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Biomedical subjects

K W Barwick

Publications and source records attributed to K W Barwick.

At least 37 records · Page 2Linked to original sources

Ranitidine therapy for gastroesophageal reflux disease. Results of a large double-blind trial.

In a multicenter, double-blind trial, 284 patients with gastroesophageal reflux disease were evaluated before, during, and after six weeks of treatment with either placebo or ranitidine (150 mg twice daily). Randomization resulted in two comparable patient groups. Ranitidine treatment was significantly more effective than placebo treatment in decreasing the frequency and the severity of heartburn during both daytime and nighttime assessment periods. There was a significant correlation between improvement in heartburn symptoms and decrease in antacid consumption; hence, patients receiving ranitidine consumed significantly fewer antacid tablets. Among patients with endoscopic esophagitis at baseline, the overall change in endoscopic classification after six weeks of therapy was significantly better for the ranitidine-treated patients. The ranitidine-treated group had less evidence of erosions and ulcerations as well as greater healing. There were no differences between the groups with respect to changes in esophageal mucosal sensitivity to acid perfusion or changes in histologic grading of esophageal mucosal biopsy specimens. The ranitidine safety profile was similar to that of previous studies. We conclude that, in patients with gastroesophageal reflux disease, ranitidine therapy, 150 mg twice daily, markedly reduced the heartburn symptoms of reflux disease and significantly improved the endoscopic appearance of the esophageal mucosa.

Adult↗

Characterization of intestinal brush border cytoskeletal proteins of normal and neoplastic human epithelial cells. A comparison with the avian brush border.

The elaborate cytoskeletal matrix underlying the intestinal epithelial cell brush border (BB) is the hallmark of a mature enterocyte. As such, alterations in this structure are potentially useful as markers aiding in the recognition of subtle defects in cell maturation, such as those accompanying dysplasia and neoplasia. For exploration of this hypothesis, the BB components of human ileal and colonic enterocytes have been compared structurally and biochemically with the well-characterized avian BB, and alterations in the BB cytoskeleton in various states of dysplasia and neoplasia have been identified. Ultrastructural analysis of isolated human ileal BBs indicate that the human BB is structurally homologous to BBs isolated from chicken and other mammalian sources. Like other mammalian BBs (eg, from rat) the terminal web cytoskeleton of the human BB is less extensive than that in the avian BB. Immunochemical analysis of isolated human BBs indicates that the major proteins of the avian microvillar actin bundle, villin, fimbrin, and the 110-kd subunit of the 110K-calmodulin complex, are all present in the human BB. The terminal web protein myosin is also present. Unlike the terminal web of the avian BB, which contains a BB-specific isoform of spectrin, TW 260/240, the human BB contains the more widely distributed spectrin isoform, fodrin. In addition, the human BB contains multiple proteins immunoreactive with antibodies to protein 4.1, a spectrin/actin binding protein that is absent from the avian BB. Immunolocalization studies examining the distribution of the BB-specific microvillar protein, villin, in human colonic mucosa indicate that the localization of this protein is disrupted in certain dysplastic and neoplastic states. Thus, both the expression and/or distribution of BB-specific proteins such as villin may be useful markers for defects in the differentiation state of the enterocyte.

Animals↗

Importance of tumor pathology and morphology in patients with surgically resected colon cancer. Findings from the Gastrointestinal Tumor Study Group.

Previous analyses of findings from the Gastrointestinal Tumor Study Group (GITSG) study GI 6175, a four-arm randomized trial of patients with adjuvant colon cancer, have revealed no efficacy for chemotherapy or immunotherapy, but Dukes' Stage was found to have prognostic significance in both survival and disease-free survival. In this study, the exophytic tumor as primary type, maximal tumor dimension, and degree of differentiation were examined for prognostic importance. In a model simultaneously including treatment effects, significance levels for prognosis in total survival were: Dukes' stage (P less than 0.0001), exophytic tumors (P = 0.05), maximal dimension (P = 0.005), and well versus poor differentiated tumors (P = 0.06). This observation about tumor length, adjusted for stage and morphology, provides evidence that size is prognostic in colonic tumors. In addition, an interaction between tumor morphology and immunotherapy, adjusted for Dukes' stage, was noted. In 100 patients with exophytic tumors, significant survival and disease-free survival benefit (P less than 0.02) from immunotherapy occurred. Tumor morphology is found to be an important prognostic variable and should be carefully considered in the construction of future trials in this disease site.

Aged↗

Obesity in celiac sprue.

Celiac sprue usually results in biochemical and clinical signs of malabsorption, nutrient loss, and resulting growth failure. We report a child with celiac sprue diagnosed at 1 year of age who was initially cachectic but who eventually developed obesity while taking a gluten-containing diet.

Celiac Disease↗

Quantitative US attenuation in normal liver and in patients with diffuse liver disease: importance of fat.

Two methods are used to estimate ultrasound attenuation in liver. These were based on amplitude change and frequency change as a result of depth dependent attenuation. Evaluation of the two methods against a family of calibrated phantoms yielded correlation coefficients of 0.98 and 0.99, respectively. Liver attenuation in 26 control subjects was 0.50 and 0.52 dB/MHz/cm, respectively. Liver attenuation was estimated in 50 patients who later underwent liver biopsy. Comparison with quantitative histologic results showed that the presence of fat alone accounted for the increased attenuation associated with cirrhosis. Similar high attenuation values were found in patients with fatty infiltration. Fibrosis alone did not result in elevated liver attenuation. Cirrhotics without fatty infiltration had attenuation similar to that of the controls. Mechanisms of action are discussed.

Adolescent↗

Amiodarone hepatotoxicity. A clinicopathologic study of five patients.

Five patients had amiodarone hepatotoxicity detected on routine biochemical monitoring. Symptoms attributable to hepatotoxicity were minimal or absent; reversible hepatomegaly was seen in two patients, whereas three patients had signs of nonhepatic amiodarone toxicity before or with hepatotoxicity. Serum aminotransferase levels were elevated in all patients and alkaline phosphatase levels in four; no patient had hyperbilirubinemia or prolongation of the prothrombin time. Light microscopy showed steatosis, cellular degeneration, and cellular necrosis in the biopsy samples of four patients, whereas the fifth patient's sample had a granulomatous injury pattern. Electron microscopic study of liver tissue done in two patients showed phospholipid-laden lysosomal lamellar bodies. These findings suggest that both toxic and hypersensitivity liver injury can occur in response to amiodarone. The presence of phospholipid-laden lysosomal lamellar bodies may help differentiate amiodarone hepatotoxicity from alcoholic liver disease or other causes of hepatic steatosis.

Aged↗

Renin in angiolymphoid hyperplasia with eosinophilia. Its possible effect on vascular proliferation.

A hypertensive man became normotensive after the surgical removal of two subcutaneous masses of angiolymphoid hyperplasia with eosinophilia. To demonstrate that angiolymphoid hyperplasia with eosinophilia is a renin-producing pathologic condition, Bowie stain for juxtaglomerular cell granules and immunohistochemistry for human renin were used. Bowie stain was positive in cells showing cytoplasmic granules similar to those found in the juxtaglomerular cells of the kidney. Immunohistochemical staining using antiserum against human renin showed the presence of renin-containing cells. This staining was not seen after substitution of the specific renin antiserum by preimmune serum, by the renin antiserum preabsorbed with pure human renin, or with plasma from a patient with high-plasma renin activity. Renin-containing cells were located in areas surrounding vascular structures and were apparently neither endothelial, mast, nor lymphoid cells. Six of eight additional cases of angiolymphoid hyperplasia with eosinophilia were positive for renin-containing cells. Renin has been described in several other histologically highly vascularized tumors. Since a product of renin, angiotensin II, has been found to have angiogenic properties, it is possible to postulate that renin, through angiotensin II, may stimulate the proliferation of vessels and, therefore, may be involved in the pathogenesis of angiolymphoid hyperplasia with eosinophilia.

Abdominal Muscles↗

Sulfasalazine-induced pulmonary disease.

Sulfasalazine has been widely used in the treatment of inflammatory bowel disease. Although a high incidence of side effects has been reported, pulmonary complications are rare. The clinical, radiographic, and histological abnormalities that occurred in a patient three months after initiation of sulfasalazine are described. A review of the literature suggests that the possibility of drug-induced pulmonary disease should be considered in any patient with inflammatory bowel disease receiving treatment with sulfasalazine who develops symptoms or radiographic evidence of pulmonary disease. Transbronchial biopsy may be useful in confirming the type of pulmonary injury.

Aged↗

Filiform polyposis: an unusual complication of inflammatory bowel disease.

Filiform polyposis is an unusual form of inflammatory polyposis which complicates inflammatory bowel disease. Recognition of this variant is important in that its radiographic and endoscopic picture may mimic villous adenoma or adenocarcinoma. Filiform polyposis may precipitate obstruction by stricture formation or give rise to major hemorrhage. We report five patients with inflammatory bowel disease complicated by asymptomatic filiform polyposis to emphasize the pathology of this lesion. We also review the literature regarding this topic.

Adult↗

Congenital polycystic tumor of the atrioventricular node. Autopsy study with immunohistochemical findings suggesting endodermal derivation.

Atrioventricular node congenital polycystic tumor, a lesion that causes heart block and sudden unexpected death, has been postulated to arise from the lymphatics, foregut endoderm, cardiac mesoderm, and mesothelium since its initial description in 1911. No theory concerning the histogenesis of this tumor has been completely satisfactory, either from an embryologic or a clinical standpoint. Biologic studies including cell culture systems from the lesions as well as optimal ultrastructural examination have been compromised due to postmortem autolysis. We studied four examples of this entity by standard histochemical stains for mucopolysaccharides, and by modified immunohistochemical labeling for carcinoembryonic antigen, factor VIII, and keratin. Results suggest an origin from foregut endoderm. The lesion has not been reported to be outside the region of the atrioventricular junction, but was demonstrated in the thymus gland in one of our cases.

Adult↗

The painful accessory navicular.

The accessory navicular is usually considered a normal anatomic and roentgenographic variant. The term may refer to two distinct patterns. First, a sesamoid bone may be present within the posterior tibial tendon (Type 1); this is anatomically separate from the navicular. Second, an accessory ossification center may be medial to the navicular (Type 2). During postnatal development this is within a cartilaginous mass that is continuous with the cartilage of the navicular. At skeletal maturity the accessory center usually fuses with the navicular to form a curvilinear bone. The Type 2 pattern may be associated with a painful foot, particularly in the athletic adolescent, and should not be arbitrarily dismissed as a roentgenologic variant in the symptomatic patient. The clinical, radiologic, pathologic, and surgical findings in ten cases are reviewed. Roentgenographically the ossicle is triangular or heart-shaped. 99mTc MDP imaging may be of value when the significance of the ossicle is uncertain. Even when the roentgenographic variant is bilateral, increased radionuclide activity occurs only on the symptomatic side. Histologic examination of surgically excised specimens reveals inflammatory chondro-osseous changes in the navicular-accessory navicular synchondrosis compatible with chronic trauma and stress fracture. Nonsurgical treatment with orthotics or cast immobilization produces variable results and resection of the accessory navicular may be the treatment of choice.

Adolescent↗

Bronchial lavage proteins as correlates of histopathologic airway changes in healthy smokers and patients with pulmonary carcinoma.

Cigarette smoking is known to be an important etiologic factor in several lung diseases; however, the number of smokers who develop these diseases represents a small segment of the smoking population. It is possible that evidence of inhalation-induced injury to bronchial epithelial cells of smokers will be reflected in the proteinaceous products of these cells, thereby identifying a high-risk subgroup. We have tested this hypothesis by analysis of 2 proteins, free secretory component (FSC) and the keratins, in lavage fluids obtained from 4 groups of subjects: 30 normal nonsmokers, 15 asymptomatic smokers, 22 symptomatic smokers, and 40 carcinoma patients. Among symptomatic smokers, FSC relative to total protein (FSC/TP) was depressed compared with that in nonsmokers and asymptomatic smokers. The keratins were detected only in symptomatic smokers and correlated with pack/years of smoking history (p = 0.017). Carcinoma patients had depressed FSC/TP and detectable keratin (33 of 38 patients studied). Lung sections from carcinoma patients studied immunohistochemically revealed an apparent inverse relationship between tissue FSC and keratins. This inverse relationship was borne out by analysis of these proteins in the lavage fluid of cancer patients (r = -0.4, p = 0.04). Thus, in cancer patients, immunohistochemical evidence of airway injury correlates with bronchial lavage levels of mucosal epithelial cell proteins. It is possible that smokers with altered levels of these proteins may be the ones at increased risk of smoking-associated lung disease.

Adolescent↗

The association of histologic gastritis with gastroesophageal reflux and delayed gastric emptying.

The aims of this study were to: 1) investigate the incidence of histologic gastritis in patients with gastroesophageal reflux (GER); 2) ascertain if gastritis in GER patients could be correlated with impaired gastric emptying; and 3) determine if the presence of histologic antral gastritis correlated with other parameters of esophageal and gastric function. Twenty-three GER patients, mean age 53.3 years (range 28-68 years) with subjective and objective evidence for GER; and 20 normal subjects (13 males and seven females), mean age 28.7 years (range 19-46 years), underwent upper gastrointestinal endoscopy. Antral biopsies obtained from the greater curvature were graded as: 0 = normal; 1 = chronic gastritis; 2 = chronic active gastritis; and 3 = chronic atrophic gastritis. All patients underwent a gastric emptying study using an isotope-labeled semisolid meal. Eighteen of the 23 GER patients (78%) had histologic gastritis compared to two (10%) of the normals. No subject had endoscopic evidence of gastritis. Gradings of histologic gastritis were significantly (p less than 0.05) correlated with delayed gastric emptying. Twelve GER patients had severe gastritis (grades 2 or 3) and their gastric emptying, 79.7% +/- 5.8 (mean +/- S.E.M.) retention of isotope at 90 minutes after the meal, was significantly slower (p less than 0.01) than the 11 GER patients with either grade 0 or 1 gastritis, 56.1% +/- 5.9 retention, or the normal subjects, 51.8% +/- 1.7. We conclude that: 1) histologic gastritis is associated with GER disease; and 2) slowing of gastric emptying can be significantly correlated with increased severity of histologic gastritis in GER patients.

Adult↗

Gastrointestinal manifestations of multiple endocrine neoplasia, type IIB.

Multiple endocrine neoplasia, type IIB (MEN 2b), is comprised of medullary carcinoma of the thyroid, pheochromocytoma, diffuse ganglioneuromatosis of the gastrointestinal tract, and skeletal abnormalities. Alimentary tract manifestations, especially enlargement of the lips and tongue by proliferative neural tissue, are often the earliest clues to the presence of the syndrome. A patient is presented here who illustrates the chronicity and diversity of symptoms characteristic of MEN 2b. It is important to recognize the typical oral manifestations of this syndrome so that the thyroid gland can be evaluated before the development of disseminated medullary carcinoma.

Adult↗

Reassessment of esophageal histology in normal subjects: a comparison of suction and endoscopic techniques.

We have examined esophageal biopsies from 18 asymptomatic volunteers. These normal subjects were also evaluated by esophageal manometry with determination of motor function of the esophagus and lower esophageal sphincter pressure, a modified Bernstein acid infusion test, and a basal pH reflux test. In 12 subjects, biopsies were obtained by suction technique; the remaining six had pinch biopsies performed during upper gastrointestinal endoscopy. Forty-nine (92.5%) of the 53 suction biopsies yielded tissue as deep as muscularis mucosa or at least ample amounts of lamina propria. In contrast, all 28 endoscopic biopsies yielded squamous epithelium only. Moreover, suction biopsies were generally well-oriented (83%), whereas endoscopic biopsies were less commonly well-oriented (35.7%). All volunteer subjects had a negative acid reflux test confirming the absence of latent or asymptomatic reflux. Only one subject (5.6%) had biopsies which met histologic criteria for gastroesophageal reflux. We conclude that: 1) more tissue, more information, and better orientation is achieved with suction than with endoscopic biopsies of the esophagus; 2) the low false-positive rate observed in volunteers in whom gastroesophageal reflux was objectively excluded emphasizes the value of esophageal biopsy as a reliable index in the evaluation of gastroesophageal reflux.

Adult↗

Use of avidin-biotin complex in an ELISA system: a quantitative comparison with two other immunoperoxidase detection systems using keratin antisera.

Three systems--the indirect, peroxidase-antiperoxidase (PAP), and avidin-biotin peroxidase complex (ABC) detection system--were compared in quantitative ELISA titration and inhibition assays and tissue labeling with keratin antisera. The ABC system was found to be the most sensitive of the three in ELISA titration assays, being approximately 4-fold more sensitive than the indirect method and 2-fold more sensitive than the PAP method. In addition, the ABC method demonstrated increased sensitivity when compared on tissue sections. Furthermore, the secondary and tertiary components of the PAP and ABC systems were titrated and optimal concentration ranges determined for use in ELISA inhibition assays. In ELISA inhibition assays the broadest usable inhibitor range and maximal sensitivity were obtained using the ABC system as compared with indirect and PAP detection systems. Finally, the effects of varying microtiter plate-coating concentrations on range and sensitivity were examined, and possible explanations are discussed including the possibility of surface-bound antigen being a competitor for the antibody of the solution phase antibody-antigen complex.

Antibodies↗