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1.
J Clin Exp Hepatol ; 13(6): 1074-1090, 2023.
Article in English | MEDLINE | ID: mdl-37975034

ABSTRACT

Endoscopic retrograde cholangiopancreatography (ERCP) has been a significant development in gastrointestinal endoscopy. I did my first ERCP at SKIMS on December 5, 1982, and over the last 40 years, I have performed 10,100 ERCP procedures, including 600 Sphincter of Oddi manometries (SOM), and 3200 therapeutic ERCPs. We were confronted with many clinical challenges that needed answers by applying ERCP as a primary diagnostic tool. These studies gave birth to and/or recognition of several clinical syndromes. The hepatobiliary and pancreatic ascariasis (HBPA) as a clinical disease was recognized in 1985. The nematode, Ascaris lumbricoides, was the most common cause of hepatobiliary and pancreatic diseases in Kashmir, and its impact on healthcare, clinical profile, management policies, and control measures was identified. Kashmir was recognized as an endemic zone for recurrent pyogenic cholangitis (RPC), which constituted 12.5% of all biliary diseases. RPC in this population was found essentially to be an aftermath of HBPA. A subset of patients with hepatic hydatidosis with rupture into the biliary tract was recognized at ERCP and primarily treated by endotherapy. Cholangiographic abnormalities in children with portal cavernoma evolved into the recognition of portal biliopathy. Extensive studies of the sphincter of Oddi manometry in patients with unexplained biliary and/or pancreatic pain following cholecystectomy identified the entity of the sphincter of Oddi dyskinesia (SOD). In a cross-over trial, Nifedipine, compared with a placebo, showed a significant clinical response in 20 of 28 such patients. ERCP studies done in patients with tropical calcific pancreatitis showed an anomalous union of bile and pancreatic ducts. Forty of the 220 patients with liver transplantation had biliary complications namely biliary leaks, bile duct strictures, SOD, and recurrence of underlying primary biliary cholangitis. Biliary complications caused considerable morbidity and mortality in patients with liver transplantation.

2.
Viruses ; 15(8)2023 08 15.
Article in English | MEDLINE | ID: mdl-37632090

ABSTRACT

The story of the discovery of hepatitis E originated in the late 1970s with my extreme belief that there was a hidden saga in the relationship between jaundice and pregnancy in developing countries and the opportunity for a massive epidemic of viral hepatitis, which hit the Gulmarg Kashmir region in November 1978. Based on data collected from a door-to-door survey, the existence of a new disease, epidemic non-A, non-B hepatitis, caused by a hitherto unknown hepatitis virus, was announced. This news was received by the world community with hype and skepticism. In the early 1980s, the world watched in awe as an extreme example of human self-experimentation led to the identification of VLP. In 1990, a cDNA clone from the virus responsible for epidemic non-A, non-B hepatitis was isolated. Over the years, we traversed three eras of ambiguity, hope, and hype of hepatitis E research and conducted several seminal studies to understand the biology of HEV and manifestations of hepatitis E. Many milestones have been reached on the long and winding road of hepatitis E research to understand the structure, biology, and diversity of the agent, changing the behavior of the pathogen in developed countries, and the discovery of a highly effective vaccine.


Subject(s)
Epidemics , Hepatitis C , Hepatitis E , Female , Pregnancy , Humans , Hepatitis E/epidemiology , Global Health , DNA, Complementary
3.
Neurosurg Rev ; 46(1): 178, 2023 Jul 19.
Article in English | MEDLINE | ID: mdl-37466764

ABSTRACT

The COVID-19 pandemic led to stringent guidelines to restrict the conduct of non-emergent surgical procedures. Consequently, neurosurgery departments experienced a decline in case volumes and greater educational time being spent on virtual research projects. In our report, we reveal how neurosurgical research has changed during the pandemic compared to the pre-pandemic phase. The WebOfScience database was searched for neurosurgical articles published between 2012-2019 (pre-pandemic) and 2020-2022 (pandemic). From this data, the keywords, terms, and countries were analyzed using networks formed by the VOS Viewer software. In addition, the analysis was repeated for neurosurgical articles specific to COVID-19. Network analyses of terms and keywords revealed an increased popularity of virtual research projects, including case reports, meta-analyses, reviews, surveys, and database studies. Additionally, there was increased interest in research pertaining to neurosurgical education during the post-pandemic era, including topics regarding virtual training modalities, mental health, and telemedicine. Our bibliometrics analysis suggests that the impact of COVID-19 restrictions on hospital systems affected neurosurgical training programs. Future investigations should explore the effects of the trainee experience during the COVID-19 pandemic on the outlook for neurosurgical education.


Subject(s)
COVID-19 , Internship and Residency , Neurosurgery , Humans , COVID-19/epidemiology , Pandemics , Neurosurgery/education , Neurosurgical Procedures/methods
4.
World Neurosurg ; 178: e147-e155, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37442538

ABSTRACT

BACKGROUND: Reports find that magnetic resonance elastography (MRE) and shear wave elastography (SWE) can classify intracranial tumors according to stiffness. However, systematic syntheses of these articles are lacking. In this report, a systematic review and meta-analysis was performed to evaluate whether SWE and MRE can predict meningioma and glioma grades. METHODS: PubMed and Scopus were searched between February 10, 2022. and March 2, 2022. using manual search criteria. Eight out of 106 non-duplicate records were included, encompassing 84 patients with low-grade tumors (age 42 ± 13 years, 71% female) and 92 patients with high-grade tumors (age 50 ± 13 years, 42% female). Standardized mean difference in stiffness between high-grade and low-grade tumors were measured using a forest plot. The I2, χ2, and t tests were performed, and bubble plots were constructed to measure heterogeneity. An adapted QUADAS-2 scale evaluated study quality. Additionally, a funnel plot was constructed, and an Egger's intercept test determined study bias. RESULTS: Low-grade tumors were stiffer than high-grade tumors (Cohen's D = -1.25; 95% CI -1.88, -0.62). Moderate heterogeneity was observed (I2 = 67%; P = 0.006) but controlling for publication year (I2 = 0.2%) and age (I2 = 0.0%-17%) reduced heterogeneity. Included studies revealed unclear or high bias for the reference standard and flow and timing (>50%). CONCLUSIONS: Elastography techniques have potential to grade tumors intraoperatively and postoperatively. More studies are needed to evaluate the clinical utility of these technologies.

6.
J Clin Exp Hepatol ; 11(5): 592-602, 2021.
Article in English | MEDLINE | ID: mdl-34511821

ABSTRACT

Over decades, surgery has been the only accepted mode of treatment for liver hydatid cysts. It had been a surgical dogma for a long that hydatid disease is an absolute contraindication for needle puncture/aspiration as it can cause anaphylaxis, death, and dissemination. We envisaged prospectively perform percutaneous drainage as a primary form of treatment for hepatic hydatidosis. Through extensive and very careful experimentation, we proved that aspiration of hydatid cysts can be performed safely and is the ideal way to manage a subset of patients with hydatid cysts in the liver. The patient and cyst characteristics good and not good for percutaneous drainage were carefully selected. The procedure of percutaneous drainage of hepatic hydatid cysts involves four sequential steps as defined in the alphabets of the title PAIR, denoting puncture (P), Aspiration (A), Instillation (I), and Reaspiration (R). During and postprocedure, we enforced strict monitoring given the anticipated anaphylaxis. The first PAIR procedure was performed in June 1988. The results of percutaneous drainage of 21 cysts in 12 patients were reported in 1991. Next, a prospective study was done to show that concomitant Albendazole therapy is recommended as an adjuvant to percutaneous drainage for hepatic hydatidosis. In a seminal prospective study comparing percutaneous drainage and surgery, we showed that percutaneous drainage is as good as surgery in the management of uncomplicated hydatid cysts with fewer complications and shorter hospital stays. Lastly, long-term follow-up results of percutaneous drainage on a large cohort of patients with hepatic hydatid cysts were reported, with excellent results and no evidence of local, peritoneal or systemic dissemination. Based on these data percutaneous drainage, the so-called PAIR technique has established itself as a novel therapeutic advance in hepatic hydatid disease.

7.
Viruses ; 13(7)2021 07 09.
Article in English | MEDLINE | ID: mdl-34372535

ABSTRACT

The adverse relationship between viral hepatitis and pregnancy in developing countries had been interpreted as a reflection of retrospectively biased hospital-based data collection by the West. However, the discovery of hepatitis E virus (HEV) as the etiological agent of an epidemic of non-A, non-B hepatitis in Kashmir, and the documenting of the increased incidence and severity of hepatitis E in pregnancy via a house-to-house survey, unmasked this unholy alliance. In the Hepeviridae family, HEV-genotype (gt)1 from genus Orthohepevirus A has a unique open reading frame (ORF)4-encoded protein which enhances viral polymerase activity and viral replication. The epidemics caused by HEV-gt1, but not any other Orthohepevirus A genotype, show an adverse relationship with pregnancy in humans. The pathogenesis of the association is complex and at present not well understood. Possibly multiple factors play a role in causing severe liver disease in the pregnant women including infection and damage to the maternal-fetal interface by HEV-gt1; vertical transmission of HEV to fetus causing severe fetal/neonatal hepatitis; and combined viral and hormone related immune dysfunction of diverse nature in the pregnant women, promoting viral replication. Management is multidisciplinary and needs a close watch for the development and management of acute liver failure. (ALF). Preliminary data suggest beneficial maternal outcomes by early termination of pregnancy in patients with lower grades of encephalopathy.


Subject(s)
Hepatitis E virus/genetics , Hepatitis E/complications , Hepatitis E/epidemiology , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/virology , Female , Genotype , Hepatitis E virus/classification , Humans , India/epidemiology , Infant, Newborn , Infectious Disease Transmission, Vertical , Liver/pathology , Liver/virology , Liver Failure, Acute/virology , Open Reading Frames , Pregnancy , RNA, Viral/genetics , Retrospective Studies , Virus Replication
8.
J Clin Exp Hepatol ; 10(6): 610-621, 2020.
Article in English | MEDLINE | ID: mdl-32837093

ABSTRACT

The coronavirus disease 2019 (COVID-19) has turned into a global human tragedy and economic devastation. Governments have implemented lockdown measures, blocked international travel, and enforced other public containment measures to mitigate the virus morbidity and mortality. As of today, no drug has the power to fight the infection and bring normalcy to the utter chaos. This leaves us with only one choice namely an effective and safe vaccine that shall be manufactured as soon as possible and available to all countries and populations affected by the pandemic at an affordable price. There has been an unprecedented fast track path taken in Research & Development by the World community for developing an effective and safe vaccine. Platform technology has been exploited to develop candidate vaccines in a matter of days to weeks, and as of now, 108 such vaccines are available. Six of these vaccines have entered clinical trials. As clinical trials are "rate-limiting" and "time-consuming", many innovative methods are in practice for a fast track. These include parallel phase I-II trials and obtaining efficacy data from phase IIb trials. Human "challenge experiments" to confirm efficacy in humans is under serious consideration. The availability of the COVID-19 vaccine has become a race against time in the middle of death and devastation. There is an atmosphere of tremendous hype around the COVID-19 vaccine, and developers are using every moment to make claims, which remain unverified. However, concerns are raised about a rush to deploy a COVID-19 vaccine. Applying "Quick fix" and "short cuts" can lead to errors with disastrous consequences.

9.
J Clin Exp Hepatol ; 10(4): 391-401, 2020.
Article in English | MEDLINE | ID: mdl-32655240

ABSTRACT

Discovery of five hepatitis viruses A to E has followed distinctive definable phases. Human experiments at Willowbrook identified two forms of hepatitis namely infectious hepatitis and serum hepatitis. The discovery of Australia antigen in 1965 led to rapid scientific developments in viral hepatitis. SH antigen was detected in sera of patients with serum hepatitis and soon SH antigen and Australia antigen were found to be identical and selectively associated with serum hepatitis. In 1970, 42-nm Dane particles were detected in Australia antigen positive sera and linked to the virus of serum hepatitis. Subsequently, a new antigen-antibody system (e-antigen/antibody) was detected in such patients and associated with infectivity. Then, DNA polymerase was found in concentrated pellets containing Australia antigen. Hepatitis B virus (HBV) DNA cloning and sequencing of HBV followed these developments. In 1973, 27 nm hepatitis A virus (HAV)-like particles were visualized in stool samples obtained during acute phase of illness after inoculation of MS-1 strain in volunteers. Cloning and sequencing of HAV followed. In 1977, a new antigen-antibody system (δ antigen-antibody system) was identified by chance associated with HBV. Based on animal transmission studies, δ agent was found to be another virus called hepatitis D virus that is defective, requires the helper functions of HBV and interferes with HBV replication. The search for hepatitis C virus started when non-A, non-B hepatitis was recognised in multiply transfused patients with subsequent successful animal transmission. HCV was identified by a novel immunoscreening approach involving screening of cDNA libraries from infectious sera. The story of hepatitis E is historically linked to discovery of waterborne epidemic non-A, non-B hepatitis from Kashmir, India. Virus-like-particles of the agent were identified in stool samples of a human volunteer after a self-experimentation. HEV cDNA was detected in bile-enriched infectious samples and full-length HEV RNA genome was subsequently cloned and sequenced.

10.
Int J Antimicrob Agents ; 56(3): 106101, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32687949

ABSTRACT

The coronavirus infection (COVID-19) has turned into a global catastrophe and there is an intense search for effective drug therapy. Of all the potential therapies, chloroquine and hydroxychloroquine have been the focus of tremendous public attention. Both drugs have been used in the treatment and prophylaxis of malaria. Long-term use of hydroxychloroquine is the cornerstone in the treatment of several auto-immune disorders. There is convincing evidence that hydroxychloroquine has strong in vitro antiviral activity against SARS-CoV-2. A few small uncontrolled trials and several anecdotal reports have shown conflicting results of such drug therapy in COVID-19. However, the results of preliminary large-scale randomized controlled trials have failed to show any survival benefit of such drug therapy in COVID-19. Despite the lack of such evidence, hydroxychloroquine has been used as a desperate attempt for prophylaxis and treatment of COVID-19. The drug has wide-ranging drug interactions and potential cardiotoxicity. Indiscriminate unsupervised use can expose the public to serious adverse drug effects.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Antiviral Agents/administration & dosage , Chloroquine/administration & dosage , Coronavirus Infections/drug therapy , Cytokine Release Syndrome/prevention & control , Hydroxychloroquine/administration & dosage , Immunologic Factors/administration & dosage , Pneumonia, Viral/drug therapy , Anti-Inflammatory Agents/adverse effects , Antiviral Agents/adverse effects , Betacoronavirus/drug effects , Betacoronavirus/growth & development , Betacoronavirus/immunology , COVID-19 , Chloroquine/adverse effects , Clinical Trials as Topic , Coronavirus Infections/mortality , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/mortality , Cytokine Release Syndrome/virology , Cytokines/antagonists & inhibitors , Cytokines/genetics , Cytokines/immunology , Drug Administration Schedule , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Hydroxychloroquine/adverse effects , Immunologic Factors/adverse effects , Pandemics/prevention & control , Pneumonia, Viral/mortality , Pneumonia, Viral/prevention & control , Pneumonia, Viral/virology , SARS-CoV-2 , Survival Analysis , Virus Internalization/drug effects , Virus Replication/drug effects
11.
World J Gastroenterol ; 22(33): 7507-17, 2016 Sep 07.
Article in English | MEDLINE | ID: mdl-27672273

ABSTRACT

Hepatobiliary and pancreatic ascariasis (HPA) was described as a clinical entity from Kashmir, India in 1985. HPA is caused by invasion and migration of nematode, Ascaris lumbricoides, in to the biliary tract and pancreatic duct. Patients present with biliary colic, cholangitis, cholecystitis, hepatic abscesses and acute pancreatitis. Ascarides traverse the ducts repeatedly, get trapped and die, leading to formation of hepatolithiasis. HPA is ubiquitous in endemic regions and in Kashmir, one such region, HPA is the etiological factor for 36.7%, 23%, 14.5% and 12.5% of all biliary diseases, acute pancreatitis, liver abscesses and biliary lithiasis respectively. Ultrasonography is an excellent diagnostic tool in visualizing worms in gut lumen and ductal system. The rational treatment for HPA is to give appropriate treatment for clinical syndromes along with effective anthelmintic therapy. Endotherapy in HPA is indicated if patients continue to have symptoms on medical therapy or when worms do not move out of ductal lumen by 3 wk or die within the ducts. The worms can be removed from the ductal system in most of the patients and such patients get regression of symptoms of hepatobiliary and pancreatic disease.


Subject(s)
Ascariasis/diagnosis , Biliary Tract Diseases/diagnosis , Liver Diseases, Parasitic/diagnosis , Pancreatitis/diagnosis , Algorithms , Animals , Ascariasis/complications , Ascaris lumbricoides , Biliary Tract/pathology , Biliary Tract Diseases/complications , Cholangitis/complications , Cholangitis/diagnosis , Cholecystitis/complications , Cholecystitis/diagnosis , Humans , India , Liver Diseases, Parasitic/complications , Pancreatitis/complications , Prevalence
12.
World J Gastroenterol ; 22(35): 7973-82, 2016 Sep 21.
Article in English | MEDLINE | ID: mdl-27672292

ABSTRACT

Portal biliopathy refers to cholangiographic abnormalities which occur in patients with portal cavernoma. These changes occur as a result of pressure on bile ducts from bridging tortuous paracholedochal, epicholedochal and cholecystic veins. Bile duct ischemia may occur due prolonged venous pressure effect or result from insufficient blood supply. In addition, encasement of ducts may occur due fibrotic cavernoma. Majority of patients are asymptomatic. Portal biliopathy is a progressive disease and patients who have long standing disease and more severe bile duct abnormalities present with recurrent episodes of biliary pain, cholangitis and cholestasis. Serum chemistry, ultrasound with color Doppler imaging, magnetic resonance imaging with magnetic resonance cholangiopancreatography and magnetic resonance portovenography are modalities of choice for evaluation of portal biliopathy. Endoscopic retrograde cholangiography being an invasive procedure is indicated for endotherapy only. Management of portal biliopathy is done in a stepwise manner. First, endotherapy is done for dilation of biliary strictures, placement of biliary stents to facilitate drainage and removal of bile duct calculi. Next portal venous pressure is reduced by formation of surgical porto-systemic shunt or transjugular intrahepatic portosystemic shunt. This causes significant resolution of biliary changes. Patients who persist with biliary symptoms and bile duct changes may benefit from surgical biliary drainage procedures (hepaticojejunostomy or choledechoduodenostomy).


Subject(s)
Biliary Tract/pathology , Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Cholestasis/metabolism , Portal Vein/pathology , Bile Ducts/pathology , Cholangiography/adverse effects , Cholangitis/complications , Cholestasis/etiology , Gallbladder Diseases/complications , Humans , Hypertension, Portal/diagnosis , Ischemia , Liver/surgery , Portal Pressure , Portal Vein/surgery , Portasystemic Shunt, Surgical , Stents/adverse effects
13.
Viruses ; 8(9)2016 Sep 20.
Article in English | MEDLINE | ID: mdl-27657112

ABSTRACT

Hepatitis E virus (HEV), an RNA virus of the Hepeviridae family, has marked heterogeneity. While all five HEV genotypes can cause human infections, genotypes HEV-1 and -2 infect humans alone, genotypes HEV-3 and -4 primarily infect pigs, boars and deer, and genotype HEV-7 primarily infects dromedaries. The global distribution of HEV has distinct epidemiological patterns based on ecology and socioeconomic factors. In resource-poor countries, disease presents as large-scale waterborne epidemics, and few epidemics have spread through person-to-person contact; however, endemic diseases within these countries can potentially spread through person-to-person contact or fecally contaminated water and foods. Vertical transmission of HEV from infected mother to fetus causes high fetal and perinatal mortality. Other means of transmission, such as zoonotic transmission, can fluctuate depending upon the region and strain of the virus. For instance, zoonotic transmission can sometimes play an insignificant role in human infections, such as in India, where human and pig HEV infections are unrelated. However, recently China and Southeast Asia have experienced a zoonotic spread of HEV-4 from pigs to humans and this has become the dominant mode of transmission of hepatitis E in eastern China. Zoonotic HEV infections in humans occur by eating undercooked pig flesh, raw liver, and sausages; through vocational contact; or via pig slurry, which leads to environmental contamination of agricultural products and seafood. Lastly, blood transfusion-associated HEV infections occur in many countries and screening of donors for HEV RNA is currently under serious consideration. To summarize, HEV genotypes 1 and 2 cause epidemic and endemic diseases in resource poor countries, primarily spreading through contaminated drinking water. HEV genotypes 3 and 4 on the other hand, cause autochthonous infections in developed, and many developing countries, by means of a unique zoonotic food-borne transmission.

14.
World J Gastroenterol ; 22(31): 7030-45, 2016 Aug 21.
Article in English | MEDLINE | ID: mdl-27610014

ABSTRACT

Hepatitis E was identified as an epidemic of non-A, non-B hepatitis from Kashmir, India in 1978. Hepatitis E virus (HEV), the etiological agent is the sole member of family Hepeviridae. The virus has marked heterogeneity and infects many animals like bats, camel, chicken, deer, boar, mongoose, pigs, rats, rabbit and cutthroat trout. Hepatitis E is a disease with a major global impact and has two distinct epidemiological patterns. Hepatitis E is an imperative health issue in developing nations, transmitted through sullied water and happens most every now in young adults. The disease is particularly severe during pregnancy and in people with underlying liver cirrhosis. Autochthonous hepatitis E is increasingly recognized in developed countries. The virus infects domestic pigs, wild boar and Sika deer in these countries. HEV infections in humans occur by eating the undercooked game flesh, raw liver from supermarkets and Figatelli sausages. Blood transfusion-associated HEV infections occur in many countries and screening of donors for HEV RNA is under consideration. Hepatitis E causes a number of extrahepatic diseases, including a wide spectrum of neurological syndromes. HEV genotype 3 causes prolonged viremia, chronic hepatitis, liver fibrosis and cirrhosis in organ transplant patients. The virus is amenable to ribavirin monotherapy and most patients clear the virus in a few weeks. Hepatitis E vaccine -239, marketed in China, has shown high efficacy with sustained protection for over four years.


Subject(s)
Hepatitis E/epidemiology , Animals , Developing Countries , Disease Reservoirs , Hepatitis E/prevention & control , Hepatitis E/therapy , Hepatitis E/transmission , Hepatitis E virus/classification , Hepatitis E virus/genetics , Hepatitis E virus/physiology , Humans , Virus Replication
15.
J Viral Hepat ; 23(2): 68-79, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26344932

ABSTRACT

Hepatitis E is a systemic disease affecting the liver predominantly and caused by infection with the hepatitis E virus (HEV). HEV has marked genetic heterogeneity and is known to infect several animal species including pigs, boar, deer, mongoose, rabbit, camel, chicken, rats, ferret, bats and cutthroat trout. HEV is the sole member of the family Hepeviridae and has been divided into 2 genera: Orthohepevirus (mammalian and avian HEV) and Piscihepevirus (trout HEV). Human HEVs included within the genus Orthohepevirus are designated Orthohepevirus A (isolates from human, pig, wild boar, deer, mongoose, rabbit and camel). Hepatitis E is an important public health concern, and an estimated one-third of the world population has been infected with HEV. In recent years, autochthonous hepatitis E is recognized as a clinical problem in industrialized countries. Several animal species especially domestic swine, wild boar and wild deer are reservoirs of genotype HEV-3 and HEV-4 in these countries. Human infections occur through intake of uncooked or undercooked meat of the infected animals and pig livers or sausages made from these livers and sold in supermarkets. HEV can be transmitted through blood and blood component transfusions, and donor screening for HEV is under serious consideration. Chronic hepatitis E resulting in rapidly progressive liver cirrhosis and end-stage liver disease has been described in organ transplant patients. Ribavirin monotherapy attains sustained virological response in most patients. HEV 239 vaccine has been marketed in China and its long-term efficacy over four and a half years reported.


Subject(s)
Hepatitis E virus/classification , Hepatitis E/transmission , Liver/pathology , Zoonoses/virology , Animals , Antiviral Agents/therapeutic use , Hepatitis E/drug therapy , Hepatitis E/virology , Hepatitis E virus/genetics , Humans , Liver/virology , RNA, Viral/genetics , Ribavirin/therapeutic use , Viral Hepatitis Vaccines/immunology
16.
PLoS One ; 10(3): e0121450, 2015.
Article in English | MEDLINE | ID: mdl-25816332

ABSTRACT

BACKGROUND: Point-of-care tests provide a plausible diagnostic strategy for hepatitis C infection in economically impoverished areas. However, their utility depends upon the overall performance of individual tests. METHODS: A literature search was conducted using the metasearch engine Metta, a query interface for retrieving articles from five leading medical databases. Studies were included if they employed point-of-care tests to detect antibodies of hepatitis C virus and compared the results with reference tests. Two reviewers performed a quality assessment of the studies and extracted data for estimating test accuracy. FINDINGS: Thirty studies that had evaluated 30 tests fulfilled the inclusion criteria. The overall pooled sensitivity, specificity, positive likelihood-ratio, negative likelihood-ratio and diagnostic odds ratio for all tests were 97.4% (95% CI: 95.9-98.4), 99.5% (99.2-99.7), 80.17 (55.35-116.14), 0.03 (0.02-0.04), and 3032.85 (1595.86-5763.78), respectively. This suggested a high pooled accuracy for all studies. We found substantial heterogeneity between studies, but none of the subgroups investigated could account for the heterogeneity. Genotype diversity of HCV had no or minimal influence on test performance. Of the seven tests evaluated in the meta-regression model, OraQuick had the highest test sensitivity and specificity and showed better performance than a third generation enzyme immunoassay in seroconversion panels. The next highest test sensitivities and specificities were from TriDot and SDBioline, followed by Genedia and Chembio. The Spot and Multiplo tests produced poor test sensitivities but high test specificities. Nine of the remaining 23 tests produced poor test sensitivities and specificities and/or showed poor performances in seroconversion panels, while 14 tests had high test performances with diagnostic odds ratios ranging from 590.70 to 28822.20. CONCLUSIONS: Performances varied widely among individual point-of-care tests for diagnosis of hepatitis C virus infection. Physicians should consider this while using specific tests in clinical practice.


Subject(s)
Hepacivirus/pathogenicity , Hepatitis C/blood , Hepatitis C/pathology , Hepatitis C/virology , Humans , Point-of-Care Systems
17.
J Clin Exp Hepatol ; 4(3): 226-40, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25755565

ABSTRACT

BACKGROUND: Rapid point-of-care tests provide plausible diagnostic strategy for hepatitis B surface antigen (HBsAg) in low resource areas. However, their utility depends upon their overall performance. Our objective was to meta-analyze the diagnostic accuracy of rapid point-of-care tests for HBsAg. METHODS: Literature search was done with the help of a metasearch engine Metta, a query interface for retrieving articles from five leading medical databases. Studies that employed rapid point-of-care tests for detection of HBsAg and compared the results with reference test were included. Two reviewers performed quality assessment of the studies and extracted data for estimating test accuracy. Twenty-seven studies were meta-analyzed and stratified by multiple parameters. RESULTS: Twenty-seven studies had evaluated 49 test brands and generated 76 data points. Sensitivity of individual tests varied widely and were heterogeneous (range 43.5%-99.8%); while specificity estimates were more robust and close to 100% (range 90%-100%). Overall pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR and diagnostic odds ratio for all tests were 97.1% (95% CI, 96.1%-97.9%), 99.9% (CI, 99.8%-100%), 118.4 (CI, 84.7-165.5), 0.032 (CI, 0.023-0.045) and 4094.7 (CI, 2504.1-6600.8) respectively. This suggested high pooled accuracy for all studies. We found substantial heterogeneity between studies. Three factors (study location, reference standard and study score) appeared most strongly associated with test estimates and observed heterogeneity. The Determine test showed consistency in performance in studies done across developed and developing countries and the Determine and the BinaxNOW tests had significantly higher estimates than pooled estimates of remaining tests. Tests revealed analytical sensitivity of 4 IU/ml against manufacturer's claim of 0.5 IU/ml; reduced sensitivity with HBsAg mutants and poor performance in seroconversion panels. CONCLUSIONS: Tests with better analytical sensitivity need to be developed and their feasibility and outcomes in various clinical settings need to be addressed.

18.
Nat Prod Res ; 27(21): 2033-8, 2013.
Article in English | MEDLINE | ID: mdl-23941615

ABSTRACT

Phytochemical investigation of the aerial parts of Rhododendron lepidotum yielded 8-[2',6'-dimethoxy-4'-(1″,2″,3″-trihydroxy-propyl)-phenyl]-7-hydroxy benzopyranone (1), 3-O-ß-d-glycopyranosyl betulinic amide (2) and 8-hydroxy-7,7'-oxydicoumarin (4) and five known compounds. Among the known molecules, betulinic amide (3) was earlier reported as a semi-synthetic product. The structures of new molecules 1, 2 and 4 were elucidated on the basis of extensive spectroscopic investigations (1D NMR, 2D NMR and mass spectrometry).


Subject(s)
Rhododendron/chemistry , Inositol/analogs & derivatives , Inositol/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure , Oleanolic Acid/analogs & derivatives , Oleanolic Acid/chemistry
19.
Nat Prod Res ; 27(2): 171-5, 2013.
Article in English | MEDLINE | ID: mdl-22401597

ABSTRACT

Chemical investigation of low polar solvent extract of Salix caprea through chromatographic techniques led to the isolation of new triterpene as 1α,3ß,25-trihydroxy-9(11)-ene-16-one-9,10-seco-9,19-cyclolanostane (1) along with fatty alcohols. The structure of compound 1 was established by IR, HRESI/MS and NMR including 1D and 2D experiments. The compound 1 showed moderate in vitro antiplasmodial activity.


Subject(s)
Flowers/chemistry , Plant Extracts/analysis , Salix/chemistry , Triterpenes/analysis , Chloroform , Chromatography , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Molecular Structure , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plasmodium falciparum/drug effects , Triterpenes/isolation & purification , Triterpenes/pharmacology
20.
Fitoterapia ; 83(2): 281-5, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22119764

ABSTRACT

The ethylacetate and n-butanol fractions of ethanolic extract of Platanus orientalis leaves led to the isolation of new acylated flavonol glycoside as 3',5,7-trihydroxy-4'-methoxyflavonol 3-[O-2-O-(2,4-Dihydroxy)-E-cinnamoyl-α-L-rhamnopyranosyl-(1→6)-ß-D-glucopyranosyl (1→2)]-ß-D-glucopyranoside, along with seven known compounds. All the compounds were characterized by NMR including 2D NMR techniques. The isolates were evaluated for NF-κB, nitric oxide (NO), aromatase and QR2 chemoprevention activities and some of them appeared to be modestly active.


Subject(s)
Flavonols/pharmacology , Glycosides/pharmacology , Magnoliopsida/chemistry , Plant Extracts/pharmacology , Acylation , Aromatase/metabolism , Cell Line , Chemoprevention , Female , Flavonols/chemistry , Flavonols/isolation & purification , Glycosides/chemistry , Glycosides/isolation & purification , Humans , Magnetic Resonance Spectroscopy , Molecular Structure , NF-kappa B/metabolism , Nitric Oxide/metabolism , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Leaves/chemistry , Plants, Medicinal/chemistry , Quinone Reductases/antagonists & inhibitors , Quinone Reductases/metabolism
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