Widespread monoclonal IgE antibody convergence to an immunodominant, proanaphylactic Ara h 2 epitope in peanut allergy.

BACKGROUND: Despite their central role in peanut allergy, human monoclonal IgE antibodies have eluded characterization. OBJECTIVE: We sought to define the sequences, affinities, clonality, and functional properties of human monoclonal IgE antibodies in peanut allergy. METHODS: We applied our single-cell RNA sequencing-based SEQ SIFTER discovery platform to samples from allergic individuals who varied by age, sex, ethnicity, and geographic location in order to understand commonalities in the human IgE response to peanut allergens. Select antibodies were then recombinantly expressed and characterized for their allergen and epitope specificity, affinity, and functional properties. RESULTS: We found striking convergent evolution of IgE monoclonal antibodies (mAbs) from several clonal families comprising both memory B cells and plasmablasts. These antibodies bound with subnanomolar affinity to the immunodominant peanut allergen Ara h 2, specifically a linear, repetitive motif. Further characterization of these mAbs revealed their ability to single-handedly cause affinity-dependent degranulation of human mast cells and systemic anaphylaxis on peanut allergen challenge in humanized mice. Finally, we demonstrated that these mAbs, reengineered as IgGs, inhibit significant, but variable, amounts of Ara h 2- and peanut-mediated degranulation of mast cells sensitized with allergic plasma. CONCLUSIONS: Convergent evolution of IgE mAbs in peanut allergy is a common phenomenon that can reveal immunodominant epitopes on major allergenic proteins. Understanding the functional properties of these molecules is key to developing therapeutics, such as competitive IgG inhibitors, that are able to stoichiometrically outcompete endogenous IgE for allergen and thereby prevent allergic cascade in cases of accidental allergen exposure.

Formulation and statistical optimization of letrozole loaded nanotransferosomal gel for tumor targeting.

Letrozole (LTZ) is used as first-line treatment for hormone-positive breast cancer (BC) in postmenopausal women. However, its poor aqueous solubility and permeability have reduced its clinical efficacy. Herein, we developed LTZ-nanotransferosomes (LTZ-NT) to address above mentioned issues. The LTZ-NT were optimized statistically using Design Expert® followed by their characterization via dynamic light scattering (DLS), Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and Differential scanning calorimetry (DSC). The optimized LTZ-NT was incorporated into 1% chitosan-gel to develop LTZ-NTG. Moreover, in vitro drug release and ex vivo permeation of LTZ-NTG were performed and compared with LTZ-dispersion and LTZ-NT. Additionally, skin irritability and histopathology of LTZ-NTG were investigated. Furthermore, in vitro antitumor study of LTZ-NTG was investigated in BC cell lines. The optimized LTZ-NT showed suitable zeta potential (30.4 mV), spherical size (162.5 nm), and excellent entrapment efficiency (88.04%). Moreover, LTZ-NT exhibited suitable thermal behavior and no interactions among its excipients. In addition, LTZ-NTG had an optimal pH (5.6) and a suitable viscosity. A meaningfully sustained release and improved permeation of LTZ was observed from LTZ-NTG. Additionally, LTZ-NTG showed significantly enhanced cell death of MCF-7 and MCC-7 cells. It can be concluded that LTZ-NTG has the potential to deliver chemotherapeutic agents for possible treatment of BC.

Racial Discrimination and Telomere Length in Midlife African American Women: Interactions of Educational Attainment and Employment Status.

BACKGROUND: Over the life course, African American (AA) women have faster telomere attrition, a biological indicator of accelerated aging, than White women. Race, sex, age, and composite socioeconomic status (SES) modify associations of institutional racial discrimination and telomere length. However, interactions with everyday racial discrimination have not been detected in AA women, nor have interactions with individual socioeconomic predictors. PURPOSE: We estimated statistical interaction of institutional and everyday racial discrimination with age, education, employment, poverty, and composite SES on telomere length among midlife AA women. METHODS: Data are from a cross-section of 140 AA women aged 30-50 years residing in the San Francisco Bay Area. Participants completed questionnaires, computer-assisted self-interviews, physical examinations, and blood draws. Adjusted linear regression estimated bootstrapped racial discrimination-relative telomere length associations with interaction terms. RESULTS: Racial discrimination did not interact with age, poverty, or composite SES measures to modify associations with telomere length. Interactions between independent SES variables were nonsignificant for everyday discrimination whereas institutional discrimination interacted with educational attainment and employment status to modify telomere length. After adjusting for covariates, we found that higher institutional discrimination was associated with shorter telomeres among employed women with lower education (ß = -0.020; 95% confidence interval = -0.036, -0.003). Among unemployed women with higher education, higher institutional discrimination was associated with longer telomeres (ß = 0.017; 95% confidence interval = 0.003, 0.032). Factors related to having a post-high school education may be protective against the negative effects of institutional racism on cellular aging for AA women.

Radiology of COVID-19 - Imaging the pulmonary damage.

A large part of the world is presently in the grip of the coronavirus disease (COVID-19) by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus), declared a pandemic in March 2020. This document is a brief commentary of the imaging modalities used in the screening, diagnosis and management of COVID-19 pneumonia. Chest x-rays, especially portable, still form a part of majority of official guidelines, with reports of the suggestive radiologic features. The potential of CT scan and ultrasound is also realised, with earlier detection rate. Typical radiologic findings of bilateral, asymmetrical, crazy-paved ground glass opacification, consolidation, reverse halo sign, opacities, progressing to fibrosis are well described for both the X-ray and CT scan. Atypical findings include airway changes, pleural effusion, pulmonary nodules and acute pulmonary embolism. Absence of lymphadenopathy, pleural effusion and pneumothorax is notable. The role of portable lung ultrasound, reported to be useful in emergency, is yet to be established in the guidelines. Disinfection of the equipment is a major concern. Governmental guidelines still advocate X-ray despite professional societies increasingly recommending CT scan.

Rational and practical use of imaging in COVID-19 pneumonia.

The severe form of the COVID-19 pandemic caused by the SARS-CoV-2 virus, has largely manifested as a predominant respiratory illness causing severe pneumonia characterized by bilateral, subpleural ground glass haze, progressing to consolidation, and fibrosis on imaging. There is some discrepancy between the governmental guidelines, professional Societies and Radiology and Respiratory Medicine specialists with divided opinions between the use of the chest X-rays and CT scan, and whether the use be screening or diagnostic. So far, the most balanced recommendations have been proposed by the Fleischner Society, which are endorsed by the Radiological Society of Pakistan as well. This writeup describes the approach for a rational use of imaging to the best advantage in the current situation according to local resources, and restricting the spread of infection. The most practical compromise for Pakistan appears to be the use of portable digital radiography equipment, and point-of- care ultrasound; with CT scan reserved for clinical situations not explained by the above two modalities, or demanding disease stratification.

Diagnostic accuracy of diffusion weighted MRI in differentiating benign and malignant meningiomas.

OBJECTIVE: To determine the diagnostic accuracy of DWI in differentiating benign and malignant meningiomas keeping histopathology as gold standard. METHODS: This was a descriptive analytical study conducted at Radiology Department, DUHS/Dr. Ruth K. M. Pfau Civil Hospital Karachi, from August 2016 to March 2018.It included152 patients clinically suspected of meningioma on conventional neuroimaging. Imaging features of DWI were compared with histopathology findings. The diagnostic accuracy of DWI was calculated in terms of sensitivity, specificity, accuracy, PPV and NPV using histopathology as gold standard. RESULTS: There were 59 male and 93 female patients with mean age of 55.38±9.8 years. Mean duration of sign and symptoms was 5.67±2.57 months. Out of 152 patients, 117(77%) and 35(23%) were differentiated into benign and malignant meningiomas respectively by DWI while 135(88.82%) and17(11.18%) patients were diagnosed respectively on histopathology. The sensitivity, specificity, PPV, NPV and accuracy of DWI of 84.4%, 82.3%, 97.4%, 40%, and 84.2% respectively keeping histopathology as gold standard. CONCLUSION: DWI features along with calculation of ADC values is a reliable non-invasive technique for differentiating benign and malignant meningiomas. However the low negative predictive value necessitates the use of histopathology.

MRA-based evaluation of anatomical variation of circle of Willis in adult Pakistanis.

OBJECTIVE: To determine the frequency and patterns of normal anatomical variation of Circle of Willis on magnetic resonance angiogram in adults without cerebrovascular disease. METHODS: This descriptive cross-sectional study was conducted at the Radiology Department of Dow University of Health Sciences / Civil Hospital, Karachi, from January to December 2016, and comprised patients referred for magnetic resonance imaging of the brain and magnetic resonance angiogram without any clinical or radiological manifestation of cerebrovascular disease, primarily including those with suspected demyelination, infection, epilepsy or metastases. Three-dimensional time-of-flight magnetic resonance angiography was performed. The Circle of Willis was assessed for its completeness along with anatomical variations of anterior and posterior components of the circle. RESULTS: Of the 135 subjects, 70(51.8%) were males and 65(48.2%) were females with an overall mean age of 49.26±9.2 years. Among all the subjects, 30(22.2%) showed a complete circle, while 82 (60.7%) and 23(17.1%) had partially complete and incomplete circles respectively. The anterior part of the circle was completed in 108 (80%) subjects, showing type 'a' as the most common variant in 93(68.9%). The posterior part of the circle was completed in 30 (22.2%) subjects with type 'e' variant in 52(38.5%). CONCLUSIONS: There was a wide variability in the anatomy of the Circle of Willis in Pakistani adults asymptomatic for cerebrovascular disease.

Pseudoaneurysm of Left proximal Common Carotid Artery following penetrating trauma.

A 33-year male with history of penetrating trauma to left upper chest in 2006, presented through Medical unit to Radiology Department with complain of hemoptysis. Chest X-ray showed a soft tissue lesion in left upper lobe with a linear metallic foreign body. Contrast enhanced CT scan of chest and later CTA was performed which showed a saccular aneurysm arising from mediastinal part of left common aortic artery surrounded by thrombosis with a cylindrical linear metallic foreign body. He was planned for endovascular repair with stenting which he could not afford due to financial constraints. He is currently on conservative follow up. Vascular lesions can be serious complications resulting from blunt or penetrating trauma, when presenting with hemoptysis due to pseudaoneurysms formation even after so many years of trauma.

To asses inter- and intra-observer variability for breast density and BIRADS assessment categories in mammographic reporting.

OBJECTIVE: To evaluate the inter- and intra-observer variability among radiologists in the characterisation of mammograms according to Breast Imaging Reporting and Data System assessment and breast density categories. METHODS: The descriptive cross-sectional study was conducted at Aga Khan University Hospital, Karachi, from January 2014 to June 2014. Using non-probability purposive sampling, all mammograms in the study were interpreted by three radiologists on the basis of Breast Imaging Reporting and Data System categories and by assessing the breast density composition. The inter-observer variability was recorded by comparing the difference in the interpretation and categorisation of each case. Intra-observer variability was noted by comparing the differences in the two sets of results from reading the same mammogram three months apart. RESULTS: A total of 254 mammograms were reviewed and the mean age of patients was 55.2±11.6 years. In the first round of diagnostic imaging, there was moderate agreement among all three possible pairs of observers regarding breast density (k= 0.50-0.41), but for Breast Imaging Reporting and Data System categories the agreement was less (k=0.27-0.13). After 3 months, variability of observer 1 showed substantial agreement (k=0.65).Variability between observer 2 and observer 3 showed moderate agreement (k=0.13).In terms of categories, intra-observer differences were variable: observer 1 (?=0.61; observer 2(?=0.17); observer 3 (k=0.45). CONCLUSIONS: Despite standardised guidelines for reporting density and assessment categories, observer variability continues to exist.

Development and Evaluation of Tacrolimus Loaded Nano-Transferosomes for Skin Targeting and Dermatitis Treatment.

Tacrolimus (TRL) is used for the treatment of atopic dermatitis (AD) due to its T-cell stimulation effect. However, its significantly poor water solubility, low penetration and cytotoxicity have reduced its topical applications. Herein, tacrolimus loaded nano transfersomes (TRL-NTs) were prepared, followed by their incorporation into chitosan gel to prepare tacrolimus loaded nano transfersomal gel (TRL-NTsG). TEM analysis of the TRL-NTs was performed to check their morphology. DSC, XRD and FTIR analysis of the TRL-NTs were executed after lyophilization. Similarly, rheology, spreadability and deformability of the TRL-NTsG were investigated. In vitro release, ex vivo permeation and in vitro interaction of TRL-NTsG with keratinocytes and fibroblasts as well as their co-cultures were investigated along with their in vitro cell viability analysis. Moreover, in vivo skin deposition, ear thickness, histopathology and IgE level were also determined. Besides, 6 months stability study was also performed. Results demonstrated the uniformly distributed negatively charged nanovesicles with a mean particle size distribution of 163 nm and zeta potential of -27 mV. DSC and XRD exhibited the thermal stability and amorphous form of the drug, respectively. The TRL-NTsG showed excellent deformability, spreadability and rheological behavior. In vitro release studies exhibited an 8-fold better release of TRL from the TRL-NTsG. Similarly, 6-fold better permeation and stability of the TRL-NTsG with keratinocytes and fibroblasts as well as their co-cultures was observed. Furthermore, the ear thickness (0.6 mm) of the TRL-NTsG was found significantly reduced when compared with the untreated (1.7 mm) and TRL conventional gel treated mice (1.3 mm). The H&E staining showed no toxicity of the TRL-NTsG with significantly reduced IgE levels (120 ng/mL). The formulation was found stable for at least 6 months. These results suggested the efficacy of TRL in AD-induced animal models most importantly when incorporated in NTsG.

MRI features of spinal Fluorosis: Results of an endemic community screening.

OBJECTIVES: Fluorosis is endemic in many parts of the world. However community studies on MRI features of fluorosis are lacking. The aim of this study was to determine MRI features of spinal changes in a community with endemic fluorosis in the Thar Desert Pakistan. METHODOLOGY: Randomly selected adults from the Village Samorindh, district Tharparker, Sindh, Pakistan, with spinal fluorosis diagnosed on plain x-rays and raised serum fluoride levels were studied from June 2008 to January 2009. MRI was carried out on 0.5 T open magnet MRI system. Features of vertebral body, spinal ligaments, intervertebral disc, facet joints, iliac wings and other incidental findings were noted. Sclerosis was defined as low signal intensity on both T1 and T2 weighted images. RESULTS were described as mean and percentage values. RESULTS: All the studied 27 subjects complained of back ache without neurological signs. The average age was 43.33 ± 10.45 years; 21 being male (77.8%). The most frequent findings included generalized vertebral sclerosis (24, 88.8%), ligamentum flavum hypertrophy (23, 85%), anterior (20, 74%) and lateral (17, 62.9%) disc herniation, thickened longitudinal ligaments, and narrowing of spinal foramina. Hemangioma was seen in 04(14.8%). The most commonly involved level was L1-2, L4-5 and lower dorsal spine. CONCLUSION: Vertebral sclerosis, a combination of premature degeneration with anterior disc herniation and an unusually high frequency of vertebral hemangioma formed the spectrum of MRI findings in subjects with spinal fluorosis having back ache but no neurological findings.

Quality by design for sumatriptan loaded nano-ethosomal mucoadhesive gel for the therapeutic management of nitroglycerin induced migraine.

Migraine is a progressive neurological condition often accompanied by nausea and vomiting. Various drugs have recently been used in the treatment of migraine, including sumatriptan (SUT). However, SUT has poor pharmacological effects mainly due to its reduced permeability, blood brain barrier (BBB) effect, half-life and bioavailability. Herein, we developed SUT loaded nano-ethosomes (SUT-NEs) for intranasal (IN) delivery, after their incorporation into chitosan based mucoadhesive gel (SUT-NEsG). The observed mean particle size of SUT-NEs was 109.45 ± 4.03 nm with spherical morphology, mono dispersion (0.191 ± 0.001), negatively charged (-20.90 ± 1.98 mV) and with excellent entrapment efficiency (96.90 ± 1.85 %). Fourier-transform infrared (FTIR) spectra have depicted the compatibility of the components. Moreover, SUT-NEsG was homogeneous having suitable viscosity and mucoadhesive strength. In vitro release and ex vivo permeation analysis showed sustained release and improved permeation of the SUT-NEsG, respectively. Additionally, histopathological studies of nasal membrane affirmed the safety of SUT-NEsG after IN application. In vivo pharmacokinetic study demonstrated improved brain bioavailability of SUT-NEsG as compared to orally administered sumatriptan solution (SUT-SL). Furthermore, significantly enhanced pharmacological effect of SUT-NEsG was observed in behavioral and biochemical analysis, immunohistochemistry for NF-κB, and enzyme linked immuno assay (ELISA) for IL-1ß and TNF-α in Nitroglycerin (NTG) induced migraine model. It can be concluded that migraine may be successfully managed through IN application of SUT-NEsG owing to the direct targeted delivery to the brain.

A detailed insight of the tumor targeting using nanocarrier drug delivery system.

Human struggle against the deadly disease conditions is continued since ages. The contribution of science and technology in fighting against these diseases cannot be ignored exclusively due to the invention of novel procedure and products, extending their size ranges from micro to nano. Recently nanotechnology has been gaining more consideration for its ability to diagnose and treat different cancers. Different nanoparticles have been used to evade the issues related with conservative anticancer delivery systems, including their nonspecificity, adverse effects and burst release. These nanocarriers including, solid lipid nanoparticles (SLNs), liposomes, nano lipid carriers (NLCs), nano micelles, nanocomposites, polymeric and magnetic nanocarriers, have brought revolutions in antitumor drug delivery. Nanocarriers improved the therapeutic efficacy of anticancer drugs with better accumulation at the specific site with sustained release, improved bioavailability and apoptosis of the cancer cells while bypassing the normal cells. In this review, the cancer targeting techniques and surface modification on nanoparticles are discussed briefly with possible challenges and opportunities. It can be concluded that understanding the role of nanomedicine in tumor treatment is significant, and therefore, the modern progressions in this arena is essential to be considered for a prosperous today and an affluent future of tumor patients.

Melatonin delivered in solid lipid nanoparticles ameliorated its neuroprotective effects in cerebral ischemia.

The current study explores the potential of melatonin (MLT)-loaded solid lipid nanoparticles (MLT-SLNs) for better neuroprotective effects in ischemic stroke. MLT-SLNs were prepared using lipid matrix of palmityl alcohol with a mixture of surfactants (Tween 40, Span 40, Myrj 52) for stabilizing the lipid matrix. MLT-SLNs were tested for physical and chemical properties, thermal and polymorphic changes, in vitro drug release and in vivo neuroprotective studies in rats using permanent middle cerebral artery occlusion (p-MCAO) model. The optimized MLT-SLNs showed particle size of ∼159 nm, zeta potential of -29.6 mV and high entrapment efficiency ∼92%. Thermal and polymorphic studies showed conversion of crystalline MLT to amorphous form after its entrapment in lipid matrix. MLT-SLNs displayed a sustained release pattern compared to MLT dispersion. MLT-SLNs significantly enhanced the neuroprotective profile of MLT ascertained by reduced brain infarction, recovered behavioral responses, low expression of inflammatory markers and improved oxidation protection in rats. MLT-SLNs also showed reduced hepatotoxicity compared to p-MCAO. From these outcomes, it is evidenced that MLT-SLNs have improved neuroprotection as compared to MLT dispersion and thereby present a promising approach to deliver MLT to the brain for better therapeutic outcomes in ischemic stroke.

After the Floods! Healthcare Response and Concerns.

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Transdermal delivery of allopurinol-loaded nanostructured lipid carrier in the treatment of gout.

BACKGROUND: Allopurinol (ALP), a xanthine oxidase inhibitor, is a first line drug for the treatment of gout and hyperuricemia. Being the member of BCS class II drugs, ALP has solubility problem, which affects its bioavailability. Also, ALP has shorter half-life and showed GI related problems. In present study, ALP was encapsulated in nanostructured lipid carriers (NLCs) to ensure enhanced bioavailability, improved efficacy and safety in vivo. METHODOLOGY: ALP-loaded NLCs were fabricated by micro-emulsion technique. The prepared NLCs were optimized via design expert in term of particle size, zeta potential and entrapment efficiency. FTIR, PXRD and TEM analysis were carried out to check chemical interaction, polymorphic form and surface morphology of the optimized formulation. ALP-loaded NLCs were then loaded into HPMC based poloxamer-407 gel and were characterized. In vitro and ex vivo analysis were carried out via dialysis membrane method and franz diffusion cell, respectively. Uric acid was used for induction of gout and the anti-gout activity of ALP-loaded NLCs gel was performed and compared with ALP suspension. RESULTS: The optimized formulation had particles in nano-range (238.13 nm) with suitable zeta potential (-31.5 mV), poly-dispersity index (0.115) and entrapment of 87.24%. FTIR results confirmed absence of chemical interaction among formulation ingredients. XRD indicated amorphous nature of ALP-loaded NLCs, whereas TEM analysis confirmed spherical morphology of nanoparticles. The optimized formulation was successfully loaded in to gel and characterized accordingly. The in vitro release and drug release kinetics models showed sustained release of the drug from ALP-loaded NLCs gel. Furthermore, about 28 fold enhanced permeation was observed from ALP-loaded NLCs gel as compared to conventional gel. Skin irritation study disclosed safety of ALP-loaded NLCs gel for transdermal application. Furthermore, ALP-loaded NLCs gel showed significantly enhanced anti-gout activity in Sprague-Dawley rats after transdermal administration as compared to oral ALP suspension. CONCLUSION: ALP-loaded NLCs gel after transdermal administration sustained the drug release, avoid gastrointestinal side effects and enhance the anti-gout performance of ALP. It can be concluded, that NLCs have the potential to deliver drugs via transdermal route as indicated in case of allopurinol.

Superwoman Schema, Racial Identity, and Cellular Aging Among African American Women.

BACKGROUND AND OBJECTIVES: African American women experience faster telomere shortening (i.e., cellular aging) compared with other racial-gender groups. Prior research demonstrates that race and gender interact to influence culturally specific norms for responding to socially-relevant stress and other stress-coping processes, which may affect healthy aging. RESEARCH DESIGN AND METHODS: Data are from African American Women's Heart & Health Study participants who consented to DNA extraction (n = 140). Superwoman Schema (SWS) was measured using 5 validated subscales: presenting strength, emotion suppression, resisting vulnerability, motivation to succeed, and obligation to help others. Racial identity was measured using 3 subscales from the Multidimensional Inventory of Black Identity: racial centrality, private regard, and public regard. Relative telomere length (rTL) was measured using DNA extracted from blood samples. Path analysis tested associations and interactions between SWS and racial identity dimensions with rTL. RESULTS: For SWS, higher resistance to being vulnerable predicted longer telomeres. For racial identity, high private regard predicted longer telomeres while high public regard predicted shorter telomeres. Interactions were found between public regard and 2 SWS dimensions: among women with high public regard, emotion suppression (ß = 0.20, p < .05) and motivation to succeed (ß = 0.18, p < .05) were associated with longer rTL. The interaction between high centrality and emotion suppression predicted shorter rTL (ß = -0.17, p < .05). DISCUSSION AND IMPLICATIONS: Culturally specific responses to gendered racism and racial identity, developed early in life and shaped over the life course, are important psychosocial determinants of cellular aging among African American women.

A Doppler-based evaluation of peripheral lower limb arterial insufficiency in diabetes mellitus.

OBJECTIVE: To determine the frequency, level and flow patterns of lower limb arterial insufficiency in diabetic patients on Doppler ultrasound study. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Radiology Department, Civil Hospital, Karachi, from February 2007 to September 2008. METHODOLOGY: One hundred adult diabetic patients with suspected peripheral vascular insufficiency irrespective of gender were included. Demographic data, presenting complaints, treatment history, and level of HbA1c were recorded. Doppler evaluated arterial status and ankle brachial index (ABI) were recorded on proforma. Statical analysis were done on SPSS version 12. RESULTS: The mean HbA1c was 8.4+/-1.4 gm/dl, a majority of 77% having a controlled level of <10mg/dl. Arterial insufficiency on Doppler ultrasound was documented in 62% (p=0.016) and the dorsalis paedis artery was the predominant site of stenosis (24%). Spectral broadening and biphasic flow were salient features. The mean value of resistive index in stenotic cases was 0.563+/-0.16 with a mean velocity difference of 0.37+/-0.29 m/s (p<0.001) at the site of stenosis. CONCLUSION: Peripheral vascular insufficiency was a significant finding in patients having diabetes for an average of 9.8 years, even in the presence of controlled HbA1c. The dorsalis paedis was the commonest site of involvement. The insufficiency was moderate with a biphasic flow pattern in a majority of cases. Difference in resistive index and flow velocities at and above the site of stenosis provided an important clue to the diagnosis of level of stenosis that helps in planning limb salvage management.

Neovascularity patterns in breast carcinoma: correlation of Doppler ultrasound features with sonographic tumour morphology.

OBJECTIVE: To determine the association and correlation between morphologic features of breast cancer on gray scale ultrasound, and vascularity patterns and indices on color and spectral Doppler ultrasound. STUDY DESIGN: Cross-sectional, analytical study. PLACE AND DURATION OF STUDY: Department of Radiology, Dow University of Health Sciences and Civil Hospital, Karachi, from August 2006 to June 2007. METHODOLOGY: Fifty adult female patients with histopathological proven breast cancer underwent ultrasound for evaluation of morphologic features on gray scale mode; vascularity patterns on color Doppler scan and flow indices measurement on spectral Doppler ultrasound. Regression analysis was conducted to determine correlation between the variables and associations of vascularity patterns. RESULTS: The 50 studied patients had predominantly solid tumour in 46 (92%) with depth to width ratio of > 1 in 37 (76%). The mean tumour size was 3.6 +/- 1.34 cm, with irregular margins in 41 (82%), posterior shadowing in 43 (86%) and calcifications in 27 (54%). Type 3 vascularity (multiple peripheral vessels) was the most frequent pattern (n=21, 42%) that showed a positive correlation with solid tumours (r=0.7, p < 0.001). Low resistance spectral waveform was seen in 44 (88%) cases. The average size was 3.69 cm in vascular and 3.1 cm in avascular tumours. Mean resistive index (RI) was 0.67. Mean pulsatility index (PI) was 1.1. RI was significantly high in cystic tumours (mean=0.8, p < 0.001) and significantly low in tumours measuring less than 2 cm (RI=0.18, p < 0.001). CONCLUSION: In this study, multiple peripheral vessels with low resistance flow was the pattern most significantly associated with all appearance of focal breast cancer. Apart from a positive correlation with solid tumours, markedly high RI in cystic tumours and markedly low RI in tumours less than 2 cm, there was no consistent correlation trend difference between Doppler findings and tumour size. Histopathology, therefore, remains the main modality to evaluate the tumour type and characteristics.

Postmortem computed tomography for diagnosis of cause of death in male prisoners.

OBJECTIVE: To determine the utility of postmortem CT (PMCT) examination in establishing the cause of death among male prisoners dying in Karachi jails. METHODS: A descriptive study was carried out from February 2006 to September 2007, CT Scan section, Civil Hospital Karachi and the Mortuary, Dow Medical College, Dow University of Health Sciences, Karachi. Adult male prisoners dying in the Karachi central prison and referred to the study setting for determining the cause of death for medico legal purpose were included. Female prisoners and those cases where the final report of cause of death was not available were excluded. CT scan of the vital body regions (head, neck, thorax, abdomen and pelvis) was carried out in all cases. The scan was read and reported by two radiologists. Anatomical dissection based autopsy was carried out by the forensic expert. Final report regarding the cause of death was issued by the forensic expert based on the combined findings, histopathology, toxicology results and circumstantial evidence. The CT scan and autopsy findings were compared and percentage agreement was determined using kappa statistics. RESULTS: There were 14 cases in all with mean age of 41.2 +/- 17 years. The alleged mode of death was custodial torture in all cases. CT scan determined the cause of death to be natural cardio-respiratory failure in 10, strangulation in 01, pulmonary tuberculosis (TB) in 02 and trauma to spine in 01 case. The autopsy determined natural death in 11 and pulmonary TB in 02 and asphyxia in 01. The percentage agreement between CT and autopsy was 92% (k = 0.92) and between CT and finalized cause of death was 100% (k = 1.0). CONCLUSION: PMCT is as effective as dissection autopsy in identifying pulmonary infections and natural causes of death. It is more effective in identifying vertebral fractures which may exclude hanging and corroborate trauma to spine.