Lacrimal gland-derived IL-22 regulates IL-17-mediated ocular mucosal inflammation.

Inflammatory damage of mucosal surface of the eye is a hallmark of dry eye disease (DED) and, in severe cases, can lead to significant discomfort, visual impairment, and blindness. DED is a multifactorial autoimmune disorder with a largely unknown pathogenesis. Using a cross-sectional patient study and a well-characterized murine model of DED, herein we investigated the immunoregulatory function of interleukin-22 (IL-22) in the pathogenesis of DED. We found that IL-22 levels were elevated in lacrimal fluids of DED patients and inversely correlated with severity of disease. Acinar cells of the lacrimal glands (LGs), not inflammatory immune cells, are the primary source of IL-22, which suppresses inflammation in ocular surface epithelial cells upon desiccating stress. Moreover, loss of function analyses using IL-22 knockout mice demonstrated that IL-22 is essential for suppression of ocular surface infiltration of Th17 cells and inhibition of DED induction. Our novel findings elucidate immunoregulatory function of LG-derived IL-22 in inhibiting IL-17-mediated ocular surface epitheliopathy in DED thus making IL-22 a new relevant therapeutic target.

Systematic review of aspirin for thromboprophylaxis in modern elective total hip and knee arthroplasty.

AIMS: There is uncertainty regarding the optimal means of thromboprophylaxis following total hip and knee arthroplasty (THA, TKA). This systematic review presents the evidence for acetylsalicylic acid (aspirin) as a thromboprophylactic agent in THA and TKA and compares it with other chemoprophylactic agents. MATERIALS AND METHODS: A search of literature published between 2004 and 2014 was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 13 studies were eligible for inclusion. RESULTS: Evidence from one good quality randomised controlled trial (RCT) showed no difference in rates of venous thrombo-embolism (VTE) in patients given aspirin or low molecular weight heparin (LMWH) following TKA. There was insufficient evidence from trials with moderate to severe risk of bias being present to suggest aspirin is more or less effective than LMWH, warfarin or dabigatran for the prevention of VTE in TKA or THA. Compared with aspirin, rates of asymptomatic deep vein thrombosis (DVT) in TKA may be reduced with rivaroxaban but insufficient evidence exists to demonstrate an effect on incidence of symptomatic DVT. Compared with aspirin there is evidence of more wound complications following THA and TKA with dabigatran and in TKA with rivaroxaban. Some studies highlighted concerns over bleeding complications and efficacy of aspirin. CONCLUSION: The results suggest aspirin may be considered a suitable alternative to other thromboprophylactic agents following THA and TKA. Further investigation is required to fully evaluate the safety and efficacy of aspirin. Cite this article: Bone Joint J 2016;98-B:1056-61.

Low incidence of complications in computer assisted total knee arthroplasty--A retrospective review of 1596 cases.

BACKGROUND: Computer assisted total knee arthroplasty (CATKA) has its own unique complications. The aim of this study was to present our experience of early complications in a large consecutive series of CATKA. METHOD: We investigated retrospective data on the complications specific to computer navigation that were encountered with a consecutive series of 1596 CATKA. RESULTS: Intraoperatively, eight episodes of software failure occurred, two requiring conversion to conventional jig based TKA. There were four broken drill bits when positioning the pins for data entry. Repeat cuts of bone due to malalignment were required on two occasions. There were 17 episodes of superficial pin site infections at the tibial pin-site managed conservatively with antibiotics. One tibial fracture occurred through an old tibial tracker pin site hole. CONCLUSION: This large study shows a low complication rate related to CATKA which is reassuring to the orthopaedic community. CLINICAL RELEVANCE: Level of evidence: III.

Quantification of allospecific and nonspecific corneal endothelial cell damage after corneal transplantation.

PURPOSE: To investigate the effect of host immunity (allospecific) and surgical manipulation (non-allospecific) on corneal endothelial cells (CECs) in corneal transplantation. METHODS: Draining lymph nodes and grafted C57BL/6 corneas were harvested from syngeneic recipients, allograft acceptors, and allograft rejectors (BALB/c) 1, 3, and 8 weeks after transplantation. We analyzed CEC apoptosis using an ex vivo cornea-in-the-cup assay, and visualized cell-to-cell junctions using immunohistochemical staining (ZO-1). Automatic cell analysis using Confoscan software was used to measure CEC density as well as changes in CEC morphology by quantifying the coefficient of variation in cell size (polymegethism) and shape (pleomorphism). RESULTS: The cornea-in-the-cup assay showed that allogeneic acceptor T cells and to an even greater extent rejector T cells (but not syngeneic T cells) induced CEC apoptosis. CEC density after corneal transplantation was significantly reduced in allogeneic acceptors compared with syngeneic grafts (P<0.001), and CEC density was even further reduced in the allo-rejector group compared with the allo-acceptor group. Allogeneic grafts showed a greater increase in the coefficient of variation in cell size (polymegethism) when compared with syngeneic grafts 1 week after transplantation (P=P<0.001). However, pleomorphism was not significantly different between syngeneic and allo-acceptor grafts, indicating that polymegethism (but not pleomorphism or cell density) is a sensitive indicator of the effect of alloimmunity on CECs. CONCLUSIONS: Our data demonstrate that host alloimmunity rather than surgical manipulation alone is the major cause of CEC damage in corneal transplantation, and such morphologic changes of CECs can be detected before the clinically visible onset of allograft rejection.

Five-year follow-up of minimally invasive computer assisted total knee arthroplasty (MICATKA) versus conventional computer assisted total knee arthroplasty (CATKA) - A population matched study.

BACKGROUND: Minimally invasive surgery (MIS) has perceived advantages in the early post-operative stage such as reduced blood loss, decreased pain, earlier return to function and earlier discharge. The aim of our study was to confirm that longer term clinical outcome of TKA is not compromised when MIS is combined with computer assisted surgery. METHODS: Eighty patients matched for age, gender, pre-operative Knee Society Score (KSS) and mechanical axis were prospectively studied. Forty patients underwent minimally invasive computer assisted total knee arthroplasty (MICATKA) and 40 patients underwent conventional computer assisted TKA (CATKA). Functional scores were determined at 6 weeks, 6, 12, 18, and 24 months and 5 years post-surgery. Long-leg alignment views were obtained 3 months post-operatively. RESULTS: KSSs in the short term were significantly better in the MICATKA group than in the CATKA group (p<000.1). Tourniquet-time was 58 min in the MICTKA group and 60 min in the CATKA group (p=0.3). Straight leg raise was achieved by day one in 93% of the MICATKA group compared to 30% of the CATKA group (p<0.001). Length of stay for the MICATKA group has a mean of 3.25 days and a mean of 6 days for the CATKA group (p<0.001). KSSs up to 2-years were significantly better in the MICTKA group (p<0.001). At 5-years there was no significant difference in KSSs (p=0.46) in the MICATKA and CATKA groups. CONCLUSION: We confirm that the use of navigation in minimally invasive TKA permits a number of early post-operative advantages and that longer-term functional outcome is not compromised with its usage. LEVEL OF EVIDENCE: Level II.

Chronic dry eye disease is principally mediated by effector memory Th17 cells.

Recent experimental and clinical data suggest that there is a link between dry eye disease (DED) and T-cell-mediated immunity. However, whether these immune responses are a consequence or cause of ocular surface inflammation remains to be determined. Thus far, only models of acute DED have been used to derive experimental data. This is in contrast to clinical DED which usually presents as a chronic disease. In the present study, using a murine model of chronic DED, it was established that the chronic phase of the disease is accompanied by T helper type 17 (Th17) responses at the ocular surface and that a significant memory T-cell population can be recovered from chronic DED. This memory response is predominantly mediated by Th17 cells. Moreover, adoptive transfer of this memory T-cell population was shown to induce more severe and rapidly progressing DED than did the adoptive transfer of its effector or naive counterparts. Not only do these results clearly demonstrate that effector memory Th17 cells are primarily responsible for maintaining the chronic and relapsing course of DED, but they also highlight a potentially novel therapeutic strategy for targeting memory immune responses in patients with DED.

'Chimeric' grafts assembled from multiple allodisparate donors enjoy enhanced transplant survival.

Certain components of a graft that provoke alloimmunity may not be vital for graft function or critical as targets of rejection. Corneal transplantation is an example of this, because graft epithelium plays a role in allosensitization, whereas corneal graft endothelium-which shares the same alloantigens-is the critical target in allorejection. In this study, we found that exploiting this biology by replacing donor epithelium of an allograft with an allodisparate third-party epithelium yields a marked enhancement in transplant survival. Such 'chimeric' allografts consisted of a C3H/He (H-2(k)) corneal epithelium over a C57BL/6 (H-2(b)) epithelial-denuded cornea (or v.v.) and orthotopically placed on BALB/c (H-2(d)) hosts. Conventional corneal allografts (C3H/He or C57BL/6) or isografts (BALB/c) were also transplanted on BALB/c hosts. Alloreactive T-cell frequencies (CD4(+) interferon [IFN]-gamma(+)) primed to the graft endothelium were strongly diminished in chimeric hosts relative to conventionally allografted hosts. This was corroborated by a decreased T-cell infiltration (p = 0.03) and a marked enhancement of allograft survival (p = 0.001). Our results represent the first successful demonstration of chimeric tissue, epithelial-denuded allograft plus third-party allodisparate epithelium, in the promotion of allograft survival. Moreover, chimeric grafting can be readily performed clinically, whereby corneal allograft rejection remains a significant problem particularly in inflamed graft beds.

Maximum exercise responses of men and women mountaineering trainees on induction to high altitude (4350 m) by trekking.

OBJECTIVE: Maximum aerobic capacity decreases at high altitude. This study was conducted to compare the changes in maximum aerobic capacity in men and women mountaineering trainees on induction to high altitude at 4350 m by trekking. METHODS: Eight men and 8 women mountaineering trainees in a mountaineering course were selected for the study. The initial study was conducted at 2100 m (586 mm Hg) and then during 6 to 7 days of sojourn at 4350 m (435 mm Hg). Maximum oxygen consumption (VO(2max)), maximum heart rate (HR(max)), pulse arterial oxygen saturation (SaO(2)), and maximum ventilation (VE(max)) were measured. RESULTS: VO(2max), HR(max), duration of work (minutes), and SaO(2) saturation decreased significantly (P < .05) with increasing altitude in both sexes. Conversely, VE(max) and ventilatory equivalent (VE/VO(2)) increased significantly (P < .05). Men showed a relatively higher value of maximum exercise variables (total exercise time, exercise intensity, and VO(2)) than women trainees at both altitude locations. The decrement of VO(2max) was 13% in women and 17% in men (P < .05). CONCLUSIONS: The results indicate that the decrement of maximum aerobic capacity at 4350 m was less in women than in men under similar modes of ascent.

Computer navigation versus conventional total knee replacement: no difference in functional results at two years.

We previously compared the component alignment in total knee replacement using a computer-navigated technique with a conventional jig-based method. We randomly allocated 71 patients to undergo either computer-navigated or conventional replacement. An improved alignment was seen in the computer-navigated group. The patients were then followed up post-operatively for two years, using the Knee Society score, the Short Form-36 health survey, the Western Ontario and McMaster Universities osteoarthritis index, the Bartlett Patellar pain questionnaire and the Oxford knee score, to assess functional outcome. At two years post-operatively 60 patients were available for assessment, 30 in each group and 62 patients completed a postal survey. No patient in either group had undergone revision. All variables were analysed for differences between the groups either by Student's t-test or the Mann-Whitney U test. Differences between the two groups did not reach significance for any of the outcome measures at any time point. At two years postoperatively, the frequency of mild to severe anterior pain was not significantly different (p = 0.818), varying between 44% (14) for the computer-navigated group, and 47% (14) for the conventionally-replaced group. The Bartlett Patellar score and the Oxford knee score were also not significantly different (t-test p = 0.161 and p = 0.607, respectively). The clinical outcome of the patients with a computer-navigated knee replacement appears to be no different to that of a more conventional jig-based technique at two years post-operatively, despite the better alignment achieved with computer-navigated surgery.

Computer-assisted total knee replacement. A controlled cadaver study using a multi-parameter quantitative CT assessment of alignment (the Perth CT Protocol).

A controlled study, comparing computer- and conventional jig-assisted total knee replacement in six cadavers is presented. In order to provide a quantitative assessment of the alignment of the replacements, a CT-based technique which measures seven parameters of alignment has been devised and used. In this a multi-slice CT machine scanned in 2.5 mm slices from the acetabular roof to the dome of the talus with the subject's legs held in a standard position. The mechanical and anatomical axes were identified, from three-dimensional landmarks, in both anteroposterior and lateral planes. The coronal and sagittal alignment of the prosthesis was then measured against the axes. The rotation of the femoral component was measured relative to the transepicondylar axis. The rotation of the tibial component was measured with reference to the posterior tibial condyles and the tibial tuberosity. Coupled femorotibial rotational alignment was assessed by superimposition of the femoral and tibial axial images. The radiation dose was 2.7 mSV. The computer-assisted total knee replacements showed better alignment in rotation and flexion of the femoral component, the posterior slope of the tibial component and in the matching of the femoral and tibial components in rotation. Differences were statistically significant and of a magnitude that support extension of computer assistance to the clinical situation.

Computer-assisted knee arthroplasty versus a conventional jig-based technique. A randomised, prospective trial.

We have compared a new technique of computer-assisted knee arthroplasty with the current conventional jig-based technique in 70 patients randomly allocated to receive either of the methods. Post-operative CT was performed according to the Perth CT Knee Arthroplasty protocol and pre- and post-operative Maquet views of the limb were taken. Intra-operative and peri-operative morbidity data were collected and blood loss measured. Post-operative CT showed a significant improvement in the alignment of the components using computer-assisted surgery in regard to femoral varus/valgus (p = 0.032), femoral rotation (p = 0.001), tibial varus/valgus (p = 0.047) tibial posterior slope (p = 0.0001), tibial rotation (p = 0.011) and femorotibial mismatch (p = 0.037). Standing alignment was also improved (p = 0.004) and blood loss was less (p = 0.0001). Computer-assisted surgery took longer with a mean increase of 13 minutes (p = 0.0001).

Impingement syndrome associated with whiplash injury.

We examined 524 patients with whiplash injuries for delayed onset of shoulder pain in order to establish whether this was due to impingement syndrome. A total of 476 patients (91%) responded to a questionnaire of which 102 (22%) were entered into the study; 43 had both a positive impingement sign and Neer test. The incidence of impingement-type pain was 9%. After treatment 23 patients (5%) had a significant improvement in their symptoms, ten (2%) had a moderate improvement and nine had no improvement. Impingement-type pain can occur after whiplash injuries and can be successfully treated.

Immediate treatment of frostbite using rapid rewarming in tea decoction followed by combined therapy of pentoxifylline, aspirin & vitamin C.

BACKGROUND & OBJECTIVES: Frostbite, the severest form of cold injury is a serious medical problem for our Armed Forces operating in the snow bound areas at high altitude. Effects of treatment by rapid rewarming in tea decoction followed by combined therapy of pentoxifylline, aspirin and vitamin C were evaluated in amelioration of tissue damage due to experimentally induced frostbite in rats. METHODS: Experiments were conducted in 2 groups (25 each) of albino rats (control i.e., untreated and experimental i.e., treated). Frostbite was produced experimentally in all the animals by exposing one of the hind limbs at -12 +/- 1 degree C with wind flow 25-30 lit/min for 30 min in a freezing-machine, with simultaneous recordings of rectal and ambient temperatures. The degree of tissue damage was assessed after 10 days. Following cold exposure, neither external thawing nor any medication was given to the animals of the control group; while the exposed limb of the experimental animals was rewarmed in tea decoction maintained at 37-39 degrees C for 30 min immediately after cold exposure, with simultaneous oral ingestion of warm tea decoction. These animals were also given pentoxifylline (40 mg/kg), aspirin (5 mg/kg) and vitamin C (50 mg/kg) twice daily orally for the next 7 days. RESULTS: In the control group, 68 per cent animals suffered from severe (56%) to very severe (12%) frostbite, while the remaining 32 per cent had moderate frostbite. No animals of this group could escape injury or suffered anything less than moderate frostbite; whereas 52 per cent of experimental animals escaped injury (no frostbite) and 32 and 16 per cent suffered only with primary and moderate degree of injury, respectively. None from this group suffered from severe or very severe frostbite. INTERPRETATION & CONCLUSION: It is evident from the study that this combined therapy resulted in significant improvement in the degree of tissue preservation and proved to be highly beneficial as an immediate treatment of frostbite in rats. The combined pharmacological properties of these drugs might have altered the haemorrheologic status of blood and produced curative beneficial effect in improving tissue survival. Clinical studies are required for confirmation of these beneficial effects in humans, which has already been taken up.

Simultaneous determination of bergenin and gallic acid in Bergenia ligulata wall by high-performance thin-layer chromatography.

A simple and reproducible high-performance thin-layer chromatographic method was developed for the simultaneous determination of bergenin and gallic acid in Bergenia ligulata. Water and methanol were used as the extracting solvents. The concentrations of bergenin and gallic acid in both of these solvents were found to be almost the same. The method involves separation of the components by thin-layer chromatography on a precoated Silica Gel 60 F254 plate with a solvent system of ethyl acetate-formic acid-acetic acid-water (100 + 11 + 11 + 27). The sensitivity of the method for bergenin was 0.30 microg, whereas for gallic acid it was 0.25 microg. The proposed method is precise and sensitive and can be used for the detection, monitoring, and simultaneous quantification of bergenin and gallic acid in B. ligulata.

Accelerated stability studies of a polyherbal preparation (eazmov(r)) capsule.

The stability of Eazmov capsule in accelerated condition ie by exposing it to the temperature at 45°C and 40°C with 75% relative humidity was studied. The samples were periodically anallysed upto six months for their organoleptic characteristics, assay of active plant ingredients and the DPTLC finger printing and their peak area analysis, which were found to be stable/ consistent during the period of study. The change in quantifiable components was within 90% of the initial amount, indicating e stability of product for more than three years at room temperature.

A TLC Identification and Spectrophotometric Estimation of Embelin in Embelia ribes.

A simple, rapid and economical procedure for estimation of Embelin by UV Spectrophotometer in Embelia ribes was developed and is described. The method is based on the identification of Embelin by TLC and on the ultra violet absorbance maxima in chloroform at 285 nm. A value of 4.80% w/w of Embelia was found in test simple.

Efficacy of pentoxifylline with aspirin in the treatment of frostbite in rats.

The efficacy of pentoxifylline--a haemorrheologic agent along with aspirin--an analgesic agent was evaluated in the amelioration of the tissue damage due to experimentally induced frostbite in 5 groups (20 each) of rats with body weights ranging between 175 and 200 g. Frostbite was produced experimentally in the hind limbs by exposing the animals to -15 +/- 1 degrees C for 1 h using the harness technique, with simultaneous recording of rectal and environmental temperatures. The degree of tissue damage was assessed on the basis of tissue necrosis after 15 days. Administration of pentoxifylline (40 mg/kg bw) 30 min before and 30 min after the cold exposure followed by two doses of the same daily for the next 5 days along with aspirin (5 mg/kg bw) twice daily for the same duration only after cold exposure, resulted in significant improvement in the degree of tissue preservation. The findings of this preliminary study have brought to light the potential usefulness of these drugs in the treatment of frostbite. The combined pharmacological properties of these two drugs might have altered the haemorrheologic status of blood and produced the curative beneficial effect in improving tissue survival following experimentally induced frostbite in rats.