The modern histopathologist: in the changing face of time

The molecular age histopathologist of today is practicing pathology in a totally different scenario than the preceding generations did. Histopathologists stand, as of now, on the cross roads of a traditional 'visible' morphological science and an 'invisible' molecular science. As molecular diagnosis finds more and more applicability in histopathological diagnosis, it is time for the policy makers to reframe the process of accreditation and re-accreditation of the modern histopathologist in context to the rapid changes taking place in this science. Incorporation of such 'molecular' training viv-a-vis information communication technology skills viz. telemedicine and telepathology, digital imaging techniques and photography and a sound knowledge of the economy that the fresh entrant would ultimately become a part of would go a long way to produce the Modern Histopathologist. This review attempts to look at some of these aspects of this rapidly advancing 'art of science.

Incipient primary biliary cirrhosis/autoimmune hepatitis overlap or hepatitic form of primary biliary cirrhosis: a case report

A 42 year old asymptomatic female detected as incipient Primary Biliary Cirrhosis/Autoimmune Hepatitis overlap during routine checkup. The biochemical profile showed evolution from a mildly deranged liver function test in 2004 along with increased erythrocyte sedimentation rate to a 4 times elevation of alkaline phosphatase in 2006 with mildly deranged alanine transaminase. Autoimmune markers demonstrable were Anti mitochondrial antibody M2 and sp100. Histopathology showed dual features, dominant findings were of autoimmune heptatitis. Features consistent with Primary Biliary Cirrhosis were minimal with an occasional portal tract showing paucity of bile ducts and occasional bile duct proliferation. Human leucocyte antigen DR/DQ genotype was as follows: DRB1*03, DRB1*07, DQB1*02, DQB1*04

Immune responses in patients with HIV infection after vaccination with recombinant Hepatitis B virus vaccine

BACKGROUND: Patients with HIV infection are at risk of co-infection with HBV, as the routes of transmission are shared and thus immunization with HBV vaccine could be protective in them. The aim of the present study was to assess the efficacy of recombinant vaccine in treatment-naive HIV positive patients and healthy controls, and to dissect out differences if any, in different limbs of immune response. METHODS: Forty HIV positive patients and 20 HIV negative controls, negative for HBsAg, HBsAbs and HBcAbs were vaccinated with three doses of 40μg and 20μg of vaccine respectively. Patients were divided into high CD4 and low CD4 group based on CD4+ lymphocytes of 200 and < 200/mm3 respectively. Group II consisted of healthy controls. Detection of phenotypic markers was done by flowcytometry. Cytokine estimation was done by sandwich ELISA. HBsAbs were estimated in serum by ELISA. RESULTS: After vaccination, CD(4)+, CD(8)+ and CD(3)+ cells increased significantly in all the groups. There was no increase in NK cell activity in patients with high CD(4)+ lymphocytes and only a marginal increase in patients with low CD(4)+ lymphocytes (170 to 293/mm3) whereas a marked increase was observed in controls (252 to 490/mm3). After vaccination, although an increase in memory cells was observed in HIV positive patients, yet HBsAb levels were significantly lower than controls (P < 0.05) indicating a functional defect of memory cells in HIV/AIDS patients. Basal IFN-γ levels were also significantly lower in HIV/AIDS patients (P < 0.01). Although the levels increased after vaccination, the peak level remained lower than in controls. HBsAb titers were much lower in HIV positive patients compared to controls. (High CD(4)+ group: 8834 mIU/ml, low CD(4)+ group: 462 mIU/ml Vs. Controls: 16,906 mIU/ml). IL-4 and IL-10 were low in patients. CONCLUSION: Despite a double dose in patients, IL-4 and IL-10, which regulate antibody response, were also lower in patients, and this together with low CD(4)+ counts and lack of T help, accounted for low HBsAb levels. Vaccination in patients with CD(4)+ lymphocytes < 50/mm(3) was ineffective. Thus early immunization is advocated in all HIV positive patients at a stage when they are still capable of mounting an adequate immune respons

Immunofluorescence profile of discoid lupus erythematosus

The direct immunofluorescence (DIF) of skin in conjunction with histopathology gives the best diagnostic yield. It is invaluable in confirming the diagnosis of small vessel vasculitides and bullous lesions of the skin and can be used as an additional tool to pinpoint the diagnosis of systemic and localized autoimmune diseases involving the skin. This study was undertaken to analyze the strength of DIF vis-à -vis histopathology in the diagnosis of discoid lupus erythematosus (DLE) and at the same time to elaborate the specific immunofluorescence findings in the lesions of DLE. The clinical profile and cutaneous lesions of 75 patients with DLE are described. DIF was positive in 68% and histopathology in 60% of cases. The most common immunoreactant was IgG at the dermoepidermal junction, followed by IgM and IgA. A conclusive diagnosis of DLE could be achieved satisfactorily in 64 cases (85%) by a combination of the two techniques

Analysis of HLA association among North Indian HIV-positive individuals co-infected with Mycobacterium tuberculosis

Background: Genetic variation in HLA genes influence the immune response and may thus contribute to differential development of tuberculosis (TB) in HIV-infected individuals. The study was designed to determine whether HLA polymorphisms influence the development of Mycobacterium tuberculosis infection in HIV-infected individuals. Materials and Methods: Fifty HIV-positive individuals without TB (HIV+TB−), 50 HIV patients co-infected with TB (HIV+TB+) and 50 control subjects (HIV-TB-) were analyzed for HLA Class I and II polymorphisms. Results: In HLA Class II, frequency of occurrence of DRB1*13 (OR 3.165, CI 1.176–8.518, P value 0.019), DRB5 (OR 2.253, CI 1.011–5.019, P value 0.045) and DQB1*06 (OR 2.705, CI 1.197–6.113, P value 0.016) were increased in HIV+TB+compared to HIV+TB−. HLA DQB1*02 (OR 0.436, CI 0.185–1.029, P value 0.05) on the other hand conferred a protective role. In HLA Class I, frequency of B*15 (OR 2.705, CI 1.040–7.036, P value 0.038) was increased, whereas B*51 (OR 0.148, CI 0.031–0.706, P value 0.007) was decreased in HIV+TB+group compared to HIV+TB−. These differences however were not significant when compared with healthy controls. Conclusion: HLA polymorphisms independently did not account for the susceptibility to either of the disease mostly, although they seem to play a role once the infection(s) has established in a particular individual. Further studies are needed on a larger sample size to confirm these observations

Evaluation of Brain Pharmacokinetic and Neuropharmacodynamic Attributes of an Antiepileptic Drug, Lacosamide, in Hepatic and Renal Impairment: Preclinical Evidence

The knowledge of pharmacokinetic and pharmacodynamic properties of antiepileptic drugs is helpful in optimizing drug therapy for epilepsy. This study was designed to evaluate the pharmacokinetic and pharmacodynamic properties of lacosamide in experimentally induced hepatic and renal impairment in seizure animals. Hepatic or renal impairment was induced by injection of carbon tetrachloride or diclofenac sodium, respectively. After induction, the animals were administered a single dose of lacosamide. At different time points, maximal electroshock (MES) seizure recordings were made followed by isolation of plasma and brain samples for drug quantification and pharmacodynamic measurements. Our results showed a significant increase in the area under the curve of lacosamide in hepatic and renal impairment groups. Reduced clearance of lacosamide was observed in animals with renal impairment. Along with pharmacokinetic alterations, the changes in pharmacodynamic effects of lacosamide were also observed in all the groups. Lacosamide showed a significant protection against MES-induced seizures, oxidative stress, and neuroinflammatory cytokines. These findings revealed that experimentally induced hepatic or renal impairment could alter the pharmacokinetic as well as pharmacodynamic properties of lacosamide. Hence, these conditions may affect the safety and efficacy of lacosamide

Diagnostic performance of various tests and criteria employed in allergic bronchopulmonary aspergillosis: a latent class analysis.

AIM: The efficiency of various investigations and diagnostic criteria used in diagnosis of allergic bronchopulmonary aspergillosis (ABPA) remain unknown, primarily because of the lack of a gold standard. Latent class analysis (LCA) can provide estimates of sensitivity and specificity in absence of gold standard. Herein, we report the performance of various investigations and criteria employed in diagnosis of ABPA. METHODS: Consecutive subjects with asthma underwent all the following investigations Aspergillus skin test, IgE levels (total and A.fumigatus specific), Aspergillus precipitins, eosinophil count, chest radiograph, and high-resolution computed tomography (HRCT) of the chest. We used LCA to estimate the performance of various diagnostic tests and criteria in identification of ABPA. RESULTS: There were 372 asthmatics with a mean age of 35.9 years. The prevalence of Aspergillus sensitization was 53.2%. The sensitivity and specificity of various tests were Aspergillus skin test positivity (94.7%, 79.7%); IgE levels>1000 IU/mL (97.1%, 37.7%); A.fumigatus specific IgE levels>0.35 kUA/L (100%, 69.3%); Aspergillus precipitins (42.7%, 97.1%); eosinophil count>1000 cells/µL (29.5%, 93.1%); chest radiographic opacities (36.1%, 92.5%); bronchiectasis (91.9%, 80.9%); and, high-attenuation mucus (39.7%, 100%). The most accurate criteria was the Patterson criteria using six components followed by the Agarwal criteria. However, there was substantial decline in accuracy of the Patterson criteria if components of the criteria were either increased or decreased from six. CONCLUSIONS: A.fumigatus specific IgE levels and high-attenuation mucus were found to be the most sensitive and specific test respectively in diagnosis of ABPA. The Patterson criteria remain the best diagnostic criteria however they have good veridicality only if six criteria are used

Clinical relevance of peripheral blood eosinophil count in allergic bronchopulmonary aspergillosis

Summary: Background and aims: Currently, there is not a uniform consensus regarding the number of criteria or specific cut-off values for the variety of tests that are used to diagnose allergic bronchopulmonary aspergillosis (ABPA). Traditionally, an eosinophil count >1000 cells/μl is considered an important criterion in the diagnosis of ABPA. The goal of this study was to delineate the significance of the peripheral blood eosinophil count in the diagnosis of ABPA, and the relationship between eosinophil counts and lung function and immunological and radiological parameters. Methods: This study was a retrospective analysis of the data from ABPA patients who were managed in our chest clinic. Based on their eosinophil count, the patients were classified into the following three categories: 1000 cells/μl. The spirometric, immunological and radiological characteristics were also assessed. Results: We studied 108 males and 101 females with a combined mean (±SD) age of 34.1 ± 12.5 years. The median (IQR) eosinophil count at diagnosis was 850 (510–1541) cells/μl, and 60% of the patients had an eosinophil count of <1000 cells/μl. We found no relationship between eosinophil count and lung function using spirometry and other immunological parameters. The median eosinophil count was higher in patients with an high resolution computed tomography (HRCT) chest finding of bronchiectasis (986 vs. 620, p < 0.001) vs. those without and in patients with high-attenuation mucus (1200 vs. 800, p < 0.001) compared to those without high-attenuation mucus. Conclusions: A peripheral blood eosinophil count has limited utility in the diagnosis of ABPA, and there is no relationship between eosinophil count and lung function or other immunological parameters. The higher eosinophil count that we observed in patients with central bronchiectasis or high-attenuation mucus suggests that eosinophils are primary mediators of inflammatory activity in ABPA. Keywords: Allergic bronchopulmonary aspergillosis (ABPA), Aspergillus fumigatus, Eosinophil