Lakshmi Rao

Acute kidney injury in scrub typhus

BackgroundWe studied the urinary abnormalities and acute kidney injury (AKI) as per RIFLE criteria in scrub typhus.MethodsA prospective case record-based study of scrub typhus was carried out from January 2009 to December 2010 in a tertiary hospital in South India. Patients were followed up until renal recovery or for at least 3xa0months after discharge. Univariate, chi-squared tests and multivariate logistic regression analyses were performed to identify the predictors of AKI.ResultsScrub typhus was diagnosed in 259 patients. Urinary abnormalities were seen in 147 patients (56.7xa0%) with 60 patients (23.2xa0%) having AKI. All AKI patients had urinary abnormalities and 17 (28.3xa0%) were oliguric. Applying RIFLE (risk, injury, failure, loss, end-stage kidney disease) criteria, R, I, F were present in 23 (38.33xa0%), 13 (21.67xa0%), and 24 patients (40xa0%), respectively. Creatine phosphokinase (CPK) was raised in 33 patients (55xa0%) and hemodialysis was required in 6 patients (10xa0%). The case fatality rate in this study was 2 out of 259 (0.77xa0%), both having AKI and others recovering clinically. Significant predictors of AKI were tachycardia [odds ratio (OR) 2.28], breathlessness (OR 2.281), intensive care requirement (OR 2.43), mechanical ventilation (OR 3.33), thrombocytopenia (OR 2.90) and CPKxa0>80xa0U/L (OR 1.76) by univariate analysis and intensive care requirement (adjusted OR 2.89) and thrombocytopenia (AOR 2.28) by multivariable logistic regression.ConclusionScrub typhus should be part of the differential diagnosis of acute febrile illness with AKI. AKI in scrub typhus is usually mild, non-oliguric, and renal recovery occurs in most patients. Rhabdomyolysis may be contributory to AKI. Thrombocytopenia and intensive care requirement are significant predictors of AKI in scrub typhus.

Hypercholesterolemia Induced Immune Response and Inflammation on Progression of Atherosclerosis in Apob tm2Sgy Ldlr tm1Her/J Mice

The effect of hypercholesterolemia induced immune response and inflammation on progression of atherosclerosis in ApoBtm25gyLDLrtm1Her mice, expressing only ApoB100 and deficient in the low density lipoprotein (LDL) receptor, thus closely resembling human cholesterol transport is not well defined. Atherosclerosis was induced by a high cholesterol diet and its progression was studied at 8, 14 and 20xa0weeks. Antibody response was determined by ELISA. Lymphocytes in spleen and aortic expression of inflammatory markers were studied by flow cytometry, and immunohistochemistry respectively. A rapid increase in plasma LDL levels in the first 8xa0weeks was followed by the exponential development of atherosclerosis between 8 and 14xa0weeks. Progression of the disease was accompanied by an accumulation of macrophages and increased expression of IL17 and IFN-γ in the aorta. Hypercholesterolemia resulted in increased immune response to modified lipids and aortic inflammation, with an expansion of Th17 cells in the spleen. Progression of atherosclerosis showed a positive correlation (rxa0=xa00.84, Pxa0<xa00.001) with Th17 cells and a negative correlation with Treg cells (rxa0=xa00.83, Pxa0<xa00.001). IgM antibodies to Ox-LDL and Th17 cells in spleen showed greatest association with disease development. Our results suggest that anti Ox-LDL IgM antibodies, Th17 cells could be developed as a potential marker to study disease progression and to study the effect of therapeutic regulation of inflammation.

Oral dosing with multi-antigenic construct induces atheroprotective immune tolerance to individual peptides in mice

Inflammatory immune response to self-antigens plays an important role in the development of atherosclerosis. Restoring immune tolerance to self-proteins reduces the pro-inflammatory response. We previously showed that oral tolerance to a combination of two peptides is atheroprotective. In the present study we expressed epitopes from apolipoprotein B 100 (ApoB), human heat shock protein (HSP60) and Chlamydia pneumonia outer membrane protein (Cpn) in a single protein scaffold and used this multi-antigenic construct to induce tolerance to individual peptides by oral route in ApoBtm2Sgy/Ldlrtm1Her/J mice. Antigen specific tolerance to individual peptides was observed in treated animals as seen by an increase in regulatory T cells. Tolerance to the peptides resulted in a 46.5% (p=0.002) reduction in the development of atherosclerosis compared with control. Atheroprotection was associated with a significant (p<0.05) decrease in plaque inflammation and an increase in the expression of immune regulatory markers in the aorta. CD11c+ cells coexpressing CD11b and CD103 increased in lymphoid organs and were found to activate regulatory T cells and reduce effector T-cell response. Adoptive transfer of CD11c+ cells was atheroprotective. Our results suggest that atheroprotection by oral tolerance to a multi-antigenic construct is mediated by antigen specific regulatory T cells and CD11c+ cells with immune regulatory properties.

Parapharyngeal space mesenchymal chondrosarcoma in childhood

A case of extra osseous mesenchymal chondrosarcoma occuring in the parapharyngeal space in a 7-year-old girl, is being presented for its rarity. It is a slow growing, locally aggressive tumour with a high incidence of local recurrence as well as distant metastasis. It is rare in the pediatric age group and rarer in the parapharyngeal space. It has a poor prognosis, the 5-year survival rate varies between 30 and 50%. Radical surgery is the treatment of choice. Radiotherapy and chemotherapy have an adjuvant role. More experience with this tumour is required to evaluate the most effective treatment. Current literature on this subject has been reviewed.

CAG repeat length polymorphism in the androgen receptor gene and breast cancer risk: data on Indian women and survey from the world

We analyzed the length of the CAG repeats of the androgen receptor gene in Indian women with breast cancer, and compared the data with that of other populations across the world in an attempt to find a potential pattern of association. The study was undertaken on 1,408 individuals comprising 747 breast cancer patients and 661 control individuals recruited from three southern states of India: Andhra Pradesh, Tamil Nadu, and Karnataka. The comparison revealed no difference in mean length of the repeat between cases and controls in any of the three groups or in the analysis of pooled data. No significant difference between pre- and post-menopausal cases in any of the three groups or in the analysis of pooled data was observed. Most of the studies to date support either positive association (longer repeats—increased disease risk) or no association, and only 2 out of 20 studies reported negative association (inverse correlation between repeat length and disease risk). Comparison of these data with those from other populations revealed several interesting facts. Particularly notable is that repeat length shows association with breast cancer risk in a population-specific manner with most of the studies on American and Canadian women showing positive association, whereas those on Australian and Israeli women showing no association. Only one study had been conducted on other populations including Asians/South Asians; this restricted us from finding any patterns of association in these populations.

Inflammatory Myofibroblastic Tumor: A Rapidly Growing Soft Tissue Mass in the Posterior Mandible

The term inflammatory myofibroblastic tumor (IMT) encompasses a diverse group of spindle cell entities that traverses a clinical and histologic spectrum, extending from reactive to benign neoplastic to highly aggressive with malignant inclinations. Head and neck IMTs are rarely seen and comprise less than 5xa0% of tumors. Here we report a case of a 30xa0year old male who presented with a rapidly enlarging and extremely painful growth in the right posterior mandible, post extraction. Histopathological examination revealed a highly cellular connective tissue stroma comprised of spindle shaped cells arranged in fascicles, admixed with inflammatory cells, predominantly plasma cells. Apart from routine hematological investigations, serum protein electrophoresis was also performed. The final diagnosis was confirmed by a panel of immunomarkers consisting of MPO, CD34, CD20, CD3, CD23, CD138, SMA and ALK. To the best of our knowledge, this is the third case of oral IMT arising from an extraction socket.

Gastric cryptococcal infection as an initial presentation of AIDS: a rare case report.

Cryptococcus neoformans has been recognized as a human pathogen over centuries. This has achieved new prominence in the recent years as it is an opportunistic fungi causing fatal, deep mycotic infections in immunocompromised states. Although cryptococcus is principally a pathogen of central nervous system, wide variety of other organs may also be involved. Gastrointestinal cryptococcosis is rarely reported either as an isolated finding or in a disseminated disease. However, even with the strikingly increased incidence of the disease, occurrence of obvious gastrointestinal symptoms directly attributable to cryptococcosis is outstandingly rare. We report a case of gastric cryptococcal infection with esophageal herpes as an initial presentation in an AIDS patient.

Pleomorphic hyalinizing angiectatic tumor of soft parts involving the upper limb

Pleomorphic hyalinizing angiectatic tumor (PHAT) of soft parts is a low grade, rare, soft tissue tumor which commonly occurs on the lower extremities of adults of either sex, though lesions in other anatomic locations have been described. We present a case of a 65-year-old female patient who presented with a left forearm swelling and underwent a wide local excision. Histopathology revealed it to be a PHAT.

Regulating Inflammatory Immune Response to Atherogenic Antigens Prevents Development and Progression of Atherosclerosis in New Zealand White Rabbits.

BACKGROUNDnInflammatory immune response to atherogenic self-antigens plays an important role in the development of atherosclerosis. We evaluated the role of oral tolerance to three peptides in controlling atherosclerosis in New Zealand white rabbits.nnnMETHODSnPeptides derived from apolipoprotein B (ApoB), heat shock protein 60, and outer membrane protein from Chlamydia pneumoniae were expressed as part of the dendroaspin protein scaffold (AHC). Groups of 3-month-old rabbits were dosed orally with purified AHC protein either before the onset of disease or 2 months after inducing atherosclerosis; they were euthanized at the age of 7 months to study disease development and progression.nnnRESULTSnOral treatment with AHC resulted in a marked increase in regulatory T cells in the lymphoid organs and reduced the development and progression of atherosclerosis by 48.6% and 28.4%, respectively (P < 0.05). Oral tolerance decreased plaque inflammation, enhanced expression of anti-inflammatory and regulatory markers in the aorta, and attenuated the adaptive immune response to self-antigens. AHC treatment in rabbits with established disease significantly decreased vascular cell adhesion molecule 1 (VCAM-1) (6.2 fold) and monocyte chemoattractant protein-1(MCP-1) (3 fold) expression and reduced the infiltration of macrophages into the aorta. Collagen content and the smooth muscle cell-to-macrophage ratio were higher in treated animals, whereas markers of plaque vulnerability, including matrix metalloproteinase expression, were reduced.nnnCONCLUSIONSnOur results suggest that oral tolerance to multiantigenic AHC molecule restores the immune balance and induces markers of plaque stability in rabbits.

Decoy cells in urine cytology: A useful clue to post-transplant polyoma virus infection

Two patients aged 50 years and 49 years, presented with worsening renal function at 4 months and 101⁄2 months respectively, following renal transplant. Both cases were on triple immunosuppressants including tacrolimus, azathioprine and steroids. We received urine samples from both patients to rule out possible viral infection. Serologic tests for cytomegalovirus (CMV) and adenovirus antigens were negative in both cases.