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In this paper we present two compact, quantum cascade laser absorption spectroscopy based, sensors developed for trace substance detection in gases and liquids. The gas sensor, in its most integrated version, represents the first system combining a quantum cascade laser and a quantum cascade detector. Furthermore, it uses a toroidal mirror cell with a volume of only 40 cm(3) for a path length of up to 4 m. The analytical performance is assessed by the measurements of isotope ratios of CO2 at ambient abundance. For the (13)CO2/(12)CO2 isotope ratio, a measurement precision of 0.2‰ is demonstrated after an integration time of 600 s. For the liquid sensor, a microfluidic system is used to extract cocaine from saliva into a solvent (PCE) transparent in the mid-infrared. This system is bonded on top of a Si/Ge waveguide and the concentration of cocaine in PCE is measured through the interaction of the evanescent part of the waveguide optical mode and the solvent flowing on top. A detection limit of <100 μg mL(-1) was achieved with this system and down to 10 μg mL(-1) with a simplified, but improved system.

The high-power semiconductor laser studied here is a modelocked integrated external-cavity surface emitting laser (MIXSEL), which combines the gain of vertical-external-cavity surface-emitting lasers (VECSELs) with the saturable absorber of a semiconductor saturable absorber mirror (SESAM) in a single semiconductor layer stack. The MIXSEL concept allows for stable and self-starting fundamental passive modelocking in a simple straight cavity and the average power scaling is based on the semiconductor disk laser concept. Previously record-high average output power from an optically pumped MIXSEL was demonstrated, however the long pulse duration of 17 ps prevented higher pulse repetition rates and many interesting applications such as supercontinuum generation and broadband frequency comb generation. With a novel MIXSEL structure, the first femtosecond operation was then demonstrated just recently. Here we show that such a MIXSEL can also support pulse repetition rate scaling from ≈5 GHz to >100 GHz with excellent beam quality and high average output power, by mechanically changing the cavity length of the linear straight cavity and the output coupler. Up to a pulse repetition rate of 15 GHz we obtained average output power >1 W and pulse durations <4 ps. Furthermore we have been able to demonstrate the highest pulse repetition rate from any fundamentally modelocked semiconductor disk laser with 101.2 GHz at an average output power of 127 mW and a pulse duration of 570 fs.

Novel surface-emitting optically pumped semiconductor lasers have demonstrated >1 W modelocked and >100 W continuous wave (cw) average output power. The modelocked integrated external-cavity surface emitting laser (MIXSEL) combines the gain of vertical-external-cavity surface-emitting lasers (VECSELs) with the saturable absorber of a semiconductor saturable absorber mirror (SESAM) in one single semiconductor structure. This unique concept allows for stable and self-starting passive modelocking in a simple straight cavity. With quantum-dot based absorbers, record-high average output power was demonstrated previously, however the pulse duration was limited to 17 ps so far. Here, we present the first femtosecond MIXSEL emitting pulses with a duration as short as 620 fs at 4.8 GHz repetition rate and 101 mW average output power. The novel MIXSEL structure relies on a single low temperature grown quantum-well saturable absorber with a low saturation fluence and fast recovery dynamics. A detailed characterization of the key modelocking parameters of the absorber and the challenges for absorber integration into the MIXSEL structure are discussed.

A multipass cell (MPC) design for laser absorption spectroscopy is presented. The development of this new type of optical cell was driven by stringent criteria for compactness, robustness, low volume, and ease of use in optical systems. A single piece of reflective toroidal surface forms a near-concentric cavity with a volume of merely 40 cm(3). Contrary to traditional MPCs, this design allows for flexible path-length adjustments by simply changing the aiming angle of the laser beam at the entrance window. Two effective optical path lengths of 2.2 and 4.1 m were chosen to demonstrate the cell's suitability for high-precision isotope ratio measurements of CO(2) at 1% and ambient mixing ratio levels.

Background: A 21-year old female suffered a cardiac arrest after a one week history of viral illness later shown to be caused by influenza B. The patient required extended cardiopulmonary resuscitation and had further complications including compartment syndrome., Methods: Plasma myoglobin concentration was measured using the Roche Diagnostics electrochemiluminescent myoglobin assay., Results: The myoglobin concentration was 205,590 μg/l in an undiluted specimen, consistent with severe rhabdomyolysis. Subsequent myoglobin concentrations measured two days later showed dramatic decreases to approximately 1000 μg/l, raising suspicion of a hook effect. Dilution and re-analysis of the specimens revealed that the actual myoglobin concentrations were >395,000 μg/l, with one specimen possessing an estimated myoglobin concentration of >600,000 μg/l. Interestingly, three specimens from this patient did not show evidence of hook effect, with undiluted specimens producing myoglobin concentrations as high as 284,000 μg/l. Retrospective analysis of myoglobin results over an 8-year period did not reveal other cases with suspicion of hook effect. The case patient had the highest myoglobin concentrations out of 7301 specimens., Conclusions: This case illustrates that while the Roche myoglobin assay has a very wide dynamic range, hook effect can occur with extremely high concentrations of plasma myoglobin., (Copyright © 2012 Elsevier B.V. All rights reserved.)

One of the initial steps of modern drug discovery is the identification of small organic molecules able to inhibit a target macromolecule of therapeutic interest. A small proportion of these hits are further developed into lead compounds, which in turn may ultimately lead to a marketed drug. A commonly used screening protocol used for this task is high-throughput screening (HTS). However, the performance of HTS against antibacterial targets has generally been unsatisfactory, with high costs and low rates of hit identification. Here, we present a novel computational methodology that is able to identify a high proportion of structurally diverse inhibitors by searching unusually large molecular databases in a time-, cost- and resource-efficient manner. This virtual screening methodology was tested prospectively on two versions of an antibacterial target (type II dehydroquinase from Mycobacterium tuberculosis and Streptomyces coelicolor), for which HTS has not provided satisfactory results and consequently practically all known inhibitors are derivatives of the same core scaffold. Overall, our protocols identified 100 new inhibitors, with calculated K(i) ranging from 4 to 250 μM (confirmed hit rates are 60% and 62% against each version of the target). Most importantly, over 50 new active molecular scaffolds were discovered that underscore the benefits that a wide application of prospectively validated in silico screening tools is likely to bring to antibacterial hit identification.

We present the first full gain characterization of two vertical external cavity surface emitting laser (VECSEL) gain chips with similar designs operating in the 960-nm wavelength regime. We optically pump the structures with continuous-wave (cw) 808-nm radiation and measure the nonlinear reflectivity for 130-fs and 1.4-ps probe pulses as function of probe pulse fluence, pump power, and heat sink temperature. With this technique we are able to measure the saturation behavior for VECSEL gain chips for the first time. The characterization with 1.4-ps pulses resulted in saturation fluences of 40-80 μJ/cm2, while probing with 130-fs pulses yields reduced saturation fluences of 30-50 μJ/cm2 for both structures. For both pulse durations this is lower than previously assumed. A small-signal gain of up to 5% is obtained with this technique. Furthermore, in a second measurement setup, we characterize the spectral dependence of the gain using a tunable cw probe beam. We measure a gain bandwidth of over 26 nm for both structures, full width at half maximum.

We present a femtosecond vertical external cavity surface emitting laser (VECSEL) that is continuously tunable in repetition rate from 6.5 GHz up to 11.3 GHz. The use of a low-saturation fluence semiconductor saturable absorber mirror (SESAM) enables stable cw modelocking with a simple cavity design, for which the laser mode area on SESAM and VECSEL are similar and do not significantly change for a variation in cavity length. Without any realignment of the cavity for the full tuning range, the pulse duration remained nearly constant around 625 fs with less than 3.5% standard deviation. The center wavelength only changed ±0.2 nm around 963.8 nm, while the output power was 169 mW with less than 6% standard deviation. Such a tunable repetition rate is interesting for various metrology applications such as optical sampling by laser cavity tuning (OSCAT).

Absolute pKa values of the amino acid side chains of arginine, aspartate, cysteine, histidine, and tyrosine; the C- and N-terminal group of tyrosine; and the tryptophan radical cation are calculated using a revised density functional based molecular dynamics simulation technique introduced previously [ Cheng , J. ; Sulpizi , M. ; Sprik , M. J. Chem. Phys. 2009 , 131 , 154504 ]. In the revised scheme, acid deprotonation is considered as a dissociation rather than a proton transfer reaction, and a correction term for treating the proton as a hydronium ion is suggested. The acidity constants of the amino acids are obtained from the vertical energy gaps for removal or insertion of the acidic proton and the computed solvation free energy of the proton. The unsigned mean error relative to experimental results is 2.1 pKa units with a maximum error of 4.0 pKa units. The estimated mean statistical uncertainty due to the finite length of the trajectories is ±1.1 pKa units. The solvation structures of the protonated and deprotonated amino acids are analyzed in terms of radial distribution functions, which can serve as reference data for future force field developments.

Feature-based pharmacophore modeling is a well-established concept to support early stage drug discovery, where large virtual databases are filtered for potential drug candidates. The concept is implemented in popular molecular modeling software, including Catalyst, Phase, and MOE. With these software tools we performed a comparative virtual screening campaign on HSP90 and FXIa, taken from the 'maximum unbiased validation' data set. Despite the straightforward concept that pharmacophores are based on, we observed an unexpectedly high degree of variation among the hit lists obtained. By harmonizing the pharmacophore feature definitions of the investigated approaches, the exclusion volume sphere settings, and the screening parameters, we have derived a rationale for the observed differences, providing insight on the strengths and weaknesses of these algorithms. Application of more than one of these software tools in parallel will result in a widened coverage of chemical space. This is not only rooted in the dissimilarity of feature definitions but also in different algorithmic search strategies.

The reaction mechanism of a type II dehydroquinase (DHQase) from Streptomyces coelicolor was investigated using molecular dynamics simulation and density functional theory (DFT) calculations. DHQase catalyzes the elimination of a water molecule from dehydroquinate (DHQ), a key step in the biosynthesis of aromatic amino acids in bacteria, fungi, and plants. In the DFT calculations, 10 models, containing up to 230 atoms, were used to investigate different proposals for the reaction mechanism, suggested on the basis of crystal structures and kinetic data. Probing the flexibility of the active site, molecular dynamics simulation reveals that deprotonated Tyr28 can act as the base that catalyzes the first reaction step, the proton abstraction of the pro-S proton at C2 of DHQ, and formation of the enolate intermediate. The computed barrier for the first transition state (TS1), 13-15 kcal/mol, is only slightly affected by the active site model used and is in good agreement with the corresponding experimental barrier of 13.4 kcal/mol for the rate-determining step. The previously proposed enol form of the intermediate is found to be significantly higher in energy than the enolate form and is thus thermodynamically not competitive. In the second and final reaction step, protonation of the hydroxyl group at C1 by His106 followed by water elimination, there is a substantial buildup of dipole moment due to the net transfer of a proton from His106 to Tyr28. A barrier for the second transition state (TS2) that fits well with the corresponding experimental barrier could only be found if the buildup of dipole moment is at least partly compensated during the second reaction step. We speculate that this could be facilitated by regeneration of the Tyr28 anion or by proton transfer to the vicinity of His106 before TS2 is reached. A revised mechanism for type II DHQase is discussed in light of the results of the present calculations.

The bacterial community (microbiota) that inhabits the gut of humans appears to be an important source of antigens that drive the chronic immunological processes characteristic of Crohn's disease (CD) and ulcerative colitis (UC). Most of the members of the microbiota have not yet been cultured, but nucleic-acid-based methods of detection and enumeration can provide information about the community. This investigation used these methods to obtain information about the bacteria associated with mucosal surfaces in the gut of 20 CD and 15 UC patients. Biopsies were collected from inflamed and non-inflamed sites in the intestines of newly diagnosed, untreated patients. Biopsies were also collected from several intestinal sites of 14 healthy subjects. The bacterial collections associated with the biopsies were analysed by generating PCR/denaturing gradient gel electrophoresis (DGGE) profiles, the preparation of 16S rRNA gene clone libraries, and qualitative PCR to detect specific groups of bacteria. The total numbers of bacteria associated with the biopsies were determined by real-time quantitative PCR. DGGE profiles generated from the terminal ileum and various colonic regions were characteristic of each individual but differed between subjects. DGGE profiles and 16S rRNA gene libraries showed that the bacteria associated with inflamed and non-inflamed tissues did not differ. UC patients had more bacteria associated with biopsies than did CD patients (P<0.01). Statistical analysis of the composition of 16S rRNA gene libraries showed that the bacterial collections in UC and CD patients differed (P<0.05). Unclassified members of the phylum Bacteroidetes were more prevalent in CD than in UC patients. Therefore, the types and numbers of bacteria associated with biopsy samples were distinctly different for UC and CD patients. The observations made in this study should permit targeting of specific bacteriological abnormalities in investigations of the pathogenesis of inflammatory bowel diseases and provide targets for medical interventions.

The phenolic hydroxy group of opiate-derived ligands is of known importance for biological activity. We have developed a SAR study around LY255582 by comparing the effect of the hydroxy group in the 2- and 4-position of the phenyl ring. Also, we have proved that the 3-position of the phenyl ring is optimal for opioid activity. Furthermore, we have successfully replaced the hydroxy group in LY255582 by carbamate and carboxamide groups. The new analogs have high affinity for the opioid receptors comparable to the corresponding phenol. Carboxamide analog 12 has an improved metabolism profile and proved to be efficacious in in vivo studies.

A metagenomic (community genomic) library consisting of 5,760 bacterial artificial chromosome clones was prepared in Escherichia coli DH10B from DNA extracted from the large-bowel microbiota of BALB/c mice. DNA inserts detected in 61 randomly chosen clones averaged 55 kbp (range, 8 to 150 kbp) in size. A functional screen of the library for beta-glucanase activity was conducted using lichenin agar plates and Congo red solution. Three clones with beta-glucanase activity were detected. The inserts of these three clones were sequenced and annotated. Open reading frames (ORF) that encoded putative proteins with identity to glucanolytic enzymes (lichenases and laminarinases) were detected by reference to databases. Other putative genes were detected, some of which might have a role in environmental sensing, nutrient acquisition, or coaggregation. The insert DNA from two clones probably originated from uncultivated bacteria because the ORF had low sequence identity with database entries, but the genes associated with the remaining clone resembled sequences reported in Bacteroides species.

The capacity of pathogens to cause disease depends strictly on the regulated expression of their virulence factors. In this study, we demonstrate that the untranslated mRNA of the recently described streptococcal pleiotropic effect locus (pel), which incidentally contains sagA, the structural gene for streptolysin S, is an effector of virulence factor expression in group A beta-haemolytic streptococci (GAS). Our data suggest that the regulation by pel RNA occurs at both transcriptional (e.g. emm, sic, nga) and post-transcriptional (e.g. SpeB) levels. We could exclude the possibility that the pel phenotype was linked to a polar effect on downstream genes (sagB-I). Remarkably, the RNA effector is regulated in a growth phase-dependent fashion and we provide evidence that pel RNA expression is induced by conditioned media., (Copyright 2004 Blackwell Publishing Ltd)

Background: Sp4 is a zinc finger transcription factor which is closely related to Sp1 and Sp3. All three proteins recognize the same DNA elements and can act as transcriptional activators through glutamine-rich activation domains. Unlike Sp1 and Sp3, which are ubiquitous proteins, Sp4 is highly abundant in the central nervous system, but also detectable in many other tissues., Results: We have disrupted the mouse Sp4 gene by a targeted deletion of the exons encoding the N-terminal activation domains. Sp4 knockout mice show a complete absence of Sp4 expression. They develop until birth without obvious abnormalities. After birth, two-thirds die within 4 weeks. Surviving mice are growth retarded. Male Sp4null mice do not breed. The cause for the breeding defect remains obscure since they show complete spermatogenesis. In addition, pheromone receptor genes in the vomeronasal organ appear unaffected. Female Sp4null mice have a smaller thymus, spleen and uterus. In addition, they exhibit a pronounced delay in sexual maturation., Conclusions: The phenotype of the Sp4null mice differs significantly from those described for Sp1-/- and Sp3-/- mice. Thus, the structural similarities, the common recognition motif and the overlapping expression pattern of these three transcription factors do not reflect similar physiological functions.

Complete activation of signal transducer and activator of transcription 1 (STAT1) requires phosphorylation at both Y701 and a conserved PMS(727)P sequence. S727 phosphorylation of STAT1 in interferon-gamma (IFN-gamma)-treated mouse fibroblasts occurred without a need for p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1 and 2 or c-Jun kinases, and required both an intact SH2 domain and phosphorylation of Y701. In contrast, UV irradiation-induced STAT1 phosphorylation on S727 required p38MAPK, but no SH2 domain- phosphotyrosine interactions. Mutation of S727 differentially affected IFN-gamma target genes, at the level of both basal and induced expression. Particularly strong effects were noted for the GBP1 and TAP1 genes. The PMS(727)P motif of STAT3 was phosphorylated by stimuli and signaling pathways different from those for STAT1 S727. Transfer of the STAT3 C-terminus to STAT1 changed the stimulus and pathway specificity of STAT1 S727 phosphorylation to that of STAT3. Our data suggest that STAT C-termini contribute to the specificity of cellular responses by linking individual STATs to different serine kinase pathways and through an intrinsically different requirement for serine phosphorylation at different target gene promoters.

The Gothenburg Profile (GP) for measurement of experienced hearing disability and handicap was developed with content partly taken from the shortened Hearing Measurement Scale (HMS25). The GP consists of 20 items divided into two subscales. The first subscale measures Experienced Disability as to hearing speech (items 1-5) and sound localization (items 6-10). The second subscale targets the Experienced Handicap in social settings (items 11-15) and the personal reactions to the experienced handicap (items 16-20). In this study, data are presented for new hearing aid candidates (NewHA) (n=441) and for experienced hearing aid users (ExpHA) (n=476). Principal components factor analyses were conducted and a three-factor solution was obtained, supporting the two factors of the Experienced Disability subscale, but just confirming one factor in the Experienced Handicap subscale. The internal consistency reliability (coefficient alpha) was good (0.85 to 0.95) for the subscales as was the test-retest reliability. The ExpHA group expressed significantly greater disability (first subscale) as well as experienced handicap (second subscale). However, when controlling for hearing level the differences disappeared. The clinical use of the GP for assessment of rehabilitation needs is recommended.

In order to investigate, in depth, the role of psychological factors in Ménière's disease, i.e. how the patients experience and interpret their symptoms during the process of this illness, a qualitative method "focus group interviews" was used as a study design. The focus group included four subjects; one woman and three men. In addition, semi-structured interviews were performed with each of four more subjects having the disease, three women and one man, in order to guarantee representativity in terms of gender and age. Through the focus interview analyses eight final codes and a number of sub-codes were developed. Results clearly pointed out the significance of the first traumatic attack of the disease as well as early signs; different "psychosomatic" symptoms prior to the attacks. The recognition of fear and phobic reactions in the manifestation of the vertigo attack was considered as an important observation, as attacks often were triggered by distressing thoughts as well as by sensory sensations. Other areas, touched upon for future investigation, were crisis adaptation and illness function.

The aim of this study of otosclerosis patients was to highlight the circumstances specific to an operable middle ear disease and to describe the psychologically unique aspects accompanying this disorder. In a first step five subjects participated in four focus group interviews, from which emanated a questionnaire answered in a second step by 28 randomly chosen subjects. Finally a second series of supplementary focus interviews were conducted with another group of subjects, after which the interview material was subjected to code-mapping, agreement and validation. The study results indicate that ear surgery was a very important occurrence in the lives of the patients and a unique aspect was that they were burdened by a sense of responsibility for deciding in favour of or against the ear surgery and in choosing the time for operation. An event as tangible as an operation impacts on the individual's psychological processing of the fact that one of his or her senses is damaged. The message to the person's surroundings is very clear: the operation makes others understand how serious the situation is, gives rise to a sense of sympathy. These factors together may promote adaptation to the handicap, or alternately, at least for some persons, may impede adaptation to the necessary hearing aids. To some individuals hearing aids were strongly associated with periods of deteriorating hearing and therefore had negative connotations. Thus the hearing aid was used while waiting for surgery or instead of surgery. The constant hope of regaining one's hearing through ear surgery, although not totally realistic in these cases of severe otosclerosis, always makes the hearing aid the second best solution. The overall conclusion from this study is that there are specific circumstances of an operable ear disease which have great impact upon quality of life, well-being and adaptation. The psychological situation is one of instability, feelings of responsibility and at times of anxiety. Patients with otosclerosis are sometimes told that they are better off than others with impaired hearing, because surgery can improve their hearing and because good amplification through hearing aids can be achieved in persons with conductive hearing losses. It is our hope that this study has helped to provide a fuller picture of the facts of life for persons with severe otosclerosis.

Eighteen patients judged the sound quality of the new Classic 300 and the existing HC 100 or HC 200 on 4 five-stage sound quality scales. Two of the scales relate to the perceptual dimensions softness and clarity, one relates to interference or noise and one relates to the overall impression. The evaluations were made, based on a questionnaire, in the patients' own homes and comprised the listening situations: TV news, music, conversation with two to three people in a noisy environment and one optional choice. The patients also stated which hearing aid was best in each situation and made a confidence rating for their selection. The patients were accustomed to wearing the HC 100 or HC 200. In these comparisons of the different bone-anchored hearing aid models, the Classic 300 received the best ratings overall. Seventeen patients changed their previously fitted hearing aid to a Classic 300 and satisfactory sound quality was undoubtedly one of the principal reasons. When it came to the confidence rating for their selections, some two-thirds of the patients stated that it was without hesitation or with little hesitation. Our overall conclusion is that the sound quality of bone-anchored hearing aids is satisfactory when it comes to clarity and overall impression. However, it may be expected that these patients with conductive losses get a better sound quality than other patients with sensorineural losses if the same type of aid is used.

Within a larger comparative environmental health screening program in East and West Germany neurobehavioral and neurophysiological measures were taken in 367 six year old children in Leipzig (N = 179), Gardelegen (N = 68), and Duisburg (N = 120). Lead concentrations from venous blood samples (PbB) and from deciduous teeth (PbT) were measured as markers of environmental lead exposure by electrothermal AAS. Dependent variables included four subtests from NES1 (tapping, reaction time, pattern comparison, and Benton visual retention), as well as VEP-latencies (N2, P100, N3) evoked by checkerboard patterns of different size and contrast. The overall median blood lead-concentration was 5 micrograms/dl (range: 1.3-19.0 micrograms/dl), and the corresponding tooth lead-concentration was 2 micrograms/g (0.2-14 micrograms/g). The 95-percentile of the overall frequency distribution for PbB was below 10 micrograms/dl. Associations between markers of lead-exposure and neurobehavioral or neurophysiological outcome were assessed by means of multiple linear or logistic regression analyses. After adjusting for relevant confounders/covariates significant (p < 0.05) Pb-related deficit was found for tapping and pattern recognition with respect to PbB but not PbT. No such associations could be established for VEP-latencies. These results are compatible with the hypothesis that subtle neurobehavioral dysfunction in children may be associated with very low PbB.

The effects of the protein kinase inhibitor H-7 on early and delayed responses to nerve growth factor (NGF) were investigated in PC12 cells. H-7 reduced the NGF-induced expression of c-Fos in a dose-dependent manner without affecting the time course of c-Fos appearance. Conversely, H-7 potentiated delayed NGF effects, i.e., neurite outgrowth and Ca2+/phospholipid-dependent protein kinase (PKC) induction, but not choline acetyltransferase induction. Long-term treatment with NGF resulted in an increase of at least four tyrosine-phosphorylated protein bands with molecular masses between 39 and 48 kDa, which was also potentiated by H-7. In the absence of NGF, H-7 had no significant effect on c-Fos expression, tyrosine phosphorylation of the 45 kDa protein, or choline acetyltransferase activity. However, 4 days of exposure to H-7 alone induced PKC activity and tyrosine phosphorylation of the 39-kDa protein. The action of H-7 derivatives on neurite outgrowth did not correlate with their inhibition profile of cyclic nucleotide-dependent protein kinases. Down-regulation of PKC activity by prolonged exposure to phorbol ester did not completely abolish the effects of NGF and H-7 on induction of c-Fos, choline acetyltransferase activity, and neurite outgrowth, indicating that PKC-independent pathways contribute to these actions. These results suggest that additional pathway(s) sensitive to H-7 may exist, which induce immediate early gene expression and suppress neuronal differentiation of PC12 cells.

Paraffin blocks from 60 patients with prostate cancer were used to study the DNA ploidy patterns by flow cytometry. Nineteen patients had stage A disease, 11 had stage B, 9 had stage C, 20 had stage D, and 1 was of unknown stage. Histologically, 32 of the cancers were well differentiated, 21 were moderately differentiated, and 7 were poorly differentiated. Eighteen patients had an aneuploid or tetraploid (A/T) pattern and 42 had a diploid pattern. Seventy-one percent (5/7) of patients with poorly differentiated, 48% (10/21) with moderately differentiated, and 9% (3/32) with well-differentiated histology had A/T patterns (P < 0.01). Forty-five percent (9/20) of patients with stage D, 44% (4/9) with stage C, 27% (3/11) with stage B, and 5% (1/19) with stage A had A/T patterns (P < 0.05). Nine patients with an A/T pattern also had DNA ploidy studies done on the "benign" part of the specimen. These specimens showed diploid patterns although three of these patients had well-differentiated tumor in the "benign" designated part of the specimen. One patient with mixed histology had an aneuploid pattern on the poorly differentiated section and a diploid pattern on the well-differentiated section of the "malignant" designated part of the same specimen. We conclude that prostate cancer patients with non-diploid tumors have more advanced disease and less differentiated tumors than patients with diploid tumors and that considerable histological and ploidy heterogeneity may be present in different parts of the same paraffin-embedded specimen.

The Communication Strategies scale of the Communication Profile for the Hearing Impaired (CPHI) was translated into Swedish and used in several studies of people with hearing impairment (Hallberg & Carlsson, in press; Hallberg, Erlandsson, & Carlsson, 1991). In this study the scale was evaluated in terms of descriptive statistics, corrected item-total correlations, principal component analysis, and internal consistency reliability. Agreement with results from American studies is surprisingly good. Normative data based on three samples are presented: a general Swedish hearing-impaired sample with predominantly sensorineural hearing loss (N = 199), a subgroup of 105 younger subjects with noise-induced hearing loss, and a subgroup of 39 older subjects with sensorineural hearing loss due to heredity and/or old age. A significantly more frequent use of maladaptive behaviors (p less than .001) and verbal communication strategies (p less than .01) was reported by older subjects with age-related and/or hereditary hearing loss than by younger subjects with noise-induced hearing loss. The Communication Strategies scale seems to be an adequately reliable and clinically useful instrument for assessing adaptive and maladaptive strategies in hearing-impaired subjects.

Background: Cutaneous manifestations are common in Wegener's granulomatosis and may occur at any time during the illness., Objective: Our purpose was to describe the relation of the appearance of cutaneous leukocytoclastic vasculitis to activity and other manifestations of Wegener's granulomatosis., Methods: Three patients with Wegener's granulomatosis who had recent onset of skin lesions are reported. Data regarding the relation of their cutaneous disease to their systemic disease was collected., Results and Conclusion: In each case, onset of the skin lesions of biopsy-proven cutaneous leukocytoclastic vasculitis was associated with activation of the systemic features of Wegener's granulomatosis.

The hearing measurement scale (HMS), targeting the experience of being hearing impaired, was translated into Swedish and answered by 122 patients with slight to moderate hearing losses. According to the item analysis the test construction of the HMS functions well with a relevant division of the sections. In all sections there were individuals utilizing all response possibilities and the homogeneity (alpha) of the test was high. One exception was section II (hearing non-verbal sounds), which may be due to lack of awareness, indicating that it might not be possible to pursue this dimension by a questionnaire approach. Normative descriptions were given for two age groups: 40 to 60 and 61 to 74 years, including both sexes. The groups had a similar outcome on the HMS, even though the older subjects, on average, had worse hearing problems, measured by pure-tone audiometry. The section covering speech perception had the strongest correlation with hearing loss, while the section covering emotional response entirely lacked such correlations for the younger group.

Acquired hearing loss has frequently been reported to cause strains in everyday life, but few attempts have been reported where the affliction is related to the concept of stress. In this within-subjects investigation of 48 middle-aged to elderly hearing impaired patients, the relationships between hearing measurements, experienced disability and handicap (HMS), and psychological and somatic distress symptoms (SCL-90(R)) were analyzed. The variations in experienced hearing disability was found to correlate to the occurrence of a few, but more severe distress symptoms, and by loss of hearing for high frequencies. The experienced handicap, defined as emotional responses and personal opinions, was found to correlate to a general level of distress. In particular those distress items expressing insecurity were related to handicap experience. It was suggested that insecurity in social settings, and diminished hearing for contextual sounds, could cause a perceived loss of control, which could induce stress reactions.

A conventional hearing aid has a frequency response that does not change much at normal listening levels. It is therefore unlikely that optimal speech intelligibility and optimal listening comfort can be obtained simultaneously, or in different listening environments. With a programmable hearing aid with multiple memories the listener can choose between a range of sound pictures, which increases the chance of finding a suitable frequency curve for each listening situation. The programmable hearing aid with eight separate settings stored in eight memories, was compared with personal hearing aids fitted according to the recommendations of the National Acoustic Laboratories (NAL) by 22 experienced hearing aid users. One memory of the programmable hearing aid was initially fitted according to the NAL recommendation. The other memories were programmed to give variations around that recommendation. One aim was to investigate whether the hearing-impaired user took advantage of different frequency responses to achieve listening improvements in acoustically different environments. Another aim was to evaluate the ergonomic and acoustical features of the programmable hearing aid, compared with other well fitted hearing aids. The evaluations were based on comparisons of the test hearing aid to the personal aid for each subject, looking at speech tests, direct paired comparison judgements, sound quality judgements and interviews. A majority of the subjects experienced substantial benefit from being able to use different frequency response curves in different environments. With the test hearing aid the subjects performed better in speech discrimination tests in noise.(ABSTRACT TRUNCATED AT 250 WORDS)

Rehabilitation of the majority of hearing handicapped in Sweden consists of hearing aid fitting, provision of technical devices and information during about four visits to a Hearing Centre. Generally there is no structured guidance of the hearing handicapped on how to proceed with the hearing aid at home between appointments. A programme of active fitting (AF) of hearing aids, with a task-oriented diary, 'Try Your Hearing Aid' as a basic part, was therefore developed. We conducted a series of studies from 1985 to 1988 with the aim of investigating the benefit and applicability of the programme. A total of 128 new hearing aid candidates participated in three studies at the Sahlgrens hospital and at four other hearing centres in smaller Swedish towns. In a controlled study the AF group was more positive to their hearing aids and to the fitting period after 10 months. They used their hearing aids more frequently and felt psychologically more secure with them. It was established that the AF programme could well be applied in the clinical routine for a majority of new hearing aid patients. Old age per se was not found to be a relevant exclusion criterion. The positive outcome of the AF programme has stimulated the Swedish Institute of the Handicapped to print 'Try Your Hearing Aid' with a manual, and to introduce it to all hearing centres in Sweden.

A basic problem in hearing-aid fitting is the difficulty in finding one setting optimal to all listening situations that might occur. The objective was to develop a behind-the-ear hearing-aid with a very flexible analog signal processor which is digitally controlled, and a memory with logic, so that the hearing-impaired person can select from eight completely different fittings. To program and adjust this multi-programmable hearing-aid (called MemoryMate®) a hearing evaluation and recommendation system (called Master-Fit®) has been developed, based on an IBM PS/2 computer. This system offers the dispenser prescriptive fitting methods and performance of real ear measurements. It can be used to manage a client database. Preliminary results from a clinical study conducted in 1988 are presented. The paper also describes the uniqueness of this multi-programmable hearing aid as a powerful new research tool.