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Biomedical subjects

J C Reynolds

Publications and source records attributed to J C Reynolds.

At least 91 records · Page 5Linked to original sources
PubMed1994

Application of high affinity binding concept to radiolabel avidin with Tc-99m labeled biotin and the effect of pI on biodistribution.

In order to label avidin with Tc-99m, we took advantage of the high affinity binding of biotin to avidin; we radiolabeled a biotin derivative with Tc-99m and then bound this Tc-99m labeled biotin derivative to avidin. For our labeling approach, N epsilon-biotinyl-L-lysine (Biocytin) was reacted with the N-hydroxy-succinimide ester of benzoylmercaptoacetyltriglycine (Bz-MAG3). The resulting Bz-MAG3-Biocytin was labeled with Tc-99m using Tc-99m glucarate as a Tc-99m transchelating agent and mixed with avidin at a 1:1 molar ratio resulting in almost a quantitative labeling yield. Tc-99m-MAG3-Biocytin/Avidin was stable in serum at 37 degrees C with 97 and 95% of the total Tc-99m activity still bound to avidin at 2 and 24 h, respectively. The biodistribution of Tc-99m-MAG3-Biocytin/Avidin in normal Balb/c mice showed a high liver and kidney uptake with 56.6 and 28.9%, respectively at 10 min. We attempted to lower the liver and the kidney activities by reducing the isoelectric point (pI) of avidin by conjugating succinic acid moieties at lysine residues of avidin (pI 10). The kidney uptake decreased to 19.0, 3.1 and 1.7% when the pI of avidin was reduced to 7.0-9.3, 5.5-6.2 and 4.0-4.8, respectively. The lowering of the pI, however, did not change the liver activity appreciably.

Animals↗
PubMed1994

Risk factors for delayed healing of duodenal ulcers treated with famotidine and ranitidine.

OBJECTIVES: 1) To validate risk factors for delayed healing of duodenal ulcers identified previously in a pilot study, and 2) To evaluate whether famotidine improves the rate of duodenal ulcer healing and pain relief, compared with ranitidine. METHODS DESIGN: prospective, multicenter, double-observer-blinded, randomized trial. SETTING: 594 patients with active duodenal ulcers seen in private practice offices, university based medical practices and Veterans Affairs hospital clinics. INTERVENTIONS: Patients were randomly assigned to receive famotidine 40 mg or ranitidine 300 mg qhs. MEASUREMENTS: Endoscopy was performed at entry and at 2, 4, and 8 wk after therapy or until complete ulcer healing. Seventeen patient variables, including demographic, past historical, presenting historical and endoscopic characteristics, were assessed for their relationship to healing. RESULTS: After 4 wk of treatment, by a "per protocol" analysis, three risk factors for nonhealing were statistically significant: prior ulcer history [63.0% healed, compared to 77.9% with no history, p = 0.001, odds ratio for not healing (OR) = 2.1, 95% CI = 1.4-3.1]; ulcer size (61.6% of ulcers > or = 10 mm healed at 4 wk compared to 75.5% of smaller ulcers, p = 0.001, OR = 1.9, 95% CI = 1.3-2.8); and smoking (62% of smokers healed vs. 77.7% of nonsmokers, OR = 2.1, 95% CI = 1.4-3.1). The presence of multiple risk factors resulted in additive risk: for patients with no risk factors, 86.8% healed at 4 wk, with any one risk factor 76.8% healed, with two factors 63.0%, and with all three risk factors only 46.9% healed. Multiple risk factors also affected healing rates at 8 wk. Bleeding, alcohol use, and prior NSAID use did not influence ulcer healing. Although famotidine resulted in statistically significant faster ulcer healing when examined on an "intention-to-treat" basis, there were no differences between the drugs when examined on a "per protocol" basis. Patients treated with famotidine achieved more rapid pain relief than those treated with ranitidine. CONCLUSIONS: 1) Smoking, prior ulcer history, and ulcer size > or = 10 mm exert independent risks for nonhealing of duodenal ulcers; 2) These risks are similar for both famotidine and ranitidine; 3) Patients with multiple risk factors for nonhealing may require more prolonged acid suppression therapy than patients who have no risks.

Double-Blind Method↗
PubMed1993

Complications during pneumatic dilation for achalasia or diffuse esophageal spasm. Analysis of risk factors, early clinical characteristics, and outcome.

UNLABELLED: A retrospective cohort study was performed to assess risk factors, early clinical characteristics, and outcome of complications in patients undergoing pneumatic dilation. Of 178 patients with achalasia or diffuse esophageal spasm who underwent 236 dilations with a Browne-McHardy dilator, 16 patients experienced a complication (9.0%). Nine major complications developed: perforations (4), hematemesis (2), fever (2), and angina (1). A prior pneumatic dilation and use of inflation pressure > or = 11 PSI were independent risk factors by multivariate analysis for developing a complication. An esophagram immediately following the dilation identified three of the four perforations. Three postdilation findings were identified as indicators of patients with an increased risk of having developed a perforation: blood on the dilator, tachycardia, and prolonged chest pain lasting > 4 hr after dilation. In all patients incurring a major complication, one of the three indicators, or the complication itself was recognized within 5 hr of dilation. All patients with complications, including the four with perforation who received prompt surgical repair and esophagomyotomy, recovered uneventfully. The symptomatic relief of dysphagia in patients with perforation undergoing emergent surgical repair and esophagomyotomy was similar to patients undergoing elective esophagomyotomy. CONCLUSIONS: (1) Pneumatic dilation is a safe treatment of achalasia, with a 1.7% risk of perforation. (2) The risk of developing a complication is increased by having had a previous pneumatic dilation or by use of inflation pressures > or = 11 psi. (3) All patients with a major complication were identified within 5 hr after dilation. (4) Complications following pneumatic dilation, if recognized and treated promptly, were not associated with adverse, long-term sequelae.

Catheterization↗
PubMed1993

Pneumatic dilatation or esophagomyotomy treatment for idiopathic achalasia: clinical outcomes and cost analysis.

The choice between pneumatic dilatation and surgical esophagomyotomy as the initial treatment for achalasia is controversial. The aims of this study were to determine the long term clinical outcome and costs of treating achalasia initially with pneumatic dilatation as compared to esophagomyotomy. Of 123 patients undergoing an initial pneumatic dilatation for achalasia at our institution from 1976 to 1986, 71 (58%) received no further treatment for achalasia during a mean follow up of 4.7 +/- 2.8 years. Only 15 of these 123 patients (12%) eventually underwent surgical esophagomyotomy (two for perforation during pneumatic dilatation, 13 for persistent or recurrent symptoms). The degree of dysphagia at follow up was improved to a similar degree in patients treated with an initial pneumatic dilatation as compared to patients treated with an initial esophagomyotomy. Patients with age > or = 45 years at time of initial pneumatic dilatation had fewer subsequent treatments for persistent or recurrent symptoms and had less dysphagia on follow up as compared to patients < 45 years. Subsequent pneumatic dilatations to treat persistent or recurrent symptoms were less beneficial than an initial pneumatic dilatation. The cost of esophagomyotomy was 5 times greater than the cost of pneumatic dilatation. When costs were analyzed to include subsequent treatments of symptomatic patients, the total expectant costs of treating with an initial esophagomyotomy remained 2.4 times greater than treating with an initial pneumatic dilatation. This study suggests that an initial pneumatic dilatation will be the only treatment needed for the majority of patients with achalasia. A treatment regimen starting with pneumatic dilatation has less overall costs than starting with esophagomyotomy. For each subsequent pneumatic dilatation, however, the clinical benefit leans toward surgery.

Catheterization↗
PubMed1993

Electrogastrography in patients with gastroparesis and effect of long-term cisapride.

Abnormalities in the gastric pacemaker potentials occur in patients with impaired gastric emptying. It is unclear if treatment effects the underlying rhythm or if normalization of dysrhythmias is important. We examined the effect of cisapride using surface electrogastrograms and radionuclide gastric emptying studies of patients with idiopathic and diabetic gastroparesis. Twelve of 14 patients had abnormal baseline electrogastrograms. After six months of cisapride, four patients had normalization of their electrical activity and six had improvement. Patients with idiopathic gastroparesis had an increase in gastric emptying at 120 min from 48.9 +/- 3.8% (baseline) to 70.9 +/- 6.0% (six months), P = 0.009. Patients with diabetes mellitus had a similar improvement. Patients who had normalization of the electrogastrogram had a greater gastric emptying rate than patients with continued dysrhythmias. Thus, dysrhythmias are important in the etiology for gastroparesis, but other factors need to be examined.

Adult↗
PubMed1993

Thyrotropin-releasing hormone: an inhibitory regulatory peptide of feline lower esophageal sphincter.

The functional role of thyrotropin-releasing hormone (TRH) at the lower esophageal sphincter (LES) was examined in the cat. The specific aims of this study were to determine: 1) the relative distribution of TRH throughout the feline gastrointestinal tract and 2) the effect of TRH on LES basal pressures and its response to exogenously induced contractions. TRH concentrations were determined by radioimmunoassay in tissue extracts from 12 sites. The mean concentration of TRH at the manometrically determined LES was 240 +/- 85 pg/g wet wt tissue, and the maximal concentration was just distal to the LES (659 +/- 189 pg/g wet wt). TRH concentration was higher in the mucosa than the underlying muscle layer of the fundus, antrum, duodenum, and ileum. In physiological studies, TRH given selectively via the left gastric artery had no effect on basal LES or esophageal pressures. TRH (2.8 x 10(-8) mol/kg) decreased the LES response to the D50 of substance P by 47.2% (34.8 +/- 3.1 to 18.4 +/- 2.9 mmHg, P < 0.01). In the presence of tetrodotoxin, TRH gave a similar inhibition of substance P-induced contractions (53.5%). TRH also decreased bombesin-induced contractions by 47.5% (29.6 +/- 6.0 to 15.8 +/- 3.9 mmHg, P < 0.025). TRH, however, had no effect on bethanechol-induced contractions. We conclude that 1) TRH is present throughout the gastrointestinal tract, with highest concentrations in the region distal to the LES; 2) TRH has no effect on basal LES tone; and 3) TRH inhibits the LES response to endogenously released and exogenous substance P but not the LES response to bethanechol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Role of magnetic resonance in the study of benign and malignant pheochromocytomas. Quantitative analysis of the intensity of the resonance signal].

In order to assess the clinical role of Magnetic Resonance (MR) imaging in patients with benign or malignant pheochromocytomas, the MR signal intensity ratios of benign and malignant tumors were evaluated. Eighteen patients (9 men and 9 women, mean age: 37 +/- 8 years) with benign (n = 10) or malignant (n = 8) pheochromocytomas were studied. A total of 27 lesions (12 benign and 15 malignant) were analyzed. In all patients, histology confirmed the disease. MR studies were performed using a 1.5-T superconducting magnet system. Sequences were used to obtain T1-weighted (TR/TE 300/12 ms) and T2-weighted (TR/TE 2000/80 ms) images. On both T1- and T2-weighted MR images, the mean absolute signal intensity values of tumor lesions, of liver, muscle and fat tissues, and of image background were measured to obtain the corresponding signal intensity ratios for each lesion. Our results exhibited no statistically significant differences in both T1 and T2 MR signal intensity ratios between benign and malignant lesions. In conclusion, our results suggest that MR imaging cannot differentiate benign from malignant lesions in patients with pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1993

Iodine-131-metaiodobenzylguanidine scintigraphy in preoperative and postoperative evaluation of paragangliomas: comparison with CT and MRI.

Iodine-131-metaiodobenzylguanidine (MIBG) scintigraphy, transmission computed tomography and magnetic resonance imaging were used to evaluate 36 patients with clinically suspected functioning paragangliomas. The patients were divided into two groups. In Group 1 (n = 21), studied before surgery, patients mainly had benign adrenal disease. In Group 2 (n = 15), studied after surgery, patients frequently had malignant or extra-adrenal tumors. In Group 1, transmission computed tomography and magnetic resonance imaging were more sensitive (100% for both) than MIBG scintigraphy (82%), which, however, was the most specific (100%). In Group 2, MIBG scintigraphy and magnetic resonance imaging were more sensitive (83% for both) than transmission computed tomography (75%), but MIBG was again the most specific (100%). Thus, all three were complementary modalities for localizing paragangliomas both preoperatively and postoperatively. MIBG imaging is indicated for both groups but it is especially recommended for postsurgical patients with recurrence because the disease is often malignant or extra-adrenal.

3-Iodobenzylguanidine↗
PubMed1992

The correct dose: pharmacologically guided end point for anti-growth factor therapy.

Strategies to block the effects of tumor growth factors, such as estrogen, and to recruit other regulatory elements, such as with retinoids, have focused interest on the possibility of successful tumor intervention approaches. Approaches that neutralize the effects of critical molecules that drive tumor promotion are attractive targets for evaluation as new intervention agents. Clinical intervention trials with early stage patients or with subjects from "high risk" populations impose stricter types of constraints than conventional chemotherapy approaches in advanced stage patients. The potential for short-term toxicity has to be considered, as it may affect subject accrual or compliance. The longer expected survival of intervention subjects mandates closer attention to the possibilities of unexpected long-term toxicities with chronic administration of an intervention agent. As part of a Phase I clinical trial evaluating the utility of a monoclonal antibody directed against the autocrine growth factor, gastrin-releasing peptide to block the growth of small cell lung cancer, we developed a mathematical model to predict the requisite amount of antibody to neutralize growth factor effect. This model requires knowledge of the equilibrium concentration of the secreted growth factor, specific receptor, and bioavailability of the antibody in the tumor interstitium. A range of possible target doses of antibody can be developed to address the potential for heterogeneity frequently encountered in such systems, including a range of levels for peptide production and specific receptor expression. This approach could be applied to rationally derive treatment or intervention in which specific information regarding the relevant binding parameters is available. Through refinement of this modeling approach more context-specific dosing of agonist/antagonists could be determined which may decrease side effects associated with the drug administration.

Antibodies, Monoclonal↗
PubMed1992

Radiolabeled products in rat liver and serum after administration of antibody-amide-DTPA-indium-111.

Anti-human serum albumin antibody (Ab) was used as a model antibody. Ab was conjugated with DTPA using cyclic DTPA dianhydride reaction and radiolabeled with 111In. The labeled Ab was purified by affinity chromatography. Size exclusion HPLC of this product showed 62% of 111In bound to monomeric Ab and 38% of the activity bound to antibody oligomers with molecular weights ranging from 300,000 to 450,000. The labeled antibody preparation was injected into the tail vein of rats. The radioactive substances in serum and the supernatant from liver homogenates were analyzed for molecular weight and immunoreactivity. Size exclusion HPLC of the serum samples indicated that the monomeric and dimeric Abs disappeared from the serum at a similar rate over a 48 h period. In addition, a new radioactive substance with an estimated molecular weight of 35,000 appeared in the serum. The immunoreactive fraction of the circulating 111In substances decreased slowly, somewhat proportional to the appearance of the metabolite. On the other hand, the immunoreactivity of the 111In substances in the supernatant from the liver homogenate decreased rapidly and no appreciable immunoreactivity was observed after 48 h. The labeled antibody was catabolized very rapidly in the liver and the major activity in the supernatant was associated with a small molecular weight metabolite which had a HPLC retention time identical to that of DTPA-111In. The second metabolite had an estimated molecular weight of 35,000. No radioactivity was associated with transferrin.

Animals↗
PubMed1992

Impact of the new cuff design on reliability of the AS800 artificial urinary sphincter.

The effect of 2 cuff design changes on the mechanical reliability of the current AS800 artificial urinary sphincter was assessed in 126 patients. The surface-treated cuff was introduced in 1983 and the narrow-back design was introduced in 1987. Mean followup for the surface-treated cuff was 40 months, while that for the narrow back was 27.2 months. The incidence of cuff leaks was 1.3%, while the revision rate for clinically significant pressure atrophy, in the absence of a bladder flap urethroplasty, was 2.3%. The overall revision rate for clinically significant pressure atrophy was 9%. No leaks involving the balloon or tubing occurred. The mechanical reliability of the current AS800 artificial urinary sphincter has improved significantly.

Evaluation Studies as Topic↗
PubMed1992

Bidirectional peritoneal transport of immunoglobulin in rats: compartmental kinetics.

Protein transport to and from fluid in the peritoneal cavity is observed during clinical procedures. Dialysate osmolality is a major determinant of net fluid flux into the cavity. We carried out experiments in rats to determine the plasma, peritoneal, and tissue concentrations of immunoglobulin (Ig) G resulting from either intravenous (iv) or intraperitoneal (ip) administration during hypertonic or isotonic dialyses. After iv injection of IgG, overall mass transfer into the cavity was not affected by the osmolality. After ip injection, tissue concentrations were dependent on the dialysis duration. Protein absorption from the hypertonic dialysate into the surrounding tissue was quantitatively less than the absorption from an isotonic dialysis solution at 20 min. By 200 min, total protein transport was not affected by dialysate osmolality. Lymphatic transport to the plasma amounted to 20-25% of the total protein loss from the peritoneal cavity; approximately 60% of the absorbed dose was found in tissues surrounding the cavity at both 20 and 200 min, with particularly high concentrations in parietal areas. We conclude that immunoglobulin transport in the peritoneal tissue, resulting from either iv or ip injection, is influenced by route of administration but is little affected by dialysate osmolality. Peritoneal absorption of proteins occurs directly into the surrounding tissue interstitial space as a result of hydrostatic pressure-driven convection and diffusion.

Absorption↗
PubMed1992

Bidirectional peritoneal transport of immunoglobulin in rats: tissue concentration profiles.

Protein transport occurs between the blood and the peritoneal cavity during clinical procedures, but events within the surrounding tissue space are poorly understood. We used quantitative autoradiography to examine the tissue concentration profiles of immunoglobulin G (IgG) in regions surrounding the peritoneal cavity. We have varied the route of administration (intravenous or intraperitoneal), the osmolality of the dialysis solution (isotonic or hypertonic), and the time of analysis (20 or 200 min). After intravenous injection, IgG profiles were relatively flat in most tissues and were not affected by time or osmolality. Concentrations corresponded to the capillary density in specific tissues. After intraperitoneal administration, the IgG tissue profiles were significantly steeper than after intravenous administration. The tissue concentrations increased with time but decreased when a hypertonic solution was substituted for an isotonic solution. Hypertonic dialysis causes a water flux into the cavity, which dilutes the contents but does not prevent penetration of protein into the surrounding tissue. Based on IgG movement in tissue during hypertonic dialysis, the peritoneum appears to function as a heterogeneous structure, which allows osmotically induced water transport into the cavity in some regions with simultaneous transport of hydrostatic pressure-driven water and solute flow from the cavity into the tissue in other regions.

Animals↗
PubMed1992

Pelvic radioiodine uptake in a rectal wall teratoma after thyroidectomy for papillary carcinoma.

A 30-yr-old woman with previously resected papillary thyroid carcinoma was found to have a pelvic lesion which concentrated radioiodine. By performing simultaneous 131I whole-body and 99mTc-methylene diphosphonate bone scans, we found the lesion to be in soft tissue between the sacrum and bladder. Radioiodine therapy was postponed so that the lesion, a benign teratoma of the rectal wall, could be surgically removed. Prior to laparotomy, the patient received a second tracer dose of 131I so that the lesion could be located at surgery with a hand-held gamma detector. A postoperative whole-body 131I scan confirmed that the lesion had been removed, thus reducing the absorbed radiation that would have been received by the ovaries during radioiodine therapy. Although the lesion contained both thyroid and gastric epithelium, accumulated 131I was limited to the area with thyroid follicles.

Adult↗