Changes in the proportions of peripheral blood lymphocytes in patients with worn implants

We compared the peripheral blood and periprosthetic tissues of 53 patients at revision arthroplasty with those of 30 patients at primary arthroplasty to determine whether there is a systemic difference in lymphocytes in patients with worn hip implants. The absolute number and relative proportion of lymphocytes bearing CD2, CD3, CD4, CD8, CD16, CD19, HLA-DR, kappa and lambda antigens were compared with the levels of IL-1beta, IL-6 and PGE2 in the pseudosynovial membrane as well as with a semiquantitative estimate of metal and polyethylene particles, necrosis and chronic inflammation and the total concentration of metals within the periprosthetic tissues. There was a significant increase in the relative proportion of CD2-positive T-cells and CD16-positive natural killer cells in the peripheral blood at revision arthroplasty compared with primary arthroplasty and an increased proportion of CD8-positive T-cells and a decreased ratio of CD4 to CD8 (helper inducer/suppressor cytotoxic cells). Three control patients, who went on to have revision surgery, had values at primary arthroplasty which were similar to those of patients at the time of revision surgery. These differences did not correlate with the local concentration of metal, plastic or cement or inflammatory response or the type of prosthesis. An inverse correlation was noted between the necrosis in the periprosthetic tissue and both the local production of IL-6 and the absolute numbers of T-cells in peripheral blood. We conclude that there may be several cell-mediated systemic immune responses to aseptic loosening, at least one of which may be directly related to events in the periprosthetic tissues. We cannot exclude the possibility that the changes in the proportion of CD8-positive cells reflected a predisposition, rather than a reaction, to loosening of the implant.     

Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study.

PURPOSE: To compare the effectiveness and side effects of methadone and morphine as first-line treatment with opioids for cancer pain. PATIENTS AND METHODS: Patients in international palliative care clinics with pain requiring initiation of strong opioids were randomly assigned to receive methadone (7.5 mg orally every 12 hours and 5 mg every 4 hours as needed) or morphine (15 mg sustained release every 12 hours and 5 mg every 4 hours as needed). The study duration was 4 weeks. RESULTS: A total of 103 patients were randomly assigned to treatment (49 in the methadone group and 54 in the morphine group). The groups had similar baseline scores for pain, sedation, nausea, confusion, and constipation. Patients receiving methadone had more opioid-related drop-outs (11 of 49; 22%) than those receiving morphine (three of 54; 6%; P =.019). The opioid escalation index at days 14 and 28 was similar between the two groups. More than three fourths of patients in each group reported a 20% or more reduction in pain intensity by day 8. The proportion of patients with a 20% or more improvement in pain at 4 weeks in the methadone group was 0.49 (95% CI, 0.34 to 0.64) and was similar in the morphine group (0.56; 95% CI, 0.41 to 0.70). The rates of patient-reported global benefit were nearly identical to the pain response rates and did not differ between the treatment groups. CONCLUSION: Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared with morphine as a first-line strong opioid for the treatment of cancer pain.     

Peripheral blood mononuclear cell responses from type 1 diabetic patients and subjects at-risk for type 1 diabetes to human fetal pancreatic tissue proteins

BACKGROUND: Fetal pancreatic tissue has been suggested to be less immunogenic than adult islets. Thus, transplantation of human fetal pancreatic tissue as treatment for type 1 diabetes has been gaining interest. To investigate this question, we tested the peripheral blood mononuclear cell (PBMC) responses from different subject populations to human adult islet proteins (AIP) versus human fetal pancreatic proteins (FPP). METHODS: PBMC responses to FPP and AIP from normal controls (n=14), newly diagnosed type 1 diabetes patients (n=5), long-term type 1 diabetes patients (n=9), and subjects at-risk for development of type 1 diabetes (n=3) were studied. RESULTS: We observed that normal controls demonstrated PBMC reactivity to 0-3 molecular weight regions (mwr) for both the AIP (mean+/-SD, 0.8+/-1.1) and the FPP (0.6+/-0.7). In contrast, newly diagnosed type 1 diabetic patients (<1 year) demonstrated PBMC responses to 9-16 mwr for the AIP (12.8+/-2.5) and 0-14 mwr for the FPP (6.8+/-5.0). The PBMCs from long-term type 1 diabetes patients (> 3 years) were responsive to 2-11 mwr for AIP (6.0+/-2.8) and 0-11 mwr for FPP (4.9+/-4.0). Three nondiabetic ICA positive subjects at-risk for development of type 1 diabetes demonstrated positive PBMC reactivity to 9-18 mwr for the AIP (12.7+/-3.9) and 4-18 mwr for the FPP (10.0+/-5.9). CONCLUSIONS: We conclude that human fetal pancreatic proteins are not significantly less stimulatory than human adult islet proteins to PBMCs of subjects with or at risk for type 1 diabetes.     

A prototype system for testing force platform dynamic performance

Previous work on in-situ calibration of force platforms has focused primarily on behaviour under static loading conditions. The prototype described in this paper is a dynamic system, designed to approximate the loading profile generated during human gait. The design, construction and performance of an oscillating lead pendulum assembly is described; including three-dimensional visual performance assessment and rigorous multi-component force analysis. No significant difference was found between measured data and a theoretical profile for vertical force and angular displacement. A significant difference was found for the horizontal force component. The authors believe that further development of this prototype model will allow accurate routine dynamic calibration.     

An assessment of the thermal safety of microwave warming of crystalloid fluids

We performed an in vitro study to determine the thermal safety of a domestic microwave to warm intravenous crystalloid solutions. Five-hundred-millilitre bags of crystalloid, randomly allocated to groups which differed in power setting, timer setting and whether or not agitation was performed after warming, were heated in a microwave oven to a calculated temperature of 39 degrees C. Timer accuracy was checked by stopwatch. Bag temperature was measured using an infrared tympanic temperature probe and fluid temperature was measured with an in-line thermocouple. Mean times measured by stopwatch were higher than set. No in-line temperatures reached 40 degrees C. Wider overall ranges and a higher mean were found with the tympanic probe compared with in-line temperature measurement. There were significant differences between the in-line temperatures of shaken and unshaken bags at each power setting, but not when groups were added together. There was no change in colour or odour of bags or fluid. One bag developed a pinhole leak when the packaging was removed.     

Radiographic appearance of the chest following therapy for Hodgkin disease

This study was carried out to define the post-treatment appearance of the chest radiographs in 44 consecutive patients with Hodgkin disease who received mantle irradiation with or without chemotherapy and to determine how the incidence and severity of post-treatment abnormalities relate to the radiation parameters and chemotherapeutic regimens. Radiographs of the chest in 44 patients, computed tomograms of the chest in 31 patients and of the abdomen of 35 patients were reviewed, prior to and following treatment, for mediastinal contours, pericardial status, cardiac size and pulmonary fibrosis. All patients were followed for a minimum of 1 year and 27 were followed for more than 5 years. Stable post-treatment imaging studies were correlated with the initial extent of disease, radiation parameters, and chemotherapeutic regimens. Stable post-treatment findings were categorised as follows: the chest radiograph was normal or showed subtle vascular reorientation; moderate paramediastinal fibrosis was present; severe pulmonary fibrosis had occurred with narrowing of the cardiomediastinal silhouette in some patients. In general, the severity of the fibrosis was dependent on (1) the size of the radiation fields and on whether or not the coverage of the hila included a 1- to 2-cm margin; (2) the amounts of chemotherapy and particularly bleomycin containing regimens and (3) individual susceptibility of normal tissue irradiation. Therapy for Hodgkin disease is not necessarily associated with radiographic sequelae regardless of the initial status of the mediastinum or the treatment. However, the post-treatment appearance of the chest radiographs in this study was related strongly to (1) the initial extent of disease and particularly the status of the hila, both of which influenced the amounts of lung parenchyma that were included in the treatment fields; (2) the use of bleomycin in chemotherapy regimens and (3) individual normal tissue radiosensitivity.     

Quantifying the effects of anesthesia on intracellular oxygen via low-cost portable microscopy using dual-emissive nanoparticles

Intracellular oxygenation is an important parameter for numerous biological studies. While there are a variety of methods available for acquiring in vivo measurements of oxygenation in animal models, most are dependent on indirect oxygen measurements, restraints, or anesthetization. A portable microscope system using a Raspberry Pi computer and Pi Camera was developed for attaching to murine dorsal window chambers. Dual-emissive boron nanoparticles were used as an oxygen-sensing probe while mice were imaged in awake and anesthetized states. The portable microscope system avoids altered in vivo measurements due to anesthesia or restraints while enabling increased continual acquisition durations.     

Mechanisms of displacement discrimination with a visual reference

A nearby visual reference point facilitates displacement discrimination. For example, a nearby stationary point of light improves discriminating left or right displacement of a point by several fold. This reference effect interacts with the temporal characteristics of displacement. Discrimination thresholds rise with increases in the delay between the offset of the initial stimulus and the onset of the displaced stimulus. Moreover, the effect of a nearby reference point is larger with a long delay than with a short delay. This interaction was investigated using two nonexclusive hypotheses of the mediating mechanisms. A single-signal hypothesis specifies a single mediating mechanism that aggregates the effect of displacement and delay. A single-noise hypothesis specifies a single mediating mechanism that aggregates the effect of reference and delay. Each of these hypotheses predicts an equivalence property similar to the equivalent background principle of adaptation research. The equivalence required by the single-signal hypothesis was not satisfied, disconfirming the hypothesis. In contrast, the equivalence required by the single-noise hypothesis was satisfied. The equivalence was extended to delays where the reported judgment was of perceived position and not of perceived movement. The second result is compatible with displacement discrimination mechanisms that are the same function of displacement, whatever their other differences.     

Simian Varicella Virus Pathogenesis in Skin during Varicella and Zoster

Primary simian varicella virus (SVV) infection and reactivation in nonhuman primates is a valuable animal model in the study of varicella zoster virus disease [varicella (chickenpox) and herpes zoster (shingles)]. To understand SVV pathogenesis in skin, we inoculated 10 rhesus macaques with SVV, resulting in varicella rash. After the establishment of latency, eight of the monkeys were immunosuppressed using tacrolimus with or without irradiation and prednisone and two monkeys were not immunosuppressed. Zoster rash developed in all immunosuppressed monkeys and in one non-immunosuppressed monkey. Five monkeys had recurrent zoster. During varicella and zoster, SVV DNA in skin scrapings ranged from 50 to 10⁷ copies/100 ng of total DNA and 2–127 copies/100 ng of total DNA, respectively. Detection of SVV DNA in blood during varicella was more frequent and abundant compared to that of zoster. During varicella and zoster, SVV antigens colocalized with neurons expressing β-III tubulin in epidermis, hair follicles, and sweat glands, suggesting axonal transport of the virus. Together, we have demonstrated that both SVV DNA and antigens can be detected in skin lesions during varicella and zoster, providing the basis for further studies on SVV skin pathogenesis, including immune responses and mechanisms of peripheral spread.