Laboratory-based X-ray phase-contrast imaging technique for material and medical science applications.

In-line X-ray phase-contrast imaging technique is an emerging method for the study of materials such as carbon fibers, carbon composite materials, polymers, etc. Similarly this technique is also well suited for the imaging of soft materials such as tissues, distinguishing between tumor and normal tissue. These represent the class of materials for which X-ray attenuation cross-section is very small. Thus this method promises a far better contrast for low X-ray absorbing substances than the conventional radiography method. We have set up an experimental facility using a combination of X-ray CCD detector and a microfocus X-ray source. This facility is dedicated to micro-imaging experiments such as microtomography and high-resolution phase-contrast experiments. In this paper, the results of X-ray phase-contrast imaging experiments are described.     

Role of Periarticular Liposomal Bupivacaine Infiltration in Patients Undergoing Total Knee Arthroplasty—A Meta-analysis of Comparative Trials

Background

Over last 2 years, many trials have evaluated newly approved liposomal bupivacaine for periarticular infiltration in total knee arthroplasty (TKA) with mixed results. Our meta-analysis attempts to consolidate the results and make evidence-based conclusions.

Comparison of digital and plain radiography preoperative templating in total knee arthroplasty

We present the results of prospective evaluation of digital compared to plain radiographic preoperative templating for primary total knee replacement. All consecutive patients undergoing primary knee replacement were eligible. Patients with previous knee replacement or without calibrated digital or plain radiographs were excluded. Plain radiographs were templated against acetate templates. Digital images were templated with the help of commercial software TraumaCad. A 25-mm spherical metal ball placed nearest to the affected knee joint acted as calibration object. The ICC value for intra-rater reliability was 0.846 for tibial templating and 0.840 for femoral templating. PFC sigma cruciate substituting components were implanted in all patients. Twenty-eight consecutive patients between April 2006 and June 2007 were included. Accurate digital templating score was 80% for tibial implant and 40% for femur. Accuracy of analog templating was 55% for tibial implant and 50% for femur. There was no mismatch of over one size. The differences between templated and implanted sizes were plotted against their mean in Bland–Altman plot. The 95% confidence interval of the differences between digital and actual sizes were: 0.78 to −0.75 sizes for tibial implant and 1.15 to −0.93 sizes for femoral implant. The 95% confidence interval of the differences between plain and actual sizes were: 0.38 to −0.99 size for tibial implant and 0.93 to −1.32 size for femoral implant. The two tailed P value for difference between digital and analog templating from a Wilcoxon matched pair signed rank test was 0.021 for tibia and 0.006 for femur. We found preoperative templating by the operating surgeon reliable and accurate but digital templating did not offer any additional advantage.     

Seizure Frequency Can Alter Brain Connectivity: Evidence from Resting-State fMRI

BACKGROUND AND PURPOSE:The frequency of seizures is an important factor that can alter functional brain connectivity. Analysis of this factor in patients with epilepsy is complex because of disease- and medication-induced confounders. Because patients with hot-water epilepsy generally are not on long-term drug therapy, we used seed-based connectivity analysis in these patients to assess connectivity changes associated with seizure frequency without confounding from antiepileptic drugs.MATERIALS AND METHODS:Resting-state fMRI data from 36 patients with hot-water epilepsy (18 with frequent seizures [>2 per month] and 18 with infrequent seizures [≤2 per month]) and 18 healthy age- and sex-matched controls were analyzed for seed-to-voxel connectivity by using 106 seeds. Voxel wise paired t-test analysis (P < .005, corrected for false-discovery rate) was used to identify significant intergroup differences between these groups.RESULTS:Connectivity analysis revealed significant differences between the 2 groups (P < .001). Patients in the frequent-seizure group had increased connectivity within the medial temporal structures and widespread areas of poor connectivity, even involving the default mode network, in comparison with those in the infrequent-seizure group. Patients in the infrequent-seizure group had focal abnormalities with increased default mode network connectivity and decreased left entorhinal cortex connectivity.CONCLUSIONS:The results of this study suggest that seizure frequency can alter functional brain connectivity, which can be visualized by using resting-state fMRI. Imaging features such as diffuse network abnormalities, involvement of the default mode network, and recruitment of medial temporal lobe structures were seen only in patients with frequent seizures. Future studies in more common epilepsy groups, however, will be required to further establish this finding.

Behind the unquestionable clinical and electroencephalographic manifestations of an epileptic seizure, there lie several molecular, metabolic, cellular, and hemodynamic events that alter the function of the brain in a complex manner. These alterations may be transient, but many such events can have a cumulative effect, resulting in psychological and memory deficits, personality changes, and reduced functioning in patients with epilepsy. Advances in neurophysiology, functional imaging, and computational neurosciences have made it possible to derive models mathematically to describe such complex diseases.Disease-state network analysis with resting-state fMRI is becoming increasingly popular because of its superior spatial resolution, nondependence on task, ease of acquisition, and ability to visualize whole-brain functional networks, which are amenable to long-term changes related to disease states.¹ Application of connectivity principles to these data has promoted research in various aspects of epileptic seizures, and there has been overwhelming report of decreased connectivity around the seizure-onset zone^2–6 and the default mode network (DMN) by several groups.^7,8 In 2012, Jehi⁷ and Morgan et al⁹ reported that connectivity patterns were different in patients with right and left mesial temporal sclerosis and that there was decreased connectivity between the regions of the DMN and the hippocampus and amygdala in patients with mesial temporal sclerosis. Similarly, hemispheric connectivity analysis in patients with unilateral mesial temporal sclerosis revealed decreased local and intrahemispheric connectivity and increased interhemispheric connectivity.¹⁰ In contradistinction to the aforementioned results, there have been reports on increased hippocampal connectivity that was presumed to be a compensatory mechanism because it linearly correlated with a disease duration of >10 years.^1–4,6 Graph-theory analysis of resting-state fMRI data from patients with epilepsy also revealed decreased functional nodal topologic properties of the DMN that were positively correlated with disease duration.^8,11–14 Regional homogeneity analysis of resting-state fMRI data was even used as a presurgical tool for seizure identification in patients with MR-negative focal epilepsy.¹⁵ Thus, various models of data analysis have helped in understanding epilepsy further, and now there is increasing interest in using these models to reclassify epilepsy as a focal epileptogenic area^10,15 or as a network of seizure-generating areas.^16–18Gower''s clinical observation that “seizures beget seizures” in 1881 triggered several studies, especially animal models that addressed the genesis of epilepsy. Kindling is a phenomenon in which the repetition of subconvulsive electrical stimuli results in a progressive epileptic state and an increased frequency of seizures.^19,20 Kindling is a continuous temporal process that remodels the mechanisms and circuits in the brain. Early changes, beginning with modulation of presynaptic and postsynaptic functioning in glutamate, N-methyl-d-aspartate, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, and late changes, including mossy fiber sprouting, synaptogenesis/neurogenesis, and neurotrophic factor regulation, are known to occur as a result of kindling.^20–22 The increased risk for seizure recurrence with increasing numbers of seizures was first demonstrated clinically by Hauser and Lee.²³ The effects of seizure frequency and chronic epilepsy have been studied sparsely by using imaging techniques.¹ For example, Widjaja et al²⁴ found no significant correlation with seizure frequency, age of seizure onset, or duration of epilepsy in a group of children with medically refractory epilepsy.Apart from other disease-related confounders such as type of seizure, duration of epilepsy, age of onset, family history of epilepsy, etc, each of which can induce connectivity differences independently, a major limitation of interpreting the results of functional connectivity in patients with epilepsy is the use of antiepileptic drugs. Patients with hot-water epilepsy (HWE) present with a history of complex partial seizures clinically suggestive of temporal lobe onset with or without secondary generalization. Most patients are drug naive at their first evaluation, which provided us an opportunity to study networks that were affected by seizure frequency and matched for other disease-related confounders but not antiepileptic drugs. On the basis of the phenomenon of kindling, we hypothesized that seizures can alter brain connectivity and that the frequency of seizures can influence the magnitude of this alteration. We predicted that patients with a higher seizure frequency would have widespread changes in comparison with patients with a lower seizure frequency. We used seed-to-voxel–based resting-state fMRI connectivity in 36 drug-naive patients with HWE who were comparable in terms of various factors such as age, sex, education, and epilepsy-related confounders. We hope that such quantifiable noninvasive in vivo evidence further enhances knowledge of the etiopathogenesis of HWE and, if applicable to refractory epilepsy, can identify such patients early to avoid time-consuming trial-and-error methods of pharmacotherapy and facilitate early intervention to minimize cognitive deficits.     

Genetic analysis of polymorphisms in biologically relevant candidate genes in patients with abdominal aortic aneurysms

BACKGROUND: Abdominal aortic aneurysms (AAAs) are characterized by histologic signs of chronic inflammation, destructive remodeling of extracellular matrix, and depletion of vascular smooth muscle cells. We investigated the process of extracellular matrix remodeling by performing a genetic association study with polymorphisms in the genes for matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and structural extracellular matrix molecules in AAA. Our hypothesis was that genetic variations in one or more of these genes contribute to greater or lesser activity of these gene products, and thereby contribute to susceptibility for developing AAAs. METHODS: DNA samples from 812 unrelated white subject (AAA, n = 387; controls, n = 425) were genotyped for 14 polymorphisms in 13 different candidate genes: MMP1(nt-1607), MMP2(nt-955), MMP3(nt-1612), MMP9(nt-1562), MMP10(nt+180), MMP12(nt-82), MMP13(nt-77), TIMP1(nt+434), TIMP1(rs2070584), TIMP2(rs2009196), TIMP3(nt-1296), TGFB1(nt-509), ELN(nt+422), and COL3A1(nt+581). Odds ratios and P values adjusted for gender and country of origin using logistic regression and stratified by family history of AAA were calculated to test for association between genotype and disease status. Haplotype analysis was carried out for the two TIMP1 polymorphisms in male subjects. RESULTS: Analyses with one polymorphism per test without interactions showed an association with the two TIMP1 gene polymorphisms (nt+434, P = .0047; rs2070584, P = .015) in male subjects without a family history of AAA. The association remained significant when analyzing TIMP1 haplotypes (chi 2 P = .014 and empirical P = .009). In addition, we found a significant interaction between the polymorphism and gender for MMP10 ( P = .037) in cases without a family history of AAA, as well as between the polymorphism and country of origin for ELN ( P = .0169) and TIMP3 ( P = .0023) in cases with a family history of AAA. CONCLUSIONS: These findings suggest that genetic variations in TIMP1, TIMP3, MMP10, and ELN genes may contribute to the pathogenesis of AAAs. Further work is needed to confirm the findings in an independent set of samples and to study the functional role of these variants in AAA. It is noteworthy that contrary to a previous study, we did not find an association between the MMP9 (nt-1562) polymorphism and AAA, suggesting genetic heterogeneity of the disease. CLINICAL RELEVANCE: Abdominal aortic aneurysms (AAAs) are an important cardiovascular disease, but the genetic and environmental risk factors, which contribute to individual's risk to develop an aneurysm, are poorly understood. Histologically, AAAs are characterized by signs of chronic inflammation, destructive remodeling of the extracellular matrix, and depletion of vascular smooth muscle cells. We hypothesized that genes involved in these events could harbor changes that make individuals more susceptible to developing aneurysms. This study identified significant genetic associations between DNA sequence changes in tissue inhibitor of metalloproteinase 1 (TIMP1), TIMP3, matrix metalloproteinase 10 (MMP10) and elastin (ELN) genes, and AAA. The results will require confirmation using an independent set of samples. After replication it is possible that these sequence changes in combination with other risk factors could be used in the future to identify individuals who are at increased risk for developing an AAA.     

Twenty years' experience of steroids in infantile hemangioma—a developing country's perspective

Background

Hemangioma is a common vascular tumor. Though it involutes spontaneously, results are unpredictable. Steroid therapy is an effective mode of its regression. We present our experience of largest series and possible recommendations for treatment.

Materials and methods

A total of 2398 patients were treated during the study period of 20 years. They were given oral prednisolone, intralesional triamcinolone, or combination of both as per the protocol and followed for the response. Response to the treatment was graded as excellent, good, poor, or no response.

Results

The male-to-female ratio was 1:2.3. In 81% of patients, hemangioma was noticed within first month of life. The commonest site of involvement was head and neck (57%). The commonest clinical presentation was discoloration and swelling. Mean age and size were 8.43 ± 7.04 months and 23.64 ± 20.13 cm². Response rate was highest for superficial type using any modality of treatment. Patients younger than 1 year showed better response (90.3%) in comparison with children older than 1 year (80.8%). The specific complications occurring were infections in 249 (12.4%), cushingoid facies and growth delay in 62 (3.1%), and hypertension in 51 (2.5%) patients.

Conclusion

Steroid therapy either oral or intralesional as per the requirement is an easy and safe modality. Results are good to satisfactory in most patients. The complications are minimal. If treatment is needed, it should be used as a first-line therapy, especially when cost is an important concern.     

Endotoxin‐induced inflammation in a rodent model up‐regulates IL‐1a expression and CD45+ leukocyte recruitment and increases the rate of reepithelialization and wound closure

Wound healing is traditionally divided into inflammation, proliferation, and remodeling phases. Several inflammatory mediators and cells regulate the inflammation phase. The specific roles for different mediators have not been clearly defined. The effects of inflammation phase modulation on wound healing were evaluated in this study. Rat full‐thickness wounds were divided into different experimental groups: (1) sterile hyper‐inflammatory wounds/endotoxin (topical endotoxin), (2) sterile hypo‐inflammatory/inhibitor group (cocktail of topical COX‐1 plus COX‐2 plus lipoxygenase inhibitors), and (3) control groups: topical saline or DMSO. After full‐thickness wound creation, custom‐made titanium chambers enclosed the wound, creating an isolated well‐controlled environment. Wound healing was followed over time; tissue biopsies and wound fluid samples were collected on days 1, 4, and 8 postoperatively. The validity of the inflammation model was confirmed by increased IL‐1a expression, increased CD45+ leukocytes recruitment in the hyper‐inflamed group as compared to the inhibitor and control groups. The reepithelialization percentage was significantly increased in the endotoxin group as compared to the inhibitor group on day 4 (60.75 vs. 22.05, p‐value <0.05) and both the inhibitor and the control group on day 8 (control group: 63.2%, inhibitor group: 28.9%, endotoxin group: 84.2%, p‐value <0.05). Also, the macroscopic wound closure was increased in the endotoxin group as compared to the inhibitor group and control group both on day 4 (control group: 69.9%, inhibitor group: 62.9%, endotoxin group: 81.9%, p‐value <0.05) and on day 8 (control group: 68.5%, inhibitor group: 69.1%, endotoxin group: 83.7%, p‐value <0.05). Endotoxin‐induced sterile inflammation up‐regulates IL‐1a expression and CD45+ leukocyte recruitment and results in faster rate of wound reepithelialization and wound closure in full‐thickness rodent wounds. Conversely, the wound reepithelialization and wound closure can be significantly delayed on treatment with a combination of cyclooxygenase and lipoxygenase inhibitors.     

Femoral neck fracture following ipsilateral total knee replacement: an analysis of associations and risk factors

There have been case reports of ipsilateral femoral neck fracture after total knee replacement. This occurrence has been attributed to risk factors such as rheumatoid arthritis, osteoporosis, steroid use and poor mobility. The aim of this study was to see if total knee replacement is a risk factor for neck of femur fracture and to study the associated risk factors. Twenty two patients who had sustained subsequent ipsilateral femoral neck fracture were identified from 1,362 patients who had previously undergone a posterior cruciate ligament-substituting total knee replacement. Clinical chart review and radiological assessment were performed. The average age of the patients was 77(±7) years and the fracture occurred 35(±27) months following the total knee replacement. Positive associations were identified between ipsilateral neck of femur fracture and total knee replacement (P < 0.01), age (P < 0.01), female sex (P < 0.025) and rheumatoid arthritis (P < 0.05). We did not find an association between ipsilateral neck of femur fracture following total knee replacement and preoperative knee deformity (P > 0.5). We also observed an increased risk of supracondylar fracture of the ipsilateral femur in patients who had sustained a neck of femur fracture following total knee replacement (P < 0.001).     

Coronary endarterectomy for diffuse extensive coronary artery disease

Introduction Atherosclerotic coronary artery disease is in an increasing trend in India. With the advancement of non-surgical methods of revascularisation, the patients coming for surgery are of less attractive anatomy. The role of coronary endarterectomy along with coronary artery bypass grafting for a selected group of these patients is quite promising. Materials and Methods From March 2000 to March 2005, out of 362 CABGs performed, 42 patients had undergone coronary endarterectomy. The age range being from 35 to 76 years, M: F is 38∶4 Hypertension was present in 26 (61%), diabetes mellitus in 20 (47.6%), smoking in 26 (61%) and dyslipidemia in 12 (28.5%) cases. Old myocardial infarction was present in 52.3% cases, unstable angina in 16.6%, stable angina in 23.8% and cardiogenic shock in 7.1% cases. All cases had undergone coronary artery bypass grafting with endarterectomy. Out of 18 LAD endarterectomies 17 cases LIMA was used as onlay patch. Result The average number of grafts anastomosed was 3.7. Single-vessel endarterectomy was done in 37, double vessel in 4 and four vessel in one case. LAD endarterectomy was done in 18, RCA in 12, diagonal in 10, intermediate in 1 and marginals in 8 cases. Postoperatively 3 patients had arrhythmia, two perioperative MI, one recurrent angina and one congestive cardiac failure (CCF). There was 2 (4.76%) mortality. Conclusion Hypertension and smoking are major risk factors. LAD is the most common artery requiring endarterectomy. Usage of LIMA following endarterectomy of LAD is quite satisfactory and short term results are encouraging.     

Backpropagation Artificial Neural Network Detects Changes in Electro-Encephalogram Power Spectra of Syncopic Patients

This paper presents an effective application of backpropagation artificial neural network (ANN) in differentiating electroencephalogram (EEG) power spectra of syncopic and normal subjects. Digitized 8-channel EEG data were recorded with standard electrodes placement and amplifier settings from five confirmed syncopic and five normal subjects. The preprocessed EEG signals were fragmented in two-second artifact free epochs for calculation and analysis of changes due to syncope. The results revealed significant increase in percentage δ and α (p<0.5 or better) with significant reduction in percentage θ activity (p<0.05). The backpropagation ANN used for classification contains 60 nodes in input layer, weighted from power spectrum data from 0 to 30 Hz, 18 nodes in hidden layer and an output node. The ANN was found effective in differentiating the EEG power spectra from syncopic EEG power spectra and the normal EEG power spectra with an accuracy of 88.87% (85.75% for syncopic and 92% for normal). Certificate of Originality—This is to certify that the article submitted for publication in ‘Journal of Medical Systems’ has not been publ-ished, nor is being considered for publication, elsewhere. (Rakesh Kumar Sinha)