Epizootic Yersinia enterocolitica in captive African green monkeys (Chlorocebus aethiops sabaeus).

Yersinia enterocolitica is a Gram-negative bacterium that typical results in enterocolitis in humans and poses significant worldwide risks to public health. An outbreak of yersiniosis in the Vervet/African green monkey colony at the WFSM during the winter of 2015-2016 accounted for widespread systemic infection with high morbidity and mortality. Most of the cases had extensive necrosis with suppuration and large colonies of bacilli in the large bowel and associated lymph nodes; however, the small intestine, stomach, and other organs were also regularly affected. Positive cultures of Yersinia enterocolitica were recovered from affected tissues in 20 of the 23 cases. Carrier animals in the colony were suspected as the source of the infection because many clinically normal animals were culture-positive during and after the outbreak. In this study, we describe the gross and histology findings and immune cell profiles in different organs of affected animals. We found increased numbers of myeloid-derived phagocytes and CD11C-positive antigen-presenting cells and fewer adaptive T and B lymphocytes, suggesting an immunocompromised state in these animals. The pathogen-mediated microenvironment may have contributed to the immunosuppression and rapid spread of the infection in the vervets. Further studies in vervets could provide a better understanding of Yersinia-mediated pathogenesis and immunosuppression, which could be fundamental to understanding chronic and systemic inflammatory diseases in humans.

Abdominal Wall Endometriosis in a Rhesus Macaque (Macaca mulatta).

Endometriosis is the presence of endometrium outside of the uterus. Although endometriosis occurs in both pelvic and extrapelvic locations, extrapelvic locations are less common. The development of abdominal wall or incisional endometriosis in women is associated with gynecologic surgeries and is often misdiagnosed. Because they naturally develop endometriosis similar to women, Old World NHP, including rhesus macaques, provide excellent opportunities for studying endometriosis. Here, we describe a case of abdominal wall endometriosis in a rhesus macaque that had undergone cesarean section. Microscopically, the tissue consisted of pseudocolumnar epithelium-lined glands within a decidualized stroma, which dissected through the abdominal wall musculature and into the adjacent subcutaneous tissue. The stroma was strongly positive for vimentin and CD10 but was rarely, weakly positive for estrogen receptors and negative for progesterone. Close examination of extrapelvic endometriosis in rhesus macaques and other NHP may promote increased understanding of endometriosis in women.

Biasing vector network analyzers using variable frequency and amplitude signals.

We report the development of a test setup designed to provide a variable frequency biasing signal to a vector network analyzer (VNA). The test setup is currently used for the testing of liquid crystal (LC) based devices in the microwave region. The use of an AC bias for LC based devices minimizes the negative effects associated with ionic impurities in the media encountered with DC biasing. The test setup utilizes bias tees on the VNA test station to inject the bias signal. The square wave biasing signal is variable from 0.5 to 36.0 V peak-to-peak (VPP) with a frequency range of DC to 10 kHz. The test setup protects the VNA from transient processes, voltage spikes, and high-frequency leakage. Additionally, the signals to the VNA are fused to ½ amp and clipped to a maximum of 36 VPP based on bias tee limitations. This setup allows us to measure S-parameters as a function of both the voltage and the frequency of the applied bias signal.

The treatment of a rupture of the Achilles tendon using a dedicated management programme.

The Swansea Morriston Achilles Rupture Treatment (SMART) programme was introduced in 2008. This paper summarises the outcome of this programme. Patients with a rupture of the Achilles tendon treated in our unit follow a comprehensive management protocol that includes a dedicated Achilles clinic, ultrasound examination, the use of functional orthoses, early weight-bearing, an accelerated exercise regime and guidelines for return to work and sport. The choice of conservative or surgical treatment was based on ultrasound findings. The rate of re-rupture, the outcome using the Achilles Tendon Total Rupture Score (ATRS) and the Achilles Tendon Repair Score, (AS), and the complications were recorded. An elementary cost analysis was also performed. Between 2008 and 2014 a total of 273 patients presented with an acute rupture 211 of whom were managed conservatively and 62 had surgical repair. There were three re-ruptures (1.1%). There were 215 men and 58 women with a mean age of 46.5 years (20 to 86). Functional outcome was satisfactory. Mean ATRS and AS at four months was 53.0 (sd 14), 64.9 (sd 15) (n = 135), six months 67.8 (sd 16), 73.8 (sd 15) (n = 103) and nine months (72.4; sd 14) 72.3 (sd 13) (n = 43). The programme realised estimated cost savings exceeding £91,000 per annum. The SMART programme resulted in a low rate of re-rupture, a satisfactory outcome, a reduced rate of surgical intervention and a reduction in healthcare costs.

Concordance of the SHEA-IDSA severity classification for Clostridium difficile infection and the ATLAS bedside scoring system in hospitalized adult patients.

PURPOSE: The Society for Healthcare Epidemiology of America and Infectious Diseases Society of America (SHEA-IDSA) guidelines for the treatment of Clostridium difficile infection (CDI) recommend initial treatment of CDI based on disease severity. This severity definition has not been validated or evaluated based on clinical outcomes. The ATLAS scoring system is a validated tool useful in predicting treatment response and mortality in CDI. The main purpose of this study is to evaluate the concordance of the ATLAS scoring system and the SHEA-IDSA staging for CDI severity. METHODS: This was a retrospective study which included hospitalized patients with confirmed CDI. Bivariate analyses compared baseline demographics and clinical information between patients with nonsevere and severe CDI based on the SHEA-IDSA criteria for CDI severity. Kappa scores were calculated to compare the concordance of the two scoring systems in defining CDI severity. Sensitivity and specificity of the ATLAS scoring system to determine CDI severity were calculated using the SHEA-IDSA criteria as the reference standard. RESULTS: Sixty-four patients met inclusion criteria. Of those, 62.5% were classified as mild to moderate CDI, 25% were severe, uncomplicated, and 12.5% were severe, complicated based on SHEA-IDSA criteria. In the bivariate analyses, ATLAS score breakpoints of ≥ 4, ≥ 5, and ≥ 6 revealed moderate agreement with the SHEA-IDSA classification for severity. The sensitivities and specificities for ATLAS scores in predicting CDI severity ranged from 58.3 to 87.5, and 67.5-87.5%, respectively. CONCLUSION: The ATLAS score may be useful in evaluating CDI severity and determining drug therapy selection.

Culturally adapting the prevention of diabetes and obesity in South Asians (PODOSA) trial.

Type 2 diabetes is extremely common in South Asians, e.g. in men from Pakistani and Indian populations it is about three times as likely as in the general population in England, despite similarities in body mass index. Lifestyle interventions reduce the incidence of diabetes. Trials in Europe and North America have not, however, reported on the impact on South Asian populations separately or provided the details of their cross-cultural adaptation processes. Prevention of diabetes and obesity in South Asians (PODOSA) is a randomized, controlled trial in Scotland of an adapted, lifestyle intervention aimed at reducing weight and increasing physical activity to reduce type 2 diabetes in Indians and Pakistanis. The trial was adapted from the Finnish Diabetes Prevention Study. We describe, reflect on and discuss the following key issues: The core adaptations to the trial design, particularly the delivery of the intervention in homes by dietitians rather than in clinics. The use of both a multilingual panel and professional translators to help translate and/or develop materials. The processes and challenges of phonetic translation. How intervention resources were adapted, modified, newly developed and translated into Urdu and Gurmukhi (written Punjabi). The insights gained in PODOSA (including time pressures on investigators, imperfections in the adaptation process, the power of verbal rather than written information, the utilization of English and the mother-tongue languages simultaneously by participants and the costs) might help the research community, given the challenge of health promotion in multi-ethnic, urban societies.

Intense pulsed light treatment of chronic mid-body Achilles tendinopathy: A double blind randomised placebo-controlled trial.

We conducted a randomised controlled trial to determine whether active intense pulsed light (IPL) is an effective treatment for patients with chronic mid-body Achilles tendinopathy. A total of 47 patients were randomly assigned to three weekly therapeutic or placebo IPL treatments. The primary outcome measure was the Victorian Institute of Sport Assessment - Achilles (VISA-A) score. Secondary outcomes were a visual analogue scale for pain (VAS) and the Lower Extremity Functional Scale (LEFS). Outcomes were recorded at baseline, six weeks and 12 weeks following treatment. Ultrasound assessment of the thickness of the tendon and neovascularisation were also recorded before and after treatment. There was no significant difference between the groups for any of the outcome scores or ultrasound measurements by 12 weeks, showing no measurable benefit from treatment with IPL in patients with Achilles tendinopathy.

An investigation of the transmission and attenuation of intense pulsed light on samples of human Achilles tendon and surrounding tissue.

BACKGROUND: Light therapy is a common mode of treatment for musculoskeletal injuries but the depth of penetration of light radiation is controversial. Evidence exists for the efficacy of intense pulsed light (IPL) treatment for the rejuvenation of skin (superficial tissue) but it is not known if the IPL can penetrate deeper. If the IPL can penetrate to the depth of the Achilles tendon it may provide a potential management options in the treatment of a chronic mid-body Achilles tendinopathy. OBJECTIVES: To examine if any optical radiation produced by an IPL transmits to the depth of the Achilles tendon when applied cutaneously to excised samples of human Achilles tissue. A secondary aim was to establish the relative amount of optical radiation that was attenuated within the tendon. MATERIALS AND METHODS: Three samples of human Achilles tendon and surrounding tissue were harvested following elective lower limb amputation operations. Each sample was irradiated 2-6 cm above the insertion into the calcaneus (area of an Achilles tendinopathy) with IPL (model iPulse; Cyden Ltd, Wales, UK) set at a single pulse of 25 millisecond, wavelength range 530-1,110 nm and fluence of 13 J/cm(2). The transmission of light radiation was evaluated using (a) standard SLR digital camera, (b) spectrometer, and (c) an external energy meter. RESULTS: Light radiation was found to have transmitted through each of the three tissue samples by all three instruments. There were observable differences in the color of light detected for the control photo and the IPL irradiated tissue samples photographs. The percentage of fluence that was detected to have transmitted through the tissue samples by the energy meter was 4-8.1% and wavelengths between 645 and 843 nm were detected to have transmitted through the tissue by the spectrometer. In addition, the percentage of light radiation that attenuated with the tendon was 10.2-17.32%. CONCLUSION: The results of this study provides evidence that IPL penetrates to the depth of the Achilles tendon and attenuates with the tendon. IPL has potential to produce physiological effects in the treatment of patients with a chronic mid-body Achilles tendinopathy.

Tennis racquets in the jaw: eosinophilic granuloma.

A healthy 4-year-old boy presented with a 4 month history of episodic pain and swelling of his left jaw which appeared to respond to antibiotics. An ultrasound, orthopantomogram (OPG), CT scan and MRI revealed a 3 cm well circumscribed lesion in the left mandible near, but not related to, his posterior molar teeth. The radiological differential diagnosis included a mandibular abscess or neoplasm such as Ewing's sarcoma, or Langerhans cell histiocytosis (LCH). A fine needle aspirate (FNA) was performed. The cytology, in conjunction with the immunohistochemistry (S100 protein and CD1a expression by the histiocyte-like cells) and electron microscopy (demonstrating Birbeck bodies) showed features characteristic of LCH. The boy was treated with an intra-lesional injection of methyl prednisolone with radiological and clinical evidence of regression of the lesion. Localised LCH is also known as eosinophilic granuloma (EG). Its pathogenesis is unknown, although recent studies suggest it is a disease that results from mononuclear phagocyte dysregulation that may be infective, autoimmune or neoplastic in origin. EG is rare, usually affecting children 5-15 years. The jaws are affected in 10-20% of cases with mandible involvement more common in adults. No consensus exists for the optimal therapy which includes curettage, intra-lesional prednisolone and chemotherapy.

A broadband ferromagnetic resonance spectrometer to measure thin films up to 70 GHz.

We report the development of a broadband ferromagnetic resonance (FMR) system operating in the frequency range from 10 MHz to 70 GHz using a closed-cycle He refrigeration system for measurements of thin films and micron/nano structures. The system is capable of carrying out measurements in frequency and field domain. Using two coplanar waveguides, it is capable of simultaneously measuring two samples in the out of plane and in plane FMR geometries. The system operates in the temperature range of 27-350 K and is sensitive to less than one atomic monolayer of a single crystal Fe film.

Increased inherent intestinal granzyme B expression may be associated with SIV pathogenesis in Asian non-human primates.

BACKGROUND: Unlike Asian non-human primates, chronically SIV-infected African non-human primates (NHP) display a non-pathogenic disease course. The different outcomes may be related to the development of an SIV-mediated breach of the intestinal mucosa in the Asian species that is absent in the African animals. METHODS: To examine possible mechanisms that could lead to the gut breach, we determined whether the colonic lamina propria (LP) of SIV-naïve Asian monkeys contained more granzyme B (GrB) producing CD4 T cells than did that of the African species. GrB is a serine protease that may disrupt mucosal integrity by damaging tight junction proteins. RESULTS: We found that the colonic LP of Asian NHP contain more CD4(+) /GrB(+) cells than African NHP. We also observed reduced CD4 expression on LP T cells in African green monkeys. CONCLUSION: Both phenotypic differences could protect against SIV-mediated damage to the intestinal mucosa and could lead to future therapies in HIV(+) humans.

Lanthanum carbonate treatment, for up to 6 years, is not associated with adverse effects on the liver in patients with chronic kidney disease Stage 5 receiving hemodialysis.

AIMS: The efficacy and tolerability of the phosphate binder, lanthanum carbonate, have been evaluated in long-term comparative studies and subsequent open-label extensions. Animal studies show that lanthanum has a very low bioavailability and absorbed lanthanum is primarily excreted in bile. A specified subset of data from four Phase III clinical trials and subsequent extension studies is presented, in order to assess the effects of lanthanum carbonate on the liver. METHODS AND MATERIALS: Hepatic biochemical tests for alanine transaminase, aspartate aminotransferase, alkaline phosphatase and bilirubin were performed. Adverse events classified as "liver and biliary system events" were recorded. RESULTS: In the four initial clinical trials, lanthanum carbonate was not associated with any adverse changes in transaminases or bilirubin. The incidence and nature of adverse events associated with the liver during lanthanum carbonate treatment was similar to that in the comparator groups. For patients who enrolled into the subsequent long-term follow-up study (up to 6 years of treatment), changes in transaminases were not clinically relevant and mean values were similar to those observed in the earlier trials. Overall, there was no increase in the incidence of adverse events associated with the liver reported after up to 6 years of treatment when compared with the results of the initial studies. CONCLUSIONS: There was no evidence of adverse effects of lanthanum carbonate on the liver in patients who received treatment for up to 6 years.

Characteristics of pulmonary hypertension in preterm neonates.

OBJECTIVE: Characteristics of preterm infants who develop pulmonary hypertension (PHT) and their response to inhaled nitric oxide (iNO) are not well described. Our objective was to identify risk factors for PHT in infants <37 weeks gestational age (GA) and to evaluate their response to iNO. STUDY DESIGN: A retrospective chart review was conducted in infants <37 weeks GA born from July/2000 to October/2005 who had an echocardiographic diagnosis of PHT in the first 4 weeks of life. A comparison non-PHT group was generated matched for GA and birth date. Data on prenatal and postnatal characteristics, response to iNO and mortality were collected. RESULTS: Low Apgar scores, preterm premature rupture of membranes, oligohydramnios, pulmonary hypoplasia and sepsis were independently predictive of PHT. Mortality was significantly higher in the PHT group (26.2% versus 4.1%; P<0.0001) compared to the control group. Low birth weight, severe intraventricular hemorrhage and male sex were significantly associated with death in infants with PHT. Thirty-seven percent (23/61) of infants with PHT were treated with inhaled NO. Infants < 29-week GA had poor response to iNO and the response to iNO increased with GA (P<0.02). CONCLUSIONS: Low Apgar scores, oligohydramnios and pulmonary hypoplasia are associated with the development of PHT in premature infants. The percentage of infants responding to iNO increases with advancing GA.

Severe acute renal failure in adults: place of care, incidence and outcomes.

BACKGROUND: Department of Health guidelines recommend specialist critical care facilities for patients with severe single-organ failure such as acute renal failure (ARF). Prospective studies examining incidence, causes and outcomes of ARF outside of intensive care settings are lacking. AIM: To determine the incidence, causes, place of care and outcomes of severe single-organ ARF. DESIGN: Prospective observational study. METHODS: For 6 weeks in June-July 2003, renal physicians were contacted daily, and ICUs on alternate days, to identify cases of severe single-organ ARF in the Greater Manchester area. All patients with serum creatinine >or=500 micromol/l and not requiring other organ support were included. Patients with end-stage renal disease were excluded. Survivors were followed up at 90 days and 1 year from admission. Two independent consultant nephrologists assessed each case using anonymized summaries. RESULTS: Eighty-five patients had multi-organ ARF and 28 had severe single-organ ARF (380 and 125 pmp/year, respectively). Of those with single-organ ARF, 10 (36%) had known pre-existing chronic kidney disease. Renal replacement therapy (RRT) was required in 15 (54%). Total bed occupancy on ICUs relating to single-organ ARF was 59 days (range per patient 1-21). At 90 days, 18 (64%) were alive, and 17 (94%) had independent renal function. At 1 year, 4/18 had died, none receiving RRT at the time of death. Survivors all had independent renal function. In 13 (46%) cases there was an unacceptable delay in patient transfer and in 7 (25%), delays in assessment or commencement of RRT may have adversely affected patient outcome. DISCUSSION: The incidence of ARF treated with RRT is rising. Delays in transfer to renal services may result in inappropriate ICU bed use, and may adversely affect patient outcomes. There are serious problems regarding the appropriate use of expensive and limited medical resources in the critical care area, and in providing safe and effective treatment of patients with ARF.

Lanthanum carbonate (Fosrenol): a novel agent for the treatment of hyperphosphataemia in renal failure and dialysis patients.

Approximately 70% of patients with end-stage renal disease and dialysis have hyperphosphataemia, which is associated with renal osteodystrophy, metastatic calcification and increased mortality and morbidity. Despite dietary restriction and dialysis, most patients will require a phosphate-binding agent to treat this condition. However, phosphate control has not significantly improved over the last two decades, mainly because of the lack of an ideal phosphate-binding agent. Aluminium-based and calcium-based agents are associated with major side-effects despite their efficacy. Although sevelamer hydrochloride represents a step forward in the management of hyperphosphataemia, it has drawbacks and therefore is not the ideal phosphate binder. Lanthanum carbonate is a non-calcium, non-aluminium phosphate-binding agent. It has shown to be effective, well-tolerated and has a positive effect on bone histology.

Efficacy, tolerability, and safety of lanthanum carbonate in hyperphosphatemia: a 6-month, randomized, comparative trial versus calcium carbonate.

BACKGROUND/AIMS: Hyperphosphatemia is an important clinical consequence of renal failure, and its multiple adverse systemic effects are associated with significantly increased risks of morbidity and mortality in dialysis patients. Existing oral phosphate binders have not permitted control of serum phosphate within currently accepted guidelines. This study compares lanthanum carbonate with calcium carbonate for control of serum phosphate in hemodialysis patients. METHODS: In this European multicentre study, 800 patients were randomised to receive either lanthanum or calcium carbonate and the dose titrated over 5 weeks to achieve control of serum phosphate. Serum levels of phosphate, calcium and parathryoid hormone were followed over the following 20 weeks. RESULTS: Around 65% of patients in each group achieved phosphate control, but in the calcium carbonate group this was at the expense of significant hypercalcemia (20.2% of patients vs. 0.4%). Consequently, calcium x phosphate product tended to be better controlled in the lanthanum group. CONCLUSION: This 6-month study demonstrates that serum phosphate control with lanthanum carbonate (750-3,000 mg/day) is similar to that seen with calcium carbonate (1,500-9,000 mg/day), but with a significantly reduced incidence of hypercalcemia. Lanthanum carbonate is well tolerated and may be more effective in reducing calcium x phosphate product than calcium carbonate.

Laryngeal and diaphragmatic muscle activities after central nervous system lesions in cats.

AIM: To examine the central control and coordination of respiratory pump muscles and laryngeal valve muscles by systematic decerebration (DECER), cerebellectomy (CBELL), pontine respiratory group lesioning (PRG) and pontomedullary section (PMED). METHODS: Activities of posterior cricoarytenoid (PCA), thyroarytenoid (TA) and diaphragm (D) muscles and their responses to inspiratory (I) and expiratory (E) total occlusions were determined in 10 adult cats. RESULTS: INTACT anesthetized cats (n = 6) exhibited inspiratory PCA (PCA(I)) and D activities. Expiratory PCA (PCA(E)) was present but TA activity was absent. It was found that successive DECER, CBELL and PRG lesions attenuated PCA(E), the intact pattern being noted in 7/10, 4/10 and 0/6 cats, respectively. After PMED, variable PCA, TA and continuous D activities occurred only with blood gas abnormalities. Augmented PCA and D responses to I- and E-loads occurred after PRG lesions: the I-load PCA(I) and D responses resembled apneusis and the E-load PCA(E) and D responses resembled central apnea. CONCLUSION: The decreasing PCA(E) activity observed with successive DECER, CBELL and PRG lesions suggests that these areas influence laryngeal abductor control of glottic size. The synchronous activities after PMED transection suggest a role for more rostral structures in coordinating laryngeal and diaphragmatic muscle activities.