Contrasting effects of physical wear on elution of two antibiotics from orthopedic cement.

The use of antibiotics as a supplement to bone cement for the purposes of providing a local release of antibiotics is common practice in arthroplasty surgery and the kinetics of elution of the antibiotics in such systems have been investigated previously. However, in these previous studies no account was taken of the potential effects that wear may have on the elution kinetics of the antibiotic. Here, we have modified an existing wear testing rig to allow the simultaneous study of the elution kinetics of bone cement samples containing antibiotics being subjected to immersion only and immersion and conjoint wear. The results show contrasting effects with two commonly used antibiotics. Bone cement containing daptomycin showed no substantial change in antibiotic elution due to wear, while cement containing gentamicin (the most commonly used antibiotic in this application) in contrast demonstrated a substantial reduction in the rate of antibiotic elution when wear was applied. Scanning electron microscopy revealed a possible explanation for these diverse results, due to wear-induced "sealing" of the surface in conjunction with the crystal morphology of the antibiotic.

Blood-derived angioblasts accelerate blood-flow restoration in diabetic mice.

Endothelial cell progenitors, angioblasts, have been detected in the peripheral blood of adult humans, mice, and rabbits. These cells have been shown to incorporate into the endothelium of newly forming blood vessels in pathological and nonpathological conditions. Here we investigated the possibility that the CD34-expressing leukocytes (CD34(+) cells) that appear to be enriched for angioblasts could be used to accelerate the rate of blood-flow restoration in nondiabetic and diabetic mice undergoing neovascularization due to hindlimb ischemia. CD34(+) cells did not accelerate the restoration of flow in nondiabetic mice, but dramatically increased it in diabetic mice. Furthermore, CD34(+) cells derived from type 1 diabetics produced fewer differentiated endothelial cells in culture than did their type 2 diabetic- or nondiabetic-derived counterparts. In vitro experiments suggest that hyperglycemia per se does not alter the ability of angioblasts to differentiate or of angioblast-derived endothelial cells to proliferate. In contrast, hyperinsulinemia may enhance angioblast differentiation but impair angioblast-derived endothelial cell survival or proliferation. Our findings suggest that CD34(+) cells may be a useful tool for therapeutic angiogenesis in diabetics.

Predictive value of common symptom combinations in diagnosing colorectal cancer.

BACKGROUND: This study compared the diagnostic values of age and single symptoms of colorectal cancer with those of age and symptom combinations. METHODS: Consecutive patients with lower gastrointestinal symptoms referred to a surgical clinic over a 12-year period were studied prospectively. The diagnostic value of age and common symptoms of bowel cancer, individually and in combination, was determined by measuring positive predictive value, sensitivity and specificity. RESULTS: In total, 467 (5.5 per cent) of 8529 patients had colorectal cancer. Symptom combination analyses showed that patients presenting with rectal bleeding and change in bowel habit without anal symptoms had the highest risk of cancer. Those with rectal bleeding and perianal symptoms without change in bowel habit were at the lowest risk of having cancer. Symptom subgroups defined by age had positive predictive values for cancer that varied from less than 1 to 35 per cent. CONCLUSION: Symptom combinations defined by age have greater diagnostic value than single symptoms alone.

Use of ulcer size and initial responses to treatment to predict the healing time of leg ulcers.

OBJECTIVE: To test the following two hypotheses: the initial healing profiles of individual leg ulcers determine the longer-term outcome; healing time can be predicted from an initial ulcer size measurement and a sequence of further measurements recorded after treatment has started. METHOD: Twenty-three patients with venous leg ulcers were studied (10 male, 13 female). Digital images of the ulcers were taken at weekly intervals; ulcer size was measured electronically and the information stored in an electronic patient record. The healing profile for each ulcer was analysed by linear regression using the correlation coefficient (r) to indicate linearity. For [r] > 0.85 ([r] = modulus of r, [where r is negative], that is good linearity and hence wound healing), the predicted healing time was calculated from the initial size (cm2) and initial healing rate (cm2/week), and was compared with the actual healing time. RESULTS: The majority of ulcers (17/23) healed with linearity ([r] > 0.85). For these ulcers there was agreement between the predicted healing time and the actual healing time (correlation coefficient 0.95). CONCLUSION: Venous ulcers that respond to treatment appear to heal at a near constant rate. The initial response to treatment can be used to reliably estimate the healing time.

Measuring sub-bandage pressure: comparing the use of pressure monitors and pulse oximeters.

OBJECTIVE: To test the use of low-cost sub-bandage pressure monitors and pulse oximeters as part of a quality-control measure for graduated compression bandaging in leg ulcer clinics. METHOD: Twenty-five healthy volunteers (mean age 40 years) providing 50 limbs were bandaged with a four-layer compression bandaging system. The ankle systolic pressure (ASP) was measured using a pulse oximeter (Nellcor NBP-40) before applying the graduated compression bandages. Interface pressure was measured by placing pressure sensors on the skin at three points (2cm above the medial malleolus; the widest part of the calf; and a point midway between them) in the supine and standing positions. The ASP was measured again with the pulse oximeter after the bandage had been applied, and the effect of the bandage on the ASP was recorded. The actual pressure created by the bandage was compared with the required pressure profile. RESULTS: Interface pressures varied with change of position and movement. With the operator blinded to the pressure monitors while applying the bandages, the target pressure of 35-40mmHg at the ankle was achieved in only 36% of limbs ([mean +/- 95% confidence interval]; 32.3 +/- 1.6mmHg [supine]; 38.4 +/- 2.4mmHg [standing position]). With the help of the pressure monitors, the target pressure was achieved in 78% of the limbs. There was no correlation between the pressure monitors and pulse oximeter pressures, demonstrating that the pulse oximeter is not a useful tool for measuring sub-bandage pressures. CONCLUSION: The results suggest a tool (interface pressure monitors) that is easy to operate should be available as part of quality assurance for treatment, training of care providers and education.

Characterization of the mouse JAB1 cDNA and protein.

JAB1 was originally described as a transcriptional coactivator of c-Jun and Jun D. Recent data suggests that JAB1 is a component of a large protein complex, the JAB1 signalosome in mammals and the COP9 complex in plants. The JAB1 signalosome is implicated in the phosphorylation of selected transcription factors, while the COP9 complex is involved in repression of photomorphogenesis in Arabidopsis. In this study, we describe the partial characterization of mouse JAB1 (mJAB1). The murine JAB1 protein is encoded by a gene located on mouse chromosome 1. mJAB1 mRNA is abundantly expressed in a variety of adult tissues as well as in mouse embryos. The JAB1 protein was readily detectable in many cell types and localized to both the nucleus and cytoplasm. Endogenous JAB1 protein is relatively stable and its degradation is not perturbed by blocking 26S proteasome activity, suggesting that this protein is not degraded by the ubiquitin-mediated proteolytic pathway.

Medicaid eligibility patterns for persons with AIDS in California and New York, 1982-1987.

An analysis of Medicaid eligibility patterns for persons with AIDS (PWAs) was conducted, based on the longitudinal Medicaid eligibility histories of 1,314 AIDS decedents in California and 6,273 AIDS decedents in New York between 1982 and 1987. The study analyzed what eligibility groups or categories and which financial standards PWAs were using to qualify for Medicaid. States have many options with regard to the categories of people they cover under Medicaid and where they set their financial thresholds. The study findings are useful in showing how these policy decisions affect PWAs. A major conclusion of the study is the importance of medically needy coverage for PWAs. Medically needy coverage, which is optional to states, opens up Medicaid to persons of any income level, assuming their medical expenses are high enough. The study also found that PWAs who qualify only through the medically needy provisions have much shorter enrollment and lower lifetime Medicaid expenditures than other PWAs on Medicaid. Presumably, most medically needy only enrollees have other sources of health care coverage in the early stages of the illness. Study data also suggested significant administrative obstacles for PWAs in dealing with the Medicaid eligibility process. Finally, an unexpected study result was that all states may not be aggressively utilizing federal Medicaid financing options for covering the medical assistance expenditures for a significant proportion of the low-income AIDS population.

An objective evaluation of the effectiveness of different methods of displaying three-dimensional information with medical x-ray images.

RATIONALE AND OBJECTIVES: The authors determine the effectiveness of stereoscopy and vertical-axis rotation for displaying three-dimensional (3-D) information in x-ray images. METHODS: Simple x-ray images were simulated using ray tracing and computer-displayed in monoscopic static (MS), monoscopic rotating (MR), stereoscopic static (SS), and stereoscopic rotating (SR) formats. In two experimental tasks, participants including experts (radiologists and radiographers) were shown images displayed in these four formats. Performance was measured by participants' accuracy of judgment, amount of time taken, and confidence in each response. The experts also informally evaluated the displays using complex fluoroscopic skull images and a simulated diagnostic task. RESULTS: The results from both tasks were consistent and showed MS to be least effective and SR to be most effective on all measures. There was no difference in performance between the nonexperts and experts, whose informal feedback consolidated the experimental findings. CONCLUSIONS: It was found that rotational stereoscopic fluoroscopy is feasible and is an effective way of portraying 3-D information using x-rays.

Effects of paroxetine on 5-HT-induced head twitches and phosphatidylinositol hydrolysis in mice.

Head-twitch response and phosphatidylinositol (PIP) hydrolysis in cortex and spinal cord were measured after single or chronic (21 days) administration of paroxetine to normal mice or to mice neonatally treated with 5,7-dihydroxytryptamine, a serotonergic neurotoxin. In normal animals, a down-regulation of 5-HT-receptor numbers after chronic paroxetine was suggested by the attenuation of head-twitch responses compared with a single dose. There was a concomitant decrease in PIP hydrolysis. In DHT-treated animals, although changes in behavioural responses were comparable to those in normals, PIP hydrolysis in cortex and spinal cord after chronic paroxetine increased significantly. These results demonstrate that head-twitch responses and PIP hydrolysis may not be mediated by the same receptor and that the effects of chronic administration of paroxetine depend on the functional state of the serotonergic pathways.

Integrating mental health services into primary care for HIV-infected pregnant and non-pregnant women: Whole Life--a theoretically derived model for clinical care and outcomes assessment.

Poor women of color who are disproportionately both infected and affected by HIV/AIDS also face multiple lifestyle and psychosocial burdens that complicate effective delivery of health care, thereby contributing to their poorer prognosis. Addressing these factors within the context of HIV/AIDS primary care for women is the aim of Whole Life, a program to integrate mental health services into primary care for HIV-infected pregnant and non-pregnant women. Whole Life utilizes a theoretically derived clinical services model that provides data for both clinical care and patient outcomes research within the constraints of a clinical setting. During a woman's first two clinic visits, data are gathered in structured interviews with standardized instruments-adapted for relevance to the population-that meet clinical and service needs, as well as measure components of the Whole Life model. Interviews are conducted by existing front-line staff who have been trained in using these instruments to gather information typically recorded in clinical notes. The implementation of Whole Life to date clearly demonstrates the feasibility of mental health-primary care services integration in a publicly funded HIV primary care clinic serving poor women of color.

Access to hospital care for California and Michigan Medicaid recipients.

This article is a comparison of the characteristics of hospitals serving the general population and Medicaid recipients in California and Michigan, using data from Medicaid uniform claims files and the American Hospital Association Annual Survey for 1984. A greater concentration of discharges in a small number of "high Medicaid volume" urban and rural hospitals in each State was observed for Medicaid recipients compared with the general population. In addition, discharge data suggest that Supplemental Security Income crossovers (individuals covered by both Medicaid and Medicare) and other recipients (mostly children not enrolled in the Aid to Families with Dependent Children program) receive inpatient care in different hospitals from the general population as well as from other Medicaid eligibility groups. Medicaid cost-containment policies and differential access to hospital care are discussed.

Experience of a Medicaid nursing home entry cohort.

Long-term care cost-containment policies have focused on reducing the numbers of persons entering nursing homes. To provide insight and background for such efforts, the authors studied the experience of Medicaid nursing home entry cohorts in three individual States. They found substantial interstate variation in rates of nursing home entry and subsequent patterns of discharge, suggesting the operation of fundamentally different policies for provision of Medicaid nursing home services. Analysis of the cost effectiveness and quality of care implications of these policies may provide guidance for future cost-containment efforts.

Histidine, histamine, and the neuroregulation of food intake: a review and hypothesis.

Feeding, a behavior regulated by the central nervous system (CNS), includes the acquisition of specific essential nutrients and the maintenance of energy balance. Modulation of feeding behavior is a normal part of survival, but certain pathological conditions interrupt or modify regulatory aspects of feeding, thereby leading to inappropriate intake. This review examines aspects of metabolism associated with the anorexia seen in animals suffering from protein-energy malnutrition (PEM). The main focus is the indispensable amino acid histidine (His), the biosynthetic precursor of the neurotransmitter histamine (HA). In kwashiorkor-like PEM, His is elevated in plasma and brain, whereas all other indispensable amino acids are decreased. The elevation of His in the brain is to concentrations five times normal. Because the rate of HA synthesis in the brain is a function of the His concentration, His elevation raises the possibility of a profound direct effect of CNS function. In children, PEM consistently produces the symptoms of depressed food intake, edema, growth failure, and psychomotor changes. One known central effect of HA is the stimulation of ACTH and corticosteroid release. Based on these observations, the hypothesis being examined is as follows: one component of the pathophysiological neuroregulation of food intake involved the His-induced variation of HA concentration in the hypothalamus and the subsequently altered neurochemical activity at the corticotropin-releasing factor (CRF) neurons o the paraventricular nucleus (PVN).

Building community partnerships to improve HIV prevention efforts: implications for nurses.

Acquired immune deficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV), is a major and complex public health crisis. The Centers for Disease Control and Prevention (CDC) issued effective community-based HIV prevention planning in its 1993 "Supplemental Guidance on HIV Prevention Community Planning" through the formation of community planning groups (CPGs). These guidelines are reviewed along with behavioral and social science theories that are the crux of HIV prevention theory-based research and program development. Nurses' roles in community-based HIV prevention as community advocates, HIV prevention program planners, practitioners, and researchers are discussed. The article concludes with nursing implications for HIV prevention.

Digital imaging versus conventional contact tracing for the objective measurement of venous leg ulcers.

OBJECTIVE: This study aimed to compare the accuracy and inter-observer reproducibility of leg ulcer measurements made using digital images and conventional contact tracing. METHOD: The accuracy of measurements made with these two methods by four observers of 11 shapes with a known area was assessed. The time taken to do this was also measured. Following this, the accuracy and inter-observer reproducibility of the two methods was measured for patients with leg ulcers presenting to the vascular clinic, with contact tracing as the reference. RESULTS: For the reference shapes, both methods had a mean error of less than 5%. Contact tracing significantly underestimated the area by 3.9% (p < 0.05), while digital tracing showed no significant error. Digital tracing was quicker than contact tracing, especially for larger shapes (p < 0.05). For leg ulcers, there was no significant difference between area measurements made by the two methods. Inter-observer variation of digital tracing was greater for the ulcers than the reference shapes. This was due to differences in subjective interpretation and technical problems in recording some images. CONCLUSION: Measurement of leg ulcer area using computer-aided tracing of digital camera images is more accurate and quicker than contact tracing provided that appropriate care is taken when taking the pictures. Digital images offer considerable advantages in the shared hospital-community care of patients with leg ulcers.

A survey of post-operative care after day case surgery.

A prospective survey of patients undergoing day surgery was performed with the main aim of identifying the need for post-operative follow-up after minor or intermediate surgery. The degree of patient satisfaction and the increased workload that this group of patients caused general practitioners was also analysed. Patients underwent either varicose vein surgery, inguinal hernia repair or vasectomy and were asked to return a prepaid reply questionnaire two weeks after surgery. Ninety-eight patients were recruited into the survey, 89 (90.8 per cent) correctly completed forms were returned. Of these patients 58 (69 per cent) believed that they would not benefit from an outpatient appointment, 19 (21.3 per cent) made one or more visits to their general practitioner but had no continuing problem at two weeks postoperation. Six (6.7 per cent) continued to have a problem and thought they would benefit from a surgical outpatient appointment. Of the five patients given routine follow-up appointments before discharge four expected no benefit from an outpatient appointment and only one wished to be seen. This survey suggests that patients should be given the option of an outpatient appointment after minor or intermediate surgery via a postal questionnaire. Unnecessary appointments would thereby be reduced.

Lithium in patients with amyotrophic lateral sclerosis (LiCALS): a phase 3 multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Lithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of lithium on survival. We aimed to assess whether lithium improves survival in patients with ALS. METHODS: The lithium carbonate in amyotrophic lateral sclerosis (LiCALS) trial is a randomised, double-blind, placebo-controlled trial of oral lithium taken daily for 18 months in patients with ALS. Patients aged at least 18 years who had ALS according to the revised El Escorial criteria, had disease duration between 6 and 36 months, and were taking riluzole were recruited from ten centres in the UK. Patients were randomly assigned (1:1) to receive either lithium or matched placebo tablets. Randomisation was via an online system done at the level of the individual by block randomisation with randomly varying block sizes, stratified by study centre and site of disease onset (limb or bulbar). All patients and assessing study personnel were masked to treatment assignment. The primary endpoint was the rate of survival at 18 months and was analysed by intention to treat. This study is registered with Eudract, number 2008-006891-31. FINDINGS: Between May 26, 2009, and Nov 10, 2011, 243 patients were screened, 214 of whom were randomly assigned to receive lithium (107 patients) or placebo (107 patients). Two patients discontinued treatment and one died before the target therapeutic lithium concentration could be achieved. 63 (59%) of 107 patients in the placebo group and 54 (50%) of 107 patients in the lithium group were alive at 18 months. The survival functions did not differ significantly between groups (Mantel-Cox log-rank χ(2) on 1 df=1·64; p=0·20). After adjusting for study centre and site of onset using logistic regression, the relative odds of survival at 18 months (lithium vs placebo) was 0·71 (95% CI 0·40-1·24). 56 patients in the placebo group and 61 in the lithium group had at least one serious adverse event. INTERPRETATION: We found no evidence of benefit of lithium on survival in patients with ALS, but nor were there safety concerns, which had been identified in previous studies with less conventional designs. This finding emphasises the importance of pursuing adequately powered trials with clear endpoints when testing new treatments. FUNDING: The Motor Neurone Disease Association of Great Britain and Northern Ireland.