Measurement of digital blood flow using the laser Doppler,impedance and strain-gauge methods

Digital volume changes and blood flow have been measured with impedance and strain-gauge plethysmography as well as with laser Doppler flowmetry. A good agreement was found between the impedance and strain-gauge flow measurements with a correlation coefficient of 0·905. The laser Doppler method recorded minor changes in finger skin blood flow following changes in posture from 30 cm below heart level to 60 cm above heart level. This result can be explained as a consequence of the limited penetration depth of laser light into the skin or as a sign of autoregulation of skin blood flow. In these experiments the total blood flow to the finger underwent major changes.     

Childhood medulloblastoma in Denmark 1960–1984 A population-based retrospective study

Medulloblastoma is a common paediatric brain tumour, located in the cerebellum and in the IV ventricle, surpassed in frequency only by astrocytomas. 180 children below the age of 15 with a medulloblastoma of the posterior fossa were treated in Denmark in the 25-year period from 1960 to 1984 and followed up until the end of 1996, or until death. During the 25 years they accounted for 20% of all intracranial tumours in children in Denmark. All tumours were histologically verified. The mean annual incidence was 6.4×10^–6, decreasing slightly with a factor of 0.12×10^–6 per year. The male/female ratio was 2.1 – twice that of the background population of children (1.05). The 5-year survival rate following diagnosis, surgery and radiotherapy was 23%, and the 25-year survival rate was 16%. The 5-year survival rate was 8% in the first 5-year period of 1960–1964, increasing to 36% in the last period 1980–1984. Presumably the increase in survival depends on many factors, e.g. improved diagnostic methods and neuroanaesthesia, better operative technique (microscope), improvements in radiotherapy and the introduction of chemotherapy. The best predictive factors of a good prognosis were preoperative CSF shunting, radical tumour removal and complete radiotherapy, i.e. irradiation of the brain, tumour bed and spinal cord. The survival rate in the last five-year period was seven times higher than the survival rate found in a comparable Danish study from the years 1935–1959. Most of the children followed Collins law of risk index. The results of treatment in children with medulloblastoma remain unsatisfactory. Accordingly, participation in international prospective studies of multimodal treatment should be encouraged, possibly using chemotherapy prior to surgery.     

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.     

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).     

Low and high LET radiation‐induced apoptosis in M059J and M059K cells

Purpose: To investigate and compare the ability of DNA‐dependent protein kinase (DNA‐PK)‐deficient and ‐proficient cells to undergo apoptosis after exposure to low and high linear energy transfer (LET) radiation.

Materials and methods: A human glioma cell line M059J lacking the catalytic subunit of DNA‐PK (DNA‐PKcs) and its DNA‐PKcs‐proficient counterpart, M059K, were exposed to 1 and 4?Gy of accelerated nitrogen ions (¹⁴N, 140?eV?nm^?1, 8–12?Gy?min^?1) or ⁶⁰Co γ‐rays (0.2?eV?nm^?1, 0.7?Gy?min^?1). The induction of apoptosis was studied up to 144?h post‐irradiation using two different methods: morphological characterization of apoptotic cells after fluorescent staining and cell size distribution analysis to detect apoptotic bodies. In parallel, protein expression of DNA‐PKcs and poly(ADP‐ribose) polymerase (PARP) as well as DNA‐PK and caspase‐3 activity were investigated.

Results: Low and high LET radiations (4?Gy) induced a time‐dependent apoptotic response in both cell lines. Low LET radiation induced a significantly elevated apoptotic response in M059J as compared with M059K cells at 144?h post‐irradiation. Following high LET radiation exposure, there was no difference between the cell lines at this time. PARP cleavage was detected in M059J cells following both low and high LET irradiation, while only high LET radiation induced PARP cleavage in M059K cells. These cleavages occurred in the absence of caspase‐3 activation.

Conclusions: M059J and M059K cells both display radiation‐induced apoptosis, which occur independently of caspase‐3 activation. The apoptotic course differs between the two cell lines and is dependent on the quality of radiation.     

Assessment of the systemic effects of inhaled glucocorticosteroids: the influence of blood sampling technique and frequency on plasma cortisol and leucocytes

Summary Twelve healthy males (mean age 27.6 y, range 23–35 y) took part in a randomized, double-blind, crossover study of the effect of blood sampling technique (separate isolated venepunctures vs use of an IV cannula) and frequency (overnight vs morning) on plasma cortisol and white blood cell count after inhalation of a single dose of budesonide 3.2 mg or placebo, in order to establish the more sensitive method for future use.Sampling technique and frequency affected neither leucocytes nor plasma or urinary cortisol. Budesonide suppressed both plasma and urine free cortisol and delayed the nocturnal rise due to the circadian rhythm, thus reducing the AUC of plasma cortisol vs time.Lymphocytes, eosinophils and monocytes were decreased and neutrophils and total white blood cells were increased by the high dose of budesonide used. Lymphocytes and neutrophils showed significant changes earlier than eosinophils and cortisol and may be the variables of choice under certain conditions.Frequent sampling gave more complete information about the systemic effect of the drug than single morning samples.     

The assessment of the systemic effects of inhaled glucocorticosteroids

Summary In a randomized, double-blind crossover study, the effects of 0.8, 1.6 and 3.2 mg/day inhaled budesonide and 5, 10 and 20 mg/day oral prednisolone on mineral metabolism were compared. Twelve healthy subjects (4 m, 8 f) were treated for 1 week at each dosage level, the graduated dosages being given in ascending order. Budesonide and prednisolone were given twice daily and once daily, respectively, which reflects the schedules common in clinical practice.Serum calcium and the regulatory hormones of calcium metabolism (parathyroid hormone, vitamin D metabolites and calcitonin) were not changed either by prednisolone or budesonide. Prednisolone significantly increased 24 h and 08.00 h fasting urinary calcium excretion and decreased renal calcium reabsorption, while budesonide had little or no effect on urinary calcium loss and increased renal reabsorption at the highest dose level. Both drugs significantly increased renal phosphate reabsorption and serum phosphate levels, but prednisolone caused greater increases than budesonide.In conclusion, during short-term treatment with the dosages used, inhaled budesonide had less effect on calcium and phosphate metabolism than oral prednisolone, and so it may have a lesser action on the skeleton of the type contributing to osteoporosis during long-term treatment.     

An assessment of the systemic effects of single and repeated doses of inhaled fluticasone propionate and inhaled budesonide in healthy volunteers

The systemic effects of single and multiple doses of inhaled fluticasone propionate (FP) and budesonide were examined in 24 healthy male volunteers (age range 18–29 years). The study was of an open, placebo-controlled, randomized, three-way crossover design. On each study day, multiple blood samples were taken over a 20 h period after drug administration (after a single dose and after the last of seven doses) and area under the curve (AUC_0–20) for plasma cortisol and white blood cell (WBC) counts was calculated. Results: The present study shows that multiple dosing with FP 1.0 mg b.i.d. for 3.5 days (seven doses) resulted in a marked cortisol suppression from placebo which, at 55%, was more than double that seen with a single dose (25% suppression). Multiple dosing with budesonide 0.8 mg b.i.d. resulted in a 34% suppression in plasma cortisol compared with a suppression of 26% with a single dose. The increase in systemic activity of FP after multiple dosing is confirmed by both the number of subjects with 0800 hours plasma cortisol values below normal limits and by the changes in WBC and differential counts. Conclusion: The results of the present study confirm previous findings with regard to the more marked systemic effect of FP following multiple dosing as compared with a single dose. This increase in systemic effect from single dosing to multiple dosing is significantly greater for FP than for budesonide.     

Central catecholamine neurons and exposure to dichloromethane. Selective changes in amine levels and turnover in tel- and diencephalic DA and NA nerve terminal systems and in the secretion of anterior pituitary hormones in the male rat

Subacute exposure of male rats to various concentrations (70–1000 ppm) of dichloromethane (DCM) produces a selective reduction of dopamine (DA) levels without a change of DA turnover in certain types of forebrain DA nerve terminal systems. In the low concentration (70 ppm) a selective reduction of DA turnover was observed in the medial palisade zone (MPZ) of the median eminence. This chlorinated organic solvent also produced a discrete dose-dependent increase of noradrenaline (NA) turnover within the