterlow PSR scale provides the medical and nursing staff at an early stage with reliable information about the risk patients have in developing a pressure sore.     

An in vitro method, based on chewing, to predict resistant starch content in foods allows parallel determination of potentially available starch and dietary fiber

The purpose of this work was to develop a method for measurement of the major forms of resistant starch (RS) in foods. The analytical procedure was chosen to mimic physiologic conditions, and included chewing as a prestep before incubation with pepsin, pancreatin and amyloglucosidase. The undigestible polysaccharides, including RS, were recovered by ethanol precipitation and subsequent filtration. RS was analyzed as total starch in the filter residue. The residues were also used for gravimetric determination of dietary fiber after correcting for remaining protein, ash and RS. The potentially available starch fraction was determined from analysis of glucose in the filtrate. The foods included were prepared to resemble products for which RS figures were available from in vivo measurements, and/or from analysis with other current in vitro methods. For six of these foods, and for three additional starchy materials, RS figures were compared with in vivo and/or in vitro data for identical products. The pooled standard deviation for the suggested RS method was 2.9%. A high correlation was obtained with in vivo figures from the literature for 19 realistic foods (r = 0.97; y = 0.77x + 0.45). After correction for RS, dietary fiber figures corresponded well with conventional gravimetric dietary fiber analysis for 14 starchy foods (r = 0.97). It is concluded that the procedure described here provides a convenient way to estimate RS content of realistic foods, allowing parallel determination of the potentially available starch fraction and dietary fiber.     

Advanced colorectal cancer is associated with impaired interleukin 12 and enhanced interleukin 10 production

Interleukin 12 (IL-12) is a heterodimeric cytokine that has been demonstrated to have a major role in stimulating a cell-mediated antitumor response. IL-10, a product of T helper 2 lymphocytes, is its most potent inhibitor. The aim of this study was to investigate whether patients with colorectal cancer had an imbalance in production of IL-12 and IL-10 preoperatively, and whether this was associated with advanced disease at surgery. Blood was obtained before surgery from 60 patients with colorectal cancer and from 30 controls. Peripheral blood mononuclear cells were incubated with Staphylococcus aureus Cowan's strain 1 in vitro for 24 h to assess IL-12 expression after stimulation, and serum was used for IL-10 measurement. IL-12 and IL-10 levels were assessed by ELISA. A single pathologist staged the tumors according to the tumor-node-metastasis (TNM) and Dukes' classifications. Patients with colorectal cancer had significantly lower levels of IL-12 (P <0.001) and higher levels of IL-10(P = 0.004) compared to controls. In addition, lower levels of IL-12 were detected in those patients who were node positive (P<0.05), had Dukes' C lesions (P < or = 0.001), and T3 or T4 lesions (P<0.033) when compared to controls. Patients with Dukes' B and C lesions (P<0.01) and T3 and T4 lesions (P<0.05) also had higher levels of IL-10 compared to controls. This study is the first to demonstrate that patients with colorectal cancer have decreased IL-12 production and increased serum IL-10. This suggests an impaired T helper 1 cell-mediated antitumor response and provides some justification for exogenous IL-12 therapy or anti-IL-10 therapy in these patients.     

Interactive MR-guided biopsies of the thyroid gland: validation of a new method

The purpose of this review was to give an answer to the question whether there are convincing data to support the hypothesis of an amino acid imbalance as one possible mechanism to explain overtraining syndrome. Animal studies point to an enhanced synthesis of the neurotransmitter 5-hydroxytryptamine through an amino acid imbalance at the blood-brain barrier with a preferable tryptophan uptake into the brain, resulting in premature fatigue. Human studies, however, show contradictory results, mainly because of nonstandardized methodology, so that a final conclusion cannot be made at present. BCAA supplementation in addition to standard carbohydrate ingestion during sustained exercise seems to be of no eminent advantage to delay fatigue. The overall results concerning the BCAA hypothesis to explain overtraining are inconclusive and require more controlled experimental research.     

Amitriptyline metabolism in elderly depressed patients and normal controls in relation to hypothalamic-pituitary-adrenal system function

The pharmacokinetics of amitriptyline (AMI) have been extensively studied, and a large interindividual variability between oral dose and concentration of the drug in plasma has been documented. The aim of this study was twofold: first, to compare AMI kinetics in depressed patients with those of healthy controls and, second, to describe the relationship between AMI levels in plasma and hypothalamic-pituitary-adrenal (HPA) system changes during depression. Thirty-eight patients with a DSM-III-R diagnosis of major depression and 13 healthy control persons received 75 mg of AMI daily for 6 weeks. Levels of AMI and nortriptyline in plasma were determined, and neuroendocrine testing with the combined dexamethasone-suppression/CRH-stimulation test (DST) was done before AMI administration and after weeks 1, 3, and 6 of medication. AMI levels in plasma were significantly higher in the patient group compared with controls during the entire treatment period, whereas nortriptyline levels did not differ between the two groups. Drug levels correlated significantly with age, but gender had no effect on the concentration of the drug in plasma. Twenty-two patients remitted after treatment. There was no difference in drug levels between responders and nonresponders. Fifteen patients were DST nonsuppressors before treatment; 23 patients and all controls suppressed cortisol after dexamethasone. DST suppressors had significantly higher AMI levels in plasma at weeks 3, 5, and 6 compared with DST nonsuppressors. In comparison to patients with high AMI levels in plasma, those with low drug concentration had higher postdexamethasone cortisol and adrenocorticotropic hormone levels and an increased hormone release after additional CRH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Are a blood alcohol concentration of 256mg/dl and minimal signs of impairment reliable indications of alcohol dependence?

This article describes a drunk-driving scenario where a woman was apprehended for driving under the influence (DUI) with a blood alcohol concentration (BAC) of 256mg/dl. The correctness of this result was vigorously challenged by a medical expert witness for the defence, who was actually a specialist in alcohol diseases. Despite reanalysis to confirm the BAC as well as a DNA profile to prove the identity of the blood specimen, the woman was acquitted of the charge of drunk driving by the lower court. However, she was subsequently found guilty in the High Court of Appeals with a unanimous decision and sentenced to four weeks imprisonment. This case report illustrates some of the problems surrounding the use of expert medical evidence by the defence to challenge the validity of the prosecution evidence based solely on a suspect's BAC. In situations such as these, an expert witness should be called by the prosecution to clarify and, if necessary, rebut medical and/or scientific opinions that might mislead the court and influence the outcome of the trial.     

The ovine pars tuberalis secretes a factor(s) that regulates gene expression in both lactotropic and nonlactotropic pituitary cells

The purpose of this study was to determine whether the cells of the ovine pars tuberalis (PT) secrete a factor(s) that can influence the activity of cells in the pars distalis (PD). By Northern blotting of total RNA isolated from PD cells that had been stimulated in the presence of cycloheximide (10 micrograms/ml), PT cell-conditioned medium was shown to induce a significant increase in the expression of the early response gene, c-fos, above both PD cell-conditioned and nonconditioned medium control levels (P < 0.05). Although forskolin (5 microM) induced a weak increase in c-fos expression in PD cells, the effect of PT medium conditioned in the presence of forskolin enhanced this expression more than additively (P < 0.05); furthermore, this effect was reversed by melatonin. These results are consistent with the release of a factor(s) from the PT, which for simplicity we have called tuberalin. This factor was released from PT cells in a time-dependent and cycloheximide-sensitive manner and was resistant to heating at 100 C for 10 min. Tuberalin activity could be size-fractionated using molecular size cut-off filters to produce activity in both the 1- to 10-kDa and more than 10-kDa size ranges. The activities in both of these fractions were sensitive to trypsin degradation and, therefore, appeared to be peptidergic. However, it was not clarified whether the biological activities were due to one or two components. Tuberalin also induced c-fos expression in other cell types, including GH3 and NIH3T3 cells. Dual labelling of PD cells by in situ hybridization using riboprobes for c-fos and PRL demonstrated that both the less than and more than 10-kDa fractions of tuberalin activated c-fos expression in some, but not all, lactotrophs in PD cell cultures, suggesting that a primary function of the PT is to regulate the activity of lactotrophs. This was supported further by enhanced secretion of PRL from PD cells in the presence of either PT-conditioned medium or PT cells in coculture. In addition, PT-conditioned medium was found to increase c-fos in a second cell type, which did not hybridize positively for PRL, indicating the existence of other endocrine interactions between the PT and PD.     

Stimulation of phosphorylation of mitogen-activated protein kinase by 1alpha,25-dihydroxyvitamin D3 in promyelocytic NB4 leukemia cells: a structure-function study

The conformations of isolated rabbit fast myosin light chains (LCs) were modified using trifluoperazine (TFP), the hydrophobic calmodulin inhibitor. CD spectroscopy showed that TFP altered secondary structural content of the LCs, with half-maximal effects at TFP concentrations of approximately 14-50 microM, which is within the range required to alter muscle fiber contraction in both agonistic and antagonistic ways [Kurebayashi, N. & Ogawa, Y. (1988) J. Physiol. 403, 407-424]. EPR spectroscopy provided structural information from paramagnetic probes on C-terminal domain surfaces. In the absence of TFP, tauR (rotational correlation time) was 1.6 ns for both alkali light chains (ALCs) and 1.8 ns for light chain 2 (LC2). This was faster than expected for proteins of this size (approximately 10 ns). TFP progressively recruited the probes into populations with tauR sevenfold to 12-fold slower, with half-maximal effects at a TFP concentration of approximately 370-800 microM. The differences probably indicate that CD spectroscopy detects changes in protein conformation due to 'specific' TFP binding at the LC hydrophobic core, while less specific binding at higher TFP concentrations is required to effect conformational changes on the protein surfaces near the paramagnetic probes. TFP binding was generally not cooperative. Comparative sequence analysis between calmodulin, troponin C, and myosin LCs indicated considerable conservation between residues expected to bind TFP.