Clostridium difficile vaccine and serum immunoglobulin G antibody response to toxin A

There is a strong association between serum antibody responses to toxin A and protection against Clostridium difficile diarrhea. A parenteral C. difficile toxoid vaccine induced very-high-level responses to anti-toxin A immunoglobulin G (IgG) in the sera of healthy volunteers. After vaccination, the concentrations of anti-toxin A IgG in the sera of all 30 recipients exceeded the concentrations that were associated with protection in previous clinical studies. Furthermore, the median concentration of serum anti-toxin A IgG in the test group was 50-fold higher than the previous threshold. These findings support the feasibility of using a vaccine to protect high-risk individuals against C. difficile-associated diarrhea and colitis.     

Role of chemotaxis in the association of motile bacteria with intestinal mucosa: fitness and virulence of nonchemotactic Vibrio cholerae mutants in infant mice.

Contrary to earlier findings with all other in vivo and in vitro models of cholera studied, nonchemotactic vibrio mutants showed a relatively greater fitness in 5-day-old infant mice as compared with chemotactic parent or chemotactic revertant strains. This trend was manifest in the relatively greater number of nonchemotactic mutants recovered from the upper small intestine at 4 and 18 h after intragastric infection. The same trend was also revealed in the significantly greater virulence (in terms of time to death) of nonchemotactic mutants as compared with the chemotactic parent or revertant strains. Histological studies in infant mice of the penetration of chemotactic and nonchemotactic vibrios into the mucus gel of the small intestine yielded the same findings as in all other models studied, i.e., significantly greater penetration by chemotactic vibrios. There was no correlation between the relative fitness of nonchemotactic vibrios in the small intestine of infant mice and the rate of recovery of viable nonchemotactic vibrios from that site. In contrast, excellent correlation was found between the relative fitness of nonchemotactic vibrios and a decrease in the recovery of viable cells of the chemotactic strain from the small intestine. This indicates that the relatively greater fitness of the nonchemotactic vibrios in infant mice was only apparent and that the observed phenomenon was actually due to an antibacterial mechanism which prevented the accumulation of the chemotactic strains in the small intestine rather than to any stimulating effect on the nonchemotactic mutant itself. To study the in vivo fate of the inoculum in infant mice, vibrios were labeled with either 32P, 35S, or [3H]thymidine. Specific activity determinations of the 32P label were compatible with the assumption of an accelerated rate of death of the chemotactic parent strain in the small intestine. Results with the other isotopes, however, were significantly different. Indeed, the amount of radioactivity retained in the small intestine after feeding labeled bacteria correlated more closely with the isotope used than with the strain of vibrio under study. Consequently, considerable doubt must be cast on the general validity of this not uncommon technique for determining the in vivo location and the death or survival of radioactively labeled bacteria.     

Biological resurfacing of the knee: a review of surgical management

Lesions of the articular surfaces of the knee have been managed by various techniques over the last 50 years. Surgical management has involved: excising the damaged area, refashioning the underlying bone to produce a fibrous response, and introducing allograft, autograft and synthetic materials to encourage a repair matrix. The techniques and their pitfalls are reviewed and discussed, and suggestions made as to the direction of future studies for the repair of osteochondral lesions in the painful knee.     

Detection of stenoses in the internal carotid artery by waveform analysis of continuous wave ultrasound signals (II)

Analysis of the morphological aspects of continuous-wave Doppler examination is a reliable means of detecting carotid stenosis involving 50% or more of the diameter of the arterial lumen. This study was undertaken to evaluate the indexes likely to increase the diagnostic accuracy of this noninvasive investigation method. The indexes studied were the variations of the maximal frequency and the systolic peak frequencies, measured proximal to and at the level of stenosis, and the ratio of the systolic peak frequency measured in the internal carotid artery and in the common carotid artery. After obtaining data on an experimental model, the study was conducted in healthy volunteers (n = 24) and in patients with carotid atherosclerotic disease (n = 23). The experimental study confirmed that stenosis greater than 50% leads to a reduction of blood flow and that there is a mathematical relationship between the frequency measured proximal to and at the level of the stenosis and the degree of stenosis. Clinical data showed that there was a significant decrease in the frequency of the systolic peak in elderly "healthy" subjects as compared with younger subjects. However there was no difference between patients with and without stenosis. The index was 0.8 in young subjects, 1.3 in healthy elderly subjects, and greater than 1.3 in subjects who had a stenosis. There was no statistically significant difference between these two last groups. At the threshold value of 2.3, the sensitivity of the FI index was 22% and the specificity was 94% in the detection of carotid artery stenosis. In the assessment of the tight stenosis, sensitivity was 44%.     

Timebanking and the co-production of preventive social care with adults; what can we learn from the challenges of implementing person-to-person timebanks in England?

This paper explores the potential contribution of timebanking, an innovative volunteering scheme, to the co-production of preventive social care with adults in England. Interest in volunteering in social care has increased as one proposed solution to the international crisis of a rising demand for services in juxtaposition with decreased resources. Volunteering has been particularly promoted in preventive services that prevent or delay care needs arising. Despite sustained interest in volunteering and co-production in social care, little is known about how theory translates into practice. Reporting implementation data from a Realistic Evaluation of six case studies in England, this paper explores one volunteering scheme, timebanking. The research explores how timebanks were working, what contribution they can make to adult social care, and whether they are an example of co-production. Data collected included interviews, focus groups or open question responses on surveys from 84 timebank members, and semi-structured interviews with 13 timebank staff. Each timebank was visited at least twice, and all timebank activity was analysed for a period of 12 months. Data were triangulated to improve reliability. The research found that in practice, timebanks were not working as described in theory, there were small numbers of person-to-person exchanges and some timebanks had abandoned this exchange model. Timebanks faced significant implementation challenges including managing risk and safeguarding and the associated bureaucracy, a paternalistic professional culture and the complexity of the timebank mechanism which required adequate resources. Lessons for timebanks are identified, as well as transferable lessons about co-production and volunteering in social care if such schemes are to be successful in the future.     

Autonomic involvement in inherited neuropathies

The inherited peripheral neuropathies constitute a large group of disorders, in some of which the causative metabolic defect has been identified whereas in the majority it is still unknown. Amongst the former, autonomic involvement is an important component in porphyric neuropathy, in the familial amyloid polyneuropathies, in Fabry's disease and in dopamine-hydroxylase deficiency. The latter group includes the hereditary sensory and autonomic neuropathies in some of which, such as the Riley-Day syndrome, autonomic disturbances are prominent, whereas in others they constitute only a minor component of the symptomatology. Autonomic dysfunction is an important component of the neurological manifestations in multiple endocrine neoplasia type IIB.     

The types of heterosexual gender identity disorder

The rationale for dividing the clinical spectrum of DSM-III-R male heterosexual gender identity disorder into three types was examined. The DSM-III-R category of fetishism for female attire, was included in the analysis. There were 266 male participants divided into three groups: 172 fetishists for female attire or gender identity patients, 52 androphiles, and 42 gynephiles. A 16 item questionnaire was used to examine the groups. A three factor scale ("Fetishism", "Gender Dysphoria" and "Androphilia") was derived from the questionnaire. Only the Gender Dysphoria Factor Scale successfully differentiated between all four conditions, supporting the notion that the three types of gender identity disorder represent a continuum of degree of severity of gender dysphoria. Defining two of the three types of gender identity disorder in terms of the patients' self-reports on fetishism, as DSM-III-R does, is therefore unnecessary.