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Biomedical subjects

J L Cameron

Publications and source records attributed to J L Cameron.

At least 127 records · Page 7Linked to original sources

A comparison of flow cytometric and absorption cytometric DNA values as prognostic indicators for pancreatic carcinoma.

BACKGROUND: The DNA content of 30 adenocarcinomas of the head of the pancreas was measured by flow and absorption cytometric analysis. METHODS: Each of the patients in this study had curative pancreatoduodenectomy. The absorption cytometric measurements were done in a research laboratory, and the flow cytometric measurements were performed in a commercial laboratory. The DNA measurements were done on nuclei disaggregated from pancreatic cancer tissue blocks without the examiner knowing whether the patient had survived. RESULTS: Twenty-one of the 30 cancers were found to be aneuploid by absorption cytometric analysis, whereas only 1 of the 30 cancers was aneuploid by flow cytometric analysis. This difference was statistically significant (P < 0.001). CONCLUSIONS: Univariate and multivariate analyses showed that the absorption cytometric DNA measurements were stronger prognostic determinants for patient survival than were the flow cytometric DNA measurements, indicating that some caution may be warranted in the interpretation of commercially obtained DNA distributions of pancreatic carcinomas.

Analysis of Variance↗

Surgical experience with pancreatic islet-cell tumors.

OBJECTIVE: To review the surgical management of pancreatic islet-cell tumors, with attention to preoperative localization, surgical therapy, and postoperative survival. DESIGN: Consecutive case series of patients treated surgically for pancreatic islet-cell tumor. SETTING: The Johns Hopkins Hospital, a large teaching hospital in Baltimore, Md, serving both as a primary and tertiary care center. PATIENTS: Thirty-seven patients with pancreatic islet-cell tumors treated surgically between 1979 and 1990. MAIN OUTCOME MEASURES: Success of preoperative localization studies, types of operations performed, and postoperative survival. RESULTS: Preoperative computed tomography correctly localized the tumor in 20 of 34 patients (59%); angiography in 21 of 28 patients (75%), and the combination of computed tomography and angiography in 23 of 28 patients (82%). Benign islet-cell tumors were found in 19 patients, and malignant tumors in 18 patients. Twenty-four patients (65%) had functional tumors. The proportion of patients with nonfunctioning tumors increased from 0% before 1984, to 43% from 1985 to 1990. Surgical therapy was curative in 27 patients and palliative in 10. The most commonly performed operative procedures were tumor enucleation (11 patients [30%]), distal pancreatectomy (10 patients [27%]). There was no operative mortality. The actuarial survival at 40 months was 100% in patients with benign tumors and significantly lower (66%) in patients with malignant tumors. CONCLUSIONS: This experience from a single institution underscores the role of preoperative localization studies and appropriate surgical management of these rare tumors.

Adenoma, Islet Cell↗

Modulation of reproductive hormone secretion by nutritional intake: stress signals versus metabolic signals.

States of chronic undernutrition can cause a profound suppression of reproductive function. To begin to determine the time course and the nature of the mechanism by which undernutrition suppresses the activity of the reproductive axis we have examined the effects of brief periods of fasting on reproductive hormone secretion in men and male rhesus monkeys. In monkeys there is a significant suppression of pulsatile luteinizing hormone (LH) and testosterone secretion after a single day of fasting, that is apparent within the first 4 h after a meal is missed. The suppression of pulsatile LH secretion on a day of fasting does not appear to be caused by the psychological stress experienced when monkeys are deprived of their daily meal in that monkeys who are maintained in a metabolically fed state (by feeding a large excess of food on the day prior to fasting), but are deprived of a meal and displayed behavioural agitation associated with fasting, have no suppression of LH secretion. The suppression of LH secretion on a day of fasting cannot be reversed by naloxone infusion, indicating that increased secretion of opioid peptides is not the primary mechanism causing the decrease in the central drive to the reproductive axis during fasting.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of portosystemic shunting on PGI2 and glucagon levels in humans.

OBJECTIVE: This study determined if the proposed mediators of splanchnic blood flow, prostacyclin and glucagon, were elevated in patients with portal hypertension undergoing portal systemic shunts. SUMMARY BACKGROUND DATA: Chronic portal hypertension results in increased portal venous pressure and increased splanchnic blood flow. Animal studies have suggested prostacyclin or glucagon, potent vasodilators, as potential mediators of this increased flow. Correlative clinical studies have been difficult to perform due to the wide variation in degree of portal-systemic shunting and the frequent association of parenchymal liver disease in patients with cirrhosis. METHODS: The authors measured portal and systemic hemodynamics in PGI2 and glucagon levels in patients with portal hypertension due to cirrhosis (partial portal systemic shunt) and Budd-Chiari syndrome (complete portal systemic shunt) undergoing portal systemic shunts and in porto normotensive patients undergoing exploratory laparotomies. RESULTS: PGI2 levels in portal hypertension were significantly increased over normal, and prostacyclin in Budd-Chiari patients were increased significantly over patients with cirrhosis. Both PGI2 and portal venous pressure decreased significantly after portal systemic shunting, and prostacyclin levels correlated directly with portal venous pressure (R = 0.37, p < 0.05). CONCLUSIONS: This is the first evidence in humans supporting the hypothesis that PGI2 is elevated in portal hypertension and is related to both the degree of portal venous obstruction and portal pressure. PGI2 probably has a role in the abnormal splanchnic hemodynamics of human portal hypertension.

Adult↗

One hundred and forty-five consecutive pancreaticoduodenectomies without mortality.

OBJECTIVE: A review of mortality and morbidity for pancreaticoduodenectomy was performed for 145 consecutive patients who underwent the operative procedure between 1988 and 1991. SUMMARY BACKGROUND DATA: In the past, pancreaticoduodenectomy has carried a high hospital morbidity and mortality. During the 1970s, many considered that the operation should be abandoned. Recent data, however, suggest that a marked drop in both morbidity and mortality have occurred for this operative procedure. METHODS: Among the 145 consecutive patients who underwent pancreaticoduodenectomy, 108 patients were 69 years of age or younger, and 37 were 70 years of age or older. Four patients were 80 years of age or older. One hundred and seven patients had a malignant neoplasm, whereas 38 patients had benign disease. There were no significant differences in preoperative risk factors when the younger and older, and benign disease and malignant disease groups were compared. RESULTS: Mean operative time was 7.3 hours. Median blood loss was 0, indicating that more than one-half of the patients underwent pancreaticoduodenectomies without blood transfusions. There were no significant differences in postoperative complications when the younger and older, and benign disease and malignant disease groups were compared. There was no hospital or 30-day mortality. CONCLUSIONS: With appropriate preoperative selection, virtually any patient in any age group, with benign or malignant disease, can undergo pancreaticoduodenectomy with minimal risk of hospital mortality.

Adult↗

Chemical splanchnicectomy in patients with unresectable pancreatic cancer. A prospective randomized trial.

OBJECTIVE: A prospective, randomized, double-blind study was completed comparing intraoperative chemical splanchnicectomy with 50% alcohol versus a placebo injection of saline in patients with histologically proven unresectable pancreatic cancer. METHODS: Standardized assessment of pain, mood, and disability due to pain was completed preoperatively and at 2-month intervals until death. Chemical splanchnicectomy with alcohol was performed in 65 patients, whereas 72 patients received the placebo. The two groups were similar with respect to age, sex, location, and stage of tumor, operation performed, the use of postoperative chemo- and radiation therapy, and initial assessment scores for pain, mood, and disability. RESULTS: No differences in hospital mortality or complications, return to oral intake, or length of hospital stay were observed. Mean pain scores were significantly lower in the alcohol group at 2-, 4-, and 6-month follow-up and at the final assessment (p < 0.05). To further determine the effect of chemical splanchnicectomy, patients were stratified into those with and without preoperative pain. In patients without preoperative pain, alcohol significantly reduced pain scores and delayed or prevented the subsequent onset of pain (p < 0.05). In patients with significant preoperative pain, alcohol significantly reduced existing pain (p < 0.05). Furthermore, patients with preexisting pain who received alcohol showed a significant improvement in survival when compared with controls (p < 0.0001). CONCLUSION: The results suggest that intraoperative chemical splanchnicectomy with alcohol significantly reduces or prevents pain in patients with unresectable pancreatic cancer.

Actuarial Analysis↗

Erythromycin accelerates gastric emptying after pancreaticoduodenectomy. A prospective, randomized, placebo-controlled trial.

OBJECTIVE: This study tested the hypothesis that erythromycin, a motilin agonist, reduces the incidence of early DGE after pancreaticoduodenectomy. SUMMARY BACKGROUND DATA: Delayed gastric emptying (DGE) is a leading cause of morbidity after pancreaticoduodenectomy, occurring in up to 40% of patients. The pathogenesis of DGE has been speculated to involve factors such as peritonitis from anastomotic leaks, ischemia to the antropyloric muscles, and gastric atony in response to resection of the duodenal pacemaker or reduction in circulating motilin levels. METHODS: Between November 1990 and January 1993, 118 patients undergoing pancreaticoduodenectomy completed this prospective, randomized, placebo-controlled trial. The patients received either 200 mg of intravenous erythromycin lactobionate every 6 hours (n = 58), or an identical volume of 0.9% saline (n = 60) from the third to tenth postoperative days. On the tenth postoperative day, a dual phase radionuclide gastric emptying study was performed. RESULTS: The erythromycin and control groups were comparable regarding multiple preoperative, intraoperative, and postoperative factors. The erythromycin group had a 37% reduction in the incidence of DGE (19% vs. 30%), a significantly reduced (p < 0.05) need to reinsert a nasogastric tube for DGE (6 vs. 15 patients), and a significantly reduced (p < 0.01) per cent retention of liquids at 30 minutes and solids at 30, 60, 90, and 120 minutes. No major adverse reactions to erythromycin were observed. CONCLUSIONS: Erythromycin is a safe, inexpensive drug that significantly accelerates gastric emptying after pancreaticoduodenectomy and reduces the incidence of DGE by 37%. These data support the use of erythromycin to decrease early DGE after pancreaticoduodenectomy.

Aged↗

Comparison of left anterior oblique, anterior, and geometric mean methods in gastric emptying assessment of postpancreaticoduodenectomy patients.

Although left anterior oblique (LAO) gastric emptying studies appear to be an adequate alternative to geometric mean (GM) measurements in patients with normal gastric anatomy, it is not clear whether they can be used after gastric or duodenal surgery. In this study, dual-phase gastric emptying studies with combined solid-liquid meal were performed in 54 patients who had undergone pancreaticoduodenectomy (Whipple procedure). Gastric emptying was studied with GM, LAO, and anterior (ANT) methods. T1/2 and percent gastric retention at 10, 30, 60, 90, and 120 minutes were calculated. Results from the three methods were compared using correlation analysis and the t test. The t test showed no significant difference in T1/2 and percent retention values between the GM and LAO or ANT views. The solid emptying T1/2 showed a better correlation between GM and LAO values (r = 0.824) than between GM and ANT (r = 0.589). For the liquid T1/2, the reverse was true. Correlation between GM and ANT (r = 0.939) was better than between GM and LAO (r = 0.839); however, both LAO and ANT views correlated well with GM liquid emptying. It is concluded that the LAO view can replace GM gastric emptying methods in postpancreaticoduodenectomy patients for evaluation of both solid and liquid emptying, although the ANT view appears completely adequate for the study of liquid emptying.

Adenocarcinoma↗

Diurnal pattern of pulsatile luteinizing hormone and testosterone secretion in adult male rhesus monkeys (Macaca mulatta): influence of the timing of daily meal intake.

Adult male rhesus monkeys have a diurnal pattern of reproductive hormone secretion that is characterized by significantly elevated LH and testosterone secretion in the evening hours and a nadir in secretion of these hormones in the morning. To test the hypothesis that the daily pattern of food intake may play a role in regulating the diurnal pattern of reproductive hormone secretion we performed three studies. First, to determine the relationship between the timing of the diurnal rise in LH secretion and meal consumption, blood samples were collected from 13 adult male rhesus monkeys via chronically indwelling venous catheters (samples every 15-20 min from 0800-0800 h) while monkeys were maintained on the standard feeding regimen in our colony (one meal of Purina monkey chow fed between 1100 and 1200 h). On a day of normal feeding there was a significant diurnal rhythm in mean LH concentrations with elevated levels at night (nadir: 13.41 +/- 0.82 ng/ml from 0800-1100 h; peak: 21.34 +/- 1.56 ng/ml from 2000-2300 h, P < or = 0.05). The rising phase of the diurnal rhythm in LH secretion was apparent starting in the early afternoon, shortly after the daily meal, at 1400 h (5 h before lights went off at 1900 h), and the diurnal rise in LH secretion was no longer apparent by 0500 h (several hours before the lights went on at 0700 h). Second, we examined the influence of missing the daily meal on the diurnal pattern of LH and testosterone secretion. Blood samples were collected for a 24-h period on a day of fasting from 9 monkeys. On a day of fasting there was no diurnal rise in plasma LH or testosterone concentrations; plasma concentrations of these hormones remained at the low morning levels throughout the day. Third, we examined the diurnal pattern of LH and testosterone secretion after adapting 5 monkeys (for 6-8 weeks) to a new meal time that was 6 h later in the day than the standard meal time (i.e. at 1700 h). After adaptation to this later feeding time monkeys showed a 6-h delay in the time of the first significant rise in LH secretion (which occurred at 2000 h).(ABSTRACT TRUNCATED AT 400 WORDS)

Algorithms↗

Cholecystokinin (CCK)-induced stimulation of luteinizing hormone (LH) secretion in adult male rhesus monkeys: examination of the role of CCK in nutritional regulation of LH secretion.

Studies were performed with the overall goal of testing the hypothesis that cholecystokinin (CCK), a peptide hormone released from the gastrointestinal tract in response to meal consumption, provides a metabolic signal which modulates LH secretion in response to changes in the body's nutritional intake. In an initial study to document the effects of CCK on LH secretion in adult male rhesus monkeys, sulfated CCK-8 (7 and 15 micrograms/kg) was administered to six monkeys, and blood samples were collected from indwelling venous catheters. The 15-micrograms/kg dose of CCK elicited a rapid release of LH, with peak LH levels of 31.29 +/- 7.19 ng/ml occurring within 5-15 min. To determine the CCK receptor type mediating the effect of CCK on LH secretion, specific CCK type-A (L-364,718) and type-B (L-365,260) receptor antagonists (1 mg/kg) were administered to five monkeys 15 min before CCK administration. The CCK-A antagonist completely blocked LH secretion in response to CCK, whereas the CCK-B antagonist had no effect. To assess whether endogenous CCK, released in response to food intake, stimulates LH secretion, six monkeys were fasted for 1 day and then provided with a normal meal of monkey chow (i.e. a refeed meal) the following day, with either no antagonist, CCK-A antagonist, or CCK-B antagonist administered 30 min before the meal. As previously demonstrated, meal consumption after a brief period of fasting caused a rapid stimulation of pulsatile LH secretion. The refeed meal led to a comparable stimulation of LH secretion regardless of whether monkeys received no antagonist (3.7 +/- 0.44 LH pulses/9 h), CCK-A antagonist (3.33 +/- 0.56 LH pulses/9 h), or CCK-B antagonist (4.0 +/- 0.78 LH pulses/9 h). These results indicate that CCK can stimulate LH secretion in adult male rhesus monkeys, acting via type-A CCK receptors. However, endogenous CCK released in response to meal intake does not appear to be responsible for the meal-induced stimulation of LH secretion that occurs when monkeys are fed a normal meal after a brief period of fasting.

Animal Feed↗

Suppression of luteinizing hormone secretion during short-term fasting in male rhesus monkeys: the role of metabolic versus stress signals.

One day of fasting leads to a significant suppression of pulsatile LH secretion in adult male rhesus monkeys that is evident within the first 4-6 h after a missed meal. Restricting food intake may suppress the central drive to the reproductive axis via metabolic signals occurring during the transition from a fed, energy storing state to a fasted, energy mobilizing state or via signals associated with the "psychological stress" imposed by withholding food. To distinguish between these two general types of signals, we chose the experimental strategy of providing monkeys with a great excess of calories on the day before fasting (i.e. overfeeding on the day before fasting) in order to maintain them in a metabolically fed state on the following day when they were fasted, without preventing the psychological stress associated with fasting. We reasoned that if metabolic signals are responsible for causing the fasting-induced suppression of LH secretion, overfeeding on the day before fasting would prevent the fasting-induced suppression of LH secretion. Eight adult male rhesus monkeys with indwelling venous catheters were studied on three occasions: on a day of normal feeding (receiving approximately 30 pellets of monkey chow at 1100 h on the day of the study), on a day of fasting after a day of normal feeding, and on a day of fasting after a day of overfeeding (receiving one meal of 100 pellets on the day before the study). Pulsatile LH secretion on a day of fasting after a day of normal feeding (0.4 +/- 0.2 pulses/6 h, measured from 1200-1800 h) was significantly suppressed, P < 0.05, compared to a day of normal feeding (1.8 +/- 0.3 pulses/6 h). In contrast, on a day of fasting after a day of overfeeding there was no significant difference in LH secretion measured from 1200-1800 h (1.5 +/- 0.3 pulses/6 h) compared to a day of normal feeding. Overfeeding the day before fasting prevented the normal fasting-induced suppression of plasma T3 concentrations and delayed the normal fasting-induced decline in plasma insulin concentrations. Overfeeding did not prevent the display of agitated behavior that we have previously documented in monkeys when they are fasted. These results support the hypothesis that the signal(s) which suppresses normal LH secretion after brief periods of fasting is related to the metabolic status of the body during the transition from a fed to a fasted state, rather than a function of the psychological state imposed by withholding food.

Animals↗

Reversal of fasting-induced suppression of luteinizing hormone (LH) secretion in male rhesus monkeys by intragastric nutrient infusion: evidence for rapid stimulation of LH by nutritional signals.

Short periods of fasting (1-2 days) significantly suppress the frequency of pulsatile LH secretion in adult male rhesus monkeys. Resumption of food intake (i.e. refeeding) after fasting rapidly restores pulsatile LH secretion. We hypothesized that the resumption of LH secretion after refeeding results from the metabolic consequences of food intake rather than from relief of the psychological stress associated with fasting. To differentiate between these two possible types of signals, we attempted to provide fasting monkeys with the nutritional signals of a refeed meal without relieving the psychological stress associated with fasting. To do this, we provided monkeys with a refeed meal via indwelling gastric cannulae while continuing to deny them access to monkey chow. Nine adult male rhesus monkeys with indwelling gastric and venous catheters were fasted for 1 day, and on the following day they received a liquid nutrient infusion (equal in caloric content and macronutrient composition to a normal meal) at the normal feeding time (1100 h) via the gastric cannulae. Blood samples were collected from 0600-2400 h at 20-min intervals. Nutrient infusions caused a restoration of pulsatile LH secretion that was not different from the restoration caused by refeeding a normal meal of Purina monkey chow. In contrast, LH secretion remained suppressed on a second day of fasting. Additionally, monkeys receiving nutrient infusions displayed behavioral agitation similar to fasting monkeys, while monkeys refed monkey chow showed very little agitation. These findings support the hypothesis that nutritional/metabolic signals, rather than the relief of psychological stress, lead to the resumption of pulsatile LH secretion after refeeding.

Animal Nutritional Physiological Phenomena↗

Lack of a role of the hypothalamic-pituitary-adrenal axis in the fasting-induced suppression of luteinizing hormone secretion in adult male rhesus monkeys (Macaca mulatta).

One day of fasting suppresses pulsatile LH secretion in adult male rhesus monkeys. In the present study, we determined whether the hypothalamic-pituitary-adrenal (HPA) axis is activated by 1 day of fasting, and if there is any evidence that an increase in the activity of the HPA axis causes the fasting-induced suppression of LH secretion. In the first experiment, blood samples were collected at 15-min intervals from nine monkeys for 24 h (0800-0800 h) on a day of normal feeding (animals fed a single daily meal at 1100 h) and again on a day of fasting (animals not fed their daily meal) to assess changes in LH and cortisol secretion caused by fasting. LH secretion on the day of fasting (4.44 +/- 0.85 LH pulses/24 h) was significantly suppressed compared to that on a day of normal feeding (7.67 +/- 0.74 LH pulses/24 h; P < or = 0.01), and there was a slight, but significant, rise in plasma cortisol levels from 17.86 +/- 2.29 to 25.14 +/- 2.74 micrograms/dl (measured at 1400 h) that was evident soon after the meal was missed on the day of fasting. However, within individual animals, there was no correlation between the rise in plasma cortisol levels and the decrease in LH secretion observed on a day of fasting (r = 0.37). A second experiment was performed to determine whether the small rise in plasma cortisol levels that occurred on a day of fasting was capable of suppressing LH secretion. Hydrocortisone acetate (HCA) was administered to six normally fed monkeys, creating a rise in plasma cortisol levels somewhat greater than the levels occurring during fasting (HCA treatment, 44.51 +/- 1.48 micrograms/dl; fasting, 18.42 +/- 1.62 micrograms/dl; measured between 1100-2400 h). However, HCA treatment had no effect on LH secretion, suggesting that the rise in cortisol that occurs during fasting does not cause LH suppression. To determine whether increased secretion of the neuropeptides that provide the central drive to the adrenal axis causes the suppression of LH secretion during fasting, six animals were treated with dexamethasone (0.25 mg/kg, im) on a day of fasting to inhibit the activity of the glucocorticoid-sensitive CRH neurons of the adrenal axis via increased glucocorticoid negative feedback. Dexamethasone treatment caused a marked suppression of circulating cortisol levels (to approximately 1.0 micrograms/dl), but it did not prevent the fasting-induced suppression of pulsatile LH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗

Current status of surgical palliation of periampullary carcinoma.

In recent years, the use of nonoperative palliation for unresectable periampullary carcinoma has increased markedly, in part, because of the high morbidity and mortality rates after surgical palliation. The current analysis was undertaken to determine whether or not decreases in morbidity and mortality rates, recently observed after resection of periampullary carcinoma, are now being seen in the surgical palliation of unresectable periampullary carcinoma. During a 54 month period, 118 consecutive patients underwent surgical exploration with the finding of unresectable periampullary adenocarcinoma. Jaundice was the most common complaint at admission, being present in 73 percent of the patients. Abdominal or back pain, or both, was present in 71 percent of the patients and weight loss was observed in 61 percent of the patients. The most commonly performed procedure was combined biliary bypass and gastrojejunostomy, being performed upon 75 percent of the patients. A gastrojejunostomy was performed upon 107 of 118 patients (91 percent). The hospital mortality rate was 2.5 percent. Postoperative complications occurred in 37 percent of the patients but were seldom life-threatening. Wound infection was the most frequent postoperative complication (10 percent), followed by cholangitis (8 percent) and delayed gastric emptying (8 percent). During the late follow-up period, only 4 percent of the patients had gastric outlet obstruction, and only 2 percent had recurrent jaundice. The mean survival time postoperatively was 7.7 months. These results demonstrate that patients with unresectable periampullary carcinoma can undergo surgical palliation with minimal perioperative mortality, acceptable morbidity and good long term palliation. We conclude that surgical palliation is the treatment of choice for carefully selected patients with unresectable periampullary carcinoma.

Adenocarcinoma↗

Oxytocin and vasopressin secretion in monkeys administered apomorphine and a D2 receptor agonist.

Nauseogenic agents, such as apomorphine, were previously reported to promote peripheral release of oxytocin (OT), but not vasopressin (AVP) in rats, and AVP, but not OT in humans (7-13). In the present study, we compared the peripheral secretory responses of OT and AVP in adult male and female rhesus and male cynomolgus monkeys administered graded doses of apomorphine and the respective dopamine D1 and D2 receptor agonists, CY 208-243 and LY 163502. Apomorphine (50-400 micrograms/kg) and LY 163502 (10-100 micrograms/kg) elicited dose-dependent stimulation of OT and AVP, whereas CY 208-243 did not significantly increase secretion of either hormone. The magnitude of the OT and AVP secretory response varied among the animals. Peripheral OT and AVP responses were robust, but the magnitude of the secretory responses was greater for AVP than OT. None of the animals displayed emetic behavior during the studies. These studies indicate that dopaminergic stimulation, particularly of D2 receptors, can regulate both AVP and OT secretion in monkeys.

Animals↗