Semiautomated determination of minimum bactericidal concentrations of antibiotics

Using a newly devised 50-channel photometer which records the opacity of growing bacterial cultures, it was shown that the time taken by cultures diluted 1/1000 in fresh broth to reach 50% of the opacity of a fully grown culture was inversely related to the concentration of organisms in the original culture. This relation was used to determine the numbers of survivors after exposure to benzylpenicillin and gentamicin alone and in combination. The procedure is commended as a labour-saving and potentially rapid method of obtaining comprehensive information on the bactericidal action and interaction of antibiotics.     

A calcium-binding monoclonal antibody that recognizes a non-calcium-binding epitope in the short consensus repeat units (SCRs) of complement C1r.

C1r is a Ca(2+)-binding serine protease that interacts with two other plasma proteins, C1q and C1s, to form C1, the first component of the complement cascade. A monoclonal antibody, BG6, has been produced which binds to C1r only in the presence of Ca2+, requiring 3-5 microM Ca2+ for half-maximal binding. The antibody reacts with native and heat-denatured C1r, and with zymogen C1r, but does not cross-react with C1s or C1q. BG6 did not significantly affect the esterolytic activity of C1r toward a synthetic thioester substrate nor the hemolytic activity of C1 reconstituted from subcomponents in the presence of the antibody. A tryptic fragment of C1r which consists of the C-terminal gamma region of the A chain disulfide-linked to the B chain (gamma B) binds in a Ca(2+)-dependent manner to BG6-Sepharose. Western blotting experiments have further localized the epitope to the gamma region of the A chain, which is composed of two short consensus repeat (SCR) units. The N-terminal alpha region contains the only previously determined Ca(2+)-binding site in the C1r molecule. Equilibrium dialysis experiments confirmed that C1r-gamma B does not bind Ca2+, and showed that antibody BG6 and the gamma B/BG6 complex do bind Ca2+. Thus, the Ca(2+)-dependent nature of this interaction is due exclusively to binding of the metal ion to the antibody. Equilibrium dialysis and immunoblotting have further localized the Ca(2+)-binding site to the Fab fragment of BG6, indicating that the metal-induced conformational change residues in or near the variable region of the IgG. BG6 may set a precedent for the preparation of Ca(2+)-dependent antibodies to non-Ca(2+)-binding epitopes in other proteins.     

Alumina-alumina artificial hip joints. Part II: characterisation of the wear debris from in vitro hip joint simulations

Until recently it was not possible to reproduce clinically relevant wear rates and wear patterns in in vitro hip joint simulators for alumina ceramic-on-ceramic hip prostheses. The introduction of microseparation of the prosthesis components into in vitro wear simulations produced clinically relevant wear rates and wear patterns for the first time. The aim of this study was to characterise the wear particles generated from standard simulator testing and microseparation simulator testing of hot isostatically pressed (HIPed) and non-HIPed alumina ceramic-on-ceramic hip prostheses, and compare these particles to those generated in vivo. Standard simulation conditions produced wear rates of approximately 0.1 mm3 per million cycles for both material types. No change in surface roughness was detected and very few wear features were observed. In contrast, when microseparation was introduced into the wear simulation, wear rates of between 1.24 (HIPed) and 1.74 mm3 per million cycles (non-HIPed) were produced. Surface roughness increased and a wear stripe often observed clinically on retrieved femoral heads was also reproduced. Under standard simulation conditions only nanometre-sized wear particles (2-27.5 nm) were observed by TEM, and it was thought likely that these particles resulted from relief polishing of the alumina ceramic. However, when microseparation of the prosthesis components was introduced into the simulation, a bi-modal distribution of particle sizes was observed. The nanometre-sized particles produced by relief polishing were present (1-35nm). however, larger micrometre-sized particles were also observed by both transmission electron microscopy (TEM) (0.021 microm) and scanning electron microscopy (SEM) (0.05-->10 microm). These larger particles were thought to originate from the wear stripe and were produced by trans-granular fracture of the alumina ceramic. In Part I of this study, alumina ceramic wear particles were isolated from the periprosthetic tissues from around Mittelmeier ceramic-on-ceramic hip prostheses. Characterisation of the particles by TEM and SEM revealed a bi-modal size distribution. SEM analysis revealed particles in the 0.05-3.2 microm size range. and TEM revealed particles in the 5-90 nm size range, indicating that microseparation of the prosthesis components may be a common event in vivo. This study (Part II) has revealed that the introduction of microseparation of the prosthesis components during the swing phase of the wear simulation reproduced clinically relevant wear rates, wear patterns and wear particles in in vitro hip joint simulators.     

Initial evaluation of a continuous speech recognition program for radiology

The aims of this work were to measure the accuracy of one continuous speech recognition product and dependence on the speaker's gender and status as a native or nonnative English speaker, and evaluate the product's potential for routine use in transcribing radiology reports. IBM MedSpeak/Radiology software, version 1.1 was evaluated by 6 speakers. Two were nonnative English speakers, and 3 were men. Each speaker dictated a set of 12 reports. The reports included neurologic and body imaging examinations performed with 6 different modalities. The dictated and original report texts were compared, and error rates for overall, significant, and subtle significant errors were computed. Error rate dependence on modality, native English speaker status, and gender were evaluated by performing ttests. The overall error rate was 10.3 +/- 3.3%. No difference in accuracy between men and women was found; however, significant differences were seen for overall and significant errors when comparing native and nonnative English speakers (P = .009 and P = .008, respectively). The speech recognition software is approximately 90% accurate, and while practical implementation issues (rather than accuracy) currently limit routine use of this product throughout a radiology practice, application in niche areas such as the emergency room currently is being pursued. This methodology provides a convenient way to compare the initial accuracy of different speech recognition products, and changes in accuracy over time, in a detailed and sensitive manner.     

Double anterograde tracing of outputs from adjacent "barrel columns" of rat somatosensory cortex. Neostriatal projection patterns and terminal ultrastructure

The sensory input to the neostriatum from groups of cortical cells related to individual facial vibrissae has been investigated at both light- and electron-microscopic resolution. The purpose of the study was to establish the extent to which corticostriatal input maintains the anatomical coding of spatial information that is present in cortex. A double anterograde tracing method was used to identify the output projections from groups of adjacent neurons in different barrel columns, so that the anatomical relationships between two groups could be studied throughout their length. Adjacent whiskers are represented in adjoining cortical barrels and an examination of corticostriatal projections from these reveals two patterns of projection. In one, the anatomical topography is partially preserved; the barrels are represented in adjoining, discrete, areas of the somatosensory neostriatum. In the second projection pattern, the neostriatal innervation is diffuse and adjacent barrels are represented in overlapping regions of the neostriatum. Moreover, the fibres are thinner, have smaller boutons, and are present in both the ipsilateral and contralateral neostriatum. The two systems also enter the neostriatal neuropile separately. The discrete topographic system enters the adjacent neostriatum as collaterals which leave the descending corticofugal fibres at right angles, while the diffuse system enters directly from the corpus callosum at an acute angle. Examination of the neostriatal terminal fields by correlated light and electron microscopy, shows that characteristic axospinous terminals on spiny neurons are made by both groups of cortical fibres, although they differ in their size and morphology. It is concluded that at least two corticostriatal pathways arise from the barrel cortex. One connection maintains some of the anatomical code implicit in the barrel pattern of primary somatosensory cortex, but another, more diffuse, system is overlaid upon it which may carry different information from this complex area of cortex.     

Exploring young people's difficulties in talking about contraception: how can we encourage more discussion between partners?

Interviews were conducted with 56 young men and women aged 16-19 within the Southampton Community Health NHS Trust to explore difficulties in talking about contraception. Concern about a partner's hostile or negative reaction to any discussion about contraception was central to explaining why some people found it so difficult to initiate such discussions. Admitting the intention to have intercourse, together with a perceived association between condom use and disease prevention, were the main concerns. There was some indication of gender differences in these findings. Furthermore, this negative reaction is perceived to be exacerbated according to the partner's reputation, the potential for harming one's own reputation and whether there is a desire for a longer-term relationship with this partner. The most important outcome of the interviews was that these concerns about a partner's negative reaction were largely unjustified, with the vast majority of participants showing only positive responses to scenarios of future partners initiating discussions with them about contraception. In addition to the need to improve communication skills, the data suggest that greater awareness about the positive reactions towards such discussions should be encouraged.     

An exploratory study of frequent pain measurement in a cancer clinical trial

The ideal methodology for quality of life (QOL) measurement in cancer clinical trials matches the evaluation to the anticipated outcomes, thereby increasing the likelihood that clinically relevant changes are captured. The present study explored the importance of such methodological tailoring in a phase II trial of paclitaxel and recombinant human granulocyte-colony stimulating factor (rhG-CSF) for metastatic breast cancer. Prior to the trial, clinical observation suggested that frequent short-lived episodes of pain might occur during this treatment regimen. Twenty-one patients provided longitudinal data for at least three cycles of chemotherapy. To assess transient pain, aroutine QOL assessment at baseline and every third cycle was supplemented with pain measurements twice weekly. The interval assessment included a multidimensional QOL instrument (Functional Living Index-Cancer) and measures of psychological state (Rand Mental Health Inventory), symptom distress (Memorial Symptom Assessment Scale), and performance status (Karnofsky Performance Status Score). The frequent pain measurements were acquired using visual analogue and categorical scales for pain intensity (Memorial Pain Assessment Card). From baseline to the end of cycle three, global pain scores declined and the results on other QOL measures were variable. The data obtained using these measures did not reveal the existence of episodic pains. In contrast, the twice weekly pain measurements clearly demonstrated transient severe pains in approximately half the patients. These data highlight the importance of specific measurement of troubling symptoms or other relevant QOL concerns at clinically appropriate intervals during the routine QOL assessment of clinical trials. The additional burden involved in these assessments is warranted if the information derived is highly relevant, would not be adequately captured otherwise and could improve therapy.     

Life stress and depressive outcome: Application of a dissipation model to life events

Summary A group of 71 patients were interviewed seven months after they had been screened for a new episode of unipolar depressive illness and the relationship between symptom severity at this time and the life stresses experienced over this period investigated. On the basis of the follow-up assessment, patients were divided into a well and ill group. The mean number of life events experienced during the study period did distinguish patients ill from patients well at follow-up but with less success than has been claimed for onset. Further analysis took into account both the severity of life stress suffered and the time of its occurrence. This improved the discrimination. Both time of event occurrence and event severity were then included in a model of adversity in which it was postulated that event stress dissipates with time. Application of the model to the study data resulted in the statistical relationship between life stress and outcome being somewhat strengthened. The possible implications of this result for further research in life stress are discussed.This work was supported by the Science Research Council, the Mental Health Research Fund (Scottish Division) and the Medical Research Council.     

The effectiveness of invitations from general practitioners in recruiting women to mammographic screening

OBJECTIVE: To evaluate the effectiveness of general practitioner patient lists as a means of recruiting women to mammography screening. DESIGN: This study constitutes the first part of a comparative study of two alternative recruitment strategies involving invitation of women identified from: (i) general practitioner lists; and (ii) the electoral roll. SETTING AND SUBJECTS: The subjects were women aged 50-64 listed as patients of the first three private practices that agreed to collaborate with the South Australian (SA) Breast X-Ray Service to recruit by this method. These practices include five locations encompassing a spread of middle and upper class socioeconomic areas in Adelaide's southern suburbs. INTERVENTIONS: In all, 1505 women who had not already attended the SA Breast X-Ray Service were sent a letter of invitation by their general practitioner to attend the Service for a screening mammogram at a specified date and time. MAIN OUTCOME MEASURES: The primary outcome measures were eligibility status (eligible, not eligible) and attendance status (attended, cancelled appointment, failed to attend without notice). RESULTS: Excluding 34 letters that were returned unopened, 10% of invitees were classified as not eligible, mostly because they had had a recent mammogram elsewhere. Of the remaining invitees, 68.6% attended, 8.4% rang to cancel the appointment and 23% failed to attend without prior notice. CONCLUSIONS: This method of recruitment is viable, and it yields high participation rates close to the "Health for All Australians" target of 70% for mammography screening. Furthermore, the actual attendance rate for this population is expected to increase over time, because some of those initially classified as ineligible, or who cancelled or failed to attend, eventually will attend. The success of this method of recruitment will be measured against the relative cost and effectiveness of the electoral roll alternative, currently under investigation by the SA Breast X-Ray Service.