Acute leukaemia in a defined geographic area – Incidence,clinical history and prognosis

A consecutive series of patients (1978–1981) comprising all patients with acute leukaemia from a population of 475000 inhabitants was reviewed. Thus, 94 patients were diagnosed as having acute leukaemia. No patients were lost from follow-up. The incidence figures of ALL and AML differed significantly from those of Sweden as a whole. 9 patients were < 15 years old. The median age of adult patients was 64 years, 60.8% being ≥ 60 years old. Of adult patients with AML, 20% had a preleukaemic history (chronic myeloproliferative disorders, myelodysplastic syndromes and others). None of 6 patients with leukaemia as a metamorphosis of a chronic myeloproliferative disorder achieved a complete remission. The overall remission rate of the remaining adult patients was 25%. Treated patients, 15–39 years old, with AML without any preleukaemic history, had a complete remission rate of 80% compared to 12% for patients ≥ 60 years old with the same diagnosis. Of 60 patients with ‘primary’ AML, 14 were not treated, mainly because of advanced age and complicating diseases. Most of these patients died within a week of admission.     

MAO-A inhibition in brain after dosing with esuprone, moclobemide and placebo in healthy volunteers: in vivo studies with positron emission tomography

Objective: The aim of the study was to investigate whether or not esuprone binds substantially to MAO-A in the human brain. Methods: In a randomised double-blind placebo-controlled study 16 male healthy volunteers were examined␣with positron emission tomography (PET) with [¹¹C]harmine. Eight of the volunteers were given daily doses of 800 mg esuprone, four were given bi-daily doses of 300 mg moclobemide, and four volunteers were given placebo tablets. PET was performed before initiation of a 7-day treatment period. On day 7, one investigation was made immediately before administration of the drug, representing 23 h after the previous day's treatment for esuprone and 11 h after the last tablets of moclobemide. Further investigations were made 4 h and 8 h after the morning dose on day 7. Results: PET showed a high degree of binding of [¹¹C]harmine, a high-affinity ligand for MAO-A, before the start of treatment, and a marked and similar reduction after treatment with esuprone and moclobemide. A slight tendency for normalisation of enzyme binding was observed at the last time point. In the placebo group no change was observed. Plasma kinetics of esuprone showed a rapid elimination with a half-life of about 4 h. Conclusion: The study demonstrates that esuprone was comparable to moclobemide in its effect on MAO-A inhibition in the brain at the doses given. This is an illustration of the potential of PET to monitor drug effects directly on target biochemical systems in the brain in human volunteers, and the possibility of using these data, rather than pharmacokinetic data, for the determination of dosing intervals. Received: 21 August 1996 / Accepted in revised form: 22 November 1996     

Host response toBothrops asper snake venom

As part of the characterization of the host reactivity to the venom ofBothrops asper, we investigated the inflammatory responses in the mouse footpad model. The subcutaneously injected venom induced a rapid increase of serum IL-6 concentration, which peaked between 3 and 6 h and returned to normal values at 12 h. In contrast, serum TNF- and IL-1 were not detectable at any time point studied. A myotoxic phospholipase A₂ isoform purified from this venom, myotoxin II, was also able to induce a systemic IL-6 release when injected into the footpad. Both venom and myotoxin induced local edema and a leukocyte infiltrate accumulating in the muscle and subdermal tissue within 6 h. The infiltrate consisted predominantly of neutrophils at 6 and 24 h, but at later times, mononuclear cells also appeared. The edema, leukocyte infiltration, and IL-6 responses did not depend on the hemorrhagic activity of venom, since all three effects were seen after injection of (1) preneutralized venom, devoid of hemorrhagic activity, and (2) purified myotoxin II. Circulating platelet numbers were significantly decreased 30 min after venom injection and returned to normal after 12 h. The venom also induced a rapid inversion in the ratio of neutrophils to lymphocytes in peripheral blood, which did not normalize until 12 h later. The present observations suggest that venom, besides its cytotoxic properties, induces early hematologic and immunologic alterations. These findings may be of relevance in future treatment modalities.     

Accuracy of pulse oximetry at various haematocrits and during haemolysis in anin vitro model

In situations in which it may be impossible and/or unethical to evaluate pulse oximetry in humans, an in vitro model with circulating blood may be a necessity. The main objective was to develop such an in vitro model and, in this model, validate the pulse oximetry technique at various haematocrit levels. The pulsating character of arterial blood flow in a tubing system was simulated by using a specially constructed pressure-regulated roller pump. The tubing system was designed to minimise damage to red blood cells. The pulse oximeter readings (SpO₂) were compared with oxygen saturation analyses by a haemoximeter (SaO₂). The pulse oximetry readings were recorded at various haematocrit levels and during haemolysis in the SaO₂ range 60–100 per cent. At a haematocrit level of 41–44 per cent, there was no correlation between SaO₂ and SpO₂ readings. After diluting the blood with normal saline to a haematocrit of 10–11 per cent, a good correlation between SaO₂ and SpO₂ was found. Following haemolysis, the agreement between SaO₂ and SpO₂ was further improved. Using the developed in vitro model, the results indicate that the accuracy of a pulse oximeter may be dependent on the haematocrit level.     

Mechanoreceptor activity from the human face and oral mucosa

Summary The feasibility of adopting the microneurography technique (Vallbo and Hagbarth 1968) as a tool to investigate the mechanoreceptive innervation of peri- and intra-oral tissues was explored. Multi-unit activity and impulses in single nerve fibers were recorded from the infraorbital nerve in healthy volunteers. The innervation territories of individual nerve fascicles were mapped. These varied considerably but most fascicle fields comprised the corner of the mouth. Twenty-four single mechanoreceptive units were recorded. Eighteen innervated the skin of the face, and six innervated the mucous membranes of the lips or cheeks. A majority of the mechanoreceptive afferent units were slowly adapting with small and well defined receptive fields. It is suggested that the various slowly adapting responses may originate from two different types of afferent units. No afferents showed response properties similar to typical Pacinian-corpuscle afferents.     

Impedance plethysmography in human limbs

Electrode design and electrode positioning are important factors in blood flow measurements using impedance plethysmography. Optimal electrode type and accurate positioning will decrease measurement errors and improve the signal-to-noise-ratio. Disk electrodes were found to be superior to tape electrodes because of their better skin-electrode stability and because they prevent limb compression. The distance between current electrodes and potential electrodes should be greater than 2·3 R (disk electrodes) and 1·5 R (tape electrodes) to avoid the influence of the so-called diffusion resistance (R is the radius of the limb at the electrode site).     

Localization of evoked potentials in the digastric,masseteric, supra- and intertrigeminal subnuclei of the cat

Summary Extracellular focal potentials were evoked and mapped in the trigeminal motor nucleus and its surrounding borderzone in the cat. Graded electrical stimulation was used for orthodromic and antidromic excitation of the masseteric and digastric motoneurones and for orthodromic stimulation of the lingual and inferior alveolar nerves. The method of referring Horsley Clarke coordinates of microelectrode recording positions to their location of the actual histological section was studied and the total error affecting the method was calculated for the H, AP and L axes. The characteristics and the distribution of the evoked focal potentials were described and related to the histological section from the actual experiment. A phase reversal of the negative focal potential evoked by the lingual and inferior alveolar nerves in the main sensory nucleus and in the intertrigeminal nucleus was observed to indicate the dorso-lateral border of the motor nucleus. Other borders were given by the antidromic potentials evoked in the nucleus. Digastric motoneurones were found medially in the caudal third and ventro-medially in the middle third of the motor nucleus. The masseteric motoneurones were located laterally in the middle and rostral thirds of the nucleus. Potentials evoked in the supratrigeminal and intertrigeminal subnuclei, adjacent to the motor nucleus, were considered and discussed in relation to the available evidence of interneurones subserving trigeminal reflex arcs.     

Evaluation of antidecubitus mattresses

Pressure sores are a current problem in hospitals and care of the elderly, leading to protracted hospital stays and a high care burden. The trauma for the patients is severe, and the cost of pressure sore prevention and treatment, is considerable. Antidecubitus mattresses are used for prevention and in treatment, but they also contribute to the cost of treating pressure sores. The problem highlighted in the review is that the mattresses' effectiveness in preventing and treating pressure sores has not been sufficiently evaluated. When antidecubitus mattresses are evaluated, it is often only with regard to aspects of the interface pressure and the mattresses' ability to redistribute the pressure. The review points out the important observation that, to be able to evaluate the efficacy of the antidecubitus mattress, the mattress's effect on tissue viability needs to be studied. The parameters that ought to be considered when evaluating a support surface are: interface pressure, pressure and blood flow distribution, temperature and humidity in the skin-support surface interface. The authors propose that the effect on tissue viability of external loading can be assessed by simultaneous measurement of the interface pressure and tissue perfusion.     

Magnetophosphenes: a quantitative analysis of thresholds

Low-frequency and transient magnetic fields of moderate flux densities are known to generate visual phenomena, so-called magnetophosphenes. In the present study, time-variable very low frequency (10–50 Hz) electromagnetic fields of moderate flux density (0–40 mT) were used to induce magnetophosphenes. The threshold values for these phosphenes were determined as a function of the frequency of the magnetic field both in normal subjects and colour defective ones. Maximum sensitivity occurred at a frequency of approximately 20–30 Hz, and with broad-spectrum light the threshold flux density was 10–12 mT. The threshola values were found to be dependent upon the intensity and the spectral distribution of the background light. Sensitivity decreased during dark adaptation. In certain respects deutans differed from subjects with normal colour vision. Possible mechanisms for generation of magnetophosphenes are discussed. The present magnetic threshold curves show a close resemblance to corresponding curves obtained by electric stimulation at various frequencies provided the electric thresholds are divided by the a.c. frequency. These problems are under current investigation in our laboratory. This is in full agreement with the assumption that the fluctuating magnetic field affects retinal neurons by inducing currents which polarise synaptic terminals.     

Sympathomimetic Bronchodilators: Increased Selectivity with Lung-Specific Prodrugs

The development of selective bronchodilator -adrenoceptor agonists is reviewed with emphasis on a pharmacodynamic approach, which is directed to drugs with high specificity for the ₂-adrenoceptor, and on a pharmacokinetic approach in which known ₂-adrenoceptor agonists are converted to prodrugs with selectivity for the lung. The pharmacodynamic approach has produced drugs that display high specificity for the ₂-adrenoceptor but still suffer from side-effects including tremor and palpitations. This is due to the fact that the ₂-adrenoceptors present in skeletal muscle and blood vessel are indistinguishable from those in the airways. On the other hand, the prodrug pharmacokinetic approach offers a promising way to obtain selectively acting bronchodilators with significantly fewer side-effects.