A guinea pig strain with recessive heredity of deafness, producing normal-hearing heterozygotes with resistance to noise trauma

A new strain of waltzing guinea pigs arose spontaneously in a guinea pig breeding facility in Germany in 1996. In addition to obvious vestibular dysfunction, the waltzing animals appear deaf already at birth. Histological analysis revealed that the waltzers lack an open scala media due to the collapse of Reissner's membrane onto the surface of the hearing organ. Subsequent breeding has shown that this strain has a recessive mode of inheritance. The homozygotes are deaf and display a waltzing behaviour throughout their lives while the heterozygotes show no significant signs of inner ear injury despite being carriers of this specific mutated gene of hearing impairment. However, the heterozygous animals offer the opportunity to study how hereditary factors interact with auditory stress. In the present study, the susceptibility of the carriers to noise was investigated. Auditory brainstem responses were obtained prior to and after noise exposure (4 kHz, 110 dB, 6 h). The carriers were significantly less affected by the noise as compared to control animals. This difference was still significant at 4 weeks following noise exposure. It is suggested that the heterozygous animals have an endogenous resistance to auditory stress.     

Kinetics of tyrosine transport and cognitive functioning in schizophrenia

BACKGROUND: Tyrosine supplementation in humans has been shown to improve cognitive functioning. Several studies have demonstrated a decreased maximal transport capacity of tyrosine (Vmax) across the cell membrane and an increased affinity (Km) of tyrosine to membrane binding sites in schizophrenic patients. A lack of tyrosine for dopamine synthesis with impairment of dopaminergic transmission could impair cognitive functioning. Aberrant tyrosine kinetics in patients with schizophrenia might therefore be associated with cognitive dysfunction--a core feature of schizophrenia. METHODS: Tyrosine kinetics was determined in cultured fibroblasts from 36 schizophrenic patients. The kinetic parameters Vmax and Km were calculated and then the patients were divided into two groups according to the median of the kinetic parameters. A comprehensive neuropsychological test battery was used to evaluate cognitive functioning. RESULTS: Patients with low Km (below the median) had poorer cognitive performance than patients with high Km (above the median). Vmax did not discriminate schizophrenic patients with cognitive dysfunction to the same extent. CONCLUSIONS: Changes in tyrosine transport probably influence cognitive functioning via the dopamine system. However, our findings of a relation between low Km and cognitive dysfunction may have a more complex background. It is suggested that the connection is related to genetically determined membrane factors that disturb communication/transmission among neurons.     

Changing patterns of female suicide: 1986-2000

A study was undertaken of the rates and methods of female suicide observed at the Forensic Science Centre in South Australia over a 15 year period from 1986 to 2000. A total of 609 cases of female suicide were found (age range= 13-88 yrs; mean= 44 yrs), with 249 drug overdoses, 114 hangings, 100 deaths due to carbon monoxide (CO) toxicity, 40 drownings, 35 firearm deaths and 71 miscellaneous deaths (including deaths due to self-immolation, jumping from heights and incised wounds). The most common age range was 26-50 yrs in all categories except for drowning where victims tended to be older. While overall suicide rates in females remained unchanged, with no changes in the rates at different ages, significant increases in hanging and CO deaths occurred over all age groups (p < 0.05), with significant falls in drug overdose deaths in the 10-25 year age group (p < 0.01), and significant overall falls in suicides due to gunshot wounds (p < 0.05). No changes were observed in female suicides due to drowning. This study has demonstrated, therefore, that although no changes in overall suicide rates for females occurred, there have been alterations in the types of methods being used. Although drug related deaths remained the largest category, hanging deaths, which were once uncommon in females, have increased markedly.     

Predicting energy response of radiographic film in a 6 MV x-ray beam using Monte Carlo calculated fluence spectra and absorbed dose

The advantage of radiographic film is that it allows two-dimensional, high-resolution dose measurement. While there is concern over its photon energy dependence, these problems are considered acceptable within small fields, where the scatter component is small. The application of film dosimetry to intensity modulated radiotherapy (IMRT) raises additional concern since the primary fluence may vary significantly within the field. The varying primary fluence in combination with a large scatter fraction, present for large fields and large depths, causes the spectrum at various points within the IMRT field to differ from the spectrum in the uniform fields typically used for calibrating the film. As a result, significant artifacts are introduced in the measured dose distribution. The purpose of this work is to quantify and develop a method to correct for these artifacts. Two approaches based on Monte Carlo (MC) simulations are examined. In the first method, the film artifact, as quantified by film and ion chamber output measurements in uniform square fields, is derived from the MC calculated ratio of absorbed doses to film and to water. In the second method, the measured film artifact is correlated with MC calculated photon spectra, revealing a strong correlation between the measured artifact and the "scatter"-to-"primary" ratio, defined by the ratio of the number of photons below to the number of photons above 0.1 MeV, independent of field size and depth. These methods are evaluated in high- and low-dose regions of a large intensity-modulated field created with a central block. The spectral approach is also tested with a clinical IMRT field. The absorbed dose method accurately corrects the measured film dose in the open part of the field and in points under the block and outside the field. The dose error is reduced from as much as 16% of the open field dose to less than 1%, as verified with an ion chamber. The spectral method accurately corrects the measured film dose in the open region of the centrally blocked field, but does not fully correct for the film artifact for points under the block and outside the field, where the spectrum is substantially different. Applied to the clinical field, the corrected film measurement shows good agreement with data obtained with a two-dimensional diode array.     

Differential macrophage expression of IL-12 and IL-23 upon innate immune activation defines rat autoimmune susceptibility

Rodents typically demonstrate strain-specific susceptibilities to induced autoimmune models such as experimental arthritis and encephalomyelitis. A common feature of the local pathology of these diseases is an extensive infiltration of activated macrophages (MPhi). Different functional activation states can be induced in MPhi during innate immune activation, and it is this differential activation that might be important in susceptibility/resistance to induction or perpetuation of autoimmunity. In this study, we present an extensive, comparative analysis of the activation phenotypes of MPhi derived from autoimmune-susceptible and autoimmune-resistant rat strains to describe a cellular phenotype that defines the disease phenotype. We included investigation of receptor function, intracellular signaling pathways, cytokines, and other soluble mediators released after activation of cells using a panel of stimuli embracing many activation routes. We report that activation of MPhi from the autoimmune-susceptible strain was associated with alternative activation indicated by induction of arginase activity, a lower production of classical proinflammatory mediators, and a high production of interleukin (IL)-23, and MPhi from the autoimmune-resistant strains were associated with a higher production of proinflammatory mediators, a classical activation phenotype, and preferential induction of IL-12. These MPhi phenotypes thus reflect disparate, genetic cellular programs that define autoimmune susceptibility.     

Staphylococcus aureus, but not Staphylococcus epidermidis, modulates the oxidative response and induces apoptosis in human neutrophils

S. epidermidis is the most common isolate in foreign body infections. The aim of this study was to understand why S. epidermidis causes silent biomaterial infections. In view of the divergent inflammatory responses S. epidermidis and S. aureus cause in patients, we analyzed how they differ when interacting with human neutrophils. Neutrophils interacting with S. epidermidis strains isolated either from granulation tissue covering infected hip prostheses or from normal skin flora were tested by measuring the oxidative response as chemiluminescence and apoptosis as annexin V binding. Different S. aureus strains were tested in parallel. All S. epidermidis tested were unable to modulate the oxidative reaction in response to formyl-methionyl-leucyl-phenylalanine (fMLP) and did not provoke, but rather inhibited, apoptosis. In contrast, some S. aureus strains enhanced the oxidative reaction, and this priming capacity was linked to p38-mitogen-activated-protein-kinase (p38-MAPK) activation and induction of apoptosis. Our results may explain why S. epidermidis is a weak inducer of inflammation compared to S. aureus, and therefore responsible for the indolent and chronic course of S. epidermidis biomaterial infections.     

Work resumption or not after rehabilitation? A descriptive study from six social insurance offices

The objective of this study was to describe measures and outcomes of vocational rehabilitation at six local national insurance offices in the same county in Sweden. Data were collected from mainframe registers and other records at each office. There were great differences in sickness allowance, incapacity rate, selected rehabilitation measures and resuming work. The percentage of sick-listed people who received any rehabilitation measure differed from 1.2 to 8.7%. The gender distribution for the study population was 36% men and 64% women and the predominant diagnosis was musculoskeletal pain conditions, which was followed by psychiatric disorders. Outcomes varied from office B, which reported 58% fully fit after completed planned rehabilitation, to office C, which reported only 24% fully fit. The clear differences in outcome between the offices indicate that various rehabilitation measures differ in effectiveness. The rehabilitation measure 'investigation of working ability' was not linked to any great proportion of people resuming work, but showed a greater correspondence to full disability pension. There were also large differences in social and demographic factors in the different municipalities. The effect of these on the rehabilitation process requires further investigation.     

Postexposure effects of DDE and butylbenzylphthalate on feeding behavior in threespine stickleback

In a laboratory experiment we documented effects of sublethal concentrations of p,p'-2,2-bis(p-chlorophenyl)-1,1-dichloroethylene (DDE) and butylbenzylphthalate (BBP) on feeding behavior in threespine stickleback Gasterosteus aculeatus. The fish were exposed for 31 days to either BBP (10 or 100 microg/L) or DDE (5 or 50 microg/L) or to a mixture of BBP and DDE in the corresponding concentrations. Five weeks after exposure termination, we showed that fish that had been exposed to the higher concentrations of DDE and/or BBP initiated feeding more often than control fish. The latency time to feeding (ranging from 0.25 to 5.0 min) differed between control fish and fish exposed to mixtures of DDE and BBP. This experiment shows that feeding behavior may be used as a suitable behavioral variable in the detection of effects of pollutants even long time after the termination of exposure.