Covered self expandable metallic airway stents (SEMS) have been used for benign tracheal stenosis, post intubation tracheal stenosis, tracheal burn or trauma, tracheo-broncho-malacia, and extrinsic compression of trachea. Their placement is considered to be permanent, with open surgery the only way to remove the stent, though there are few cases reports of their removal with the bronchoscope, but the complications after their removal are very high. In our patient, one and a half years after placement of SEMS, she developed cough with dyspnoea, video bronchoscopy showed stenosis above the level of stent with granulation tissue inside the stent, stent fracture in lower part and stent migration to right main bronchus, thus she had all conceivable complications of stent placement. The stent was removed with the help of rigid bronchoscope under general anaesthesia. She was discharged the following day. The case is being reported because it was unique in having all the possible complications of stent placement, and rare as we could take out the stent in Toto. Thirdly, the stent could be removed without any complication.
Granulation tissue inside the stent; stenosis above the stent; stent fracture; stent migration
The incidence of tracheo-esophageal (TO) fistula is on the rise, especially after palliative management for esophageal malignancies. We report a case of cancer of esophagus who after chemotherapy and radiotherapy developed TO fistula. Placement of an esophageal stent helped him in taking food orally, but his cough and dyspnoea continued to worsen. Fibreoptic bronchoscopy demonstrated a severely compressed trachea secondary to protrusion of esophageal stent which responded very well to an Ultraflex-covered tracheal stent and the patient achieved relief from cough and dyspnoea.
Fibreoptic bronchoscopy; tracheo-esophageal fistula; Ultraflex stent
Hemoptysis is defined as the spitting of blood derived from the lungs or bronchial tubes as a result of pulmonary or bronchial hemorrhage. There is a large chunk of patients with hemoptysis who do not respond to conservative treatment including use of cough suppressants, antibiotics, vitamin C, hemostatics, and anxiolytics. The advanced management of such a situation is bronchial artery embolization (BAE) or open thoracic surgery, which is often not possible. We have attempted a cheap, effective, and safe alternative in the form of intrabronchial instillation of glue (n-butyl cyanoacrylate) under vision with the help of a therapeutic video bronchoscope (OLYMPUS T-180). The glue is instilled through a polyethylene catheter placed through the working channel of the video bronchoscope.
Hemoptysis; video bronchoscopy; glue therapy; n-butyl cyanoacrylate (glue)
Genitourinary histoplasmosis is very rare and to our knowledge only four cases of epididymal histoplasmosis and nine cases of prostatic histoplasmosis have been reported in literature. We hereby report a case of a middle-aged male, who presented three years after renal transplant, with complaints of fever, pain, and swelling in the scrotum. Imaging disclosed an enlarged right epididymis with prostatic and retrotrigonal abscess, suggesting tuberculosis infection. However, histopathology of the epididymal biopsy revealed histoplasmosis, and the drained pus on culture confirmed infection with Histoplasma capsulatum.
Epididymis; histoplasmosis; prostate
Bronchopleural fistula (BPF) is a communication between the pleural space and bronchial tree.
Materials and Methods:
A series of 9 cases are reported where BPF was identified and managed with intrabronchial instillation of glue (N-butyl-cyanoacrylate) through a video bronchoscope.
Out of 9 patients the BPF was successfully sealed in 8 cases (88.88%). In 1 patient of postpneumonectomy, the fistula was big, that is >8 mm who had a recurrence after the procedure. In one case of pyopneumothorax the leak reduced slowly and it took us 14 days to remove the intercostal drainage tube. Rest of the patients had a favorable outcome. No complications were observed in a follow-up of 6 months.
In our opinion, it is a cost-effective, viable, and safe alternative compared with costly, time-consuming, and high-risk surgical procedures.
Bronchopleural fistula; intercostal drainage tube; N-butyl cyanoacrylate glue; video bronchoscopy
Hemoptysis is a very common symptom in the practice of pulmonary physicians of India. We present a case of uncontrolled hemoptysis managed with bronchial artery embolization. Bronchial artery embolization is an effective treatment for patients with hemoptysis. Serious complications are rare, but may occur if the arterial supply to other structures is compromised.
Bronchial artery embolization; bronchogenic carcinoma; fiber optic bronchoscopy; hemoptysis
Rationale and Objectives
Correlation Imaging (CI) is a form of multi-projection imaging technique in which multiple images of a patient are acquired from slightly different angles. Information from these images is combined to make the final diagnosis. A critical factor affecting the performance of CI is its data acquisition scheme since a non-optimized acquisition may quickly distort the pathological indicators. In this article, we are presenting a Computer Aided Detection (CADe)-based methodology to optimize the acquisition scheme of CI towards superior diagnostic accuracy.
Materials and Methods
Images from 106 subjects were employed. For each subject, 25 angular projections of a single breast were acquired. Projection images were supplemented with a simulated 3 mm 3D lesion. Each projection was then processed by a traditional CADe algorithm at high sensitivity, followed by reduction of false positives by combining geometrical correlation information available from the multiple images. Performance of the CI system was determined in terms of free-response receiver operating characteristic (FROC) curves and the area under the ROC curves. For optimization, the components of acquisition such as the number of projections, and their angular span were systematically changed to investigate which one of the many possible combinations maximized the obtainable CADe sensitivity and specificity.
Performance of the CI system improved by increasing the angular span. Increasing the number of angular projections beyond a certain number does not improve performance. Maximum performance was obtained between 7–10 projections spanning our maximum angular arc of 45°.
Findings suggested the existence of an optimum acquisition for CI of the breast. CADe-based results confirmed earlier predictions based on observer models. Optimized CI system may potentially be an important diagnostic tool for improved breast cancer detection.
Multi-projection Imaging; Correlation Imaging; Breast Tomosynthesis; FROC; CADe
The nature of the dyslipidemia associated with diabetes mellitus is complex and is the major risk factor for atherosclerosis and coronary artery disease. Aim of this study was to assess the effect of glycemic control, achieved by metformin, glibenclamide and insulin, on lipid profile in type 2 diabetic patients. One hundred and sixty-five type 2 diabetes mellitus patients were classified into good glycemic control (Group I) and poor glycemic control (Group II) on the basis of their blood HbA1c values. The Group II was characterized with high serum triglyceride (190.46 ± 15.20 mg/dl), total cholesterol (175.3 ± 6.31 mg/dl) as well as high LDL-cholesterol (109.0 ± 5.88 mg/dl). Significant correlations were evident between HbA1c and dyslipidemia, particularly serum TG (r = 0.28, P < 0.05), and between HbA1c and total cholesterol (r = 0.310, P < 0.05). Better glycemic control and improved dyslipidemia were observed in patients on combination therapy of metformin plus glibenclamide.
Diabetes mellitus; Glycemic control; HBA1c; Dyslipidemia; Metformin; Glibenclamide
Formation of cystic artery pseudo aneurysm is a rare complication of a common problem that is, acute cholecystitis. Here the authors present a case of 58-year-man with history of upper abdominal pain and fever. Ultrasound initially showed huge subhepatic collection and distended gall bladder with gall stones. Later on, CT scan showed the cystic artery pseudo aneurysm in the wall of gall bladder. Selective angioembolisation of cystic artery followed by elective open cholecystectomy was done and patient recovered well postprocedure. Pathology report later on showed xanthogranulomatous cholecystitis. Case emphasises the need of high index of suspicion to diagnose this rare entity, which in this case was successfully treated with two staged approach that is, angioembolisation of aneurismal vessel and then interval open cholecystectomy.
Studies using Helicobacter-infected mice show that bone marrow-derived mesenchymal stem cells (MSCs) can repopulate the gastric epithelium and promote gastric cancer progression. Within the tumor microenvironment of the stomach, pro-inflammatory cytokine interferon-gamma (IFNγ) and Sonic hedgehog (Shh) are elevated. IFNγ is implicated in tumor proliferation via activation of the Shh signaling pathway in various tissues but whether a similar mechanism exists in the stomach is unknown. We tested the hypothesis that IFNγ drives MSC proliferation and recruitment, a response mediated by Shh signaling. The current study uses transplantation of an in vitro transformed mesenchymal stem cell line (stMSCvect), that over-expresses hedgehog signaling, in comparison to non-transformed wild-type MSCs (wtMSCs), wtMSCs transfected to over-express Shh (wtMSCShh), and stMSCs transduced with lentiviral constructs containing shRNA targeting the Shh gene (stMSCShhKO). The effect of IFNγ on MSC proliferation was assessed by cell cycle analysis in vitro using cells treated with recombinant IFNγ (rmIFNγ) alone, or in combination with anti-Shh 5E1 antibody, and in vivo using mice transplanted with MSCs treated with PBS or rmIFNγ. In vitro, IFNγ significantly increased MSC proliferation, a response mediated by Shh that was blocked by 5E1 antibody. The MSC population collected from bone marrow of PBS- or IFNγ-treated mice showed that IFNγ significantly increased the percentage of all MSC cell lines in S phase, with the exception of the stMSCsShhKO cells. While the MSC cell lines with intact Shh expression were recruited to the gastric mucosa in response to IFNγ, stMSCsShhKO were not. Hedgehog signaling is required for MSC proliferation and recruitment to the stomach in response to IFNγ.
Innate lymphoid type 2 cells maintain eosinophils and alternatively activated macrophages in visceral fat via the production of IL-5 and IL-13.
Eosinophils in visceral adipose tissue (VAT) have been implicated in metabolic homeostasis and the maintenance of alternatively activated macrophages (AAMs). The absence of eosinophils can lead to adiposity and systemic insulin resistance in experimental animals, but what maintains eosinophils in adipose tissue is unknown. We show that interleukin-5 (IL-5) deficiency profoundly impairs VAT eosinophil accumulation and results in increased adiposity and insulin resistance when animals are placed on a high-fat diet. Innate lymphoid type 2 cells (ILC2s) are resident in VAT and are the major source of IL-5 and IL-13, which promote the accumulation of eosinophils and AAM. Deletion of ILC2s causes significant reductions in VAT eosinophils and AAMs, and also impairs the expansion of VAT eosinophils after infection with Nippostrongylus brasiliensis, an intestinal parasite associated with increased adipose ILC2 cytokine production and enhanced insulin sensitivity. Further, IL-33, a cytokine previously shown to promote cytokine production by ILC2s, leads to rapid ILC2-dependent increases in VAT eosinophils and AAMs. Thus, ILC2s are resident in VAT and promote eosinophils and AAM implicated in metabolic homeostasis, and this axis is enhanced during Th2-associated immune stimulation.
Patients with congenital heart disease (CHD) and heterotaxy show high postsurgical morbidity/mortality, with some developing respiratory complications. Although this finding is often attributed to the CHD, airway clearance and left-right patterning both require motile cilia function. Thus, airway ciliary dysfunction (CD) similar to that of primary ciliary dyskinesia (PCD) may contribute to increased respiratory complications in heterotaxy patients.
Methods and Results
We assessed 43 CHD patients with heterotaxy for airway CD. Videomicrocopy was used to examine ciliary motion in nasal tissue, and nasal nitric oxide (nNO) was measured; nNO level is typically low with PCD. Eighteen patients exhibited CD characterized by abnormal ciliary motion and nNO levels below or near the PCD cutoff values. Patients with CD aged >6 years show increased respiratory symptoms similar to those seen in PCD. Sequencing of all 14 known PCD genes in 13 heterotaxy patients with CD, 12 without CD, 10 PCD disease controls, and 13 healthy controls yielded 0.769, 0.417, 1.0, and 0.077 novel variants per patient, respectively. One heterotaxy patient with CD had the PCD causing DNAI1 founder mutation. Another with hyperkinetic ciliary beat had 2 mutations in DNAH11, the only PCD gene known to cause hyperkinetic beat. Among PCD patients, 2 had known PCD causing CCDC39 and CCDC40 mutations.
Our studies show that CHD patients with heterotaxy have substantial risk for CD and increased respiratory disease. Heterotaxy patients with CD were enriched for mutations in PCD genes. Future studies are needed to assess the potential benefit of prescreening and prophylactically treating heterotaxy patients for CD.
genomic studies; heart defects; congenital; heterotaxy; nitric oxide; primary ciliary dyskinesia
Tailoring three-dimensional (3D) biomaterial environments to provide specific cues in order to modulate function of encapsulated cells could potentially eliminate the need for addition of exogenous cues in cartilage tissue engineering. We recently developed saccharide-peptide copolymer hydrogels for cell culture and tissue engineering applications. In this study, we aim to tailor our saccharide-peptide hydrogel for encapsulating and culturing chondrocytes in 3D and examine the effects of changing single amino acid moieties differing in hydrophobicity/hydrophilicity (valine (V), cysteine (C), tyrosine (Y)) on modulation of chondrocyte function. Encapsulated chondrocytes remained viable over 21 days in vitro. Glycosaminoglycan and collagen content was significantly higher in Y-functionalized hydrogels compared to V-functionalized hydrogels. Extensive matrix accumulation and concomitant increase in mechanical properties was evident over time, particularly with the presence of Y amino acid. After 21 days in vitro, Y-functionalized hydrogels attained a modulus of 193±46 kPa, compared to 44±21 kPa for V-functionalized hydrogels. Remarkably, mechanical and biochemical properties of chondrocyte-laden hydrogels were modulated by change in a single amino acid moiety. This unique property, combined with the versatility and biocompatibility, makes our saccharide-peptide hydrogels promising candidates for further investigation of combinatorial effects of multiple functional groups on controlling chondrocyte and other cellular function and behavior.
tissue engineering; chondrocyte; cartilage; sacchride-peptide; amino acid; functional group
Large oro-facial defects consequences in serious functional as well as cosmetic deformities. Acceptable cosmetic results usually can be obtained with a facial prosthesis. This article describes prosthetic rehabilitation of a 35 year-old female having a left orbital defect with HTV silicone material. A modified technique to fabricate an acrylic substructure in heat-polymerizing polymethyl-methacrylate to support silicone facial prosthesis was illustrated. The resultant facial prosthesis was structurally durable and esthetically acceptable with satisfactory retention. This technique is advantageous as there is no need to fabricate the whole prosthesis again in case of damage of the silicone layer because the outer silicone layer can be removed and repacked on the substructure if the gypsum-mold is preserved.
Host-generated oxidative stress is considered one of the main mechanisms constraining Mycobacterium tuberculosis (Mtb) growth. The redox-sensing mechanisms in Mtb are not completely understood. Here we show that WhiB4 responds to oxygen (O2) and nitric oxide (NO) via its 4Fe-4S cluster and controls the oxidative stress response in Mtb. The WhiB4 mutant (MtbΔwhiB4) displayed an altered redox balance and a reduced membrane potential. Microarray analysis demonstrated that MtbΔwhiB4 over-expresses the antioxidant systems including alkyl hydroperoxidase (ahpC-ahpD) and rubredoxins (rubA-rubB). DNA binding assays showed that WhiB4 [4Fe-4S] cluster is dispensable for DNA binding. However, oxidation of the apo-WhiB4 Cys thiols induced disulfide-linked oligomerization, DNA binding and transcriptional repression, whereas reduction reversed the effect. Furthermore, WhiB4 binds DNA with a preference for GC-rich sequences. Expression analysis showed that oxidative stress repressed whiB4 and induced antioxidants in Mtb, while their hyper-induction was observed in MtbΔwhiB4. MtbΔwhiB4 showed increased resistance to oxidative stress in vitro and enhanced survival inside the macrophages. Lastly, MtbΔwhiB4 displayed hypervirulence in the lungs of guinea pigs, but showed a defect in dissemination to their spleen. These findings suggest that WhiB4 systematically calibrates the activation of oxidative stress response in Mtb to maintain redox balance, and to modulate virulence.
Fibrin sheaths are a heterogeneous matrix of cells and debris that form around catheters and are a known cause of central venous stenosis and catheter failure. A total of 50 cases of central venous catheter fibrin sheath angioplasty (FSA) after catheter removal or exchange are presented. A retrospective review of an outpatient office database identified 70 eligible patients over a 19-month period. After informed consent was obtained, the dialysis catheter exiting the skin was clamped, amputated, and a wire was inserted. The catheter was then removed and a 9-French sheath was inserted into the superior vena cava, a venogram was performed. If a fibrin sheath was present, angioplasty was performed using an 8 × 4 or 10 × 4 balloon along the entire length of the fibrin sheath. A completion venogram was performed to document obliteration of the sheath. During the study, 50 patients were diagnosed with a fibrin sheath, and 43 had no pre-existing central venous stenosis. After FSA, 39 of the 43 patient's (91%) central systems remained patent without the need for subsequent interventions; 3 patients (7%) developed subclavian stenoses requiring repeat angioplasty and stenting; 1 patent (2.3%) developed an occlusion requiring a reintervention. Seven patients with prior central stenosis required multiple angioplasties; five required stenting of their central lesions. Every patient had follow-up fistulograms to document long-term patency. We propose that FSA is a prudent and safe procedure that may help reduce the risk of central venous stenosis from fibrin sheaths due to central venous catheters.
inferior vena cava thrombosis; percutaneous; proximal; renal failure; subclavian stenosis; vascular access; deep vein thrombosis
Immunization is one of the most important public health interventions and a cost effective strategy to control the infectious diseases especially in children. Complete immunization coverage in India has increased from below 20% in the 1980s to nearly 61% at present, but still more than 1/3rd children remain un-immunized. Advent of combination vaccines has facilitated incorporation of additional vaccines into immunization schedule. Pentavalent vaccine, against five killer diseases–diphtheria, pertussis, tetanus, hepatitis B and Hemophilus influenza type B (Hib), has been introduced in almost all GAVI eligible countries by 2011. Government of India introduced the vaccine in two states in pilot phase and has given green signal to six more states. The use of pentavalent vaccine automatically raises the coverage level of hepatitis B and Hib vaccines. If the vaccines are provided individually, the coverage of hepatitis B and Hib vaccines usually lags behind DPT coverage. This gap can be filled by using pentavalent vaccine in routine immunization programmes.
Haemophilus influenza type b; DPT; cost-effectiveness; hepatitis B; immunization; immunogenicity; pentavalent vaccine
Escherichia coli-mycobacterium shuttle vectors are important tools for gene expression and gene replacement in mycobacteria. However, most of the currently available vectors are limited in their use because of the lack of extended multiple cloning sites (MCSs) and convenience of appending an epitope tag(s) to the cloned open reading frames (ORFs). Here we report a new series of vectors that allow for the constitutive and regulatable expression of proteins, appended with peptide tag sequences at their N and C termini, respectively. The applicability of these vectors is demonstrated by the constitutive and induced expression of the Mycobacterium tuberculosis pknK gene, coding for protein kinase K, a serine-threonine protein kinase. Furthermore, a suicide plasmid with expanded MCS for creating gene replacements, a plasmid for chromosomal integrations at the commonly used L5 attB site, and a hypoxia-responsive vector, for expression of a gene(s) under hypoxic conditions that mimic latency, have also been created. Additionally, we have created a vector for the coexpression of two proteins controlled by two independent promoters, with each protein being in fusion with a different tag. The shuttle vectors developed in the present study are excellent tools for the analysis of gene function in mycobacteria and are a valuable addition to the existing repertoire of vectors for mycobacterial research.
Isolated renal mucormycosis is rarely identified and has been described in only a handful of cases. We hereby report a case of isolated renal mucormycosis with an atypical presentation in an immunocompetent patient with no identifiable risk factors. A 30-year-old nondiabetic male presented with a poorly functioning right kidney with minimal constitutional symptoms. The patient underwent a right simple nephrectomy. Histopathology revealed necrotizing xanthogranulomatous pyelonephritis with mucormycosis. The postoperative period was uneventful and the patient was managed without any antifungal administration. We hereby emphasize that renal mucormycosis can affect immunocompetent healthy adults without any previously known risk factors and that asymptomatic patients with no evidence of fungemia or disseminated disease can be managed without administration of intravenous amphotericin.
Amphotericin B; Immunocompetence; Mucormycosis; Urinary tract infection
In this study, we hypothesized that higher level of comorbidity and greater body mass index (BMI) may mediate the association between diabetes and access to transplantation.
We used data from the United States Renal Data System (01/01/2000–24/09/2007) (n=619,151). We analyzed two outcomes using Cox model: 1) time to being placed on the waiting list or transplantation without being listed; 2) time to transplantation after being listed. Two primary Cox models were developed based on different levels of adjustment.
In Cox models adjusted for priori defined potential confounders, history of diabetes was associated with reduced transplant access (compared with non-diabetic population) - both for wait-listing/transplant without being listed [HR 0.80, p < 0.001] and for transplant after being listed [HR 0.72, p < 0.001]. In Cox models adjusted for BMI and comorbidity index along with the potential confounders, history of diabetes was associated with shorter time to wait-listing or transplantation without being listed [HR 1.07, p < 0.001] and there was no significant difference in time to transplantation after being listed [HR 1.01, p = 0.42].
We demonstrated that higher level of comorbidity and greater BMI mediate the association between diabetes and reduced access to transplantation.
Body Mass Index; Comorbidities; Diabetes; Pre-transplant evaluation; Renal transplantation access
To examine whether frontal lobe abnormalities on magnetic resonance spectroscopy (MRS) in amyotrophic lateral sclerosis (ALS) correlate with poor letter fluency (LF).
Twenty-five patients with ALS (20 with definite, probable, or possible ALS and 5 with progressive muscular atrophy) performed an LF task, involving F word generation in 1 minute, and underwent MRS. Comparisons were made between patients with ALS with impaired LF and unimpaired LF based on an empirically derived cutoff score. A Spearman correlation was performed between the patient's N-acetyl acetate/creatinine-phosphocreatinine ratio (NAA/Cr) and the number of F words generated.
LF was impaired in 50% of patients with ALS. Patients with impaired LF had reduced NAA/Cr in the DLPFC compared with those with unimpaired LF (p = 0.007). There was a significant correlation between LF and NAA/Cr in the DLPFC (r = 0.51, p = 0.0009). The ALS Functional Rating Scale score, clinical region of motor onset, and disease category had no effect on LF or NAA/Cr in the DLPFC.
A reduced NAA/Cr in the DLPFC of patients with ALS is a marker of neuronal dysfunction and correlates with impaired performance on a clinical measure of executive function.
Under typical dark chest radiography reading room conditions, a radiologist’s pupils contract and dilate as their visual focus intermittently shifts between the high luminance monitor and the darker background wall, resulting in increased visual fatigue and degradation of diagnostic performance. A controlled increase of ambient lighting may minimize these visual adjustments and potentially improve comfort and accuracy. This study was designed to determine the effect of a controlled increase of ambient lighting on chest radiologist nodule detection performance. Four chest radiologists read 100 radiographs (50 normal and 50 containing a subtle nodule) under low (E = 1 lx) and elevated (E = 50 lx) ambient lighting levels on a DICOM-calibrated, medical-grade liquid crystal display. Radiologists were asked to identify nodule locations and rate their detection confidence. A receiver operating characteristic (ROC) analysis of radiologist results was performed and area under ROC curve (AUC) values calculated for each ambient lighting level. Additionally, radiologist selection times under both illuminance conditions were determined. Average AUC values did not significantly differ (p > 0.05) between ambient lighting levels (estimated mean difference = −0.03; 95% CI, (−0.08, 0.03)). Average selection times decreased or remained constant with increased illuminance. The most considerable decreases occurred for false positive identification times (35.4 ± 18.8 to 26.2 ± 14.9 s) and true positive identification times (29.7 ± 18.3 to 24.5 ± 15.5 s). No performance differences were statistically significant. Study findings suggest that a controlled increase of ambient lighting within darkly lit chest radiology reading rooms, to a level more suitable for performance of common radiological tasks, does not appear to have a statistically significant effect on nodule detection performance.
Chest radiographs; Image perception; Visual perception