De Novo Head and Neck Cancer After Liver Transplant With Antibody-Based Immunosuppression Induction.

BACKGROUND: Powerful antibody-based immunosuppression induction is now used routinely during organ transplantation and may place patients at even higher risk of post-transplant cancer. MATERIALS AND METHODS: Incidence of de novo head and neck cancer was extracted from the records of 1685 consecutive adult deceased donor liver transplant recipients with a minimum 1-year follow-up from 2001 to 2015. There were 121 patients positively identified as having developed de novo head and neck cancer post-liver transplant. Records of these patients were analyzed to determine demographics, history of cancer pre-liver transplant, de novo cancer type and location, treatment modalities, and alcohol and tobacco exposure. RESULTS: Of the 121 patients who developed cancer of the head and neck (7%), there were 103 cutaneous (6%) and 25 noncutaneous (1%). For noncutaneous cancers, factors associated with increased risk of cancer included alcohol abuse (P < .001), any smoking history (P = .05), and increasing exposure to tobacco (P < .01). Ten-year Cox regression patient survival demonstrates a survival disadvantage for patients who develop noncutaneous cancer (P  = .06) but a survival advantage for patients who develop cutaneous cancer (P < .01). CONCLUSIONS: The incidence and pattern of head and neck cancer in this population of liver transplant recipients was similar to those published previously, suggesting that induction immunosuppression does not increase risk of these types of cancers. Long-term survival was worse for patients with noncutaneous cancers, but better for those with cutaneous cancers, though the reason is unclear.

Diagnostic and Therapeutic Applications of Quantum Dots in Nanomedicine.

The interest in Quantum Dots as a class of nanomaterials has grown considerably since their discovery by Ekimov and Efros in the early 1980s. Although this early work focussed primarily on CdSe-based nanocrystals, the field has now expanded to include various classes of nanoparticles with different types of core, shell or passivation chemistry. Such differences can have a profound effect on the optical properties and potential biocompatibility of the resulting constructs. Although QDs have predominantly been used for imaging and sensing applications, more examples of their use as therapeutics are beginning to emerge. In this chapter we discuss the progress made over the past decade in developing QDs for imaging and therapeutic applications.

Optical probes for the detection of protons, and alkali and alkaline earth metal cations.

Luminescent sensors and switches continue to play a key role in shaping our understanding of key biochemical processes, assist in the diagnosis of disease and contribute to the design of new drugs and therapies. Similarly, their contribution to the environment cannot be understated as they offer a portable means to undertake field testing for hazardous chemicals and pollutants such as heavy metals. From a physiological perspective, the Group I and II metal ions are among the most important in the periodic table with blood plasma levels of H(+), Na(+) and Ca(2+) being indicators of several possible disease states. In this review, we examine the progress that has been made in the development of luminescent probes for Group I and Group II ions as well as protons. The potential applications of these probes and the mechanism involved in controlling their luminescent response upon analyte binding will also be discussed.

Effect of a blend of essential oil compounds on the colonization of starch-rich substrates by bacteria in the rumen.

AIMS: To investigate the mode of action of a blend of essential oil compounds on the colonization of starch-rich substrates by rumen bacteria. METHODS AND RESULTS: Starch-rich substrates were incubated, in nylon bags, in the rumen of sheep organized in a 4 x 4 latin square design and receiving a 60:40 silage : concentrate diet. The concentrate was either high or low in crude protein, and the diet was supplemented or not with a commercial blend of essential oil compounds (110 mg per day). The total genomic DNA was extracted from the residues in the bags. The total eubacterial DNA was quantified by real-time PCR and the proportion of Ruminobacter amylophilus, Streptococcus bovis and Prevotella bryantii was determined. Neither the supplementation with essential oil compounds nor the amount of crude protein affected the colonization of the substrates by the bacteria quantified. However, colonization was significantly affected by the substrate colonized. CONCLUSIONS: The effect of essential oils on the colonization of starch-rich substrates is not mediated through the selective inhibition of R. amylophilus. SIGNIFICANCE AND IMPACT OF THE STUDY: This study enhances our understanding of the colonization of starch-rich substrates, as well as of the mode of action of the essential oils as rumen manipulating agents.

A prospective study of physiotherapist prescribed community based exercise in inflammatory peripheral neuropathy.

There is insufficient evidence to support the use of exercise in the management of chronic disablement in people with inflammatory peripheral neuropathy. Therefore, our study aimed to determine the feasibility and effectiveness of a physiotherapist prescribed community based exercise programme for reducing chronic disablement in patients with stable motor neuropathy. We assessed the effects of a 12 week unsupervised, community based strengthening, aerobic and functional exercise programme on activity limitation and other measures of functioning in 16 people with stable motor neuropathy and 10 healthy control subjects. Fourteen of 16 patients and 8 out of 10 healthy control subjects completed the study and exercised safely in the community with no adverse events. Significant improvements were seen in all measures of activity limitation and in wider measures of health including anxiety, depression and fatigue in the patient group. Improvements were sustained at six months after completion of the exercise programme, except for depression. Ten patients continued to exercise regularly at six months. These findings demonstrate that individually prescribed community based exercise is feasible and acceptable for people with stable motor neuropathy and participation in exercise may be successful in reducing chronic disablement. Future randomised controlled trials are needed to examine the efficacy of this complex community based intervention.

A modified peripheral neuropathy scale: the Overall Neuropathy Limitations Scale.

A new peripheral neuropathy activities measure, the Overall Neuropathy Limitations Scale (ONLS), was derived by modifying the Overall Disability Sum Score (ODSS) slightly. Its inter-rater reliability was found to be high and its correlation with the ODSS (r = 0.97), 36-item Short Form Questionnaire Physical Component Summary Score, and participation and impairment measures was significant. Acceptable responsiveness (standardised response mean 0.76) was shown by the ONLS. The results obtained from the questionnaire agreed closely with those obtained from observation of the tasks on the ONLS, but were not equivalent. The simplicity of the ODSS is shared by the ONLS, but the ONLS has better content validity and less ceiling effect, which may make it more useful for clinical practice and research.

Clinimetric properties of a walking scale in peripheral neuropathy.

Difficulty in walking is seen in many people with peripheral neuropathies, but walking ability is not comprehensively measured by commonly used outcome measures. The clinimetric properties of the 12-Item Multiple Sclerosis Walking Scale (MSWS-12, renamed the Walk-12) were investigated in 65 patients with peripheral neuropathies. Owing to its excellent internal consistency and reliability, and strong correlation with measures of physical and social function (r>0.8), the Walk-12 is recommended for measuring walking ability in peripheral neuropathies.

Health professionals' perspectives in exercise referral: implications for the referral process.

The number of exercise referral schemes expanded rapidly across the UK during the 1990s. Health professionals are thought to be one of the most credible sources of health advice for patients and, hence, are thought to have a pivotal role to play in exercise referral schemes. The aim of the study was to investigate the exercise referral process from the health professional's perspective, specifically examining perceived barriers to referral, priority given to an exercise referral scheme in day-to-day consultations, perceived importance of their role in the process and referring practices. Quantitative and qualitative research methods were utilized with 49% (n = 71) of general practitioners and practice nurses (collectively referred to as health professionals throughout), in a large North West borough (population size approximately 287,000) responding to a postal survey and 11 health professionals (general practitioners n = 9 and practice nurses n = 2) volunteering to take part in a semi-structured interview. Barriers to the referral of patients included lack of time, lack of feedback regarding the patients referred, medico-legal responsibility, a feeling that patients may not take exercise advice given and the belief that physical activity promotion is not a priority during routine consultations. Health professionals refer individuals to an exercise referral scheme on an unsystematic basis and express mixed opinions regarding their perceived role in patient physical activity behaviour change. This study calls for closer partnership working, involving training for promoting physical activity in general practice. Also, greater feedback with regard to patient benefits is needed, in order to overcome some of the practical and perceived barriers for health professionals when referring patients to an exercise referral scheme.

Water source utilization by Pinus jeffreyi and Arctostaphylos patula on thin soils over bedrock.

Stable isotopes were used to evaluate water sources for co-occurring Jeffrey pine (Pinus jeffreyi Grev & Balf.) and greenleaf manzanita (Arctostaphylos patula Greene) in the southern Sierra Nevada, California, where soils averaged only 75 cm thick but were underlain by up to 5 m of weathered granitic bedrock. Soils and underlying weathered bedrock were sampled three times during both the 1997 and 1998 growing seasons, in 25 cm increments, from 0 to 400 cm or until hard bedrock was reached, and plant stem tissue was sampled simultaneously. Extracted water from the soil/bedrock substrate and plant tissue was analyzed for delta(18)O and/or deltaD, and depth of water source was determined by inference in conjunction with moisture status of the substrate. Water source utilization over the growing seasons for both plants generally followed a pattern similar to that observed for water depletion. Predominant water use was initially from the surface soils. Progressively deeper water sources, including weathered bedrock to a depth of several meters, were exploited as the season progressed and the overlying substrate was depleted of moisture. Early in the growing season, stable isotope values were slightly lower for pine than for manzanita (e.g., average deltaD in June 1997 was -81 per thousand for pine and -77 per thousand for manzanita), and suggest that the functional rooting depth for pine may have been slightly greater than for manzanita. In September 1997, manzanita deltaD values averaged -57 per thousand while pine values averaged -85 per thousand, indicating that manzanita opportunistically utilized summer precipitation while pine used more dependable bedrock water. In 1998, soils remained moist through July due to a late snowfall. Unlike the previous year, pine and manzanita deltaD values were not significantly different in mid- and late-growing season, and both plants exploited bedrock-derived water as soil water was depleted. Water held within bedrock was essential for meeting plant transpirational requirements over the summer drought.

Reconstruction of the historical changes in mycorrhizal fungal communities under anthropogenic nitrogen deposition.

Archived soil samples (1937-1999) and historic air quality data from the Los Angeles Basin were used for reconstructing the record of change between atmospheric NO(x) loads, soil delta(15)N values and the diversity of arbuscular mycorrhizae (AM), which are ubiquitous plant-fungus mutualists that control plant community productivity. A tripling of atmospheric NO(x) loads between 1937 and the 1970s was paralleled by soil nitrogen enrichment (delta(15)N = 3.18). From 1975 onwards, atmospheric NO(x) declined, but soils became nitrogen saturated (delta(15) N = -4 and NO(3)-nitrogen = 171mgkg(-1)). The shifts in the AM community followed 28 years of atmospheric nitrogen enrichment and coincided with the onset of soil nitrogen saturation. Such changes were manifest in the loss of AM productivity, species richness (one species per year), three genera (Acaulospora, Scutellospora and Gigaspora) in the spore community and Gigaspora within the roots. Nitrogen enrichment also enhanced the proliferation of potentially less mutualistic species of Glomus. Autoregressive models implied that such patterns will persist and be driven by soil nitrogen cycling patterns. Chronic nitrogen enrichment from air pollution thus alters the diversity and mutualistic functioning of AM communities, which, in turn, may influence the plant community.

Predisposing factors of systemic fungal infections of the genitourinary tract.

We reviewed 50 patients with genitourinary fungal infections between 1982 and 1992. Infections were classified as simple--localized to the bladder and complex--demonstrated evidence of upper tract and/or systemic infection. Predisposing factors of fungal infections, including diabetes mellitus, prolonged Foley catheter drainage and corticosteroid use, were not significantly different. The incidence of obstructive uropathy (88% versus 20%), malnutrition (88% versus 48%), neoplasia (56% versus 16%), renal failure (24% versus 8%) and prolonged antibiotic use (60% versus 32%) were significantly greater in patients with complex infections. The incidence of fungemia in patients with complex infections was 81% with an associated mortality rate of 36%. Of the patients with complex infections 56% required urological intervention. Given the high incidence of obstructive uropathy with complex fungal infections, upper tract imaging is essential.

Simulation of the uptake of a reactive gas in a rat respiratory tract model with an asymmetric tracheobronchial region patterned on complete conducting airway cast data.

Generally, the uptake of reactive gases by the respiratory tract is simulated assuming that all paths from the trachea to the most distal airspaces are equivalent. As this is not the case, especially for nonhumans, the adequacy of this approach to predict doses that can be useful in the fields of toxicology and risk assessment is subject to question. To explore this issue, a dosimetry model is developed which combines the use of one-dimensional convection-dispersion equations in conjunction with multiple path anatomic models so that the dosimetry model simultaneously simulates transport and uptake in all the airways and airspaces of the anatomic model. For this work, the anatomic model of the tracheobronchial (TB) region is patterned on cast data which describe the dimensions and branching network of the 4807 airways of the TB region of a rat. Distal to each of the 2404 terminal bronchioles of the anatomical model, the air space is modeled as a single path. The results presented are preliminary; they focus on the predictions themselves to obtain an understanding of what the model has to say about uptake in a complex set of branching airways. Results include the following predictions: (1) Regardless of path there is a similarity along different paths in the shape of concentration profiles as well as a similarity in the shape of dose profiles. (2) Along a path in the TB or pulmonary region, dose decreases distally. (3) Generally, proximal alveolar region (PAR, a region of major morphological damage due to O3 and NO2) dose decreases the more distal the PAR. (4) There is considerable variation in the doses of the different airways or alveolar surfaces in the same generation. (5) The maximum and minimum PAR doses do not correspond to paths with, respectively, the smallest and largest number of generations from the trachea to the PAR. (6) The ratio of the maximum to minimum PAR dose is very sensitive to tidal volume. These results give a more realistic understanding of respiratory tract gas transport and uptake. The model also predicts aspects that equivalent path models cannot, such as the dose distribution of different but morphologically equivalent sites.

Sarcoid myopathy in a patient with human immunodeficiency virus infection.

Although neither sarcoidosis nor HIV infection is rare, only eight patients with both diseases have been described. None of the eight had sarcoid myopathy. We describe a patient who had HIV infection and decreased CD4+ T-lymphocytes as well as sarcoidosis with muscle involvement. During 3 years of observation, primary sarcoidosis remitted and myopathic symptoms were controlled with prednisone. No opportunistic infections occurred during more than 3 years of prednisone therapy.

Effect of corticosteroid therapy on human immunodeficiency virus-associated nephropathy.

PURPOSE: Human immunodeficiency virus-associated nephropathy (HIV-AN) occurs predominantly in blacks and is characterized histologically by focal segmental glomerulosclerosis or mesangial proliferation and a lymphohistiocytic tubulointerstitial infiltrate. Patients manifest heavy proteinuria and, once azotemia occurs, progress rapidly to end-stage renal disease within 2 to 6 months. No treatment has been shown to be useful for HIV-AN. The purpose of this study was to determine the effect of corticosteroid agents on the progression of HIV-AN. PATIENTS AND METHODS: Four consecutive HIV-infected adults with fewer than 200 CD4 cells/microL, moderate to severe renal insufficiency, proteinuria greater than 2 g per 24 hours, and HIV-AN demonstrated by renal biopsy were treated with 60 mg of prednisone daily for 2 to 6 weeks. Patients were followed with respect to serum creatinine level, 24-hour protein excretion, adverse drug reactions, and the occurrence of opportunistic infections. RESULTS: CD4 counts ranged from 30 to 80 cells/microL before therapy with steroids. The mean (+/- SD) pretreatment serum creatine concentration was 9.1 +/- 5.7 mg/dL and decreased to 3.3 +/- 1.8 mg/dL (P < 0.05) after 2 to 6 weeks of corticosteroid therapy. Twenty-four hour protein excretion did not change (5.2 +/- 2.4 g pretreatment versus 4.6 +/- 4.1 g posttreatment). One patient was able to discontinue dialysis after 10 days. Two patients developed Mycobacterium avium-complex infections and steroid-associated psychosis. One of these patients developed a recurrence of genital herpes, and the other developed dermatomal zoster. None of the four required dialysis during a 1.5- to 5.5-month period of follow-up after cessation of steroid treatment. CONCLUSION: In selected patients with HIV-AN, short-term treatment with corticosteroid agents improves renal function and prevents the development of end-stage renal disease during a 1.5- to 5.5-month period of observation, but may be associated with an increased risk of opportunistic infection.

Young Investigator Award. In vivo treatment of infected prosthetic graft material with urokinase: an animal model.

PURPOSE: Pyogenic infection of vascular grafts represents a serious complication that may necessitate graft removal. If better treatment methods could be developed, perhaps some infected grafts could be salvaged and not removed. This study reports an animal model that evaluates the sterilization of contaminated vascular graft material implants with urokinase and antibiotics. MATERIALS AND METHODS: Polytetrafluoroethylene (PTFE) implants were incubated overnight in a known concentration of bacteria (Staphylococcus epidermidis) and were then implanted subcutaneously into four groups of anesthetized hamsters. The first group (control) received no treatment. The second group received urokinase injections twice daily into each abscess. The third group received intraabscess urokinase and systemic gentamicin twice daily. The fourth group received only systemic gentamicin. The hamsters were killed after 1 week. The graft implants and surrounding tissues were excised and submitted for quantitative cultures. RESULTS: With use of a cutoff value of 100 organisms per milliliter, below which the abscesses were considered noninfected, the following rates of noninfectivity were observed: group 1 (control), 5% noninfected; group 2 (urokinase only), 19.4%; group 3 (urokinase and gentamicin), 63.2%; and group 4 (gentamicin only), 32.5%. The noninfectivity rate of group 3 was significantly higher than that of all other groups combined (P < .001) and was significantly better than that of group 4 alone (P = .013). CONCLUSION: The combination of intraabscess urokinase and systemic gentamicin is very synergistic in graft sterilization. Urokinase may assist in the degradation of both fibrin and the biofilm produced by S epidermidis, thus improving penetration of antibiotics and local host defense mechanisms.

Radon progeny dosimetry in the rat lung.

Deposition, mucociliary clearance, and dosimetry for the inhalation of radon progeny in the rat lung have been simulated for a variety of inhalation conditions. Computations indicate that the exposure-dose conversion factor for the rat lung is approximately twice as high as the corresponding value for the human lung for the same exposure conditions. However, if typical aerosol characteristics are used for animal inhalation experiments and human indoor exposures, the resulting exposure-dose conversion factors are comparable, thereby suggesting similar lung cancer risks per unit exposure. The predicted relative effects of radon progeny disequilibrium and unattached fractions on bronchial doses agree with results from inhalation experiments with laboratory rats.

Estimation of kinetic parameters from thermochemical data.

A method is described by which kinetic parameters may be calculated from the measured temperature changes caused by the heat produced during a chemical reaction. An isoperibol titration calorimeter with an ampoule-breaking facility is used to obtain the temperature data. The temperature changes resulting from the reaction between tri-isopropyl phosphite and sulphur (S(8)) are used as an example to demonstrate the effectiveness of the method. The temperature changes are used to calculate an enthalpy of reaction. From the enthalpy of reaction and intermediate heats, instantaneous concentrations of the reactants may be calculated.