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Introduction: Fasting is a practice of abstaining from certain or all kinds of food and beverages depending on the cultural and religious values of the individual. The objective of this study was to observe the effects of intermittent fasting on the weight of Muslim university students in Karachi, Pakistan. Methods: A longitudinal study was undertaken at the public sector university in Karachi, Sindh, Pakistan from 13 April to 12 May 2021. Using a predefined questionnaire at the beginning and end of one month of intermittent fasting, personal data and weight changes were recorded for a total of 95 participants. Results: The sample was based on primary medical students with a predominance of 73.7% females (70). Most of them (67.4%) were in the age range between 20 and 29 years. About 44 (62.90%) were under the normal BMI of 18.5. When comparing the participants' weight, the mean weight pre-fasting was 58.66±12.12 kg, and the weight after one month of fasting was 58.76±12.67 kg showing a difference of 0.10 kg and a non-significant p-value of 0.73. 17.9% of the subjects had gained over 1 kilogram, 23.2% had lost over 1 kilogram, and 22.1% maintained their weight, after fasting. Conclusion: The study indicated a weight change in most individuals enrolled. Although the weight change was not significant, an increase was seen among most of the individuals. Factors such as decreased physical activity due to COVID-19 quarantine practices, consumption of high-calorie dense foods, and reduced metabolism during fasting may contribute to the results. more...

Colorectal cancer is a sporadic, hereditary, or familial based disease in its origin, caused due to diverse set of mutations in large intestinal epithelial cells. Colorectal cancer (CRC) is a common and deadly disease that accounts for the 4th worldwide highly variable malignancy. For the early detection of CRC, the most common predictive biomarker found endogenously are KRAS and ctDNA/cfDNA along with SEPT9 methylated DNA. Early detection and screening for CRC are necessary and multiple methods can be employed to screen and perform early diagnosis of CRC. Colonoscopy, an invasive method is most prevalent for diagnosing CRC or confirming the positive result as compared to other screening methods whereas several non-invasive techniques such as molecular analysis of breath, urine, blood, and stool can also be performed for early detection. Interestingly, widely used medicines known as non-steroidal anti-inflammatory drugs (NSAIDs) to reduce pain and inflammation have reported chemopreventive impact on gastrointestinal malignancies, especially CRC in several epidemiological and preclinical types of research. NSAID acts by inhibiting two cyclooxygenase enzymes, thereby preventing the synthesis of prostaglandins (PGs) and causing NSAID-induced apoptosis and growth inhibition in CRC cells. This review paper majorly focuses on the diversity of natural and synthetic biomarkers and various techniques for the early detection of CRC. An approach toward current advancement in CRC detection techniques and the role of NSAIDs in CRC chemoprevention has been explored systematically. Several prominent governing mechanisms of the anti-cancer effects of NSAIDs and their synergistic effect with statins for an effective chemopreventive measure have also been discussed in this review paper. more...

Introduction: Cataract arises because of aging of the crystalline lens of the eye which prevents clear vision. X-ray Cross-complementing Group 1 (XRCC1) is a Deoxyribonucleic Acid (DNA) repair protein which is involved in Single-Strand Breaks (SSBs) and Base Excision Repair (BER) pathway which is responsible for the efficient repair of DNA damage is mainly responsible for cataract in patients. Aim: To study the prevalence, risk factors and the molecular characterisation with its special association to XRCC1 gene in senile cataract patients. Materials and Methods: This was a cross-sectional study carried out in the Department of Anatomy and Ophthalmology, Rama Medical College Hospital and Research Centre, Kanpur, Uttar Pradesh, India, from April 2021 to April 2022. A total of 500 clinical patients were included in which 250 patients were confirmed as cataract positive patients. Venous blood of 5 mL was collected in Ethylene diamine tetra-acetic acid tubes. The DNA extraction for the detection of XRCC1gene was done using Qiagen DNA extraction kit as per manufactures guidelines, which was further confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Results: A total of 500 clinically suspected patients were included in which 250 cases were confirmed as cataract positive patients. The ratio of females was more (n=130, 52%) compared to males (n=120, 48%) with the mean age for females with 57.6% and for males with 61.13%. Hypertension (n=173, 69.2%) was the most common disease associated with the cataract patients. The ratio of males were more (n=91, 75.8%) compared to females (n=82, 63.07%). The mean age of males was 64.40 years and that of females were 62.45 years. The other co-morbidity included diabetes (48.8%), in which males constituted 67 (55.83%) participants compared to the females with 55 (42.3%) participants. The presence of XRCC1 gene was detected in all cataract positive patients, which was also confirmed by RT-PCR. Conclusion: The polymorphisms of DNA repair genes decreased their ability to repair DNA damage, leaving human body a greatly increased susceptibility to cancer or agerelated diseases. The association of XRCC1 gene with agerelated cataract susceptibility observed in the present study supports the view that XRCC1 gene plays an important role in susceptibility to age-related cataract, so early screening and its molecular profiling will help the clinician in the early diagnosis as well as early treatment. more...

Introduction: Latarjet coracoid bone block is an effective treatment for the management of recurrent anterior shoulder instability. Minimally invasive technique modified by Saragaglia helps in preservation of subscapularis, leaves a minimal scar and helps in early rehabilitation and recovery. Aim: To assess the midterm clinical outcome of minimally invasive Latarjet procedure for recurrent anterior shoulder instability. Materials and Methods: This was a prospective cohort study conducted from April 2013 to March 2019 at a tertiary care Orthopaedic and Trauma Hospital in patients above 20 years of age of either sex with instability severity score index of >6 were included. A detailed history and clinical examination was done with special reference to hand dominance and number of episodes. Special tests like shift and load test, sulcus test, anterior apprehension test shoulder anterior drawer test and Jobe’s relocation test were done and found to be positive. Preoperative Rowe score was assessed in all the patients. Mean follow-up in present study was 60±18 months. Quantitative variables were analysed using Student’s t-test and qualitative variables using Fisher’s-exact test or Chi-square test. A p-value of more...

Background Asthma and chronic obstructive pulmonary disease are the major airway diseases and are increasingly important causes of mortality, morbidity, and disability globally. This cross-sectional study was conducted to determine monthly and seasonal patterns of asthma and chronic obstructive pulmonary disease in the study area during 2020–2021. The data of the indoor patients for the study period were obtained from the official records maintained in the District Head Quarter teaching hospital Dera Ismail Khan. Results A total of 2179 cases of asthma were recorded including 1609 (73.8%) in 2020 and 570 (26.2%) in 2021, and 740 cases of the chronic obstructive pulmonary disease were also recorded in 2020. Overall asthma was highest in March with 1128 (51.8%) cases and was lowest in July with 29 (1.3%) cases. Seasonal prevalence/pattern show that asthma relatively more prevailed during winter and early spring (December through March). Out of a total of 740 cases of chronic obstructive pulmonary disease, the highest 405 (54.7%) cases were recorded in February and the lowest 0 in April. Seasonal distribution indicated that chronic obstructive pulmonary disease was relatively higher in winter (January–February). Conclusions Seasonal variation and pattern in prevalence exist both in asthma and chronic obstructive pulmonary disease as both indicated relatively higher prevalence in winter compared to summer and autumn. more...

Objective: To determine the role of low-dose aspirin in preventing preeclampsia for previously hypertensive pregnant women. Method: The meta-analysis was conducted from February to May 2021 and comprised search on PubMed and Cochrane Library databases for randomised controlled trials consisting of previously hypertensive women aged 18-55 years, aspirin dosage range 60-100mg, and a comparison between aspirin and placebo groups. Duration of intervention till the end of gestation, the dosage of aspirin given, risk ratios or odds ratio with the confidence intervals, and preeclampsia were the main variables recorded. Data was analysed using RevMan 5.4. Result: Of the 144 articles found, 4(%) were included, having 2238 participants. Pooled estimates revealed that aspirin, compared to placebo, did not significantly reduce the manifestation of preeclampsia (p=0.06). Besides, heterogeneity between the different trials was moderate at 59%. Conclusion: Aspirin was not found to substantially diminish the risk of incidence of preeclampsia, but it did show some beneficial effects. Key Words: Preeclampsia, Low-dose aspirin, Hypertensive pregnant women. more...

A new, simple and stability-indicating gas chromatography-flame ionization detection (GC-FID) method was developed and validated for the quantitative determination of busulfan and its organic impurities (OI) in drug substance without derivatization. The chromatographic attributes were achieved on a fused silica capillary column (0.53 mm × 30 m, 1.0 μm, USP Phase G42), using hydrogen as a carrier gas with a split ratio of 1:1. Forced degradation studies were conducted to establish the stability-indicating capability and method specificity that showed the stressed busulfan peak was free from any co-elution. Robustness study demonstrated the chromatograms remained mostly unaffected under deliberate, but small variations of chromatographic parameters, establishing the reliability of the method during routine usage. The method was shown to be reliable, sensitive, specific, linear, accurate, precise and rugged in the 1,4-butanediol concentration range of 1–20 μg/mL. The method, intended for compendial uses, is suitable for quantitative analysis of busulfan and its organic impurities in drug substances. more...

The burden of occupational health hazards in dentists, final year bachelor of dental surgery (BDS) students and dental assistants are tremendous. Developing countries have controversial situation about the prevalence because of inadequate facilities in rural and urban areas of each nation. Objective: To determine the prevalence of occupational health hazards in dentists, final year BDS students and dental assistants of Lahore. Methods: A total of 300 subjects comprising of 150 dentists, 50 final year BDS students and 100 dental assistants were selected through simple random sampling technique. The cross sectional study was carried out in both private and public based teaching hospitals of Lahore to assess the differences of prevalence of occupational health hazards between them with a pre-tested questionnaire. Results: Among all the occupational health hazards under study a maximum problem of stress was manifested and reported in 87% of all the subjects of private university hospital and 66% in public university dental hospital. Minimum health hazard in the term of prevalence of hearing impairment among public university dental hospitals was 25% in public and 36% in private university dental hospital. Conclusions: The burden of occupational health hazards and its prevalence was higher as an average in private university dental hospitals as compared to public university dental hospitals. more...

The surgical safety checklist consists of three components: sign-in, performed before the induction of anesthesia; time-out, performed before skin incision; and sign-out, performed immediately after skin closure or before the patient leaves the operating theatre. This study aims to assess compliance with the World Health Organization (WHO) Surgical Safety Checklist (SSC) and explore the barriers facing in properly implementing the surgical safety checklist in operation theatres of a tertiary care hospital.The observational clinical audit was conducted in Surgical Unit I, Benazir Bhutto Hospital, Rawalpindi, Pakistan. Compliance with the surgical safety checklist was observed before and after the educational intervention. After completion of the clinical audit operating theatre staff was asked about the barriers to compliance with the surgical safety checklist using an interview sheet. Mean, and standard deviation was calculated for quantitative variables, whereas frequencies and percentages were calculated for categorical variables using SPSS version 25.0.Compliance with all the steps of the surgical safety checklist was improved after an educational intervention, with the highest improvement in compliance (66.7%) observed with the Sign-out step "Count of sponges and needlesinstruments complete?" Moreover, filling of the patient board and documentation of procedure in the patient file were also improved. Lack of awareness and training to follow the surgical safety checklist was the commonest barrier to compliance with the surgical safety checklist.Implementing the surgical safety checklist will not only upgrade the patient safety measures but also integrate teamwork skills and improve the local departmental culture. more...

The objective of this systematic review is to give a comprehensive interpretation of menstrual cycle changes after the COVID-19 vaccination. Additionally, it is imperative to assess reports of menstrual changes following vaccination to dispel concerns that COVID-19 vaccines hinder the likelihood of pregnancy in the long run. A literature review was conducted using digital databases to systematically identify the studies reporting any menstrual abnormalities after the COVID-19 vaccine. Detailed patient-level study characteristics including the type of study, sample size, administered vaccines, and menstrual abnormalities were abstracted. A total of 78 138 vaccinated females were included in this review from 14 studies. Of these, 39 759 (52.05%) had some form of a menstrual problem after vaccination. Due to the lack of published research articles, preprints were also included in this review. Menorrhagia, metrorrhagia, and polymenorrhea were the most commonly observed problems and the overall study-level rate of menstrual abnormality ranged from 0.83% to 90.9%. Age, history of pregnancy, systemic side-effects of COVID-19, smoking, and second dose of COVID-19 vaccine were predictors of menstrual problems after vaccination.Alteraciones menstruales tras la vacunación contra la COVID-19: revisión sistemática Resumen El objetivo de esta revisión sistemática es aportar una interpretación amplia sobre los cambios de los ciclos menstruales tras la vacunación contra la COVID-19. Además, es imperativo evaluar los informes sobre los cambios menstruales tras la vacunación, para disipar preocupaciones en cuanto a que las vacunas contra la COVID-19 dificultan la probabilidad de embarazo a largo plazo. Se realizó una revisión de la literatura utilizando bases de datos digitales para identificar sistemáticamente los estudios que reportan cualquier alteración menstrual tras la vacuna contra la COVID-19. Se resumieron las características detalladas del estudio al nivel del paciente, incluyendo tipo de estudio, tamaño de la muestra, vacunas administradas, y alteraciones menstruales. Se incluyó en la revisión a un total de 78 138 mujeres vacunadas, procedentes de 14 estudios. De ellas, 39 759 (52,05%) tuvieron algún tipo de problema menstrual tras la vacunación. Debido a la falta de artículos de investigación publicados, también se incluyeron preimpresos en esta revisión. Menorragia, metrorragia, y polimenorrea fueron los problemas más comúnmente observados, oscilando la tasa global de alteraciones menstruales a nivel de estudios entre el 0,83 y el 90,9%. La edad, los antecedentes de embarazos, los efectos secundarios sistémicos de la COVID-19, el tabaquismo y la segunda dosis de la vacuna contra la COVID-19 fueron factores predictivos de problemas menstruales tras la vacunación. more...

Background: Blood group of an individual is commonly determined by ABO & Rh status. The objectives of the study were to determine the frequency of ABO, Rh and ABO-Rh blood groups in students of Gomal Medical College, D.I.Khan, Pakistan. Materials & Methods: This cross-sectional study was conducted in the Department of Community Medicine, Gomal Medical College, D.I.Khan, Pakistan from April 1 to May 23, 2019. The population being accessible was taken as sample. Sample size was 452. Our research variables (attributes) were ABO (A, B, AB, O), Rh (positive and negative) and ABO-Rh (A+, B+, AB+ O+, A-, B-, AB-, O-) respectively. All variables being nominal were described by count and percentage. The estimated parameters were given as confidence interval for proportion at 95% confidence level. The observed frequency of ABO, Rh and ABO-Rh blood groups was tested against their expected frequency using chi-square goodness of fit test. Results: Out of 452 students, the frequency of ABO blood group was; A 127 (28.12%), B 165 (36.53%), AB 57 (12.62%) & O 103 (22.73%); Rh blood group was; Rh+ 408 (90.33%) & Rh- 44 (9.67%) and ABO-Rh was; A+ 116 (25.60%), B+ 148 (32.05%), AB+ 50 (11.30%), O+ 91 (20.10%), A- 11 (2.40%), B- 17 (03.70%), AB- 7 (1.50%) & O- 12 (2.60%). The observed frequency of ABO & ABO-Rh blood groups was significantly different whereas of Rh blood group was similar to expected prevalence. Conclusion: In our population, most common blood group was B+ and the least common was AB-. The observed frequency of ABO & ABO-Rh blood groups was different while of Rh was same as expected. Awareness of blood groups in populations will help in the effective management of blood banks record in routine as well as during blood related life emergency situations. more...

Amalgam has been the gold standard for restorations in posterior teeth. Mercury, a major component of dental amalgam, is considered an environmental pollutant. The Minamata Convention on mercury recomends a reduction in the use of mercury-containing products. Since Pakistan is a signatory to the Convention, the same amalgam phase-out limitations are implemented in Pakistan.To identify and assess the use of amalgam and its waste management by dentists in Pakistan post-Minamata Convention guidelines.A cross-sectional study was conducted in Lahore among 520 general dental practitioners in 2019.The sample size for the study was calculated as 500; the questionnaire was distributed among 550 dentists. Dental amalgam was used by only 41.6% of the dentists in their practice; 55.0% perceived it to be a health risk. Most of the dentists (76.3%) were unaware of the proper disposal protocols for dental amalgam and 76.5% were unaware of any guidelines regarding amalgam use and disposal.Although there is a gap in knowledge among the dentists regarding amalgam disposal, dentists in Pakistan are reducing their use of dental amalgam in accordance with the guidelines of the Minamata Convention.التخلص التدريجي من الأمالجم، أحد الشواغل المتعلقة بالسلامة البيئية: دراسة مقطعية على مستوى الممارسين العامِّين لطب الأسنان في باكستان.سلمان خان، نعيمة خالد، عبيد بجوة، طه قمر، علي كاظمي، أمينة طارق.كان الأمالجم هو العلاج المعياري في عمليات الترميم في الأسنان الخلفية. كما يعد الزئبق، وهو عنصر رئيسي في أمالجم الأسنان، ملوثًا بيئيًا. وتنص اتفاقية ميناماتا بشأن الزئبق على الحدّ من استخدام المنتجات المحتوية على الزئبق. وبما أن باكستان من الدول الموقعة على هذه الاتفاقية، فإن القيود نفسها المفروضة على التخلص التدريجي من الأمالجم تُنفَّذ في باكستان.هدفت هذه الدراسة إلى تحديد استخدام الأمالجم وتقييمه وإدارة نفاياته بواسطة أطباء الأسنان في باكستان بعد وضع المبادئ التوجيهية لاتفاقية ميناماتا.أُجريت دراسة مقطعية في مدينة لاهور على 520 ممارسًا عامًّا لطب الأسنان في عام 2019.تم حساب حجم العينة الخاصة بالدراسة على أنه 500، كما تم توزيع الاستبيان على 550 طبيبًا للأسنان. وكان 41.6٪ فقط من أطباء الأسنان يستخدمون أمالجم الأسنان في ممارساتهم، بينما رأى 55.0٪ أنه يُشكِّل خطرًا على الصحة. ولم يكن معظم أطباء الأسنان (76.3٪) على علم بالبروتوكولات المناسبة للتخلص من أمالجم الأسنان، كما لم يكن 76.5٪ من أطباء الأسنان على علم بأي مبادئ توجيهية تتعلق باستخدام الأمالجم والتخلص منه.على الرغم من وجود فجوة معرفية لدى أطباء الأسنان عندما يتعلق الأمر بالتخلص من الأمالجم، فإن أطباء الأسنان في باكستان يقللون من استخدامهم لأمالجم الأسنان وفقًا للمبادئ التوجيهية لاتفاقية ميناماتا.Élimination progressive des amalgames dentaires, une préoccupation de sécurité environnementale : étude transversale parmi les dentistes généralistes au Pakistan.L'amalgame dentaire a été le matériau de référence pour les restaurations des dents postérieures. Le mercure, composant majeur des amalgames dentaires, est considéré comme un polluant environnemental. La Convention de Minamata sur le mercure impose de réduire l'utilisation des produits qui en contiennent. Le Pakistan étant signataire de ladite Convention, les mêmes limitations relatives à l'élimination progressive des amalgames dentaires lui sont appliquées.Identifier et évaluer l'utilisation de l'amalgame dentaire et la gestion des déchets qui en résultent par les dentistes au Pakistan suite aux directives de la Convention de Minamata.Une étude transversale a été menée à Lahore auprès de 520 dentistes généralistes en 2019.La taille de l'échantillon pour l'étude a été fixée à 500 ; le questionnaire a été distribué à 550 dentistes. Les amalgames dentaires n'étaient utilisés que par 41,6 % des dentistes dans leur pratique ; 55,0 % estiment qu'ils représentent un risque pour la santé. La plupart des dentistes (76,3 %) ne connaissaient pas les protocoles d'élimination des amalgames dentaires et 76,5 % ne connaissaient aucune directive concernant l'utilisation et l'élimination des amalgames.Bien que les connaissances des dentistes en matière d'élimination des amalgames soient insuffisantes, les dentistes pakistanais réduisent leur utilisation des amalgames dentaires conformément aux directives de la Convention de Minamata. more...

Introduction: Stress is one of the most important issues among medical students, often defined as the “wear and tear” the body experiences and multiple factors contribute to its prevalence. It can exert a negative impact on the emotional/psychological well-being of an individual, if not treated at the proper time. Proper management and timely interventions will lessen the negative effects of stress, thereby enhancing their academic performance and skill development as medical graduates. Aim: To measure and compare the perceived stress level among medical students studying in three main medical colleges located at Srinagar, Anantnag, and Baramulla (in the government sector), Jammu and Kashmir, India. Materials and Methods: This cross-sectional study was multiinstitutional, conducted in the first and second year medical students of Government Medical College (GMC)-Srinagar/GMC-Anantnag and GMC- Baramulla, Jammu and Kashmir, India in the age group of 18-25 years who voluntarily consented to participate. A total of 264 students were taken for the study. Data as per structured/standard questionnaire was collected on Google form in a password-protected electronic format. The already validated and reliable Perceived Stress Scale (PSS)- Cohen et al., 1983, was used to analyse the stress levels. Categorical data were analysed using the Pearson Chi-square test. Results: Overall maximum students, 145 (54.9%) had moderate stress, followed by 83 (31.5%) who had high or perceived stress and 36 (13.6%) had low stress levels. College analysis indicated that perceived high stress was highest in GMC-Srinagar students with 38.1%, followed by 31.6% from GMC-Baramulla and 22.22% from GMC-Anantnag. Conclusion: Present study indicate an overall high prevalence of moderate stress followed by perceived high stress among the medical students of three medical colleges located in Kashmir, India. Interestingly, the location of the medical colleges had little impact on the stress level among such undergraduate students. more...

BACKGROUND Trichogramma pretiosum Riley is an important egg parasitoid and biological control agent of caterpillar pests. We studied the acute toxicity of 20 pesticides (14 insecticides/miticides, three fungicides and three herbicides) exposed to recommended field rates. Egg, larval, and pupal stages of the parasitoid in their hosts were dipped in formulated solutions of the pesticides and evaluated 10 days later for percentage of host eggs with holes, number of parasitoids emerged per egg with holes, and stage-specific mortality of immature as well as adult wasps within the host eggs. RESULTS Seven insecticides (buprofezin, chlorantraniliprole, spirotetramat, flonicamid, flubendiamide) and miticides (spiromesifen, cyflumetofen), one herbicide (nicosulfuron), and three fungicides (myclobutanil, pyraclostrobin, trifloxystrobin + tebuconazole) caused no significant mortality to immature stages or pre-emergent adult parasitoids relative to controls. By contrast, seven insecticides/miticides (abamectin, acetamiprid, dinotefuran, fipronil, novaluron, spinetoram, tolfenpyrad) adversely affected immature and pre-emergent adult T. pretiosum, with tolfenpyrad being particularly lethal. Two herbicides had moderate (glufosinate ammonium) to severe (s-metolachlor) acute lethal effects on the immature parasitoids. CONCLUSIONS This study corroborates earlier findings with adult T. pretiosum. Over half of the pesticides – and all the fungicides – tested in the current study would appear to be compatible with the use of T. pretiosum in integrated pest management programs, with respect to acute parasitoid mortality. © 2017 Society of Chemical Industry more...

Candida albicans N-acetylglucosaminylphosphatidylinositol de-N-acetylase (CaGpi12) recognises N-acetylglucosaminylphosphatidylinositol (GlcNAc-PI) from Saccharomyces cerevisiae and is able to complement ScGPI12 function. Both N- and C-terminal ends of CaGpi12 are important for its function. CaGpi12 was biochemically characterised using rough endoplasmic reticulum microsomes prepared from BWP17 strain of C. albicans. CaGpi12 is optimally active at 30°C and pH 7.5. It is a metal-dependent enzyme that is stimulated by divalent cations but shows no preference for Zn2+ unlike the mammalian homologue. It irreversibly loses activity upon incubation with a metal chelator. Two conserved motifs, HPDDE and HXXH, are both important for its function in the cell. CaGPI12 is essential for growth and viability of C. albicans. Its loss causes reduction of GlcNAc-PI de-N-acetylase activity, cell wall defects and filamentation defects. The filamentation defects could be specifically correlated to an upregulation of the HOG1 pathway. more...

Background: The purpose of this study is to test the hypothesis of the new classification system of distal end radius fractures (Barzullah working classification) proposed by one of the author in a prospective cohort study, among the orthopaedic residents. Methods: The initial post-injury radiographs of 300 patients with distal radius fractures in a tertiary centre were classified by two junior residents (JR1 and JR2) and two senior residents (SR1 and SR2) in the emergency department over a period of two years. The collected data was analysed statistically by using Cohan's kappa for measuring Intraobserver reproducibility and Fleiss kappa for measuring Interobserver agreement. Results: The mean kappa value for Interobserver agreement was 0.53 (moderate agreement) at the end of one year and the mean kappa value at the end of study period was 0.64 (substantial agreement). The mean kappa value for Intraobserver reproducibility of JR1 was 0.45 (moderate agreement), JR2 was 0.39 (fair agreement), SR1 was 0.62 (substantial agreement) and SR2 was 0.67 (substantial agreement). Conclusions: Barzullah working classification of distal radius fractures presented in this study has good characteristics compared to those of already studied classification systems among orthopaedic residents. more...

ContextThyroid carcinoma is the most common malignant tumor of endocrine organs, yet it only accounts for approximately 1% of all cancers in the United States with more than 35 000 new cases diagnosed each year and more than 450 000 people living with this disease. While most tumors can be diagnosed without much difficulty, a few tumor types, especially tumors with follicular pattern, sometimes pose a diagnostic challenge.ObjectiveTo discuss morphologic, immunohistochemical, and molecular features of thyroid tumors. We also explore the clinicopathologic features of papillary microcarcinoma and medullary microcarcinoma and how the latter is related and differentiated from C-cell hyperplasia. Finally with the ever-growing list of organ systems involved in immunoglobulin (Ig) G4–related diseases, we discuss the still not completely explored IgG-4–related thyroid disease.Data SourcesData were obtained from review of the pertinent peer-reviewed literature and institutional experience.ConclusionsHistomorphologic evaluation still remains the gold standard for diagnosis in most cases of thyroid diseases. The application of ancillary studies such as immunohistochemistry and molecular diagnosis, including next-generation sequencing, is becoming more common. more...

The GPI (Glycosylphosphatidylinositol) biosynthetic pathway is a multistep conserved pathway in eukaryotes that culminates in the generation of GPI glycolipid which in turn anchors many proteins (GPI-APs) to the cell surface. In spite of the overall conservation of the pathway, there still exist subtle differences in the GPI pathway of mammals and other eukaryotes which holds a great promise so far as the development of drugs/inhibitors against specific targets in the GPI pathway of pathogens is concerned. Many of the GPI structures and their anchored proteins in pathogenic protozoans and fungi act as pathogenicity factors. Notable examples include GPI-anchored variant surface glycoprotein (VSG) in Trypanosoma brucei, GPI-anchored merozoite surface protein 1 (MSP1) and MSP2 in Plasmodium falciparum, protein-free GPI related molecules like lipophosphoglycans (LPGs) and glycoinositolphospholipids (GIPLs) in Leishmania spp., GPI-anchored Gal/GalNAc lectin and proteophosphoglycans in Entamoeba histolytica or the GPI-anchored mannoproteins in pathogenic fungi like Candida albicans. Research in this active area has already yielded encouraging results in Trypanosoma brucei by the development of parasite-specific inhibitors of GlcNCONH(2)-β-PI, GlcNCONH(2)-(2-O-octyl)-PI and salicylic hydroxamic acid (SHAM) targeting trypanosomal GlcNAc-PI de-N-acetylase as well as the development of antifungal inhibitors like BIQ/E1210/gepinacin/G365/G884 and YW3548/M743/M720 targeting the GPI specific fungal inositol acyltransferase (Gwt1) and the phosphoethanolamine transferase-I (Mcd4), respectively. These confirm the fact that the GPI pathway continues to be the focus of researchers, given its implications for the betterment of human life. more...

BACKGROUND: Growing demand for reduced chemical inputs in agricultural systems requires more effective integration of biological control with pesticides. The egg parasitoid Trichogramma pretiosum Riley is an important natural enemy of lepidopteran pests, used in biological control. In an investigation of the interaction of T. pretiosum and pesticides, we studied the acute toxicity of 19 pesticides (insecticides, miticides, fungicides and herbicides) to adult parasitoids and the behavioral effects of 11 pesticides on foraging parasitoid females, including host antennation, stinging and host feeding. RESULTS: At recommended field doses, fipronil, dinotefuran, spinetoram, tolfenpyrad and abamectin induced nearly 100% adult mortality within 24 h of exposure to treated cotton leaves by comparison with controls. Acetamiprid was also toxic, but significantly less so than the former materials. The other pesticides had no significant toxic effects. Only glufosinate ammonium exhibited increased toxicity among the non-toxic materials when increased two- or fourfold over recommended rates. The foraging behavior of parasitoids was affected only by tolfenpyrad among the materials tested. CONCLUSION: Most novel pesticides, except for several insecticides, exhibited little to no acute toxicity to the parasitoid. Parasitoid foraging behavior was only affected by tolfenpyrad, indicating that parasitoids could successfully forage on eggs treated with most pesticides evaluated. Therefore, many of these pesticides may have good compatibility with Trichogramma. © 2015 Society of Chemical Industry more...

Context.—Axillary nodal status remains one of the most important prognostic indicators in the management of breast cancer. Axillary node metastases are seen in fewer than half of breast cancer cases, and axillary lymph node dissection is associated with significant morbidity. Sentinel lymph node biopsy (SLNB) has become the gold standard for axillary staging of breast cancer. Objective.—To present a detailed review of the existing studies on SLNB in relation to the various techniques, the pathologic evaluation of the sentinel node, and special situations that can involve SLNB. We discuss recent trials that have already had an influence on surgical and pathologic management of breast cancer. In this article, we also discuss our practice and experience at UMass Memorial Medical Center, Worcester, Massachusetts, from a pathologic and surgical perspective. Data Sources.—Published articles from peer-reviewed journals in PubMed (US National Library of Medicine). Conclusions.—Sentinel node biopsy has become standard of care in the surgical management of breast cancer, and emerging data show that the survival benefits of axillary lymph node dissection may not be greater than sentinel node biopsy alone in patients with up to 2 positive sentinel nodes. Therefore, there have been recent changes to the role of intraoperative sentinel node evaluation, and an impact on overall breast cancer management. more...

Downregulation of apoptosis and high expression of bcl-2 play an important role in the development of follicular lymphoma. However, little is known about apoptosis in thyroid disease, particularly with respect to the development of papillary carcinoma from Hashimoto’s thyroiditis. To study the early stages of cell death in various types of thyroid disease, surgical specimens from 31 patients including Hashimoto’s thyroiditis (HT,n=7), papillary carcinoma (PC,n=12), Hashimoto’s thyroiditis with papillary carcinoma (HTPC,n=5), and Graves’ disease (GD,n=7) were examined by anin situ nucleotidyl transferase assay (ISNTA), which detects DNA fragmentation. Control normal thyroid tissue (NT,n=7) was obtained from surgically resected papillary thyroid carcinomas sampled away from the primary tumor. An immunohistochemical (IHC) method was used to detect bcl-2 expression. Positive ISNTA nuclei in thyroid follicular cells or tumor cells per section were counted in all parenchymal areas, excluding areas of lymphocyte aggregates. The intensity of bcl-2 staining was graded on a scale of 1+ to 3+. The number of ISNTA-positive thyroid follicular cells was a significantly higher in HT compared to GD. In addition, there was significantly lower number of ISNTA positive non-neoplastic thyroid follicular cells in HTPC compared to HT alone. Strong expression of bcl-2 was found in all cases of GD and NT, but much less bcl-2 staining was seen in HT. There was moderate expression of bcl-2 in HTPC and PC. These findings suggest that (1) DNA fragmentation of the thyroid follicular cells plays an important role in the thyroid injury in HT but not in GD, (2) expression of bcl-2 may overcome the apoptosis in GD but not in HT, and (3) downregulation of DNA fragmentation of the follicular cells in Hashimoto’s thyroiditis associated with papillary carcinoma may suggest an important mechanism for tumor pathogenesis. more...

Sixty subjects were selected and were divided into two groups. Group A included 30 patients of end stage renal disease on regular dialysis and group B included 30 normal healthy subjects as control. Absolute values and Hb were done by hematology auto analyzer and serum and red cell folate were done by commercially available kits. Results were analyzed by using Student`s `t` test and level of significance was done. A significant decreased in serum and red cell folate in end stage renal disease patients with regular dialysis as compared to control. more...

A 52-year-old man was referred to our medical centre for the evaluation of persistent dyspepsia for several months. He denied nausea, vomiting, regurgitation, weight loss, haematemesis or melena. He had no history of pre-existing gastrointestinal disorders or non-steroidal anti-inflammatory drug use more...

Micro-RNAs (miRNAs) belong to a class of small non-coding messenger RNA species that have emerged as potent regulators of a variety of biological processes including oncogenesis. They serve as master regulators with a single miRNA capable of regulating as many as 100 different target genes. Thyroid carcinomas encompass a wide spectrum ranging from well-differentiated thyroid carcinomas to poorly differentiated and anaplastic carcinoma. Currently, a considerable degree of interobserver variability exists in the morphological diagnosis of certain types of thyroid carcinomas especially the follicular pattern neoplasm. The prediction of progression of these differentiated carcinoma to more aggressive forms like poorly differentiated and anaplastic types is of considerable interest to physicians and pathologists for determining prognosis and making therapeutic decisions. Several investigators have proposed a more cohesive approach to thyroid cancer diagnosis incorporating molecular and proteomics based tools in addition to the conventional morphological diagnosis. In this context, miRNAs serve as an important diagnostic tool, and several studies have demonstrated their utility as class identifiers especially in the context of follicular thyroid carcinoma, papillary thyroid carcinoma and anaplastic thyroid carcinoma. Larger studies and/or meta-analyses could further delineate their role in predicting cancer progression and prognosis. In the same vein, miRNAs and their target genes could be targeted for novel therapeutics in the future. more...

Objectives: To explore the implications of cervical conization specimens lacking the targeted high-grade squamous intraepithelial lesions (negative cone). Methods: We studied 540 conization procedures: 400 positive cones and 140 negative cones. Clinicopathologic features and 2-year follow-up results were reported. Results: Negative cones comprised 22% of procedures triggered by CIN2 or higher biopsies. Procedures triggered by cytology produced much higher percentages of negative cones (37% high-grade squamous intraepithelial lesion [HSIL], 46% atypical squamous cells—cannot exclude high-grade squamous intraepithelial lesion [ASC-H], and 76% low-grade squamous intraepithelial lesion—cannot exclude high-grade squamous intraepithelial lesion [LSIL-H]). Upon reviewing negative excision-triggering biopsy and cytology, we downgraded 24 (24%) CIN2 biopsies, three (14%) HSIL, five (83%) ASC-H, and 12 (92%) LSIL-H. One-third of our negative cones can be attributed to overdiagnosis either on biopsy or cytology. Patients with negative cones were older and had smaller excisions, negative colposcopic findings, and negative/equivocal high-risk human papillomavirus (HR-HPV). Within 2 years, 35 (25%) women with negative cones experienced ASCUS or LSIL. Only one (0.7%) recurred as CIN3, a significantly lower percentage than women with positive cones (13%). Conclusions: We advocate careful review of all excision-triggering biopsy and cytology, especially in cases of LSIL-H. Patients with negative cones should be surveyed with cytology and HR-HPV testing. more...

The morphologic distinction of benign and malignant thyroid follicular lesions can sometimes be challenging, therefore an immunohistochemical marker to aid in this distinction would be useful. beta-Catenin is one such potential marker. It is part of a membrane-bound cell growth-signaling complex that plays a role in cell adhesion, as well as in promotion of growth through activation of the Wnt signaling pathway. Oncogenic signaling occurs when beta-catenin is released, accumulates in the cytoplasm, translocates into the nucleus, and promotes transcription of genes including bcl-1 (cyclin D1) and c-myc that induce cell proliferation. Paraffin blocks from 133 thyroidectomy specimens were stained with monoclonal antibodies reactive with beta-catenin and cyclin D1. These included 53 cases of papillary thyroid carcinoma (PTC), 46 cases of follicular variant of papillary carcinoma (FVPC), 10 cases of follicular carcinoma (FC), and 24 cases of follicular adenoma (FA). Tissue from six normal thyroid specimens served as a control. The malignant lesions (PTC, FC, and FVPC) expressed strong cytoplasmic/nuclear staining and minimal residual membranous staining in 87%, 80%, and 71% of cases, respectively. In contrast, all normal thyroid tissue and 79% of FAs showed strong membranous reactivity with very minimal cytoplasmic staining. Interestingly, in 83% of PTC cases and 20% FVPCs, the intranuclear inclusions were distinctly beta-catenin positive. Cyclin D1 over expression correlated with cytoplasmic relocalization of beta-catenin in almost all cases, and no evidence of cyclin D1 gene amplification was observed. beta-Catenin can be of a diagnostic utility for thyroid lesions, because it highlights intranuclear inclusions in PTC, and shifts from a membranous localization to a cytoplasmic localization in malignant lesions. We speculate that the localization of beta-catenin in intranuclear inclusions may reflect a cytoskeletal remodeling activity of beta-catenin that is functionally significant for the PTC pathway. more...

Aim To compare the diagnostic quality of tissue cores obtained using cranial and caudal angulation of the renal biopsy needle. Comparison was made in terms of the number of glomeruli and proportion of renal cortex with medulla on pathological analysis. Methods A total of 40 desktop, renal biopsies were performed on 10 ex vivo porcine kidneys using two different targeting angles. Biopsies were obtained from the ‘lower pole’ of each kidney using both cephalad and caudad angulations of the biopsy needle. Ten 18-gauge semi-automated cutting needles were used during twenty biopsies obtained per each angle; two biopsies were made using each needle. The resulting samples were collected in 40 separate and labelled formalin containers according to the used targeting angle. Two pathologists blinded to the corresponding biopsy angles reviewed the samples in consensus. Results Samples with a cephalad targeting angle had a mean length of 14.5 mm with mean number of 9.6 glomeruli and average 82% cortex and 18% medulla. Samples obtained using a caudad needle angulation had a mean length of 14.1 mm with mean number of 11.6 glomeruli and on the average 99% cortex. The P-values comparing the two samples were as follows: 0.63 comparing the mean length of cores, 0.08 for number of glomeruli and 0.002 comparing the proportion of cortex. Conclusion The proportion of cortical tissue in the core biopsy specimen using the caudad angle approach was statistically significantly higher, compared with the cephalad needle trajectory. more...

Previous studies have established that calcitonin (CT) and the calcitonin generelated peptide (CGRP) are synthesized and stored in subsets of hyperplastic parathyroid cells that also contain chromogranin B (Schmid, KW, et al. Lab Invest 73:90, 1995). The purpose of the current study was to determine whether other generic but variably expressed neuroendocrine markers, i.e., synaptophysin (SYN) and CD57 (Leu7), are also present in normal, hyperplastic, and neoplastic parathyroid tissue and to assess their relationships to the presence of CT. Immunoperoxidase stains for chromogranin A (CgA), chromogranin B (CgB), SYN CD57, and CT were performed on 54 hyperplastic, 17 neoplastic (adenoma), and 16 normal parathyroid glands. Sequential sections were stained with antibodies to CgA, CgB, SYN, CD57, and CT using standard avidin-biotin-peroxidase techniques. Results: CgA was diffusely expressed in all normal, hyperplastic, and neoplastic glands. In hyperplasia, CgB was variably expressed in 6 cases (11%), SYN in 6 (11%), CD57 in 15 (28%), and CT in 8 (15%). In adenomas, CgB was variably expressed in 3 (17%), SYN in 3 (17%)., CD57 in 4 (23%), and CT in 4 (23%). All normal glands were negative for CgB, SYN, and CT, while CD57 was variably expressed in 17%. Of the 12 glands that were CT positive, 8 were also positive for CgB, 2 for SYN, and 9 for CD57. Four glands that were strongly and diffusely positive for CT were CgB and SYN negative. Conclusions: CgB, SYN, and CD57 are markers for subsets of hyperplastic and neoplastic parathyroid glands. CT is also expressed in a significant proportion of hyperplastic and neoplastic parathyroid glands, and may be independent of the presence of CgB, SYN, or DD57. The significance of these findings in relationship to the abnormal calcium metabolism in patients with parathyroid hyperplasia remains to be determined. more...

Cyclins are prime cell-cycle regulators central to the control of cell proliferation in eukaryotic cells. The formation of cyclin/cyclin-dependent kinases (CDK) complexes activates the kinases and initiates a cascade of events, which directs cells through the cell cycle. CDK inhibitors (CDKIs) such as p27(kip1) inhibit cyclln-CDK complexes and function as negative regulators of the cell cycle. Previous studies have shown that p27(kip1) is decreased In malignant relative to benign thyroid tumors, but its role and Interaction with other cell cycle regulatory proteins have not been well established In oncocytic lesions of the thyroid. We studied the expression of p27(kip1), cyclins D1 and E, and Ki67 In 20 cases of oncocytic adenoma (AD). 6 cases of oncocytic carcinoma (CA). 8 cases of Hashimoto's thyroiditis (HT). and 9 cases of nodular goiter with oncocytic change (NG) by Immunohistochemlstry. In the latter two lesions only oncocytic cells were evaluated. The positive staining was stratified Into four groups. Statistical analysis was done using the Kruslcal-Wallis one-way analysis of variance test, and, when significant the Dunn multiple-comparisons procedure was used to determine pairwise differences. AllI 20 AD were p27(kip1) posItive, 10 were 4+, 2 were 3+, and the remaining 8 were 1+. In contrast all 6 CA showed 4+ p27(kip1) staining, of the 8 HT 2 were 4+, two 3+, three1+, and I was negative.All 9 NG were p27 positive, 7 showed 4+, one 3+, and one 1+ staining. On pairwise comparison differences in p27(kip1) staining between AD and CA and between HT and CA were statistically significant (p=0.0243 and p=0.0142, respectively). In all but one case Ki67 expression was either very low ( more...

Previous studies have established that thyroid follicular neoplasms of higher malignant potential show a high p53 and low bc1-2 expression. This however has not been well studied in Oncocytic (Hurthle cell) neoplasms, the management of which remains controversial. We therefore studied the expression of p53 and bc1-2 in 18 Hurthle cell adenomas (HCA) and 8 Hurthle cell carcinomas (HCC) and compared them with their benign and malignant counterparts, respectively, including 16 follicular adenomas (FA) and 68 papillary carcinomas (PC). All 16 FA were bc1-2 positive, 4 were 2+, and 12 were 3+. On the other hand, 14/18 (78%) HCA showed bc1-2 expression, 5 were 1+, 6 were 2+, and only 3 were 3_. Similarly, HCC showed a weaker bc1-2 staining pattern compared to PC. Only 1 FA showed grade 1, p53 staining, the remaining 15 were negative, and 15/18 HCA showed p53 expression of varying grades. This difference in p53 staining was statistically significant (p=0.005). A significant p53 overexpression was also seen in HCC compared to PC (p=0.005). In conclusion, there appears to be an inverse relationship between p53 and bc1-2 expression in thyroid follicular neoplasms. A higher expression of p53 and lower levels bc1-2 in Hurthle cell neoplasms may have biological and clinical implications. This may support a more aggressive surgical treatment for HCA compared to FA. more...

Context.—Despite advances in breast cancer management, women continue to relapse and die of breast cancer. Traditionally, evaluation for hormone receptors (estrogen and progesterone), as well as HER2 overexpression, have guided therapy-related decision-making because they are both prognostic and predictive indicators. However, there are limitations with those studies, which can lead to improper treatment. Gene signatures have recently been shown to be of value in identifying molecular portraits of breast carcinoma and are beginning to play role in management and treatment algorithms.Objective.—To provide a summary of the prognostic and predictive indicators of breast cancer, such as hormone receptors, HER2, and molecular gene signatures that currently help guide clinical decision making.Data Sources.—Published articles from peer-reviewed journals in PubMed (US National Library of Medicine).Conclusions.—Emerging evidence shows promise that, in addition to hormone receptors and HER2 studies, evaluating tumors with gene expression profiling can provide additional prognostic and predictive information, further aiding clinical management and leading to a more personalized approach to treating breast cancer. more...

Context.—Basal-like breast carcinoma (BLBC) is a distinct molecular subtype of breast carcinoma identified through gene expression profiling studies. Objective.—To provide the clinical background, the histologic profile, and the immunohistochemical profile of these tumors and discuss the current knowledge of their molecular signature and their implications on targeted molecular therapy. Data Sources.—Data were obtained from review of the pertinent peer-reviewed literature. Conclusions.—Basal-like breast carcinomas are aggressive tumors with poor prognosis. Lack of targeted therapy makes their treatment a challenging task. Traditional chemotherapy is still associated with a high risk of relapse and death in a high percentage of patients. Platinum-based chemotherapy has been considered as a candidate for the treatment of BLBCs owing to their BRCA1 phenotype. Approximately 22% of patients treated with single-agent cisplatin show pathologic complete response, which is a comparable rate to that seen with nonplatinum agents. Antiangiogenic agents have been promising, but their currently demonstrated limited response is considered disappointing. Additionally, epidermal growth factor receptor was not shown to be a helpful target for BLBC. A recent study has shown that BLBC appears to be especially sensitive to MEK inhibitors, making it a promising therapeutic possibility. The list of new targets is still evolving and the “magic” therapeutic target is yet to be discovered. more...

Context.—The 2 main prototypes of fibroepithelial tumors of the breast include fibroadenoma and phyllodes tumor (PT). Although both tumors share some overlapping histologic features, there are significant differences in their clinical behavior and management. Phyllodes tumors have been further divided into clinically relevant subtypes, and there is more than one classification scheme for PT currently in use, suggesting a lack of consistency within different practices. Accurate differentiation between fibroadenoma and PT, as well as the grading of PT, may sometimes be challenging on preoperative core needle biopsy. Some immunohistochemical markers have been suggested to aid in the pathologic classification of these lesions.Objective.—To discuss the salient histopathologic features of fibroepithelial tumors and review the molecular pathways proposed for the initiation, progression, and metastasis of PTs. Also, to provide an update on immunohistochemical markers that may be useful in their differential diagnosis and outline the practice and experience at our institution from a pathologic perspective.Data Sources.—Sources included published articles from peer-reviewed journals in PubMed (US National Library of Medicine).Conclusions.—Fibroepithelial tumor of the breast is a heterogenous group of lesions ranging from fibroadenoma at the benign end of the spectrum to malignant PT. There are overlapping histologic features among various subtypes, and transformation and progression to a more malignant phenotype may also occur. Given the significant clinical differences within various subtypes, accurate pathologic classification is important for appropriate management. Although some immunohistochemical markers may be useful in this differential diagnosis, histomorphology still remains the gold standard. more...

Context.—Immunohistochemistry plays a vital role in the evaluation of breast pathology specimens.Objective.—To discuss the role of myoepithelial cell markers in the evaluation of various breast lesions. Other markers, such as E-cadherin and those used to differentiate mammary carcinoma from metastatic tumors to the breast, and markers used in the differential diagnosis of Paget disease, are also discussed.Data Sources.—Data were obtained from review of the pertinent peer-reviewed literature.Conclusions.—Myoepithelial cell markers vary in their sensitivity and specificity, and one should be aware of the potential pitfalls in interpretation. Using panels of 2 or more myoepithelial cell markers is always recommended, either singly or in cocktail forms. Although negative E-cadherin staining supports the diagnosis of lobular origin, positive staining does not rule it out. Immunohistochemistry can be helpful in differentiating Paget disease from its mimics. Although metastatic tumors to the breast are rare, a triple-negative immunophenotype and absence of an in situ component should be a “red flag” for such possibility, especially in patients with clinical history of an extramammary malignancy. more...

The thyroid gland is an uncommon site for metastatic disease but cases have been well-documented in the literature, particularly in autopsy series. A retrospective review of surgical pathology and autopsy pathology database for patients with metastatic carcinoma to the thyroid was performed at the University of Massachusetts Medical Center between January 1993 to January 2013. We identified a total of 10 patients with metastatic carcinoma to the thyroid; 6 were in surgical pathology specimens out of a total of 1,295 thyroid carcinoma (0.46 %) and 4 were diagnosed at autopsy out of a total of 2,117 (0.19 %) autopsy cases during this period. Cases with direct extension of the tumor into the thyroid from local primary sites such as larynx, esophagus or soft tissues of the neck were excluded. The primary tumors in these cases comprised of four lung carcinomas, three colorectal carcinomas, a renal cell carcinoma, a pleural malignant mesothelioma, and an unknown primary. Therefore, it is important to keep intrathyroidal metastases in the differential diagnosis when evaluating a thyroid nodule, particularly in patients with a previous history of malignancy. Furthermore, a literature review reveals over 1,400 cases have been previously reported, with the most common malignancies from the kidney (34 %), lung (15 %), gastrointestinal tract (14 %), and breast (14 %). more...

Solitary fibrous tumor (SFT) is an uncommon spindle cell neoplasm of increasing incidence that was originally described to be of pleural origin; however, more recently, SFT has been reported in extrapleural sites, including the orbit, liver, salivary glands, tongue, nose, paranasal sinuses, larynx, retroperitoneum, meninges, and thyroid. The increase in the number of SFTs does not necessarily mean increased incidence of this tumor but rather an increased understanding of this tumor, especially recognition of this tumor in extrapleural locations, which has been aided by immunohistochemical analysis. We report a case of SFT in the auditory canal, which to our knowledge has not been previously reported, as evident by morphologic findings and immunophenotype. more...

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign, proliferative mesenchymal lesion with possible hormonal etiology. It typically affects women in the reproductive age group. Pseudoangiomatous stromal hyperplasia is frequently an incidental histologic finding in breast biopsies performed for other benign or malignant lesions. Rarely, it can present as a firm, painless breast mass, which has been referred to as nodular or tumorous PASH. Grossly, tumorous PASH is a well-circumscribed, firm, rubbery mass with solid, homogenous, gray-white cut surface. On histologic examination, it is characterized by the presence of open slitlike spaces in dense collagenous stroma. The spaces are lined by a discontinuous layer of flat, spindle-shaped myofibroblasts with bland nuclei. The spindle cells express progesterone receptors and are positive for vimentin, actin, and CD34. The most important differential diagnosis on histopathology is angiosarcoma. Pseudoangiomatous stromal hyperplasia discovered incidentally does not require any additional specific treatment. Tumorous PASH is treated by local surgical excision with clear margins and the prognosis is excellent, with minimal risk of recurrence after adequate surgical excision. more...

The purpose of this study was to compare the size of biopsy cores obtained using a biopsy needle before and after manual curving of its inner stylet.A total of 40 open renal biopsies were randomly performed on two ex vivo beef kidneys using four different semiautomated cutting needles. Two 18-gauge and two 20-gauge needles were used; one needle of each gauge had its inner stylet manually curved. Ten biopsy specimens were obtained using each needle and then were put into four different formalin containers, one for each needle, and sent to the pathology laboratory. Two pathologists who were blinded to the corresponding needles reviewed the samples in consensus and measured the dimensions of obtained cores.The mean diameter of the cores was larger when curved needles were used: for the 18-gauge needles, the core diameters were 0.866 mm for the curved needle and 0.688 mm for the straight needle, and for the 20-gauge needles, the core diameters were 0.522 mm for the curved needle and 0.480 mm for the straight needle. The length of the samples was also longer when they were obtained using the curved needle. When we considered the cores as cylinders, the calculated volumes of samples obtained using the curved needles were significantly larger.Manually curving of the inner stylet of the cutting biopsy needle results in larger cores, in terms of diameter and length, and results in significantly larger overall volume. more...

Trichobezoar is a rare intriguing disorder in which swallowed hairs accumulates in the stomach. Being indigestible and slippery, it could not be propulsed and becomes entrapped within the stomach. Large amounts can thus accumulate over the years forming a hair ball. Rapunzel syndrome is a variant where hair accumulation reaches the small gut and beyond in some cases. Although the syndrome has been known for many years, only 24 cases have been reported in the literature and the discovery of a new case is always surprising. In this report, we present two cases discovered within a period of three months. One of them was pregnant and had small bowel intussusception and perforation, a very rare combination. We hereby add two more cases to the literature. To our knowledge, this is the first report on two cases of Rapunzel syndrome, the diagnosis of which demands a high index of suspicion. more...

Correspondence ackn owledgements British Lung Foundation UK and Lung Pathology Departmental Funds for funding. M Tsoumakidou J Zhu Z Wang A Thorley 1 S Kemp 1 T Tetley 1 P K Jeffery Lung Pathology, Department of Gene Therapy, and Lung Cell Biology, Section of Airways Disease, National Heart & Lung Institute, Imperial College London, London, UK 1. Vermaelen K, Pauwels R. Pulmonary dendritic cells. Am. J. Respir. Crit. Care Med. 2005; 172; 530–551. 2. Demedts I, Brusselle G, Vermaelen K et al. Identification and characterization of human pulmonary dendritic cells. Am. J. Respir. Cell Mol. Biol. 2005; 32; 177–184. 3. Tsoumakidou M, Tzanakis N, Papadaki HA et al. Isolation of myeloid and plasmacytoid dendritic cells from human broncho- alveolar lavage fluid. Immunol. Cell Biol. 2006; 84; 267–273. 4. Todate A, Chida K, Suda T et al. Increased numbers of dendritic cells in the bronchiolar tissues of diffuse panbronchiolitis. Am. J. Respir. Crit. Care Med. 2000; 162; 148–153. 5. Witherden IR, Vanden Bon EJ, Goldstraw P et al. Primary human alveolar type II epithelial cell chemokine release: effects of cigarette smoke and neutrophil elastase. Am. J. Respir. Cell Mol. Biol. 2004; fixation. The metal suture is later trimmed off, allowing perpendicular slices to be made across the lung ⁄ pleural tissue, permitting detailed analysis. One issue not covered in any detail in the review is that of occupational dust-related pathology and emphysema. Assessment of emphysema is particularly important at autopsy in this regard, as it is used to substantiate ⁄ refute medicolegal claims by relatives of the deceased. It is vital to try to inflate postmortem lung tissue (in a similar manner) for ideal quantification of disease and, even if whole mount lung tissue sections are not available, small, adequately inflated lung samples can produce significant information that can be tested in the legal setting. In addition, it is worth considering other occupa- tional disease, particularly in relation to metal fumes. Cadmium exposure (for example) can produce signifi- cant emphysematous change many years after expo- sure. 2 Retention of some lung tissue for mass spectroscopy can be particularly useful if one is considering metal or other chemical-related disease. Finally, whilst I would entirely concur with the pathological approach to classification given in the review, I would suggest that any analysis of lung parenchyma must be cross-correlated against respira- tory function tests and other clinical information. Of particular value is computerized tomography ⁄ magnetic resonance imaging in terms of extrapolation of small biopsy ⁄ autopsy sample histology in order to derive full appreciation of overall pulmonary pathology status. 3 S K Suvarna Advances in the pathology of COPD Department of Histopathology, Northern General Hospital, Sheffield, UK DOI: 10.1111/j.1365-2559.2007.02816.x Sir: I read with great interest the very detailed and helpful review on emphysema, 1 and agree this is the gold standard approach to assessment of lung tissue for chronic obstructive pulmonary disease (COPD). Regret- tably, autopsy and tissue retention issues in the UK have led to problems with examining lung parenchyma in this format and in most cases only small samples of tissue can be retained for COPD assessment. For surgical samples, often submitted as thoraco- scopic (video-assisted thorascopic surgery) samples with wire suture material at the margins, I would recommend inflation of these samples upon receipt in the laboratory by injecting formalin (by syringe ⁄ needle) into the lung parenchyma through the pleura, until the sample looks adequately inflated for ideal 1. Wright JL, Churg A. Advances in the pathology of COPD. Histopathology 2006; 49; 1–9. 2. Churg A, Colby TV. Diseases caused by metals and related com- pounds. In Churg A, Green FHY eds. Pathology of occupational lung disease, 2nd edn, Baltimore: Williams and Wilkins, 1998; 77–128. 3. Muller NL, Fraser RS, Lee KS, Jokhoh T. Diseases of the lung. Radiological and pathological correlations. Philadelphia: Lippincott Williams & Wilkins, 2003; 239–254. Myofibroblastoma of the male breast: a rare entity of increasing frequency that can be diagnosed on needle core biopsy DOI: 10.1111/j.1365-2559.2007.02808.x Sir: Myofibroblastoma is a rare benign mesenchymal tumour that was first described by Wargotz et al. in 2007 The Authors. Journal compilation 2007 Blackwell Publishing Ltd, Histopathology, 51, 552–580. more...

Two major limitations of breast fine needle aspiration (FNA) compared with core needle biopsies (CNB) are the inability to determine whether a cancer is invasive and to classify proliferative lesions. We studied 40 consecutive "rapid cell blocks" from breast FNAs with surgical pathology follow-up to test whether cell blocks can overcome these limitations. Of 25 carcinomas, invasion could be identified in the cell block sections in 11 (44%). One cystosarcoma phyllodes was suspected based on the cell block sections. Cell blocks from 12 of 14 benign breast FNAs showed sufficient cells to assign a histologic diagnosis of no hyperplasia (1 case, confirmed on follow-up) and usual hyperplasia (11 cases; confirmed in eight of 11 on follow-up). Specific histologic diagnoses included intraductal papilloma (2 cases), and in situ lobular neoplasia (2 cases). Cell blocks complement smears and monolayers and appear to overcome major limitations of breast FNA. more...

Hashimoto’s thyroiditis is the archetype of organ-specific autoimmune disease. The key pathogenetic feature is the activation of thyroid-specific T-cells by properly presented endogenous thyroid antigens. There is strong indication that thyrocytes themselves present self-antigens, based on the finding of antigen presenting human leukocyte antigen-DR (HLA-DR) molecules on the thyrocytes in Hashimoto’s thyroiditis. Because class II-associated invariant chain (li) is tightly bound to the antigen-binding groove of the DR molecules in the endoplasmic reticulum and is found to compete with the endogenous peptides for binding with DR, it is speculated that li prevents endogenous peptides from binding to, and being presented by, DR on the cell surface. We hypothesize that in Hashimoto’s thyroiditis, Ii is insufficient, leaving DR molecules open for endogenous peptides. In this article, we test our hypothesis of discordance between DR and li in the thyroid epithelial cells in Hashimoto’s thyroiditis by immunohistochemistry. Formalin-fixed, paraffin-embedded archival tissue from eight cases of Hashimoto’s thyroiditis and four cases of normal thyroid specimen were randomly selected and immunostained with monoclonal antibodies (MAbs) against HLA-DR and li using avidin-biotin-peroxidase method. We found that in all eight cases of Hashimoto’s thyroiditis, li is significantly reduced relative to DR. The results support our hypothesis that presentation of self-antigen may be a result of insufficient li in the thyrocytes in Hashimoto’s thyroiditis. more...

Objective: To characterize the histopathologic features of follicular variant of papillary thyroid carcinoma (FVPC) and its cytology results on fine-needle aspiration (FNA) biopsy and compare them with those of papillary thyroid carcinoma (PC). Methods: We searched the University of Massachusetts Medical Center pathology database for all surgical specimens associated with a diagnosis of FVPC or PC between January 1992 and February 1998 and reviewed the related pathology reports. In addition, the associated preoperative FNA results were analyzed. Results: On initial assessment, FVPC was associated with a significantly lower incidence of cervical lymph node metastatic involvement in comparison with PC (5.6% versus 35.7%; P more...

Summary Background Thyroid cancer is the most common endocrine malignant disease, but preoperative diagnosis remains a challenge. Fine-needle aspiration cytology has greatly improved the clinical management of thyroid nodules, but the preoperative characterisation of follicular lesions is very difficult. Many patients are thus referred to surgery more for diagnosis than for therapeutic necessity. We undertook an international multicentre study to assess the usefulness of immunohistocytochemical staining for two potential markers of malignant thyrocytes. Methods Expression of galectin-3 and CD44v6 was tested on 1009 thyroid lesions (tissue specimens and cytological cell-blocks) and 226 fresh cytological samples obtained preoperatively by ultrasound-guided fine-needle aspiration of thyroid nodules (prospective analysis). The test used monoclonal antibodies specific for CD44v6 and galectin-3, the indirect avidin-biotin complex immunoperoxidase method, and 3-amino-9-ethyl-carbazole as substrate. Findings The sensitivity, specificity, positive predictive value, and diagnostic accuracy of this test method (for coexpression of the two markers) in the prospective analysis were 88%, 98%, 91%, and 97%, respectively. The sensitivity and specificity of galectin-3 immunodetection alone in discriminating benign from malignant thyroid lesions were more than 99% and 98% respectively, and the positive predictive value and diagnostic accuracy were 92% and 99%. Interpretation The integration of galectin-3 immunostaining with conventional cytomorphological and clinical diagnostic procedures represents a sensitive and reliable diagnostic approach for preoperative identification of thyroid carcinomas. This test method improves the diagnostic accuracy of conventional cytology and provides the molecular basis for a new nosological assignation of the not yet classified thyroid neoplasms of indeterminate malignant behaviour. more...

CD57 (HNK-1) is a oligosaccharide antigen that is expressed by cells of several lineages. It is present on multipotential neuroepithelial cells during embryogenesis, and tumours of epithelial, neuroectodermal and nerve sheath origin also express CD57. Its role in the diagnosis of thyroid tumours is controversial. We have studied CD57 expression by immunohistochemistry to determine its utility in the classification of thyroid follicular lesions. Study material included 114 normal thyroid sections, 77 benign thyroid lesions (29 colloid nodules, 22 follicular adenomas, 20 cases of Hashimoto's thyroiditis and 6 of Grave's disease) and 83 thyroid carcinomas, including 31 follicular variants of papillary carcinoma. We observed CD57 positivity in 95% of thyroid carcinomas, 27% of follicular adenomas and 10% of colloid nodules. It was not expressed in the normal thyroid. CD57 expression in thyroid carcinomas was significantly different from that in normal and benign thyroid lesions (P < 0.0001). The follicular variant of papillary thyroid carcinoma also showed significantly higher CD57 expression than colloid nodules (P < 0.0009) or follicular adenomas (P < 0.0009). No significant difference was seen between colloid nodules and follicular adenomas. We conclude that CD57 immunohistochemistry is valuable in the classification of thyroid follicular lesions into benign and malignant groups and is also helpful in the diagnosis of the follicular variant of papillary thyroid carcinoma. more...