The effect of palytoxin on neuromuscular junctions in the anococcygeus muscle of the rat

Palytoxin, a highly toxic natural product isolated from zoanthids of the genus Palythoa, is accumulated by a wide range of fishes and marine invertebrates used as food in the Indo-Pacific. It is responsible for many incidents of human morbidity and mortality. The toxin is a potent smooth muscle spasmogen. The cause of the contraction of smooth muscle is unclear, but recent work strongly suggests that it is primarily initiated by the release of neurotransmitters from the motor innervation of the smooth muscle. We show here that palytoxin caused the swelling of the muscle cells and some internal organelles of the anococcygeus muscle of the rat, but no substantial structural damage to the tissue. Axons and Schwann cells were also swollen but the most dramatic feature was the depletion of synaptic vesicles from putative release sites in the axons. Some axons were physically damaged following exposure to the toxin, but this was relatively uncommon (<10% of all axons studied). In the majority of axons there was no damage to nerve terminal membranes, but there was damage to mitochondria. The depletion of vesicles involved all types – clear, dense-cored, large and small. Our observations and pharmacological data gathered elsewhere, provide a neuropathological basis for the spasmogenic activity of palytoxin.     

Smoking and coffee intake following alcohol withdrawal in alcoholic inpatients

The aim of this study was to assess alcoholic inpatients' smoking and coffee intake variation following withdrawal. Only moderate smokers (less than 30 cigarettes/day) showed a significant increase of cigarette consumption after alcohol withdrawal. However, their urinary cotinine level did not vary, suggesting a behavioral, and not biological, compensation through smoking following alcohol withdrawal. Heavy smokers (30 cigarettes/day or more) showed no significant clinical or biological variation of smoking behavior. Coffee consumption increased after alcohol withdrawal in all patients, irrespective of smoking habits.     

Effect of nifedipine on the contractile responses of the isolated rat bladder

The effect of the calcium channel blocker nifedipine on the motor transmission in isolated preparations of rat detrusor smooth muscle has been studied. Nifedipine blocked the major part (75 to 80%) of the contractile response to electrical field stimulation, while atropine only blocked 20 to 25%. In preparations pretreated with atropine, the response to electrical field stimulation was completely abolished by nifedipine. The converse was also true; in preparations pretreated with nifedipine the response was fully blocked by atropine. The nifedipine-resistant response was greatly potentiated by the anticholinesterase eserine. The blocking action of nifedipine on motor transmission was partially antagonised by raising Ca2(+)-concentration. Acetylcholine concentration-response curve was shifted to the right by nifedipine. It is concluded that the non-cholinergic motor neurotransmitter evokes contraction of the rat detrusor smooth muscle by activating external Ca2(+)-transport channels whereas the cholinergic contraction is mediated partly or wholly by alternative mechanisms.     

Validation in the sheep of an ultrasound velocity dilution technique for haemodialysis graft flow

BACKGROUND: A simple, rapid, inexpensive method for measuring the flow in a patient's vascular access would permit routine monitoring during haemodialysis, and hence provide information of access graft deterioration sufficiently early to increase the success of minimally invasive remedial procedures. This paper reports the validation of such a method in animals. METHODS: A PTFE graft was implanted in sheep between the carotid artery and the jugular vein. While the sheep was under general anaesthesia and on an haemodialysis circuit, ultrasound velocity in its blood was perturbed by the injection of a 5-10 ml bolus of isotonic NaCl. The pump tubing flow was measured by a transit-time blood flow meter. This flow was combined with the areas of perturbation generated by the injection before and after mixing in the access flow to estimate graft flow. The calculated graft flow was compared to flow measured directly by a transit-time probe on the same carotid artery. RESULTS: Over a 10-fold range, 120-1260 ml/min, graft flow measured by ultrasound velocity dilution agreed well with graft flow measured directly with a scatter of 76 ml/min about the regression line. CONCLUSION: Ultrasound velocity dilution provides a method for measuring flow in the graft accurate enough for clinical evaluation of patients on dialysis.      

A 500‐ml plastic bottle: An effective spacer for children with asthma

Inhaled therapy using a metered‐dose inhaler (MDI) with attached spacer has been increasingly recognized as the optimal method for delivering asthma medication for acute attacks and chronic prophylaxis. However, in developing countries the cost and availability of commercially produced spacers limit the use of MDI‐spacer delivery systems. A 500‐ml plastic bottle has been recently adapted to function as a spacer. This article reviews the current data on the efficacy of this bottle‐spacer and discusses its advantages and limitations. It is concluded that a modified 500‐ml plastic bottle is an effective spacer; modification and use of this device should be incorporated into international guidelines for the management of children with asthma.     

Combination of ABO blood group incompatibility and glucose-6-phosphate dehydrogenase deficiency: effect on hemolysis and neonatal hyperbilirubinemia

The incidence (%) of hyperbilirubinemia (serum bilirubin ≥257 μmol/l) was similar in neonates with a combination of ABO incompatibility and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency (45%), with ABO incompatibility (54%) or G-6-PD deficiency (37%), alone (ns). Carboxyhemoglobin values, corrected for inspired CO, were similarly elevated in all three groups (0.87 ± 0.32%, 0.82 ± 0.29%, 0.76 ± 0.18%, respectively, ns), but correlated with bilirubin only in those with ABO incompatibility alone. ABO-incompatible/G-6-PD-deficient neonates, compared with those with either condition alone, are not at increased risk for hemolysis or hyperbilirubinemia.     

Randomised controlled trial of the efficacy of a metered dose inhaler with bottle spacer for bronchodilator treatment in acute lower airway obstruction.

BACKGROUND: Inhaled bronchodilator treatment given via a metered dose inhaler (MDI) and spacer is optimal for relief of bronchoconstriction. Conventional spacers are expensive or unavailable in developing countries, but there is little information on the efficacy of low-cost spacers in young children. OBJECTIVE: To compare the response to bronchodilator treatment given via a conventional or a low-cost bottle spacer METHODS: A randomised controlled trial of the efficacy of a conventional spacer compared with a bottle spacer for bronchodilator treatment in young children with acute lower airway obstruction. Bronchodilator treatment was given from an MDI via an Aerochamber or a bottle spacer. Clinical score and oximetry recording were carried out before and after 15 min of treatment. MDI-spacer treatment was repeated up to three times, depending on clinical response, after which nebulisation was used. The primary outcome was hospitalisation. RESULTS: 400 children, aged (median (25th-75th centile)) 12 (6-25) months, were enrolled. The number of children hospitalised (n = 60, 15%) was identical in the conventional and bottle spacer groups (n = 30, 15% in each). Secondary outcomes including change in clinical score (-2 (-3 to -1)), oxygen saturation (0 (-1 to 1)) and number of bronchodilator treatments (2 (1 to 3)) were similar in both groups. Oral corticosteroids, prescribed for 78 (19.5%) children, were given to a similar number in the conventional (37 (18.5%)) and bottle spacer groups (41 (20.5%)). CONCLUSION: A low-cost bottle spacer is as effective as a conventional spacer for bronchodilator treatment in young children with acute obstruction of the lower airways.     

A comparative analysis of estimation of age at menarche by various methods in women participating in the Krakow Longitudinal Growth Study, Poland.

The purpose of this study was to see whether menarcheal age assessment by means of the most frequently used methods that were conducted every time on the same group of girls would yield the same results. One hundred and one Polish girls, whose ages at menarche were recorded in a longitudinal study between 1976 and 1990, were asked to recall the age of menarche in 2004. The mean menarcheal ages of those women were calculated by means of the probit (PA), prospective (AA), retrospective method without age correction (RA), and retrospective method with the recall age corrected by 0.5 year (RcA). The PA, AA, and retrospective methods: RA and RcA revealed results: 13.14 +/- 1.1; 13.10 +/- 1.1; 13.12 +/- 1.36, and 14.39 +/- 1.34 years, respectively. The menarcheal AA was insignificantly different from the PA (95% CI) and RA. The RcA was significantly higher than the AA and RA (P = 0.05). The correlation coefficient (r) between AA and RA was 0.70. Only 16% of the interviewed women accurately remembered the date of their menarche, 63% of them missed their menarche time by about 1 year, whereas 22% were wrong by 2 and more years. (1) The PA and the AA method yield comparable results when estimating menarcheal age. (2) The menarcheal age determined by the retrospective methods is not very reliable and the application of age correction overestimates the results.     

The effects of co-culture with human fibroblasts on human embryo development in vitro and implantation

In a human in-vitro fertilization (IVF) programme, the effect of co- culture of embryos with human fibroblasts was evaluated with respect to pregnancy rate and embryo development. Patients were included in the study after giving informed written consent. The IVF treatments were randomly assigned by stratification of both age (<36 versus > or =36 years) and previous IVF attempts (yes versus no). After fertilization was established, the zygotes were transferred to a 4-well dish with or without fibroblasts and cultured for 2 days. On the third day after ovum pick-up (OPU), cell number and quality [5 (good) to 1 (poor)] of the embryos were scored and a maximum of three embryos was transferred. Supernumerary embryos of good quality were cryopreserved. The design of this study was a group sequential trial with the objective of detecting differences between pregnancy rates following IVF with conventional incubation or incubation in co-culture with fibroblasts. This design included one evaluation at half-way data collection. In the study, 148 patients had an OPU, of whom 77 were allocated to the co-culture group. There was no statistically significant difference in pregnancy rate, cell number and embryo quality between the two groups. The ongoing pregnancy rate per embryo transfer was 27% in co-culture and 30% in the conventional culture group. The implantation rates per transferred embryo were 17 and 18% respectively. Using a multivariate logistic regression model for the probability of ongoing pregnancies, the odds ratio of co-culture, adjusted for age and previous IVF attempts, was not statistically significant. In conclusion, co-culture with human fibroblasts does not contribute to an improvement of embryo quality nor to a higher pregnancy rate after IVF in an unselected group of patients.