Bone mineral density, turnover, and microarchitecture assessed by second-generation high-resolution peripheral quantitative computed tomography in patients with Sheehan's syndrome.

Sheehan's syndrome (SS) is a rare but well-characterized cause of hypopituitarism. Data on skeletal health is limited and on microarchitecture is lacking in SS patients. PURPOSE: We aimed to explore skeletal health in SS with bone mineral density (BMD), turnover, and microarchitecture. METHODS: Thirty-five patients with SS on stable replacement therapy for respective hormone deficiencies and 35 age- and BMI-matched controls were recruited. Hormonal profile and bone turnover markers (BTMs) were measured using electrochemiluminescence assay. Areal BMD and trabecular bone score were evaluated using DXA. Bone microarchitecture was assessed using a second-generation high-resolution peripheral quantitative computed tomography. RESULTS: The mean age of the patients was 45.5 ± 9.3 years with a lag of 8.3 ± 7.2 years prior to diagnosis. Patients were on glucocorticoid (94%), levothyroxine (94%), and estrogen-progestin replacement (58%). None had received prior growth hormone (GH) replacement. BTMs (P1NP and CTX) were not significantly different between patients and controls. Osteoporosis (26% vs. 16%, p = 0.01) and osteopenia (52% vs. 39%, p = 0.007) at the lumbar spine and femoral neck (osteoporosis, 23% vs. 10%, p = 0.001; osteopenia, 58% vs. 29%, p = 0.001) were present in greater proportion in SS patients than matched controls. Bone microarchitecture analysis revealed significantly lower cortical volumetric BMD (vBMD) (p = 0.02) at the tibia, with relative preservation of the other parameters. CONCLUSION: Low areal BMD (aBMD) is highly prevalent in SS as compared to age- and BMI-matched controls. However, there were no significant differences in bone microarchitectural measurements, except for tibial cortical vBMD, which was lower in adequately treated SS patients.

Sex differences in cognitive function among people with HIV-1 clade C infection in Northern India.

Human immunodeficiency virus-1 (HIV-1) clade C is the most prevalent form of HIV-1 comprising nearly 46% of global infections and is the dominant subtype in India. Despite its predominance, the impact of HIV-1 clade C infection on cognitive function has been understudied in comparison with other subtypes, notably clade B, which is primarily found in Europe and North America. Few studies have assessed cognitive impairment in antiretroviral therapy (ART) naïve men and women with HIV-1 clade C infection. In this study conducted in Northern India, differences in neuropsychological functioning were compared between 109 participants (70 men, 39 women) with untreated HIV-1 clade C infection and 110 demographically matched healthy controls (74 men, 36 women). A comprehensive neuropsychological battery was used to examine depression, self-assessment of functioning, and cognitive performance in six domains of functioning. Group differences were assessed by HIV-1 status and sex, controlling for age and education. Results indicated that cognitive deficits were substantially greater among male participants with HIV-1 clade C compared to male controls in all domains of cognitive functioning; in contrast, women with HIV-1 clade C had only minor deficits compared to healthy female participants. In addition, a larger proportion of men with HIV-1 clade C exhibited high levels of depression than women with HIV-1 clade C. These findings suggest that untreated HIV-1 clade C infection in men can have debilitating effects on neuropsychological function and depression, and stress the importance of facilitating rapid access to treatment to reduce the impact of HIV-1 infection.

Serum Calcitonin Gene-Related Peptide Is Elevated in Patients With Migraine and Ophthalmoplegia.

BACKGROUND: There is ongoing debate about whether the oculomotor (III), trochlear (IV), or abducens (VI) nerve paresis in patients with migraine is directly attributable to migraine (ophthalmoplegic migraine [OM]) or is due to an inflammatory neuropathy (recurrent painful ophthalmoplegic neuropathy [RPON]). As migraine is associated with elevated serum calcitonin gene-related peptide (CGRP) levels, we studied serum CGRP levels among patients with OM/RPON to determine whether they are elevated during and between attacks. This is the first study assessing CGRP levels in the serum of patients with OM/RPON. METHODS: The aim of this case-control study was to assess serum CGRP levels in patients with ophthalmoplegia and a headache consistent with migraine according to ICHD-3 criteria. Serum CGRP levels were measured during the ictal and interictal phases in 15 patients with OM/RPON and compared with age-matched and sex-matched controls without migraine (12 patients). RESULTS: The median serum CGRP levels were significantly elevated ( P = 0.021) during the ictal phase (37.2 [36.4, 43.6] ng/L) compared with controls (32.5 [30.1, 37.3] ng/L). Serum CGRP levels during the attack correlated with the total duration of ophthalmoplegia. A CGRP level of 35.5 ng/L in the ictal phase of the attack had a sensitivity of 86.7% and specificity of 75.0% in diagnosing a patient with OM/RPON. CONCLUSIONS: Elevated serum CGRP levels during the ictal phase of OM/RPON favor migraine as the underlying cause of episodic headache with ophthalmoplegia.

Heavy and less common metals in rainwater and the kinetics of the oxidation of hydrogen sulfide by oxygen in rainwater medium.

As a sequel to our recent study on the oxidation by O2, i. e., autoxidation of dissolved hydrogen sulfide, H2S, in aqueous medium, we present here the results of a similar study in rain water medium. The rainwater sampling was done sequentially for four years (2016-2019). In all 67 samples of rainwater were collected on event basis during monsoon period (June-October) in and around the Campus of University of Rajasthan, Jaipur (26°50̛ N-75°52̛ E), which is situated in a semi-arid region adjacent to the Thar Desert in the North-Western part of the India having an annual average rainfall of 54 cm. ICP-MS technique was used in the analysis of rainwater and more than 30 metals were detected, which included transition metals, rare earths, less common metals. Beryllium, vanadium, silver, selenium, manganese, cerium, gallium, yttrium, barium, cesium, copper, rubidium, arsenic, lanthanum, cadmium, lead, uranium and bismuth were common to all rain water samples.H2S oxidation by dissolved oxygen was studied in rainwater as well as in laboratory water media for comparison. The kinetics rate law was: -d[O2]/dt = k1K1[H+][S][O2]t/( [H+]2 + K1[H+] + K1K2), where K1 is first dissociation constant of H2S and k1 is the rate constant for the dominant reaction step:HS- + O2 → products.

MR vessel wall imaging in cerebral bacterial and fungal infections.

PURPOSE: Central nervous system (CNS) bacterial and fungal infections can cause secondary vasculitis which worsens the prognosis due to development of complications like infarctions or hemorrhages. In this prospective study, we aim to study intracranial vessel wall imaging findings in bacterial and fungal infections. METHODS: We included 12 cases of nontubercular bacterial and fungal CNS infections each, in whom definitive microbiological diagnosis could be made. High-resolution vessel wall imaging (VWI) and time of flight MR angiography (TOF MRA) were incorporated in the routine imaging protocol. All cases were evaluated for the presence of vascular enhancement, pattern of enhancement, and stenosis on VWI. Statistical analysis was done to evaluate association between findings of vessel wall imaging and infarctions. RESULTS: We found infarctions in 5 out of 12 cases (41.7%) of the bacterial group and 7 out of 12 cases (58.3%) of the fungal group. Vessel wall enhancement was seen in 5 cases (41.7%) of the bacterial group and 9 cases (75%) of the fungal group. There was a significant association between infarctions and vessel wall enhancement in the fungal group. However, pattern of enhancement or stenosis on VWI was not significantly associated with presence of infarction. VWI detected more cases of vascular involvement than TOF MRA. CONCLUSION: Secondary infectious vasculitis in bacterial and fungal infections can be detected by VWI, which can play an important role in better patient management as detection of vascular involvement can prompt early treatment to prevent complications like infarctions or hemorrhages.

High-resolution intracranial vessel wall imaging in cerebral viral infections evaluations.

PURPOSE: Vascular complications can be seen in various viral CNS infections. Variable neuro-imaging findings have been described in the literature elucidating the parenchymal changes with vascular involvement. Vessel wall imaging (VWI) can help to detect these vascular involvements. We aimed to describe the role and usefulness of VWI in the evaluation of various viral CNS infections. METHODS: In this prospective study, we included 15 cases of various diagnosed viral CNS infections (varicella, HIV encephalopathy, HSV encephalitis, Japanese encephalitis, dengue, COVID-19). VWI and time-of-flight MR angiography (TOF MRA) were included in imaging protocol. All cases were evaluated for the presence of cerebral parenchymal changes, vascular enhancement, and vascular stenosis. RESULTS: We found infarctions in all 5 cases of varicella, 1 case of HIV encephalopathy, and 1 case of COVID-19 encephalopathy. All these cases also showed vascular enhancement and stenosis on VWI. The rest of the cases, including 1 case of HIV encephalopathy, 3 cases of herpes encephalitis, 2 cases of dengue, and 2 cases of Japanese encephalitis did not have any vascular complication, and also did not show vascular enhancement or stenosis. CONCLUSION: VWI can be useful in the detection of vascular involvement in various viral infections of CNS which show a relatively higher cerebrovascular complication rate like varicella, HIV encephalopathy, and COVID-19. However, VWI may not be useful in the routine evaluation of other viral infections like herpes, dengue, and Japanese encephalitis, which have a very low rate of cerebrovascular complication rate.

Long-term hepatic and cardiac health in patients diagnosed with Sheehan's syndrome.

PURPOSE: Sheehan's syndrome (SS) is characterised by chronic pituitary insufficiency following a vascular insult to the pituitary in the peripartum period. There is a lack of substantial evidence on the long-term hepatic and cardiac consequences in these patients, following hormone replacement. METHODS: Patients with a diagnosis of SS were recruited for the study. Detailed clinico-biochemical and radiological evaluation were performed in all patients (n = 60). Hepatic and cardiac complications were assessed using fibroscan and echocardiography (2D speckle-tracking) respectively, in a subset of patients (n = 29) as well as age-and BMI-matched controls (n = 26). Controlled attenuation parameter (for steatosis) and liver stiffness measurement (for fibrosis) were used to define non-alcoholic fatty liver disease (NAFLD). Diastolic cardiac function was evaluated using standard criteria and systolic function by ejection fraction and global longitudinal strain (GLS). RESULTS: The mean age of the cohort was 42.7 ± 11.6 years. Multiple (≥ 2) hormone deficiencies were present in 68.8% of patients, with hypothyroidism (91.4%), hypocortisolism (88.3%), and growth hormone (GH) deficiency (85.7%) being the most common. At a mean follow-up of 9.8 ± 6.8 years, NAFLD was present in 63% of patients, with 51% having severe steatosis, which was predicted by the presence of GH deficiency and higher body mass index. Though the ejection fraction was similar, increased left ventricular GLS (18.8 vs. 7.7%) was present in a significantly higher number of patients versus controls. CONCLUSION: NAFLD, especially severe hepatic steatosis, is highly prevalent in SS. Subclinical cardiac systolic dysfunction (impaired GLS) is also more common, but of mild intensity.

Analytical Study of the Risk Factors Affecting the Fracture Risk in Rheumatoid arthritis Patients using FRAX Algorithm.

OBJECTIVES: The present study aimed to calculate the risk of osteoporotic fracture in patients of Rheumatoid arthritis (RA) by Fracture Risk Assessment Tool (FRAX) and its relationship with osteoporotic-specific risk factors. METHODS: This was a observational cross-sectional analytical study conducted from January 2019 to September 2020 where 185 patients, aged 40-90 years, who presented to the Rheumatology Clinic meeting the ACR/EULAR (2010) Classification Criteria for Rheumatoid Arthritis were included in the study and matched with 185 healthy individuals. We assessed the severity of the disease by using the DAS28 score. In addition, we evaluated the FRAX algorithm for all patients and controls to determine the 10-year fracture risk of major osteoporotic fracture and hip fracture. RESULTS: RA patients had a significantly higher mean 10-year risk of major osteoporotic fracture (4.77 ± 5.04 vs 2.05 ± 1.84, P<0.05) and significantly higher mean 10-year risk of hip fracture (1.71 ± 2.81 vs 0.5 ± 0.95) (p<0.05).There was a significant positive correlation of duration of disease, previous fracture; parent fractured hip with major osteoporotic fracture (r=0.257, 0.435, 0.169 respectively) and with hip fracture (r=0.26, 0.369, 0.212 respectively). We saw no correlation of fracture risk with ESR (mm/hr), DAS28, CRP (mg/dL), glucocorticoid use, smoking, and alcohol use. CONCLUSION: The risk of hip fracture and major osteoporotic fracture significantly increased in both male and female patients with RA as assessed by the FRAX algorithm. Duration of the disease, previous fracture, and parent fracture hip showed a significant correlation with major osteoporotic fracture and hip fracture. Therefore, the early recognition and treatment of RA hold importance in reducing the fracture risk.

Advanced multiparametric MRI-based scoring for isocitrate dehydrogenase mutation prediction of gliomas.

Purpose: To propose an advanced multiparametric magnetic resonance imaging (MRI)-based scoring system and evaluate its diagnostic accuracy with respect to the isocitrate dehydrogenase (IDH) mutation status of gliomas. Material and methods: This prospective observational study included 50 consecutive patients with suspected gliomas, enrolled for pre-operative MRI. The exclusion criteria were previous surgery, biopsy, or chemo/radiotherapy and contraindications to the gadolinium-based contrasts or MRI acquisition. A standardized brain-MRI protocol using a 3-Tesla machine and 16-channel head coil consisted of pre-contrast axial-T2WI, FLAIR, DTI, 3D-ASL perfusion, SWI, 3D-T1WI, and post-contrast axial-DSC perfusion followed by 3D-T1WI and MR spectroscopy. ROIs were drawn from the tumoral centre, periphery, and peritumoral oedema (3 ROIs for each) followed by normalization using the ROIs over the contralateral normal white matter. The cut-off values for the statistically significant (p <0.05) continuous variables were derived by drawing receiver operating characteristic (ROC) curves. A 7-point "glioma-score" was derived from the 3 categorical (T2/FLAIR-mismatch, contrast enhancement, and intratumoral susceptibility signals) and 4 continuous ROI-based variables (ADC, FA, ASL-CBF, and DSC-CBV). Results: The predictability of IDH mutant status using the multiparametric advanced MRI-based glioma score was statistically significant (sensitivity = 69.23%, specificity = 95.65%, PPV = 94.74%, NPV = 73.33%). A glioma score of more than 4.5 out of 7 predicted the IDH-mutation status with higher specificity and sensitivity compared to each of the individual imaging variables. Conclusions: The advanced multiparametric MRI-based glioma score can predict the IDH-mutation status with high statistical significance.

Neuroimaging Spectrum of Severe Hypernatremia in Infants with Neurological Manifestations.

BACKGROUND: Variable neurological manifestations and imaging findings have been described in children with severe hypernatremia. We aimed to describe the spectrum of neuroimaging changes in infants with severe hypernatremia. METHODS: This retrospective study included infants with severe hypernatremia (serum sodium >160 mEq/L), abnormal neurological examination, and an abnormal magnetic resonance imaging (MRI) of the brain over a period of 2 years in a tertiary care hospital. Relevant clinical data, including the feeding practices, clinical features, complications, and biochemical and radiological parameters, were entered in a structured pro forma. MRI findings were classified as vascular (hemorrhages and cerebral sinus venous thrombosis), osmotic demyelination syndrome (pontine and extrapontine myelinolyses), and white matter changes. RESULTS: The common clinical features in the neonates were poor feeding (n = 4) and decreased urine output (n = 4); the older infants presented with gastrointestinal losses (n = 5). All cases had dehydration with encephalopathy. The patterns of radiological injury were vascular (hemorrhages, n = 5 and venous thrombosis, n = 3), osmotic demyelination (n = 8), and white matter changes (n = 7). Coagulopathy was correlated with the vascular complications (r = 0.8, p < 0.0001); the degree of dehydration was correlated with the venous thrombosis (r = 0.7, p < 0.04) and acute kidney injury (r = 0.8, p < 0.001). Neurological sequelae were seen in four cases and correlated with hypernatremia (r = 0.6, p = 0.03) and hyperosmolarity (r = 0.6, p = 0.03). CONCLUSION: Characteristic neuroimaging findings are vascular changes in the form of venous thrombosis and hemorrhages, osmotic demyelination and white matter tract injury, and/or mostly combinations of these findings. Severe hypernatremia and resulting hyperosmolarity frequently cause neurological sequelae in neonates and infants.

Non-invasive assessment of cerebral microvascular changes for predicting postoperative cerebral hyperperfusion after surgical revascularisation for moyamoya disease: an arterial spin labelling MRI study.

PURPOSE: Cerebral hyperperfusion syndrome (CHPS) can result after anastomotic surgery as the reperfusion is established in chronically ischemic cerebral territories in patients of moyamoya disease (MMD). In this study, we have evaluated the feasibility of arterial spin labelling (ASL) perfusion MRI to predict cerebral hyperperfusion syndrome based on changes of cerebral blood flow (CBF) after revascularisation surgery in patients of MMD. METHODS: Our prospective study included 25 patients with MMD who underwent superficial temporal artery-middle cerebral artery (STA-MCA) bypass with or without dural/muscle synangiosis. ASL MRI was performed before and 1-7 days after surgery. On the side planned for operation, 5-mm ROI circle was drawn on the predetermined regions in frontal lobe, temporal lobe, parietal lobe and basal ganglia in proximal and distal territories of MCA to calculate ipsilateral CBF values (CBFi). An attempt was made to select the same location on contralateral side (non-operative) (CBFc) for each measurement for calculation of hemispheric normalised CBF (nCBFh) ratios. To adjust for inter individual variation among MR imagers and CBF, additional regions of interest were drawn within the cerebellum (CBFcbl) for cerebellar CBF normalised ratios (nCBFCbl). RESULTS: Of the 25 patients (26 operated hemispheres), 5 patients showed significant immediate postoperative symptoms suggestive of CHPS. Based on our findings, sensitivity and specificity of ASL perfusion to detect CHPS were evaluated. ASL was found to have 47-100% sensitivity and 45-88% specificity to detect CHPS. We have tried to calculate the prevalence of CHPS in postoperative patients of moyamoya disease, which in our study ranged from 6.83 to 40.70%. CONCLUSION: Based on our results, we concluded that ASL perfusion is an appropriate alternative to standard nuclear medicine studies to monitor the changes in perfusion after STA-MCA bypass surgery in moyamoya patients. ASL MR perfusion can be used to identify changes in cerebral blood flow (CBF) for early detection of cerebral hyperperfusion syndrome in patients with otherwise normal conventional MRI sequences with very high sensitivity but moderate specificity.

MR vessel wall imaging in tubercular meningitis.

PURPOSE: Tubercular meningitis (TBM) has the propensity to cause secondary vasculitis through various mechanisms leading to development of cerebrovascular complications. These vascular involvements can be detected by vessel wall imaging (VWI). In this study, we aimed to study detailed findings of vessel wall imaging in cases of tubercular meningitis. METHODS: All consecutive patients of suspected tubercular meningitis in whom diagnosis of TBM could be made according to diagnostic criteria given by Ahuja et al. were included in the study. High-resolution MR VWI and time of flight (TOF) magnetic resonance angiography (MRA) were done along with routine MRI sequences. Arteries up to second-order branches were studied, and statistical analyses were done with respect to stage of tubercular meningitis, infarctions and TOF MRA findings. RESULTS: Out of all 101 cases of TBM, infarctions were found in 49 cases (48.5%), and vessel wall enhancement was seen in 67 cases (66.3%). With increasing severity of disease, more severe vascular involvement was seen on VWI. There was significant association between enhancement of individual arteries and infarctions in their territories. VWI had better sensitivity than the MRA, while MRA had better specificity than VWI for detection of vascular complications. CONCLUSION: Tubercular vasculitis can be detected by VWI in the form of nodular or smooth segmental enhancement of vessel wall with or without stenosis. Incorporation of VWI in routine MR imaging can play a greater role in early detection and management of cerebrovascular complications which can help to improve prognosis of the disease.

Intracranial Germinoma Masquerading as Secondary Granulomatous Hypophysitis: A Case Report and Review of Literature.

Germinomas are highly immunogenic tumors eliciting a strong peri-tumoral immune response that can spillover into the surrounding healthy tissues. This phenomenon can also occur in intracranial germinomas, manifesting as secondary hypophysitis. Herein, we report a case of 12-year-old-girl presenting with polyuria and polydispsia. She had central diabetes insipidus (CDI) and panhypopituitarism. Imaging revealed a sellar-suprasellar mass with infundibular stalk thickening. Transphenoidal biopsy revealed epithelioid granulomas with immunostaining negative for germinomatous cells. Other causes of hypophysitis were ruled out. Accordingly, she was diagnosed as primary granulomatous hypophysitis and treated with high-dose corticosteroids. Three years later she again presented with headache, vomiting and diminution of vision. Imaging showed a heterogeneous, solid-cystic peripheral rim-enhancing lesion at the same location with involvement of hypothalamus, ependyma and pineal gland. Cerebrospinal fluid beta-human chorionic gonadotropin was markedly elevated, confirming the diagnosis of an intracranial germ cell tumor. She was started on chemotherapy; however, she succumbed to febrile neutropenia. We performed a literature search and found 18 anecdotal cases of secondary hypophysitis associated with intracranial germinomas. There was a slight male preponderance (male:female 5:4). Two-thirds of the cases were below 18 years of age. Polyuria was the most common presenting manifestation (83%). CDI and panhypopituitarism were seen in 89 and 78% cases, respectively. Imaging evidence of pituitary stalk thickening was seen in 12 cases (67%), while pituitary enlargement and/or sellar mass were reported in 11 cases (61%). Pineal involvement was extremely rare, being reported in only 1 case, implying the predilection of suprasellar (rather than pineal) germinomas in causing secondary hypophysitis. Histologically, 82% had lymphocytic hypophysitis, while 18% had granulomatous hypophysitis. Initially, the diagnosis of germinoma was missed in 60% of the cases who were wrongly treated with corticosteroids. To conclude, physicians should make it a dictum that all children and adolescents presenting with CDI and pituitary stalk thickening should be rigorously screened for an underlying intracranial germinoma before labeling them as primary hypophysitis.

Role of Plasma Exchange in a Steroid- and IVIG-Refractory Patient with Acute Disseminated Encephalomyelitis: A Case Report.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease usually affecting children and is treated with high-dose steroid therapy. CASE REPORT: An 8-year boy presented with limbs weakness and complete loss of vision and was resistant to steroid therapy. He was further treated with plasma exchange and showed full recovery from the neurological deficit. CONCLUSION: Therapeutic plasma exchange appears to be effective in ADEM patients in reversing the neuropathological process especially refractory to steroids and intravenous immunoglobulin.

Identification of a unique loss-of-function mutation in IGF1R and a crosstalk between IGF1R and Wnt/ß-catenin signaling pathways.

IGF1R is a ubiquitous receptor tyrosine kinase that plays critical roles in cell proliferation, growth and survival. Clinical studies have demonstrated upregulation of IGF1R mediated signaling in a number of malignancies including colon, breast, and lung cancers. Overexpression of the IGF1R in these malignancies is associated with a poor prognosis and overall survival. IGF1R specific kinase inhibitors have failed in multiple clinical trials partly because of the complex nature of IGF1R signaling. Thus identifying new binding partners and allosteric sites on IGF1R are emerging areas of research. More recently, IGF1R has been shown to translocate into the nucleus and perform many functions. In this study, we generated a library of IGF1R deletion and point mutants to examine IGF1R subcellular localization and activation of downstream signaling pathways. We show that the nuclear localization of IGF1R is primarily defined by its cytoplasmic domain. We identified a cross-talk between IGF1R and Wnt/ß-catenin signaling pathways and showed, for the first time, that IGF1R is associated with upregulation of TCF-mediated ß-catenin transcriptional activity. Using loss-of-function mutants, deletion analysis and IGF1R specific inhibitor(s), we show that cytoplasmic and nuclear activities are two independent functions of IGF1R. Furthermore, we identified a unique loss-of-function mutation in IGF1R. This unique loss-of-function mutant retains only nuclear functions and sits in a pocket, outside ATP and substrate binding region, that is suited for designing allosteric inhibitors of IGF1R.

Diagnostic accuracy of magnetic resonance imaging in the evaluation of pulmonary infections in immunocompromised patients.

PURPOSE: To evaluate the accuracy of magnetic resonance imaging (MRI) for diagnosing pulmonary infections in immunocompromised adults. MATERIAL AND METHODS: Computed tomography (CT) and MRI chest were performed in 35 immuno-compromised patients suspected of pulmonary infection. The MRI sequences that were performed included axial and coronal T2 half-Fourier acquisition single-shot turbo spin-echo (HASTE), spectrally attenuated inversion recovery (SPAIR), true fast imaging with steady-state free precession (TRUFI), and three-dimensional fast low angle shot (3D FLASH) using breath-hold and respiratory triggered BLADE (proprietary name for periodically rotated overlapping parallel lines with enhanced reconstruction). The presence of nodules, consolidations, and ground-glass opacities was evaluated. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for MRI using CT scan as a reference standard. RESULTS: The sensitivity of MRI in nodule detection was 50% overall and 75% for nodules measuring more than 5 mm. Consolidation was detected with 100% sensitivity. Sensitivity and PPV for the detection of ground-glass opacities (GGOs) were 77.7% and 53.8%, respectively. T2 HASTE axial had the fewest image artefacts. Respiratory triggered MR pulse sequence did not add any significant diagnostic information as compared to the non-respiratory triggered MR pulse sequences. CONCLUSIONS: Sensitivity for detecting small nodules and GGOs on MR is poor; CT scan remains the imaging modality of choice for the evaluation of pulmonary infections in immunocompromised patients. However, MRI can be used in the follow-up imaging of these patients.

Perfusion magnetic resonance imaging in differentiation of neurocysticercosis and tuberculoma.

PURPOSE: Tuberculoma and neurocysticercosis (NCC) are two of the most common intracranial infections in developing countries and cause of seizures or focal neurological deficit. They often present on neuroimaging as ring-enhancing lesions, and in absence of typical imaging features, can cause significant diagnostic dilemma. Differentiation is extremely important to avoid empirical exposure to anti-tubercular treatment or nonspecific treatment causing disease progression. The aim our study was to evaluate the MR perfusion characteristics of brain tuberculoma and NCC and to assess the potential role of the perfusion in differentiating the two entities. METHODS: Fifty untreated patients (20 tuberculoma and 30 NCC) were prospectively evaluated by using conventional imaging and dynamic susceptibility contrast (DSC) MR perfusion. Relative cerebral blood volume (rCBV) values were calculated from the wall and core of the lesion and were compared with contralateral normal white matter. RESULTS: rCBV values from the wall of the lesion were significantly different in tuberculoma and NCC (P < 0.05). Tuberculomas showed high mean rCBV values than NCC (3.3 and 1.3 respectively). The core of these lesions showed lower rCBV values in both the lesions which were lower than normal white matter. A cutoff value of rCBV from the wall of the lesion 1.965 for tuberculoma showed 90% sensitivity and 100% specificity. CONCLUSION: Perfusion MRI in combination with conventional sequences can better characterize and differentiate similar-appearing tuberculoma and NCC and may be incorporated in routine protocol which may help in avoiding brain biopsy and empirical therapy.

Neuroimaging Abnormalities in Patients With Nontransfusion-dependent Thalassemia.

Independence from regular transfusions is the hallmark of nontransfusion-dependent thalassemia (NTDT). However, the associated complications need anticipation and screening. One such complication is a hypercoagulable state predisposing to development of thrombosis. We evaluated children with NTDT >10 years of age for prevalence of neuroimaging abnormalities (NIA) and identified associated risk factors. In total, 29 patients were evaluated. Blood counts, serum ferritin, protein C, protein S, antithrombin III, brain magnetic resonance imaging, and angiography was done in all patients. Possible risk factors for thrombosis or cerebrovascular disease were analyzed for association with NIA. The median age was 14 (12 to 15) years. Fifty percent were splenctomized and 31.5% were transfusion naïve. Eleven patients (37.9%) had NIA: 6 with silent cerebral infarction (SCI); 2 with cerebral arteriopathy (CA) and 3 having both CA and SCI. Higher white blood cell (WBC) count was associated with NIA (P=0.034) [silent cerebral infarction (P=0.047) and cerebral arteriopathy (P=0.067)]. Presence of 7 or more risk factors had 4.5 times greater risk of a NIA, especially silent cerebral infarction (SCI) (P=0.03). We conclude that cerebral infarction and arteriopathy seem to start in late childhood. There is a need to develop strategies for preventing neurologic complications in NTDT similar to sickle cell disease.

Terminal regions of ß-catenin are critical for regulating its adhesion and transcription functions.

ß-Catenin, the central molecule of canonical Wnt signaling pathway, has multiple binding partners and performs many roles in the cell. Apart from being a transcriptional activator, ß-catenin acts as a crucial effector component of cadherin/catenin complex to physically interact with actin cytoskeleton along with α-catenin and E-cadherin for regulating cell-cell adhesion. Here, we have generated a library of ß-catenin point and deletion mutants to delineate regions within ß-catenin that are important for α-catenin-ß-catenin interaction, nuclear localization, and transcriptional activity of ß-catenin. We observed a unique mechanism for nuclear localization of ß-catenin and its mutants and show that N-terminal exon-3 region and C-terminal domain of ß-catenin are critical for this activity of ß-catenin. Furthermore, we show HepG2 cells have high ß-catenin mediated transcriptional activity due to the presence of an interstitial deletion at the N-terminal region of ß-catenin. Due to this deletion mutant (hereupon called TM), GSK3ß and HDAC inhibitors failed to show any impact whereas curcumin significantly inhibited ß-catenin mediated transcriptional activity reiterating that TM is primarily responsible for the high transcriptional activity of HepG2 cells. Moreover, we show the recombinant TM does not physically interact with α-catenin, localizes predominantly in the nucleus, and has nearly two-fold higher transcriptional activity than the wildtype ß-catenin.

Role of preoperative versus postoperative itraconazole in allergic fungal rhinosinusitis.

Antifungals used as adjuvant to surgery in AFRS (Allergic Fungal Rhinosinusitis) have shown varying success in delaying recurrences. Itraconazole has been used both as preoperative and postoperative adjuvant. This study investigates the role of itraconazole in AFRS and compares its role between preoperative and postoperative administration of the drug. Patients were randomly divided into groups as: Group 1 (n = 25), received 4 weeks itraconazole in the preoperative period and operated subsequently, Group 2 (n = 25), received 4 weeks itraconazole in the postoperative period, Group 3 (n = 50), matched patients of AFRS, who didn't receive itraconazole. All the groups received oral steroids in tapering doses staring from 1 mg/kg for 6 weeks in the postoperative period. Symptomatic (SNOT 20), radiologic (Lund Mackay, LM) scores and endoscopic (Kupferberg's NE Grades) were noted. Primary postoperative follow-up was for 24 weeks with routine CT scans and nasal endoscopies, followed by which all the patients were followed with nasal endoscopies only with CT scans when required. Both preoperative and postoperative itraconazole showed significant improvement in the SNOT, LM, and Kupferberg's grades in the follow-up period. Preoperative itraconazole therapy showed significantly better results compared to postoperative itraconazole therapy though the recurrence rates were similar in both groups. Itraconazole is a better preoperative adjunct in AFRS than postoperative.