A comparative histological analysis of early and late graft dysfunction in different time zones following living donor liver transplantation

Background: Liver biopsy plays a crucial role in evaluating allograft dysfunction. Comprehensive analysis of the histological spectrum of complications, particularly rejection, in different time zones is lacking. Aim: To evaluate the histological spectrum of rejection, in four time zones, in a large Living donor liver transplant series. Patients and Methods: Retrospective analysis of 313 biopsies for the last 10 years of living donor liver transplantation (LDLT) recipients. 123 of which had rejection as diagnosis, were redistributed in four time zones [1-early (<3), 2-intermediate (3–6), 3 and 4-late (6–12 and > 12) months] and were assessed for sixteen histological parameters. Results: Biopsies in time zone 1 (26.5%), 2 (20.7%), 3 (24.6%), and 4 (28.1%)] were nearly equal. Multiple coexistent complications existed in 12% of the cases. Rejection diagnosed in time zone groups: 1 = 22 (17.9%), 2 = 27 (22%), 3 = 36 (29.3%), and 4 = 38 (30.9%). Portal inflammation mixed type (P < 0.000), portal vein (P = 0.001) and hepatic vein endothelialitis (P < 0.000), portal eosinophils (P = 0.001), and lymphocytic bile duct damage (P = 0.01) were most pronounced in group 1. Perivenulitis without hepatic vein endothelialitis was observed (P = 0.03) in groups 3, whereas bile duct atypia (P = 0.01) and duct loss (P < 0.000) were observed in group 4. Multiple episodes of rejection displayed significant association with central perivenulitis (P = 0.002) and bile duct loss (P < 0.001). Conclusions: Histological analysis in large series of LDLT recipients highlights the spectrum of complications in different time zones. Late acute and chronic rejection occurred as early as 3 months posttransplant. Central perivenulitis and bile duct atrophy were associated with repeated episodes of rejection and deterioration.

Liver transplant biopsy interpretation: Diagnostic considerations and conundrums

Liver transplantation is now a well-established therapeutic strategy for irreversible acute and chronic liver diseases. There is a broad spectrum of complications encountered in early and late period after transplantation and these contribute to significant morbidity and mortality. Distinguishing among these complications often requires interpretation of allograft biopsies. Histology is the gold standard for the diagnosis of rejection. However, interpretation of these biopsies is quite challenging due to the atypical and complex histomorphology. Multiple simultaneous insults, effects of immunosuppression (IMS), de novo complications, and presentations distinct from non-transplant setting are a few cardinal concerns. Awareness of the time period of occurrence of various complications, the most characteristic histological features or patterns, and distinguishing features between various complications are crucial. The management can be completely divergent; hence, recognition of dominant problem and interpretation in appropriate clinical context is much needed. This review focuses on histopathology of major complications accountable for early and late graft dysfunction. Tabulation of clinico-pathological features to distinguish various complications helps to solve the conundrums and arrive at the correct diagnosis.

Non-Alcoholic Fatty Liver Disease and other Non-Communicable Diseases: Time for an Integrated Approach

Non-Alcoholic fatty liver disease (NAFLD) is a broad term covering a spectrum of conditions ranging from hepatic steatosis, steatohepatitis and cirrhosis. NAFLD is highly prevalent across all regions of the world with its global prevalence of 25.2%(95%CI:22.1-28.7). It is commonly referred as the ‘hepatic manifestation’ of metabolic syndrome (MetS). Moreover, it is strongly associated with the individual components as well as MetS as a whole. NAFLD has been independently associated with other non-communicable diseases (NCDs) like chronic kidney disease (CKD), Polycystic ovary Syndrome (PCOS), Stroke and Cancers. This strong association of NCDs with NAFLD not only affects the prevalence but also the progression and management of the disease. Thus, this review aims at highlighting the association of NAFLD with other NCDs. A literature search was undertaken in the MEDLINE database using the necessary MeSH terms. The review concludes NAFLD is a systemic disease, not just confined to liver-specific morbidity and mortality, but also associated with numerous extra-hepatic manifestations, such as metabolic syndrome, cardiovascular diseases, chronic renal diseases, and malignancy. With coexistence of NAFLD with various NCDs it is expected to become the most overwhelming liver disease in the world in coming years. Hence, to reduce medical and economic impact associated with these comorbidities, it is recommended that all countries should estimate and predict the burden on comorbidities associated with NAFLD and galvanize its health resources in providing integrated therapeutic approaches for management of NAFLD and related comorbidities at an early stage.

Comparative evaluation of rotational stability and visual outcome of toric intraocular lenses with and without a capsular tension ring

Purpose: To evaluate the rotational stability of toric intraocular lens (IOL) when co-implanted with a capsular tension ring (CTR) as compared to that of a toric IOL without a CTR. Methods: This was a prospective randomized clinical trial performed in a tertiary care centre in India. Fifty adult human eyes with visually significant cataract and regular corneal astigmatism ?1.5D divided into two groups of 25 eyes each, A and B by simple randomization. Eyes with corneal pathology, lens subluxation, and a specular endothelial cell count <2000/mm2 were excluded from the study. The eyes in both the groups underwent standard phacoemulsification and were implanted with a toric IOL. In Group A, a CTR was put in the bag before IOL implantation. The groups were called for follow-up on day 1, 1 week, 1 month, and 3 months, postoperatively. The axis of the toric IOL on each visit was measured by slit lamp imaging in retroillumination and analyzed digitally. Results: Mean rotation of toric IOL at 3 months postoperatively was 1.85 ± 1.72° in Group A and 4.02 ± 2.04° in Group B. The difference was statistically significant (P = 0.003). Conclusion: Coimplantation of a CTR is a safe and effective technique for ensuring better rotational stability of toric IOLs

Demographic profile of head injury cases in Agra region.

Head injury is a serious health problem throughout the world. Increasing vehicles on roads work as catalyst for high incidence of casualties especially of Cranio-cerebral injuries. This is an autopsy based study of head injury cases, conducted in the Department of Forensic Medicine, S.N. Medical College Agra in year 2009-2010 for their demographic and etiological profile. Majority of the victims of head injury are male (76%) and of 3rd – 4th decade of life (54.4%). 66.4% head injury cases due to accident, Road traffic accident is the single largest cause i.e. 59.2%; out of which two wheelers are responsible for one-third (33%) of the casualties. Most common external injury is laceration of the scalp with or without contusion. Fracture of skull bones (97.2% cases; mostly fissured and comminuted fracture of parietal & temporal) and intracranial hemorrhages (96.4%) are seen in almost all the cases. Contre-coup injuries seen in about 2.8% cases, contre-coup haemorrhage observe mostly fronto-temporal area. Majority of the victim died on the spot or in the way to hospital without any medical assistance where the Cause of death mostly haemorrhage and shock.

Blunt injuries of chest: A medicolegal analysis.

Chest injuries are always a great challenge for medical professionals as two of the vital organs, which are present there, very often involved & damaged causing excessive bleeding and death. These injuries are usually caused by blunt forces or sharp penetrating weapons. Here in this paper 60 cases of chest injuries by blunt forces are studied for their epidemiological, medicolegal and clinico-pathological aspects. Most of them are adult/ middle aged male between 20-50years of age, hit or run over by heavy vehicles in road traffic accidents. Lungs are lacerated in almost all the cases and internal haemorrhage & shock is the prime cause of death. Heart, aorta & other organs were also involved in substantial number of cases. Though majority of them died within two hours, either on the spot or in the way to the hospital, an attempt is also made to correlate the prognosis & the nature of injuries.

Incorporation and biodegradation of hydroxyapatite-tricalcium phosphate implanted in large metaphyseal defects--an animal study.

Incorporation and biodegradation of hydroxyapatite(HA)-tricalcium phosphate(TCP) granules implanted in 5 x 5 x 5 mm distal femoral metaphyseal defects created in 18 adult rabbits were studied. In two rabbits, the defects were left to heal spontaneously without any implant. Roentgenographic and histological study by light microscopy was done on silver nitrate stained undecalcified sections as well as haematoxylin-eosin stained decalcified sections. The synthetic HA-TCP was biocompatible and produced no adverse reactions. The implant was osteoconductive and allowed good new bone formation to occur, mainly from periphery to center, but mature trabeculae could be delineated only at 4-6 months. The HA-TCP biomaterial had very low biodegradability with marked amount of intact implant still present at final follow up. Bonding between implant and bone, though a close biological bond, was not uniformly strong. Rate of bone ingrowth was very slow and large areas of implant at center did not show new bone formation at 12 months.

Symmetric peripheral gangrene with mixed malaria.

Symmetric peripheral gangrene (SPG) in a case of mixed malaria (P. falciparum and P. vivax) is a rare and relatively unknown complication of malaria. We report a case of 10-yr-old female with mixed malaria infection and SPG (Symmetric Peripheral Gangrene) of foot, which is most likely due to interaction between parasite factors (P. Falciparum and P. viavx) and host factors.

In vivo model for dyslipidemia with diabetes mellitus in hamster.

Due to similarities in lipid metabolism to those in humans, hamster is considered as a good model for the study of regulatory mechanisms of plasma lipoproteins in response to cholesterol or fatty acid-enriched diet. This model of hyperlipidemia has been modified to produce dyslipidedmia with diabetes complexities by feeding with high fat diet added with 9% (w/w) fructose. Feeding this diet to hamster for 10 days markedly increases plasma levels of triglyceride, cholesterol, fatty acids followed by a significant increase in glycerol, beta lipoproteins, high density lipoprotein, glucose and glycosylated proteins. This model is being used for research and development of lipid lowering drugs with hypoglycemic activity in collaboration with Novo Nordisk, Denmark. The modified high fat diet formulation has now been prepared (Research diet D.99122211) and supplied by Research Diets Inc, Burnswick USA.

Stones associated renal pelvic malignancies.

BACKGROUND: The clinico-pathological characteristics of renal pelvic malignancies associated with stones were retrospectively analyzed. AIMS: The main objective was to define the biological behavior and prognostic factors for these malignancies. SETTINGS & DESIGN: The tumors were classified according to the pathological types. The clinical data, imaging features and pathological features were analyzed with relation to prognosis. MATERIAL AND METHODS: Eighteen cases of malignancies associated with stone disease were retrospectively studied. The institute review board permitted the study. RESULTS: High incidence (15/18) of squamous cell carcinoma (SCC) was noted. The prognosis in this group of patients was uniformly poor. The median survival time was 3.6 months in the SCC group, 7.5 months in the Transitional Cell Carcinoma (TCC) group and 24 months in the Adenocarcinoma (AC) group. Infectious and systemic symptoms were noted in the majority of the patients. Preoperative Imaging techniques revealed tumor in only 2 cases. Both underwent radical extirpation and the median survival is 18 months till date. In the other 16 patients, where the initial diagnosis was made only on histological analysis of incomplete nephrectomy specimens, the survival was 3.56 months. All patients had prolonged history of staghorn stone disease with associated non-functioning kidney. We found that the main prognostic factor was the stage of the disease. CONCLUSIONS: Malignancies associated with stone disease have insidious onset of clinical symptoms and need a high degree of suspicion to identify them pre-operatively. The grave prognosis associated with incomplete excision makes it imperative to diagnose them earlier.

Identification of amastigote-specific antigens of Leishmania donovani using kala-azar patient sera.

Antigenic characterization of the soluble fraction of axenic amastigotes of Leishmania donovani ( strain Dd8, causative agent of Indian kala-azar) and their comparison with promastigotes is reported. The axenic amastigotes were assessed for their immunological status employing anti-A2 monoclonal antibody which is extremely specific for L. donovani amastigotes. SDS-PAGE of 35[S] methionine labeled proteins of the two parasite stages exhibited few stage specific and some conserved antigens in both the stages. An increased synthesis of heat shock proteins was observed in axenic amastigotes. Western blot experiments employing sera of kala azar positive patients identified immunodominent antigens of 116,83,26 and 12 kDa in axenic amastigotes which were not present in promastigotes. These amastigote stage specific antigens may have immense potential in immunodiagnosis and prophylaxis of kala-azar.

Meningoencephalitis in brucellosis.

Human brucellosis, more specifically neurobrucellosis, is a less commonly reported disease in India; although, animal brucellosis and seroprevalence in specific areas is well reported. We are reporting 4 cases of neurobrucellosis presenting as meningoencephalitis. Diagnosis was confirmed by serological test and agglutination titre was > 1:320 in all the patients. All these patients had close contact with animals and history of raw milk ingestion was present in 3 cases. The aim of presenting these cases is to create awareness among physicians while treating meningitis in persons, engaged in occupations related to brucellosis or having a history of ingestion of raw milk or milk product.

Clinical profile of neurobrucellosis--a report on 12 cases from Bikaner (north-west India).

OBJECTIVE: To study the spectrum of neurobrucellosis in a prospective study at Bikaner which is supposed to be uncommon in India. METHOD: This study was done on admitted patients of brucellosis from June 1996 to June 1999 in whom the diagnosis was done by history of exposure to animals, fever and arthralgia and demonstration of brucella antibody titres in serum 1:160. CSF examination was done in all the patients. All cases were treated by combination of doxycycline 100 mg twice daily, rifampicin 900 mg daily for 6-8 weeks and injection streptomycin 0.75 to 1 gm i.m. per day for initial 14 days. Detailed neurological examination and antibody titres of serum and CSF again measured at the end of treatment. RESULTS: Twelve out of 92 patients revealed evidence of neurobrucellosis in which four cases were of meningoencephalitis, two cases of myelitis leading to spastic paraparesis, five cases of polyradiculoneuropathy and one case of polyneuroradiculomyeloencephalopathy. The treatment regimen used was associated with a high cure rate and significant reduction in antibody titres in serum and CSF. CONCLUSION: Neurobrucellosis is an uncommon but serious manifestation affecting central and peripheral nervous system. The clinical profile of the disease mimicks closely to commonly seen neurological infective diseases like tubercular meningitis, viral encephalitis, aseptic meningitis, cerebral malaria and viral encephalopathy. Serum and CSF testing for brucella antibody titre is an important test for the diagnosis. Blood culture is not an ideal test for neurobrucellosis because of low yield and longer time required for the diagnosis. High degree of suspicion is prudent for the diagnosis. High degree of cure rate can be achieved by treatment with present regimen in a disease which is otherwise having high mortality and morbidity.

Testicular biopsy in infertility.

Eighty-eight infertile couples attended the infertility clinic. Semen analysis was abnormal in 64 cases. The cases were divided into 3 groups according to sperm count:Group I (count zero), group II (count < 20 million/ml) and group III (20-50 million/ml). The morphology of testicular biopsy categorised into 5 groups were normal--10(15.63%), hypospermatogenesis--42(65.63%), the Sertoli cell only syndrome--2(3.13%), maturation arrest--2(3.13%) and tubular hyalinization--8(12.50%). Quantitative analysis of biopsies was done using mean Johnson score(MJS) and Silber score(SS). The morphology in any single section was not uniform but of mixed type. Normal spermatogenesis in azoospermics indicated bilateral ductal obstruction. As compared to MJS, SS showed a more direct correlation between number of mature spermatids per tubular cross section and sperm count in unobstructed cases.

Evaluation of serological status of rubella & mumps in children below five years.

A cross-sectional study was carried out on 321 serum samples to detect rubella and mumps antibodies in children below five years and to assess the optimum age for immunization against rubella and mumps. Seropositivity to rubella was 33.3 per cent in children below nine months, 16.9 per cent at 9-12 months and 25.5 per cent by two years. Mean antibody levels for rubella were low at nine months to one year and remained so till five years of age. Similarly, seropositivity for mumps was 53.3 per cent below nine months, 20.3 per cent at 9-12 months and 40 per cent by two years. Mean antibody levels for mumps were low between nine months to two years with a slight rise by five years. The findings suggest that a large majority of children are at risk by the age of nine months in our population and the measles, mumps and rubella (MMR) vaccination at this age may be most beneficial.

Aetiology of chronic diarrhoea in tropical children.

AIM: We studied the causes and presentations of chronic diarrhoea in post-weaned children. METHODS: Forty seven children (6 months to 12 years) with diarrhoea of more than 2 weeks duration were recruited and subjected to detailed clinical examination and investigations. RESULTS: Primarily on the basis of history, clinical examination and duodenal biopsy, children could be classified into 5 groups namely tropical enteropathy (46.8%), irritable bowel syndrome (10.6%), giardiasis (14.8%), celiac disease (6.8%) and non specific diarrhoea (21.8%). Children with tropical enteropathy improved with broad spectrum antimicrobial therapy, those with irritable bowel syndrome and non specific chronic diarrhoea with dietary interventions while children with celiac disease required definite withdrawal of gluten from diet.