Patelloplasty with and without circumpatellar denervation in reducing anterior knee pain in primary total knee arthroplasty: a comparative prospective study

Background: Anterior knee pain (AKP) following total knee arthroplasty (TKA) ­­­­­­is one of the complication which cause dissatisfaction in patients. Incidence estimated to be 4-49%. The aim of our study is to know the efficacy of patelloplasty with circumpatellar denervation with diathermy in reducing AKP in primary TKA.Methods: A total of 130 unilateral TKAs’ are divided into 2 groups. Group I (control) includes 65 patients in which only patelloplasty was done. Group II (intervention) includes 65 patients in which both patelloplasty and circumpatellar denervation with diathermy was done and analysed. Mean follow up period was 18 months. Patients were assessed both preoperatively and postoperatively at final follow up.Results: The overall incidence of AKP at follow up (18 months) was 16.9%, with 7.7% in the intervention group and 26.1% in the control group (p<0.05).  Western Ontario and McMaster Universities osteoarthritis index scores were significantly  better in intervention group when compared to control group (28.71±3.948 vs 31.40±3.860). Better results were also found in knee society scores for intervention group compared to control group (166.57±7.941 vs 161.23±11.219); Feller patellar score of  intervention group was significantly better when compared to control group (23.28±2.546 vs 20.69±3.729); the range of knee flexion was similar in both the groups (94.62±12.6 vs 93.54±10.7). In terms of pain referred by the patient at 72 hrs postoperatively, there was statistically significant difference observed according to visual analogue scale.Conclusions: There is statistically significant difference with respect to AKP in patients who have undergone patelloplasty with circumpatellar denervation using diathermy compared with patelloplasty alone.

Alteration of the conserved residue tyrosine-158 to histidine renders human O6-alkylguanine-DNA alkyltransferase insensitive to the inhibitor O6- benzylguanine

The DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) protects cells from alkylation damage. O6-Benzylguanine (BG) is a potent inactivator of human AGT (ED50 of 0.1 μM) that is currently undergoing clinical trials to enhance chemotherapy by alkylating agents. In a screen of AGT mutants randomly mutated at position glycine-160, we found that the double mutant Y158H/G160A protected Escherichia coli from killing by N- methyl-N'-nitro-N-nitrosoguanidine (MNNG) even in the presence of BG and that the AGT activity of this mutant was strongly resistant to BG (ED50 of 180 μM). Because the single mutant G160A was not resistant to BG, this suggested that the presence of the charged histidine residue at position 158 was responsible. This hypothesis was confirmed by the construction of the single mutation Y158H. The Y158H-mutant AGT was slightly less active than wild-type AGT for the repair of mcthylated DNA in vitro, but it protected E. coli from killing by MNNG even in the presence of BG and had an ED50 for the inactivation by BG of 620 μM. In contrast, mutant Y158F had an ED50 of 0.2 μM. Previous studies (M. Xu-Welliver et al., Cancer Res., 58: 1936-1945, 1998) have shown that mutant P140K is highly resistant to BG (ED50 of > 1200 μM). Models of human AGT suggest that the side chain of the lysine inserted into this mutant is close to tyrosine-158 and that the positively charged lysine side-chain may interfere with BG binding. The double mutants P140K/Y158H and P140K/Y158F resembled P140K and Y158H in being highly resistant to BG, but the use of a sensitive assay for reaction of BG with AGT indicated that their abilities to react were in the order P140K/Y158H < P140K < P140K/Y158F. These results confirm that the presence of a positively charged residue close to the active site of human AGT renders it highly resistant to BG without substantially affecting activity toward methylated DNA substrates. Such mutants may limit the value of BG therapy if they arise in malignant cells during chemotherapy, but the mutant sequences may be useful for gene therapy approaches in which BG-resistant human AGTs are used to prevent hematopoietic toxicity. At least 28 AGT sequences (from 25 species) have now been described. In 25 of these, the position equivalent to 158 in the human AGT is also a tyrosine, and in the other 3, it is a phenylalanine. The importance of an aromatic ring side chain at this position is emphasized by previous studies (S. Edara et al., Carcinogenesis, 16: 1637- 1642, 1995), which show that the replacement by alanine renders human AGT inactive. Our results show that histidine can also substitute for tyrosine at this position

A rare association of brucellosis and pulmonary hydatid cyst in a patient with human immunodeficiency virus

Background: Hydatid disease, or cystic echinococcosis, is a parasitic infection caused by a tapeworm. Pulmonary hydatid infection is the second common manifestation of hydatid disease. We present a patient who was diagnosed with recurrent hydatid cyst in lung and later diagnosed with brucellosis, which is a highly contagious zoonotic disease. Case presentation: A 47-years-old male was diagnosed with pulmonary hydatid disease after a computed tomography (CT) chest-plain was done. As the patient had high intermittent fever for 4 months which could not be explained by an intact cyst in the followup, the patient was diagnosed with brucellosis with both IgG and IgM antibodies positive. Conclusions: Hydatid cyst present with varied symptomatology. A high degree of clinical suspicion combined with meticulous history and clinical examination supported by laboratory investigations are required for its diagnosis. This case highlights the importance of considering brucella as a differential diagnosis

Factors determining the range of motion in primary total knee arthroplasty

Background: Total knee arthroplasty (TKA) ­­­­­­is one of the most successful surgical procedure with over 90% survival rate at 10 to 15 years. It provides a stable, pain free range of motion (ROM) for day to day activities. The aim of this study is to evaluate various factors determining ROM after TKA.Methods: 348 patients with 390 knees treated with TKA using cruciate retaining (CR) and posterior stabilized (PS) prosthesis were included and analysed. Mean follow up period was 18 months. Patients were analysed for factors like age, sex, diagnosis, body mass index (BMI), pre-operative exercises, ROM, deformity, posterior femoral condylar offset (PFCO), posterior tibial slope (PTS), post-operative rehabilitation and implant design (CR vs PS). Statistical analysis of above factors on knee ROM was done. Patients were assessed pre-operatively, at 6 weeks, 3, 6, 12 and 18 months post-operatively.Results: Age and sex did not affect the final ROM. The mean knee ROM improved from 86.87° to 96.95°. Factors like BMI, deformity had negative correlation and Pre-operative diagnosis, exercises, knee scores, good preoperative ROM, PFCO, PTS had positive correlation on ROM.Conclusions: Pre-operative exercises, diagnosis, ROM, deformity, BMI, PFCO and PTS were important factors which influence ROM in TKA. Patient selection and preoperative counselling are important for good clinical outcome

Influence of posterior tibial slope on knee flexion in posterior stabilized fixed bearing primary total knee arthroplasty

Background: The goal of total knee arthroplasty (TKA) is to relieve pain and maintain stable range of motion (ROM) for day to day activities. Among the various factors, posterior tibial slope slope (PTS) may play an important role in achieving good postoperative knee flexion. Our study aims to know the effectiveness of PTS on the ROM of the knee in a posterior cruciate ligament (PCL)-substituting TKA.Methods: A total of 125 unilateral PCL-substituting TKA’s were included in the study. Based on postoperative PTA which was measured on lateral radiograph, patients were divided into 3 groups, Group A (PTS of ≤2) comprise of 24 patients. Group B consists of 91 patients (PTS of 3 to 7). Group C includes 10 patients (PTS of 8 or more). Functional outcome was measured by using knee society score (KSS) and Western Ontario and McMaster Universities osteoarthritis index (WOMAC) which were evaluated preoperatively and at 18months post operatively.Results: Mean postop ROM was 92.91 ± 10.632; 107.24±10.905; 107.49±13.944 in group A, B, C respectively which was significantly related to mean postop PTS (0.74; 5.62; 9.87 in group A, B, C respectively) (P&lt;0.05). Functional outcome was measured by KSS and WOMAC which showed no significant difference pre and postoperatively.Conclusions: The results of our study validate the hypothesis that a positive correlation exists between the postoperative flexion and PTS in the PCL-substituting TKA, an increase in PTS can lead to a greater degree of the knee flexion for every extra degree of PTS.

Gold Nanoparticles with Self-Assembled Cysteine Monolayer Coupled to Nitrate Reductase in Polypyrrole Matrix Enhanced Nitrate Biosensor

We have developed here a novel, highly sensitive and selective nitrate (NO– 3) biosensor by covalent immobilization of nitrate reductase (NaR) in self-assembled monolayer (SAM) of cysteine on gold nanoparticles (GNP)-polypyrrole (PPy) modified platinum electrode. Incorporation of GNP in highly microporous PPy matrix was confirmed by morphological scanning electron microscope (SEM) images. The electrochemical behavior of the NaR modified electrode exhibited the characteristic reversible redox peaks at the potential, –0.76 and –0.62 V versus Ag/AgCl. Further, the GNP-PPy nanocomposite enhanced the current response by 2-fold perhaps by enhancing the immobilization of NaR and also direct electron transfer between the deeply buried active site and the electrode surface. The common biological interferences like ascorbic acid, uric acid were not interfering with the NO– 3 measurement at low concentration levels. This biosensor showed a wide linear range of response over the concentration of NO– 3 from 1 μM to 1 mM, with higher sensitivity of 84.5 nA μM–1 and a detection limit of 0.5 μM. Moreover, the NO– 3 level present in the nitrate-rich beetroot juice and the NO– 3 release from the lipopolysaccharide treated human breast cancer cells were estimated

DNA aggregation by an archaeal DNA binding protein Sac10b and its novel DNA nicking activity

166-173The solution structure of an archaeal DNA binding protein Sac10b (DBNP-B) by cross-linking with formaldehyde and its interaction with DNA were studied. Results indicated that Sac10b existed as oligomeric structure in solution and the oligomerization was greatly stimulated by Mg²⁺ ions and elevated temperatures. In light of our earlier observation that Sac10b interacts with DNA forming different types of complexes with DNA at different protein concentrations, its DNAbinding properties were also studied. Results demonstrated that the protein formed rapidly sedimentable co-aggregation complexes with both native and denatured DNA in a protein concentration-dependent manner. These protein DNA complexes were fluid-like crystalline material at a protein DNA ratio (3-6:1 w/w). Gel mobility shift assays carried out to study the interaction of the protein with plasmid DNA indicated possible DNA nicking by the protein. The DNA nicking activity of Sac10b was optimal in pH range of 7-8.5 and was dependent on Mg²⁺ ions. It was maximal at protein to DNA ratio of (8:1, w/w) and very little activity was observed above and below this ratio. Nicking of DNA at this ratio indicated structure-specific DNA nicking by the protein. The protein might have important multi-functional role in the DNA metabolism in this organism

The Role of Cancer-Associated Fibroblasts in Tumor Progression

In the era of genomic medicine, cancer treatment has become more personalized as novel therapeutic targets and pathways are identified. Research over the past decade has shown the increasing importance of how the tumor microenvironment (TME) and the extracellular matrix (ECM), which is a major structural component of the TME, regulate oncogenic functions including tumor progression, metastasis, angiogenesis, therapy resistance, and immune cell modulation, amongst others. Within the TME, cancer-associated fibroblasts (CAFs) have been identified in several systemic cancers as critical regulators of the malignant cancer phenotype. This review of the literature comprehensively profiles the roles of CAFs implicated in gastrointestinal, endocrine, head and neck, skin, genitourinary, lung, and breast cancers. The ubiquitous presence of CAFs highlights their significance as modulators of cancer progression and has led to the subsequent characterization of potential therapeutic targets, which may help advance the cancer treatment paradigm to determine the next generation of cancer therapy. The aim of this review is to provide a detailed overview of the key roles that CAFs play in the scope of systemic disease, the mechanisms by which they enhance protumoral effects, and the primary CAF-related markers that may offer potential targets for novel therapeutics