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Biomedical subjects

W Silen

Publications and source records attributed to W Silen.

At least 37 records · Page 2Linked to original sources

Isoperistaltic jejunal interposition for intractable postgastrectomy alkaline reflux gastritis.

BACKGROUND: The Roux-en-Y gastrojejunostomy is a popular method in the operative treatment of alkaline reflux gastritis and other postgastrectomy sequelae, but is associated with a high incidence of the so-called "Roux stasis syndrome." The Henley jejunal interposition has been used occasionally, albeit not widely, as an alternative to the Roux-en-Y reconstruction. STUDY DESIGN: Six patients underwent Henley gastrojejunoduodenostomy to treat severe (Visick grade IV) symptoms following Billroth I and II procedures for peptic ulcer disease. All interposed jejunal segments were 40 cm in length and isoperistaltic in orientation. All patients had follow-up examination and telephone interview (mean 4.3 years, range 2.2 to 7.8 years). RESULTS: All patients noted dramatic improvement after remedial surgery in the first year of follow-up. After the first postoperative year, all patients remained virtually symptom-free (Visick grade I and II) with no complaints of gastrojejunal stasis or bile acid reflux. CONCLUSIONS: This experience suggests that the Henley jejunal interposition is our effective method of treating reflux gastritis and is not associated with the poor emptying frequently associated with the Roux-en-Y reconstruction.

Adult↗

Histologic and microbiologic features of biopsy samples from patients with normal and inflamed pouches.

PURPOSE: This study was undertaken to assess the electron microscopic and microbiologic findings in tissue biopsy samples from patients with pouchitis and to compare them with findings in patients with normal pouches, conventional ileostomies, and normal ileum. METHODS: Tissue samples were obtained from 78 patients: 23 patients with normal pouches endoscopically and histologically (Group 1), 12 patients with endoscopic and histologic evidence of inflammation (pouchitis) (Group 2), 14 patients who had either endoscopic or histologic evidence of inflammation but not both (Group 3), 20 patients with conventional ileostomies (Group 4), and 9 patients without ileostomies from whom biopsy samples of normal ileum were obtained (Group 5). RESULTS: The mean total aerobic facultative counts in the biopsy samples from the pouchitis patients were significantly higher when compared with biopsy samples from Groups 4 and 5 (P < 0.05). There were no significant differences in the mean anaerobic counts among the five groups. Positive cultures were obtained in 90 percent of patients with pouches compared with 69 percent of patients with conventional ileostomies or normal ileum (P < 0.05). Intramural bacteria were observed on electron microscopy in biopsy specimens of 47 percent patients with pouches compared with 14 percent of patients with conventional ileostomies or normal ileum (P < 0.05). However, the proportion of patients with positive cultures or intramural bacteria was not increased in the pouchitis group compared with the normal pouch group. CONCLUSION: These data suggest that intramural aerobic facultative bacterial counts are elevated in patients with pouchitis and may play a role in the pathogenesis of pouchitis.

Adult↗

Fine-needle aspiration of normal thyroid tissue may result in the misdiagnosis of microfollicular lesions.

BACKGROUND: Inadvertent sampling of normal thyroid tissue surrounding a nodule may occur when clinically inexperienced personnel perform fine-needle aspiration (FNA) or when a nodule is small. Because the cytologic characteristics of normal thyroid tissue are not well known, we prospectively studied 42 patients undergoing thyroidectomy. METHODS: FNA was performed from the grossly normal contralateral lobe during thyroidectomy. Cytopathologists examined the slides without knowing the source of the tissue. RESULTS: FNA of grossly normal thyroid tissue was adequate for interpretation in 32 of 42 patients, and in nine of 42 cases it was interpreted as unremarkable. However, the remaining specimens were classified as microfollicular lesions (18), mixed macromicrofollicular lesions (three), Hürthle cell lesion (one), and papillary thyroid carcinoma (one). CONCLUSIONS: FNA of grossly normal thyroid tissue suggested a microfollicular lesion in 18 (56%) patients, a result that would raise the possibility of a follicular carcinoma and often lead to the recommendation for operation. When FNA is performed, normal thyroid tissue surrounding a nodule should be avoided, and the possibility of a sampling error should be considered when a microfollicular pattern is obtained in a patient with a small nodule.

Biopsy, Needle↗

Restitution of frog gastric mucosa in vitro: effect of basic fibroblast growth factor.

BACKGROUND: Rapid re-epithelialization after superficial gastric mucosal injury is caused by migration of persisting viable epithelial cells. Basic fibroblast growth factor (bFGF) has been reported to enhance the healing of experimental duodenal ulcer, but its mode of action is unclear. The present experiments examine whether an effect of bFGF on restitution might contribute to such healing. METHODS: Paired halves of bullfrog fundic gastric mucosa in Ussing chambers were injured by luminal exposure to 1 mol/L NaCl for 10 minutes. RESULTS: Luminal protamine or suramin, both known to interfere with endogenous bFGF, significantly inhibited electrophysiological recovery at neutral luminal pH (pHL). Luminal sucrose octasulfate, which prevents acid degradation of bFGF, and an exogenous, acid-resistant form of bFGF allowed electrophysiological recovery at a pHL of 3.0 that completely prevented restitution in control tissues. Electrophysiological recovery correlated well with morphological restitution. The presence of endogenous bFGF in normal and restituting bullfrog mucosa was confirmed by positive staining with a monoclonal antibody. CONCLUSIONS: It is concluded that rapid epithelial repair after surface injury is at least in part mediated by bFGF.

Animals↗

Effects of ammonium ion and ammonia on function and morphology of in vitro frog gastric mucosa.

The effects of ammonium ion (NH+4) and ammonia (NH3) on function and morphology of gastric epithelial cells were studied in intact sheets of in vitro frog (Rana catesbeiana) gastric mucosa. Luminal 115 mM NH4Cl at luminal pH 8.0 (calculated [NH3] 2.7 mM), but not at 5.0 (calculated [NH3] 3 microM) induced 1) an increase in intracellular pH (pHi) in oxynticopeptic cells (OPC) and decreases in transmucosal potential difference (PD) and electrical resistance (R) in resting tissues, 2) a decrease in histamine-stimulated H+ secretion and an increase in H+ backdiffusion after removal of luminal NH4Cl, and 3) augmented acidification of OPC during luminal acidification. Serosal 30 mM NH4Cl at serosal pH 7.2 (calculated [NH3] 0.47 mM) induced 1) an increase in pHi in OPC and inhibition of the alkalinization of OPC after removal of ambient Cl-, 2) a decrease in PD associated with the increase in R and decrease in short-circuit current, effects attenuated by serosal 15 mM K+, accentuated by 0.2 mM Ba2+, and abolished by removal of ambient Cl-, 3) a sudden drop of PD in resting, but not in stimulated tissues, effects prevented by high serosal pH (7.8), serosal HCO3-, or removal of luminal Cl-, 4) a decrease in histamine-stimulated H+ secretion and an increase in H+ backdiffusion after removal of NH4Cl, and 5) augmented acidification of OPC during luminal acidification. These results suggest that 1) luminal NH3, but not NH+4, increases backdiffusion of H+ from the lumen to the mucosa, 2) serosal NH3 and/or NH+4 induces depolarization of OPC and decreases electrogenic Cl- transport, thereby attenuating the activity of the basolateral Cl(-)-HCO3- exchanger in OPC, and 3) both of these effects contribute to the augmented acidification of OPC during exposure to high luminal [H+].

Ammonia↗

Cell survival in rabbit gastric glands: effect of extracellular pH, osmolarity, and anoxia.

Although backdiffusion of luminal acid is regarded as a common mechanism of gastric injury, the extracellular pH (pHo) at which cells are irreversibly injured is not well defined. Exclusion of the fluorescent dye propidium iodide was used to estimate cell survival in rabbit gastric glands incubated in buffers of pHo 8.0-2.0. Mean survival (+/- SE) for n = 6 experiments at 2 h in a HEPES buffer of 300 mosM at pHo 8.0, 7.0, 6.0, 4.0, and 2.0 was 80 +/- 3, 91 +/- 2, 90 +/- 2, 71 +/- 2, and 17 +/- 4%, respectively. Survival at acidic pHo was improved in a high KCl buffer: 78 +/- 3 and 38 +/- 7% at pHo 4.0 and 2.0, respectively. Survival in HCO3- buffers was 73 +/- 3, 88 +/- 2, and 92 +/- 3% at pHo 8.0, 7.4, and 6.0. Brief (5 min) exposure to pHo 4.0 followed by reexposure to pHo 7.4 had no effect on acid secretion as estimated by [14C]aminopyrine uptake or cellular viability over 4 h. The influence on cell survival of changes in pHo under conditions of chemical anoxia and in buffers of different osmolarity was investigated. Chemical anoxia was induced using 2.5 mM KCN and 2.0 mM iodoacetic acid (IAA) to inhibit oxidative phosphorylation and anaerobic glycolysis. Survival in glands exposed to KCN and IAA in HEPES buffer was 54 +/- 5, 82 +/- 3, and 87 +/- 2% at pHo 8.0, 7.0, and 6.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopyrine↗

Microbiologic assessment of tissue biopsy samples from ileal pouch patients.

Tissue biopsy samples from patients with and without ileal pouches were examined by electron microscopic and microbiologic culture techniques to determine the numbers and types of microorganisms closely associated with or within the tissue biopsy samples. The disease status of each patient was determined by endoscopic and histopathologic methods. Of the 78 biopsy samples included in this study, 64 (82%) yielded obligately anaerobic and/or facultative bacteria when they were cultured. Fourteen of the 78 samples (17.9%) were negative by culture. Of the positive samples, 54 contained facultatively anaerobic bacterial species and 50 yielded obligately anaerobic species. The total counts for facultatively anaerobic bacteria for samples from patients with pouchitis were significantly greater than for samples from patients in control groups. In addition, the number of samples from patients with normal pouches that did not contain obligate anaerobes was significantly less than that from patients with pouchitis; 4 of 23 and 6 of 12 samples, respectively (P less than 0.043). For samples in which organisms were detected, there was agreement with electron microscopic detection of bacteria in 23 of 27 samples, for an overall sensitivity of electron microscopy compared with that of culture of 85%. The qualitative studies resulted in the characterization of 273 isolates comprising 77 different phenotypes. The specificity of these findings in patients with ileal pouchitis is discussed.

Bacteria, Anaerobic↗

Prostaglandin stimulates Cl(-)-HCO3- exchange in amphibian oxynticopeptic cells.

Prostaglandins, shown to stimulate Cl- transport in epithelial cells of several different tissues, protect gastric mucosa against physiological injury induced by luminal acid. To clarify the relationship between the stimulation of Cl(-)-transport and the protection of gastric mucosa, the effect of prostaglandin on Cl(-)-HCO3- exchange in oxynticopeptic cells (OPC) was examined in intact sheets of in vitro frog gastric mucosa, in which OPC were selectively loaded with the pH-sensitive fluorescent dye 2',7'-bis(carboxyethyl)-5(6')-carboxyfluorescein (BCECF). In omeprazole (0.3 mM)-pretreated frog fundic mucosae, in which H+ secretion was totally inhibited, 16,16-dimethyl prostaglandin E2 (dmPGE2) induced a significant decrease in intracellular pH (pHi) in OPC simultaneously with a significant increase in pHi in adjacent muscularis mucosae, an effect abolished by removal of ambient Cl- or addition of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) (0.5 mM). dmPGE2 accentuated the rates of alkalinization of OPC after either removal of ambient Cl- or addition of serosal H2DIDS. During exposure to luminal or serosal acid, dmPGE2 significantly attenuated acidification of OPC induced by the exogenous H+, effects abolished either by removal of ambient Cl- or by addition of H2DIDS (0.5 mM). These results suggest that 1) dmPGE2 stimulates extrusion of HCO3- through the basolateral Cl(-)-HCO3- exchanger in resting OPC (H+ secretion inhibited) and that 2) relatively high extracellular [HCO3-] on the basolateral surface afforded by dmPGE2 protects OPC from acidification during exposure to luminal or serosal acid.

Animals↗

Influence of acid secretory state on Cl(-)-base and Na(+)-H+ exchange and pHi in isolated rabbit parietal cells.

Parietal cell apical proton secretion is accompanied by apical Cl- secretion, K+ cycling, and the generation of intracellular base. We examined the ability of the parietal cell to maintain intracellular pH (pHi) during its transformation from the resting to the stimulated state and evaluated the ion transport mechanisms involved in the maintenance of ionic equilibrium. Isolated rabbit parietal cells were loaded with the pH-sensitive fluorescent dye BCECF, and pHi was monitored in maximally stimulated, resting (absence of a secretagogue), and omeprazole-inhibited cells. Although [14C]aminopyrine (AP) accumulation increased up to 30-fold above basal during stimulation, the mean pHi of maximally stimulated cells was not different from that of inhibited cells both immediately and late after stimulation in an extracellular pH range from 6.2 to 7.8 in either HEPES or CO2/HCO3- buffer. When the stilbene DIDS was added 2 min after stimulation of acid formation, pHi rapidly increased (0.09 +/- 0.02 vs. 0.04 +/- 0.02 pH units in unstimulated cells in 6 min), indicating an increased base efflux through a DIDS-sensitive transporter (most likely the Cl(-)-base exchanger). Stimulation of acid secretion did not change the transport capacity, apparent affinity for extracellular Cl-, or dependency of the anion flux rate on pHi of the DIDS-sensitive base exporter. For a given pHi, amiloride-inhibitable proton efflux rates during pHi recovery from an acid load were identical in resting and stimulated cells, suggesting that neither the transport capacity not the pHi set point of the parietal cell Na(+)-H+ exchanger is altered by cAMP-dependent stimulation of acid formation. We conclude that, during the cAMP-mediated stimulation of acid formation in isolated rabbit parietal cells, the pHi remains constant, but an increased base efflux occurs without a change in the transport capacity of the involved base extrusion mechanisms or an inhibition of the parietal cell base loading mechanisms. Whether changes in the intracellular Cl- concentration on stimulation of acid formation initiate the increased base efflux and whether additional ion transporters are involved in the maintenance of ion homeostasis during acid secretion remain to be determined.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Effects of hypoxia on function and morphology of in vitro frog gastric mucosa.

The effects of gaseous hypoxia and reoxygenation on oxynticopeptic (OPC) and surface mucous cells (SMC) were examined in in vitro bullfrog gastric fundic mucosae mounted in Ussing chambers. Forskolin-stimulated H+ secretion, transmucosal potential difference (PD), and electrical resistance (R) were monitored in tissues incubated in HCO3(-)-free or HCO3(-)-containing buffer. At serosal pH (pHs) 7.2, 1 h of hypoxia with 100% N2 resulted in a decrease in PD, increase in R, and complete inhibition of H+ secretion. After 30 min of hypoxia, the morphology of OPC changed from the secretory to the nonsecretory state without recognizable cytopathology. Destructive changes in OPC increased progressively at pHs 7.2 as the hypoxic period was prolonged from 4 to 24 h. After 4 h of reoxygenation following 12-24 h of hypoxia, OPC remained necrotic and H+ secretion showed no recovery, whereas in some areas where SMC were exfoliated adjacent SMC showed epithelial restitution. The recovery of H+ secretion and PD during 2 h of reoxygenation after 4 h of hypoxia at pHs 6.0 and 6.8 was less than that at 7.2 and 8.0 and was greater in the presence of serosal HCO3- than its absence at pHs 7.2. These results suggest that, in in vitro frog gastric mucosa, 1) OPC are more vulnerable to hypoxia than SMC, 2) basolateral acidosis exaggerates hypoxic injury of OPC, and 3) serosal HCO3- protects OPC from hypoxic injury.

Animals↗

Recurrence in the breast following conservative surgery and radiation therapy for early-stage breast cancer.

This report summarizes the experience of the Joint Center for Radiation Therapy (JCRT) in treating patients with clinical stage I and II breast cancer with conservative surgery and radiation therapy. The study population consisted of 1396 patients treated between 1968 and 1985. All patients underwent a gross excision of the tumor and received breast irradiation (with or without nodal irradiation) including a "boost" to bring the primary tumor site to a total dose of at least 60 Gy. The method of treatment evolved over the study-time period. During the interval from 1968 to 1982, patients typically underwent a limited gross excision of the tumor without regard to the microscopic margins of resection. During the period 1983 to 1985, film-screen mammography, inking of specimen margins, and reexcisions for inevaluable or involved margins were more commonly performed. With a median follow-up of 80 months, the 5-year crude rate of failure in the breast (as the first site of failure) was 8% (106/1396) and the crude rate of regional nodal/distant failure (as the first site of failure) was 16% (228/1396). The time-course of failures in the breast was protracted, occurring at a fairly constant rate over the first 7 years after treatment, but still seen beyond that point. Most recurrences in the breast (75%) developed at or near the original tumor site. The most important risk factor for developing a breast recurrence was the presence of an extensive intraductal component in the tumor. The cosmetic results following treatment were excellent or good in the majority of patients (87%) and were most adversely affected by extensive surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗

Effect of luminal acid on intracellular pH in oxynticopeptic cells in intact frog gastric mucosa.

The effect of changes in luminal [H+] on intracellular pH in oxynticopeptic cells was examined using intact sheets of frog (Rana catesbeiana) gastric mucosa in which oxynticopeptic cells were selectively loaded with the pH-sensitive fluorescent dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). The serosal solution was buffered with either HCO3- or N-2-hydroxymethylpiperazine-N'-2-ethanesulfonic acid (HEPES). Luminal pH was decreased from 7.2 to 1.5 and changed back to 7.2. In stimulated (forskolin-treated) tissues, intracellular pH decreased at luminal pH 1.5 only in HEPES, with complete recovery at 7.2. In resting (omeprazole-treated) tissues, intracellular pH began to decrease at luminal pH 2.0 in HEPES and at 1.5 in HCO3-, with complete recovery at 7.2 in both. In resting tissues bathed in Cl(-)-free HEPES, the recovery of intracellular pH at luminal pH 7.2 was completely prevented by serosal amiloride (1 mmol/L) but was not affected by serosal 4,4'-diisothiocyanatodihydrostilbene-2-2'-disulfonic acid (H2-DIDS; 0.5 mmol/L). In resting tissues bathed in Cl(-)-free HCO3-, the recovery of intracellular pH at luminal pH 7.2 was not affected by amiloride but was prevented partially by H2-DIDS and completely by combination of H2-DIDS and amiloride or by removal of ambient Na+. These results suggest that during exposure to high luminal [H+]: (a) stimulated oxynticopeptic cells maintain a steady intracellular pH more readily than resting cells; (b) serosal HCO3- protects oxynticopeptic cells from intracellular acidosis; and (c) both Na+/H+ exchange and Na(+)-HCO3- cotransport are involved in the recovery from intracellular acidosis in resting oxynticopeptic cells.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

The optimal extent of resection for patients with stages I or II breast cancer treated with conservative surgery and radiotherapy.

The optimal extent of breast resection before irradiation for treatment of early breast cancer has not been defined. Increasing the size of the resection may decrease the risk of local recurrence but will also have an adverse impact on the cosmetic outcome. The 5-year likelihood of a recurrence of the tumor was analyzed in relation to the volume of resected breast tissue in 507 patients with infiltrating ductal carcinoma treated with conservative surgery and radiation therapy between 1968 and 1982. Patients were stratified by clinical T-stage and for each T-stage patients were divided into three groups of equal numbers based on the volume of excised tissue. All patients had at least a gross excision of the tumor and the extent of breast resection was determined at the discretion of the surgeon without knowledge of the histologic features of the tumor. The median follow-up time was 100 months. The 5-year actuarial recurrence rates were analyzed in relation to clinical T-stage (T1 or T2) and the presence or absence of an extensive intraductal component (EIC+ or EIC-). For patients with EIC+ tumors, the largest resections were associated with a substantially lower risk of recurrence in the breast than the smallest resections. This effect was seen both for T1 tumors (10% versus 29%, p = 0.07) and for T2 tumors (9% versus 36%, p = 0.04). For patients with EIC-tumors, recurrence rates were significantly lower than for EIC+ tumors and were not influenced by the volume of resection to the same degree as EIC+ tumors. In the absence of an EIC, recurrence rates for the largest and smallest resections were 0% and 9% (p = 0.02) for T1 tumors and 3% and 6% (p = NS) for T2 tumors. It is concluded that a limited breast resection is acceptable for an EIC- tumor but that a more extensive resection is required for an EIC+ tumor. These results stress the importance of assessing the presence or absence of an EIC in determining the optimal extent of breast resection required before radiation therapy.

Breast Neoplasms↗

H(+)-K(+)-ATPase contributes to regulation of pHi in frog oxynticopeptic cells.

The effect of intracellular acidosis on luminal H+ secretion and the role of H(+)-K(+)-ATPase in regulation of intracellular pH (pHi) in oxynticopeptic cells (OPC) (measured with a pH-sensitive fluorescent dye) were examined in intact sheets of in vitro frog (Rana catesbeiana) gastric mucosa. Intracellular acidosis of OPC induced by decreasing pH in the serosal solution (pHs) from 7.2 to 6.0 reversibly increased forskolin-stimulated H+ secretion without increasing endogenous histamine release. The observed increase in H+ secretion was unaffected by either 1 mM cimetidine or 1 mM histamine, but was accentuated by 1 mM amiloride, an effect abolished by 0.3 mM omeprazole. Steady-state pHi values in stimulated or resting OPC at pHs 7.2 were not significantly different. However, pHi in OPC was significantly higher in stimulated than in resting tissues at pHs 6.9, a difference accentuated by decreasing pHs to 6.4 or by 1 mM amiloride. Amiloride completely prevented recovery from intracellular acidosis induced by pHs 6.4 or 6.9 in omeprazole-treated tissues, but only partially mitigated recovery in cimetidine- or forskolin-treated tissues. At pHs 6.4, high luminal [K+] (100 mM) increased H+ secretion and hastened recovery of pHi in cimetidine-treated tissues in the presence of amiloride. These results suggest that, in intact sheets of in vitro frog gastric mucosa, 1) intracellular acidosis stimulates luminal H+ secretion via histamine-independent mechanisms and 2) H(+)-K(+)-ATPase contributes to the recovery of OPC from intracellular acidosis.

Acidosis↗