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S R Hamilton

Publications and source records attributed to S R Hamilton.

At least 37 records · Page 2Linked to original sources
PubMed2000

Aberrant methylation of the Cyclooxygenase 2 CpG island in colorectal tumors.

Cyclooxygenases (COXs) are key enzymes that convert arachidonic acid to prostaglandins. Overexpression of one of the COX isozymes, COX2, has been shown to play an important role in colorectal cancer progression. Recently, however, low expression of COX2 has been reported in a subset of colorectal and gastric cancers. Aberrant CpG island methylation and associated transcriptional silencing are common in colorectal cancer, and we therefore investigated the potential role of methylation in the transcriptional silencing of COX2. We examined the methylation status of the COX2 5' CpG island in a series of tumor cell lines. Among the 33 cell lines examined, dense methylation (>70%) of COX2 was detected in 5 cell lines, and partial methylation was detected in 10 cell lines. Detailed methylation mapping using bisulfite genomic sequencing revealed that loss of expression of COX2 mRNA was closely correlated with methylation of a region upstream of exon 1, and expression could be restored by demethylation using the DNA methyltransferase inhibitor 5-aza-deoxycytidine. Aberrant methylation of COX2 was also detected in 12 of 92 (13%) unselected sporadic primary colorectal cancers and 7 of 50 (14%) colorectal adenomas. COX2 methylation was strongly associated with the presence of the CpG island methylator phenotype (P<0.01), inversely related to p53 gene mutation (P<0.01), and unrelated to microsatellite instability status. We propose that COX2 expression in colorectal tumors is modulated by functional factors that favor high expression and by the CpG island methylator phenotype that favors silencing in a subset of cases. These results raise the possibility that tumors with COX2 methylation may be less sensitive to treatment using specific COX2 inhibitors.

Colorectal Neoplasms↗
PubMed2000

Fundic gland polyps in familial adenomatous polyposis: neoplasms with frequent somatic adenomatous polyposis coli gene alterations.

Fundic gland polyps (FGPs) are the most common gastric polyps in patients with familial adenomatous polyposis (FAP). FGPs have traditionally been regarded as nonneoplastic, possibly hamartomatous lesions, but the pathogenesis of FGPs in both FAP and sporadic patients remains unclear. FGPs in FAP can show foveolar dysplasia, and rarely invasive gastric adenocarcinoma has been reported in patients with FAP and fundic gland polyposis. Using direct gene sequencing and allelic loss assays at 5q, we analyzed somatic adenomatous polyposis coli (APC) gene alterations in 41 FAP-associated FGPs (20 with foveolar dysplasia, six indefinite for dysplasia, and 15 nondysplastic) and 13 sporadic FGPs. The foveolar epithelium and dilated fundic glands of the polyps were separately microdissected and analyzed in 25 of 41 FAP-associated FGPs and 13 of 13 sporadic FGPs. Somatic APC gene alterations were identified frequently (21 of 41 cases, 51%) in FAP-associated FGPs. Both the foveolar epithelium and the dilated fundic gland epithelium comprising the FGPs were shown to carry the same somatic APC gene alteration in 24 (96%) of 25 cases. Furthermore, there was no difference in the frequency of somatic APC gene alterations between FGPs with foveolar dysplasia (10 of 20, 50%), indefinite for dysplasia (four of six, 67%), and nondysplastic (seven of 15, 47%) in FAP patients (P: = 0.697). In contrast, FGPs from non-FAP patients showed infrequent (one of 13, 8%) APC gene alterations (P: = 0.008). These results show that FGPs in FAP patients are pathogenetically distinct from sporadic FGPs. Somatic, second-hit APC gene alterations, which precede morphological dysplasia in many FAP-associated FGPs, indicate that FGPs arising in the setting of FAP are neoplastic lesions.

Adenomatous Polyposis Coli↗
PubMed2000

Tissue prostanoids as biomarkers for chemoprevention of colorectal neoplasia: correlation between prostanoid synthesis and clinical response in familial adenomatous polyposis.

Recent studies indicate that sulindac, a nonsteroidal anti-inflammatory drug (NSAID), lowers mucosal prostanoid levels and regresses colorectal adenomas in patients with familial adenomatous polyposis (FAP). To determine whether they are biomarkers for sulindac-mediated chemoprevention of colorectal adenomas, levels of 5 prostanoids [prostaglandin (PG) D2, PGE2, PGF2alpha, thromboxane B2, and 6-keto-PGF1alpha] in the normal-appearing rectal mucosa from 7 FAP patients with a history of subtotal colectomy and ileorectal anastomosis and 4 FAP patients without surgery, were measured in the absence or presence of exogenously added arachidonic acid before the initiation and at the end of 3 months of sulindac treatment. The addition of arachidonic acid resulted in a uniform increase in the levels of all 5 prostanoids although this increase was selectively attenuated in patients with ileorectal anastomosis who took sulindac. In the latter patients, arachidonic acid also augmented the inhibition of prostanoid synthesis by sulindac. In contrast, sulindac failed to attenuate the increase in prostanoid levels resulting from arachidonic acid in patients without previous surgery. Importantly, when measured in the presence of arachidonic acid, the reduction in the levels of all 5 prostanoids due to sulindac was statistically correlated with a reduction in the size and number of adenomas in the two groups of patients combined. These results suggest that tissue prostanoids measured in the presence of arachidonic acid may serve as sensitive and reliable biomarkers in monitoring the clinical responsiveness of FAP patients undergoing chemoprevention for colorectal neoplasia with NSAIDs.

Adenomatous Polyposis Coli↗
PubMed2000

Detection of microsatellite instability by fluorescence multiplex polymerase chain reaction.

We have created a clinical molecular diagnostic assay to test for microsatellite instability (MSI) at multiple loci simultaneously in paraffin-embedded surgical pathology colon resection specimens. This fluorescent multiplex polymerase chain reaction (PCR) assay analyzes the five primary microsatellite loci recommended at the 1997 National Cancer Institute-sponsored conference on MSI for the identification of MSI or replication errors in colorectal cancer: Bat-25, Bat-26, D2S123, D5S346, and D17S250. Amplicon detection is accomplished by capillary electrophoresis using the ABI 310 Genetic Analyzer. Assay validation compared 18 specimens previously assessed by radioactive PCR and polyacrylamide gel electrophoresis detection to results generated by the reported assay. Germline and tumor DNA samples were amplified in separate multiplex PCR reactions, sized in separate capillary electrophoresis runs, and compared directly to identify novel length alleles in tumor tissue. A concordance of 100% between the two modalities was achieved. The multiplex assay routinely detected a subpopulation of 10% tumor alleles in the presence of 90% normal alleles. A novel statistical model was generated that corroborates the validity of using results generated by analysis of five independent microsatellites to achieve a single overall MSI diagnosis. The assay presented is superior to standard radioactive monoplex PCR, polyacrylamide gel electrophoretic analysis, primarily due to the multiplex PCR format.

Alleles↗
PubMed2000

Phenotypic and molecular characteristics of hyperplastic polyposis.

BACKGROUND & AIMS: Patients with hyperplastic polyposis are reported to have multiple and/or large hyperplastic polyps (HPs) and an increased risk of colorectal cancer, but the phenotype and genetic alterations in hyperplastic polyposis have not been studied in detail. METHODS: We evaluated clinical-pathological and molecular characteristics of 129 HPs, 6 serrated adenomas, and 3 admixed hyperplastic-adenomatous polyps from 13 patients with hyperplastic polyposis (more than 20 HPs), 5 patients with a large HP (>/=1 cm in diameter), and 5 patients with multiple HPs (5-10 HPs). RESULTS: HPs in the right colon in contrast to the left colorectum had more frequent topographic dysregulation of p21(Waf-1/Cip1) expression (94% vs. 76%, P = 0.03) and of proliferation (92% vs. 53%, P = 0. 0001), but less frequent allelic loss of chromosome 1p (4% vs. 17%, P = 0.03). K-ras mutation was present in 8% of HPs, p53 gene product overexpression in none, and microsatellite instability in 3% without relationship to microsatellite instability in synchronous cancer. Patients with a large HP differed from those with multiple HPs in having a high frequency of right-sided HP (63% vs. 22%, P = 0.01) and of right-sided colon cancer (100% vs. 8%, P = 0.003). Hyperplastic polyposis was associated with a family history of colorectal cancer (P = 0.01) and with loss of chromosome 1p in HP (21% vs. 0%, P = 0.001). CONCLUSIONS: A hyperplastic polyp/dysplasia-to-adenocarcinoma sequence can be manifested in 3 distinct phenotypes consisting of patients with hyperplastic polyposis and chromosome 1p allelic loss in some HPs, in contrast to patients who have large, right-sided HPs or small numbers of HPs that lack 1p loss.

Adenoma↗
PubMed2000

Hemodynamic pathogenesis of ischemic hepatic injury following cardiogenic shock/resuscitation.

Post-ischemic hepatic injury is observed commonly following cardiogenic or hypovolemic shock. We evaluated the putative roles of the alpha-adrenergic sympathetic nervous system and the renin-angiotensin axis in the pathogenesis of hepatic injury following cardiogenic shock. Previous studies have characterized the hepatic hemodynamic response to shock, while the relationship of these hemodynamic changes to ischemic hepatic injury has not been defined. Sustained (4 h) periods of pericardial tamponade (after mild hemorrhage) followed by 2 h of resuscitation generated a reproducible model of cardiogenic shock and consequent post-ischemic hepatic injury in anesthetized pigs. In a separate group of pigs, the alpha-adrenergic component of the sympathetic nervous system was ablated with phenoxybenzamine or, in other groups, the renin-angiotensin axis was ablated by either prior nephrectomy or, separately, by confirmed angiotensin converting enzyme inhibition with teprotide. The hepatic injury response in each case was reevaluated. Compared to sham-shocked pigs, those subjected to tamponade alone manifested selective splanchnic vasospasm and consequent biochemical and histological evidence of classic post-ischemic liver injury (centrilobular necrosis involving about a third of each hepatic lobule). These manifestations of splanchnic vasospasm and the consequent ischemic injury were not ameliorated by confirmed alpha-adrenergic blockade, but significantly attenuated by either method of prior ablation of the renin-angiotensin axis. This model of sustained cardiogenic shock and resuscitation generates the manifestations of ischemic hepatic injury associated with selective splanchnic vasospasm, findings consistent with previous, short-term, hemodynamic studies. The major mediator of this response, and the consequent hepatic injury, is the selective hypersensitivity of the mesenteric vasculature to the renin-angiotensin axis.

Alanine Transaminase↗
PubMed2000

Neuro-ophthalmology of movement disorders.

Movement disorders are a diverse group of neurologic disorders that share in common the frequent development of clinical abnormalities in ocular motility or visual perception. This article reviews the recent literature pertaining to the neuro-ophthalmologic advances in the basal ganglia disorders (Parkinson disease, progressive supranuclear palsy, corticobasal degeneration, multiple system atrophy, and Huntington disease), the spinocerebellar ataxias and episodic ataxias, amyotrophic lateral sclerosis, benign essential blepharospasm, hemifacial spasm, and Tourette syndrome.

Humans↗
PubMed2000

Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999.

BACKGROUND: Under the auspices of the College of American Pathologists, the current state of knowledge regarding pathologic prognostic factors (factors linked to outcome) and predictive factors (factors predicting response to therapy) in colorectal carcinoma was evaluated. A multidisciplinary group of clinical (including the disciplines of medical oncology, surgical oncology, and radiation oncology), pathologic, and statistical experts in colorectal cancer reviewed all relevant medical literature and stratified the reported prognostic factors into categories that reflected the strength of the published evidence demonstrating their prognostic value. Accordingly, the following categories of prognostic factors were defined. Category I includes factors definitively proven to be of prognostic import based on evidence from multiple statistically robust published trials and generally used in patient management. Category IIA includes factors extensively studied biologically and/or clinically and repeatedly shown to have prognostic value for outcome and/or predictive value for therapy that is of sufficient import to be included in the pathology report but that remains to be validated in statistically robust studies. Category IIB includes factors shown to be promising in multiple studies but lacking sufficient data for inclusion in category I or IIA. Category III includes factors not yet sufficiently studied to determine their prognostic value. Category IV includes factors well studied and shown to have no prognostic significance. MATERIALS AND METHODS: The medical literature was critically reviewed, and the analysis revealed specific points of variability in approach that prevented direct comparisons among published studies and compromised the quality of the collective data. Categories of variability recognized included the following: (1) methods of analysis, (2) interpretation of findings, (3) reporting of data, and (4) statistical evaluation. Additional points of variability within these categories were defined from the collective experience of the group. Reasons for the assignment of an individual prognostic factor to category I, II, III, or IV (categories defined by the level of scientific validation) were outlined with reference to the specific types of variability associated with the supportive data. For each factor and category of variability related to that factor, detailed recommendations for improvement were made. The recommendations were based on the following aims: (1) to increase the uniformity and completeness of pathologic evaluation of tumor specimens, (2) to enhance the quality of the data needed for definitive evaluation of the prognostic value of individual prognostic factors, and (3) ultimately, to improve patient care. RESULTS AND CONCLUSIONS: Factors that were determined to merit inclusion in category I were as follows: the local extent of tumor assessed pathologically (the pT category of the TNM staging system of the American Joint Committee on Cancer and the Union Internationale Contre le Cancer [AJCC/UICC]); regional lymph node metastasis (the pN category of the TNM staging system); blood or lymphatic vessel invasion; residual tumor following surgery with curative intent (the R classification of the AJCC/UICC staging system), especially as it relates to positive surgical margins; and preoperative elevation of carcinoembryonic antigen elevation (a factor established by laboratory medicine methods rather than anatomic pathology). Factors in category IIA included the following: tumor grade, radial margin status (for resection specimens with nonperitonealized surfaces), and residual tumor in the resection specimen following neoadjuvant therapy (the ypTNM category of the TNM staging system of the AJCC/UICC). (ABSTRACT TRUNCATED)

Biomarkers, Tumor↗
PubMed1999

Risk factors for Ki-ras protooncogene mutation in sporadic colorectal adenomas.

The Ki-ras protooncogene frequently is mutated in colorectal adenocarcinomas, but the etiology of this molecular event is uncertain. We investigated the association between variables known or suspected to be related to risk for colorectal cancer and the occurrence of Ki-ras mutations in colorectal adenomas. This study was conducted among 678 male and female participants, 40-80 years of age, enrolled in a phase III trial testing the effects of a wheat bran fiber supplement on adenoma recurrence. Exposure information on the risk factors of interest was assessed through self-administered questionnaires. Mutations in codons 12 and 13 of the Ki-ras protooncogene were analyzed in baseline adenomas 0.5 cm or larger by PCR amplification followed by direct sequencing. Eighteen percent (120 of 678) of the participants had one or more adenoma(s) with Ki-ras mutations. A higher risk of Ki-ras mutations was associated with increasing age and a lower intake of total folate. The odds ratio (OR) for Ki-ras mutations for individuals >72 years of age was 1.98 [95% confidence interval (CI) = 1.19-3.27; P for trend = 0.008] compared with those less than 65 years of age. Compared with individuals in the lower tertile of total folate, those in the upper tertile had an approximately 50% lower risk of having Ki-ras mutation-positive adenomas (OR = 0.52; 95% CI = 0.30-0.88; P for trend = 0.02). There was a suggestion of a stronger inverse association of total folate with G-->T transversions (OR = 0.41; 95% CI = 0.20-0.87) than G-->A transitions (OR = 0.61; 95% CI = 0.31-1.21), although the CIs for the associations overlap. The results of these analyses suggest that the protective effect of folate in colon cancer observed in published studies may be mediated through folate's effect on Ki-ras mutations.

Adenoma↗
PubMed1999

Differential expression of the lysosome-associated membrane proteins in normal human tissues.

The lysosome-associated membrane proteins LAMP-1 and LAMP-2 have closely related structures, with 37% sequence homology, and are major constituents of the lysosomal membrane. Their roles are unknown, but they are thought to be structural or functional components of the lysosomal membrane. Recent reports suggest that despite their similar structure and common localization, LAMP-1 and LAMP-2 may have different functions. In our further study of these two molecules, the presence of LAMP-1 and LAMP-2 in a variety of human tissues was analyzed by immunohistochemistry, and their localization was compared to that of cathepsin D, a lysosomal hydrolase. the tissue content of LAMP-1 and LAMP-2 and their respective mRNAs were also analyzed by Northern and Western blotting. The LAMP molecules were detected by immunohistochemistry primarily in metabolically active cells, with a cytoplasmic distribution similar to that of cathepsin D and consistent with their predominant localization in lysosomes. However, there were marked differences in the intensity of staining and, in some cases, the localization of the three proteins. For example, there was much stronger staining for LAMP-2 than LAMP-1 in brain tissue and prostate ductal cells. These differences in localization were consistent with the results obtained in Western blotting of protein extracted from the tissues. The pattern of mRNA expression was similar in all of the examined tissues, with a single mRNA identified for LAMP-1 and two splice variant forms seen for LAMP-2. Our studies of these molecules in human tissues support the conclusion that the expression of the molecules is independently controlled in some tissues, suggesting that the molecules may have independent as well as similar functions.

Antigens, CD↗
PubMed1999

Analysis of masked mutations in familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is an autosomal-dominant disease characterized by the development of hundreds of adenomatous polyps of the colorectum. Approximately 80% of FAP patients can be shown to have truncating mutations of the APC gene. To determine the cause of FAP in the other 20% of patients, MAMA (monoallelic mutation analysis) was used to independently examine the status of each of the two APC alleles. Seven of nine patients analyzed were found to have significantly reduced expression from one of their two alleles whereas two patients were found to have full-length expression from both alleles. We conclude that more than 95% of patients with FAP have inactivating mutations in APC and that a combination of MAMA and standard genetic tests will identify APC abnormalities in the vast majority of such patients. That no APC expression from the mutant allele is found in some FAP patients argues strongly against the requirement for dominant negative effects of APC mutations. The results also suggest that there may be at least one additional gene, besides APC, that can give rise to FAP.

Adenomatous Polyposis Coli↗
PubMed1999

Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia.

The DNA repair protein O6-methylguanine DNA methyltransferase (MGMT) removes alkyl adducts from the O6 position of guanine. MGMT expression is decreased in some tumor tissues, and lack of activity has been observed in some cell lines. Loss of expression is rarely due to deletion, mutation, or rearrangement of the MGMT gene, but methylation of discrete regions of the CpG island of MGMT has been associated with the silencing of the gene in cell lines. We used methylation-specific PCR to study the promoter methylation of the MGMT gene. All normal tissues and expressing cancer cell lines were unmethylated, whereas nonexpressing cancer cell lines were methylated. Among the more than 500 primary human tumors examined, MGMT hypermethylation was present in a subset of specific types of cancer. In gliomas and colorectal carcinomas, aberrant methylation was detected in 40% of the tumors, whereas in non-small cell lung carcinomas, lymphomas, and head and neck carcinomas, this alteration was found in 25% of the tumors. MGMT methylation was found rarely or not at all in other tumor types. We also analyzed MGMT expression by immunohistochemistry in relation to the methylation status in 31 primary tumors. The presence of aberrant hypermethylation was associated with loss of MGMT protein, in contrast to retention of protein in the majority of tumors without aberrant hypermethylation. Our results suggest that epigenetic inactivation of MGMT plays an important role in primary human neoplasia.

CpG Islands↗
PubMed1999

Cytomegaloviral enterocolitis: clinical associations and outcome.

PURPOSE: Cytomegaloviral enterocolitis is an uncommon disorder that can complicate inflammatory bowel disease. It is more common in patients with acquired immunodeficiency syndrome and can occur in patients on immunosuppressive therapy for autoimmune or inflammatory diseases and in allograft recipients. Mortality rates of up to 71 percent have been reported for cytomegaloviral enterocolitis. The aims of this study were 1) to identify the presentation, underlying medical conditions, treatment, and outcome of patients with cytomegaloviral enterocolitis and 2) to determine the prevalence of this infection in patients undergoing intestinal resection for inflammatory bowel disease. METHODS: A retrospective chart review of patients with pathologic evidence of cytomegaloviral enterocolitis from 1985 through 1996 was performed. To determine the prevalence of this condition, the hospital discharge database was searched for the diagnoses of ulcerative colitis and Crohn's disease in patients who underwent bowel resection. RESULTS: 93 patients (mean age, 44 years; 66 percent males) had cytomegaloviral infection in the small intestine (n = 6), large intestine (n = 86), or appendix (n = 1). Patients with acquired immunodeficiency syndrome (n = 42), with ulcerative colitis (n = 11), with Crohn's disease (n = 11), receiving organ transplant (n = 12), receiving bone marrow transplant (n = 8), and in other immunosuppressed states (n = 11) comprised this study. Seventeen patients (18 percent) underwent intestinal resection, and the remaining 76 patients were treated medically. Abdominal pain (77 vs. 37 percent; P < 0.01) and gastrointestinal bleeding (65 vs. 34 percent; P < 0.05) were more common presenting symptoms in patients who required resection than patients in the medically managed group. Mortality was 17.6 percent in the surgically managed group and 14.5 percent in the patients who were managed medically. The median duration of ulcerative colitis in patients with coexisting cytomegaloviral infection was 12 months. The prevalence of cytomegaloviral enterocolitis was 4.6 percent in patients with ulcerative colitis and 0.8 percent in patients with Crohn's disease. CONCLUSIONS: These data suggest that cytomegaloviral infection more frequently complicates ulcerative colitis than Crohn's disease. Furthermore, a short and fulminant course of ulcerative colitis may indicate coexisting cytomegaloviral infection. The overall low mortality in this retrospective study suggests that aggressive medical and surgical treatment improves survival in patients with cytomegaloviral enterocolitis.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Origin of microsatellite instability in gastric cancer.

Microsatellite instability (MSI) is observed in 13-44% of gastric carcinoma. The etiology of MSI in gastric carcinoma has not been clearly defined. To assess the role of mismatch repair in the development of MSI in gastric cancer, expression of hMSH2 and hMLH1 was explored. We examined 117 gastric carcinomas for MSI and observed instability at one or more loci in 19 (16%) of these tumors. Of the 19 tumors with MSI, nine exhibited low-rate MSI (MSI-L) with instability at <17% of loci, whereas the remaining 10 exhibited high-rate MSI (MSI-H) with instability at >33% of loci examined. Immunohistochemical staining for hMLH1 and hMSH2 was performed on eight of the tumors with MSI-H, five with MSI-L, and 15 tumors without MSI. All eight tumors with MSI-H showed loss of staining for either hMLH1 (n = 5) or hMSH2 (n = 3). In contrast, tumors with MSI-L or without MSI all showed normal hMSH2 and hMLH1 protein expression patterns. Moreover, all eight of the tumors with MSI-H also showed instability at BAT-26, whereas none of the MSI-L tumors or tumors without instability showed instability at BAT-26. These findings suggest that the majority of high-level MSI in gastric cancer is associated with defects of the mismatch repair pathway. Although larger studies are needed, BAT-26 appears to be a sensitive and specific marker for the MSI-H phenotype in gastric carcinoma.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Genetic alterations in hepatocellular carcinomas: association between loss of chromosome 4q and p53 gene mutations.

The major risk factors for hepatocellular carcinomas (HCC) in high incidence areas include infection with hepatitis B and C viruses (HBV, HCV) and exposure to aflatoxin. Genetic alterations in 24 liver resection specimens from Shanghai and Qidong were studied. Hepatitis B virus was integrated in all patient samples, and a null phenotype for the GSTM1 enzyme was present in 63% of patients. Alteration of p53 was present in 95% (23/24) of cases: mutations of the p53 gene in 12 HCC, p53 overexpression in 13 and loss of heterozygosity (LOH) of chromosome 17p in 17. All seven HCCs with a p53 mutation from Qidong and three of five from Shanghai had the aflatoxin-associated point mutation with a G to T transversion at codon 249, position 3. No HCC had microsatellite instability. LOH of chromosome 4q, 1p, 16q and 13q was present in 50%, 46%, 42% and 38%, respectively, and 4q was preferentially lost in HCCs containing a p53 mutation: LOH of 4q was present in 75% (9/12) of HCC with, but only 25% (3/12) of HCC without, a p53 gene mutation (P = 0.01). These data indicate a possible interaction between p53 gene mutation and 4q loss in the pathogenesis of HCC.

Carcinoma, Hepatocellular↗
PubMed1999

Lymphocytic gastritis: association with etiology and topology.

Lymphocytic gastritis (LG) is an uncommon chronic gastritis characterized by lymphocytosis of foveolar and surface epithelium. Lymphocytic gastritis is associated with celiac disease, Helicobacter pylori (HP) gastritis, and varioliform gastritis, but its topology and severity with respect to the associated entities have not been studied in detail. Therefore, we studied 103 patients with LG classified according to the associated entities, including the distribution and severity of LG in the 70 patients from whom biopsy specimens of both antrum and body were available. In 84 patients (82%), a distinct associated entity was identified, including 39 with celiac disease, 30 with HP infection, 4 with varioliform gastritis, 2 each with inflammatory polyp, Crohn's disease, human immunodeficiency virus infection, lymphoma, and esophageal carcinoma, and 1 with lymphocytic gastroenterocolitis. Lymphocytic gastritis was found in 33% of patients with celiac disease and 4.1% of histopathologically defined HP gastritis. The severity of intraepithelial lymphocytosis was greater in antrum than in body in 83% (20 of 24) of LG associated with celiac disease, but in only 19% (4 of 21) of LG associated with HP infection (p < 0.00002). All four patients with varioliform gastritis had more severe involvement of body. Lymphocytic colitis was common (38%, 5 of 13) in celiac disease with LG. Our results indicate that lymphocytic gastritis most commonly occurs in celiac disease and HP infection, but rarely with other entities. The topology of LG can direct the clinical evaluation for associated disease.

Adolescent↗
PubMed1999

Neuro-ophthalmology of eye-movement disorders.

Magnetic resonance and functional brain imaging continue to expand their roles in complementing the clinical examination to localize the causes of eye-movement disorders. A retrospective review from county-based clinical practices emphasized generally benign causes of third, fourth, and sixth cranial nerve palsies in children, but a study from a tertiary referral center found a high incidence of neoplasms causing sixth-nerve palsies in children. A prospective study found that 38% of diabetic patients with third-nerve palsies had anisocoria up to 2.5 mm. An initial attempt to develop an evidence-based practice pathway for the evaluation of ocular motor nerve palsies has been developed for isolated sixth-nerve palsies in adults. In an important study of Graves hyperthyroidism, treatment with radioactive iodine was more likely than methimazole therapy alone to be associated with the appearance or worsening of ophthalmopathy. The clinical worsening of eye findings could be prevented by concurrent administration of corticosteroids for 3 months. Smoking is still a major controllable risk factor for thyroid ophthalmopathy.

Abducens Nerve Diseases↗