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Biomedical subjects

R K Vartanian

Publications and source records attributed to R K Vartanian.

13 recordsLinked to original sources
PubMed2000

Substance P mediates inflammatory oedema in acute pancreatitis via activation of the neurokinin-1 receptor in rats and mice.

Pancreatic oedema occurs early in the development of acute pancreatitis, and the overall extent of fluid loss correlates with disease severity. The tachykinin substance P (SP) is released from sensory nerves, binds to the neurokinin-1 receptor (NK1-R) on endothelial cells and induces plasma extravasation, oedema, and neutrophil infiltration, a process termed neurogenic inflammation. We sought to determine the importance of neurogenic mechanisms in acute pancreatitis. Pancreatic plasma extravasation was measured using the intravascular tracers Evans blue and Monastral blue after administration of specific NK1-R agonists/antagonists in rats and NK1-R(+/+)/(-/-) mice. The effects of NK1-R genetic deletion/antagonism on pancreatic plasma extravasation, amylase, myeloperoxidase (MPO), and histology in cerulein-induced pancreatitis were characterized. In rats, both SP and the NK1-R selective agonist [Sar(9) Met(O(2))(11)]SP stimulated pancreatic plasma extravasation, and this response was blocked by the NK1-R antagonist CP 96,345. Selective agonists of the NK-2 or NK-3 receptors had no effect. In rats, cerulein stimulated pancreatic plasma extravasation and serum amylase. These responses were blocked by the NK1-R antagonist CP 96,345. In wildtype mice, SP induced plasma extravasation while SP had no effect in NK1-R knockout mice. In NK1-R knockout mice, the effects of cerulein on pancreatic plasma extravasation and hyperamylasemia were reduced by 60%, and pancreatic MPO by 75%, as compared to wildtype animals. Neurogenic mechanisms of inflammation are important in the development of inflammatory oedema in acute interstitial pancreatitis.

Acute Disease↗
PubMed1998

A novel Alcian yellow-toluidine blue (Leung) stain for Helicobacter species: comparison with standard stains, a cost-effectiveness analysis, and supplemental utilities.

Helicobacter pylori (Hp) gastritis is a worldwide problem significantly associated with duodenal and gastric peptic ulcer disease, gastric carcinomas, and MALT-type lymphomas. A simple, rapid, reproducible, reliable, and inexpensive stain to detect the organism in gastric biopsy specimens is thus of great value. To assess the reliability and cost-effectiveness of a novel Alcian yellow-toluidine blue (Leung) stain for Hp, we stained 60 endoscopic mucosal biopsy specimens from patients with Hp gastritis and measured time to detection of organism, Hp numbers (scale, 1-5), and technical costs. We also stained serial 5-microm step sections of 17 of these cases with the Giemsa and modified Steiner (MS) methods, and similar measurements were made. Also, specimens from various normal gastrointestinal sites and metaplastic lesions, as well as four cases each of giardiasis and cryptosporidiosis, were stained with the Leung method. In the subset of 17 cases, the Leung stain enhanced detection time and compared favorably with the Giemsa method, though the MS method was somewhat superior. Hp scores were similar among all groups. Mean time to detection and Hp scores were similar in the larger (n = 60) group stained with hematoxylin and eosin and the Leung stain. Material costs and technologist's time for Giemsa stains, however, were greater than for the Leung stain, and technologist's time for MS was nearly fourfold that of the Leung stain. With the Leung method, mucus from all gastrointestinal sites and metaplastic lesions stained yellow, and this stain provided excellent contrast and morphologic definition in giardiasis and cryptosporidiosis. We suggest that the newly developed Alcian yellow-toluidine blue (Leung) histochemical stain is a good choice as the standard for routine Hp staining because it is the cheapest and easiest to prepare and because pathologists' detection with this stain compares favorably with detection times achieved with more traditional and established methods.

Coloring Agents↗
PubMed1997

Alteration of the dismal natural history of fibrosing cholestatic hepatitis secondary to hepatitis B virus with the use of lamivudine.

BACKGROUND: Fibrosing cholestatic hepatitis (FCH) is a severe form of hepatitis B virus (HBV) infection occurring as either primary allograft reinfection after liver transplantation for HBV or as severe HBV reactivation induced by immunosuppression in patients with previously latent infection. Without treatment, FCH is universally fatal within a few months of diagnosis. Some improvement has been reported with long-term ganciclovir, with and without foscarnet, but an effective and easily available treatment has not yet been reported. METHODS: We report the prolonged survival of a renal transplant recipient who developed histologically confirmed FCH 6 months after transplantation and was treated with lamivudine. RESULTS: At the time of diagnosis, the patient had jaundice, ascites, and a serum HBV-DNA level of 3868 pg/ml. Lamivudine was instituted 2 months later, and after 6 months of treatment, the HBV-DNA level was undetectable with the serum bilirubin within the normal range. Twelve months after the diagnosis of FCH, the patient remains stable without progression of liver dysfunction. CONCLUSION: Our experience demonstrates that lamivudine therapy can improve the dismal natural history of FCH.

Antiviral Agents↗
PubMed1997

Late recurrent post-transplant primary biliary cirrhosis in British Columbia.

Late recurrent primary biliary cirrhosis (PBC) following orthotopic liver transplant remains a controversial topic. The first documented case of recurrence occurring in 16 patients transplanted for PBC and followed at the authors' institution for longer than one year is presented. A 54-year-old man transplanted for PBC developed a cholestatic pattern of enzyme elevation on post-transplant day (PTD) 1305. Repeat antimitochondrial antibody was strongly positive (1:300 to 1:400). A liver biopsy revealed severe bile duct damage, lymphocytic cholangitis, focal periductal noncaseating granuloma and minimal endotheliitis. Recurrent PBC was diagnosed. At the time of orthotopic liver transplant this patient received induction immunosuppression with OKT3 crossed over to cyclosporine (CsA), azathioprine (AZA) and prednisone. AZA was discontinued early and maintenance CsA tapered to a target trough level of 150 to 200 ng/mL by PTD 365. Prednisone was withdrawn by PTD 664. CsA levels during PTDs 1225 to 1305 (before elevation of hepatobiliary enzymes) were below target at 114 to 166 ng/mL. Of the 16 patients, all but three were maintained on CsA, AZA and prednisone. One was on CsA (trough levels on target) and AZA; the other two, including the patient with recurrent PBC, were on CsA only. The trough CsA level of the patient without recurrent PBC has been within the target range. The authors speculate that the underlying defect in immunoregulation in PBC persists post-transplant and that in the patient without recurrent PBC this defect was unmasked by lowered maintenance immunosuppression--allowing recurrence of PBC in a previously stable liver allograft.

Biopsy, Needle↗
PubMed1996

Renal cell carcinoma after therapy for neuroblastoma.

OBJECTIVE: An unfortunate consequence of increased success in childhood cancer survival rates is the increase in the number of secondary malignant neoplasms after therapy for the initial lesion. Renal cell carcinoma can occur as a secondary malignant neoplasm after therapy for neuroblastoma and may become more common as more patients with treated neuroblastomas survive into adulthood. We studied one case and reviewed four cases of secondary renal cell carcinoma to determine if the relationship between these two neoplasms is significant. CONCLUSION: An awareness of the association between these two neoplasms is important in the diagnostic follow-up of neuroblastoma so that secondary renal cell carcinoma is not confused with recurrence of primary disease.

Carcinoma, Renal Cell↗
PubMed1995

Histopathological concordance of paired renal allograft biopsy cores. Effect on the diagnosis and management of acute rejection.

To assess the effect of sampling error on renal allograft biopsies, we determined the concordance of diagnoses between 2 biopsy samples from the same renal allograft and the frequency with which 1 biopsy sample would underdiagnose or lead to the undertreatment of acute rejection. Two core samples from the same allograft biopsy procedure were labeled as core A and core B and presented to both unblinded and blinded pathologists, and each pathologist independently assigned an acute and a chronic rejection grade. A set of clinical data with pertinent prebiopsy information was combined with either the core A or core B histopathological diagnosis and presented to 3 transplant nephrologists who made treatment recommendations for each combination. Two cores were obtained in 79 allograft biopsies. Core pairs differed by > or = 1 grade of acute rejection in 30% and 50% of cases for unblinded and blinded pathologist readings, respectively. Moderate or severe acute rejection would have been missed with a 1 core in 9.5% of cases, increasing to 25.6% if only biopsy pairs containing at least 1 reading of moderate or severe acute rejection are included. Therapy would have failed to be increased with a single core in 7.5% of cases, increasing to 10.5% if only pairs containing at least one recommendation of an increase in therapy are included. The use of 2 cores of renal allograft tissue provides better diagnostic information and thereby leads to appropriate increases in antirejection therapy without increasing the complication rate of the procedure.

Adult↗
PubMed1995

Unreliability of the abdominal fat pad biopsy in the evaluation of nephrosis: report of 3 consecutive cases.

In the workup of unexplained nephrotic syndrome in the elderly patient, renal biopsy has shown amyloidosis to be the cause in 15-30% of the cases. Most of the cases of amyloidosis are primary and are, therefore, treatable with alkylating agents, albeit at a high level of toxicity. Abdominal fad pad biopsy has been suggested as a minimally invasive, low-cost method for diagnosing amyloidosis that is 100% specific. We report our experience with 3 consecutive cases of fat pad biopsy in the workup of unexplained nephrosis in the elderly patient: including the first false positive reported with respect to nephrotic renal disease, a false negative, and a true positive. We feel that in an elderly patient with unexplained nephrosis though the abdominal fat pad biopsy may be helpful, the patient should not be committed to a regimen with potentially very high toxicity on the basis of a positive fat pad biopsy alone. We recommend that the more invasive renal biopsy be performed should therapy with alkylating agents be contemplated.

Abdomen↗
PubMed1995

Endothelial cell proliferation in prostatic carcinoma and prostatic hyperplasia: correlation with Gleason's score, microvessel density, and epithelial cell proliferation.

BACKGROUND: Tumor angiogenesis is necessary for tumor growth and metastasis, and increasing intratumoral microvessel density (MVD) in prostate carcinoma has been shown in several studies to be associated with increasing tumor stage. But, the relationships of endothelial cell proliferation to intratumoral MVD, tumor cell proliferation, and Gleason's score remain unknown in prostate carcinoma. EXPERIMENTAL DESIGN: Using a double-immunolabeling technique (paraffin-reactive MIB1 Ab to determine Ki67 labeling index (Ki67LI) and anti-CD34 to quantify microvessels), we immunostained 20 prostatic carcinomas and adjacent benign prostate hyperplasia (BH) and four cases of trauma-induced granulation tissue. We correlated intratumoral endothelial cell proliferation with intratumoral MVD, tumor cell proliferation, and Gleason's score, and we compared these measurements with endothelial cell proliferation, MVD, and epithelial cell proliferation in adjacent BH. RESULTS: The intratumoral endothelial cell proliferation index (mean 0.15%) and intratumoral MVD measured 30-fold (p = 0.00007) and 1.9-fold (p = 0.000003) greater than that of adjacent BH, respectively. However, the intratumoral endothelial cell proliferation index did not correlate with intratumoral MVD, tumor cell proliferation, or Gleason's score. Nor did intratumoral MVD correlate with tumor cell proliferation. In comparison, the mean MVD and endothelial cell proliferation rates in granulation tissue were 199 and 6.50%, respectively, the latter 43-fold greater than the mean intratumoral endothelial cell proliferation index (p = 0.00023). CONCLUSIONS: Endothelial cells are actively proliferating in prostatic carcinoma, and their proliferation appears independent of intratumoral MVD and tumor cell proliferation. Yet, the relatively low intratumoral hyperplasia, suggests that endothelial cell migration and capillary remodeling play an important role in neovascularization of prostatic carcinoma, especially when compared with granulation tissue, which showed a 43-fold greater endothelial cell proliferation index. Moreover, the lack of correlation of intratumoral endothelial cell proliferation and intratumoral MVD with tumor cell proliferation suggests that tumor angiogenesis and tumor-cell proliferation are regulated by different mechanisms.

Cell Division↗
PubMed1994

Correlation of intratumoral endothelial cell proliferation with microvessel density (tumor angiogenesis) and tumor cell proliferation in breast carcinoma.

Tumor angiogenesis is essential for tumor growth and metastasis, and intratumoral microvessel density correlates with prognosis in breast carcinoma. Yet, how intratumoral microvessel density correlates with tumor cell and intratumoral endothelial cell proliferation remains incompletely understood. To this end, we stained 57 formalin-fixed, paraffin-embedded breast carcinomas with antibody MIB1 to determine tumor cell Ki67 labeling index and with anti-CD34 to observe microvessels. We correlated the tumor cell Ki67 labeling index and mitotic figure index with intratumoral microvessel density. Using a double labeling technique combining antibody MIB1 and anti-CD34, we measured intratumoral endothelial cell proliferation in 20 of these cases and correlated these findings with tumor cell Ki67 labeling index, mitotic figure index, and intratumoral microvessel density. The intratumoral Ki67-labeling index was 45-fold greater (P < 0.000001) than that of microvessels in adjacent benign breast. Yet, endothelial cell Ki67 labeling index did not correlate with intratumoral microvessel density, tumor cell Ki67 labeling index, or mitotic figure index nor did intratumoral microvessel density correlate with tumor cell Ki67 labeling index or mitotic figure index. These findings suggest that, although endothelial cells are actively proliferating within the tumor, intratumoral microvessel density and intratumoral endothelial cell proliferation are independent of each other and of tumor cell proliferation. Thus, intratumoral microvessel density, endothelial cell proliferation, and tumor cell proliferation may be regulated by separate mechanisms.

Antigens, CD↗