International round-robin study on the Ames fluctuation test.

An international round-robin study on the Ames fluctuation test [ISO 11350, 2012], a microplate version of the classic plate-incorporation method for the detection of mutagenicity in water, wastewater and chemicals was performed by 18 laboratories from seven countries. Such a round-robin study is a precondition for both the finalization of the ISO standardization process and a possible regulatory implementation in water legislation. The laboratories tested four water samples (spiked/nonspiked) and two chemical mixtures with and without supplementation of a S9-mix. Validity criteria (acceptable spontaneous and positive control-induced mutation counts) were fulfilled by 92-100%, depending on the test conditions. A two-step method for statistical evaluation of the test results is proposed and assessed in terms of specificity and sensitivity. The data were first subjected to powerful analysis of variance (ANOVA) after an arcsine-square-root transformation to detect significant differences between the test samples and the negative control (NC). A threshold (TH) value based on a pooled NC was then calculated to exclude false positive test results. Statistically, positive effects observed by the William's test were considered negative, if the mean of all replicates of a sample did not exceed the calculated TH. By making use of this approach, the overall test sensitivity was 100%, and the test specificity ranged from 80 to 100%.

Modelling the transmission dynamics of acute haemorrhagic conjunctivitis: application to the 2003 outbreak in Mexico.

We model an outbreak of acute haemorrhagic conjunctivitis (AHC) using a simple epidemic model that includes susceptible, infectious, reported, and recovered classes. The model's framework considers the impact of underreporting and behaviour changes on the transmission rate and is applied to a recent epidemic of AHC in Mexico, using a fit to the cumulative number of cases to estimate model parameters, which agree with those derived from clinical studies. The model predicts a 'mean time from symptomatic onset to diagnosis' of 1.43 days (95 per cent CI: 1-2.5) and that the final size of the Mexican epidemic was underreported by 39 per cent. We estimate that a primary infectious case generates approximately 3 secondary cases (R0* = 2.64, SD 0.65). We explore the impact of interventions on the final epidemic size, and estimate a 36 per cent reduction in the transmission rate due to behaviour changes. The effectiveness of the behaviour changes in slowing the epidemic is evident at 21.90 (SD 0.19) days after the first reported case. Results therefore support current public health policy including expeditious announcement of the outbreak and public health information press releases that instruct individuals on avoiding contagion and encourage them to seek diagnosis in hospital clinics.

A discrete epidemic model for SARS transmission and control in China.

Severe acute respiratory syndrome (SARS) is a rapidly spreading infectious disease which was transmitted in late 2002 and early 2003 to more than 28 countries through the medium of international travel. The evolution and spread of SARS has resulted in an international effort coordinated by the World Health Organization (WHO). We have formulated a discrete mathematical model to investigate the transmission of SARS and determined the basic reproductive number for this model to use as a threshold to determine the asymptotic behavior of the model. The dependence of the basic reproductive number on epidemic parameters has been studied. The parameters of the model have been estimated on the basis of statistical data and numerical simulations have been carried out to describe the transmission process for SARS in China. The simulation results matches the statistical data well and indicate that early quarantine and a high quarantine rate are crucial to the control of SARS.

Models for transmission of disease with immigration of infectives.

Simple models for disease transmission that include immigration of infective individuals and variable population size are constructed and analyzed. A model with a general contact rate for a disease that confers no immunity admits a unique endemic equilibrium that is globally stable. A model with mass action incidence for a disease in which infectives either die or recover with permanent immunity has the same qualitative behavior. This latter result is proved by reducing the system to an integro-differential equation. If mass action incidence is replaced by a general contact rate, then the same result is proved locally for a disease that causes fatalities. Threshold-like results are given, but in the presence of immigration of infectives there is no disease-free equilibrium. A considerable reduction of infectives is suggested by the incorporation of screening and quarantining of infectives in a model for HIV transmission in a prison system.

Surgical techniques for arteriovenous malformations in functional areas: focus on the superior temporal gyrus.

Direct surgical intervention of arteriorvenous malformations (AVMs) in functional areas has been accepted as a standard mode of treatment. However, safe and successful intervention requires that such factors as exact location, size, vascular supply, and drainage be considered. Importantly, surgical techniques must be individualized to each patient, based on hemodynamic anatomy of the AVM. This paper discusses AVMs in the superior temporal lobe, which have a complex neuronal anatomy and circulatory system; the authors present 22 patients with AVMs of various sizes and describe the surgical techniques specific for the indicated location. Surgical procedures adhered to the following principles: 1) avoid brain tissue removal; 2) preserve microcirculation; 3) maintain circulation of the isolated major draining vein to access the AVM core; 4) compartmental isolation; and 5) preservation of functional area cortex covering the AVM. All patients underwent total resection except one, who had a subtotal resection. Neurological and occupational recovery was remarkable except for partial hemianesthesia in one patient; two patients are still in rehabilitation. This is the first description of a direct surgical approach to AVMs in the superior temporal gyrus, where management is challenging because the lesions may extend elsewhere, such as to Broca's and Wernicke's areas. The results suggest that the procedure is promising.

Effects of treatment and prevalence-dependent recruitment on the dynamics of a fatal disease.

This paper studies models for the sexual transmission of HIV/AIDS that incorporate changes in behaviour and the effects associated with HIV treatment. The recruitment rate into the core is assumed to be a function of the prevalence of the disease within the core, and it may trigger the existence of periodic solutions through Hopf bifurcations, provided that there is at least a weak demographic interaction with the noncore. The recruitment function is set up for two cases: dependence on the total proportion of infectious individuals and dependence on the proportion of treated infectious individuals only. In the general model, numerical evidence suggests that both cases may produce periodic solutions when the perception of the risk of joining the core group is sufficiently high. Two limiting cases are also studied: when the growth rate of the core and noncore groups are essentially the same, and when treatment has no effect on the transmission rate of infected individuals.

Models for diseases with vertical transmission and nonlinear population dynamics.

Vertical transmission, the direct transfer of a disease from an infective parent to a new born offspring, is an important aspect of many diseases. Most of what is known for vertical transmission models assumes birth rates proportional to population size. We consider models with nonlinear population dynamics and finite carrying capacity and analyze the stability of equilibria in the special case in which the overall birth rate does not depend on infective population size.

Total blood flow to arteriovenous malformations.

Normal perfusion pressure breakthrough is considered to be a great hazard during or after resection of large arteriovenous malformations (AVMs). This article presents the total blood flow to the AVMs, particularly those of greater than 3 cm in diameter (greater than 14.1 cm3 in volume), which have multiple compartments. The total blood flow into the AVMs in the sensory-motor area in 6 patients averaged 830 +/- 285 cc/min and those in the visual area in 4 patients averaged 358 +/- 33 cc/min. These flow values were compared to total flow through the intracranial arteries (756 cc/min). Large volume of blood flow into the AVMs carries a significant post-operative risk of normal profusion pressure breakthrough. Redistribution of blood flow from large AVMs into the cerebrovascular bed is an important factor for circulatory regulation to occur after their resection. The risk of normal profusion pressure breakthrough must be minimized by surgical technique discussed in the text.

The effect of measurement conditions on MCG inverse solutions.

A magnetic inverse solution that uses a single current dipole in a homogeneous volume conductor with realistic torso shape was tested numerically to establish the effect of magnetic noise, number of measurement points, and torso size on the localization accuracy. Seven different sites of cardiological interest were selected as locations for the source dipole. The three components of the magnetic field were calculated as if measured by second order gradiometers, Gaussian noise was added, and Monte Carlo tests performed for inverse solutions using a single field component, or all three combined. It was found that for any of the single component solutions, and a signal-to-noise ratio of 100, 25 measuring points are sufficient for good accuracy; just 12 points are needed if all three components are used together. If, however, the torso size of the inverse solution is different from that of the field data by 10 or 20%, a larger error occurs, even for 56 measurement points and no noise. In this case, the field component orthogonal to the measurement grid, Bz, yields better results than the other two components, or even all three combined. We conclude that a multichannel system measuring the z component of the magnetic field in about 30 locations would be the best choice to locate a dipolar source, provided the torso of the field data is closely matched by the model used in the inverse solution. To this effect, scaling of the torso model can easily be included in the computation. Imaging techniques could be used to accommodate different torso shapes.

Can somatosensory evoked potential monitoring predict energy dynamics during controlled hypotension?

Somatosensory evoked potentials and redox (reduction/oxidation ratio) of cytochrome a,a3 were studied simultaneously before, during, and after controlled hypotension used for arteriovenous malformation resection. These studies were also conducted before and after ED-IC (external-internal carotid) bypass procedures for treatment of patients with transient ischaemic attacks. The former served as an acute model and the latter as a chronic model of low blood flow (ischaemia). The use of non-invasive reflection spectrophotometry (for redox studies) in conjunction with somatosensory evoked potentials (SSEP) has demonstrated that metabolic and electrophysiological changes parallel each other during "controlled" hypotension. The authors conclude that an analysis of SSEP changes are valuable in the study of metabolic and functional states of the brain during controlled hypotension.

Persistent sacral nerve root deficits after continuous spinal anaesthesia.

Neurological deficits following spinal anaesthesia are rare. We report two cases of persistent sacral nerve root deficits after continuous spinal anaesthesia (CSA) performed with hyperbaric lidocaine through a lumbar microcatheter. In both cases the dose of 5% lidocaine (5.7 and 4.3 ml) was greater than usual. In the immediate postoperative period the constellation of neurological deficits included perianal hypaesthesia, lower extremity paresis, urinary retention, and difficult defaecation. Both patients have residual perianal hypaesthesia and difficult defaecation. In these cases, the high-dose requirements of local anaesthetic via microcatheter CSA with focal sensory block suggests nonuniform distribution of the hyperbaric lidocaine. Microcatheter CSA may convey a unique risk of maldistribution of the local anaesthetic solution and local neurotoxicity.

Investigations of phagocytosis concerning the immunological defence mechanism of Mytilus edulis using a sublethal luminescent bacterial assay (Photobacterium phosphoreum).

1. A simple method for the determination of phagocytosis activity using mussel hemocytes by measuring the bioluminescence is presented. 2. The immunological defence activity based on phagocytosis is measured and quantified by a luminescent bacterial assay with Photobacterium phosphoreum. 3. The measuring system allows us to establish the stress of the immunological defence mechanism of organisms exposed to chemicals and polluted rivers or sewage. Results with reference substances and the phagocytosis indices of exposed mussels from Norwegian aquaculture plants compared to those of mussels from the German Wadden Sea are given as examples.

Direct approach to arteriovenous malformations in functional areas of the cerebral hemisphere.

The natural history of patients with arteriovenous malformations (AVM's) suggests that serious morbidity associated with AVM's in functional areas is likely to be much greater than in silent areas. Various modes of treatment of AVM's in functional areas, including direct surgical intervention, embolization, and irradiation, have been considered to carry high risks. The authors advocate direct surgical intervention to these AVM's via a microsurgical technique based on knowledge of the hemodynamic anatomy of AVM's. The technique is designed to circumscribe the AVM without removing any surrounding cortical tissue or white matter and to preserve microcirculation in the functional area. Controlled hypotension (mean arterial blood pressure 40 to 60 mm Hg) is appropriate to enhance the safety of surgical procedures without causing metabolic and electrophysiological dysfunction. Another means to prevent neurological complications is multi-staged resection of larger AVM's, which permits obliteration compartment by compartment. This technique has the advantage of maintaining circulatory sufficiency in the functional area. There was no mortality among 56 patients who underwent the surgical procedure described. Of those, 55 patients resumed their preoperative occupation and one patient became self-sufficient.

Models for the spread of universally fatal diseases.

In the formulation of models of S-I-R type for the spread of communicable diseases it is necessary to distinguish between diseases with recovery with full immunity and diseases with permanent removal by death. We consider models which include nonlinear population dynamics with permanent removal. The principal result is that the stability of endemic equilibrium may depend on the population dynamics and on the distribution of infective periods; sustained oscillations are possible in some cases.

The effect of hypervolemic hemodilution with and without hypertension on cerebral blood flow following middle cerebral artery occlusion in rats anesthetized with isoflurane.

The effect of hypervolemic hemodilution or hypervolemic hemodilution with dopamine-induced hypertension on cerebral blood flow (CBF) was investigated during 1.2 MAC isoflurane anesthesia in rats (n = 24) subjected to middle cerebral artery occlusion (MCAO). Prior to MCAO each animal was randomized to one of the following groups: 1) control, mean arterial pressure (89 +/- 10 mmHg [mean +/- SD]), blood volume, and hematocrit (46 +/- 1) were not manipulated; 2) hypervolemic hemodilution (HH), 30 min before MCAO, 5% albumin was administered to reduce the hematocrit to 29-32%; or 3) hypervolemic hemodilution/dopamine hypertension (HH/Dop), hemodilution was accomplished and dopamine (10 micrograms.kg-1.min-1) was infused during the ischemic period to achieve a mean arterial pressure of 111 +/- 10 mmHg (mean +/- SD). Ten minutes after occlusion of the left middle cerebral artery, CBF was determined using 14C-iodoantipyrine. Five coronal brain sections were analyzed to determine the area within each brain section with CBF ranges of 0-15 ml.100 g-1.min-1 and 15-23 ml.100 g-1.min-1. The area of 0-15 ml.100 g-1.min-1 CBF was less in both the HH and HH/Dop groups compared with control (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of fentanyl anesthesia and intrathecal naloxone on neurologic outcome following spinal cord injury in the rat.

Whereas opiate receptor agonists have resulted in spinal cord damage; opiate receptor antagonists have demonstrated protection against spinal cord injury. Because opioids are used in clinical anesthesia, the effect of an opiate antagonist was evaluated on neurologic outcome in a rat model of spinal cord injury occurring during opioid anesthesia. One day prior to spinal cord injury, a catheter was inserted into the spinal subarachnoid space with the tip at T8. On the day of spinal cord injury a balloon tipped catheter was inserted in the epidural space with the tip at the thoracolumbar junction. Spinal cord injury was produced by balloon inflation during one of the following states: 1) group 1 (A/S), injury was produced in awake rats and saline was administered in the subarachnoid space immediately following injury; 2) group 2 (F/S), injury was produced during a fentanyl/nitrous oxide (N2O) anesthetic, and subarachnoid saline administered; and 3) group 3 (F/Nx), injury was produced during a fentanyl/N2O anesthetic, and subarachnoid naloxone (1 mg/kg) was administered immediately following injury. Dose-response curves describing the relationship between the duration of balloon inflation and the percentage of animals with a persistent neurologic deficit were constructed and compared for differences by use of a group t test. The duration of balloon inflation required to produce a neurologic deficit was greater in both the F/S and F/Nx groups than in the A/S group (P less than 0.05). There was no difference between the F/S and F/Nx groups. In summary, in rats receiving a fentanyl/N2O anesthetic, neurologic outcome was improved compared with the awake state.(ABSTRACT TRUNCATED AT 250 WORDS)

Safety limits of controlled hypotension in humans.

Controlled hypotension is a safe and convenient means of allowing a surgeon to perform intracranial aneurysm, arteriovenous malformation and vascular tumor surgery. The mean arterial pressure between 40 and 60 mmHg induces diminished pulsatile arterial pressure, thus preventing rupture of these abnormal vasculatures. It is still possible to maintain cerebral metabolism in the functional level within this 40-60 mmHg blood pressure range. This statement is based on our experience of the physical and neurological outcome of patients after surgery, and on analyses of somatosensory evoked potential and redox of cytochrome a, a3 in the mitochondria of the cerebral cortical cells.

Effect of chronic alcohol consumption on rat brain microsome lipid composition, membrane fluidity and Na+-K+-ATPase activity.

The present study reports differences in phospholipid classes, fatty acids of individual phospholipids, and changes in membrane fluidity and Na+-K+-ATPase activity in brain microsomes of rats maintained on an alcohol diet for 35 days compared to sex, age and weight-matched control rats maintained on a calorically-equivalent, non-alcohol diet. Although no difference in Na+-K+-ATPase activity was found in microsomes from alcohol vs control rats when measured in the absence of added alcohol, the presence of low concentrations of ethanol (less than 100 mM) stimulated, while high concentrations (greater than 100 mM) inhibited enzyme activity. The stimulation was differentially expressed in that the microsomal enzyme from alcohol rats was stimulated to a lesser extent than the enzyme from control rats. However, the inhibiting effect of high concentrations of alcohol was similar in microsomes from both alcohol and control rats. Also in membranes from alcohol rats, there was a lower quantity of phosphatidylethanolamine (PE) and higher quantities of phosphatidylserine (PS) and phosphatidylinositol (PI) compared to membranes from control rats. The major change in fatty acid composition was a reduction in the level of polyunsaturated fatty acids, which was particularly evident in PI and PS. The linoleic acid: arachidonic acid ratio (18:2/20:4) and the saturation:unsaturation ratio were also increased in PI and PS in membranes from alcohol animals. However, the ratio of n-6/n-3 fatty acids remained the same or was reduced in membranes from alcoholic animals. Although no difference in the inherent "fluidity" of membranes from alcohol vs control rats could be demonstrated by electron paramagnetic resonance, molecular tolerance to ethanol was demonstrated in the membranes from alcohol rats by the resistance to the disordering effects of added ethanol.