Associations among depression, demographic variables, and language impairments in chronic post-stroke aphasia.

INTRODUCTION: Depression may influence treatment participation and outcomes of people with post-stroke aphasia, yet its prevalence and associated characteristics in aphasia are poorly understood. Using retrospective data from an overarching experimental study, we examined depressive symptoms and their relationship to demographic and language characteristics in people with chronic aphasia. As a secondary objective, we compared prevalence of depressive symptoms among the overarching study's included and excluded participants. METHODS: We examined retrospective data from 121 individuals with chronic aphasia including depression scale scores, demographic information (sex, age, time post onset of stroke, education, race/ethnicity, and Veteran status), and scores on assessments of general and modality-specific language impairments. RESULTS: Approximately 50% of participants reported symptoms indicative of depressive disorders: 23% indicative of major depression and 27% indicative of mild depression. Sex (males) and comparatively younger age emerged as statistically significant variables associated with depressive symptoms; naming ability was minimally associated with depressive symptoms. Time post onset of stroke, education level, race/ethnicity, Veteran status, and aphasia severity were not significantly associated with depressive symptoms. Depression-scale scores were significantly higher for individuals excluded from the overarching study compared to those who were included. CONCLUSIONS: The rate of depressive disorders in this sample was higher than rates of depression reported in the general stroke literature. Participant sex, age, and naming ability emerged as factors associated with depressive symptoms, though these links appear complex, especially given variable reports from prior research. Importantly, depressive symptoms do not appear to diminish over time for individuals with chronic aphasia. Given these results and the relatively limited documentation of depression in aphasia literature, depression remains a pressing concern for aphasia research and routine clinical care.

A case report of dyshidrotic bullous pemphigoid developing after partial anterior circulation ischaemic stroke.

Dyshidrotic bullous pemphigoid is a rare form of bullous pemphigoid that affects predominantly a patient's hands and feet. It has been associated in the literature with neurologic, psychiatric and cerebrovascular disorders. We present an interesting case of this rare skin condition developing in a patient following a diagnosis of partial anterior circulation stroke.

Can audiometric results predict qualitative hearing improvements in bone-anchored hearing aid recipients?

INTRODUCTION: Patients receiving a bone-anchored hearing aid have well-documented improvements in their quality of life and audiometric performance. However, the relationship between audiometric measurements and subjective improvement is not well understood. METHODS: Adult patients enrolled in the Nova Scotia bone-anchored hearing aid programme were identified. The pure tone average for fitting the sound-field threshold, as well as the better and worse hearing ear bone conduction and air conduction levels, were collected pre-operatively. Recipients were asked to complete the Speech, Spatial and Qualities of Hearing questionnaire; their partners were asked to complete a pre- and post-bone anchored hearing aid fitting Hearing Handicap Inventory for Adults questionnaire. RESULTS: Forty-eight patients who completed and returned the Speech, Spatial and Qualities of Hearing questionnaire had partners who completed the Hearing Handicap Inventory for Adults questionnaire. The results from the Speech, Spatial and Qualities of Hearing questionnaire correlated with the sound-field hearing threshold post-bone-anchored hearing aid fitting and the pure tone average of the better hearing ear bone conduction (total Speech, Spatial and Qualities of Hearing Scale to the pre-operative better hearing ear air curve (r = 0.3); worse hearing ear air curve (r = 0.27); post-operative, bone-anchored hearing aid-aided sound-field thresholds (r = 0.35)). An improvement in sound-field threshold correlated only with spatial abilities. In the Hearing Handicap Inventory for Adults questionnaire, there was no correlation between the subjective evaluation of each patient and their partner. CONCLUSION: The subjective impressions of hearing aid recipients with regards to speech reception and the spatial qualities of hearing correlate well with pre-operative audiometric results. However, the overall magnitude of sound-field improvement predicts an improvement of spatial perception, but not other aspects of hearing, resulting in hearing aid recipients having strongly disparate subjective impressions when compared to those of their partners.

Identification of mRNA for endocannabinoid biosynthetic enzymes within hippocampal pyramidal cells and CA1 stratum radiatum interneuron subtypes using quantitative real-time polymerase chain reaction.

The hippocampus is required for short-term memory and contains both excitatory pyramidal cells and inhibitory interneurons. These cells exhibit various forms of synaptic plasticity, the mechanism underlying learning and memory. More recently, endocannabinoids were identified to be involved in synaptic plasticity. Our goal was to describe the distribution of endocannabinoid biosynthetic enzymes within CA1 stratum radiatum interneurons and CA3/CA1 pyramidal cells. We extracted mRNA from single interneurons and pyramidal cells and used real-time quantitative polymerase chain reaction (RT-PCR) to detect the presence of 12-lipoxygenase, N-acyl-phosphatidylethanolamine-specific phospholipase D, diacylglycerol lipase α, and type I metabotropic glutamate receptors, all known to be involved in endocannabinoid production and plasticity. We observed that the expression of endocannabinoid biosynthetic enzyme mRNA does occur within interneurons and that it is coexpressed with type I metabotropic glutamate receptors, suggesting interneurons have the potential to produce endocannabinoids. We also identified that CA3 and CA1 pyramidal cells express endocannabinoid biosynthetic enzyme mRNA. Our data provide the first molecular biological evidence for putative endocannabinoid production in interneurons, suggesting their potential ability to regulate endocannabinoid-mediated processes, such as synaptic plasticity.

Quality of life improvement for bone-anchored hearing aid users and their partners.

OBJECTIVES: Bone-anchored hearing aid recipients experience well documented improvements in their audiometric performance and quality of life. While hearing aid recipients may understate their functional improvement, their partners may be more aware of such improvement. We sought to investigate patients' partners' perceptions of functional improvement following bone-anchored hearing aid fitting. METHODS: Surveys were sent to 153 patients who had received a bone-anchored hearing aid through the Nova Scotia bone-anchored hearing aid programme. The validated survey asked patients' partners to give their subjective impression of the bone-anchored hearing aid recipient's functional status. RESULTS AND CONCLUSIONS: Surveys were completed by 90 patients (58.8 per cent), of whom 72 reported having a partner. Partners reported a significant improvement in hearing (p ≤ 0.0001). Partners reported improvement in 87.0 per cent of functional scenarios, no change in 12.6 per cent, and a decline in 0.4 per cent. These findings demonstrate a significant improvement in the emotional and social effects of hearing impairment, as perceived by bone-anchored hearing aid recipients' partners.

Effects of online augmented kinematic and perceptual feedback on treatment of speech movements in apraxia of speech.

Apraxia of speech (AOS) is a motor speech disorder characterized by disturbed spatial and temporal parameters of movement. Research on motor learning suggests that augmented feedback may provide a beneficial effect for training movement. This study examined the effects of the presence and frequency of online augmented visual kinematic feedback (AVKF) and clinician-provided perceptual feedback on speech accuracy in 2 adults with acquired AOS. Within a single-subject multiple-baseline design, AVKF was provided using electromagnetic midsagittal articulography (EMA) in 2 feedback conditions (50 or 100%). Articulator placement was specified for speech motor targets (SMTs). Treated and baselined SMTs were in the initial or final position of single-syllable words, in varying consonant-vowel or vowel-consonant contexts. SMTs were selected based on each participant's pre-assessed erred productions. Productions were digitally recorded and online perceptual judgments of accuracy (including segment and intersegment distortions) were made. Inter- and intra-judge reliability for perceptual accuracy was high. Results measured by visual inspection and effect size revealed positive acquisition and generalization effects for both participants. Generalization occurred across vowel contexts and to untreated probes. Results of the frequency manipulation were confounded by presentation order. Maintenance of learned and generalized effects were demonstrated for 1 participant. These data provide support for the role of augmented feedback in treating speech movements that result in perceptually accurate speech production. Future investigations will explore the independent contributions of each feedback type (i.e. kinematic and perceptual) in producing efficient and effective training of SMTs in persons with AOS.

Candidemia in pediatric outpatients receiving home total parenteral nutrition.

This is a cohort study of pediatric outpatients receiving total parenteral nutrition (TPN) and follow-up care in a Tennessee hospital between January and June 1999. The study was conducted following an increase in the incidence of candidemia. Of 13 children receiving home TPN, five had candidemia; three were due to Candida parapsilosis. Case patients were more likely to have an underlying hematologic disease (P = 0.02) as well as previous history of fungemia (P = 0.02). Two case patients had successive candidemia episodes 3 months apart; karyotypes and RAPD profiles of each patient's successive C. parapsilosis isolates were similar. Candida spp. were frequently detected in hand cultures from cohort members (four of 10) and family member caregivers (nine of 11); C parapsilosis was isolated from five caregivers. Our findings underscore the challenges of maintaining stringent infection control practices in the home health care setting and suggest the need for more intensive follow-up and coordination of home TPN therapy among pediatric patients.

Effects of two types of brief intervention and readiness to change on alcohol use in hazardous drinkers.

OBJECTIVE: Brief interventions for hazardous and low-dependent drinkers in the primary care setting have considerable empirical support. The purpose of this study was to (1) evaluate the effects of brief advice (BA) and motivational enhancement (ME) interventions on alcohol consumption. In addition, a hindsight matching design was used to (2) study the moderator effects of patient readiness to change (alcohol use) on alcohol consumption. METHOD: The subjects (N = 301, 70% men) were patients 21 years of age or older who presented for treatment at one of 12 primary care clinics. After screening for eligibility and providing consent to participate in the study, the patients completed a baseline assessment and were randomly assigned to the BA, ME or standard care (SC) interventions condition. Follow-up assessments were completed at 1-, 3-, 6-, 9- and 12-months postbaseline assessment. RESULTS: Evaluation of the first hypothesis (n = 232 for these analyses) showed that all participants tended to reduce their alcohol use considerably between the baseline and 12-month assessments. In addition, evaluation of the second hypothesis showed a moderator effect of readiness to change in predicting the number of drinks at 12 months, such that the BA intervention seemed more effective for patients relatively low in readiness to change compared to those higher in readiness. Readiness to change did not seem to be related to changes in drinking of participants in the SC or ME conditions. CONCLUSIONS: The results confirm that, among primary care patients, substantial changes in alcohol consumption are possible. They further suggest that matching studies of patient readiness to change their alcohol use, as well as other variables, are warranted.

The relationship between eligibility criteria for participation in alcohol brief intervention trials and other alcohol and health-related variables.

In clinical trials of brief interventions for alcohol use, individuals typically are defined as eligible for the research through meeting quantity-frequency (QF) of alcohol consumption criteria, alcohol-related problems criteria, or both. The purpose of this study was to evaluate preintervention and posttreatment differences among three groups of research participants eligible for participation in a brief intervention clinical trial by meeting the AUDIT total score criterion only, the QF criterion only, or both. The participants were 301 men and women 21 years of age or older who presented for medical treatment at one of twelve primary care clinics and were screened for participation in the clinical trial. Participants completed an assessment protocol at preintervention and 1, 3, 6, 9, and 12 months postintervention. The analyses showed statistical differences among the three subgroups on three outcome dimensions of alcohol consumption, related consequences and behaviors, and medical complications; for both consumption and complications, the AUDIT + QF participants showed greater severity than participants in either of the other two groups. For consequences, AUDIT + QF participants scored higher than the QF participants on one variable constituting this dimension. The overall subgroup differences were maintained at six months in the consumption and consequences data. The implications of these findings for sensitivity of brief intervention trial design, the discovery of patient moderators of intervention effectiveness, and clinical practice are discussed.

The role of the embA and embB gene products in the biosynthesis of the terminal hexaarabinofuranosyl motif of Mycobacterium smegmatis arabinogalactan.

The emb genes are conserved among different mycobacteria. In Mycobacterium smegmatis and Mycobacterium tuberculosis, they belong to an operon comprising three genes, embC, embA, and embB. The EmbB protein has been proposed to be the target of ethambutol, a drug which is known to inhibit the synthesis of the arabinan portion of the mycobacterial cell wall arabinogalactan (AG). To further define the role of EmbB protein in arabinan biosynthesis, embA, -B, and -C genes were inactivated individually by homologous recombination in M. smegmatis. All three mutants were viable, and among the three, the slowest growing embB(-) mutant encountered profound morphological changes and exhibited a higher sensitivity to hydrophobic drugs and detergents, presumably due to an increase in cell wall permeability. Furthermore, chemical analyses showed that there was a diminution in the arabinose content of arabinogalactan from the embA(-) and embB(-) mutants. Specifically, in comparison with the wild-type strain, the crucial terminal hexaarabinofuranosyl motif, which is a template for mycolylation, was altered in both embA(-) and embB(-) mutants. Detailed nuclear magnetic resonance studies coupled with enzyme digestion, chromatography, and mass spectrometry analyses revealed that the disaccharide beta-d-Ara(f)-(1-->2)-alpha-d-Ara(f) extension from the 3-position of the 3,5-linked alpha-d-Ara(f) residue is markedly diminished. As a consequence, a linear terminal beta-d-Ara(f)-(1-->2)-alpha-d-Ara(f)-(1-->5)-alpha-d-Ara(f)-(1-->5)-alpha-d-Ara(f) is formed, a motif which is a recognized, nonreducing terminal feature of lipoarabinomannan but not of normal AG. Upon complementation with the embB and embA wild-type genes, the phenotype of the mutants reverted to wild-type, in that normal AG was resynthesized. Our results clearly show that both EmbA and EmbB proteins are involved in the formation of the proper terminal hexaarabinofuranoside motif in AG, thus paving the way for future studies to identify the complete array of arabinosyltransferases involved in the synthesis of mycobacterial cell wall arabinan.

UDP-galactopyranose mutase has a novel structure and mechanism.

Uridine diphosphogalactofuranose (UDP-Galf ) is the precursor of the d-galactofuranose (Galf ) residues found in bacterial and parasitic cell walls, including those of many pathogens, such as Mycobacterium tuberculosis and Trypanosoma cruzi. UDP-Galf is made from UDP-galactopyranose (UDP-Galp) by the enzyme UDP-galactopyranose mutase (mutase). The mutase enzyme is essential for the viability of mycobacteria and is not found in humans, making it a viable therapeutic target. The mechanism by which mutase achieves the unprecedented ring contraction of a nonreducing sugar is unclear. We have solved the crystal structure of Escherichia coli mutase to 2.4 A resolution. The novel structure shows that the flavin nucleotide is located in a cleft lined with conserved residues. Site-directed mutagenesis studies indicate that this cleft contains the active site, with the sugar ring of the substrate UDP-galactose adjacent to the exposed isoalloxazine ring of FAD. Assay results establish that the enzyme is active only when flavin is reduced. We conclude that mutase most likely functions by transient reduction of substrate.

Molecular epidemiology of Candida albicans strains isolated from the oropharynx of HIV-positive patients at successive clinic visits.

Candida albicans strain diversity and fluconazole resistance were prospectively analyzed in oral strains from 29 adult human immunodeficiency virus (HIV)-positive patients followed for > 1 year who had five or more culture-positive clinic visits. Molecular typing consisted of genomic blots probed with the Ca3 repetitive element. Sixteen patients had one or more episodes of oropharyngeal candidiasis (OPC), 12 (75%) maintained the original genotype, whereas the remaining four patients had a succession of 2-3 genotypes. The original genotype, either alone or mixed with another strain or with non-C. albicans Candida spp., was recovered from oral lesions in 13 of 15 evaluable (86.7%) patients. C. dubliniensis was the infecting yeast in the remaining two patients. Different patterns of fluconazole resistance occurred in three OPC patients. One patient's infecting strain became less susceptible. A second patient was infected with a resistant genotype and a progressively more susceptible minor genotype variant. C. dubliniensis isolates from the third patient varied in susceptibility. Thirteen colonized patients who never developed OPC harbored a greater variety of C. albicans genotypes (2-6) than their infected counterparts (P = 0.35). OPC patients maintained their original endogenous C. albicans strains for prolonged periods, whether or not they demonstrated decreased in vitro susceptibility to fluconazole. The adaptation and maintenance of an endogenous C. albicans strain within its host may be linked to as yet uncharacterized factors.

Trends in mortality due to invasive mycotic diseases in the United States, 1980-1997.

To determine national trends in mortality due to invasive mycoses, we analyzed National Center for Health Statistics multiple-cause-of-death record tapes for the years 1980 through 1997, with use of their specific codes in the International Classification of Diseases, Ninth Revision (ICD-9 codes 112.4-118 and 136.3). In the United States, of deaths in which an infectious disease was the underlying cause, those due to mycoses increased from the tenth most common in 1980 to the seventh most common in 1997. From 1980 through 1997, the annual number of deaths in which an invasive mycosis was listed on the death certificate (multiple-cause [MC] mortality) increased from 1557 to 6534. In addition, rates of MC mortality for the different mycoses varied markedly according to human immunodeficiency virus (HIV) status but were consistently higher among males, blacks, and persons > or =65 years of age. These data highlight the public health importance of mycotic diseases and emphasize the need for continuing surveillance.

Cell wall core galactofuran synthesis is essential for growth of mycobacteria.

The mycobacterial cell wall core consists of an outer lipid (mycolic acid) layer attached to peptidoglycan via a galactofuranosyl-containing polysaccharide, arabinogalactan. This structural arrangement strongly suggests that galactofuranosyl residues are essential for the growth and viability of mycobacteria. Galactofuranosyl residues are formed in nature by a ring contraction of UDP-galactopyranose to UDP-galactofuranose catalyzed by the enzyme UDP-galactopyranose mutase (Glf). In Mycobacterium tuberculosis the glf gene overlaps, by 1 nucleotide, a gene, Rv3808c, that has been shown to encode a galactofuranosyl transferase. We demonstrate here that glf can be knocked out in Mycobacterium smegmatis by allelic replacement only in the presence of two rescue plasmids carrying functional copies of glf and Rv3808c. The glf rescue plasmid was designed with a temperature-sensitive origin of replication and the M. smegmatis glf knockout mutant is unable to grow at the higher temperature at which the glf-containing rescue plasmid is lost. In a separate experiment, the Rv3808c rescue plasmid was designed with a temperature-sensitive origin of replication and the glf-bearing plasmid was designed with a normal original of replication; this strain was also unable to grow at the nonpermissive temperature. Thus, both glf and Rv3808c are essential for growth. These findings and the fact that galactofuranosyl residues are not found in humans supports the development of UDP-galactopyranose mutase and galactofuranosyl transferase as important targets for the development of new antituberculosis drugs.

Three questions can detect hazardous drinkers.

OBJECTIVE: The researchers evaluated the Alcohol Use Disorders Identification Test (AUDIT), the first 3 questions of the AUDIT (AUDIT-C), the third AUDIT question (AUDIT-3), and quantity-frequency questions for identifying hazardous drinkers in a large primary care sample. STUDY DESIGN: Cross-sectional survey. POPULATION: Patients waiting for care at 12 primary care sites in western Pennsylvania from October 1995 to December 1997. OUTCOMES MEASURED: Sensitivity, specificity, likelihood ratios, and predictive values for the AUDIT, AUDIT-C, and AUDIT-3. RESULTS: A total of 13,438 patients were surveyed. Compared with a quantity-frequency definition of hazardous drinking (> or =16 drinks/week for men and > or =12 drinks/week for women), the AUDIT, AUDIT-C, and AUDIT-3 had areas under the receiver-operating characteristic curves (AUROC) of 0.940, 0.949, and 0.871, respectively. The AUROCs of the AUDIT and AUDIT-C were significantly different (P=.004). The AUROCs of the AUDIT-C (P<.001) and AUDIT (P <.001) were significantly larger than the AUDIT-3. When compared with a positive AUDIT score of 8 or higher, the AUDIT-C (score > or =3) and the AUDIT-3 (score > or =1) were 94.9% and 99.6% sensitive and 68.8% and 51.1% specific in detecting individuals as hazardous drinkers. CONCLUSIONS: In a large primary care sample, a 3-question version of the AUDIT identified hazardous drinkers as well as the full AUDIT when such drinkers were defined by quantity-frequency criterion. This version of the AUDIT may be useful as an initial screen for assessing hazardous drinking behavior.

Outbreak of Pichia anomala infection in the pediatric service of a tertiary-care center in Northern India.

An outbreak of nosocomial fungemia due to the unusual yeast, Pichia anomala occurred in the pediatric wards of our hospital over a period of 23 months (April 1996 to February 1998). A total of 379 neonates and children (4.2% admissions) were infected. The probable index case was admitted to the pediatric emergency ward, with subsequent transmission to the premature nursery, pediatric intensive care units, and other children wards. Carriage on the hands of health care personnel was likely to be responsible for dissemination of the fungus. The outbreak could only be controlled after a health education campaign to improve hand-washing practices was instituted and after nystatin-fluconazole prophylaxis to all premature neonates and high-risk infants was introduced. In a case-control study, we identified a lower gestational age, a very low birth weight (<1,500 g), and a longer duration of hospital stay as significant risk factors associated with P. anomala fungemia in premature neonates. We conducted a culture prevalence survey of 50 consecutive premature neonates and found that 28% were colonized with P. anomala at a skin or mucosal site on the date of delivery and that 20% of these neonates subsequently developed P. anomala fungemia. We performed multilocus enzyme electrophoresis on 40 P. anomala outbreak isolates (including patient and health care workers' hand isolates), and the results suggested that these isolates were identical. Our study highlights the importance of P. anomala as an emerging nosocomial fungal pathogen.

Galactan biosynthesis in Mycobacterium tuberculosis. Identification of a bifunctional UDP-galactofuranosyltransferase.

The cell wall of Mycobacterium tuberculosis and related genera is unique among prokaryotes, consisting of a covalently bound complex of mycolic acids, D-arabinan and D-galactan, which is linked to peptidoglycan via a special linkage unit consisting of Rhap-(1-->3)-GlcNAc-P. Information concerning the biosynthesis of this entire polymer is now emerging with the promise of new drug targets against tuberculosis. Accordingly, we have developed a galactosyltransferase assay that utilizes the disaccharide neoglycolipid acceptors beta-d-Galf-(1-->5)-beta-D-Galf-O-C(10:1) and beta-D-Galf-(1-->6)-beta-D-Galf-O-C(10:1), with UDP-Gal in conjunction with isolated membranes. Chemical analysis of the subsequent reaction products established that the enzymatically synthesized products contained both beta-D-Galf linkages ((1-->5) and (1-->6)) found within the mycobacterial cell, as well as in an alternating (1-->5) and (1-->6) fashion consistent with the established structure of the cell wall. Furthermore, through a detailed examination of the M. tuberculosis genome, we have shown that the gene product of Rv3808c, now termed glfT, is a novel UDP-galactofuranosyltransferase. This enzyme possesses dual functionality in performing both (1-->5) and (1-->6) galactofuranosyltransferase reactions with the above neoglycolipid acceptors, using membranes isolated from the heterologous host Escherichia coli expressing Rv3808c. Thus, at a biochemical and genetic level, the polymerization of the galactan region of the mycolyl-arabinogalactan complex has been defined, allowing the possibility of further studies toward substrate recognition and catalysis and assay development. Ultimately, this may also lead to a more rational approach to drug design to be explored in the context of mycobacterial infections.

Drug targeting Mycobacterium tuberculosis cell wall synthesis: genetics of dTDP-rhamnose synthetic enzymes and development of a microtiter plate-based screen for inhibitors of conversion of dTDP-glucose to dTDP-rhamnose.

An L-rhamnosyl residue plays an essential structural role in the cell wall of Mycobacterium tuberculosis. Therefore, the four enzymes (RmlA to RmlD) that form dTDP-rhamnose from dTTP and glucose-1-phosphate are important targets for the development of new tuberculosis therapeutics. M. tuberculosis genes encoding RmlA, RmlC, and RmlD have been identified and expressed in Escherichia coli. It is shown here that genes for only one isotype each of RmlA to RmlD are present in the M. tuberculosis genome. The gene for RmlB is Rv3464. Rv3264c was shown to encode ManB, not a second isotype of RmlA. Using recombinant RmlB, -C, and -D enzymes, a microtiter plate assay was developed to screen for inhibitors of the formation of dTDP-rhamnose. The three enzymes were incubated with dTDP-glucose and NADPH to form dTDP-rhamnose and NADP(+) with a concomitant decrease in optical density at 340 nm (OD(340)). Inhibitor candidates were monitored for their ability to lower the rate of OD(340) change. To test the robustness and practicality of the assay, a chemical library of 8,000 compounds was screened. Eleven inhibitors active at 10 microM were identified; four of these showed activities against whole M. tuberculosis cells, with MICs from 128 to 16 microg/ml. A rhodanine structural motif was present in three of the enzyme inhibitors, and two of these showed activity against whole M. tuberculosis cells. The enzyme assay was used to screen 60 Peruvian plant extracts known to inhibit the growth of M. tuberculosis in culture; two extracts were active inhibitors in the enzyme assay at concentrations of less than 2 microg/ml.