Support of vulnerable patients throughout TB treatment in the UK.

Despite well-established treatment regimens, tuberculosis (TB) remains a public health burden; it disproportionately affects poor and marginalized populations who may not have access to social support, including migrants, homeless people and those dependent on drugs or alcohol. There is a clearly demonstrated need for housing and other appropriate social support, as part of a package of integrated clinical and social care. However, TB prevention and control efforts in the UK often do not address the specific vulnerabilities of these groups and it can be a challenge to support the continued TB treatment of these underserved populations. This challenge is exacerbated by complex issues concerning funding, immigration and the law. In this paper, we have reviewed current UK guidance and legislation, discussed several case studies and highlighted examples of existing models of community support for TB patients. Finally, we lay out our recommendations for ensuring a co-ordinated, whole system approach to successful TB treatment.

[Cognitive remediation program for individuals living with schizophrenia (Recos): preliminary results]. / Programme de remédiation cognitive pour patients présentant une schizophrénie ou un trouble associé (Recos) : résultats préliminaires.

BACKGROUND: Nowadays, cognitive remediation is widely accepted as an effective treatment for patients with schizophrenia. In French-speaking countries, techniques used in cognitive remediation for patients with schizophrenia have been applied from those used for patients with cerebral injury. As cognitive impairment is a core feature of schizophrenia, the Département de psychiatrie du CHUV in Lausanne (DP-CHUV) intended to develop a cognitive remediation program for patients with a schizophrenia spectrum disease (Recos-Vianin, 2007). Numerous studies show that the specific cognitive deficits greatly differ from one patient to another. Consequently, Recos aims at providing individualized cognitive remediation therapy. In this feasibility trial, we measured the benefits of this individualized therapy for patients with schizophrenia. Before treatment, the patients were evaluated with a large battery of cognitive tests in order to determine which of the five specific training modules - Verbal memory, visuospatial memory and attention, working memory, selective attention, reasoning - could provide the best benefit depending on their deficit. OBJECTIVES: The study was designed to evaluate the benefits of the Recos program by comparing cognitive functioning before and after treatment. METHOD: Twenty-eight patients with schizophrenia spectrum disorders (schizophrenia [n=18], schizoaffective disorder [n=5], schizotypal disorder [n=4], schizophreniform disorder [n=1], DSM-IV-TR) participated in between one and three of the cognitive modules. The choice of the training module was based on the results of the cognitive tests obtained during the first evaluation. The patients participated in 20 training sessions per module (one session per week). At the end of the training period, the cognitive functioning of each patient was reevaluated by using the same neuropsychological battery. RESULTS: The results showed a greater improvement in the cognitive functions, which were specifically trained, compared to the cognitive functions, which were not trained. However, an improvement was also observed in both types of cognitive functions, suggesting an indirect cognitive gain. CONCLUSION: In our view, the great heterogeneity of the observed cognitive deficits in schizophrenia necessitates a detailed neuropsychological investigation as well as an individualized cognitive remediation therapy. These preliminary results need to be confirmed with a more extended sample of patients.

CFD modeling of pharmaceutical isolators with experimental verification of airflow.

Computational fluid dynamics (CFD) models have been developed to predict the airflow in a transfer isolator using a commercial CFD code. In order to assess the ability of the CFD approach in predicting the flow inside an isolator, hot wire anemometry measurements and a novel experimental flow visualization technique consisting of helium-filled glycerin bubbles were used. The results obtained have been shown to agree well with the experiments and show that CFD can be used to model barrier systems and isolators with practical fidelity. This indicates that CFD can and should be used to support the design, testing, and operation of barrier systems and isolators.

Modifications in protein binding to upstream sequences of the sea urchin cytoplasmic actin gene CyIIa in comparison to its linked neighbors, CyI and CyIIb.

The sequences corresponding to regions upstream of the ATG and transcription start site of the CyIIa cytoplasmic actin gene of the sea urchin Strongylocentrotus purpuratus were determined and compared to the genomically linked CyI and CyIIb actin genes. Sites of protein-DNA interaction in the CyIIa upstream sequences were identified by DNase I footprinting. The similarity between CyIIa and CyI (and CyIIb) upstream sequences was limited and included a consensus octamer sequence, serum response element (SRE) and some short sequences within the proximal promoter region. The octamer sequence was found to bind protein. A single DNase I hypersensitive site was detected within the SRE and to two flanking nucleotides, but otherwise, the SRE did not appear to be protected. This is in contrast to strong protein binding to the CyIIb SRE. A region in the CyIIa gene with limited identity to the functionally significant protein binding site D in CyI also did not bind protein. Four additional sites of protein-DNA interaction were identified in CyIIa upstream sequences. One of these is similar to a protein binding site previously located in the CyI upstream sequences, whereas the others appear to be unique. These data indicate that the CyIIa upstream sequences differ extensively from those of CyI. The pattern of CyIIa expression is likely a consequence of these alternations in DNA sequence and protein-DNA interactions.

Long-term impact of Drug Abuse Resistance Education (D.A.R.E.). Results of a 6-year follow-up.

The long-term effectiveness of Drug Abuse Resistance Education (D.A.R.E.) was assessed by contrasting drug use and other D.A.R.E.-related attitudinal latent variables among 356 twelfth-grade students who had received the program in the 6th grade with 264 others who did not receive it. A prior study of these subjects when they were in 9th grade had shown no significant differences. A follow-up survey in 12th grade assessed central D.A.R.E. concepts such as self-esteem, police bonds, delay of experimentation with drugs, and various forms of drug use. Although the authors found no relationship between prior D.A.R.E. participation and later alcohol use, cigarette smoking, or marijuana use in 12th grade, there was a significant relationship between earlier D.A.R.E. participation and less use of illegal, more deviant drugs (e.g., inhalants, cocaine, LSD) in a development sample but not in a validation sample. Findings from the two studies suggest a possible sleeper effect for D.A.R.E. in reference to the use of harder drugs, especially among teenage males.

Three-year follow-up of Drug Abuse Resistance Education (D.A.R.E.).

The long-term effectiveness of D.A.R.E. was assessed by contrasting 9th-grade students who received the program in the 6th grade with others who did not receive the program. Of 38 elementary schools eligible for D.A.R.E. programs, 21 received the program and 17 did not. A follow-up survey assessed central D.A.R.E. concepts such as self-esteem, resistance to peer pressure, delay of experimentation with drugs, and drug use. Employing latent variables to represent the concepts, no significant differences were found between D.A.R.E. participants and controls. The authors discuss attenuation of effects and the generally antidrug context of schools.

Prejudice toward persons living with a fatal illness.

Vignettes depicting a person living with a fictitious fatal illness were presented to 222 undergraduates. Manipulated variables in a completely randomized 3 x 2 x 2 factorial design were method of transmission of the illness (genetic/contagious/infectious), the population likely to become ill (anyone/primarily marginal persons), and the amount of suffering (little/much). Subjects reported on perceptions of ease of transmission of the illness, danger of contact with the ill person, blame, support of sanction, and social distance. Multivariate analysis of covariance showed that the manipulated variables affected the dependent variables considered together. Greatest prejudice was shown toward persons suffering greatly from an infectious illness that affected primarily marginal persons. Results are discussed relative to HIV.

The impact of ethgender on self-esteem among adolescents.

This study examined the impact of ethgender, the combination of race and gender, on global and public domain aspects of adolescent self-esteem. Using the Rosenberg Self-Esteem Scale and a 3-item index, differences were observed among 10 ethgenders. Black and Hispanic males had the highest levels of global self-esteem, and Asian and Native American Females had the lowest. On public domain components white and black males had the highest scores, and Asian and Native American females had the lowest. Females (except blacks) had lower levels of both global and public domain self-esteem than did males.

Transient locked-in syndrome after vascular injection during stellate ganglion block.

Intravertebral artery injection of local anesthetics is a rare and alarming complication of neural blocks of the neck. Although seizures, apnea, and loss of consciousness occur, an unusual syndrome with sparing of eye movement might also occur. In transient locked-in syndrome, the patient remains conscious despite inability to breathe or move. The authors report a patient with apparent transient locked-in syndrome that resulted during a stellate ganglion block. This complication is different from frequently reported stroke-like complications. Needle position in the vertebral artery is a possible explanation for the negative aspiration of blood this patient experienced.

Stereotypes of pilots and apprehension about flying with them: a study of commercial aviation scenarios.

This study explored the effects of gender, experience, and performance of a commercial aviation pilot on concern of passengers about flying with him or her. It used scenarios that represented two aspects of pilot behavior: skill and judgment. We cast 112 adult subjects in the role of passengers. They read vignettes that described their captain and the flight in a 2 x 2 x 2 factorial design (male or female, newly promoted or veteran captain, strong or weak performance). Results showed that of the three manipulated variables, only pilot performance had a statistically significant main effect upon apprehension about making a continuation flight with the pilot (F = 41.52; p less than or equal to 0.001 for the skill scenario and F = 41.73; p less than or equal to 0.001 for the judgment scenario). Statistical interactions showed that the level of passenger concern was not based entirely on pilot performance. For instance, on the skill scenario, when a female pilot performed well, her rating was higher than that of an equally performing male, but when she performed poorly, her rating was lower than his (F = 5.38; p less than or equal to 0.02).

Effects of witness characteristics on the perception and reportage of child abuse.

Vignettes depicting the physical mistreatment, psychological mistreatment and neglect of children were used in an experimental design to test for bias in perception and reportage of child abuse. Subjects were 160 jurors and 176 child protective service (CPS) and police personnel. Jurors born before 1945 were less critical of such mistreatment than those born later. Female jurors pledged to report mistreatment more often than did male jurors, and they pledged to report the abuse of a female victim more often than a male victim. The other groups did not show this bias in reporting. Findings might explain discrepancies between studies of the incidence of child abuse and reportage of it.

Epidemiologic differences between chlamydia and gonorrhea.

To assess the prevalence, demographics, and transmission patterns of genital chlamydia infection, we screened 3,078 patients, and compared identified cases (N = 511) to gonorrhea cases (N = 291) diagnosed in the same setting. Chlamydia cases were younger and more likely to be White than their gonorrhea counterparts. Chlamydia cases were distributed diffusely; geographic overlap between the two diseases was only about 40 percent. Gonococcal coinfection was noted in less than 10 percent of patients with chlamydia. Nearly half of men with chlamydia and four-fifths of women were asymptomatic and most cases were identified through screening or contact tracing. Populations at high risk for chlamydia are seemingly different from those for gonorrhea. Differences may be due to control interventions (active for gonorrhea, passive for chlamydia). Chlamydia case reporting and control initiatives are recommended.

High-performance liquid chromatographic analysis of radiolabeled inositol phosphates.

Separation of inositol phosphates by low-pressure anion-exchange chromatography yields unsatisfactory results, while previously described anion-exchange HPLC methods require such extensive processing times that they preclude efficient sample analysis. Using a low-capacity Vydac nucleotide anion-exchange column, we have developed a method which allows complete separation of myo-inositol, inositol 1-phosphate, inositol 1,4-bisphosphate, inositol 1,4,5-trisphosphate, and inositol 1,3,4,5-tetrakisphosphate in approximately 10 min followed by a 5-min column regeneration time. This method provided exceptional reproducibility and quantitative recovery of each inositol phosphate. One column was used for over 300 separations with no loss in performance or alteration in elution pattern. A modified procedure with a 14-min gradient was developed to separate the 1,3,4- and 1,4,5-isomers of inositol trisphosphate. These separation procedures were used to characterize the kinetics of degradation of inositol phosphates by lysates of erythrocytes and neutrophils. We conclude that these procedures are applicable for rapid and quantitative analysis of radiolabeled inositol phosphates in cellular extracts.

The effects of school, family, self-concept, and deviant behaviour on adolescent suicide ideation.

In this study of a population of junior and senior high school students in a mid-sized, Western city, adolescent emotional and ideological disparity with parents and disparity between the importance the adolescent placed on academic achievement and satisfaction with academic achievement were linked to suicide ideation through the intervening variables of self-esteem, purpose in life, and two forms of deviant behaviour--alcohol use and eating disorder. Self-confidence and the deviant behaviours of delinquency and drug use did not prove to be meaningful intervening variables.

An experimental study of gender and situation in the perception and reportage of child abuse.

This study examined the effects of gender, situation, and characteristics of witnesses in the perception and reportage of child abuse. Three scenarios representing themes of neglect, psychological, and physical abuse were evaluated by 144 nonprofessionals not mandated by law to report child abuse. The variables of gender and age of the child, gender of parent, and whether or not the abuse was precipitated by an act of the child were systematically manipulated to produce a 2 X 2 X 2 X 2 X 3 randomized design. Some demographic data on subjects were treated as covariates. Multivariate analysis of variance (MANOVA) was performed on the data. No gender bias in subject's evaluations of victim or perpetrator was discovered. Female subjects viewed the scenarios more critically than did males. Younger subjects were less critical of mistreatment than were older subjects. Perception of the mistreatment as serious was not a good predictor of subsequent official reporting. The scenario involving physical abuse was rated as serious by 86.1% of the subjects, but only 39.5% of these subjects indicated that they would have reported it. Subjects indicated the highest rate of reporting for the neglect scenario which they rated as less serious than physical abuse. These results suggest that official reports are unreliable as an indicator of the incidence of abuse.

Function of neutral endopeptidase on the cell membrane of human neutrophils.

Intact human neutrophils hydrolyzed N-formyl-Met-Leu-[3H]Phe (fMLP) and released Leu-[3H]Phe, cleaving 45-50% of the peptide within 20 min at 37 degrees C. The dipeptide after its release was then hydrolyzed to free amino acids by a dipeptidase (EC 3.4.13.11). This activity, present in plasma membrane-enriched fractions of neutrophil lysates, was also inhibited over 90% by phosphoramidon, an inhibitor of neutral endopeptidase (NEP, EC 3.4.24.11). Dithiothreitol and EDTA inhibited the activity to a comparable degree, suggesting the requirement for a heavy metal cofactor. Bestatin and amastatin, inhibitors of aminopeptidases (but not human kidney NEP), did not inhibit the rate of fMLP degradation but prevented the production of free phenylalanine and enhanced the accumulation of Leu-Phe. Of other inhibitors, alpha 1-antitrypsin and alpha 2-macroglobulin slightly enhanced the rate of fMLP hydrolysis by neutrophils, and others tested were ineffective. Rabbit antiserum to homogeneous human kidney NEP reacted specifically with a 100-kDa protein present in sodium dodecyl sulfate-solubilized neutrophils. The Mr of this protein was slightly larger than that of the kidney enzyme in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The antiserum incubated with intact cells specifically inhibited the degradation of fMLP over 70%. First, we confirm that NEP present on the plasma membrane cleaves fMLP at the Met-Leu bond; then the dipeptide Leu-Phe is cleaved by a dipeptidase. Finally, inhibition of NEP completely blocks fMLP-mediated chemotaxis. Thus, the enzyme may play an important role in modulating chemotactic responses.

Regulation of the affinity state of the N-formylated peptide receptor of neutrophils: role of guanine nucleotide-binding proteins and the cytoskeleton.

Previous studies have indicated that the receptor for N-formylated peptides present on human neutrophils can exist in several ligand-dissociation states at least one of which is sensitive to guanine nucleotides. Human neutrophil membranes rich in cell surface enzyme markers have been isolated from cells pretreated at 37 degrees C with 5 nM fluoresceinated chemotactic peptide (N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein; Fl-peptide) or a buffer control and analyzed for receptor-ligand dissociation states using a previously published fluorescence assay for estimating ligand binding and dissociation rates (Sklar, L. A., et al. 1984. J. Biol. Chem. 259:5661-5669). Fractionation of crude microsomes derived from homogenates of unstimulated cells by ultracentrifugation on linear D2O gradients yielded two plasma membrane-rich fractions termed fast and slow microsomes. Analysis of Fl-peptide dissociation rates from receptor present in fast membrane fractions of unstimulated cells yielded data that could be best fit by assuming that the receptor exists in three distinct ligand-dissociation states. The intermediate ligand-dissociation state (state B) accounted for 47% of the total and was converted to the fastest ligand-dissociation state (state A) by incubation of membranes with GTP or GTP-gamma-S. The remainder of the receptor (17%) present in unstimulated membranes was in a state from which ligand was virtually nondissociable (state C). This form of the receptor was insensitive to GTP-gamma-S. When cells were stimulated with Fl-peptide, most of the receptor present in slow and fast membranes was of the state C type. In contrast to unstimulated cells, slow membranes derived from cells exposed to Fl-peptide contained the majority of the recoverable receptor indicating that receptor was transferred to a physically isolatable membrane domain after ligand binding to the intact cell. The ligand-induced formation of state C in both fast and slow microsome fractions was inhibited by treatment of cells with dihydrocytochalasin B. However, the drug had no effect on translocation of the receptor to slow membranes. Pertussis toxin treatment of intact cells had no effect on ligand-induced formation of state C in either fraction even though other cellular responses were inhibited. Both slow and fast membranes contained a 41-kD G protein as assayed by immunoblot analysis. The data suggest that ligand induces a segregation of receptor-ligand complexes into a membrane domain in which the receptor is functionally uncoupled from the 41-kD neutrophil G protein.(ABSTRACT TRUNCATED AT 400 WORDS)

Disease transmission by heterosexual men with gonorrhea: an empiric estimate.

In Colorado Springs, Colorado, between January and June 1981, approximately 400 cases of gonorrhea in heterosexual men generated approximately 200 "spread" cases in women. The ratio of spread cases to index cases (0.5) is an empiric measure of the reproductive rate for the disease, i.e., the rate at which an infected person replaces himself. Although a reproductive rate of less than one theoretically should produce extinction of the disease, the rate derived from these data is shown to be a weighted average of the rates in symptomatic men (0.31), subsymptomatic men (0.79), and asymptomatic men (1.30). Approximately 35% of gonorrhea transmitted by men may be attributed to the asymptomatic group, which constitutes 10-15% of the infected population. If the observations in this community are applied to the nation as a whole, we estimate that approximately 1.7 million cases of gonorrhea occurred in 1981, as compared with the 990,864 cases actually occurred in 1981, as compared with the 990,864 cases actually reported. This estimate is close to those usually quoted but differs in gender composition. Whereas the observed male-to-female ratio is 1.48:1, the predicted ratio, based on estimates of reproductive rates in subgroups, is 0.8. This analysis supports the theoretical notion that the endemicity of gonorrhea is maintained by heightened transmission within small groups, and it suggests that underdetection is more important than underreporting in the assessment of the "true" incidence of this infection.

Inspiratory muscle training in patients with chronic obstructive pulmonary disease.

To investigate the effects of inspiratory muscle resistive loading training (IMT) on exercise performance in chronic obstructive pulmonary disease (COPD), 13 patients undergoing standard pulmonary rehabilitation were divided into control (n = 6) and experimental (n = 7) groups. Prior to training, we measured inspiratory muscle strength and endurance, resting pulmonary function, and exercise performance on a bicycle ergometer (a progressive test and an endurance test at two thirds of maximal work load). We then determined their resistive loads for training by measuring their 10-min maximal sustainable resistance. Training by patients in the experimental group involved inspiring against a predetermined resistive load. The control subjects breathed through a sham training tube, so that studies were performed in double-blind fashion. The training consisted of 15-min sessions twice daily for 4 wk. The IMT dramatically improved inspiratory muscle endurance--represented as either sustainable inspiratory pressure (SIP) or endurance time at 60% of maximal inspiratory mouth pressure (Pimmax) at functional residual capacity. The SIP of the trained group increased from 29 +/- 11 to 46 +/- 11% of Pimmax (p less than 0.005). Training slightly increased inspiratory muscle strength (p less than 0.05), as determined by Pimmax. In contrast, resting pulmonary function and performance of both progressive and constant-load exercise remained unchanged. We conclude that 4-wk IMT in a pulmonary rehabilitation setting improves inspiratory muscle endurance in patients with COPD without changing pulmonary function or exercise performance.