The "Christmas Tree" Sign on MR Cholangiogram in Left-Sided Cholangiohepatitis.

We report the "Christmas tree" sign on the magnetic resonance cholangiogram in two patients with left-sided cholangiohepatitis.

Role of inflammatory and hemostatic biomarkers in Alzheimer's and vascular dementia - A pilot study from a tertiary center in Northern India.

INTRODUCTION: A reliable plasma biomarker in differentiating between Alzheimer's disease (AD) and Vascular dementia (VaD) is the need of the hour, in most memory clinics. Even though there is no disease modifying treatment, it is important to know the type of dementia for both symptomatic treatment and prognostication. METHODS: Neuropsychological assessment, MRI brain, FDG-PET brain and CSF biomarkers of AD (Aß42 and total tau) were used for establishing the diagnosis of Mild Cognitive Impairment (MCI), AD or VaD. RESULTS: 68 diagnosed patients of AD/MCI/VaD were included. FDG PET brain, plasma fibrinogen, d dimer, IL6 and CRP were done in all 68 patients while 48 patients underwent CSF biomarker analysis. Sixteen patients had MCI, of which 11 were MCI-AD and 5 were MCI-VaSC. There were 41 patients with AD (Mild AD-9, Mod AD-23, Severe AD-9) and 11 patients with VaD. Alzheimer group (MCI-AD and AD) and Vascular group (MCI VaSC & VaD) consisted of 52 and 16 patients respectively. Alzheimer and Vascular groups did not exhibit significant difference in IL6 and CRP levels. Plasma fibrinogen levels were significantly higher in VaD and vascular group as compared to Alzheimer group. But MCI-VaSC was not significantly different from MCI-AD. Plasma d dimer levels were significantly higher in all vascular subgroups compared to Alzheimer subgroups except between MCI-VaSC and MCI-AD. CONCLUSION: Hemostatic biomarkers were higher in Vascular group compared to Alzheimer group whereas there was no difference in inflammatory biomarkers. But the sensitivity and specificity of fibrinogen and d-dimer were not high enough for routine clinical use. Further studies in a larger sample are required to confirm these results.

Cytokines do play a role in pathogenesis of tuberculous meningitis: A prospective study from a tertiary care center in India.

BACKGROUND: Though animal studies have suggested a role for proinflammatory cytokines in pathogenesis their exact role in pathogenesis of human meningeal tuberculosis continues to be controversial with different studies yielding contradictory results. AIM AND OBJECTIVES: To study the levels of proinflammatory cytokines in serum and cerebrospinal fluid (CSF) of patients with tubercular meningitis (TBM) and to determine whether these correlate with disease severity. PATIENTS AND METHODS: Present study included 146 patients with TBM (90- Definite TBM; 56- Probable TBM), diagnosed according to criteria laid by Ahuja et al. which were modified to include CSF nucleic acid based tests. Serum (n=146) and CSF (n=140) levels of various proinflammatory cytokines (IL-1ß, IL-2, IL-6, TNF-α and IFNγ) were compared between TBM patients and healthy volunteers (n=99). These levels were correlated with various clinical, radiological and CSF parameters of TBM patients. RESULTS: Proinflammatory cytokines include cytokines which promote systemic inflammation. In current study, the serum and CSF levels of various cytokines (IL-2, IL-4, IL-6, IL-1ß, IFN-γ and TNF-α) were significantly elevated in TBM patients compared to controls. A significant correlation was found between a) Higher stage of TBM and various cytokines (except for serum IL-6 and CSF IFN-γ); b) High CSF TNF-α, IL-4 and IL-1ß with severity of hydrocephalus; c) High CSF IL1ß and IFN-γ with presence of exudates on MRI; d) Serum and CSF levels of all cytokines with poor outcome as determined by death or as defined by S and E ADL (Schwab and England activities of daily living) score or by GOS (Glasgow outcome scale) (except for interferon gamma); and e) Serum and CSF IL-4 and IL1ß with presence of infarcts on MRI brain. CONCLUSION: Proinflammatory cytokines play an important role in the pathogenesis of TBM and contribute significantly towards severity of disease.

Laparoscopic Transplantation Following Transvaginal Insertion of the Kidney: Description of Technique and Outcome.

Laparoscopic kidney transplantation (LKT) is well accepted modality of treatment for ESRD patients at our center. Usually, the kidney is inserted through small Pfannenstiel incision. With the permission of the Internal Review Board, we carried out LKT in eight female recipients following insertion of the kidney through the vagina. The kidney was procured by the retroperitoneoscopic approach. Antibiotic prophylaxis was given. All cases were carried out successfully with immediate graft function and 100% graft and patient survival at 1 year of follow-up. Estimated glomerular filtration rate at 1 month and 1 year was similar to eight randomly selected female recipients who underwent open kidney transplantation (OKT). No analgesia was required in seven out of eight patients after the 3rd postoperative day. In summary, vaginal insertion of kidney and LKT is safe and feasible in a selected group of patients. It is associated with better analgesia and has similar allograft function as compare to OKT.

'Single-Sitting' Laparoscopic Cholecystectomy and Endoscopic Removal of Common Bile Duct Stone for Cholelithiasis and Choledocholithiasis: a Feasibility Study.

'Single-sitting' laparoscopic cholecystectomy followed by endoscopic common bile duct clearance is emerging as a viable option for management of cholelithiasis and concomitant choledocholithiasis. The only disadvantage of the procedure is logistical since it requires co-ordination between two teams-the surgeons and the endoscopists. This limitation can be overcome in centres where both the procedures are performed by one team. With a considerable experience in endoscopy, we conducted a prospective study in a select group of patients to assess the feasibility of this single-sitting approach. The study included 38 patients with a radiological diagnosis of choledocholithiasis or jaundice at presentation. After laparoscopic cholecystectomy, the patients were turned prone and subjected to endoscopic retrograde cholangiogram, sphincterotomy and extraction of the common bile duct stone. The procedure was successful in 33 (87 %) of patients. The mean procedure time and hospital stay were 2 h, 20 min and 2 days, respectively. None of the patients had any major complications. We conclude that in a select group of patients, single-sitting laparoscopic cholecystectomy followed by endoscopic clearance of the common bile duct stone is safe and effective.

Spilled Gallstone: Late Presentation.

Spilled gallstone, in a female patient, presented with an abscess 2 years after laparoscopic cholecystectomy. Computerized tomography scan of the abscess cavity containing the spilled stone that clinched the diagnosis has been presented.

Outcome of live and deceased donor renal transplantation in patients aged ≥55 years: A single-center experience.

Renal transplantation (RTx) has now become an accepted therapeutic modality of choice for elderly ESRD patients. This single-center study was undertaken to evaluate the outcome of RTx in ESRD patients ≥55 years. A total of 103 patients underwent RTx 79 living related living donors [LD], 24 deceased donors [DD]) at our center. Post-transplant immunosuppression consisted of calcineurin inhibitor-based regimen. The mean donor age was 58.3 years in the LD group and 59.5 years in the DD group. Male recipients constituted 92% in LD and 75% in DD group. In living donor renal transplantation, 1- and 5-year patient survival was 93% and 83.3% respectively and death-censored graft survival was 97.3% and 92.5% respectively. There were 12.6% biopsy proven acute rejection (BPAR) episodes and 12.6% patients were lost, mainly due to infections. In deceased donor renal transplantation, 1- and 5-year patient survival was 79.1% and 74.5% respectively and death-censored graft survival was 95.8% and 85.1% respectively. There were 12.5% BPAR episodes and 25% of patients were lost, mainly due to infections. RTx in ESRD (≥55 years) patients has acceptable patient and graft survival if found to have cardiac fitness and therefore should be encouraged.

Primary tuberculous pyomyositis of quadriceps femoris in an immunocompetent individual.

Primary tuberculous pyomyositis is a rare manifestation of musculoskeletal tuberculosis especially in immunocompetent individuals without a focus of tuberculosis in the body and the underlying bone disease. It can cause a diagnostic dilemma for a physician and surgeon because of its similar presentation to soft tissue sarcomas, hematomas, and myopathies. We present a case of a 45-year-old immunocompetant gentleman with a thigh swelling with sepsis due to pyomyositis of the quadriceps requiring a multimodal management of drainage of abscess, debridement of devitalized muscle, antitubercular drugs, and physiotherapy. In a tubercular endemic country, a high index of suspicion is required to diagnose this disease which can be cured completely.

Catatonia in systemic lupus erythematosus: a case report and review of literature.

Although, neuropsychiatric morbidity is quite high in patients with systemic lupus erythematosus (SLE), catatonia has been rarely reported. We report a case of a 22-year-old female who presented with catatonic symptoms at the time of relapse of SLE and have discussed the presentation in the context of existing literature with regard to phenomenology of catatonia, psychiatric co-morbidity and treatment of catatonia in patients with SLE.

Non-traumatic myelopathy at the Chris Hani Baragwanath Hospital, South Africa--the influence of HIV.

BACKGROUND: Non-traumatic myelopathy from developing regions has been described widely. In these regions infections, mainly tuberculosis, followed by acute transverse myelitis and neoplasms, dominate. These are also regions of high HIV prevalence. In developed regions, the most prominent reported spinal cord disease in HIV/AIDS is vacuolar myelopathy (VM). Other myelopathy causes in HIV/AIDS include opportunistic infections, neoplasms, vascular lesions and metabolic disease. In developing regions, opportunistic infections are more commonly encountered with VM occurring less frequently. AIM: To determine the influence of HIV on the myelopathy spectrum in an HIV endemic region. DESIGN: Prospective case series. METHODS: Hundred unselected consecutive in-patients admitted with myelopathy were studied. Myelopathy aetiologies were established by collating information obtained from magnetic resonance imaging (MRI) scans, CSF and blood studies, CXR findings, non-neurological illness and response to treatment. Data were analysed in terms of two cohorts, HIV positive and HIV negative. RESULTS: Approximately 50% of the patients presenting and admitted to our hospital with non-traumatic myelopathy are HIV positive. The HIV positive myelopathy patients were younger (20-40 years) and had infectious aetiologies. Tuberculosis was the most frequently identified cause of myelopathy. The majority of HIV-positive patients had advanced HIV infection. Anti-retroviral treatment did not influence myelopathy aetiologies. The HIV-negative patients were older and had neoplasms, followed by degenerative spondylosis as the main myelopathy causes. CONCLUSION: HIV influences the non-traumatic myelopathy spectrum in regions with high HIV prevalence. Empiric treatment of HIV-myelopathy patients with anti-tuberculous medications where resources are severely limited has merit.

A novel mutation (S227T) in domain II of the envelope gene of Japanese encephalitis virus circulating in North India.

Japanese encephalitis (JE) is an important arboviral infection of public health concern. There is a significant variation in mortality (10-30%) in JE viral infection. Epidemics of JE have become regular features in the northern states of India. The recent resurgence of the A226V mutation leading to a widespread Chikungunya epidemic motivated the investigators to search for any such mutational occurrence with Japanese encephalitis virus (JEV) isolated from this region. This study looked for mutation of clinical strains at amino-acid positions 176, 177, 227, 244, 264 and 279. A novel mutation S227T was detected corresponding to the loop region of domain II, E gene of JEV in comparison to Indian and other isolates from different parts of the world. Genotype III was found to be circulating in this geographical area. Further studies are required to ascertain its role in JE pathogenesis and vector competency.

A diagnostic and therapeutic scheme for a solitary cysticercus granuloma.

BACKGROUND: Solitary cysticercus granuloma (SCG) is one of the most common forms of presentation of neurocysticercosis (NCC). The diagnostic workup and management approach to this condition remain uncertain and controversial. OBJECTIVE: To review evidence and develop a consensus approach to the diagnosis and treatment of SCG. METHODS: A multidisciplinary expert group meeting was convened in order to review and discuss various aspects of management of patients with SCG. Evidence reviewed was classified and a consensus was evolved according to standard protocols. RESULTS: SCG is commonly recognized on CT as an enhancing lesion measuring <20 mm. Further evaluation with MRI does not add much information. The use of antihelminthic agents (specifically, albendazole in combination with corticosteroids) and corticosteroids alone have been shown to improve radiologic resolution and seizure outcome in patients with SCG. However, the sizes of the effects are modest. By convention, all patients with SCG presenting with seizures are initiated on antiepileptic drugs (AEDs). Available evidence suggests that withdrawal of AEDs after complete resolution of the SCG is safe. There is a high risk of seizure relapse after AED withdrawal in patients with calcific residue following resolution of the SCG. The duration of AED prophylaxis in these individuals is unclear. CONCLUSIONS: It is desirable to have large, multicenter trials with sufficiently long follow-up, comparing outcomes with the use of antihelminthics with or without corticosteroids and corticosteroids alone in order to dissect out the benefits accrued due to each of these classes of drugs.

Acro-osteolysis and mononeuritis multiplex as a presenting symptom of systemic angiitis of Wegener's type.

Wegener's granulomatosis is a multisystem disorder involving small- and medium-sized vessels, leading to granuloma formation and involvement of upper and lower respiratory tract with or without glomerulonephritis. However, limited forms of angiitis and granulomatosis of the Wegener's type with oligosymptomatic and atypical site involvement are known to occur. We present here a rare case of limited form of angiitis and granulomatosis of Wegener's type who presented sequentially with spontaneous resorption of digits with acro-osteolysis and mononeuritis multiplex over a period of 10 months. His vasculitic workup revealed high proteinase 3 antibodies (c-ANCA) titers and an almost asymptomatic lung involvement, detected on high-resolution computed tomography of chest. The patient was aggressively treated with immunosuppressive therapy, following which he showed good improvement.

Combined administration of iron and monoisoamyl-DMSA in the treatment of chronic arsenic intoxication in mice.

Co-administration of iron in combination with monoisoamyl dimercaptosuccinic acid (MiADMSA) against chronic arsenic poisoning in mice was studied. Mice preexposed to arsenic (25 ppm in drinking water for 6 months) mice were treated with MiADMSA (50 mg/kg, intraperitoneally) either alone or in combination with iron (75 or 150 mg/kg, orally) once daily for 5 days. Arsenic exposure led to a significant depletion of blood delta-aminolevulinic acid dehydratase (ALAD) activity, hematocrit, and white blood cell (WBC) counts accompanied by small decline in blood hemoglobin level. Hepatic reduced glutathione (GSH) level, catalase and superoxide dismutase (SOD) activities showed a significant decrease while, oxidized glutathione (GSSG) and thiobarbituric acid-reactive substances (TBARS) levels increased on arsenic exposure, indicating arsenic-induced hepatic oxidative stress. Liver aspartate and alanine transaminases (AST and ALT) activities also decreased significantly on arsenic exposure. Kidney GSH, GSSG, catalase level and SOD activities remained unchanged, while, TBARS level increased significantly following arsenic exposure. Brain GSH, glutathione peroxidase (GPx), and SOD activities decreased, accompanied by a significant elevation of TBARS level after chronic arsenic exposure. Treatment with MiADMSA was marginally effective in reducing ALAD activity, while administration of iron was ineffective when given alone. Iron when co-administered with MiADMSA restored blood ALAD activity. Administration of iron alone had no beneficial effects on hepatic oxidative stress, while in combination with MiADMSA it produced significant decline in hepatic TBARS level compared to the individual effect of MiADMSA. Renal biochemical variables were insensitive to any of the treatments. Combined administration of iron with MiADMSA also had no additional beneficial effect over the individual protective effect of MiADMSA on brain oxidative stress. Interestingly, combined administration of iron with MiADMSA provided more pronounced depletion of blood arsenic, while no additional beneficial effects on tissue arsenic level over the individual effect of MiADMSA were noted. The results lead us to conclude that iron supplementation during chelation has some beneficial effects particularly on heme synthesis pathway and blood arsenic concentration.

Hyperhomocysteinemia as a risk factor for ischemic stroke: an Indian scenario.

BACKGROUND: Hyperhomocysteinemia has been proposed as an important risk factor for ischemic stroke worldwide, but data available from the Indian subcontinent is scarce. AIM: To study homocysteine levels in patients with ischemic stroke and compare it with age- and sex-matched controls. SETTINGS AND DESIGN: Case-control prospective study. MATERIALS AND METHODS: Fifty-seven patients with ischemic stroke and 30 controls were recruited for the study. They were subdivided into two subgroups (< 40 years and> 40 years of age) and plasma fasting total homocysteine (tHcy) levels were measured. STATISTICAL ANALYSIS USED: Student's 't' test and chi-square test. RESULTS: The tHcy were significantly high in patients with stroke, compared to controls (9.91 +/- 2.25 vs 8.00 +/- 2.74 micromol/l; P vs 8.45 +/- 2.72 micromol/l; P = 0.01) and female patients compared to controls (9.08 +/- 1.81 vs 6.79 +/- 2.60 micromol/l; P = 0.04). The tHcy levels were significantly high in patients with hypertension compared to normotensive patients (10.96 vs 9.49 micromol/l; P = 0.01) and smokers compared to nonsmokers (11.17 vs 9.33 micromol/l; P = 0.01). CONCLUSIONS: Hyperhomo-cysteinemia emerged as an important independent risk factor for ischemic stroke. A strong positive correlation was also observed between hypertension, smoking, and high-tHcy levels in the present study.

Management of HIV-associated focal brain lesions in developing countries.

BACKGROUND: HIV-associated focal brain lesions (HFBL) are caused by opportunistic infections, neoplasms, or cerebrovascular diseases. In developed countries, toxoplasma encephalitis (TE) is the most frequent cause, followed by primary CNS lymphoma (PCNSL). Guidelines based on these causes however are poorly suited to developing countries, where treatable infections predominate as causes of HFBL. AIM: To determine a practical approach to the management of HFBL in developing countries. DESIGN: Case series. METHODS: Patients (n = 32) were managed based on presumed aetiologies of the focal brain lesions, determined by collating information from CT scans, CSF and blood studies, concurrent non-neurological illness and response to treatment. RESULTS: The principal presumed cause of HFBL was tuberculosis (69%). The therapeutic response was good in 69% of patients. DISCUSSION: In developing countries, infections are the predominant cause of HFBL, the principal causes being infections that are endemic to the populations being studied. Empiric treatment based on limited investigations should be directed according to the nature of such infections. A modified algorithm is proposed.

Lenercept (p55 tumor necrosis factor receptor fusion protein) in severe sepsis and early septic shock: a randomized, double-blind, placebo-controlled, multicenter phase III trial with 1,342 patients.

OBJECTIVE: Phase III study to confirm a trend observed in a previous phase II study showing that a single dose of lenercept, human recombinant p55 tumor necrosis factor receptor-immunoglobulin G1 (TNFR55-IgG1) fusion protein, decreased mortality in patients with severe sepsis or early septic shock. DESIGN: Multicenter, double-blind, phase III, placebo-controlled, randomized study. SETTING: A total of 108 community and university-affiliated hospitals in the United States (60), Canada (6) and Europe (42). PATIENTS: A total of 1,342 patients were recruited who fulfilled the entry criteria within the 12-hr period preceding the study drug administration. INTERVENTION: After randomization, an intravenous dose of 0.125 mg/kg lenercept or placebo was given. The patient was monitored for up to 28 days, during which standard diagnostic, supportive, and therapeutic care was provided. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was 28-day all-cause mortality. Baseline characteristics were as follows: a total of 1,342 patients were randomized; 662 received lenercept and 680 received placebo. The mean age was 60.5 yrs (range, 17-96 yrs); 39% were female; 65% had medical admissions, 8% had scheduled surgical admissions, and 27% had unscheduled surgical admissions; 73% had severe sepsis without shock, and 27% had severe sepsis with early septic shock. Lenercept and placebo groups were similar at baseline with respect to demographic characteristics, simplified acute physiology score II-predicted mortality, profiles of clinical site of infection and microbiological documentation, number of dysfunctioning organs, and interleukin-6 (IL-6) plasma concentration. Lenercept pharmacokinetics were similar in severe sepsis and early septic shock patients. Tumor necrosis factor was bound in a stable manner to lenercept as reflected by the accumulation of total serum tumor necrosis factor alpha concentrations. There were 369 deaths, 177 on lenercept (27% mortality) and 192 on placebo (28% mortality). A one-sided Cochran-Armitage test, stratified by geographic region and baseline, predicted 28-day all-cause mortality (simplified acute physiology score II), gave a p value of .141 (one-sided). Lenercept treatment had no effect on incidence or resolution of organ dysfunctions. There was no evidence that lenercept was detrimental in the overall population. CONCLUSION: Lenercept had no significant effect on mortality in the study population.

Rational design of a potent, long-lasting form of interferon: a 40 kDa branched polyethylene glycol-conjugated interferon alpha-2a for the treatment of hepatitis C.

A potent, long-lasting form of interferon alpha-2a mono-pegylated with a 40 kilodalton branched poly(ethylene glycol) was designed, synthesized, and characterized. Mono-pegylated interferon alpha-2a was comprised of four major positional isomers involving Lys31, Lys121, Lys131, and Lys134 of interferon. The in vitro anti-viral activity of pegylated interferon alpha-2a was found to be only 7% of the original activity. In contrast, the in vivo antitumor activity was severalfold enhanced compared to interferon alpha-2a. Pegylated interferon alpha-2a showed no immunogenicity in mice. After subcutaneous injection of pegylated interferon alpha-2a, a 70-fold increase in serum half-life and a 50-fold increase in mean plasma residence time concomitant with sustained serum concentrations were observed relative to interferon alpha-2a. These preclinical results suggest a significantly enhanced human pharmacological profile for pegylated interferon alpha-2a. Results of Phase II/III hepatitis C clinical trials in humans confirmed the superior efficacy of pegylated interferon alpha-2a compared to unmodified interferon alpha-2a.

Identification of a calcium channel modulator using a high throughput yeast two-hybrid screen.

The interaction of the N-type calcium channel beta3 subunit with the alpha1B subunit alters the activation/inactivation kinetics and the maximal conductance of the channel. The defined protein-protein interaction of the human alpha1B and beta3 subunits provides a target for small-molecule modulation of N-type channel activity. We describe a high throughput screen based on a counterselection yeast two-hybrid assay, which was used to identify small molecules that disrupt alpha1B-beta3 subunit interactions and inhibit N-type calcium channel activity. These small molecules may be a new class of calcium channel antagonists with therapeutic potential.

Prolonged protection against exercise-induced bronchoconstriction by the leukotriene D4-receptor antagonist cinalukast.

OBJECTIVES: The degree and duration of protection against exercise-induced bronchoconstriction afforded by three doses of a specific leukotriene D4 receptor antagonist, cinalukast, were assessed after an initial dosing and after 1 week of therapy. METHODS: A placebo-controlled crossover study was performed in eight male patients who had mild, stable asthma and exercise-induced bronchoconstriction. Treatment consisted of four 7-day periods of placebo and three dose levels of the drug (10, 50, and 200 mg administered orally). Exercise challenge was performed at 2 hours and 8 hours after treatment on the first and seventh treatment days. The response was measured as the area under the FEV1-time effect curve (AUEC). RESULTS: On the first day of treatment, the mean (+/- SEM) AUEC at 2 hours was 24.2 +/- 3.3 L.min after placebo and was 5.5 +/- 2.2 L.min, 6.3 +/- 2.7 L.min, 3.3 +/- 3.8 L.min after 10 mg, 50 mg, and 200 mg, respectively (p < 0.05 for all values compared with placebo). The AUEC at 8 hours on the first day was 25.1 +/- 4.4 L.min after placebo and was 6.8 +/- 4.1 L.min, 11.2 +/- 2.5 L.min, and 5.0 +/- 2.8 L.min after 10 mg, 50 mg, and 200 mg, respectively (p < 0.05 for all values compared with placebo). The protection afforded by 10 mg of cinaluicast was lost after 7 days of treatment but persisted with 50 mg and 200 mg doses. CONCLUSION: Orally administered cinalukast provides at least 8 hours of protection against exercise-induced bronchoconstriction. This protection is lost with regular treatment for 1 week for the lowest dose studied.