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Biomedical subjects

P Sharma

Publications and source records attributed to P Sharma.

At least 109 records · Page 6Linked to original sources
PubMed2001

Barrett esophagus.

There continues to be great interest in Barrett esophagus, the premalignant lesion for adenocarcinoma of the esophagus and the esophagogastric junction. There were several publications this past year related to the epidemiology, pathogenesis, new methods for detection, biomarkers for stratifying patients by risk, and the treatment of patients with Barrett esophagus. Patients with intestinal metaplasia in short lengths of columnar mucosa in the distal esophagus (ie, short-segment Barrett esophagus) appear to be distinct from those with intestinal metaplasia in the gastric cardia. The reported risk of cancer in patients with Barrett esophagus is probably subject to publication bias, with small series reporting a higher incidence of cancer. New methods for the diagnosis and detection of intestinal metaplasia and dysplasia are being evaluated and may, in future, help in obtaining more accurate screening and more focused surveillance of patients with Barrett esophagus. The validation of biomarkers may help us to risk stratify patients at high risk for cancer development. Endoscopic mucosal resection appears to be a safe and effective technique for the resection and accurate diagnosis of dysplastic or cancerous areas within Barrett esophagus.

Journal Article↗
PubMed2001

Incidence and management of esophageal stricture formation, ulcer bleeding, perforation, and massive hematoma formation from sclerotherapy versus band ligation.

OBJECTIVES: The aim of this study was to compare the incidence and endoscopic management of esophageal stricture formation, significant ulcer bleeding, massive esophageal hematoma, and perforation resulting from endoscopic band ligation or sclerotherapy of esophageal varices. METHODS: Consecutive esophagogastroduodenoscopies in which band ligation or sclerotherapy was performed for acute or obliterative therapy were entered into a computerized endoscopy database during a 7-yr period. Patients were excluded if they died within 72 h of treatment session from complications unrelated to the procedure. Sclerotherapy was performed using a 25-gauge needle with 1.5% sodium tetradecyl sulfate and banding was primarily performed with a Wilson-Cook 6 or 10 shooter. Complications were assessed at scheduled endoscopy and outpatient clinic visits, review of quality assurance data tallied on a monthly basis, and patient records. RESULTS: Two hundred twenty-one cases of sclerotherapy were performed in 59 patients compared to 110 cases of band ligation in 52 patients. Five patients were excluded because of death within 72 h of the procedure. The incidence of complications from sclerotherapy:banding on a per patient basis included: esophageal stricture formation 25.6%:1.9%, ulcer bleed 25.4%:5.7%, esophageal perforation 2.2%:0%, and massive esophageal hematoma 1.6%:0%. A significant difference in complications between sclerotherapy and band ligation was noted for both stricture formation (p < 0.0005) and ulcer bleeding (p < 0.0001). The majority of ulcer bleeds required no therapeutic intervention, whereas stricture formation required multiple dilation sessions. CONCLUSIONS: Band ligation has a significantly lower incidence of stricture formation and ulcer bleeding compared to sclerotherapy. The majority of complications can be managed with endoscopic interventions.

Databases, Factual↗
PubMed2001

p53 protein overexpression in low grade dysplasia (LGD) in Barrett's esophagus: immunohistochemical marker predictive of progression.

OBJECTIVES: The presence of low grade dysplasia (LGD) within Barrett's esophagus (BE) has a multitude of ramifications. Identification of markers that could risk stratify LGD would be of great clinical benefit. We aimed to prospectively evaluate the prognosis of the immunohistochemical overexpression of p53 protein in BE colocalized to LGD. METHODS: Consecutive BE patients in whom LGD was found had a repeat esophagogastroduodenoscopy within 8-12 wk per an ongoing prospective study. At each esophagogastroduodenoscopy, a therapeutic scope was used in conjunction with the Seattle Biopsy Protocol. Patients were observed until development of multifocal high grade dysplasia (mHGD), presence of an HGD dysplasia-associated lesion or mass (DALM) lesion, or frank adenocarcinoma. p53 protein overexpression was determined by computerized immunoquantitation using image analysis software on step serial-sectioned specimens of BE segment(s) harboring LGD. Kaplan-Meier survival curves were made on the ability of p53 staining colocalized to areas of LGD to predict progression to mHGD, HGD DALM, or cancer during prospective follow-up. RESULTS: Forty-eight BE patients with LGD were observed for a mean of 41.2+/-22.5 months. During this period, five of 48 patients progressed to mHGD with a focus in which intramucosal cancer could not be excluded (one), mHGD/DALM with one or more foci in which intramucosal cancer could not be excluded (two), cancer (one), or mHGD (one). Twelve had persistent LGD and 31 had regressed to no dysplasia. p53 staining was positive and colocalized to areas of LGD in 4/31 of patients that regressed, 3/12 that persisted, and 3/5 that progressed. Kaplan-Meier curves differed significantly between p53 positive and negative patients for outcome defined as progression of LGD. CONCLUSIONS: p53 colocalization with LGD at index LGD diagnosis is a risk factor for progression of LGD. This can potentially be used to risk stratify BE LGD patients in terms of surveillance intervals or enrollment into secondary prevention studies.

Adult↗
PubMed2001

Disruption of the Cockayne syndrome B gene impairs spontaneous tumorigenesis in cancer-predisposed Ink4a/ARF knockout mice.

Cells isolated from individuals with Cockayne syndrome (CS) have a defect in transcription-coupled DNA repair, which rapidly corrects certain DNA lesions located on the transcribed strand of active genes. Despite this DNA repair defect, individuals with CS group A (CSA) or group B (CSB) do not exhibit an increased spontaneous or UV-induced cancer rate. In order to investigate the effect of CSB deficiency on spontaneous carcinogenesis, we crossed CSB(-/-) mice with cancer-prone mice lacking the p16(Ink4a)/p19(ARF) tumor suppressor locus. CSB(-/-) mice are sensitive to UV-induced skin cancer but show no increased rate of spontaneous cancer. CSB(-/-) Ink4a/ARF(-/-) mice developed 60% fewer tumors than Ink4a/ARF(-/-) animals and demonstrated a longer tumor-free latency time (260 versus 150 days). Moreover, CSB(-/-) Ink4a/ARF(-/-) mouse embryo fibroblasts (MEFs) exhibited a lower colony formation rate after low-density seeding, a lower rate of H-Ras-induced transformation, slower proliferation, and a lower mRNA synthesis rate than Ink4a/ARF(-/-) MEFs. CSB(-/-) Ink4a/ARF(-/-) MEFs were also more sensitive to UV-induced p53 induction and UV-induced apoptosis than were Ink4a/ARF(-/-) MEFs. In order to investigate whether the apparent antineoplastic effect of CSB gene disruption was caused by sensitization to genotoxin-induced (p53-mediated) apoptosis or by p53-independent sequelae, we also generated p53(-/-) and CSB(-/-) p53(-/-) MEFs. The CSB(-/-) p53(-/-) MEFs demonstrated lower colony formation efficiency, a lower proliferation rate, a lower mRNA synthesis rate, and a higher rate of UV-induced cell death than p53(-/-) MEFs. Collectively, these results indicate that the antineoplastic effect of CSB gene disruption is at least partially p53 independent; it may result from impaired transcription or from apoptosis secondary to environmental or endogenous DNA damage.

Age Factors↗
PubMed2001

Neurovascular lessons from a pair of identical twins with cerebral aneurysms.

A pair of hypertensive identical twins are reported, one of whom was non-compliant with her antihypertension medication, and after a subarachnoid haemorrhage was found to have multiple cerebral aneurysms. The other asymptomatic compliant twin was noted to have only a single small cerebral aneurysm. As both identical twins are likely to share the same cerebral vascular architecture it is suggested that good control of blood pressure contributed to the cerebral vascular integrity of the asymptomatic twin. This is the first report on the role of blood pressure in the formation of cerebral aneurysms and provides insights for an alternative approach to the controversial management of asymptomatic cerebral aneurysms.

Adult↗
PubMed2001

Helicobacter pylori: a debated factor in gastroesophageal reflux disease.

The prevalence of Helicobacter pylori infection is steadily decreasing in developing countries, and this has been paralleled by an increasing incidence of gastroesophageal reflux disease (GERD) and adenocarcinomas of the esophagus and of the esophagogastric junction. The prevalence of H. pylori infection, which is on the decline in Europe and in the United States, is probably related to improvements in sanitary conditions and socioeconomic status. These epidemiological data do not support a role for H. pylori in the pathogenesis of GERD, but at the same time suggest a negative association with the rising incidence in esophageal diseases. While H. pylori infection clearly does not cause GERD, it may protect certain susceptible individuals from the development of GERD and its complications. There are conflicting reports that GERD can develop after H. pylori eradication and that proton pump inhibitors are less effective in suppressing intragastric acidity in H. pylori negative patients--reasons not to eradicate H. pylori in GERD patients. On the contrary, other data suggest an increase in the development of atrophic gastritis in GERD patients (H. pylori positive) on long-term proton pump inhibitor therapy - a reason to eradicate H. pylori. Preexisting lower esophageal sphincter dysfunction, susceptibility to GERD, unmasking of latent GERD, and patterns and severity of gastritis may be important factors contributing to the development of GERD rather than just the presence or absence of infection with H. pylori.

Adenocarcinoma↗
PubMed2001

Syringomyelia in spontaneous intracranial hypotension. Case report.

The authors describe the presence of a syrinx in a patient with spontaneous intracranial hypotension. The likely pathophysiological basis of this hitherto unreported association is also presented. It is believed that chronic obstruction at the foramen magnum may be the most important factor for the development of syringes.

Adult↗
PubMed2001

Short segment Barrett esophagus and specialized columnar mucosa at the gastroesophageal junction.

The rising incidence of adenocarcinoma of the esophagus and the gastric cardia has generated interest in the finding of intestinal metaplasia or specialized columnar mucosa in this location. Short segment Barrett esophagus is defined by the presence of columnar-appearing mucosa in the distal esophagus (<3 cm in length) with intestinal metaplasia on biopsy. In contrast, intestinal metaplasia may also be present if biopsy specimens are obtained from a normal-appearing squamocolumnar junction or from the gastric cardia (ie, immediately below the gastroesophageal junction) in the absence of columnar lining of the distal esophagus. This has been termed cardia intestinal metaplasia, gastroesophageal junction intestinal metaplasia, or specialized columnar mucosa at the gastroesophageal junction. This article reviews the currently available data on these rapidly evolving entities of short segment Barrett esophagus and specialized columnar mucosa at the gastroesophageal junction.

Barrett Esophagus↗
PubMed2001

Controversies in Barrett's esophagus: management of high grade dysplasia.

Barrett's esophagus is the premalignant lesion for adenocarcinoma of the esophagus and the esophagogastric junction. The incidence of esophageal adenocarcinoma has been rapidly rising in the Western world over the last two decades, and Barrett's esophagus is the only known premalignant lesion for this cancer. Esophageal adenocarcinoma develops through the metaplasia-dysplasia sequence with progression from no dysplasia, low grade dysplasia, high grade dysplasia, and ultimately to esophageal adenocarcinoma. The diagnosis and management of high grade dysplasia (HGD) in patients with Barrett's esophagus is extremely controversial. Patients with HGD within Barrett's esophagus are at the highest risk for development of esophageal adenocarcinoma if concurrent adenocarcinoma doesn't already exist. Given the high likelihood of metastatic disease and poor prognosis associated with invasive cancer, detection of HGD within Barrett's esophagus is considered by many as the final endpoint requiring definitive therapy in the form of surgical resection. However, other limited data seem to suggest that a number of patients with HGD may actually regress or persist and not develop cancer, thus suggesting a less aggressive approach for management. Finally with the advent of local endoscopic therapy, reversal therapy is being studied in patients with HGD and may be validated for this major indication. Currently, surgery remains the goal standard and the most definitive therapy for HGD. This articles critically reviews the risks and benefits associated with each approach of managing HGD.

Adenocarcinoma↗
PubMed2001

Karyometry in Barrett's esophagus.

OBJECTIVE: To derive a progression curve for lesions in Barrett's esophagus based on karyometric features. STUDY DESIGN: High-resolution imagery of 900 nuclei from normal gastric tissue, Barrett's metaplasia, Barrett's high grade dysplasia and adenocarcinoma of the esophagus was recorded. Karyometric features were computed, and nuclear signatures and lesion signatures for these lesions were derived. A progression curve was defined. RESULTS: Esophageal lesions were distinctly different from the normal gastric fundus tissue, with nuclei from Barrett's metaplasia deviating from normal almost as much as nuclei from high grade dysplasia and adenocarcinoma. There was considerable case-to-case variability and overlap between lesions histologically assigned to different diagnostic categories. CONCLUSION: The karyometric data suggest that Barrett's metaplasia is a more developed lesion than previously assumed.

Adenocarcinoma↗
PubMed2001

Cyclin-dependent protein kinase 5 (Cdk5) and the regulation of neurofilament metabolism.

Cyclin-dependent kinase 5 (Cdk5), a complex of Cdk5 and its activator p35 (Cdk5/p35), phosphorylates diverse substrates which have multifunctional roles in the nervous system. During development, it participates in neuronal differentiation, migration, axon outgrowth and synaptogenesis. Cdk5, acting together with other kinases, phosphorylates numerous KSPXK consensus motifs in diverse cytoskeletal protein target molecules, including neurofilaments, and microtubule associated proteins, tau and MAPs. Phosphorylation regulates the dynamic interactions of cytoskeletal proteins with one another during all aspects of neurogenesis and axon radial growth. In this review we shall focus on Cdk5 and its regulation as it modulates neurofilament metabolism in axon outgrowth, cytoskeletal stabilization and radial growth. We suggest that Cdk5/p35 forms compartmentalized macromolecular complexes of cytoskeletal substrates, other neuronal kinases, phosphatases and activators ('phosphorylation machines') which facilitate the dynamic molecular interactions that underlie these processes.

Animals↗
PubMed2001

Solid variant of alveolar rhabdomyosarcoma with unbalanced t(2;13) and hypotetraploidy, without MYCN amplification.

The histological subtype of alveolar rhabdomyosarcoma (AR) is characterised by the cytogenetic translocation t(2;13)(q35;q14) in approximately 70% of cases, a rearrangement rarely present in the embryonal rhabdomyosarcoma (ER) subtype. The MYCN gene is amplified in some cases of AR. We present a young man with an unusual pattern, namely solid variant of AR with hypotetraploidy and the t(2;13) in an unbalanced form. The MYCN gene was not amplified on FISH, but showed increased copy number, consistent with ploidy.

Adult↗
PubMed2001

How important is history of unconsciousness in head injury patients?

A total of 100 patients of head injury were studied. They all underwent thorough clinical and neurological examination, skull radiography and CT scan of head. And with the help of all these parameters an evaluation was done to find out the importance of history of unconsciousness on risk of intracranial complications. A lot of controversies exist about detection of factors that make a patient of head injury a high risk candidate for developing intracranial complications. Young active population was the most commonly affected group in head injury with male preponderance at all ages. Roadside accident found to be the main cause of head trauma in adults while fall from height in paediatric age group. Although Glassgow Coma Index (GCI) was found to be a good predictor for intracranial complications as well as final outcome in patients with total score of 12 or less but it was not equally good in patients of minor head injury (GCI = 13-15). Similarly history of unconsciousness was not found to be correlating well with risk of intracranial complications but longer duration of unconsciousness was found to be a poor prognostic index.

Adult↗