Relation between electromyography and anal manometry of the external anal sphincter.

Thirteen patients with faecal incontinence and 26 control subjects were studied to investigate whether a quantitative electromyographic (EMG) signal could be correlated to anal manometry. Three different electrodes were used--a concentric needle electrode, a disposable sponge electrode, and a hard anal plug electrode. The maximum amplitude of the EMG recording was used as a quantitative parameter. Linear regression showed significant correlation between EMG and anal manometry with the sponge electrode, both at rest and during squeeze. Significant correlation was also found with the concentric needle electrode during squeeze but not at rest. No correlation was found with the hard anal plug electrode either during squeeze or at rest. Reproducibility studies using the sponge electrode showed acceptable day to day variation. In conclusion, quantitative EMG recordings from a disposable sponge electrode placed in the anal canal correlate well to anal manometry and may be used for assessment of sphincter function, but the hard anal plug electrode cannot be recommended.     

Thrombopoietin stimulates megakaryocytopoiesis, myelopoiesis, and expansion of CD34+ progenitor cells from single CD34+Thy-1+Lin- primitive progenitor cells

Thrombopoietin (TPO) or MpI ligand is known to stimulate megakaryocyte (MK) proliferation and differentiation. To identify the earliest human hematopoietic cells on which TPO acts, we cultured single CD34+Thy- 1+Lin- adult bone marrow cells in the presence of TPO alone, with TPO and interleukin-3 (IL-3), or with TPO and c-kit ligand (KL) in the presence of a murine stromal cell line (Sys1). Two distinct growth morphologies were observed: expansion of up to 200 blast cells with subsequent differentiation to large refractile CD41b+ MKs within 3 weeks or expansion to 200-10,000 blast cells, up to 25% of which expressed CD34. The latter blast cell expansions occurred over a 3- to 6-week period without obvious MK differentiation. Morphological staining, analysis of surface marker expression, and colony formation analysis revealed that these populations consisted predominantly of cells committed to the myelomonocytic lineage. The addition of IL-3 to TPO-containing cultures increased the extent of proliferation of single cells, whereas addition of KL increased the percentage of CD34+ cells among the expanding cell populations. Production of multiple colony- forming unit-MK from single CD34+Thy-1+Lin- cells in the presence of TPO was also demonstrated. In limiting dilution assays of CD34+Lin- cells, TPO was found to increase the size and frequency of cobblestone areas at 4 weeks in stromal cultures in the presence of leukemia inhibitory factor and IL-6. In stroma-free cultures, TPO activated a quiescent CD34+Lin-Rhodamine 123lo subset of primitive hematopoietic progenitor cells into cycle, without loss of CD34 expression. These data demonstrate that TPO acts directly on and supports division of cells more primitive than those committed to the MK lineage.     

Adrenergic effects on secretion of amylase from the rat salivary glands

The present study was undertaken to investigate the effect of adrenergic agents on secretion of amylase from the salivary glands in vivo. Saliva was collected from the distal oesophagus in conscious rats. Adrenaline increased the concentration of amylase in saliva and serum significantly. The result of infusion of alpha- and beta-adrenergic antagonists as well as noradrenaline and isoproterenol showed that secretion of salivary amylase is predominantly mediated by stimulation of beta-adrenergic receptors, especially of the beta 1-subtype. Investigation of the isoenzyme pattern in saliva, pancreatic juice and serum demonstrated that the major component in serum is salivary amylase. This study has shown that beta-adrenergic agents stimulate secretion of amylase from the salivary glands in rats. Though the secretion is mainly exocrine small amounts of amylase is found in serum, which seems to originate from the salivary glands.     

Excretion pattern of branched-chain amino acid metabolites during the course of acute infections in a patient with methylmalonic acidaemia

A 1-year-old boy with a typical B₁₂-responsive form of methylmalonic acidaemia was hospitalized twice due to acute bacterial infections. On both occasions, the child was lethargic with a severe ketoacidosis on admission. Intensive therapy with protein restriction, intravenous administration of electrolytes and antibiotics was effective within 4 days on both occasions. The urinary excretion of organic acids showed the same pattern on both occasions. There were rising excretion concentrations, reaching a peak value within the first 24-hour period, for the following compounds: 3-hydroxybutyric acid, 3-hydroxypropionic acid, 3-hydroxyisobutyric acid and 3-hydroxyisovaleric acid. Excretion concentrations of the following rose for 48 h: isobutyric acid, 2-methylbutyric acid, isovaleric acid, lactic acid and the 2-oxo-acids. There was no increase until 12–24 h after the onset of severe illness in the excretion of propionic acid and methylmalonic acid. Propionic acid excretion was maximal at about 48 h, while peak excretion of methylmalonic acid was delayed until about 72 h after the onset of severe illness; at this time there was clinical improvement. The biochemical implications of this excretion pattern are discussed. This work has been supported by a grant from the Danish Medical Research Council.     

Improvement of anticoagulant treatment using a dynamic decision support algorithm: A Danish Cohort study

Introduction

Warfarin is the most widely prescribed vitamin K antagonist and in the United States and Europe more than 10 million people are currently in long-term oral anticoagulant treatment. This study aims to retrospectively validate a dynamic statistical model providing dosage suggestions to patients in warfarin treatment.

Materials and methods

The model was validated on a cohort of 553 patients with a mean TTR of 83%. Patients in the cohort were self-monitoring and managed by a highly specialised anticoagulation clinic. The predictive model essentially consists of three parts handling INR history, warfarin dosage and biological noise, which allows for prediction of future INR values and optimal warfarin dose to stay on INR target. Further, the model is based on parameters initially being set to population values and gradually individualised during monitoring of patients.

Primary outcome

Time in therapeutic range was used as surrogate quality measure of the treatment, and model-suggested dosage of warfarin was used to assess the accuracy of the model performance.

Results

The accuracy of the model predictions measured as median absolute error was 0.53 mg/day (interquartile range from 0.25 to 1.0). The model performance was evaluated by the difference between observed and predicted warfarin intake in the preceding week of an INR measurement. In more than 70% of the cases where INR measurements were outside the therapeutic range, the model suggested a more reasonable dose than the observed intake.

Conclusion

Applying the proposed dosing algorithm can potentially further increase the time in INR target range beyond 83%.