Intermediate to long-term clinical outcomes and survival analysis of the Salto Mobile Bearing total ankle prothesis.

INTRODUCTION: Osteoarthritis of the ankle is a major burden to affected patients. While tibio-talar arthrodesis has been the gold-standard regarding the treatment of osteoarthritis of the ankle joint for many years, at present total ankle arthroplasty (TAA) provides appealing clinical outcomes and is continually gaining popularity. The aim of this study was to evaluate the intermediate- to long-term clinical outcome including the survival rate of Salto Mobile Bearing TAA (Tonier SA, Saint Ismier, France). MATERIAL AND METHODS: In this retrospective study intermediate- to long-term outcomes measures [Ankle Range of Motion (ROM), American Orthopaedic Foot and Ankle Score (AOFAS score) and survival rate] of 171 consecutive TAA were analysed and compared before and after surgery. Revision was defined as secondary surgery with prothesis component removal, while reoperation was defined as a non-revisional secondary surgery involving the ankle. RESULTS: At a mean follow-up (FU) period of 7.2 ± 2.7 years (range 2.0 to 14.1 years) there was a significant improvement in ankle ROM (total ROM improved from 25.0° ± 15.0° to 28.7° ± 11.3°, p = 0.015; plantarflexion improved from 18.4° ± 11.7° to 20.6° ± 8.2°, p = 0.044; dorsiflexion improved from 6.6° ± 5.7° to 8.1° ± 4.9°, p = 0.011). AOFAS score increased significantly by 41 ± 15 points after surgery (43.3 ± 11.1 before and 84.3 ± 12.0 after surgery, p < 0.001). Overall survival rate within the FU was 81.3% (95% CI 75.3% to 87.3%) with any secondary surgery, 89.9% (95% CI 84.1% to 93.6%) with revision and 93.6% (95% CI 89.8% to 97.3%) with reoperation as endpoint. CONCLUSION: This study endorses the previously reported appealing intermediate- to long-term outcomes of the Salto Mobile Bearing TAA. There was a significant increase in ROM and AOFAS score as well as decent implant survival at final FU.

TNF receptors 1 and 2 exert distinct region-specific effects on striatal and hippocampal grey matter volumes (VBM) in healthy adults.

Tumour necrosis factor alpha (TNFα) has been implicated in the pathophysiology of neurodegenerative and neuropsychiatric disease, with research highlighting a role for TNFα in hippocampal and striatal regulation. TNFα signals are primarily transduced by TNF receptors 1 and 2 (TNFR1 and TNFR2), encoded by TNFRSF1A and TNFRSF1B, which exert opposing effects on cell survival (TNFR1, neurodegenerative; TNFR2, neuroprotective). We therefore sought to explore the respective roles of TNFR1 and TNFR2 in the regulation of hippocampal and striatal morphology in an imaging genetics study. Voxel-based morphometry was used to analyse the associations between TNFRSF1A (rs4149576 and rs4149577) and TNFRSF1B (rs1061624) genotypes and grey matter structure. The final samples comprised a total of 505 subjects (mean age = 33.29, SD = 11.55 years; 285 females and 220 males) for morphometric analyses of rs1061624 and rs4149576, and 493 subjects for rs4149577 (mean age = 33.20, SD = 11.56 years; 281 females and 212 males). Analyses of TNFRSF1A single nucleotide polymorphisms (SNPs) rs4149576 and rs4149577 showed highly significant genotypic associations with striatal volume but not the hippocampus. Specifically, for rs4149576, G homozygotes were associated with reduced caudate nucleus volumes relative to A homozygotes and heterozygotes, whereas for rs4149577, reduced caudate volumes were observed in C homozygotes relative to T homozygotes and heterozygotes. Analysis of the TNFRSF1B SNP rs1061624 yielded a significant association with hippocampal but not with striatal volume, whereby G homozygotes were associated with increased volumes relative to A homozygotes and heterozygotes. Our findings indicate a role for TNFR1 in regulating striatal but not hippocampal morphology, as well as a complementary role for TNFR2 in hippocampal but not in striatal morphology.

[Complications of Descemet Stripping Automated Endothelial Keratoplasty (DSAEK)]. / Komplikationen der Descemet Stripping Automatisierten Endothelkeratoplastik (DSAEK).

BACKGROUND: Lamellar keratoplasties, e.g. Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) are considered the procedures of choice for corneal endothelial diseases. In comparison to penetrating keratoplasty (PK) they are associated with faster visual rehabilitation, a lower risk of complications and a decreased necessity for follow-up visits, which reduces the burden on quality of life in elderly patients. In order to advise patients regarding the indications for surgery and to facilitate the follow-up management, it is important to know the most important complications associated with these keratoplasty techniques. RESULTS AND DISCUSSION: The most important preoperative complication is a delayed indication for the operation. In contrast to PK, DSAEK and DMEK surgery should be provided at an earlier stage of disease as chronic edema alters the stroma and reduces the speed of visual recovery. The most important complications during or early after surgery are detached lamellae, pupillary blocks with increased pressure or air bubbles in the vitreous cavity in patients with previous vitrectomy. The main long-term complications include chronic increased intraocular pressure and immune-mediated graft rejections in DSAEK patients after reducing or stopping topical corticosteroid therapy. This article describes the potential complications of endothelial keratoplasty and provides a detailed explanation of strategies to avoid these complications.

Ocular pulse amplitude as a diagnostic adjunct in giant cell arteritis.

BACKGROUND: To develop an algorithm based on the ocular pulse amplitude (OPA) to predict the probability of a positive temporal artery biopsy (TAB) result in the acute phase of suspected giant cell arteritis (GCA). METHODS: Unilateral TAB was performed and ipsilateral OPA measurements were taken by Dynamic Contour Tonometry. Among the clinical signs and laboratory findings tested in univariate analyses, OPA, Erythrocyte Sedimentation Rate (ESR) and thrombocyte count showed a strong association with a positive TAB result. Algorithm parameters were categorized into three groups (OPA >3.5, 2.5-3.5, and <2.5 mm Hg; ESR <25, 25-60, and >60 mm/h; thrombocyte count <250'000, 250'000-500'000, and >500'000/µl). Score values (0, 1, and 2) were attributed to each group, resulting in a total score range from 0 to 6. A univariate logistic regression analysis using the GCA diagnosis as the dependent and the total score as the independent variate was fitted and probability estimates were calculated. RESULTS: Thirty-one patients with suspected GCA undergoing TAB during an eighteen-month observation period were enrolled. Twenty patients showed histologically proven GCA. Four patients had score values ≤2, fourteen between 3 and 4, and thirteen of ≥5. The corresponding estimated probabilities of GCA were<7, 52.6, and >95%. CONCLUSION: The present study confirms previous findings of reduced OPA levels, elevated ESR, and elevated thrombocyte counts in GCA. It indicates that a sum score based on OPA, ESR, and thrombocyte count can be helpful in predicting TAB results, especially at the upper and the lower end of the sum score range.

Intraoperative testing of opening and closing pressure predicts risk of low intraocular pressure after Ahmed glaucoma valve implantation.

PURPOSE: The aim of this study was to assess whether intraoperative testing of silicone Ahmed glaucoma valves (AGVs) would identify valves with an increased risk of low postoperative intraocular pressure (IOP). METHODS: In 30 consecutive cases of glaucoma surgery with AGV implantation, after priming the AGV, we intraoperatively measured the opening pressure A, closing pressure B, and re-opening pressure C using the active infusion pump of a phako-machine. IOP was checked postoperatively on the same day. Low IOP was defined as <5 mm Hg. Intraoperatively measured pressure characteristics of the valve function were analysed for their ability to predict postoperative IOP outcomes. RESULTS: Opening A, closing B, and re-opening C pressures (mean, (SD)) were 18.4 (5.1), 8.3 (4.7), and 11.7 (4.8)mm Hg, respectively. Ten patients (33.3%) had low IOP. An opening pressure of ≤18 mm Hg predicted low postoperative IOP with a sensitivity (10/10) of 100% (95% CI, 69.2-100) and a specificity (13/20) of 65.0% (95% CI, 40.8-84.6). CONCLUSIONS: AGVs have a high variability of opening, closing, and re-opening pressures. An opening pressure of ≤18 mm Hg, a closing pressure of ≤10 mm Hg, or a re-opening pressure of ≤11 mm Hg identified all patients with low postoperative IOP.

Effects and adverse events after CXL for keratoconus are independent of age: a 1-year follow-up study.

PURPOSE: To compare the effect, failure rate and the risks of corneal cross-linking (CXL) in keratoconus patients aged ≥35 years to patients <35 years. METHODS: In 141 eyes of 116 keratoconus patients we compared the changes in best phoropter-corrected visual acuity (BCVA) and maximum keratometry values (Kmax) before and 12 months after CLX in patients aged ≥35 years (n=34, 38 eyes) to the cohort of patients below 35 years of age. RESULTS: Overall, CXL significantly improved BCVA from 0.487 logMAR (95% confidence interval (CI) 0.426-0.548) by -0.197 logMAR (95% CI -0.243 to -0.150; P<0.001) and reduced Kmax from 48.96 diopter (Dpt) by -1.33 Dpt (95% CI -1.85 to -0.81: P<0.001). Age ≥35 years had no effect on the changes of BCVA (-0.02 (95% CI -0.13 to 0.09); P=0.757) or Kmax (0.58 (95%CI -0.51 to 1.68); P=0.294) as compared with younger patients. In 54 patients (55 eyes, 38.5%) aged <35 years and in 18 patients (18 eyes, 47.4%) aged ≥35 years, BCVA increased by ≥2 Snellen lines. Failure (increase in Kmax ≥1 Dpt) was observed in 17 eyes (16.5%) of patients aged <35 years and in 3 eyes (7.9%) of patients aged ≥35 years during the 12-month follow-up period. Adverse outcomes (loss of ≥2 Snellen lines) occurred in 4 (3.9%) eyes of patients aged <35 years and 1 (2.6%) eye of a patient aged ≥35 years. CONCLUSION: Effects and adverse events of CXL treatment do not seem to differ between subjects younger or older than 35 years.

Prospective, randomized-controlled trial comparing postoperative pain after plug and patch open repair with totally extraperitoneal inguinal hernia repair.

PURPOSE: The aim of this study was to compare postoperative pain between the open tension-free plug and patch (PP) technique and the totally extraperitoneal patch (TEP) hernioplasty. METHODS: One hundred and fifty-four male patients with unilateral inguinal hernia were randomized to undergo PP and TEP from 2005 to 2009. Pain assessment was conducted using the numerical rating scale (NRS) and the McGill Pain Questionnaire preoperatively, 6, 12 and 24 months postoperatively. All patients received the same analgesic regimen and documented pain in a NRS-based 4-week diary. RESULTS: Of the 154 patients 77 underwent TEP and 77 PP. Median follow-up was 3.8 years. One recurrent hernia was observed in the TEP and two in the PP group (p = 0.56). Median preoperative NRS scores were 2 and 2, 0.3 and 0.4 at 6 months, 0.1 and 0.3 at 12 months, 0.2 and 0.1 at 24 months postoperatively in the PP and TEP groups, respectively (p > 0.05). Data from the 4-week pain diaries revealed significant differences in pain intensity between the two different techniques from the second postoperative week (p < 0.05). Patients in the PP group required more additional analgesics on day four and five postoperatively (p = 0.037 and 0.015, respectively). CONCLUSIONS: Our data favor the TEP technique concerning postoperative pain as primary endpoint between tension-free PP and TEP hernia repair.

Prevalence of diabetes mellitus secondary to pancreatic diseases (type 3c).

BACKGROUND: Diabetes mellitus secondary to pancreatic diseases is a condition seldom thought of in clinical practice. Yet, a high percentage of exocrine pancreatic insufficiency has been reported for the general population and especially for diabetic subjects. Thus, we investigated the prevalence of diabetes mellitus due to pancreatic diseases. METHODS: In this study, we investigated 1868 patients diagnosed with diabetes mellitus who had been admitted to our hospital during the last 24 months. Patient data were diligently studied, and patients were reclassified according to the diabetes classification as proposed by the American Diabetes Association. RESULTS: Among 1868 subjects, 172 patients could be classified as type 3c diabetes mellitus (9.2%). Among these were 135 diagnosed with chronic pancreatitis (78.5%), 12 with hereditary haemochromatosis, 14 with pancreatic cancer and 7 with cystic fibrosis. Thus, diabetes mellitus due to chronic pancreatitis occurred in this collective in 7.2% of all diabetic subjects. Misclassification of these patients was very common. Only 51.2% (88/172) were initially classified correctly. Most type 3 diabetes patients were initially misclassified as type 2 diabetes (69/84). CONCLUSIONS: Diabetes mellitus secondary to pancreatic diseases (especially chronic pancreatitis) seems more common than generally believed with a prevalence of 9.2% among the subjects studied here. Because the awareness of this diabetes type is poor, misclassification is quite frequent. A common problem seems to be the differentiation between type 2 and type 3. Yet, the right classification of diabetes mellitus is important, because there are special therapeutic options and problems in patients with diabetes secondary to pancreatic diseases.

A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer.

BACKGROUND: This trial was designed to prove superiority of irinotecan over etoposide combined with carboplatin in extensive-disease small-cell lung cancer. PATIENTS AND METHODS: Patients were randomly assigned to receive carboplatin area under the curve 5 mg x min/ml either in combination with irinotecan 50 mg/m2 on days 1, 8, and 15 (IP) or etoposide 140 mg/m2 on days 1-3 (EP). Primary end point was progression-free survival (PFS) at 6 months. Secondary end points were overall survival (OS), response rate, and toxicity. RESULTS: Of 226 patients, 216 were eligible. Median PFS was 6.0 months [95% confidence interval (CI) 5.0-7.0] in the IP arm and 6.0 months (95% CI 5.2-6.8) in EP arm (P = 0.07). Median survival was 10.0 months (95% CI 8.4-11.6) and 9.0 months (95% CI 7.6-10.4) in the IP and EP arm (P = 0.06), respectively. Hazard ratios for disease progression and OS were 1.29 (95% CI 0.96-1.73, P = 0.095) and 1.34 (95% CI 0.97-1.85, P = 0.072), respectively. No difference in response rates was observed. Grade 3 and 4 hematologic toxicity favored the IP arm, whereas diarrhea was significantly more frequent in the IP arm. CONCLUSION: This trial failed to show superiority of irinotecan over etoposide in combination with carboplatin.

Effectiveness of switching between TNF inhibitors in ankylosing spondylitis: data from the NOR-DMARD register.

OBJECTIVE: To assess the effectiveness of switching to a second tumour necrosis factor inhibitor (TNFi) in patients with ankylosing spondylitis (AS). METHODS: Data were extracted from an ongoing longitudinal observational multicentre study in Norway. This study included anti-TNF naïve patients with AS starting treatment with a TNFi as well as treatment with a second TNFi in these same patients. Effectiveness data and 2-year drug survival were compared between switchers and non-switchers and within switchers (first and second TNFi). RESULTS: 514 anti-TNF naïve patients with AS were included; 77 patients switched to a second TNFi while 437 patients did not switch. The percentages of non-switchers using etanercept, infliximab or adalimumab were 53%, 32% and 15%, and the percentages of first and second TNFi in the switchers were 42%, 53% and 5% and 40%, 23% and 36%, respectively. The reason for switching was insufficient response (IR) in 30, adverse events (AEs) in 44 and not reported in 3 patients. Baseline disease activity was similar between the groups. Three-month BASDAI 50 and ASAS 40 responses were achieved by 49% and 38% of non-switchers, by 25% and 30% of switchers after the first TNFi and by 28% and 31% after the second TNFi. The 3-month disease activity level was higher for switchers on the second TNFi than for non-switchers. Drug withdrawal rate was higher during the second TNFi among switchers than for non-switchers (p=0.001). No difference was found in the effectiveness of the second TNFi between switchers due to IR and AE. CONCLUSION: This study confirms that switching to a second TNFi can be effective in AS and can be as useful as in rheumatoid arthritis, although overall effectiveness seems to be somewhat lower than in non-switchers.

Long-term stability of self-assembled monolayers on 316L stainless steel.

316L stainless steel (316L SS) has been extensively used for making orthopedic, dental and cardiovascular implants. The use of phosphonic acid self-assembled monolayers (SAMs) on 316L SS has been previously explored for potential biomedical applications. In this study, we have investigated the long-term stability of methyl (-CH(3)) and carboxylic acid (-COOH)-terminated phosphonic acid SAMs on 316L under physiological conditions. The stability of SAMs on mechanically polished and electropolished 316L SS was also investigated as a part of this study. Well-ordered and uniform -CH(3)- and -COOH-terminated SAMs were coated on mechanically polished and electropolished 316L SS surfaces. The long-term stability of SAMs on 316L SS was investigated for up to 28 days in Tris-buffered saline (TBS) at 37 degrees C using x-ray photoelectron spectroscopy, atomic force microscopy and contact angle goniometry. A significant amount of phosphonic acid molecules was desorbed from the 316L SS surfaces within 1 to 7 days of TBS immersion followed by a slow desorption of molecules over the remaining days. The -COOH-terminated SAM was found to be more stable than the -CH(3)-terminated SAM on both mechanically and electropolished surfaces. No significant differences in the desorption behavior of SAMs were observed between mechanically and electropolished 316L SS surfaces.

Alemtuzumab: key for minimization of maintenance immunosuppression in reconstructive transplantation?

Minimization of immunosuppression has become the key effort in solid organ transplantation. Alemtuzumab, the humanized CD-52 monoclonal antibody, is an effective depleting agent increasingly used in transplantation trials. In this article, we summarize the current experience with alemtuzumab use in hand transplantation and discuss its role in current and future approaches toward minimization of maintenance immunosuppression in reconstructive transplantation.

Antibody-based immunosuppressive agents for corneal transplantation.

The progress in antibody engineering over the last 20 years has created the tools for the development of novel antibody-based drugs and constructs, such as small antibody fragments, suitable for topical administration. In rheumatology, oncology, transplantation medicine and ophthalmology, therapeutic antibody constructs, and antibody fragments have been responsible for the clinical progress seen over the last decade. Although antibody-based therapies have become a well-established immunosuppressive option in solid organ transplantation, there are only very few reports with regard to corneal transplantation. The following review explains some of the important aspects of engineered antibody-based therapeutic agents and summarises the current use of such immunosuppressive therapies in transplantation medicine and corneal transplantation.

Comparison of work disability and health-related quality of life between males and females with rheumatoid arthritis below the age of 45 years.

OBJECTIVES: To compare work disability (WD) and health status between males and females with rheumatoid arthritis (RA) in the age group 18-45 years, and to compare health status between patients with and without WD within each gender, and finally to identify factors independently associated with WD in this age group. METHODS: A cross-sectional study of RA patients at the time starting with disease-modifying antirheumatic drug (DMARD) therapy and/or biological treatment. Patients receiving a permanent, national WD pension corresponding to >or= 50% were defined as work disabled. We examined gender differences with regard to disease characteristics, health status and WD. The Mann-Whitney U-test and Pearson's chi(2)-test were applied for group comparisons. Multiple logistic regression analyses with adjustments for duration of education, disease duration, age, erosive disease, disability score [using the Modified Health Assessment Questionnaire (MHAQ)], Disease Activity Score-28 (DAS-28), the Short Form Health Survey (SF-36) mental health score and gender were used to identify variables associated with WD. RESULTS: Out of 474 (372 females) patients, the number (%) of work-disabled females/males was 91 (24.7)/8 (8.1) (p<0.001). WD was associated with worse health status in both genders. The odds ratio (95% confidence interval) [OR (95% CI)] for WD in females vs. males was 4.84 (1.85-12.65) in the multivariate analyses. Other factors independently associated with WD were worse mental health, disease duration and low level of education. CONCLUSION: Females with RA had a fourfold increased risk of WD compared to men. Low level of education, disease duration and worse mental health were also independently associated with WD.

Work disability and health-related quality of life in males and females with psoriatic arthritis.

OBJECTIVES: To compare health status, demographic variables and work disability (WD) between males and females with psoriatic arthritis (PsA) in the 18-45 age group, and further to compare health status between those with and without WD for each gender and to identify variables associated with WD. METHODS: A cross-sectional study was carried out of patients with PsA with peripheral arthritis at the time at which they started disease-modifying antirheumatic drug therapy (DMARD) and/or biological treatment. Patients receiving a permanent national WD pension corresponding to >or=50% were defined as work disabled. Gender differences were examined with regard to health status, demographic variables and WD. Mann-Whitney U test and Pearson chi(2) were applied for group comparisons between males and females and work disabled versus not work disabled for each gender. Multiple logistic regression analyses with adjustments for duration of education, disease duration, age, erosive disease, disability score (Modified Health Assessment Questionnaire; MHAQ), the short form-36 (SF-36) mental health score, and gender were used to identify variables associated with WD. RESULTS: Out of 271 (102 females) patients, the number (%) of work-disabled females/males was 33 (32.7%)/29 (17.4%) (p = 0.004). Work-disabled patients had generally worse health status than non-work-disabled patients, and these differences were generally more pronounced in males than in females. In the multiple logistic regression model, low educational level, increasing disability score (MHAQ), presence of erosive disease, female gender and disease duration were independently associated with WD. CONCLUSIONS: WD in patients with PsA below 45 years of age was independently associated with educational level, disability score, erosive disease, female gender and disease duration.

[Enzootic nasal adenocarcinoma in a dairy sheep flock]. / Enzootische nasale Adenokarzinome in einem Milchschafbestand.

In a herd of dairy sheep several losses occurred due to a respiratory syndrome in combination with progressive wasting. Clinical and pathomorphological diagnostics of 3 sheep revealed the presence of cancerous masses in the nasal cavities. These neoplasms were identified as adenocarcinomas originating from the nasal mucosa. Etiologically, they were attributed to JRSV (Jaagsiekte Sheep Retrovirus) by detection of capsid protein 24 in western blot. The significance of the disease in Switzerland is discussed, also in the context of lung adenomatosis.

[Visual field defects after cerebral lesions from the patient's perspective: health- and vision-related quality of life assessed by SF-36 and NEI-VFQ]. / Zerebral bedingte Gesichtsfelddefekte aus Patientensicht : Gesundheitsbezogene und sehspezifische Lebensqualität unter Verwendung des SF-36 und des NEI-VFQ.

BACKGROUND: In patients with visual field defects, measurement of health-related quality of life (hQoL) and vision-related quality of life (vQoL) is an important adjunct to clinical measures such as perimetry. The purpose of this study was to describe hQoL and vQoL of patients with visual field defects after cerebral lesions such as infarction, traumatic brain injury, and tumor. METHODS: The National Eye Institute -- Visual Function Questionnaire (NEI-VFQ) for vQoL and the SF-36 Health Survey for hQoL were administered to 24 patients about 2 years after occurrence of the visual field defect. Visual fields were measured by standard perimetry and a near-threshold campimetric method. Visual acuity was measured by the Landolt-Ring-Test. RESULTS: The NEI-VFQ scores -- but not SF-36 scores -- were not only lower than those of a disease-free group but also lower than those of patients with visual impairments not caused by cerebral damage. Rank correlations between the size of the visual field defect and NEI-VFQ subscales were significantly high or modest. With SF-36 scores these correlations were generally low and moderate at best. CONCLUSION: The NEI-VFQ is a valuable measure of self-reported visual impairment in patients with visual field defects after cerebral lesions. The measurement of unspecific hQoL is not sufficient to reflect the problems of patients with visual field defects.

Pollakisuria in a dwarf goat due to pathologic enlargement of the uterus.

Pollakisuria in adult goats can be caused by diseases of the urinary tract and by distension of parts of the genital tract leading to irritation of the bladder. Hydrometra is the most common cause of uterine distension in goats and usually can be resolved by prostaglandin injections. But other pathologies of the uterus can generate a similar syndrome. A dwarf goat was presented at the clinic with a history of chronic pollakisuria and tenesm. An initial ultrasonographic examination of the abdomen led to the suspicion of hydrometra, but treatment with injections of prostaglandin were not successful. Blood samples revealed low progesterone and high oestrogen values. A laparotomy was performed and an enlarged uterus with 1.5 L of mucous content and cystic ovaries were found and partially removed. A single solid leiomyoma was diagnosed histologically in the uterine wall. Two months later the goat's condition had deteriorated and therefore she was euthanized. Necropsy and pathohistological examination revealed the presence of a metastasized adenocarcinoma of the uterus. In this case, the pollakisuria provoqued by distension of the uterus was not caused by hydrometra, but by neoplasia. The syndrome and the pathogenesis of the adenocarcinoma in consideration of the hormonal status of the patient is discussed.

Lentivirus-mediated gene transfer to the rat, ovine and human cornea.

Gene therapy of the cornea shows promise for modulating corneal transplant rejection but the most appropriate vector for gene transfer has yet to be determined. We investigated a lentiviral vector (LV) for its ability to transduce corneal endothelium. A lentivector expressing enhanced yellow fluorescent protein (eYFP) under the control of the Simian virus type 40 early promoter (LV-SV40-eYFP) transduced 80-90% of rat, ovine and human corneal endothelial cells as detected by fluorescence microscopy. The kinetics of gene expression varied among species, with ovine corneal endothelium showing a relative delay in detectable reporter gene expression compared with the rat or human corneal endothelium. Vectors containing the myeloproliferative sarcoma virus promoter or the phosphoglycerate kinase promoter were not significantly more effective than LV-SV40-eYFP. The stability of eYFP expression in rat and ovine corneas following ex vivo transduction of the donor cornea was assessed following orthotopic corneal transplantation. Following transduction ex vivo, eYFP expression was maintained in corneal endothelial cells for at least 28 days after corneal transplantation in the sheep and >60 days in the rat. Thus, rat, ovine and human corneal endothelial cells were efficiently transduced by the LV, and gene expression appeared stable over weeks in vivo.

The comparative effectiveness of anti-TNF therapy and methotrexate in patients with psoriatic arthritis: 6 month results from a longitudinal, observational, multicentre study.

OBJECTIVES: To compare the response to treatment with tumour necrosis factor (TNF) inhibitors and methotrexate (MTX) monotherapy in patients with psoriatic arthritis (PsA) within a real-life clinical setting. METHODS: We analysed data from an ongoing longitudinal, observational multicentre study in Norway. Our data comprised 526 cases of patients with PsA who received either anti-TNF treatment (n = 146) or MTX monotherapy (n = 380) and were followed for at least 6 months with measures of disease activity, health status and utility scores. A propensity score was computed to adjust for channelling bias. The changes in measures of disease activity and health-related quality of life from baseline to 3- and 6-month follow-up were compared between the groups with adjustments for the baseline value of the dependent variable and the propensity score (analyses of covariance (ANCOVA)). RESULTS: The groups were significantly different at baseline with respect to demographic and disease activity measures. The variables included in the propensity score were age, sex, number of previous disease modifying anti-rheumatic drugs (DMARDs), presence of erosive disease, treatment centre and investigator's global assessment. The adjusted changes at 6 months were significantly larger in the anti-TNF group for ESR, DAS-28, M-HAQ, patient's assessments of pain, fatigue and global disease activity on a visual analogue scale (VAS) and 4 out of 8 SF-36 dimensions. CONCLUSIONS: Clinical improvement was superior with TNF inhibitors compared to MTX monotherapy in patients with PsA, when assessed in this setting of daily clinical practice.