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1.

Background

Psoriasis is a chronic inflammatory disease of the skin. Vascular endothelial growth factor (VEGF), a pro-angiogenic factor, is involved in the pathogenesis of psoriasis. Being highly polymorphic, several SNPs of VEGF have been reported to be associated with increased risk of psoriasis.

Objectives

We determined the association of VEGF gene polymorphisms with risk of psoriasis in South Indian Tamils.

Methods

300 cases of psoriasis and 300 controls were recruited in this case-control study. Genotyping of SNPs of VEGF gene was done using Taqman 5′ allele discrimination assay. Estimation of VEGF levels in plasma was done by ELISA.

Results

VEGF (rs2010963) polymorphism and the CTC haplotype were found to confer an increased risk of psoriasis. However, two other VEGF SNPs, rs833061, and rs699947, showed no association with psoriasis susceptibility. VEGF levels were higher in patients with psoriasis, as compared with controls and significantly correlated with disease severity.

Conclusions

Our results indicate that VEGF (rs2010963) polymorphism and CTC haplotype of the VEGF SNPs (rs699947, rs833061, and rs2010963) confer an increased risk of psoriasis in the South Indian Tamil population. Plasma VEGF levels are higher in patients with psoriasis, as compared with controls and are significantly correlated with disease severity.  相似文献   

2.

Background

Patellofemoral instability may lead to osteoarthritis, anterior knee pain, and patellar luxation. The purpose of this study was to conduct an exploratory investigation into the difference of patellar kinematics of healthy knees during extension/flexion cycles in neutral, varus and valgus alignment.

Methods

The three-dimensional patellar kinematics of 10 lower extremities of whole body cadavers were examined during passive motion, in neutral position, and under valgus and varus stress. Kinematics was recorded by means of an optical computer navigation system.

Results

The study samples did not significantly differ with regard to mediolateral patellar shift and epicondylar distance. Varus stress led to significantly higher external rotation than valgus stress (P = 0.04) and to a significantly higher lateral patellar tilt than neutral position (P = 0.016) and valgus stress (P = 0.016). No difference was found between valgus stress and neutral position.

Conclusion

Analysis of tibiofemoral alignment alone is insufficient for predicting patellar kinematics.  相似文献   

3.

Background

Tunnel widening after anterior cruciate ligament reconstruction (ACLR) is influenced by the surgical and fixation techniques used. Computed tomography (CT) is the most accurate image modality for assessing tunnel widening, but magnetic resonance imaging (MRI) might also be reliable for tunnel volume measurements. In the present study tunnel widening after ACLR using biodegradable interference screw fixation was compared with all-inside ACLR using button fixation, with tunnel volume changes being measured on CT and MRI scans.

Study design

Randomized controlled trial; Level of evidence, 2.

Methods

Thirty-three patients were randomly assigned to hamstring ACLR using a biodegradable interference screw or all-inside cortical button fixation. CT and MRI scanning were done at the time of surgery and six months after. Tunnel volume changes were calculated and compared.

Results

On CT, femoral tunnel volumes changed from the postoperative state (100%) to 119.8% with screw fixation and 143.2% with button fixation (P = 0.023). The changes in tibial tunnel volumes were not significant (113.9% vs. 117.7%). The changes in bone tunnel volume measured on MRI were comparable with those on CT only for tunnels with interference screws. Tibial tunnels with button fixation were significantly underestimated on MRI scanning (P = 0.018).

Conclusions

All-inside ACLR using cortical button fixation results in increased femoral tunnel widening in comparison with ACLR with biodegradable interference screw fixation. MRI represents a reliable imaging modality for future studies investigating tunnel widening with interference screw fixation.  相似文献   

4.
5.

Objective

To determine the association of antibodies against angiotensin II type 1 receptor (AT1R Ab) and histopathologic changes seen in patients with kidney allograft rejection and negative donor specific HLA antibodies (DSA).

Methods

Stored sera from 27 patients who had biopsy-proven rejection in the absence of DSA were tested for AT1R Ab. Biopsy slides of all patients were re-examined and classified according to Banff 2013 criteria. Histopathologic changes were compared between AT1R positive and negative patients.

Results

75% of patients with positive pre-transplant AT1R Ab had antibody mediated rejection (AMR) compared to 37% of AT1R Ab-negative patients. A trend towards increased interstitial inflammation was observed in the AT1R Ab positive group (p = 0.08). More patients in the AT1R Ab positive group had microcirculation inflammation (88% vs 58% with glomerulitis scores ≥1; 75% vs 58% with peritubular capillaritis scores ≥1).

Conclusion

In kidney transplant recipients with rejection and no DSA, a higher incidence of AMR and worse inflammation scores are observed in the presence of positive pre-transplant AT1R antibodies.  相似文献   

6.

Background

A simplified protocol for HLA-typing -by NGS, developed for use with the Illumina MiSeq, was performed by technologists with varying NGS experience to assess accuracy and reproducibility.

Methods

Technologists from six laboratories typed the same 16 samples at HLA-A, B, C, DRB1, and DQB1. The protocol includes long range PCR, library preparation, and paired-end 250 bp sequencing. Two indexing strategies were employed: locus-specific indexing whereby each locus was tagged uniquely and sample-specific indexing whereby all 5 loci for a sample were pooled prior to library preparation. Sequence analysis was performed with two software packages, Target HLA (Omixon) and NGSengine (GenDx).

Results

The average number of sequence reads per library was 387,813; however, analysis was limited to 40,000 reads for locus-indexed libraries and 200,000 reads for sample-indexed libraries resulting in an average depth of coverage of 1444 reads per locus. Sufficient reads for genotype analysis were obtained for 98.4% of libraries. Genotype accuracy was >97% in pooled amplicons and >99% in individual amplicons by both software analysis. Inter-laboratory reproducibility was 99.7% and only cause of discordance was cross-contamination of a single amplicon.

Conclusions

This NGS HLA-typing protocol is simple, reproducible, scalable, highly accurate and amenable to clinical testing.  相似文献   

7.

Background

There are unanswered questions about knee–ankle alignment after total knee arthroplasty (TKA) for varus and valgus osteoarthritis (OA) of the knee. The aim of this retrospective study was to assess knee–ankle alignment after TKA.

Methods

The study consisted of 149 patients who had undergone TKA due to varus and valgus knee OA. The alignment and angles in the selected knees and ankles were measured on full-length standing anteroposterior radiographs, both pre-operatively and post-operatively. The paired t-test and Pearson's correlation tests were used for statistical analysis.

Results

The results showed that ankle alignment correlated with knee alignment both pre-operatively and postoperatively (P < 0.05). The pre-operative malalignment of the knee was corrected (P < 0.05), and the ankle tilt angle was accordingly improved in the operative side after TKA (P < 0.05). In addition, TKA had little effect on knee–ankle alignment on the non-operative side (P > 0.05).

Conclusion

These findings indicated that routine TKA could correct the varus or valgus deformity of a knee, and improve the tilt of the ankle. Ankle alignment correlated with knee alignment both pre-operatively and postoperatively. Both pre-operative knee and ankle malalignment can be simultaneously corrected following TKA.

Level of evidence

Level III.  相似文献   

8.

Background

Psoriasis is known to be associated with an up-regulation of T-helper (Th)-1 & Th-17 cytokines and a relative down-regulation of Th-2 and T-regulatory (T-reg) cytokines. Certain allelic variants of these cytokine genes may alter Th1/Th17 and Th2/T-reg balance and may be associated with the risk of psoriasis. Hence we aimed to determine the association of IL-4 (rs2243250), IL-10 (rs1800871 and rs1800896) and FOXP3 (rs3761548) gene polymorphisms with risk of psoriasis in South Indian Tamils.

Methods

A total of 360 cases of psoriasis and 360 healthy controls were recruited. The polymorphism in IL-4 (rs2243250) & IL-10 (rs1800871) were typed by ARMS-PCR and IL-10 (rs1800896) & FOXP3 (rs3761548) were typed by TaqMan 5′allele discrimination assay.

Results

We observed that IL-4 (rs2243250) had a reduced risk of psoriasis, while the IL-10 (rs1800871) conferred an increased susceptibility to psoriasis, as compared with controls. However, IL-10 (rs1800896) and FOXP3 (rs3761548) gene polymorphisms were not associated with psoriasis risk. The plasma IL-4 levels was not different between the cases and controls, however the heterozygous CT genotype demonstrated significant high IL-4 levels. Plasma IL-10 levels were significantly increased in cases compared to controls, however none of the genotypes were associated with the plasma IL-10 levels.

Conclusion

Our results suggest that IL-4 (rs2243250) polymorphism is protective against psoriasis, while IL-10 (rs1800871) polymorphism confers increased risk of psoriasis in South Indian Tamils. Detection of these genetic variants as predictive risk factors may lead to the selection of patient-tailored therapy to maximize the effectiveness of therapy.  相似文献   

9.

Background

Detection of circulating tumor DNA (ctDNA) in blood of cancer patients is regarded as an important step towards personalized medicine and treatment monitoring. In the present study, we investigated the clinical applicability of ctDNA as liquid biopsy in renal cancer.

Methods

ctDNA in serum and plasma samples derived from ccRCC and colon cancer patients as well as ctDNA isolated from RCC xenografts with known VHL mutation status was investigated using next generation sequencing (NGS). Additionally, a Taqman mutation specific assay was used for specific VHL mutation detection in blood.

Results

In our study, we successfully identified KRAS mutation in colon cancer patients. We also confirmed the presence of specific VHL mutations in ctDNA derived from RCC xenografts indicating the capability of renal tumors to release DNA into the blood circulation. However, we could not detect any VHL mutation in plasma or serum samples derived from nine ccRCC patients. To increase the sensitivity, a VHL mutation specific Taqman assay was tested. With this approach, the pVHL mutation p.Val130Leu in exon 2 in one patient was successfully detected.

Conclusion

These data suggest a reduced tumor DNA shedding and an increased clearance of the tumor DNA from the circulation in renal cancer patients independently of tumor size, metastases, and necrosis. This implies that highly sensitive detection methods for mutation calling and prior knowledge of the mutation are required for liquid biopsies in ccRCC.  相似文献   

10.

Background

Dislocation of the patella can occur around its vertical as well as horizontal axis. However, near 180 degree rotation of the patella around its vertical axis within the intercondylar notch without its complete dislocation has never been previously reported to the best of our knowledge. We report one such neglected case along with its management.

Methods

The patient underwent open reduction and de-rotation of patella with repair of the medial and lateral patellar retinacula. The orientation of the patellar tendon intra-operatively was used as a guide for the reduction manoeuvre required.

Results

The patient had a good functional result at more than one year of follow-up.

Conclusions

A skyline view of the knee in symptomatic patients with normal AP and lateral radiographs of the knee can be useful in diagnosing a rare intra-articular dislocation of the patella around its vertical axis. Neglected cases of such injuries can be easily treated with open reduction with the orientation of the patellar tendon guiding the manoeuvre to de-rotate the patella. Careful repair of lateral and medial retinacula in such cases is important in preventing future patellar instability.  相似文献   

11.

Background

Patellar tendon rupture is rare in the general population. Typically, failure occurs proximally or at the mid-substance. Distal avulsion from the tibial tubercle in adults is rare and not well described in the orthopedic literature.

Methods

We present the largest series of patients with distal patellar tendon injury with associated multi-ligamentous disruption of the knee. A series of six patients with distal patellar tendon avulsion were identified at a single institution. The cases were reviewed and are presented.

Results

Each case of distal patellar tendon rupture was associated with high-energy trauma to the knee. There was multi-ligamentous disruption in all cases, associated tibial plateau fracture in one case, and a compartment syndrome diagnosed in another. We propose that distal patellar tendon avulsion is a distinct pathology of the extensor mechanism in healthy adults. When present, it should prompt clinicians to assess patients for occult knee dislocation, monitor their neurovascular status, and obtain an MRI to evaluate for associated multi-ligamentous injury.

Conclusion

We propose a modification to the Schenk classification to include extensor mechanism injury to help guide steps of operative intervention.  相似文献   

12.

Background

Aseptic loosening is a common failure mode in cemented unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA). This led to the development of cementless designs but the historical outcomes were poor. Recent developments in cementless designs have improved outcomes, but the current status is unknown. Therefore, a systematic review was performed to assess recent outcomes of cementless knee arthroplasty.

Methods

A search was performed using PubMed, Embase and Cochrane systems and national registries for studies reporting outcomes since 2005. Fifty-two cohort studies and four registries reported survivorship, failure modes or functional outcomes of cementless UKA and TKA.

Results

Nine level I studies, six level II studies, three level III studies, 34 level IV studies and four registries were included. Three hundred eighteen failures in 10,309 cementless TKA procedures and 62 failures in 2218 cementless UKA procedures resulted in extrapolated five-year, 10-year and 15-year survivorship of cementless TKAs of 97.7%, 95.4% and 93.0%, respectively, and cementless UKA of 96.4%, 92.9% and 89.3%, respectively. Aseptic loosening was more common in cementless TKA (25%) when compared to UKA (13%). Functional outcomes of cementless TKA and UKA were excellent with 84.3% and 84.5% of the maximum possible scores, respectively.

Conclusions

This systematic review showed that good to excellent extrapolated survivorship and functional outcomes are seen following modern cementless UKA and TKA, with a low incidence of aseptic loosening following cementless UKA.

Level of evidence

Level IV.  相似文献   

13.

Background

To evaluate, by way of intraoperative tissue culture and pathological study, the pre-operative presence of micro-organisms in knee joints of patients with rheumatoid arthritis (RA) who need total knee arthroplasty (TKA).

Methods

From November 2012 to January 2014, 47 patients with RA (53 knees) who needed TKA were included in this study. Patients received routine pre-operative examination and joint fluid routine and culture. Each RA patient was match-paired with one osteoarthritis (OA) patient. During arthrotomy, synovial tissue was reserved and portioned for culture, frozen section, and routine pathologic examination.

Results

Pre-operative infection in all knees was ruled out. There were 12 RA patients (13 knees) with positive culture results: two Escherichia coli, two Staphylococcus epidermidis, two Staphylococcus aureus, one Proteus mirabilis, one Staphylococcus warneri, one Enterococcus faecalis, one Acinetobacter baumannii, one Candida albicans, one Ochrobactrum anthropi, and one Candida glabrata. Except for microabscess found in one RA patient, all pathological sections showed mild chronic inflammation but no infection. All patients with positive culture results were administered sensitive antibiotics for six weeks after surgery. Two patients had deep infection: one had a fused knee after a failed debridement, and the second was previously treated with an amphotericin injection.

Conclusion

Pre-operative presence of micro-organism in knee joints of RA patients is common (24.5%). This finding of a high incidence of pre-operative presence of micro-organism in joints of RA patients before arthroplasty may suggest a role of micro-organism in the pathogenesis of prosthetic joint infection (PJI). Intraoperative synovial tissue culture is valuable for diagnosis of this condition and in instruction of antibacterial treatment.  相似文献   

14.

Background

The anterior part of the distal femur in trochlear dysplasia has been well investigated; however, to date, posterior morphological characteristics have not been well studied. This study aimed to evaluate whether the posterior femoral condyle in patients with trochlear dysplasia differs from those without trochlear dysplasia.

Methods

Computed tomography scans of 75 knees with trochlear dysplasia and 55 knees with normal anatomy of the patellofemoral joint were analyzed retrospectively. Three observers assessed the width, length, and height of the posterior condyle between the two groups. The intra-class correlation coefficient was used to evaluate inter-observer reliability. The independent Student's t-test was used to assess the statistical significance of the qualitative variables.

Results

There was excellent inter-observer reliability (intra-class correlation coefficient 0.91–0.99) for all of the quantitative measurements. There were significant differences between trochlear dysplastic and normal knees. The trochlear dysplasia group had a larger medial posterior condyle and smaller lateral posterior condyle than the control group. Furthermore, proportion of the posterior condyle in the distal femur markedly differed between the two groups: in the trochlear dysplasia group, the medial posterior condyle accounted for a bigger proportion, while the lateral posterior condyle accounted for a smaller proportion.

Conclusion

Patients with trochlear dysplasia have different posterior femoral condyles compared with those without trochlear dysplasia. Patients with this condition have bigger medial posterior condyles and smaller lateral posterior condyles. A greater amount of attention needs to be paid to this abnormality.  相似文献   

15.

Objectives

To assess genetic association between single nucleotide polymorphisms (SNPs) in genes encoding T-helper cytokines and Takayasu Arteritis (TA) susceptibility in Asian Indian population.

Methods

In Phase-1, the genomic DNA of 120 TA patients and 119 healthy controls were genotyped for SNPs rs1800795 (interleukin (IL)-6), rs763780 (IL-17F), rs1800871, rs1800872, rs1800896 (IL-10) and rs1800468, rs1800469, rs1800470 (transforming growth factor-β). Allele frequencies between cases and controls were compared using chi-squared test and also reassessed empirically (pe) by 10,000 permutations. In Phase-2, additional 98 TA patients and 101 controls were genotyped for replicating the significant associations noted in Phase-1 of the study.

Results

All 8 SNPs in Phase 1 were in Hardy-Weinberg proportions. The G allele at rs763780 (IL-17F) was significantly associated with TA (p = 0.014). We also found that rs1800795 (IL-6) was associated with tuberculosis (p = 0.001) under a dominant model. In Phase-2 replication part of the study, the rs763780 showed a trend towards association with TA (p = 0.08), and the magnitude and direction of the odds ratio (OR) also were consistent with results of Phase-1. In the combined analysis, protective association of the G allele of rs763780 with TA was again significant [OR (95% CI) = 0.44 (0.25–0.77); p = 0.0029]. The G allele was also significantly associated (p < 0.05) with underlying tuberculosis (TB) and occurrence of syncope in TA.

Conclusion

G allele of rs763780 in IL-17F gene was protectively associated against susceptibility to TA. GG genotypes of rs1800795 in IL-6 was also associated with occurrence of tuberculosis in our patients with TA.  相似文献   

16.

Objective

Pharmacists play a relevant role in the real-life management of asthma because they are a first-line referral for patients. In fact, the role of pharmacies has been underlined and evidenced also in guidelines. Nonetheless, the true effect of pharmacy-based management of asthma has been assessed in only a few studies. We review the available literature on asthma management in a territorial pharmacy setting.

Data Sources

The literature was searched for the keywords pharmacy, bronchial asthma, control, and management.

Study Selections

The available studies were subdivided into observational and interventional and described.

Results

Seven observational studies and 14 interventional trials were found, involving approximately 20,000 individuals. Most of those studies were performed in Europe and Australia. A high proportion of patients had poorly controlled asthma in the observational studies. The active involvement of pharmacists, in the interventional trials, consistently led to an improvement of the quality of life, a better inhalation technique, and a reduction of exacerbations.

Conclusion

The literature analysis confirms the relevance of the role of pharmacists in the real-life management of bronchial asthma and underlines the need for a more specific training for those health care professionals.  相似文献   

17.

Aims

To investigate the extent of CCR5 polymorphism in the healthy Saudi population.

Method

A total of 321 healthy Saudi individuals were sequenced using the ion Ampliseq? Exome kit (Life Technologies, USA) on genomic DNA following manufacturer’s protocol. Whole Exome Sequencing (WES) reads were aligned to the human reference genome (hg19 build) with Torrent Suite Software (v5.0.2) and the variants were called using the Torrent Variant Caller plugin (v5.0) and imported into Ion Reporter Server (v5.0) for the annotation. CCR5 coding exons variants were filtered and checked against the NHLBI GO Exome Sequencing Project (NHLBI), NCBI Reference dbSNPs database, 1000 genomes and Exome Aggregation Consortium datasets (ExAC).

Results

A total of 475 variants were identified. Table 1 shows polymorphisms/mutations detected within exons that introduced an amino acid change, deletion or copy number variants (CNV). Three mutations are predicted to influence CCR5 function, including the 32 bp deletion (Rs333). Four polymorphisms were detected, plus two CNV.

Conclusions

This is the first report on sequencing the full CCR5 gene using NGS in the Saudi population. Here we demonstrate seven polymorphisms/mutations that were reported before. All were detected within very low frequency including the delta 32 mutation. However, we report for the first time copy number variants at two CCR5 gene locations; 45072265 and 38591712.  相似文献   

18.

Background

Prior knee surgery and arthroscopy is known to increase complications and re-operations in subsequent total knee arthroplasty (TKA). We set out to examine the time dependant effect of arthroscopy on Patient Reported Outcome Measures following subsequent TKA.

Methods

A retrospective review of theatre and clinical records identified 186 patients who underwent TKA within a year of arthroscopy (2009–2013). Oxford knee score (OKS) data was compared with a published cohort from the same department (1708 patients).

Results

One hundred and eighty six patients were identified who underwent TKA within a year of arthroscopy; 112 females, 74 males; mean age 64 (SD 10); mean BMI 31.4 (SD 4.6). There was no significant difference between groups with respect to sex, age, BMI, or pre-operative OKS.One hundred and three patients underwent TKA within six months of arthroscopy. This group had a significant reduction in OKS compared to the previously published cohort (32.8 vs 36.3, p < 0.005). There was no significant difference in OKS when TKA was performed more than six months after arthroscopy (35.3).The re-operation rate was 14% in the arthroscopy group, with a revision rate of 3.8% vs 1.6% in a previously published large cohort from the same institution.

Conclusions

There appears to be a negative impact of arthroscopy in relation to subsequent TKA which seems to be time dependent. TKA should not routinely be performed within six months of arthroscopy. This should inform guidelines on the management knee osteoarthritis.  相似文献   

19.

Aims

To determine the temporal changes in patient dissatisfaction following primary knee arthroplasty surgery (TKA).

Patients and methods

Three hundred and ninety patients that had previously indicated they were either dissatisfied or unsure with their TKA at one-year post-surgery in our region were mailed a simple questionnaire in addition to the Oxford Knee Score and EQ-5D.

Results

A 55% response rate was achieved. The mean follow-up time period was 9.1 years. Of the 120 patients who were initially dissatisfied, 46.7% remained so. Of the 96 patients who were initially unsure, 20.8% remained so, 21.9% and 57.3% became dissatisfied and satisfied, respectively. The primary reason for continued dissatisfaction was persistent pain. Of the 19.4% of patients who had revision surgery, 47.6% remained dissatisfied. 54.2% of patients stated that they would be happy to have a primary TKA again and 55.6% indicated that they would recommend one to a friend. Patients who had concurrent hip pain were six times more likely to remain unsure or dissatisfied over time (OR 6.7, p-value 0.0000). Patients who had back pain or contralateral knee pain were two or three times as likely to remain unsure or dissatisfied.

Conclusion

In time half of the patients who stated that they were not satisfied with their arthroplasty, at one year, go on to be satisfied with their knee.  相似文献   

20.
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