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Biomedical subjects

J Sparks

Publications and source records attributed to J Sparks.

31 records · Page 2Linked to original sources

Failure of secretin to stimulate gastrin release and adenylate cyclase activity in gastrinoma in vitro.

It has been hypothesized that secretin may act directly on gastrinoma through the adenylate cyclase system to cause stimulation of gastrin release. We studied gastrinoma cells in vitro to determine whether secretin would stimulate gastrin release directly and whether the gastrinoma cell membrane had a functional secretin receptor adenylate cyclase system. Fresh tumor was prepared in cell suspensions containing 1.5 X 10(6) viable cells and incubated for 2 hours with either 2 mM CaCl2 alone (control) or 2 mM CaCL2 and 0.025 U/ml secretin. The gastrin content of the cells in each incubation chamber and the medium were determined by radioimmunoassay and results were expressed as mean gastrin pg/microgram protein +/- SD. Under basal conditions the cellular gastrin content was 39.9 +/- 6.4 (control) compared with 16.7 +/- 2.1 (secretin). After 2 hours of incubation, cellular gastrin content increased in both groups: 68.5 +/- 11.9 (control) to 68.3 +/- 5.5 (secretin). However, the percent of gastrin released into the medium during incubation decreased by one half in both groups (control 37.3% +/- 4.0% to 22.2% +/- 3.0%; secretin 42.8% +/- 7.0% to 18.9% +/- 1.8%). Adenylate cyclase activity was assessed by measuring cAMP generation in fresh-frozen gastrinoma and cultured gastrinoma cell membranes. Isoproterenol (10(-5) M), PGE1 (10(-4) M), and GppNHp (guanine nucleotide) (10(-5) M) caused fivefold to 25-fold increases in cAMP generation. Secretin did not stimulate adenylate cyclase activity above basal (21.73 +/- 4.07 and 2.29 +/- 1.2 pmol cAMP/mg protein/min) for frozen and cultured gastrinoma, respectively. Secretin failed to stimulate gastrin release and adenylate cyclase in vitro. This suggests that secretin-stimulated gastrin release in vivo may not be due to a direct effect of secretin on the gastrinoma.

Adenylyl Cyclases↗

Calcium homeostasis in patients with acute pancreatitis.

Calcium homeostasis was studied serially in six patients admitted to the surgical intensive care unit because of acute pancreatitis. All developed ionized hypocalcemia. Serial assays of serum parathyroid hormone (PTH) revealed a prompt response to this hypocalcemia (1143 +/- 239 versus 574 +/- 24 pg/ml, P less than 0.05). Serum 1,25-dihydroxyvitamin D (1,25(OH)2D) levels rose from 26 +/- 8 to 104 +/- 17 pg/ml (P less than 0.01) in the expected time frame subsequent to the PTH peak, confirming the biologic significance of the PTH increases observed. Despite these significant elevations of PTH and 1,25(OH)2D, the expected prompt return of ionized calcium concentrations to normal levels was not seen. Also, urinary cyclic adenosine monophosphate production was not stimulated. These results suggest an acute functional resistance of bone to physiologic levels of PTH stimulation during the acute phase of pancreatitis. Fluid sequestration and hypovolemia are marked at this time. We suggest that pancreatitic hypocalcemia may occur when oligemic bone cannot respond normally to PTH and 1,25(OH)2D stimulation. As such, it may represent an end organ failure syndrome associated with shock and poor tissue perfusion.

Acute Disease↗

Isoelectric focusing studies on Mycobacterium chelonei.

Analytical IEF has been used to give a direct visual comparison of beta-lactamases, down to extremely low levels, from very crude intracellular preparations. Identity and non-identity of strains could be proved by the pattern of bands produced by their beta-lactamases. Mycobacterial species gave a variety of beta-lactamase patterns. Identity was established between some strains of M. chelonei. IEF distinguished between enzymes within both the chelonei and abscessus sub-species that could not be differentiated by other methods. This technique could provide a means of identifying the source of a M. chelonei infection.

Child↗

Primary peptic ulcerations of the jejunum associated with islet cell tumors. Twenty-five-year appraisal.

A review of 42 patients with gastrinoma, who either survived five years or longer or who died during this period of evaluation, was carried out to define the surgical principles which might be combined with the recent trend toward cimetidine therapy. Thirty-four (80%) of the patients had total gastrectomy with an operative mortality rate of 2.3%, and eight patients (20%) had less than total gastrectomy. No tumor was found in six patients with hypergastrinemia and an abnormal secretin bolus whose five-year survival rate was 100%. Of the thirty-six patients having tissue proof of gastrinoma, twenty-two (61%) had complete resection of all gross tumor resulting in a 76% five-year survival rate. Fourteen patients had unresectable tumor or partial resection with a five-year survival rate of 21%. Complete gross tumor resection increased mean survival by six years (p < 0.01), but resulted in persistent eugastrinemia in only two patients. Long-term survival was possible with a combination of vagotomy, lesser gastric procedures, tumor resection, and cimetidine, seven of eight patients living more than five years. Surgical management of gastrinoma should be directed toward aggressive tumor resection and vagotomy, with reliance on cimetidine therapy postoperatively to control the gastric hypersecretion. Total gastrectomy should be reserved for cimetidine failures and those who do not wish to take cimetidine for the rest of their lives.

Adenoma, Islet Cell↗

Parietal cell autoantibodies and hypergastrinemia in achlorhydria and the Zollinger-Ellison syndrome.

Parietal cell autoantibody (PCA), basal gastrin, and calcium-stimulated gastrin were measured in twenty patients with achlorhydria, in eight patients with the Zollinger-Ellison syndrome, and in fifty control subjects. In twelve patients with achlorhydria with a spared antrum, PCA was positive and basal gastrin was elevated. In contrast, eight achlorhydric patients with antral gastritis had negative PCA and significantly lower basal gastrin levels. Patients with the Zollinger-Ellison syndrome did not demonstrate positive PCA despite elevated levels of basal gastrin, nor was PCA present in normal controls. This study suggests that certain achlorhydric states are caused by an autoimmune response, particularly if antral function is spared.

Achlorhydria↗

Observations on the postoperative tumor growth behavior of certain islet cell tumors.

Over a period of 21 years 39 patients with gastrinoma were surgically treated. Thirty-three patients had total gastrectomy with two postoperative deaths, and 6 patients had a lesser procedure. The postoperative fasting gastrin levels remained elevated and did not always indicate the extent of tumor involvement. Further mobilization of tumor gastrin by provocative infusion of calcium gluceptate, 15 mg/kg of body weight, should be carried out routinely. A hepatic angiogram should be considered when the gastrin levels exceed 1,000 picograms per ml. Chemotherapy consisting of Tubercidin, Streptozotocin and 5-Fluorouracil was given to 5 patients with extensive gastrinoma. All patients felt better and gained from three to 35 pounds in weight. Since 60% of the patients died or have definite evidence of tumor activity it is assumed that the tumor growth was not inhibited and that it is malignant. Approximately 40% of the patients seem to do well despite modest elevations in gastrin levels suggesting that the retained tumor could be considered benign.

Adenoma, Islet Cell↗

Concrete strategies for sensitizing youth-serving agencies to the needs of gay, lesbian, and other sexual minority youths.

In the past few years, several authors have detailed the needs of gay and lesbian youths and the obstacles youth-serving agencies face in addressing their needs. How administrators and practitioners can make changes in agencies that are not adequately serving sexual minority youths has been unclear. This article uses the experiences of two youth-serving agencies to offer recommendations on agency philosophies concerning the social realities of sexual minority youths and on several ways of creating a safe, welcoming, and productive environment.

Adolescent↗