Medical postgraduate (MD) program in Laboratory Medicine in India: The Past, Present and Future.

A medical postgraduate course in the field of Laboratory Medicine for the Bachelor of Medicine and Bachelor of Surgery (MBBS) degree holders has existed for more than two decades in India, initiated and offered by the All India Institute of Medical Sciences, New Delhi, which was created under the special Act of Parliament of India 1956. This course has recently been included in the draft of National Medical Commission's Post Graduate Regulation 2021 list of medical courses, and the foundation guidelines have been laid for other medical colleges and teaching hospitals across the country to start this course. This article, written purely in academic interest, describes the past, present and future of this postgraduate training program in India with an aim to answer several doubts regarding this unique and holistic course with a view to providing a direction to those who are willing to become a laboratory physician through this post-graduation.

Nesfatin-1-like peptide is a negative regulator of cardiovascular functions in zebrafish and goldfish.

Nucleobindins (NUCB1 and NUCB2) were originally identified as calcium and DNA binding proteins. Nesfatin-1 (NEFA/nucleobindin-2-Encoded Satiety and Fat-Influencing proteiN-1) is an 82 amino acid anorexigenic peptide encoded in the N-terminal region of NUCB2. We have shown that nesfatin-1 is a cardiosuppressor in zebrafish. Both NUCB1 and NUCB2 possess a -very highly conserved bioactive core. It was found that a nesfatin-1-like peptide (NLP) encoded in NUCB1 suppresses food intake in fish. In this research, we investigated whether NLP has nesfatin-1-like effects on cardiovascular functions. NUCB1/NLP-like immunoreactivity was found in the atrium and ventricle of the heart and skeletal muscle of zebrafish. Intraperitoneal injection (IP) of either zebrafish NLP or rat NLP suppressed cardiac functions in both zebrafish and goldfish. Irisin and RyR1b mRNA expression was downregulated by NLP in zebrafish cardiac and skeletal muscles. However, cardiac ATP2a2 mRNA expression was elevated after NLP injection. Administration of scrambled NLP did not affect irisin, RyR1b or ATP2a2 mRNA expression in zebrafish. Together, these results implicate NLP as a suppressor of cardiovascular physiology in zebrafish and goldfish.

Loss of Placental P-Glycoprotein May Be a Common Pathophysiologic Pathway for First Trimester Spontaneous Miscarriages.

INTRODUCTION: P-glycoprotein the highly conserved mammalian adenosine triphosphate-binding cassette transmembrane multidrug protein transporter is involved in peri-implantation events and fetal placental development. Greater expression in early versus late pregnancy and localization in both syncytio- and cytotrophoblast indicate that P-glycoprotein transports substances across the uterine epithelium during early pregnancy and protects the conceptus from toxic substances during implantation and early embryogenesis. We hypothesized that P-glycoprotein is involved in the physiologic maintenance of early pregnancy and that P-glycoprotein dysregulation may be involved in early pregnancy pathologies. METHODS: First trimester dilation and curettage specimens were selected retrospectively from the archives of the Department of Pathology from spontaneous miscarriages (n = 36) and elective termination of pregnancy (n = 20). Two P-glycoprotein specific monoclonal antibodies JSB1and C219 were used on formalin-fixed, paraffin-embedded 5µ tissue sections. The location, intensity, and percentage of P-glycoprotein chorionic villous immunostaining were semiquantitated. RESULTS: Spontaneous miscarriages demonstrated absence or significant reduction in P-glycoprotein compared to elective terminations; 75% (27/36) showed total absence of P-glycoprotein, 19% (7/36) showed only rare villi with discontinuous immunostaining, and 6% (2/36) showed weak immunostaining. In contrast, 90% of elective terminations (18/20) showed positive immunostaining for P-glycoprotein and only 10% (2/20) showed loss of P-glycoprotein expression (P < .0001). DISCUSSION: We report a dramatic loss/decrease of P-glycoprotein in first trimester spontaneous miscarriages. This finding in conjunction with the known high expression of P-glycoprotein in normal first trimester placental tissues suggests an important role of P-glycoprotein in the maintenance of early pregnancy.

Massive Splenic Infarction in a Child With Sickle Cell Disease on Chronic Transfusion Therapy.

Massive splenic infarction (MSI) is a rare complication of sickle cell disease, as the spleen generally atrophies within the first few years of life. We report a case of MSI in a 12-year-old boy with homozygous sickle cell anemia (Hb SS) whose chronic transfusion therapy resulted in hypersplenism. The occurrence of a complicated MSI in our patient should perhaps further encourage elective splenectomy in such patients, despite known potential perioperative complications and postsplenectomy risks of infection and thrombosis.

Loss of PTEN and Increased pAKT Expression Distinguishes Aggressive Low-grade Neuroendocrine Tumors.

A major problem in neuroendocrine pathology is the identification and separation of aggressive low-grade neuroendocrine tumors (LGNETs) from those with a benign or more indolent behavior. Presently there are no known morphologic or molecular parameters which can predict how localized LGNETs will behave. The phosphatase and tensin homolog (PTEN) gene negatively regulates the PI3K-AKT-mTOR pathway and inhibits neoplastic cell survival and proliferation and has recently been identified as a neuroendocrine tumor differentiation marker. We hypothesized loss of PTEN may also identify LGNETs that demonstrate aggressive behavior. We studied PTEN and pAKT expression in 18 LGNETs using specific monoclonal antibodies. Follow up was obtained for a minimum of five years on all patients. 8/18 cases had strong PTEN expression and showed no evidence of disease on >5 years follow-up. 10 cases demonstrated loss of PTEN expression; 9/10 had positive pAKT expression, and 7/9 had recurrence and/or metastases. Lung and appendiceal LGNETs uniformly had high PTEN expression and a markedly better prognosis than their gastroenteropancreatic (GEP) counterparts. Loss of PTEN correlated significantly with the positive expression of pAKT (P=0.0027) and aggressive behavior of LGNETs (p=0.0002). Loss of PTEN and increased pAKT correlated with the metastatic potential of LGNETs (p=0.0011 and 0.0248 respectively). Loss of PTEN and increased pAKT expression distinguishes aggressive LGNETs from those with more indolent behavior.

Postirradiation Leiomyosarcoma of Rectum Presenting as a Polyp: Case Report and Review of the Literature.

Radiation-induced leiomyosarcomas of the gastrointestinal tract are rare. Very few cases have been documented to date. The histological similarity to gastrointestinal stromal tumor has raised doubts if many of the cases originally reported to be leiomyosarcoma before the widespread use of CD117 were indeed gastrointestinal stromal tumors. We present a case of post-irradiation leiomyosarcoma presenting as a rectal polyp and review the literature.

An acute hemolytic transfusion reaction due to the "anti-c" rhesus antibody: A case report emphasizing the role of transfusion medicine.

Rhesus (Rh) mediated hemolytic transfusion reactions (HTR) are usually immunoglobulin G mediated and delayed onset. Rh antibodies being the cause of acute HTR (AHTR) and intravascular hemolysis are still under debate. We report here a case of a 53-year-old male who developed AHTR due to "anti-c" antibodies within 3 h of blood transfusion, precipitating fatal acute liver failure in a patient with hepatitis C related chronic liver disease. This case emphasizes the need of inclusion of antibody screening in routine pretransfusion testing as well as a critical role of transfusion medicine specialists for early diagnosis and minimizing transfusion-related morbidity and mortality.

Laboratory evaluation of three regimens of treatment of chronic hepatitis B: tenofovir, entecavir and combination of lamivudine and adefovir.

BACKGROUND: Chronic hepatitis B is a disease of concern due to its life-threatening complications like cirrhosis, and hepatocellular carcinoma (HCC) in 20-40% of patients. There are about 400 million people affected worldwide with HBV, and over 300,000 die every year from HBV-related diseases. Oral antivirals like lamivudine, adefovir, entecavir, and tenofovir are commonly used to treat chronic hepatitis B. In this study, we tried to evaluate the comparative efficacy of these drugs alone and in combination. MATERIALS AND METHODS: Chronic hepatitis B patients with HBV-DNA more than 104Copies/mL irrespective of their HBeAg status (n=60) were enrolled in a prospective study. 21, 20, and 19 patients were treated with lamivudine (100 mg/day) plus adefovir (10 mg/day) combination entecavir monotherapy (0.5 mg/day) and tenofovir monotherapy (300 mg/day), respectively and were followed up for 24 weeks with their virological, serological, and biochemical markers measured at 12 and 24 weeks. RESULTS: After 24 weeks of treatment, there was no significant difference between the 3 groups in suppressing HBV-DNA to undetectable levels. The median decrease in HBV-DNA levels from baseline was better with tenofovir and entecavir monotherapies than lamivudine and adefovir combination, which was statistically significant. There was no significant difference between the 3 groups in HBsAg and HBeAg seroconversion and normalization of biochemical parameters. CONCLUSION: Entecavir and tenofovir monotherapy were found to be more effective than lamivudine plus adefovir combination in reducing the HBV-DNA levels. However, lamivudine plus adefovir combination was not too inferior, especially when cost of treatment was taken into consideration.