A 57-year-old male patient suffering from Buerger's disease presented with pre-gangrenous changes in right foot and ischemic symptoms in right hand. Computed tomographic angiography revealed diffuse distal disease not suitable for vascular bypass and angioplasty. Right lumbar sympathectomy was done using a retroperitoneal approach followed 1 year later by right thoracic sympathectomy using a transaxillary approach. Postoperatively, the patient had severe bronchospasm and excessive secretions in the respiratory tract resistant to theophylline and sympathomimetic group of drugs and without any clinical, laboratory and radiological evidence of infection. The patient was started on anticholinergics in anticipation that sympathectomy might have lead to unopposed cholinergic activity and the symptoms improved rapidly. The patient recovered well and was discharged on 10th post-operative day.
Anticholinergics; bronchospasm; thoracic sympathectomy
Entamoeba histolytica is the etiological agent of human amoebic colitis and liver abscess, and causes a high level of morbidity and mortality worldwide, particularly in developing countries. There are a number of studies that have shown a crucial role for Ca2+ and its binding protein in amoebic biology. EhCaBP5 is one of the EF hand calcium-binding proteins of E. histolytica. We have determined the crystal structure of EhCaBP5 at 1.9 Å resolution in the Ca2+-bound state, which shows an unconventional mode of Ca2+ binding involving coordination to a closed yet canonical EF-hand motif. Structurally, EhCaBP5 is more similar to the essential light chain of myosin than to Calmodulin despite its somewhat greater sequence identity with Calmodulin. This structure-based analysis suggests that EhCaBP5 could be a light chain of myosin. Surface plasmon resonance studies confirmed this hypothesis, and in particular showed that EhCaBP5 interacts with the IQ motif of myosin 1B in calcium independent manner. It also appears from modelling of the EhCaBP5-IQ motif complex that EhCaBP5 undergoes a structural change in order to bind the IQ motif of myosin. This specific interaction was further confirmed by the observation that EhCaBP5 and myosin 1B are colocalized in E. histolytica during phagocytic cup formation. Immunoprecipitation of EhCaBP5 from total E. histolytica cellular extract also pulls out myosin 1B and this interaction was confirmed to be Ca2+ independent. Confocal imaging of E. histolytica showed that EhCaBP5 and myosin 1B are part of phagosomes. Overexpression of EhCaBP5 increases slight rate (∼20%) of phagosome formation, while suppression reduces the rate drastically (∼55%). Taken together, these experiments indicate that EhCaBP5 is likely to be the light chain of myosin 1B. Interestingly, EhCaBP5 is not present in the phagosome after its formation suggesting EhCaBP5 may be playing a regulatory role.
Entamoeba histolytica is the etiologic agent of amoebiasis, a major cause of morbidity and mortality in developing countries. The genome of this organism encodes 27 EF-hand containing calcium binding proteins suggesting an intricate Ca2+ signalling system that plays crucial role in phagocytosis and pathogenesis. Calcium binding protein-5 (EhCaBP5) is one of these CaBPs that displays sequence similarity with Calmodulin (CaM) but has only two possible calcium binding EF-hand loops in two separate domains. Interestingly crystal structure of EhCaPB5 showed more structural similarity with essential light chain (ELC) of myosin than that of CaM. The binding studies of EhCaBP5 with IQ motif peptides of myosins, showed that it interacts with IQ motif of unconventional Myosin IB. A number of experiments were carried out to show that EhCaBP5 indeed binds myosin IB and that this binding is Ca2+ independent. We also show here that EhCaBP5 participates in erythrophagocytosis and that its role in phagocytosis is different from that of EhCaBP3, another myosin 1B interacting calcium binding protein of E. histolytica. Our results presented here and in a number of other reports point towards a unique phagocytic pathway involving a number of calcium binding proteins in E. histolytica.
Calcium-binding protein 5 from E. histolytica was cloned, expressed in E. coli and purified. The purified protein crystallized in space group C222 and the crystals diffracted to 2 Å resolution.
Entamoeba histolytica is the causative agent of human amoebiasis. Phagocytosis is the major route of food intake by this parasite and is responsible for its virulence. Calcium and calcium-binding proteins play major roles in its phagocytosis. Calcium-binding protein 5 from E. histolytica (EhCaBP5) is a cytoplasmic protein; its expression is very sensitive to serum starvation and it seems to be involved in binding to myosin I. In this study, EhCaBP5 was cloned, expressed in Escherichia coli and purified using affinity and size-exclusion chromatography. The purified protein crystallized in space group C222 and the crystals diffracted to 2 Å resolution. The Matthews coefficient indicated the presence of one molecule in the asymmetric unit, with a V
M of 2.35 Å3 Da−1 and a solvent content of 47.7%.
calcium-binding protein 5; Entamoeba histolytica
The ultimate goal in surgical endodontics is not only the eradication of periapical pathosis but also preservation of periodontal tissues using suitable surgical techniques. Treatment outcomes are no longer acceptable without considering the esthetic consequences of all involved dentoalveolar structures. It is critical that incisions and tissue elevations and reflections are performed in a way that facilitates healing by primary intention. The large variety of flaps available for periapical surgeries reflects the number of variables to be considered before choosing an appropriate flap design. In this study; Ocshenbein-Leubke (OL) and trapezoidal (TZ) flaps have been compared in terms of their efficacy and comfort. Twenty patients of ASA category I, between the age group of 12–40 years were randomly selected to undergo periapical surgery by utilizing one of two flaps. All the subjects were free of periodontal disease. Demographic variables were found to be statistically similar. OL flap was found to be better than TZ flap with respect to time of flap reflection, accessibility, duration of surgery and post-operative pain. The OL flap takes less time for reflection with nearly the same accessibility, less post-operative pain and less complication as compared to TZ flap. We conclude that OL flap gives better results when compared to TZ flap.
Periapical surgery; Ocshenbein-Leubke flap; Trapezoidal flap
Intestinal obstruction due to sigmoid colon volvulus during pregnancy is a rare complication but associated with significant fetomaternal mortality. We describe a case of sigmoid volvulus in a patient with 37 wk pregnancy causing huge dilation of left colon. Patient developed rectovaginal fistula following nonmedical method to relieve distention by inserting stick as told by patient.
Pregnancy; Rectovaginal fistula; Sigmoid volvulus
Cervical spondylosis is essentially a degenerative disorder common after fourth decade. It has been seen that radiological evidence of cervical spondylosis do not necessarily co-relate with clinical findings. This discrepancy has been attributed to the morphometric dimensions of the vertebrae, age, sex, race, occupation, weight and height of the patients.
The objective of this study is to co-relate the variables like age, sex, race, occupation, vertebral body diameter, canal diameter, canal body ratio of cervical spine vertebrae with cervical spondylosis cases with normal population.
In this hospital based, case control, consent based, cross-sectional, clinico-radiological study 200 individuals (controls-100, cases-100) who were subjected to lateral projection radiographs of cervical spine. Their age, sex, race, occupation, height, weight and mid-sagittal canal diameter (CD), sagittal vertebral body diameter (VBD) and the canal-body ratio (CBR) of the cervical vertebrae was recorded and analyzed statistically.
There was no relation between vertebral dimensions and clinical groups. In radiculopathy group, age and height showed significance on univariate analysis. While only age remained significant on multivariate analysis. In neck pain group age, sex, and height showed significance on univariate analysis while in multivariate analysis age, sex and occupation were significant risk factors.
Cervical spondylosis; Risk factors; Multivariate analysis
The aim of the present study is to develop and verify the single film calibration procedure used in intensity-modulated radiation therapy (IMRT) quality assurance.
Radiographic films have been regularly used in routine commissioning of treatment modalities and verification of treatment planning system (TPS). The radiation dosimetery based on radiographic films has ability to give absolute two-dimension dose distribution and prefer for the IMRT quality assurance. However, the single therapy verification film gives a quick and significant reliable method for IMRT verification.
Materials and methods
A single extended dose rate (EDR 2) film was used to generate the sensitometric curve of film optical density and radiation dose. EDR 2 film was exposed with nine 6 cm × 6 cm fields of 6 MV photon beam obtained from a medical linear accelerator at 5-cm depth in solid water phantom. The nine regions of single film were exposed with radiation doses raging from 10 to 362 cGy. The actual dose measurements inside the field regions were performed using 0.6 cm3 ionization chamber. The exposed film was processed after irradiation using a VIDAR film scanner and the value of optical density was noted for each region. Ten IMRT plans of head and neck carcinoma were used for verification using a dynamic IMRT technique, and evaluated using the gamma index method with TPS calculated dose distribution.
Sensitometric curve has been generated using a single film exposed at nine field region to check quantitative dose verifications of IMRT treatments. The radiation scattered factor was observed to decrease exponentially with the increase in the distance from the centre of each field region. The IMRT plans based on calibration curve were verified using the gamma index method and found to be within acceptable criteria.
The single film method proved to be superior to the traditional calibration method and produce fast daily film calibration for highly accurate IMRT verification.
IMRT; EDR 2 film; Patient specific quality assurance; Sensitometric curve
The fixed dose combinations (FDCs) of muscle relaxants, non-steroidal anti-inflammatory drugs and paracetamol are commonly prescribed in the treatment of acute lower backache.
The present study was undertaken with the aim of comparing the efficacy and safety of FDCs of thiocolchicoside and aceclofenac versus chlorzoxazone, aceclofenac and paracetamol in patients with acute lower backache associated with muscle spasm.
Materials and Methods:
A total of 100 patients between ages range from 18 and 55 years having low back pain of ≤7 days duration were randomly divided into two groups. Group A was prescribed thiocolchicoside (4 mg) + aceclofenac (100 mg) while Group B was prescribed chlorzoxazone (500 mg) + aceclofenac (100 mg) + paracetamol (325 mg) orally twice daily for 7 days. Severity of pain at rest and on movement was recorded using visual analogue scale. Muscle spasm was evaluated by hand-to-floor distance and Lasegue's maneuver. Readings were noted on day 1 (baseline), day 3 and day 7.
There was statistically significant reduction in severity of pain and muscle spasm on day 3 and day 7 in both groups. There was no statistically significant difference in pain relief and muscle spasm among the treatment groups but clinically showed better improvement in the Group A. The adverse drug reactions occurring during study showed a statistically significant better safety profile in the Group A than Group B.
These findings confirm that FDC of thiocolchicoside and aceclofenac is a preferred option for patients with lower backache pain associated with muscle spasm.
Fixed dose combinations; low backache; muscle relaxants; non-steroidal inflammatory drugs; visual analog scale
Rabies is the most severe and neglected public health problem in India. Management of animal bite with post exposure prophylaxis is the only existent strategy to prevent rabies related deaths. Cost-effective and sustainable programme for provision of post exposure prophylaxis (PEP) is needed in India.
In this study, we have documented the experience of implementation of intra-dermal anti rabies vaccination in Animal Bite Management (ABM) clinic at Primary Health Centre (PHC). This study facility belonged to Comprehensive Rural Health Services Project, Ballabgarh in Faridabad district of Haryana. Hospital service record of ABM clinic was analyzed and various feasibility issues such as costing of services, vaccine wastage and other operational issues in providing PEP services at PHC level were documented.
A total of 619 patients were treated in the ABM clinic. Service utilization of ABM clinic was increased by 38% in the second year of implementation. Mean age of the patients was 23.9 years (SD: 18.8) and majority (70.4%) were males. Majority (86%) of the patients received the first dose of anti-rabies vaccine within the recommended 48 hours. A total 446 vaccine vials (1 ml) were consumed of which 20.8% was contributed in vaccine wastage. User-fee (350 Indian Rupees) collected from the patients. User-fee was re-used to purchase vaccines, intradermal (ID) syringes and other consumables required to ensure regular availability of ARV services at the PHC.
This study demonstrated the cost-effective and sustainable model of provision of PEP against rabies at primary care level. ID PEP provision at primary care level not only address the unmet need of animal bite management in the community also reduces the out of pocket expenditure of the patients.
Intra-dermal PEP; Rabies; Primary care; Rural; India
The purpose of this study was to compare the outcome of open treatment of mandibular fracture (symphysis or parasymphysis) using lag screw or mini plate clinically as well as radiologically in young (age range 12–45 years) and healthy individuals of poor socioeconomic status.
This prospective study was conducted on 30 patients diagnosed as cases of displaced mandibular anterior fractures treated with open reduction and internal fixation. The patients were then randomly allocated to either of two groups––Group A: Two 2.5 mm stainless steel lag screws were placed in 15 patients. Group B: Two 2.5 mm stainless steel mini plates were placed in 15 patients for the fixation of fractures. Subsequent follow up was done on 2nd, 4th, 6th and 8th week postoperatively. During every follow up patient was assessed clinically for infection, malocclusion, loosening of plate/screw, sensory disturbance, plate fracture, malunion/non-union, devitalisation of associated dentoalveolar segment and masticatory efficiency. Radiographs were taken if necessary and patients were further assessed for any complaint. Pain was objectively measured using a visual analogue scale, bite force was measured using a bite force transducer at biweekly interval. The data collected was subjected to unpaired t test and paired t test for statistical analysis.
During follow up period a significant improvement in bite force was present in both the groups, with more improvement seen in the lag screw group (p < 0.01). There was a significant pain reduction present in the lag screw group (p < 0.01) and also masticatory efficiency showed a steadier improvement in lag screw group while mini plate group patients showed a tendency to masticate only food items of medium hard consistency.
The sample size is small to conclude lag screws are better than mini plates but the result of our study provides a basis for further studies done to conclude that the application of LAG SCREW is an effective, inexpensive, quick treatment modality to accelerate healing of fresh, displaced mandibular anterior fracture.
Mandibular anterior fracture; Lag screw; Miniplates; Bite force
A crossed-fused ectopic kidney is a rare congenital anomaly, and uncommonly we see an aberrant vessel as a cause of hydronephrosis in a kidney. We report a case of 4-year-old boy with crossed-fused right renal ectopia with hydronephrosis in the both kidneys. The aberrant renal vessel was found pressing the left pelvi-ureteric junction causing hydronephrosis. Dismembered pyeloplasty of the left kidney was performed anterior to the aberrant vessel. The patient is doing well in the follow-up visits and his renal function is stabilized. Aberrant blood supply may be a cause of hydronephrosis in the crossed-fused ectopic ipsilateral kidney. Keeping this entity in differential diagnosis will help in successful management of the crossed-fused ectopic kidney.
Crossed fused renal ectopia; Aberrant vessel; Hydronephrosis
Microalbuminuria is a risk factor for cardiovascular disease. It is gaining importance as a marker of atherogenic milieu and indicates the target organ damage and can be a valuable tool in screening and identification of patients with cardiovascular disease. Markers of inflammation, such as C-reactive protein (CRP), were found to be related to cardiovascular disease (CVD) events in patients with chest pain. In addition, recent studies have shown that, in the case of atherosclerosis, increased levels of CRP, reflects inflammatory condition of vessel wall. In the present study, CRP and microalbuminuria were estimated in patients of acute chest pain. The patients were divided into two study groups (gp-1 patients of chest pain with CVD and gp-2 patients of chest pain of causes other than CVD) along with one healthy control group. It was found that microalbuminuria was higher in CVD patients (RR = 6.250,95% CI 2.346–16.45,P < 0.05) and also CRP was much higher in CVD patients (RR = 13.667,95% CI 4.528–41.253, P < 0.05) as compared to other two groups. Sensitivity, specificity and positive predictive value of CRP and microalbuminuria were also higher in gp-1 (CVD) patients as compared to other two groups. Therefore, CRP and microalbuminuria can be used as important biomarkers in screening CVD.
Chest pain; Coronary disease; C-reactive protein; Microalbuminuria
In the generation of a traditional immune response against invading pathogens, innate cells guide T cells by programming their differentiation. However, here we demonstrate that αβ T cells play an essential role in priming innate immunity in the lung after Staphylococcus aureus enterotoxin A (SEA) inhalation. We found that SEA induces waves of cellular activation, cytokine production, and migration into the lung tissue and airways. However, this innate response was completely inhibited in the absence of αβ T cells. Specifically, we found that IL-17A was required for the recruitment of neutrophils and monocytes into the lung. The cellular source of IL-17A was γδ T cells, which increased their IL-17A production following SEA, but only in an αβ T cell-dependent manner. Thus, rapid T cell activation orchestrates innate immunity and may be a new point of therapeutic intervention for acute lung injury.
Acute kidney injury (AKI) promotes an abrupt loss of kidney function that results in substantial morbidity and mortality. Considerable effort has gone toward identification of diagnostic biomarkers and analysis of AKI-associated molecular events; however, most studies have adopted organ-wide approaches and have not elucidated the interplay among different cell types involved in AKI pathophysiology. To better characterize AKI-associated molecular and cellular events, we developed a mouse line that enables the identification of translational profiles in specific cell types. This strategy relies on CRE recombinase–dependent activation of an EGFP-tagged L10a ribosomal protein subunit, which allows translating ribosome affinity purification (TRAP) of mRNA populations in CRE-expressing cells. Combining this mouse line with cell type–specific CRE-driver lines, we identified distinct cellular responses in an ischemia reperfusion injury (IRI) model of AKI. Twenty-four hours following IRI, distinct translational signatures were identified in the nephron, kidney interstitial cell populations, vascular endothelium, and macrophages/monocytes. Furthermore, TRAP captured known IRI-associated markers, validating this approach. Biological function annotation, canonical pathway analysis, and in situ analysis of identified response genes provided insight into cell-specific injury signatures. Our study provides a deep, cell-based view of early injury-associated molecular events in AKI and documents a versatile, genetic tool to monitor cell-specific and temporal-specific biological processes in disease modeling.
Study undertaken to find any association of metformin intake to that of survival in ovarian cancer.
In this retrospective case control study, ovarian cancer patients who took metformin (cases) were compared with patients having ovarian cancer but no metformin (controls). Two-layered analysis was conducted. In preliminary analysis, all cases (OC cohort) were compared with controls in 1:2 ratio. Subsequently in definitive analysis, only Epithelial Ovarian Cancer cases (EOC cohort) were compared with controls in 1:3 ratio. In EOC cohort, cases were matched with controls for age (+/−5 years), FIGO stage and residual disease. Prognostic variables and Disease Specific Survival (DSS) were compared with Chi square, Kaplan-Meier (log rank) and Cox proportional hazards.
In the preliminary analysis on the OC cohort (72 cases, 143 controls), cases had a better survival (5 year DSS for cases 73% vs. controls 44%; p=0.0002). In the definitive analysis on the EOC cohort (61 cases, 178 controls) distribution of age, stage, optimal cytoreduction, serous histology and platinum chemotherapy remained similar amongst the cases and controls (p>0.05). Despite these similarities, cases had a significantly better survival (5 year DSS for cases 67% vs. controls 47%; p=0.007). On a multivariate analysis, metformin remained an independent predictor of survival (hazards ratio 3.7; 95% CI 1.6–9.0; p=0.002) after controlling for stage, grade, histology, chemotherapy, body mass index and surgical cytoreduction.
This study reports association rather than causation. Metformin intake was associated with better survival in ovarian cancer. Metformin is worthy of clinical trials in ovarian cancer.
Metformin; ovarian cancer; survival; drug repositioning
Recent observations suggest a lower incidence of malignancies in patients infected with HIV during treatment with Highly Active Anti-Retroviral Therapy (HAART) utilizing protease inhibitors. We investigated the effects of ritonavir, a FDA approved HIV protease inhibitor, on proliferation of pancreatic ductal adeno-carcinoma (PDAC) cell lines. Human PDAC cell lines BxPC-3, MIA PaCa-2, and PANC-1 were propagated under standard conditions and treated with serial dilutions of ritonavir. Ritonavir inhibited cell growth in a dose-dependent manner as well as activated the intrinsic apoptotic pathway in human pancreatic ductal adenocarcinoma (PDAC) cell lines. We observed down-modulation of cell-cycle promoting and up-regulation of cell-cycle inhibitory genes; enhanced interaction of retinoblastoma protein (RB) with E2F-1 transcription factor; inhibition of phosphorylation of RB, resulting in sequestration of E2F-1 and subsequent down-regulation of S phase genes; decreased interaction of E2F-1 with its consensus binding sites; inhibition of cell motility and invasiveness; and inhibition of the AKT pathway. Our results demonstrate a potential use of ritonavir as part of combination chemotherapy for PDAC. Since ritonavir is FDA approved for HIV, drug repositioning for PDAC would limit the costs and reduce risks.
ritonavir; pancreatic adenocarcinoma; AKT; retinoblastoma; 2F-1
Vascular malformations consist of a spectrum of lesions involving all parts of the body. They have different terminologies like vascular tumors, vascular malformations, vascular anomalies, and so on, which create a lot of confusion in understanding and treating these pathologies. Of late, classification on the basis of cellular kinetics and clinical behavior has been devised. Hemangioma is the most common vascular tumor. Vascular malformations are of either lymphatic or capillary and venous origin. Sometimes they are of a mixed origin. Lymphangiomas are common in the face and neck area. They are also not unusual in the mediastinum. We present a case where a huge lymphangioma occupied the right supraclavicular area of the neck, extending to nearly the entire right thoracic cavity, compressing the whole lung. The patient had occasional symptoms of cough. Ultrasonography (US) and computed tomography (CT) images clearly described the lesion as cystic, occupying both the supraclavicular and thoracic cavity compressing the lung parenchyma. Surgical excision was planned and we approached the lesion via both cervical and thoracotomy incisions. Complete excision was done, and the lung expended fully after the surgery.
Cystic hygroma; dysphasia; lymphangioma
Venous malformations (VMs) are slow-flow vascular malformations, caused by abnormalities in the development of the veins. Venous malformations vary in size and location within the body. When the skin or tissues just under the skin are affected, they appear as slightly blue-colored skin stains or swellings. These can vary in size from time to time because of swelling within the malformation. As these are vascular malformations, they are present at birth and grow proportionately with the child. Venous malformations can be very small to large in size, and sometimes, can involve a significant area within the body, When the venous malformation is well localized, this may cause localized swelling, however, when the venous malformation is more extensive, there may be more widespread swelling of the affected body part. Some patients with venous malformations have abnormal blood clotting within the malformation. Most venous malformations cause no life-threatening problems for patients. Some venous malformations cause repeated pain due to intermittent swelling and congestion of the malformation or due to the formation of blood clots within the malformation. Rarely, venous malformations may be part of a syndrome (an association of several clinically recognizable features) or be linked to an underlying genetic abnormality. We present 12 cases of venous malformations of the head and neck area, which have been managed at our hospital.
Dysmorphogenesis; ectasia; hemangioma; vasculogenesis
Multiferroic materials, in which ferroelectric and magnetic ordering coexist, are of fundamental interest for the development of multi-state memory devices that allow for electrical writing and non-destructive magnetic read-out operation. The great challenge is to create multiferroic materials that operate at room-temperature and have a large ferroelectric polarization P. Cupric oxide, CuO, is promising because it exhibits a significant polarization, i.e. P ~ 0.1 μC.cm−2, for a spin-spiral multiferroic. Unfortunately CuO is only ferroelectric in a temperature range of 20 K, from 210 to 230 K. Here, using a combination of density functional theory and Monte Carlo calculations, we establish that pressure-driven phase competition induces a giant stabilization of the multiferroic phase of CuO, which at 20-40 GPa becomes stable in a domain larger than 300 K, from 0 to T > 300 K. Thus, under high-pressure, CuO is predicted to be a room-temperature multiferroic with large polarization.