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Biomedical subjects

T J Howard

Publications and source records attributed to T J Howard.

12 recordsLinked to original sources

Contributions of the Zollinger-Ellison syndrome.

The salient contributions of the Zollinger-Ellison syndrome have made it unique. No pancreatic endocrine tumor described before (insulinoma) or subsequently (glucagonoma, somatostatinoma, vipoma, pancreatic-polypeptidoma) has been the topic of such a variety of studies, or has been such an inspiration and rich source of new ideas for investigation and ultimate improvement in patient care.

Gastrinoma

Strong gastric contractions cause mucosal ischemia.

Contractions of a segment of bowel result in alterations of its blood flow. However, the precise temporal and spacial relationships between contractions and mucosal blood flow are unknown. Rats were fitted with strain gauge force transducers and implanted with silver wire electrodes into the muscularis externa of the stomach. In vivo microscopic observation of motility and of the gastric mucosal blood flow was performed during electrical field-stimulated contractions. Contractions originated in the midcorpus, were 0.237 +/- 0.018 cm wide, traveled along the corpus at 0.133 +/- 0.024 cm/s, and had a duration of 5.9 +/- 0.1 s. Antral contractions were 0.174 +/- 0.032 cm wide, traveled at 0.070 +/- 0.009 cm/s, and had a duration of 5.6 +/- 0.7 s. During the contraction, capillary flow velocity in the corpus decreased from a basal value of 410 +/- 105 to 206 +/- 104 microns/s at the peak of a contraction. Five seconds after the contraction was released hyperemia was observed with the flow velocity increasing to 570 +/- 102 microns/s. In the antrum, flow stopped completely during the contraction irrespective of the initial flow velocity and no hyperemia occurred with release of the contraction; rather, flow velocity slowly returned to baseline values. In both regions the flow reductions were in phase with the contractions as measured by the force transducers. These studies provide direct evidence that strong gastric contractions can effectively reduce or stop gastric mucosal blood flow.

Animals

Xanthogranulomatous cholecystitis: a chronic inflammatory pseudotumor of the gallbladder.

Xanthogranulomatous cholecystitis is a benign chronic inflammation of the gallbladder that can morphologically mimic carcinoma. In severe cases, the diagnosis is made intraoperatively using frozen section histology and pathologic consultation. Once the diagnosis of xanthogranulomatous cholecystitis is confirmed, cholecystectomy should be performed. Occasionally, the inflammatory reaction and fibrosis within the gallbladder is so severe that conventional cholecystectomy is unsafe. In these instances, a subtotal cholecystectomy is required.

Adult

Source of plasma chromogranin A elevation in gastrinoma patients.

Chromogranin A (Cg A) is a protein that is coreleased with peptide hormones from gut endocrine cells and tumors. Plasma levels of Cg A, pepsinogen group I, and gastrin were measured in 31 patients with gastrinoma. Mean Cg A level in 10 patients with gastrinoma who were not operated on was 169 +/- 32 ng/mL, while in 9 control patients it was 28 +/- 5 ng/mL. In 18 patients with gastrinoma with residual tumor after total gastrectomy, the mean Cg A level was 45 +/- 6 ng/mL, and in 10 patients with normal gastrin levels after total gastrectomy and tumor excision, the mean Cg A level was 40 +/- 4 ng/mL. In 7 patients in whom pregastrectomy and postgastrectomy Cg A levels were measured, the mean reduction was 94 +/- 27 ng/mL, or 66%. There was no correlation between Cg A levels and amount of tumor, presence of metastases, or multiple endocrine neoplasia type I syndrome. There was a significant correlation between Cg A and pepsinogen I levels but no correlation between Cg A and gastrin levels. The results suggest that the elevated plasma Cg A levels in patients with gastrinoma are determined primarily by the trophic effects of gastrin on gastric enterochromaffinlike cells rather than by corelease from the gastrin-producing tumor itself.

Adult

Heterotopic tissue in lymph nodes. An unrecognized problem.

Heterotopic tissue in lymph nodes is both unknown to clinicians and a potential source of confusion with metastatic disease. We reviewed the English literature and found 289 cases of heterotopic tissue in lymph nodes. The majority (84%) of these patients were operated on for malignant neoplasms. The most frequent sites of occurrence was the pelvis (67%), followed by the axilla (14%), neck (14%), groin (3%), abdomen (2%), and mediastinum (less than 1%). The tissue seen is site-specific and frequently resembles a neighboring organ. Three cases have been reported in which heterotopic tissue was mistaken for metastatic disease. These cases illustrate the importance of being familiar with heterotopic tissue in lymph nodes and identifying it when it does occur, to avoid inappropriate therapy.

Adolescent

The dichotomous distribution of gastrinomas.

Our experience with 47 sporadic gastrinomas suggests that no less than 85% of these tumors are located to the right of the superior mesenteric artery. This finding is unexpected because approximately 75% of insulinomas and glucagonomas are located to the left of the superior mesenteric artery. All of our extrapancreatic gastrinomas have been located to the right. These observations prompted us to determine if other extrapancreatic gastrinomas were also predominantly located to the right side. We searched the world's literature and found 10 cases of ovarian gastrinomas and one case of a renal gastrinoma. Nine of these remote extrapancreatic gastrinomas were located on the right side. This distribution of remote extrapancreatic gastrinomas is similar to our experience with peripancreatic gastrinomas. This unexpected right-sided preponderance of both remote and peripancreatic gastrinomas suggests a common origin for both.

Adult

Anatomic distribution of pancreatic endocrine tumors.

Pancreatic endocrine tumors are grouped together by their common histologic, cytochemical, and ultrastructural features. Although useful conceptually, this paradigm has been unable to predict the anatomic location of different tumor types. Successful surgical excision of these tumors would be facilitated by an improved understanding of their anatomic distribution. Based on the available data, a bimodal distribution of pancreatic endocrine tumors was identified. Cluster 1 (gastrinomas, pancreatic polypeptide (PP)-secreting tumors, somatostatinomas) had 75% of tumors to the right of the superior mesenteric artery, whereas cluster 2 (insulinoma, glucagonoma) had 75% of tumors to the left of the superior mesenteric artery (p less than 0.05). This distribution is similar to that distribution predicted based on the volume density of the corresponding islet cells for insulinoma, glucagonoma, and PP-secreting tumors, but not for somatostatinoma. These findings suggest that pancreatic endocrine tumors are derived from similar cytologic precursors as pancreatic islet cells, and their distribution may be a consequence of embryologic development from either the ventral (cluster 1) or dorsal (cluster 2) pancreatic buds.

Adenoma, Islet Cell

Gastrinoma excision for cure. A prospective analysis.

The role of surgery in the treatment of gastrinoma is unclear. The purpose of this study was to determine prospectively the surgical cure rate using a controlled clinical trial. Eleven patients who fit the entry criteria underwent abdominal exploration and attempted tumor resection for cure. A historical control group was used for comparison. Cure was defined as: (1) normal serum gastrin level, (2) no response to intravenous secretin, (3) no symptoms when antisecretory medications are stopped, and (4) no tumor recurrence on follow-up examination. Tumors found in both groups tended to be small (1.5 cm vs. 2.2 cm), multiple (71% vs. 40%), and in lymph nodes (70% vs. 70%). All tumors identified were located anatomically within the gastrinoma triangle. Tumors were found in 10 of 11 patients (91%) in the study group, and significantly more patients had their tumors excised for cure as compared to controls (82% vs. 27%, p less than 0.05). The current prospective cure rate for gastrinoma is higher than previously appreciated and tumors within lymph nodes do not preclude curative resection.

Adult

Topical isoproterenol protects the rat gastric mucosa from ethanol-induced injury.

This study evaluated the effects of topical isoproterenol, a beta-adrenergic agonist, on the morphologic damage produced in the gastric mucosa by ethanol. The orogastric instillation of 100% ethanol in rats resulted in gross lesion formation and deep histologic injury in the gastric mucosa. Animals pretreated with oral isoproterenol (50 micrograms/kg, 500 micrograms/kg, 50 mg/kg) showed dose-dependent protection from both the gross and the histologic mucosal injury (P less than 0.01, ANOVA). Pretreatment with propranolol (2 mg/kg/sec) but not indomethacin (5 mg/kg/sec) blocked this protective effect. Isoproterenol had no effect on ethanol-induced mast cell degranulation as both mucosal and submucosal mast cell counts were significantly and equally decreased in all groups treated with 100% ethanol (P less than 0.05). These findings show that topical isoproterenol protects the rat gastric mucosa from both the gross and the histologic injury caused by 100% ethanol. This protection is mediated by a beta-adrenergic receptor mechanism as it can be blocked by prior treatment with propranolol, but does not involve stabilization of mucosal or submucosal mast cell membranes.

Administration, Topical

Gastrinoma. New medical and surgical approaches.

The clinical presentation of gastrinoma has changed since the original description by Zollinger and Ellison in 1955. Tumors currently found are smaller, extrapancreatic or extraintestinal in location, and frequently occult within lymph nodes. The incidence of hepatic metastases on initial presentation has decreased. In addition, the clinical course of patients with tumor in lymph nodes is benign, suggesting that more patients than were previously thought are now candidates for cure. Improved knowledge of the anatomic location of gastrinomas has enhanced our ability to find and remove them at laparotomy. As a result of these factors, more patients are being cured than ever before, and in the future, cure rate may be even higher. On the basis of these recent advances, the optimal treatment of gastrinoma is surgical excision for cure.

Anti-Ulcer Agents