GERD, DGER, or both in Barrett's esophagus?
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Barrett Esophagus↗
Biomedical subjects
P Sharma
Publications and source records attributed to P Sharma.
A correlative study of histology and imprint cytology in the diagnosis of gastrointestinal tract malignancies.
Endoscopic mucosal biopsies from 323 patients (201 from upper gastrointestinal tract and 122 from lower gastrointestinal tract) were studied to correlate the diagnostic efficacy of histology and imprint cytology in the diagnosis of malignant lesions of gastrointestinal tract. Of these 71 were from normal controls, 113 from benign lesions and 131 from malignant lesions. Histology showed no false positive reports but it was false negative in 6 cases (3 in oesophagus, 1 in stomach and 2 from colon). Imprint was false positive in 3 cases (2 oesophagus, 1 colon) and false negative in 2 cases (both oesophagus). The overall diagnostic accuracy of histology and imprint cytology in oesophagus, stomach and lower gastrointestinal tract was 95%, 98%, 98% and 95%, 100%, 98% respectively. When combined, the diagnostic accuracy increased to 98%, 100% and 100% in oesophagus, stomach and lower gastrointestinal tract respectively. The sensitivity, specificity, positive predictive value, negative predictive value and overall diagnostic accuracy for histology and cytology irrespective of the site was 96%, 100%, 100%, 94%, 97% and 98.5%, 97%, 98%, 98%, 98% respectively. Thus imprint cytology can act as an adjunct to bioptic histology to increase the diagnostic efficacy and save the time but definitely it cannot replace it as chances of false positives are high.
Biopsy↗
Duodenal seromyectomy in the management of adherent colonic carcinoma in elderly patients.
OBJECTIVE: To determine if partial denudation of the duodenum by seromyectomy can achieve tumour clearance in elderly patients with adherent primary colonic carcinoma. DESIGN: A case series. SETTING: An urban tertiary care centre. PATIENTS: Seven elderly patients with Dukes' class C primary adenocarcinoma of the ascending colon adherent to the duodenum but without distant metastases. The follow-up ranged from 29 to 41 months. INTERVENTIONS: Right hemicolectomy and seromyectomy of the duodenum at the site of adhesion. MAIN OUTCOME MEASURES: Patient survival and tumour recurrence. RESULTS: One patient died 29 months postoperatively of myocardial infarction but without tumour recurrence. Another patient had a solitary metastasis in the right liver lobe 7 months postoperatively. She was disease free 34 months after a right hemihepatectomy. The other 5 patients were alive and disease free at their last follow-up. CONCLUSION: Duodenal seromyectomy with postoperative chemotherapy for locally advanced adherent colonic cancer seems to be an acceptable management strategy for elderly patients in whom major en bloc resections present a greater than average risk of death.
Adenocarcinoma↗
Dysplasia in short-segment Barrett's esophagus: a prospective 3-year follow-up.
OBJECTIVE: Short segments of intestinal metaplasia in the distal esophagus are being recognized with increasing frequency. Both long and short segments of Barrett's esophagus can progress to dysplasia and cancer. However, the risk of short-segment Barrett's esophagus (SSBE) for the development of dysplasia and adenocarcinoma of the esophagus is not yet known. Our purpose, therefore, was to determine the frequency with which dysplasia occurs in patients with SSBE. METHODS: Patients with SSBE were followed prospectively for the development of dysplasia. SSBE was defined as <3 cm of Barrett's-appearing epithelium above the gastroesophageal junction at endoscopy, with intestinal metaplasia on biopsy as documented by alcian blue stain at pH 2.5 on at least two endoscopic biopsies 6 months apart. Patients had interval upper endoscopy with systematic biopsy of the Barrett's segment. RESULTS: Fifty-nine SSBE patients were identified. The mean length of Barrett's mucosa was 1.5 +/- 0.1 cm; the mean age of the patients was 63.1 +/- 1.3 yr. Five patients had low-grade dysplasia (LGD) at initial endoscopy, for a prevalence of 8.5%; none had high grade dysplasia (HGD). Thirty-two patients had follow-up endoscopy over a mean period of 36.9 +/- 5.4 months. Five of these patients developed dysplasia on follow-up, three with LGD and two with HGD, the incidence of any dysplasia being 5.7% per year. One patient with HGD that developed during surveillance progressed to adenocarcinoma of the esophagus over a 2-yr period. The other patient with HGD had LGD on follow-up endoscopy. Six patients with initial LGD had no evidence of dysplasia on follow-up. CONCLUSIONS: The prevalence of dysplasia was 8.5% with an incidence of 5.7% per year in this group of SSBE patients, followed prospectively. Although dysplastic changes may not be identified on follow-up examination, some patients progress to adenocarcinoma. Therefore, we recommend surveillance endoscopy and biopsy in patients with SSBE just as in those with long-segment Barrett's esophagus.
Adenocarcinoma↗
Torsional changes in surgery for A-V phenomena.
The role of torsion in the aetiopathogenesis of A-V phenomena has not been sufficiently emphasized. The success of vertical displacement of horizontal recti in correction of A or V has not been attributed to torsional changes. To evaluate this aspect, 21 cases of A or V phenomena were subjected to monocular recession-resection procedure with vertical shifting. Preoperative and postoperative torsional changes were evaluated on synoptophore (subjective torsion), and confirmed by fundus photography (objective torsion). Intorsion with A phenomenon was seen preoperatively in 5 of 8 cases which increased after surgery and was seen postoperatively in the other 3 cases also. Extorsion was observed in 5 of 13 cases pre operatively in 'V' phenomenon, but the changes in extorsion after surgery were less dramatic than those in intorsion. The oblique overactions were reduced in cases where they were present. Correction of A-V phenomena by torsion induced by vertical shifting of horizontal recti muscles is proposed, highlighting the role of torsion in A-V phenomena.
Follow-Up Studies↗
Transgenic mice expressing the thymus leukemia antigen fail to control cutaneous herpes simplex virus infection.
TL-transgenic mice expressing the thymus leukemia antigen demonstrate a lack of viral clearance following cutaneous HSV infection of the footpad. In this study, both uninfected and HSV-infected TL-transgenic mice demonstrate increased concentrations of IL-4 as well as decreased concentrations of IFN-gamma which may possibly underlie the impairment of viral clearance. Furthermore, lymphocytes from HSV-infected nontransgenic mice, adoptively transferred into HSV-infected TL-transgenic mice, promoted viral clearance and led to an increase in IFN-gamma production. Transgenic mice which were subcutaneously injected with IFN-gamma in the right footpad were also capable of clearing the viral challenge; however, clearance was restricted solely to the right footpad. These studies support the possibility of perturbations in the immune system of TL-transgenic mice and effectively demonstrate the utility of this model system in the study of HSV clearance, persistence, and potential spontaneous reactivation. Moreover, the TL-transgenic animals may provide a useful model system for additional studies requiring a host system skewed toward a Th2 phenotype.
Adoptive Transfer↗
Pancreatitis may occur with a normal amylase concentration in hypertriglyceridaemia.
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Acute Disease↗
Expansion of natural (NK1+) T cells that express alpha beta T cell receptors in transporters associated with antigen presentation-1 null and thymus leukemia antigen positive mice.
Thymic selection of natural killer-1+ natural T cells that express alpha beta T cell receptors requires a conserved beta 2-microglobulin-associated molecule, presumably CD1d, displayed by CD4+8+ thymocytes. Here we demonstrate that positive selection of natural T cells occurs independent of transporters associated with antigen presentation-1 (TAP-1) function. Moreover, natural T cells in TAP-1o/o mice are numerically expanded. Several H-2 class Ib molecules function in a TAP-independent manner, suggesting that if expressed in TAP-1o/o thymocytes, they could play a role in natural T cell development. Of these class Ib molecules, H-2TL is expressed by TAP-1o/o thymocytes. Moreover, we find that thymi of TL+ mice congenic or transgenic for H-2T18 also have a numerically expanded natural T cell repertoire compared with TL- mice. This expansion, as in TAP-1o/o thymi, is evident in each of the limited T cell receptor V beta chains expressed by natural T cells, suggesting that TL and CD1d impact similar repertoires. Thus TL, in addition to CD1d, plays a role in natural T cell development.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Cyclosporine nephrotoxicity in the ischemic kidney and the protective effect of pentoxifylline--a study in the rat.
In order to prevent cyclosporine nephrotoxicity in the ischemic kidney, pentoxifylline was used in a rat model. Seventy-two rats were divided into six groups according to treatment after right nephrectomy: Group I was the control, group II was treated with 25 mg/kg cyclosporine, group III underwent renal ischemia for 45 min, group IV was given 25 mg/kg cyclosporine and subjected to renal ischemia, and group V was subjected to renal ischemia and given 45 mg/kg pentoxifylline (repeated at 12, 36, and 48 hr), group VI underwent renal ischemia and was then given both cyclosporine and pentoxifylline. BUN, creatinine, and potassium levels were significantly elevated 24 hr after cyclosporine (group II), ischemia (group III), and cyclosporine and ischemia (group IV). Sodium levels remained unaffected. BUN levels normalized in all but groups III and IV after 48 hr. Creatinine levels normalized in all but group IV after 48 hr. Creatinine clearance fell in all groups and remained low even after 48 hr. Pentoxifylline prevented dramatic rises in BUN and creatinine and levels nearly normalized after 48 hr. It also histologically prevented extensive tissue damage seen after ischemia. In conclusion, pentoxifylline has a protective effect upon the kidney when subjected to cyclosporine in the presence of ischemia.
Animals↗
Structure and content of the major histocompatibility complex (MHC) class I regions of the great anthropoid apes.
The origins of the functional class I genes predated human speciation, a phenomenon known as trans-speciation. The retention of class Ia orthologues within the great apes, however, has not been paralleled by studies designed to examine the pseudogene content, organization, and structure of their class I regions. Therefore, we have begun the systematic characterization of the Old World primate MHCs. The numbers and sizes of fragments harboring class I sequences were similar among the chimpanzee, gorilla, and human genomes tested. Both of the gorillas included in our study possessed genomic fragments carrying orthologues of the recently evolved HLA-H pseudogene identical to those found in the human. The overall megabase restriction fragment patterns of humans and chimpanzees appeared slightly more similar to each other, although the HLA-A subregional megabase variants may have been generated following the emergence of Homo sapiens. Based on the results of this initial study, it is difficult to generate a firm species tree and to determine human's closest evolutionary neighbor. Nevertheless, an analysis of MHC subregional similarities and differences in the hominoid apes may ultimately aid in localizing and identifying MHC haplotype-associated disease genes such as idiopathic hemochromatosis.
Animals↗
Correlates of immune protection after vaccination with attenuated live murine leukemia virus.
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Animals↗
Thymus-leukemia antigen interacts with T cells and self-peptides.
The functional role of the class Ib thymus-leukemia (TL) Ag expressed within the thymic cortex and intestinal mucosa of the mouse remains unknown. In an approach to elucidate the potential functionality of TL, we developed transgenic mice that ectopically express the H-2T18d gene product on essentially all nucleated cells through the control of a heterologous H-2Kb gene promoter. Transgenic mice demonstrated an increase in the number of CD4+ lymphocytes within the thymus and lymph nodes; these cells displayed an altered T cell receptor repertoire possibly suggesting a role for the ectopically expressed TL protein. The TL protein additionally displayed the characteristics of a bona fide transplantation Ag, because skin grafts from transgenic animals onto MHC- and minor histocompatibility Ag-matched nontransgenic recipient mice resulted in a rapid and vigorous immunologic rejection of the allograft. In MLR studies, transgenic stimulator cells induced the proliferation of responders to a level intermediate between genetically identical and H-2-disparate responder-stimulator combinations. The TL protein was also capable of stimulating cytotoxic T lymphocytes, thereby resulting in specific lysis of TL+ target cells. Further data demonstrated that the TL protein assembles with peptides that are modified at the amino terminus, and that TL retains these molecules at the cell surface. Together, these data suggest that H-2T18d is capable of interacting with T cells via a bound peptide. These data further support the possibility that TL may subserve a specialized function within the immunologic system.
Animals↗
Design of specific peptide structures and subtilisin enzyme inhibitors using alpha,beta-dehydro-residues.
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Drug Design↗
Isolation and characterization of a cDNA encoding a plant defensin-like protein from roots of Norway spruce.
We are studying the interaction between the roots of Norway spruce seedlings (Picea abies L. Karst) and a highly pathogenic isolate of Pythium dimorphum. Here, we report the isolation of a cDNA from spruce roots encoding a protein with high sequence similarity to plant defensins, designated as SPI1 (Spruce Pathogen Induced No.1). The transcript hybridizing to the SPII cDNA probe is highly induced in uninfected roots when the seedlings are transferred from solid to liquid incubating malt medium (hypoxic conditions). However, when the seedlings are transferred from solid to liquid malt media containing a saturating amount of P. dimorphum hyphae, the amount of transcript is unchanged the first day after infection, but then decreases on day 1, and is no longer detectable 2 days after infection. Since plant defensins may play a role in plant defence, their negative regulation upon infection might reflect a strategy employed by this pathogenic fungus to evade the effect of toxic gene products.
Amino Acid Sequence↗
Incidence of human papilloma virus in patients with invasive cervical carcinoma.
The dot-blot hybridization of biotin-dUTP-labeled HPV-16 DNA with genomic DNA extracted from biopsies taken from patients with invasive carcinoma and abnormal cytology showed the presence of HPV-DNA in 88% and 80% cases under relaxed conditions and 40% and 20% cases under stringent conditions of hybridization, respectively. Southern blot revealed the HPV-DNA in randomly integrated form in two cases and in episomal form in the other two.
Blotting, Southern↗
Effect of ascorbic acid on hyperoxic rat astrocytes.
The effect of ascorbic acid on cell size and ascorbic acid transport was studied in hyperoxic astrocytes. Subcultured rat astrocytes plated on poly-L-lysine-coated coverslips or on plastic dishes were exposed to serum-free culture medium and 20% or 42% ambient oxygen for 48 h. Vehicle (homocysteine) or L-ascorbic acid was added to the medium at 0 and 24 h. Cell size and relative optical density of glial fibrillary acidic protein-positive astrocytes were measured by a computerized imaging system. Cells on the dishes were used for ascorbic acid transport studies. Hyperoxia significantly increased the cell size of astrocytes, and this effect was inhibited by ascorbic acid. The rate of L-[14C]ascorbic acid Na(+)-dependent uptake was also inhibited by hyperoxia in vehicle-treated cultures but not in ascorbic acid-supplemented cultures. These results indicate that the presence of ascorbic acid during the hyperoxic episode can prevent astrocytic cell swelling and preserve membrane transport function.
Animals↗
Mn-DPDP enhanced MR imaging of the liver: analysis of pulse sequence performance.
AIM: To compare liver enhancement and lesion-liver contrast on T1-weighted (T1W) gradient recalled echo (GRE), spin-echo (SE) and fat-suppressed SE (FS-SE) pulse sequences at Manganese-DPDP (Mn-DPDP) enhanced magnetic resonance (MR) imaging of the liver. PATIENTS AND METHODS. Twenty-one patients with known liver lesions were administered 5 mumol/kg of Mn-DPDP. TIW GRE (78/2.3/80 degrees), SE and F-SE (300/12) images were obtained before and 15 min after Mn-DPDP. Signal/noise ratio (SNR) and lesion-liver contrast/noise ratio (CNR) were calculated for each pulse sequence. RESULTS: Liver SNR (n = 21) and lesion-liver CNR (n = 10) increased significantly after Mn-DPDP on all three pulse sequences (P < 0.0001). Liver SNR was highest on the FS-SE and GRE pulse sequences (FS-SE = 43.8, GRE = 38.4, SE = 29.2). Lesion-liver CNR was highest on the FS-SE pulse sequence (FS-SE = -29.3, SE = -23.2, GRE = -19.8), which was significantly higher than the GRE pulse sequence (P < 0.05). CONCLUSION: The T1-weighted fat-suppressed SE (FS-SE) pulse sequence provides highest liver enhancement and lesion-liver contrast and is recommended for Mn-DPDP enhanced MR imaging.
Adult↗
Native and oxidized low density lipoproteins modulate mesangial cell apoptosis.
Hyperlipidemia has been demonstrated to contribute to hypercellularity of the mesangium in experimental animal models of glomerulosclerosis. We studied whether it also has the potential to convert a hypercellular mesangium into a hypocellular one by inducing mesangial cell (MC) apoptosis. Low density lipoprotein (LDL) enhanced (P < 0.001) mouse mesangial cell (MMC) proliferation at lower concentrations (control, 10.3 +/- 0.3 vs. LDL 100 micrograms/ml, 24.2 +/- 0.3 x 10(4) cells/ml) but augmented (P < 0.001) apoptosis at higher concentrations (control, 5.6 +/- 0.5% vs. LDL, 500 micrograms/ml 26.2 +/- 3.4% apoptotic cells/field). Oxidized (OX) LDL enhanced MMC apoptosis in concentrations of 50 to 200 micrograms/dl. There was a direct relationship between MMC apoptosis and oxidation of LDL as judged by measuring thiobarbituric acid reactive species (TBARS). Since superoxide dismutase (SOD) attenuated (P < 0.001) LDL-induced MMC apoptosis, it seems to be mediated through the generation of free radicals by mesangial cells (control, 4.3 +/- 1.5%; LDL, 200 micrograms/ml, 19.4 +/- 0.5%; LDL + SOD, 8.1 +/- 1.3% apoptotic cells/field). LDL also induced a similar effect on human mesangial cells. These studies were further confirmed by DNA fragment assays and ELISA for programmed cell death. LDL treated cells also showed enhanced mRNA expression for RSG-2, a marker for active cell death. These in vitro results provide a basis for the speculation that LDL has the potential to cause an initial hypercellular and subsequent hypocellular mesangium in the course of the development of glomerulosclerosis.
Animals↗