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Total knee arthroplasty surgery is an increasingly common procedure for the treatment of uni- and tricompartmental knee osteoarthritis, particularly in advanced stages and in the older population. Its usage is being extended to younger patients, where implant longevity is of concern. In the younger age group, especially with early disease, other options merit consideration. On the other hand, it may not be possible for elderly patients with medical comorbidities to undergo joint replacement surgery. Proximal fibular osteotomy (PFO) has recently been advocated to treat medial knee osteoarthritis. Although there have been clinical reports showing promising outcomes, the biomechanical basis of this procedure is still unclear. We performed a cadaveric study to investigate the effect of PFO on proximal tibial strain. Eight unpaired cadaveric lower limb specimens were loaded in compression at 2 times body weight. Strain gauges were mounted on various sites on the proximal tibia and fibula. After PFO, there was a significant increase in the lateral tibial strain adjacent to the proximal tibiofibular joint ( P Orthopedics . 2022;45(5):314–319.]

Injuries to the pelvic vasculature during total hip arthroplasties are rare but have serious consequence. They demand urgent and early identification so that appropriate treatment can be instituted. If the bleeding is severe, cardiovascular compromise occurs intraoperatively and this will alert the surgeon of this possibility during acetabular screw placement. Alternatively, a delay in diagnosis can occur because the bleeding and the injured vessel are in the pelvic cavity and not visualized during the surgery. In this article, we report two cases from our center occurring within a six-month interval that sustained a vascular injury during acetabular drilling for screw placement for cementless cup fixation. Each case had a different vessel injury and different lessons can be learned from these rare injuries. The first case had an injury of the inferior gluteal artery following a breach of the sciatic notch. The vessel was treated with percutaneous embolization. The second case demonstrated a venous injury, following a medial protrusio technique for congenital hip dysplasia and a short anterosuperior screw, transecting the external iliac vein. This was subsequently repaired using an endovascular technique. We conclude the reasons for these vessel injuries after analyzing advanced imaging, discuss measures to avoid vessel injury and detail the minimally invasive method for their treatment.

Background We have described the diversity of complete mtDNA sequences from ‘relic’ groups of the Russian Far East, primarily the Nivkhi (who speak a language isolate with no clear relatedness to any others) and Oroki of Sakhalin, as well as the sedentary Koryak from Kamchatka and the Udegey of Primorye. Previous studies have shown that most of their traditional territory was dramatically reshaped by the expansion of Tungusic-speaking groups. Results Overall, 285 complete mitochondrial sequences were selected for phylogenetic analyses of published, revised and new mitogenomes. To highlight the likely role of Neolithic expansions in shaping the phylogeographical landscape of the Russian Far East, we focus on the major East Eurasian maternal lineages (Y1a, G1b, D4m2, D4e5, M7a2, and N9b) that are restricted to the coastal area. To obtain more insight into autochthonous populations, we removed from the phylogeographic analysis the G2a, G3a2, M8a1, M9a1, and C4b1 lineages, also found within our samples, likely resulting from admixture between the expanding proto-Tungus and the indigenous Paleoasiatic groups with whom they assimilated. Phylogenetic analysis reveals that unlike the relatively diverse lineage spectrum observed in the Amur estuary and northwestern Sakhalin, the present-day subpopulation on the northeastern coast of the island is relatively homogenous: a sole Y1a sublineage, conspicuous for its nodal mutation at m.16189 T > C!, includes different haplotypes. Sharing of the Y1a-m.16189 T > C! sublineages and haplotypes among the Nivkhi, Ulchi and sedentary Koryak is also evident. Aside from Y1a, the entire tree approach expands our understanding of the evolutionary history of haplogroups G1, D4m, N9b, and M7a2. Specifically, we identified the novel haplogroup N9b1 in Primorye, which implies a link between a component of the Udegey ancestry and the Hokkaido Jomon. Conclusions Through a comprehensive dataset of mitochondrial genomes retained in autochthonous populations along the coast between Primorye and the Bering Strait, we considerably extended the sequence diversity of these populations to provide new features based on the number and timing of founding lineages. We emphasize the value of integrating genealogical information with genetic data for reconstructing the population history of indigenous groups dramatically impacted by twentieth century resettlement and social upheavals.

Background New treatments are currently offering new opportunities and challenges in clinical management and research in the migraine field. There is the need of homogenous criteria to identify candidates for treatment escalation as well as of reliable criteria to identify refractoriness to treatment. To overcome those issues, the European Headache Federation (EHF) issued a Consensus document to propose criteria to approach difficult-to-treat migraine patients in a standardized way. The Consensus proposed well-defined criteria for resistant migraine (i.e., patients who do not respond to some treatment but who have residual therapeutic opportunities) and refractory migraine (i.e., patients who still have debilitating migraine despite maximal treatment efforts). The aim of this study was to better understand the perceived impact of resistant and refractory migraine and the attitude of physicians involved in migraine care toward those conditions. Methods We conducted a web-questionnaire-based cross-sectional international study involving physicians with interest in headache care. Results There were 277 questionnaires available for analysis. A relevant proportion of participants reported that patients with resistant and refractory migraine were frequently seen in their clinical practice (49.5% for resistant and 28.9% for refractory migraine); percentages were higher when considering only those working in specialized headache centers (75% and 46% respectively). However, many physicians reported low or moderate confidence in managing resistant (8.1% and 43.3%, respectively) and refractory (20.7% and 48.4%, respectively) migraine patients; confidence in treating resistant and refractory migraine patients was different according to the level of care and to the number of patients visited per week. Patients with resistant and refractory migraine were infrequently referred to more specialized centers (12% and 19%, respectively); also in this case, figures were different according to the level of care. Conclusions This report highlights the clinical relevance of difficult-to-treat migraine and the presence of unmet needs in this field. There is the need of more evidence regarding the management of those patients and clear guidance referring to the organization of care and available opportunities.

Objectives: To assess the outcome and impact of multiple sclerosis (MS) using validated Arabic versions of the Barthel index (BI) multiple sclerosis impact scale (MSIS-29), the modified Rankin scale (mRS), and the expanded disability status scale (EDSS). Methods: A cross-sectional study conducted at King Abdulaziz Medical City in Riyadh, Kingdom of Saudi Arabia, during July-November 2017. All Saudi adult patients diagnosed with MS between 2000-2016 (269 patients) were included. Patients were contacted via phone calls and were assessed using a newly developed and validated multi-component questionnaire that included demographic data, disease course, and Arabic versions of the scales. Results: Out of 269 patients, 210 (78.2%) responded. The average patient age was 37.44±10.3 years. The majority were females (69.5%). Only, 51 (24.3%) patients reported worsening conditions. Annually, the average relapse rate was 2.28±1.91. In regard to patient outcomes, 120 (57.1%) showed no significant disability in mRS, 146 (69.5%) were ambulatory without aid in EDSS, and 185 (89.4%) were independent in BI scores. The average MSIS-29-PHYS score was 33.6±27.6 and MSIS-29-PSYCH score was 38.2±25.8. Modified Rankin scale and EDSS were significantly associated with the current use of disease-modifying therapy (DMT). Modified Rankin scale was negatively associated with delayed diagnosis. Barthel index showed significant association with medication compliance and the absence of attacks. Conclusion: Majority of patients had a favorable outcome that was linked with the use of DMT, compliance, early diagnosis, and absence of attacks.

The Central Siberian Plateau was the last geographic area in Eurasia to become habitable by modern humans after the Last Glacial Maximum (LGM). Through a comprehensive dataset of mitochondrial DNA (mtDNA) genomes retained in the remnats of earlier (“Old”) Siberians, primarily the Ket, Tofalar, and Todzhi, we explored genetic links between the Yenisei-Sayan region and Northeast Eurasia (best represented by the Yukaghir) over the last 10,000 years. We generated 218 new complete mtDNA sequences and placed them into compound phylogenies with 7 newly obtained and 70 published ancient mitochondrial genomes. We have considerably extended the mtDNA sequence diversity (at the entire mtDNA genome level) of autochthonous Siberians, which remain poorly sampled, and these new data may have a broad impact on the study of human migration. We compared present-day mtDNA diversity in these groups with complete mitochondrial genomes from ancient samples from the region and placed the samples into combined genealogical trees. The resulting components were used to clarify the origins and expansion history of mtDNA lineages that evolved in the refugia of south-central Siberia and beyond, as well as multiple phases of connection between this region and distant parts of Eurasia.

We hypothesized that there is a correlation between the distal femoral rotation and proximal tibial joint line obliquity in nonarthritic knees. This has significance for kinematic knee arthroplasty, in which the target knee alignment desired approximates the knee before disease.Fifty computed tomography scans of nonarthritic knees were evaluated using three-dimensional image processing software. Four distal femoral rotational axes were determined in the axial plane: the transepicondylar axis (TEA), transcondylar axis (TCA), posterior condylar axis (PCA), and a line perpendicular to Whiteside's anterior-posterior axis. Then, angles were measured relative to the TEA. Tibial joint line obliquity was measured as the angle between the proximal tibial plane and a line perpendicular to the axis of the tibia.There was a strong positive correlation between PCA-TEA and tibial joint line obliquity (r = 0.68, P.001) as well as TCA-TEA and tibial joint line obliquity (r = 0.69, P.001). In addition, the tibial joint line obliquity and TCA-TEA angles were similar, 3.7° ± 2.2° (mean ± standard deviation) and 3.5° ± 1.7°, respectively (mean difference, 0.2° ± 0.2°; P = .369).Both PCA-TEA and TCA-TEA strongly correlated with proximal tibial joint line obliquity indicating a relationship between distal femoral rotational geometry and proximal tibial inclination. These findings could imply that the native knee in flexion attempts to balance the collateral ligaments toward a rectangular flexion space. A higher tibial varus inclination is matched with a more internally rotated distal femur relative to the TEA.

Our data first represent the variety of Leber&rsquo, s hereditary optic neuropathy (LHON) mutations in Western Siberia. LHON is a disorder caused by pathogenic mutations in mitochondrial DNA (mtDNA), inherited maternally and presents mainly in young adults, predominantly males. Clinically, LHON manifests itself as painless central vision loss, resulting in early onset of disability. The epidemiology of LHON has not been fully investigated yet. In this study, we report 44 genetically unrelated families with LHON manifestation. We performed whole mtDNA genome sequencing and provided genealogical and molecular genetic data on mutations and haplogroup background of LHON patients. Known &ldquo, primary&rdquo, pathogenic mtDNA mutations (MITOMAP) were found in 32 families: m.11778G&gt, A represents 53.10% (17/32), m.3460G&gt, A&mdash, 21.90% (7/32), m.14484T&gt, C&ndash, 18.75% (6/32), and rare m.10663T&gt, C and m.3635G&gt, A represent 6.25% (2/32). We describe potentially pathogenic m.4659G&gt, A in one subject without known pathogenic mutations, and potentially pathogenic m.6261G&gt, A, m.8412T&gt, C, m.8551T&gt, C, m.9444C&gt, T, m.9921G&gt, A, and m.15077G&gt, A in families with known pathogenic mutations confirmed. We suppose these mutations could contribute to the pathogenesis of optic neuropathy development. Our results indicate that haplogroup affiliation and mutational spectrum of the Western Siberian LHON cohort substantially deviate from those of European populations.

To compare the occurrence, distribution and management of clefts of lip and palate in local patients with the available data from India and China.The retrospective study was conducted at the Interdisciplinary Research Centre in Biomedical Materials, COMSATS University Islamabad, Lahore Campus, Lahore, Pakistan, and comprised data related to a three-month period from January to March 2015 at two medical centres in Lahore. Data from Pakistani centres was analysed based on province, gender, age and clefts of lip and palate conditions and Spearman's correlation matrix.Of the 1574 cases, 1061(67.4%) were from Punjab, 361(23%) Khyber Pakhtunkhwa, 85(5%) Sindh and 67(4.2%) were from Azad Jammu and Kashmir. The incidence of clefts of lip and palate was higher in males than females. There was higher awareness of the need for timely management in new borns with clefts of lip and palate. Some patients seeking secondary treatment were also being surgically corrected. There is no national registry of children born with cleft defect, making it difficult to assess the full scale of the problem..Based on available data, it is likely that there are many adults who have not been treated when younger..

Osteoarthritis (OA) of the knee is a multifactorial degenerative disease typically defined as the 'wear and tear' of articular joint cartilage. However, recent studies suggest that OA is a disease arising from chronic low-grade inflammation. We conducted a study to investigate the relationship between chronic inflammatory mediators present in both the systemic peripheral blood system and localised inflammation in synovial fluid (SF) of OA and non-OA knees; and subsequently made direct comparative analyses to understand the mechanisms that may underpin the processes involved in OA.20-Plex proteins were quantified using Human Magnetic Luminex® assay (RD Systems, USA) from plasma and SF of OA (n = 14) and non-OA (n = 14) patients. Ingenuity Pathway Analysis (IPA) software was used to predict the relationship and possible interaction of molecules pertaining to OA.There were significant differences in plasma level for matrix metalloproteinase (MMP)-3, interleukin (IL)-27, IL-8, IL-4, tumour necrosis factor-alpha, MMP-1, IL-15, IL-21, IL-10, and IL-1 beta between the groups, as well as significant differences in SF level for IL-15, IL-8, vascular endothelial growth factor (VEGF), MMP-1, and IL-18. Our predictive OA model demonstrated that toll-like receptor (TLR) 2, macrophage migration inhibitory factor (MIF), TLR4 and IL-1 were the main regulators of IL-1B, IL-4, IL-8, IL-10, IL-15, IL-21, IL-27, MMP-1 and MMP-3 in the plasma system; whilst IL-1B, TLR4, IL-1, and basigin (BSG) were the regulators of IL-4, IL-8, IL-10, IL-15, IL-18, IL-21, IL-27, MMP-1, and MMP-3 in the SF system.The elevated plasma IL-8 and SF IL-18 may be associated with the pathogenesis of OA via the activation of MMP-3.

Background: There is a common perception among surgeons that Asian tibiae are significantly more varus compared to non-Asians, contributed both by an acute medial tibial proximal angle (MPTA) and diaphyseal bowing. Insight into the normative morphology of the tibia allows generation of knowledge towards disease processes and subsequently planning for corrective surgeries. Methods: Computed tomography (CT) scans of 100 normal adult knees, aged 18 years and above, were analysed using a 3-dimensional (3D) analysis software. All tibiae were first aligned to a standard frame of reference and then rotationally aligned to the tibial centroid axis (TCAx) and the transmalleolar axis (tmAx). MPTA was measured from best-fit planes on the surface of the proximal tibia for each rotational alignment. Diaphyseal bowing was assessed by dividing the shaft to three equal portions and establishing the angle between the proximal and distal segments. Results: The mean MPTA was 87.0° ± 2.2° (mean ± SD) when rotationally aligned to TCAx and 91.6° ± 2.7° when aligned to tmAx. The mean diaphyseal bowing was 0.1° ± 1.9° varus when rotationally aligned to TCAx and 0.3° ± 1.6° valgus when aligned to tmAx. The mean difference when the MPTA was measured with two different rotational alignments (TCAx and tmAx) was 4.6° ± 2.3°. No statistically significant differences were observed between males and females. Post hoc tests revealed statistically significant difference in MPTA between different ethnic sub-groups. Conclusion: The morphology of the proximal tibiae in the disease-free Asian knee is inherently varus but not more so than other reported populations. The varus profile is contributed by the MPTA, with negligible diaphyseal bowing. These implications are relevant to surgical planning and prosthesis design.

Background Cartilage damage, which can potentially lead to osteoarthritis, is a leading cause of morbidity in the elderly population. Chondrocytes are sensitive to mechanical stimuli and their matrix-protein synthesis may be altered when chondrocytes experience a variety of in vivo loadings. Therefore, a study was conducted to evaluate the biosynthesis of isolated osteoarthritic chondrocytes which subjected to compression with varying dynamic compressive strains and loading durations. Methods The proximal tibial was resected as a single osteochondral unit during total knee replacement from patients (N = 10). The osteoarthritic chondrocytes were isolated from the osteochondral units, and characterised using reverse transcriptase-polymerase chain reaction. The isolated osteoarthritic chondrocytes were cultured and embedded in agarose, and then subjected to 10% and 20% uniaxial dynamic compression up to 8-days using a bioreactor. The morphological features and changes in the osteoarthritic chondrocytes upon compression were evaluated using scanning electron microscopy. Safranin O was used to detect the presence of cartilage matrix proteoglycan expression while quantitative analysis was conducted by measuring type VI collagen using an immunohistochemistry and fluorescence intensity assay. Findings Gene expression analysis indicated that the isolated osteoarthritic chondrocytes expressed chondrocyte-specific markers, including BGN, CD90 and HSPG-2. Moreover, the compressed osteoarthritic chondrocytes showed a more intense and broader deposition of proteoglycan and type VI collagen compared to control. The expression of type VI collagen was directly proportional to the duration of compression in which 8-days compression was significantly higher than 4-days compression. The 20% compression showed significantly higher intensity compared to 10% compression in 4- and 8-days. Interpretation The biosynthetic activity of human chondrocytes from osteoarthritic joints can be enhanced using selected compression regimes.

Objectives To compare mechanobiological response of synovial fibroblasts (SFb) from OA patient cohorts under mechanical load and inflammatory stressors for better understanding of SFb homeostatic functions. Methods Primary SFb isolated from knee synovium of OA obese (OA-ob:SFb), OA-pre-obese (OA-Pob:SFb), non-OA arthroscopic (scope:SFb), and non-OA arthroscopic with cartilage damage (scope-CD:SFb) were exposed to OA-conditioned media (OA CM), derived from OA obese (OA-ob:CM), OA-pre-obese (OA-Pob:CM), and mechanical stretch at either 0 %, 6 % or 10 % for 24 h. Differences in the mRNA levels of genes involved in extracellular matrix production, inflammation and secretory activity were measured. Results Despite the significant BMI differences between the OA-ob and OA-Pob groups, OA-Pob has more patients with underlying dyslipidaemia, and low-grade synovitis with higher levels of secreted proteins, CXCL8, COL4A1, CCL4, SPARC and FGF2 in OA-Pob:CM. All primary SFb exhibited anti-proliferative activity with both OA-CM. Mechanical stretch stimulated lubricin production in scope:SFb, higher TGFβ1 and COL1A1 expressions in scope-CD:SFb. OA-Pob:CM stimulated greater detrimental effects than the OA-ob:CM, with higher pro-inflammatory cytokines, IL1β, IL6, COX2 and proteases such as aggrecanases, ADAMTS4 and ADAMTS5, and lower ECM matrix, COL1A1 expressions in all SFb. OA-ob:SFb were unresponsive but expressed higher pro-inflammatory cytokines under OA-Pob:CM treatment. Conclusion Both mechanical and inflammatory stressors regulate SFb molecular functions with heterogeneity in responses that are dependent on their pathological tissue of origins. While mechanical stretch promotes a favorable effect with enhanced lubricin production in scope:SFb and TGFβ1 and COL1A1 in scope-CD:SFb, the presence of excessively high OA-associated inflammatory mediators in OA-Pob:CM, predominantly SPARC, CXCL8 and FGF2 drive all SFb regardless of pathology, towards greater pro-inflammatory activities.

The patterns of prehistoric migrations across the Bering Land Bridge are far from being completely understood: there still exists a significant gap in our knowledge of the population history of former Beringia. Here, through comprehensive survey of mitochondrial DNA genomes retained in ‘relic' populations, the Maritime Chukchi, Siberian Eskimos, and Commander Aleuts, we explore genetic contribution of prehistoric Siberians/Asians to northwestern Native Americans. Overall, 201 complete mitochondrial sequences (52 new and 149 published) were selected in the reconstruction of trees encompassing mtDNA lineages that are restricted to Coastal Chukotka and Alaska, the Canadian Arctic, Greenland, and the Aleutian chain. Phylogeography of the resulting mtDNA genomes (mitogenomes) considerably extends the range and intrinsic diversity of haplogroups (eg, A2a, A2b, D2a, and D4b1a2a1) that emerged and diversified in postglacial central Beringia, defining independent origins of Neo-Eskimos versus Paleo-Eskimos, Aleuts, and Tlingit (Na-Dene). Specifically, Neo-Eskimos, ancestral to modern Inuit, not only appear to be of the High Arctic origin but also to harbor Altai/Sayan-related ancestry. The occurrence of the haplogroup D2a1b haplotypes in Chukotka (Sireniki) introduces the possibility that the traces of Paleo-Eskimos have not been fully erased by spread of the Neo-Eskimos or their descendants. Our findings are consistent with the recurrent gene flow model of multiple streams of expansions to northern North America from northeastern Eurasia in late Pleistocene–early Holocene.

BACKGROUND: Amphetamine type stimulants (ATS) use is highly prevalent and frequently co-occurs with opioid dependence in Malaysia and Asian countries. No medications have established efficacy for treating ATS use disorder. This study evaluated the safety, tolerability, and potential efficacy of atomoxetine for treating ATS use disorder. METHODS: Participants with opioid and ATS dependence (N=69) were enrolled in a pilot, double-blind, placebo-controlled randomized clinical trial; all received buprenorphine/naloxone and behavioral counseling and were randomized to atomoxetine 80 mg daily (n=33) or placebo (n=33). The effect size of the between-group difference on the primary outcome, proportion of ATS-negative urine tests, was estimated using Cohen’s d for the intention-to-treat (ITT) sample and for higher adherence subsample (≥60 days of atomoxetine or placebo ingestion). RESULTS: Participants were all male with mean (SD) age 39.4 (6.8) years. The proportion of ATS-negative urine tests was higher in atomoxetine- compared to placebo-treated participants: 0.77 (0.63–0.91) vs. 0.67 (0.53–0.81, d=0.26) in the ITT sample and 0.90 (0.75–1.00) vs. 0.64 (0.51–0.78, d=0.56) in the higher adherence subsample. The proportion of days abstinent from ATS increased from baseline in both groups (p

Background The posterior tibial slope (PTS) is an important consideration in knee arthroplasty. However, there is still no consensus for the optimal slope. The objectives of this study were (1) to reliably determine the native PTS in this population using 3-dimensional computed tomography scans and (2) to determine the normal reference range for PTS in this population. Methods One hundred computed tomography scans of disease-free knees were analyzed. A 3-dimensional reconstructed image of the tibia was generated and aligned to its anatomic axis in the coronal and sagittal planes. The tibia was then rotationally aligned to the tibial plateau (tibial centroid axis) and PTS was measured from best-fit planes on the surface of the proximal tibia and individually for the medial and lateral plateaus. This was then repeated with the tibia rotationally aligned to the ankle (transmalleolar axis). Results When rotationally aligned to the tibial plateau, the mean PTS, medial PTS, and lateral PTS were 11.2° ± 3.0 (range, 4.7°-17.7°), 11.3° ± 3.2 (range, 2.7°-19.7°), and 10.9° ± 3.7 (range, 3.5°-19.4°), respectively. When rotationally aligned to the ankle, the mean PTS, medial PTS, and lateral PTS were 11.4° ± 3.0 (range, 5.3°-19.3°), 13.9° ± 3.7 (range, 3.1°-24.4°), and 9.7° ± 3.6 (range, 0.8°-17.7°), respectively. Conclusion The PTS in the normal Asian knee is on average 11° (mean) with a reference range of 5°-17° (mean ± 2 standard deviation). This has implications to surgery and implant design.

The role for mechanical stimulation in the control of cell fate has been previously proposed, suggesting that there may be a role of mechanical conditioning in directing mesenchymal stromal cells (MSCs) towards specific lineage for tissue engineering applications. Although previous studies have reported that calcium signalling is involved in regulating many cellular processes in many cell types, its role in managing cellular responses to tensile loading (mechanotransduction) of MSCs has not been fully elucidated. In order to establish this, we disrupted calcium signalling by blocking stretch-activated calcium channel (SACC) in human MSCs (hMSCs) in vitro. Passaged-2 hMSCs were exposed to cyclic tensile loading (1 Hz + 8% for 6, 24, 48, and 72 hours) in the presence of the SACC blocker, gadolinium. Analyses include image observations of immunochemistry and immunofluorescence staining from extracellular matrix (ECM) production, and measuring related tenogenic and apoptosis gene marker expression. Uniaxial tensile loading increased the expression of tenogenic markers and ECM production. However, exposure to strain in the presence of 20 μM gadolinium reduced the induction of almost all tenogenic markers and ECM staining, suggesting that SACC acts as a mechanosensor in strain-induced hMSC tenogenic differentiation process. Although cell death was observed in prolonged stretching, it did not appear to be apoptosis mediated. In conclusion, the knowledge gained in this study by elucidating the role of calcium in MSC mechanotransduction processes, and that in prolonged stretching results in non-apoptosis mediated cell death may be potential useful for regenerative medicine applications.

Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p, Author Summary Coronary artery disease (CAD) has a strong genetic basis that remains poorly characterised. Using a custom-designed array, we tested the association with CAD of almost 50,000 common and low frequency variants in ∼2,000 genes of known or suspected cardiovascular relevance. We genotyped the array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin) and attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. We report the novel association of variants in or near four genes with CAD and in additional studies identify potential mechanisms by which some of these novel variants affect CAD risk. Interestingly, we found that these variants, as well as the majority of previously reported CAD variants, have similar associations in Europeans and South Asians. Contrary to prior expectations, many previously suggested candidate genes did not show evidence of any effect on CAD risk, and neither did we identify any novel low frequency alleles with strong effects amongst the genes tested. Discovery of novel genes associated with heart disease may help to further understand the aetiology of cardiovascular disease and identify new targets for therapeutic interventions.

Background: Patellofemoral instability is a major cause of anterior knee pain. The aim of this study was to examine how the medial and lateral stability of the patellofemoral joint in the normal knee changes with knee flexion and measure its relationship to differences in femoral trochlear geometry. Methods: Twelve fresh-frozen cadaveric knees were used. Five components of the quadriceps and the iliotibial band were loaded physiologically with 175 N and 30 N, respectively. The force required to displace the patella 10 mm laterally and medially at 0°, 20°, 30°, 60° and 90° knee flexion was measured. Patellofemoral contact points at these knee flexion angles were marked. The trochlea cartilage geometry at these flexion angles was visualized by Computed Tomography imaging of the femora in air with no overlying tissue. The sulcus, medial and lateral facet angles were measured. The facet angles were measured relative to the posterior condylar datum. Results: The lateral facet slope decreased progressively with flexion from 23° ± 3° (mean ± S.D.) at 0° to 17 ± 5° at 90°. While the medial facet angle increased progressively from 8° ± 8° to 36° ± 9° between 0° and 90°. Patellar lateral stability varied from 96 ± 22 N at 0°, to 77 ± 23 N at 20°, then to 101 ± 27 N at 90° knee flexion. Medial stability varied from 74 ± 20 N at 0° to 170 ± 21 N at 90°. There were significant correlations between the sulcus angle and the medial facet angle with medial stability (r = 0.78, p < 0.0001). Conclusions: These results provide objective evidence relating the changes of femoral profile geometry with knee flexion to patellofemoral stability.

Background: Several trials have compared the clinical results between anatomic double-bundle and single-bundle anterior cruciate ligament reconstruction procedures. However, it remains controversial whether the anatomic double-bundle procedure is superior to the single-bundle procedure. Hypothesis: The anatomic double-bundle procedure will be better than the single-bundle procedure at resisting anterior laxity, internal rotation laxity, and pivot-shift instability. Study Design: Controlled laboratory study. Methods: Eight cadaveric knees were tested in a 6 degrees of freedom rig using the following loading conditions: 90-N anterior tibialforce, 5-N·m internal and external tibial torques, and a simulated pivot-shift test. Tibiofemoral kinematics during the flexion-extension cycle were recorded with an optical tracking system for (1) intact, (2) anterior cruciate ligament–deficient knee, (3) anatomic double-bundle reconstruction, and (4) single-bundle reconstruction placed at 11 o’clock in the intercondylar notch. Results: There were significant reductions of anterior laxity of 3.5 mm at 20° of flexion, internal rotational laxity of 2.5° at 20° of flexion, and anterior translations (2 mm) and internal rotations (5°) in the simulated pivot-shift test in the double-bundle reconstruction com-pared with the single-bundle reconstruction. There were no significant differences between the 2 procedures for external rotation laxity. Conclusion: The postoperative anterior translation and internal rotation stability after anatomic double-bundle anterior cruciate ligament reconstruction were significantly better than after single-bundle reconstruction, in both static tests and the pivot shift. Clinical Relevance: Unlike previous laboratory studies, this work used clinical arthroscopic methods for anterior cruciate ligament reconstruction, and found that the anatomic reconstruction was superior to a single graft placed at 11 o’clock.

Patellofemoral dysfunction following total knee replacement (TKR) is a significant clinical problem, but little information exists on the mechanics of the patellofemoral retinacula or the effects of TKR on these structures. We hypothesized that TKR would cause significant elongation of the retinacula. Retinacular length changes were measured by threading sutures along the retinacula, fixing the sutures to the patella and the iliotibial band (ITB), and attaching the femoral ends to displacement transducers. The intact knee was flexed-extended while the quadriceps and ITB were tensed and the retinacular length change patterns were recorded. The measurements were repeated post-TKR. The medial patellofemoral ligament (MPFL) was close to isometric, stretching 2 mm in terminal knee extension, whereas the lateral retinaculum slackened 8 mm from 110 degrees to 0 degrees flexion. TKR did not cause significant elongation of either of the retinacula, the largest change being 3 mm elongation of the MPFL around 40 degrees , which stretched the MPFL by 1.4 mm above its maximum natural length. Thus, this work did not support the hypothesis that TKR causes significant elongation of the retinacula sufficient to affect knee function.

Overstuffing the patellofemoral compartment during TKR leads to complications such as maltracking and wear, predisposing to early failure. However, there is no data describing how the patellar construct thickness affects the retinacula. This study instrumented cadaveric knees that had a Genesis II (Smith & Nephew, Memphis, TN, USA) TKR in situ. Sutures were passed along the medial patellofemoral ligament (MPFL) and the deep transverse fibre band of the lateral retinaculum, from the ilio-tibial band (ITB) to the patella. These sutures were attached to displacement transducers. Length changes in the retinacula were measured during knee flexion-extension against the actions of 175 N quadriceps and 30 N ITB tensions. This was done with the natural patellar thickness, then repeated with the patella 2 mm thinner, 2 mm thicker and 4 mm thicker (overstuffed). Each thickness change caused a significant overall slackening or stretching of the MPFL (P < 0.0001 by ANOVA), with 2.3 mm mean stretching (P < 0.001 all angles of knee flexion by post-testing) at 4 mm thicker. The ITB-patellar band was not slackened (P = 0.491) or stretched (P = 0.346) significantly by 2 mm thickness changes. 4 mm thickening stretched the lateral retinaculum 1.1 mm (P = 0.0108). Patellar thickness affected the MPFL more than the lateral retinaculum. This difference reflected the mobile attachment of the lateral retinaculum to the ITB, whereas the MPFL was stretched directly between bony attachments. 2 mm overstuffing did not stretch the retinacula sufficiently to cause mechanical effects.

Background: The survival motor neuron 1 (SMN1) gene has been recognized to be responsible for spinal muscular atrophy (SMA) because it is homozygously deleted in more than 90% of SMA patients, irrespective of their clinical severity, whereas the neuronal apoptosis inhibitory protein (NAIP) gene is now considered to be a modifying factor of the severity of SMA. In Malaysia, it remains to be elucidated whether deletion of the SMN1 gene is also a main cause of SMA or whether deletion of the NAIP gene is found in the SMA patients. Methods: To clarify the pathogenesis of SMA in Malaysia, a deletion analysis of the SMN1 and NAIP genes was performed in 24 Malaysian SMA patients. Deletion analysis of exons 7 and 8 of the SMN1 gene was performed according to the method described by van der Steege et al., while deletion analysis of exon 5 of the NAIP gene was performed according to a method described by Roy et al. Results: Homozygous deletion of SMN1 exon 7 and exon 8 were identified in 19 out of 24 patients (79%). As to the NAIP gene, deletion of exon 5 was detected in six out of 24 patients (25%). NAIP gene deletion was correlated with severity of the disease. Conclusions: Deletion of the SMN1 exon 7 is a major cause of SMA in Malaysia, and NAIP gene deletions are not rare in type I SMA in Malaysia. The lower percentage of the SMN1 gene deletion may be due to the possibility that the present study included some patients without SMN1 gene abnormality and/or some patients with non-deletion type mutations in the SMN1 gene.

Acquired or inherent drug resistance is the major problem in achieving successful cancer treatment. However, the mechanism(s) of pleiotropic drug resistance remains obscure. We have identified and characterized a cellular metabolic strategy that differentiates drug-resistant cells from drug-sensitive cells. This strategy may serve to protect drug-resistant cells from damage caused by chemotherapeutic agents and radiation. We show that drug-resistant cells have low mitochondrial membrane potential, use nonglucose carbon sources (fatty acids) for mitochondrial oxygen consumption when glucose becomes limited, and are protected from exogenous stress such as radiation. In addition, drug-resistant cells express high levels of mitochondrial uncoupling protein 2 (UCP2). The discovery of this metabolic strategy potentially facilitates the design of novel therapeutic approaches to drug resistance.

INTRODUCTION Hip arthroplasty is commonly performed worldwide. The objective of this study was to determine the diameter of the femoral head in the Malaysian population in relation to gender and race (i.e. among Malay, Chinese and Indian patients). METHODS This was a retrospective cross-sectional study performed between January 1995 and December 2006, evaluating the femoral head diameters of all patients aged 50 years and above who underwent hemiarthroplasty at two major hospitals in Malaysia. RESULTS A total of 945 femoral heads (663 women, 282 men) were evaluated. The mean age of the patients in our cohort was 75.2 ± 9.4 (range 50-101) years. The mean femoral head diameter (with intact articular cartilage) was 44.9 ± 3.2 (range 38-54) mm. In our study, men had a significantly larger mean femoral head diameter than women (47.7 ± 2.8 mm vs. 43.7 ± 2.4 mm; p < 0.05). Patients of Chinese ethnicity were also found to have significantly larger femoral head diameters, when compared among the three races studied (p < 0.05). CONCLUSION Malaysians have a mean femoral head diameter of 44.9 ± 3.2 mm. Among our patients, Chinese patients had a significantly larger femoral head size than Malay and Indian patients. We also found that, in our cohort, men had significantly larger femoral head diameters than women.

It has been previously demonstrated that mechanical stimuli are important for multipotent human bone marrow-derived mesenchymal stromal cells (hMSCs) to maintain good tissue homeostasis and even to enhance tissue repair processes. In tendons, this is achieved by promoting the cellular proliferation and tenogenic expression/differentiation. The present study was conducted to determine the optimal loading conditions needed to achieve the best proliferation rates and tenogenic differentiation potential. The effects of mechanical uniaxial stretching using different rates and strains were performed on hMSCs cultured in vitro. hMSCs were subjected to cyclical uniaxial stretching of 4, 8 or 12 % strain at 0.5 or 1 Hz for 6, 24, 48 or 72 h. Cell proliferation was analyzed using alamarBlue $$^\circledR $$ assay, while hMSCs differentiation was analyzed using total collagen assay and specific tenogenic gene expression markers (type I collagen, type III collagen, decorin, tenascin-C, scleraxis and tenomodulin). Our results demonstrate that the highest cell proliferation is observed when 4 % strain $$+$$ 1 Hz was applied. However, at 8 % strain $$+$$ 1 Hz loading, collagen production and the tenogenic gene expression were highest. Increasing strain or rates thereafter did not demonstrate any significant increase in both cell proliferation and tenogenic differentiation. In conclusion, our results suggest that 4 % $$+$$ 1 Hz cyclic uniaxial loading increases cell proliferation, but higher strains are required for superior tenogenic expressions. This study suggests that selected loading regimes will stimulate tenogenesis of hMSCs.

Purpose: The purpose of this study was to clarify the changes in the kinematics of the knee that result from isolated deficiency of the anteromedial (AM) or posterolateral (PL) bundle. Methods: Fourteen cadaveric knees were mounted in a6 -df rig and tested using the following 5 loading conditions: 90-N anterior and posterior tibial loads, 5-Nm internal and external tibial torques, and a simulated pivot-shift test. Tibiofemoral kinematics during flexion-extension was recorded with an optical tracking system for (1) intact knees, (2) knees in which the isolated AM bundle was cut, (3) knees in which the isolated PL bundle was cut, and (4) anterior cruciate ligament (ACL)edeficient knees. The distances between the femoral and tibial attachments of the AM and PL bundles of the ACL were also calculated. Results: Anterior translation laxity under an anterior tibial load, rotational laxity under an internal tibial torque, and anterior translation laxity under pivot-shift loading were significantly different between the knees with AM and PL bundle deficiencies (P < .024), but the changes were small: less than 3 mm or 1.5 � . The AM bundle distance increased significantly more after an AM bundle tear (P ¼ .004) than after a PL bundle tear in flexion. Cutting the PL bundle did not have a significant effect on the lengths between the bundle attachments. Conclusions: An isolated AM or PL bundle tear caused a small increase in laxity (

To study the effect of increasing patellar thickness (overstuffing) on patellofemoral kinematics in total knee arthroplasty and whether subsequent lateral retinacular release would restore the change in kinematics. The quadriceps of eight fresh-frozen knees were loaded on a custom-made jig. Kinematic data were recorded using an optical tracking device for the native knee, following total knee arthroplasty (TKA), then with patellar thicknesses from −2 to +4 mm, during knee extension motion. Staged lateral retinacular releases were performed to examine the restoration of normal patellar kinematics. Compared to the native knee, TKA led to significant changes in patellofemoral kinematics, with significant increases in lateral shift, tilt and rotation. When patellar composite thickness was increased, the patella tilted further laterally. Lateral release partly corrected this lateral tilt but caused abnormal tibial external rotation. With complete release of the lateral retinaculum and capsule, the patella with an increased thickness of 4 mm remained more laterally tilted compared to the TKA with normal patellar thickness between 45° and 55° knee flexion and from 75° onwards. This was on average by 2.4° ± 2.9° (p

The use of growth differentiation factor 5 (GDF-5) in damaged tendons has been shown to improve tendon repair. It has been hypothesized that further improvements may be achieved when GDF-5 is used to promote cell proliferation and induce tenogenic differentiation in human bone marrow-derived mesenchymal stem cells (hMSCs). However, the optimal conditions required to produce these effects on hMSCs have not been demonstrated in previous studies. A study to determine cell proliferation and tenogenic differentiation in hMSCs exposed to different concentrations of GDF-5 (0, 5, 25, 50, 100 and 500 ng/ml) was thus conducted. No significant changes were observed in the cell proliferation rate in hMSCs treated at different concentrations of GDF-5. GDF-5 appeared to induce tenogenic differentiation at 100 ng/ml, as reflected by (1) a significant increase in total collagen expression, similar to that of the primary native human tenocyte culture; (2) a significant upregulation in candidate tenogenic marker gene expression, i.e. scleraxis, tenascin-C and type-I collagen; (3) the ratio of type-I collagen to type-III collagen expression was elevated to levels similar to that of human tenocyte cultures, and (4) a significant downregulation of the non-tenogenic marker genes runt-related transcription factor 2 and sex determining region Y (SRY)-box 9 at day 7 of GDF-5 induction, further excluding hMSC differentiation into other lineages. In conclusion, GDF-5 does not alter the proliferation rates of hMSCs, but, instead, induces an optimal tenogenic differentiation response at 100 ng/ml.

Total knee arthroplasty (TKA) is a procedure with function dependent upon correct tensioning of the soft-tissue constraints. The purpose of this study was to examine the length-change behaviour of the collateral ligaments during knee flexion–extension before and after TKA. The influence of differing degrees of internal-external rotation of the femoral component on slackening/tightening of the collateral ligaments during knee flexion was to be studied. The length-change patterns of the collateral ligaments were measured in eight intact knees in vitro: sutures were passed along the ligaments and attached to displacement transducers. Measurements were repeated after TKA with the femoral component in neutral rotation, then with 5° internal and 5° external rotation. Both the MCL and LCL slackened during knee flexion from 0° to 110° flexion, at all stages of the experiment. In the native knee, the MCL slackened 2 mm, whilst the LCL slackened 7 mm. The MCL slackened a further 3 mm and the LCL a further 4 mm during flexion post-TKA. A 5° external rotation of the femoral component slackened the MCL 2 mm more and tightened the LCL by 2 mm. The opposite effects resulted from 5° internal rotation. The collateral ligaments slackened more than normal following TKA, and these length changes were increased by femoral component rotation. External rotation of the femoral component to address patellar tracking may slacken the MCL and thus lead to valgus instability in the flexed knee.

Background: Although both anatomic double-bundle and single-bundle anterior cruciate ligament reconstruction procedures are in use, it remains controversial whether the anatomic double-bundle procedure is biomechanically superior.Hypothesis: The anatomic double-bundle procedure would be better than both laterally placed anatomic and nonanatomic transtibial single-bundle procedures at restoring to normal the tibial anterior translation, internal rotation, and pivot-shift instability. It was also hypothesized that tibial internal rotation would be closer to normal after laterally placed anatomic single-bundle reconstruction than after the nonanatomic reconstruction.Study Design: Controlled laboratory study.Methods: Eight cadaveric knees were mounted in a 6 degrees of freedom rig and tested using the following loading conditions: 90-N anterior and posterior tibial forces, 5-N·m internal and external tibial rotation torques, and a simulated pivot-shift test. Tibiofemoral kinematics during the flexion-extension cycle were recorded with an optical tracking system for (1) intact, (2) anterior cruciate ligament–deficient knee, (3) anatomic double-bundle reconstruction, (4) nonanatomic single-bundle reconstruction, and (5) laterally placed single-bundle reconstruction.Results: Rotational laxity with internal tibial torque and anterior laxity in the simulated pivot shift were significantly less in the double-bundle reconstruction and laterally placed single-bundle reconstruction compared with the nonanatomic single-bundle reconstruction. There were no significant differences between the 3 procedures when anterior and posterior tibial translation forces and external rotation torques were applied. In addition, there were no significant differences between the double-bundle reconstruction and laterally placed single-bundle reconstruction.Conclusion: The postoperative rotational and pivot-shift laxity after anatomic double-bundle anterior cruciate ligament reconstruction was significantly better than that after nonanatomic single-bundle reconstruction. However, there were no significant differences between the double-bundle reconstruction and laterally placed single-bundle reconstruction.Clinical Relevance: This work suggests that a single-bundle reconstruction may be better able to control both knee laxity and pivot-shift instability if the femoral tunnel is moved to a more lateral position and that then the double-bundle reconstruction may not offer significant further advantages.

BACKGROUND: Vaginitis due to Trichomonas vaginalis is one of the most common of sexually transmitted diseases. Trichomoniasis affects women during pregnancy as well but it is not clearly established whether it causes preterm birth and other pregnancy complications. OBJECTIVES: The objective of this review was to assess the effects of various treatments for trichomoniasis during pregnancy. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (14 January 2011). SELECTION CRITERIA: Randomized trials comparing anti-trichomonas agents during pregnancy. Trials including symptomatic or asymptomatic women with trichomoniasis were eligible. DATA COLLECTION AND ANALYSIS: Two review authors assessed eligibility and trial quality. MAIN RESULTS: We included two trials with 842 pregnant women. In both trials around 90% of women were cleared of trichomonas in the vagina after treatment. In the US trial, women with asymptomatic trichomoniasis between 16 and 23 weeks were treated with metronidazole on two occasions at least two weeks apart. The trial was stopped before reaching its target recruitment because metronidazole was not effective in reducing preterm birth and there was a likelihood of harm (risk ratio 1.78; 95% confidence interval 1.19 to 2.66). The South African trial recruited women later in pregnancy and did not have the design and power to address adverse clinical outcomes. We excluded two recent studies, identified for the current update, because they did not address the primary question. AUTHORS' CONCLUSIONS: Metronidazole, given as a single dose, is likely to provide parasitological cure for trichomoniasis, but it is not known whether this treatment will have any effect on pregnancy outcomes. The cure rate could probably be higher if more partners used the treatment.

Malrotation of the femoral component may cause patellofemoral complications after total knee replacement (TKR). We hypothesized that femoral component malrotation would cause excessive lengthening of the retinacula. Retinacular length changes were measured by threading fine sutures along them and attaching these to the patella and to displacement transducers. The knee post-TKR was flexed-extended while the quadriceps were tensed, then the measurements repeated after rotating the femoral component 5 degrees internally and then 5 degrees externally. Internal rotation shortened the medial patellofemoral ligament (MPFL) significantly from 100 degrees to 0 degrees extension. External rotation lengthened the MPFL significantly from 90 degrees to 0 degrees extension. The transverse fibers of the lateral retinaculum showed no significant differences. The MPFL attaches directly from bone to bone, so it was lengthened directly by movement of the trochlea and patella, whereas the deep transverse fibers of the lateral retinaculum attach to the mobile iliotibial tract, so they were not lengthened directly.

To find out the knowledge and practices among the general practitioners (GPs) of Karachi regarding dog bite management.This cross sectional study was carried out in private and public Qlinics of Karachi using a pre-tested self-administered questionnaire. The study population was composed of 151 GPs with MBBS degree. Data was analyzed on SPSS version 12.0.Out of total 151 general practitioners, 124 were male and 27/female doctors. The majority (77.5%) of GPs knew the cause of rabies, but only 51.7% knew about the incubation period. Only 19.4% GPs had appropriate knowledge about the first line treatment. Almost all GPs (98%) had no knowledge about the types of anti-rabies vaccine and only 19.2% knew about anti-rabies serum.There is an apparent lack of awareness among GPs regarding appropriate animal wound management and vaccine administration. Reorientation programmes and continued medical education (CME) for GPs are required to highlight WHO guidelines regarding treatment of animal bite.

Differing descriptions of patellar motion relative to the femur have resulted from previous studies. We hypothesized that patellar kinematics would correlate to the trochlear geometry and that differing descriptions could be reconciled by accounting for differing alignments of measurement axes. Seven normal fresh-frozen knees were CT scanned, and their kinematics with quadriceps loading was measured by an optical tracker system. Kinematics was calculated in relation to the femoral epicondylar, anatomic, and mechanical axes. A novel trochlear axis was defined, between the centers of spheres best fitted to the medial and lateral trochlear articular surfaces. The path of the center of the patella was circular and uniplanar (root-mean-square error 0.3 mm) above 16+/-3 degrees (mean+/-SD) knee flexion. In the coronal plane, this circle was aligned 6+/-2 degrees from the femoral anatomical axis, close to the mechanical axis alignment. It was 91+/-3 degrees from the epicondylar axis, and 88+/-3 degrees from the trochlear axis. In the transverse plane it was 91+/-3 degrees and 88+/-3 degrees from the epicondylar and trochlear axes, respectively. Manipulation of the data to different axis alignments showed that differing previously published data could be reconciled. The circular path of patellar motion around the trochlea, aligned with the mechanical axis of the leg, is easily visualized and understood.

In routine coronary angiography, bifurcation lesion is not uncommon. Current practice of dealing with type 4a coronary bifurcation lesions (lesions of main branch without significant lesions of the side branch) may lead to true bifurcation lesions after stenting due to axial plaque redistribution. This series describes an experience with Greek technique for treatment of type 4a bifurcation lesions in 18 patients for primary stenting of main vessel with simultaneous kissing balloon of side branch in an effort to avoid snow plough effect.

We carried out a prospective study of 47 Exeter (Stryker Inc, Warsaw, Ind) small stem total hip arthroplasty in 42 patients with an average age of 58 years and a mean follow-up of 8.5 years. The Oxford hip score improved from a preoperative mean of 47 to 17 at last follow-up. More than 87% patients had excellent or good Harris hip scores, and 90% were able to walk with little or no pain. Stem subsidence within the cement mantle was observed in 26% of cases, and none showed evidence of aseptic loosening or implant failure. Two stems were removed due to infection. The survival rate of this implant was 95.7% at 10 years. This first series of Exeter small stem showed excellent medium-term results, comparable to its larger counterparts.

In the natural and prosthetic knees the position, shape, and orientation of the trochlea groove are three of the key determinants of function and dysfunction, yet the rules governing these three features remain elusive.The aim was to define the three-dimensional geometry of the femoral trochlea and its relation to the tibiofemoral joint in terms of angles and distances.Forty CT scans of femurs of healthy patients were analyzed using custom-designed imaging software. After aligning the femur using various axes, the locations and orientations of the groove and the trochlear axis were examined in relation to the conventional axes of the femur.The trochlear groove was circular and positioned laterally in relation to the mechanical, anatomic, and transcondylar axes of the femur; it was not aligned with any of these axes. We have defined the trochlear axis as a line joining the centers of two spheres fitted to the trochlear surfaces lateral and medial to the trochlear groove. When viewed after aligning the femur to this new axis, the trochlear groove appeared more linear than when other methods of orientation were used.Our study shows the importance of reliable femoral orientation when reporting the shape of the trochlear groove.

Despite improvements in component design and surgical technique, some patients still require lateral retinacular release during TKA to improve patella tracking. We studied 148 fixed-bearing TKAs to identify parameters in pre-operative knee radiographs that would predict intraoperative patellar maltracking. Digital radiographs and software were used to measure coronal alignment, distal femoral valgus angle, proximal tibia varus angle, patellar tilt, patellar shift, Insall–Salvati ratio, and patellar component placement and alignment. Patellar tracking was assessed after all components had been cemented, using both no-touch and modified “towel clip” techniques. The only radiographic parameter independently associated with maltracking was patellar shift. The median pre-operative patellar lateral shift in patients who had maltracking was 4.1 mm compared to 0.0 mm in those who did not. Patients who had a patellar shift of more than 3.0 mm had a high likelihood of maltracking, with estimated positive and negative predictive values of 78 and 95%, respectively. Pre-operative patellar shift may thus be clinically relevant for identifying osteoarthritic patients who have a higher likelihood for patellar maltracking during TKA. Variations in the intrinsic risk for maltracking within patient study populations may account for the widely differing reported rates of patellar maltracking, and our data suggest that information on pre-operative patellar shift may be helpful in stratifying these sample populations.

This study investigated the effect of loading the iliotibial band (ITB) on the stability of the patellofemoral joint. We measured the restraining force required to displace the patella 10 mm medially and laterally (defined as medial and lateral stability, respectively) in 14 fresh-frozen knees from 0 to 90 degrees knee flexion. The testing rig allowed the patella to rotate and translate freely during this displacement. The quadriceps was separated into five components and loaded with 175 N total tension. Testing was performed at 0 to 90 N ITB tension. With no ITB tension, the lateral restraining force ranged from 82 to 101 N across 0 to 90 degrees flexion. Increasing ITB tension caused progressive reduction of the lateral restraining force. The maximum reduction was 25% at 60 degrees flexion and 90 N ITB tension. Medial restraining force increased progressively with increasing knee flexion and increasing ITB loads; it ranged from 74 N at 0 degrees knee flexion and 0 N ITB tension to 211 N at 90 degrees knee flexion and 90 N ITB tension. The maximum effect was an increase of medial restraining force of 50% at 90 degrees flexion and 90 N ITB tension.

This paper describes a longitudinal patellar-splitting approach to the knee that includes provision for accurate reconstruction. Our in vitro experiments showed that patellofemoral kinematics and length-change patterns of specific bands of the peripatellar retinacula were not changed significantly by opening and closing the knee via the transpatellar approach. This surgical approach will be useful for in vitro experiments on the knee, when effects due to alterations of internal structures such as cruciate ligament reconstructions or joint replacement are to be studied, avoiding confounding effects caused by changes to the retinacula.

The iliotibial band (ITB) has an important role in knee mechanics and tightness can cause patellofemoral maltracking. This study investigated the effects of increasing ITB tension on knee kinematics. Nine fresh-frozen cadaveric knees had the components of the quadriceps loaded with 175 N. A Polaris optical tracking system was used to acquire joint kinematics during extension from 100 degrees to 0 degrees flexion. This was repeated after the following ITB loads: 30, 60 and 90 N. There was no change with 30 N load for patellar translation. On average, at 60 and 90 N, the patella translated laterally by 0.8 and 1.4mm in the mid flexion range compared to the ITB unloaded condition. The patella became more laterally tilted with increasing ITB loads by 0.7 degrees, 1.2 degrees and 1.5 degrees for 30, 60 and 90 N, respectively. There were comparable increases in patellar lateral rotation (distal patella moves laterally) towards the end of the flexion cycle. Increased external rotation of the tibia occurred from early flexion onwards and was maximal between 60 degrees and 75 degrees flexion. The increase was 5.2 degrees, 9.5 degrees and 13 degrees in this range for 30, 60 and 90 N, respectively. Increased tibial abduction with ITB loads was not observed. The combination of increased patellar lateral translation and tilt suggests increased lateral cartilage pressure. Additionally, the increased tibial external rotation would increase the Q angle. The clinical consequences and their relationship to lateral retinacular releases may be examined, now that the effects of a tight ITB are known.

Patient selection for lateral retinacular release (LRR) and its efficacy are controversial. Iatrogenic medial subluxation can occur with inappropriate LRR. The aim of this study was to determine the reduction in patellofemoral stability with progressively more extensive LRR. The force required to displace the patella 10mm medially and laterally in nine cadaveric knees was measured with and without loading of the quadriceps and iliotibial band. The knee was tested intact, then after progressive release beginning proximal to the patella (PR), the mid-level between the proximal and distal limit of the patella (MR) where the fibres are more transverse, then distally till Gerdy's tubercle (DR) and finally the joint capsule (CR). Both medial and lateral stability decreased with progressive releases, larger for the medial. The MR caused a significant reduction of lateral stability between 30 degrees and 90 degrees of knee flexion. There was an 8% reduction in medial stability at 0 degrees flexion with a complete LRR (DR). A comparable reduction in medial stability in the loaded knee at 20 degrees and 30 degrees flexion was obtained with MR alone, with no further reduction after DR. A capsular release caused a further reduction in medial stability at 0 degrees and 20 degrees and this was marked in the unloaded knee. In extension, the main lateral restraint was the joint capsule. At 30 degrees flexion, the transverse fibres were the main contributor to the lateral restraint.

Anatomical descriptions of the lateral retinaculum have been published, but the attachments, name or even existence of its tissue bands and layers are ill-defined. We have examined 35 specimens of the knee. The deep fascia is the most superficial layer and the joint capsule is the deepest. The intermediate layer is the most substantial and consists of derivatives of the iliotibial band and the quadriceps aponeurosis. The longitudinal fibres of the iliotibial band merge with those of the quadriceps aponeurosis adjacent to the patella. These longitudinal fibres are reinforced by superficial arciform fibres and on the deep aspect by transverse fibres of the iliotibial band. The latter are dense and provide attachment of the iliotibial band to the patella and the tendon of vastus lateralis obliquus. Our study identifies two important new findings which are a constant connection of the deep fascia to the quadriceps tendon superior and lateral to the patella, and, a connection of the deeper transverse fibres to the tendon of vastus lateralis obliquus.

Optimal patellar tracking and component alignment are important in achieving a well-functioning total knee arthroplasty (TKA). The patella is constrained partly by design of the prosthetic trochlear groove, and patellar tracking is governed by a combination of static and dynamic factors. Maltracking may result from excessive or unbalanced tension in the surrounding soft tissues. This article describes a staged progressive lateral release of the patellar retinaculum in TKA, which is classified into 6 stages. Stage 1 transects the deep lateral patellofemoral ligament; stages 2 to 6 extend the lateral patellar incision distally from vastus lateralis to the tibial tubercle. This technique was used in a series of 96 primary TKAs. We report the rates of the various stages of lateral release and the variables that might affect the decision to perform such a release.

Neurofibromas are relatively common lesions of the nervous system, but only a few cases involving the pinna have been reported. The emphasis in most of these reports was on the cosmetic deformity; functional impairment in the form of hearing loss has been mentioned in only a few reports. We report a case of pinnal neurofibroma in which the primary complaint was otitis externa; hearing loss and cosmetic deformity were also present. Surgical excision resulted in an excellent functional and cosmetic outcome. This case demonstrates that neurofibroma of the pinna in the area of the external meatus can produce functional as well as cosmetic impairment, and surgery can produce a very satisfactory result.

To describe the distribution of over weight and body mass index, waist circumference and waist/ hip ratio, correlate obesity measures to coronary heart disease risk factors in comparison to Pakistan National Survey (PNS).The Metroville Health Study (MHS) was an urban risk factor reduction intervention study in Metroville Karachi. Base line data was used which was not a random sample. Demographic data including serum cholesterol, glucose, haemoglobin, and blood pressure were collected.In MHS high cholesterol was 16% and 24% in men and women respectively, and 25% had hypertension. Self-reported diabetes was 8%, over-weight/obesity 34% and 49% for men and women, compared to 16% and 25% for PNS, while high risk waist-hip ratio (WHR) was present in 41% and 72% of men and women respectively. Under-weight in Metroville men was 12% and 9% in women, compared to 26% and 27% in PNS. The anthropometry variables were significantly correlated with each other while weight was significantly correlated with TC and waist circumference (WC).Obesity was alarmingly prevalent in urban Metroville in comparison to PNS. Cardio Vascular Disease (CVD) risk factors were prevalent in Metroville and TC and WC were significantly correlated with obesity measures. For prevention of increasing CVD in urban communities, targeted programs of intervention are required.

This study was carried out to determine the pattern of coronary arterial distribution and its relation with coronary artery diameter in adult Pakistani population as demonstrated by selective coronary angiography.Consecutive series of 220 adult subjects who underwent diagnostic coronary angiography at National Institute of Cardiovascular Disease (NICVD) between May 2000 and December 2000 were studied. Patients whose age was more than 18 years, with no apparent disease in the proximal arterial segment, proximal artery and tip of the catheter in the middle of the frame and catheter of a No. 6 French size of same manufacturer used were included in this study. Patients who were given vasodilator before or during the procedure, angiograms showing complete proximal occlusions or ectatic arteries were excluded.Sixty percent subjects had right dominance pattern of which 78.1% were male and 21.8% female. By contrast 15% had left coronary dominance, of which 78.7 % were male and 21.2% female. Where as, 24% patients had co-dominant (balanced) circulation with 83.3% male and 16.6 % female. In patients with left dominant pattern, the mean diameter of the right coronary artery (RCA) was significantly smaller (p0.001) as compared to dominant right or co-dominant pattern. Where as in patients with right dominant pattern, the mean diameter of the circumflex (CX) artery was significantly smaller (p0.001) as compared to dominant left.The coronary arterial distribution in Pakistani population is not significantly different from that given in the literature and the diameter of the RCA and the CX artery are significantly affected by dominance pattern.

The National Action Plan for Non-Communicable Disease Prevention, Control and Health Promotion in Pakistan (NAP-NCD) incorporates prevention and control of cardiovascular diseases (CVD) as part of a comprehensive and integrated non-communicable Disease (NCD) prevention effort. In this programme, surveillance of cardiovascular risk factors is part of an integrated population-based NCD surveillance system. The population approach to CVD prevention is a priority area in this programme with a focus on broad policy measures and behavioural change communication. The former include revision of the current policy on diet and nutrition to expand its focus on under-nutrition; the development of a physical activity policy; strategies to limit the production of, and access to, ghee as a medium for cooking and agricultural and fiscal policies that increase the demand for, and make healthy food more accessible. The programme focuses attention on improving the quality of prevention programmes within primary and basic health sites and integrates concerted primary and secondary prevention programmes into health services as part of a comprehensive and sustainable, scientifically valid, and resource-sensitive programme for all categories of healthcare providers. It promotes screening for raised blood pressure at the population level and screening for dyslipidaemia and diabetes in high-risk groups only. It highlights the need to ensure the availability of aspirin, beta blockers, thiazides, ACE inhibitors, statins and penicillin at all levels of healthcare. The programme points out the need to conduct clinical end-point trials in the native Pakistani setting to define cost-effective therapeutic strategies for primary and secondary prevention of CVDs. Emphasis is laid on building capacity of health systems in support of CVD prevention and control and building a coalition or network of organizations to add momentum to CVD prevention and control efforts.