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Biomedical subjects

J Sparks

Publications and source records attributed to J Sparks.

At least 19 recordsLinked to original sources
PubMed2001

Using eye movement desensitization and reprocessing to enhance treatment of couples.

Eye Movement Desensitization and Reprocessing (EMDR) as a clinical technique may enhance treatment effectiveness when applied within a couple therapy approach that is emotionally and experientially oriented. Clinical experience indicates that EMDR-based interventions are useful for accessing, activating, tolerating, and reprocessing the intense emotions that often fuel dysfunctional couple interactions. Using EMDR within conjoint sessions to reprocess negative emotions can amplify intimacy, increase connection, and subsequently lead to a change in problematic relationship patterns.

Adult↗
PubMed2000

Dignity or denial? Decisions regarding initiation of dialysis and medical therapy in the institutionalized severely mentally retarded.

Decisions regarding health care of the severely mentally retarded can be difficult. We present 2 cases of patients with severe mental retardation who lived in long-term care facilities. Both patients had progressive loss of renal function and eventually reached end-stage renal disease. In each case, the decision was made not to initiate dialysis. We discuss issues of dialysis and medical care of the severely mentally retarded and advocate using the principles of "best respect" and "best interest" in making medical decisions in this population.

Adult↗
PubMed1999

An analysis of polygenes affecting wing shape on chromosome 3 in Drosophila melanogaster.

Loci on the third chromosome of Drosophila melanogaster that affect an index of wing shape were mapped, using recombinant isogenic lines, with transposable elements as markers. Many genes with small subequal effects are dispersed along the whole chromosome. Their alleles act nearly additively in heterozygotes. They have small correlated effects on leg shape, but no detectable effects on halteres. Small negative net interactions occur over most of the chromosome. The data set of 519 recombinant isogenic lines can be explained reasonably well by two models. One model posits an indefinitely large number of loci with no interactions. The other model posits 11 loci with additive effects whose sum equals the total phenotypic range and with large positive and negative interactions that nearly cancel each other.

Animals↗
PubMed1999

Tracing the evolution of critical evaluation skills in students' use of the Internet.

This paper documents the evolving uses of the Internet made by public health graduate students and traces the development of their search methods and critical evaluative criteria. Early in the first semester and again six months later, twenty-four graduate students in a problem-based learning curriculum, which emphasizes evidence-based critical thinking skills, were required to describe their most helpful resources and to evaluate these resources critically. The answers were coded for the types of resources the students used, how frequently they were used, and why they were used. Student perception of the usefulness of resources, especially the Internet, and ability to evaluate these resources critically changed greatly. Initially, 96% of the students stated that the Internet was their most helpful resource. Six months later, these students continued to use the Internet; however, it was not their most useful source. At the later point, students had very specific uses for the Internet. Their most frequently used evaluation criterion was the reliability and objectivity of the source of the information. By the end of the first year of study, the majority of the students demonstrated an understanding of the principles of evidence-based practice and applied them to their research and analysis of information resources.

Curriculum↗
PubMed1996

Effect of background interference on accelerant detection by canines.

Additional studies were performed with respect to examining the lower limits at which canines can reliably detect products commonly used as accelerants and distinguish them from pyrolysis products or background hydrocarbons. As part of a testing exercise performed in conjunction with a national conference of the Canine Accelerant Detection Association (CADA), 34 canines were subjected to a series of tests, some of them were a recertification proficiency. In one of the tests, the dogs were nearly unanimously successful in locating one can (out of five) containing 50% evaporated gasoline at the 5 microL level on a burnt carpet matrix, and pinpointing the 6-in. square sector on a piece of plain carpeting where the same amount of gasoline (5 microL) was applied. However, only half were able to detect a second doped sample containing a lesser amount (0.05, 0.1, or 0.2 microL) of gasoline, and registered a number of alerts on samples containing only burnt carpeting material. The dogs were also tested on measured amounts (2 or 5 microL) of a variety of other light, medium, and heavy petroleum products applied to a variety of substances containing significant pyrolysis products. As a group, the canines were much less successful in pinpointing these products than they were with gasoline at this same level, and again registered a number of alerts on cans containing only pyrolysis products. The significant number of alerts by canines on samples not containing gasoline or other products points out the importance of obtaining laboratory confirmation on samples on which dogs alert, and on keeping accurate field and training records of canines to establish their credibility.

Animals↗
PubMed1993

Long-term prognosis of Zollinger-Ellison syndrome in multiple endocrine neoplasia.

BACKGROUND: The long-term prognosis of Zollinger-Ellison Syndrome (ZES) is not well defined. The findings of other endocrinopathies, the need for long-term surveillance, and the role of surgical treatment are controversial. METHODS: To help provide more information about these topics the records of 76 patients with ZES were reviewed. RESULTS: Nineteen patients with gastrinoma had multiple endocrine neoplasia (MEN). Fifteen had hyperparathyroidism from 14 years before to 38 years after the diagnosis of ZES. Three patients had pituitary adenomas. The unusual findings of pheochromocytoma were also seen in three patients. Sixteen patients were followed at least 10 years and 12 were followed for more than 20 years. Surgical cure was achieved in only one patient after a 12-year follow-up. The actual 5-, 10-, 15-, and 20-year survival rates of 94%, 75%, 61%, and 58%, respectively, were compared with patients with sporadic ZES with 5-, 10-, 15-, and 20-year survival rates of 62%, 50%, 37%, and 31%, respectively. CONCLUSIONS: Multiple endocrinopathies are common but are rarely diagnosed synchronously, mandating life-long surveillance for patients with ZES. Long-term prognosis is good. Survival is longer for patients with ZES and MEN compared with patients with sporadic ZES. Surgical cure is rare. Surgical excision without a single localized lesion does not seem justified.

Adenoma↗
PubMed1989

Gastrinoma: the predictive value of preoperative localization.

In the management of gastrinoma, a variety of preoperative tests for tumor localization are recommended. Their value in predicting surgical outcome is not well defined. We reviewed the preoperative investigation and operative outcome in 23 patients to assess the predictive value of localization before surgery. With results of laparotomy used as reference, the efficacy of computed tomography, angiography, ultrasonography, and magnetic resonance imaging, individually and combined for primary and metastatic disease, was determined. All investigative modalities were poor for the detection of primary gastrinomas, with individual sensitivities in the range of 20% to 29%. Their combined sensitivity was 53%, with a negative predictive value of only 38%. The detection of metastatic disease was better, with a combined accuracy of 83%. At laparotomy, tumor was identified in 19 of 23 (83%) patients. In 14 patients with negative preoperative workup, primary gastrinoma was found in 10 of 14 (71%) and resected for long-term cure in three of 14 (21%) patients. In all nine patients with positive preoperative test results, tumor was found and was resected for cure in four (44%) patients. In conclusion, preoperative localization of primary gastrinoma is unreliable, and a negative workup does not preclude cure. Therefore, despite the availability of effective palliative antiulcer therapy, all patients exclusive of those with multiple endocrine neoplasia, type I, or metastasis should undergo laparatomy with curative resection in mind.

Angiography↗
PubMed1987

Purification and renaturation of recombinant human interleukin-2.

Recombinant human interleukin-2 (IL-2) expressed as Escherichia coli was isolated as insoluble aggregates of protein (inclusion bodies) after cell breakage. IL-2 and contaminants were dissolved in 6 M-guanidinium chloride/10 mM-dithiothreitol, pH 8.5, and further purified in reduced and denatured form by gel-permeation chromatography in the same solvent. Renaturation was effected by dilution and autoxidation; IL-2 of native specific activity was isolated at over 95% purity by reversed-phase h.p.l.c.; an additional peak of reduced protein was also observed. Most losses of native IL-2 occurred on refolding, probably because of an aggregation process; concentrations around 1 microgram/ml were necessary to achieve 30% recovery. It was essential to maintain the denatured protein in reduced form before renaturation and autoxidation, which was most efficient at pH 8.5 with 1.5 microM-CuSO4. A procedure based on these observations has been used to prepare IL-2 on the 50 micrograms scale.

Chromatography, Gel↗
PubMed1987

Micropreparative purification of recombinant human interleukin-2.

Recombinant Interleukin-2 (IL-2) is expressed in E. coli as insoluble aggregates; a protocol has been developed for solubilization, renaturation and purification of IL-2 from such aggregates at the 5-10-mg level. IL-2 aggregates were isolated from soluble proteins by centrifugation, subjected to a 1 M guanidine hydrochloride wash and a butan-1-ol wash (the latter to remove lipid), dissolved in 8 M guanidine hydrochloride-10 mM dithiothreitol and partly purified by gel permeation chromatography. Refolding/oxidation was then performed by dilution into Tris-HCl, pH 8.5 containing 1.5 microM copper sulphate to accelerate autoxidation. Final purification was by successive cation-exchange and reversed-phase high-performance liquid chromatographic steps, yielding over 99.5% pure IL-2 with an overall recovery of 20%.

Chromatography, Gel↗
PubMed1987

Early surgical treatment of gastrinoma.

Medical treatment of the Zollinger-Ellison syndrome has been generally accepted because of the proven efficacy of the histamine (H2)-receptor antagonists in achieving symptomatic relief, and because of early reports indicating that few, if any, gastrinomas were resectable for cure. Gastrin radioimmunoassay (RIA) has made earlier and more certain diagnosis possible, and therefore reevaluation of the surgical management of gastrinomas is necessary. Experience with 60 gastrinoma patients is reported. Comparison between the pregastrin RIA years (before 1970) and post-gastrin RIA years was made to determine whether there was evidence to support the continuation of medical treatment without attempts to resect the gastrinoma. Twenty-five cases were diagnosed in the pre-RIA years. Age at diagnosis ranged from 17 to 68 years (median, 45 years). All patients were operated on. Metastases were found in 56 percent. No tumor was identified in 8 percent. Tumor was resected for "cure" (normal fasting gastrin levels for two years postoperatively) in one patient. Seventeen patients have died, and tumor was the cause of death in 70 percent. The five-year survival rate was 44 percent; the 10-year survival rate was 40 percent. Thirty-five cases were diagnosed after 1970. Age at diagnosis ranged from 39 to 61 years (median, 46 years). Thirty patients were operated on. Metastases were identified in 23 percent and no tumor was found in 17 percent. Tumor was resected for "cure" in 30 percent of patients. Seven patients have died and tumor caused death in 42 percent. The five-year survival rate was 82 percent; the 10-year rate was 64 percent. Advances in diagnosis and surgical technique since 1970 have made early operative treatment applicable in patients with gastrinoma. Because death in most cases is caused by progression of the tumor, an aggressive surgical approach to resect the tumor is advised soon after the diagnosis of Zollinger-Ellison syndrome is established.

Duodenal Neoplasms↗
PubMed1987

Effect of somatostatin analogue (SMS 201-995) on molecular species of gastrin in gastrinoma.

Somatostatin analogue (SMS 201-995) has been shown to decrease total serum gastrin in patients with gastrinoma; however, the gastrin level rarely returns to normal, despite the near-complete inhibition of acid secretion. This implies that SMS may have an inhibitory action on the biologically active molecular species of gastrin and have little effect on biologically inactive species. To test this hypothesis, we determined the effect of SMS on the molecular species of gastrin in eight patients with the Zollinger-Ellison syndrome. Serum obtained before treatment and 6 hours and 18 hours after treatment (SMS 1 microgram/kg, subcutaneously) was sampled and assayed for molecular species of gastrin by means of gel filtration chromatography and fractional quantitation of gastrin species by radioimmunoassay. There was a significant decrease in the amount of G-34 and G-17 species. BBG and G-14 decreased, a change not significant at 6 hours but significant 18 hours after SMS. The distribution of the various molecular species as a percent of total immunoreactive gastrin was analyzed before and after SMS. There was a shift in the distribution of the molecular species, so that 6 hours after SMS treatment nearly 50% of total gastrin activity was accounted for by BBG and component I. SMS seems to have a different potency to inhibit release of the various gastrin molecular species. This observation may explain the failure of total gastrin levels to return to normal after SMS treatment in patients with the Zollinger-Ellison syndrome.

Aged↗
PubMed1986

Characterization of the in vivo and in vitro inhibition of gastrin secretion from gastrinoma by a somatostatin analogue (SMS 201-995).

Earlier experiments characterized the effect of SMS 201-995 on gastrin secretion from gastrinoma in vivo. The results showed that the somatostatin analogue inhibits basal as well as secretin- and calcium-stimulated gastrin secretion. The current study examined the effect of SMS 201-995 on gastrin secretion from gastrinoma in vitro. Gastrinoma cells were prepared in cell culture or acute cell dispersion to study basal gastrin release. In cell culture, SMS 201-995 at 10(-9) M, 10(-8) M, and 10(-7) M significantly stimulated gastrin secretion (basal medium gastrin, 157 +/- 7.9 pg/ml; with SMS 201-995 10(-9) M, 786 +/- 62 pg/ml; with SMS 201-995 10(-8) M, 569 +/- 72 pg/ml; and with SMS 201-995 10(-7) M, 258 +/- 26 pg/ml). In contrast, in acute cell dispersion, the somatostatin analogue inhibited gastrin secretion (basal medium gastrin, 12.8 +/- 1.3 ng/ml; with SMS 201-995 10(-9) M, 9.0 +/- 0.1 ng/ml; with SMS 201-995 10(-8) M, 8.4 +/- 1.5 ng/ml; and with SMS 201-995 10(-7) M, 7.9 +/- 0.2 ng/ml). Gastrinoma cells were prepared in cell culture to study the effect of SMS 201-995 on gastrin secretion stimulated by secretin and by post-receptor increases in adenosine cyclic nucleotide. The somatostatin analogue inhibited gastrin secretion stimulated by secretin (10(-6) M) (797 +/- 48 pg/ml for secretin alone, compared with 396 +/- 9.4 pg/ml for secretin plus SMS 201-995). SMS 201-995 did not inhibit gastrin secretion stimulated by dibutyryl cyclic AMP (10(-7) M) (617 +/- 62 pg/ml for dibutyryl cyclic AMP alone, compared with 778 +/- 55 pg/ml for the two together). In vitro, SMS 201-995 inhibits basal gastrin secretion from gastrinoma prepared in acute cell dispersion, but not gastrinoma in cell culture, probably due to differences in basal secretory rates. The effect in vitro is less than that in vivo. SMS 201-995 does not inhibit postreceptor increases in adenosine nucleotide. This indirectly supports the hypothesis that SMS 201-995 acts in gastrinoma cells to inhibit gastrin secretion by inhibition of adenylate cyclase activity.

Adult↗
PubMed1986

Somatostatin-like peptides alter calcium but not secretin sensitivity of gastrinoma cells.

The provocation of gastrin release by calcium or secretin is accepted as a method to differentiate the hypergastrinemia of the Zollinger-Ellison syndrome from that of other causes. We have previously shown that calcium and secretin failed to provoke gastrin release from acutely dispersed gastrinoma cells. This disparity between the in vivo and in vitro effects of these two provocative agents suggests that intermediates may be necessary for calcium- or secretin-induced gastrin release. In an acute cell dispersion, serum-free model, two gastrinomas with low levels of endogenous somatostatin (SRIF) and other peptides failed to respond to calcium or secretin provocation. Conversely, a third tumor containing high levels of endogenous SRIF-like peptides and low levels of other gut peptides did respond to calcium, but not to secretin provocation in vitro. We suggest that in vivo, SRIF modulation of gastrin release is a prerequisite for calcium-simulated gastrin secretion.

Animals↗
PubMed1986

Observations on the effect of a somatostatin analog in the Zollinger-Ellison syndrome: implications for the treatment of apudomas.

Somatostatin is known to inhibit hormone release and gastrointestinal secretion and hence may be useful in the treatment of amine precursor uptake, decarboxylase tumors. Clinical application has been limited by the short half-life, potency, and specificity of the natural hormone. Our study evaluated the effect of a synthetic analog of somatostatin, SMS 201-995 (Sandoz, Inc., E. Hanover, N.J.) on basal and stimulated gastrin release and gastric acid secretion in 10 patients with the Zollinger-Ellison syndrome. In experiment 1, H2-receptor antagonists were discontinued for 48 hours; SMS 201-995, 1 microgram/kg, was given subcutaneously; gastrin and SMS levels in plasma were determined by radioimmunoassay; and gastric secretion was measured and titrated at 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, and 18 hours. The mean +/- SEM baseline gastrin level (1526 +/- 733 pg/ml) was significantly inhibited for 16 hours (p less than 0.05, paired t test). Gastric secretion was neutralized for as long as 18 hours (p 0.05). In experiment 2, three patients received either a secretin (2 U/kg) or a calcium stimulation test (2 mg/kg) with or without pretreatment with SMS 201-995, 1 microgram/kg, subcutaneously. The mean +/- SEM interpreted change in gastrin (ng X 60 min/ml) without SMS 201-995, 36.8 +/- 11 (secretin), and 129 +/- 30 (calcium) were reduced with SMS 201-995 to -1.1 +/- 0.76 (secretin) and -29 +/- 28 (calcium) (p less than 0.05). In the Zollinger-Ellison syndrome, SMS 201-995 caused significant and long-lasting inhibition of both tumor gastrin release and gastric acid secretion, probably by direct action on both the gastrinoma and the stomach. SMS 201-995 blocks acid secretion and secretin- and calcium-stimulated gastrin release, indicating that SMS 201-995 inhibits peptide secretion by postreceptor mechanisms. SMS 201-995 will be useful in the palliative treatment of apudomas.

Adult↗
PubMed1986

Effect of secretin on gastrin release from gastrinoma cells in vitro.

Secretin appears to have a direct effect on gastrinoma cells, which results in a paradoxic increase in the serum gastrin level in patients with the Zollinger-Ellison syndrome. To evaluate this effect, gastrinoma cells were challenged with secretin in acute cell dispersion or after 2 weeks in culture. Acutely dispersed cells were incubated for 15 minutes or 3 hours with and without secretin 10(-6) mol/L. (sec). There was no significant difference in gastrin release between control and sec groups in the two acute incubation periods. At 15 minutes the control value was 47 +/- 1 and the sec value was 54 +/- 1 ng/ml, while at 3 hours the control value was 59 +/- 1 and the sec value was 61 +/- 1 ng/ml. In the cell culture preparation, secretin stimulated gastrin release at all doses (control 463 +/- 85, SEC 10(-10) mol/L 603 +/- 37, sec 10(-8) mol/L 706 +/- 37, sec 10(-6) mol/L 798 +/- 48 pg/ml ([p less than 0.05, Student t test]). These results indicate that secretin stimulates gastrin release directly from cultured gastrinoma cells in a dose-dependent manner but does not stimulate gastrin release from acute cell dispersion. This might be attributed partly to the recovery of secretin receptors in the cultured cells.

Cells, Cultured↗
PubMed1985

Gastrin release from dispersed gastrinoma cells: effects of calcium and calcium ionophore (A23187).

Dispersed single-cell suspensions of human gastrinoma tissue were incubated for 15, 60, and 120 min in a calcium-containing medium, (0.1, 2, 10 mM) in calcium-free medium and in calcium-free medium containing the calcium ionophore A23187 (0.01, 1, and 100 micrograms/ml). Supernatant and pellet (intracellular) gastrin levels were determined by radioimmunoassay. Supernatant gastrin levels remained stable over 120 min in calcium chloride or calcium gluconate containing medium, while intracellular pellet gastrin approximately tripled during the same incubation period. Total gastrin (supernatant plus pellet) approximately doubled during the 2-hr incubation in calcium. However, calcium (0.1, 2, or 10 mM) failed to produce a dose-dependent rise in supernatant, pellet, or total gastrin when compared to calcium-free incubates. Contrary to the expected gastrin response to calcium, supernatant and pellet gastrin levels were higher in incubates in calcium-free medium than in calcium-containing incubates. A23187 (0.01 or 1 mcg/ml) in a calcium-free medium decrease supernatant gastrin while high dose ionophore (100 mcg/ml) increased supernatant gastrin. All doses of ionophore stimulated pellet and total gastrin levels. Thus, it appears that the clinical augmentation of gastrin levels, seen with calcium challenge in vivo may not be solely due to changes in serum calcium.

Adult↗