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PubMed1989

Barium ions enter chromaffin cells via voltage-dependent calcium channels and induce secretion by a mechanism independent of calcium.

Barium ions enter chromaffin cells via voltage-sensitive calcium channels, although the intracellular site of barium action is distinct from that of calcium. The entry of barium primarily through voltage-sensitive channels was indicated by experiments showing inhibition of 133Ba2+ uptake by blockers of voltage-dependent calcium channels. In addition, 133Ba2+ uptake was stimulated by 50 mM KCl but not by nicotine. Furthermore, 133Ba2+ uptake was inhibited by hyperosmolarity, which specifically blocks the voltage-sensitive calcium channel but not the receptor-associated calcium channel. These conclusions from studies on barium uptake were also borne out by experiments measuring catecholamine secretion. Thus, blockers of voltage-dependent calcium channels which inhibited barium uptake also inhibited barium-induced catecholamine secretion. In other experiments, simultaneous stimulation with nicotine and barium in the presence of calcium evoked coincident and additive catecholamine secretion. By contrast, when 50 mM KCl was substituted for nicotine in the same experimental design, barium ions inhibited potassium-induced catecholamine secretion at low calcium concentrations. Only at high calcium concentrations were barium-induced and potassium-induced secretion additive. These data also indicate that barium and calcium compete at the voltage-sensitive pathway. Furthermore, these additivity data suggest that once inside the cell, barium and calcium have two distinct mechanisms of action. As predicted by this hypothesis, in digitonin-permeabilized chromaffin cells either calcium or barium stimulated catecholamine release, and in the presence of both cations catecholamine secretion was equivalent to the sum of secretion with either cation alone. Additional support of this concept comes from experiments showing that while calcium-mediated catecholamine secretion is sensitive to trifluoperazine and imipramine, barium-mediated secretion is not. Taken together, all these data indicate that there are two distinct intracellular sites of action for barium and calcium. In contrast to catecholamine secretion, non-exocytotic ascorbic acid secretion was induced by nicotine and potassium in the presence of calcium, but not by barium alone. These data provide additional evidence that barium acts by a different mechanism than calcium, in still another secretory system in chromaffin cells.

Animals↗
PubMed1994

NTP Toxicology and Carcinogenesis Studies of Barium Chloride Dihydrate (CAS No. 10326-27-9) in F344/N Rats and B6C3F1 Mice (Drinking Water Studies).

Barium chloride dihydrate, a white crystalline granule or powder, is used in pigments, aluminum refining, leather tanning and coloring, the manufacture of magnesium metal, ceramics, glass, and paper products, as a pesticide, and in medicine as a cardiac stimulant. Toxicology and carcinogenicity studies were conducted by administering barium chloride dihydrate (99% pure) in drinking water to F344/N rats and B6C3F1 mice for 15 days, 13 weeks, and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse lymphoma cells. 15-DAY STUDY IN RATS: Groups of five males and five females received barium chloride dihydrate in the drinking water at concentrations of 0, 125, 250, 500, 1,000, or 2,000 ppm for 15 days, corresponding to average daily doses of 10, 15, 35, 60, or 110 mg barium/kg body weight to males and females. No chemical-related deaths, differences in final mean body weights, or clinical findings of toxicity were observed. Water consumption by male and female rats exposed to 2,000 ppm was slightly less (S16%) than controls during week 2. There were no significant differences in absolute or relative organ weights between exposed and control rats. No biologically significant differences in hematology, clinical chemistry, or neurobehavioral parameters occurred in rats. 15-DAY STUDY IN MICE: Groups of five males and five females received barium chloride dihydrate in the drinking water at concentrations of 0, 40, 80,173, 346, or 692 ppm for 15 days, corresponding to average daily doses of 5,10, 20, 40, or 70 mg barium/kg body weight to males and 5, 10, 15, 40, or 85 mg barium/kg body weight to females. No chemical-related deaths, differences in mean body weights or in water consumption, or clinical findings of toxicity were observed in mice. The relative liver weight of males receiving 692 ppm was significantly greater than that of the controls. The absolute and relative liver weights of females that received 692 ppm were significantly greater than those of the controls. No histopathologic evidence of toxicity was observed in mice. 13-WEEK STUDY IN RATS: Groups of 10 males and 10 females received barium chloride dihydrate in the drinking water at concentrations of 0, 125, 500, 1,000, 2,000, or 4,000 ppm for 13 weeks, corresponding to average daily doses of 10, 30, 65, 110, or 200 mg barium/kg body weight to males and 10, 35, 65, 115, or 180 mg barium/kg body weight to females. Three males and one female in the 4,000 ppm groups died during the last week of the study. The final mean body weights of male and female rats receiving 4,000 ppm were significantly lower (13% and 8%) than those of the controls. Water consumption by male and female rats in the 4,000 ppm groups was approximately 30% lower than that by the controls. No clearly chemical-related clinical findings of toxicity or neurobehavioral or cardiovascular effects were noted. Serum phosphorus levels in 2,000 and 4,000 ppm male and female rats were significantly higher than those in controls, but there were no biologically significant differences in hematology parameters or in serum sodium, potassium, or calcium levels. Renal tubule dilatation in the outer stripe of the outer medulla and cortex occurred in male and female rats receiving 4,000 ppm. 13-WEEK STUDY IN MICE: Groups of 10 males and 10 females received barium chloride dihydrate in the drinking water at concentrations of 0, 125, 500, 1,000, 2,000, or 4,000 ppm for 13 weeks, corresponding to average daily doses of 15, 55, 100, 205, or 450 mg barium/kg body weight to males and 15, 60, 110, 200, or 495 mg barium/kg body weight to females. Six males and seven females that received 4,000 ppm and one male that received 125 ppm died during the study. Final mean body weights of male and female mice receiving 4,000 ppm were significantly lower (>30%) than those of controls. Water consumption by male mice in the 4,000 ppm group was 18% lower than that by the controls; water consumption by other exposed groups of male and female mice was similar to thatd groups of male and female mice was similar to that by the controls. Clinical findings of toxicity were limited to debilitation in the surviving male and female mice receiving 4,000 ppm. The absolute and/or relative liver weights of mice receiving 1,000, 2,000, and 4,000 ppm were significantly lower than those of the controls. Multifocal to diffuse nephropathy characterized by tubule dilatation, regeneration, and atrophy occurred in 4,000 ppm male and female mice. 2-YEAR STUDY IN RATS: Groups of 60 males and 60 females received barium chloride dihydrate in the drinking water at concentrations of 0, 500, 1,250, or 2,500 ppm for 104 (males) or 105 weeks (females), corresponding to average daily doses of 15, 30, or 60 mg barium/kg body weight for males and 15, 45, or 75 mg barium/kg body weight for females. The high dose of 2,500 ppm was selected based on decreased final mean body weights, mortality, decreased water consumption, and chemical-related kidney lesions observed in the 4,000 ppm groups in the 13-week study. Survival, Body Weights, Water Consumption, and Clinical Findings: Two-year survival of exposed male and female rats was similar to that of the controls. The final mean body weights of male and female rats that received 2,500 ppm were (5% and 11%) lower than those of controls. Beginning as early as week 5, water consumption by male and female rats receiving 2,500 ppm was substantially lower than that by controls (male: 11% to 30%; female: 19% to 33%). There were no chemical-related clinical findings. Hematology and Clinical Chemistry: There were no chemical-related differences in hematology or clinical chemistry parameters in male or female rats. Special Studies: At the 15-month interim evaluation, the plasma barium concentrations (mg/ml) were significantly increased in males receiving 1,250 and 2,500 ppm and in all exposed groups of females (male: 0 ppm, 0.98; 500 ppm, 1.00; 1,250 ppm, 1.23; 2,500 ppm, 1.68; female: 0 ppm, 0.74; 500 ppm, 0.99; 1,250 ppm, 0.97; 2,500 ppm, 1.43). Barium levels in bone in rats from the 2,500 ppm groups were about 400 times greater than those in the controls. Pathology Findings: At the end of 2 years, there were no increased incidences of neoplasms or nonneoplastic lesions that could be attributed to barium chloride dihydrate. However, there were dose-related decreased incidences of adrenal medulla pheochromocytomas and mononuclear cell leukemia in male rats. 2-YEAR STUDY IN MICE: Groups of 60 males and 60 females received barium chloride dihydrate in the drinking water at concentrations of 0, 500, 1,250, or 2,500 ppm for 103 (males) or 104 weeks (females), corresponding to average daily doses of 30, 75, or 160 mg barium/kg body weight for males and 40, 90, or 200 mg barium/kg body weight for females. The high dose of 2,500 ppm was selected based on decreased final mean body weights, mortality, decreased water consumption, and chemical-related kidney lesions observed in the 4,000 ppm groups in the 13-week study. Survival, Body Weights, Water Consumption, and Clinical Findings: Two-year survival of male and female mice receiving 2,500 ppm was significantly lower than that of the controls due to renal toxicity. Final mean body weights of 2,500 ppm males and females were 9% and 12% lower than those of controls. Water consumption by male and female mice receiving barium chloride was similar to that by the controls. There were no chemical-related clinical findings. Hematology and Clinical Chemistry: There were no differences in hematology or clinical chemistry parameters measured at the 15-month interim evaluation. Special Studies: At the 15-month interim evaluation, plasma barium concentrations (mg/mL) were significantly increased in all exposed groups of mice (male: 0 ppm, 0.62; 500 ppm, 0.77; 1,250 ppm, 0.89; 2,500 ppm, 1.49; female: 0 ppm, 0.52; 500 ppm, 0.74; 1,250 ppm, 1.01; 2,500 ppm, 1.35). Pathology Findings: At the end of the 2-year study, there were increased incidences of nephropathy in male and female mice (male: 1/50, 0/50, 2/48, 19/50; female: 0/50, 2/53, 1/50, 37/54). There were no chemical-related increased incidences of neoplasms in male or female mice. The incidence of hepatocellular adenoma was significantly decreased in male mice receiving 2,500 ppm. GENETIC TOXICOLOGY: Barium chloride dihydrate was not mutagenic in Salmonella typhimurium strains TA97, TA98, TA100, TA1535, or TA1537, with or without exogenous metabolic activation (S9). It was mutagenic in L5178Y mouse lymphoma cells in the presence of S9, but it did not induce sister chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells, with or without S9. CONCLUSIONS: Under the conditions of these 2-year drinking water studies, there was no evidence of carcinogenic activity of barium chloride dihydrate in male or female F344/N rats that received 500, 1,250, or 2,500 ppm. There was no evidence of carcinogenic activity of barium chloride dihydrate in male or female B6C3F1 mice that received 500, 1,250, or 2,500 ppm. There were chemical-related increased incidences of nephropathy in male and female mice.

Journal Article↗
PubMed1989

Perforation of the rectum and sigmoid colon during barium-enema examination. Management and prevention.

Perforation of the rectum or sigmoid colon complicated 5 of 2200 barium-enema examinations performed during a 4-year period. Three patients with rectal perforations manifested by air extravasation were successfully treated with intravenous antibiotics and complete bowel rest. Two patients with barium extravasation were treated with immediate operation and colostomy. All five patients recovered. Perforation was found to be associated with a rectal stricture due to ulcerative colitis, a rectal cancer, an incarcerated inguinal hernia, fulminant ulcerative colitis, and a normal colon in an elderly patient. To determine the pressure in the rectum that could potentially be generated during a barium-enema examination, the pressures created by a standard barium delivery set were measured, using 1-meter columns of water, 25 percent diatrizoate sodium (Hypaque), 20 percent barium, and 80 percent barium. The columns generated pressures of 70, 85, 95, and 120 mm Hg respectively. Squeezing the delivery bag increased the pressure 21 to 79 percent or a maximum of 55 mm Hg. Colorectal perforation during barium-enema examination that was not accompanied by barium extravasation could be successfully treated nonoperatively. The associated pathology and our studies of pressures generated during a barium-enema examination allow us to suggest that the incidence of colorectal perforation during barium-enema radiography can be reduced by 1) performing proctoscopy prior to barium enema, 2) avoiding the use of the rectal balloon in patients with known rectal lesions, 3) avoiding barium studies in patients with active colitis, 4) avoiding generation of pressure greater than that created by a column of barium suspension of one meter, and 5) using a lower concentration of barium when possible.

Aged↗
PubMed1987

Suppression of delayed cutaneous hypersensitivity and inflammatory cell delivery by sterile barium peritonitis.

We have previously shown that experimental peritonitis secondary to fecal bacteria plus barium sulfate suppresses delayed cutaneous hypersensitivity (DCH) in rats. We examined herein the role of barium sulfate. In a series of experiments presensitized rats were simultaneously skin tested with intradermal keyhole limpet hemocyanin and given an intraperitoneal injection of either (1) a mixture of four fecal bacteria in their nutrient broths, (2) bacteria and broths plus barium sulfate, (3) sterile broths plus barium, (4) sterile barium alone, (5) nutrient broths, or (6) saline. In rats given sterile barium we measured phagocyte delivery to subcutaneous polyvinyl alcohol sponges. We found that (1) the coadministration of barium sulfate was necessary for rats given bacteria to die (P = 0.03) or develop abdominal abscesses (P less than 0.005), (2) suppression of DCH occurred in 70% of rats receiving sterile barium sulfate vs 0% in saline controls (P = 0.0001), (3) early suppression of DCH was associated with subsequent death and abscess formation in rats given bacteria plus barium (P = 0.00002) and with intraabdominal barium collections in rats given barium alone (P less than 0.02), (4) barium sulfate administration caused suppression of phagocyte delivery to subcutaneous sponges: 23.2 X 10(6) cells/site vs 43.1 X 10(6) cells/site in saline controls (P less than 0.005). We conclude that barium sulfate itself has profound systemic effects in the rat model of intraabdominal sepsis. Early suppression of DCH is associated with a poor outcome in septic rats.

Animals↗
PubMed2004

Prospective comparison of air-contrast barium enema and colonoscopy in patients with fecal occult blood: a pilot study.

BACKGROUND: The utility of air-contrast barium enema and colonoscopy for evaluation of the colon has been debated. Air-contrast barium enema is less expensive and invasive than colonoscopy, but it also is less sensitive and specific. Further, although air-contrast barium enema may be less painful than colonoscopy, it often is poorly tolerated by patients. Thus, this study compared the sensitivity and the specificity of air-contrast barium enema and colonoscopy for detection of colonic lesions in patients with fecal occult blood. METHODS: Over a 30-month period, patients with fecal occult blood were recruited. Patients underwent standard air-contrast barium enema, followed by colonoscopy 7 to 14 days later. Colonoscopists were blinded to the results of air-contrast barium enema until the colonoscopy was completed, after which the results were disclosed. If the findings were discrepant, colonoscopy was repeated. RESULTS: A total of 100 patients were evaluated. Nine air-contrast barium enemas were reported to be inadequate, and the cecum was not intubated at colonoscopy in two patients. In the remaining patients, 5 cancers were identified (1 each cecum, transverse colon, descending colon, sigmoid colon, and rectum) by both studies. Sixty-six polypoid lesions were identified in 30 patients. Diverticula were identified in 42 patients by air-contrast barium enema and in 18 patients by colonoscopy. Air-contrast barium enema detected 3 of 36 polypoid lesions 5 mm or less in diameter, 5 of 15 adenomas 6 to 9 mm in size, and 4 of 15 adenomas 10 mm or greater in diameter (sensitivity 8%, 33%, and 27%, respectively). After excluding patients with diverticula, air-contrast barium enema detected 3 of 7 adenomas 10 mm or greater in size. Overall, 12 polypoid lesions or filling defects were identified by air-contrast barium enema that could not be verified by colonoscopy. The specificity of air-contrast barium enema for lesions 1.0 cm or greater in size was 100%; for those 6 mm or greater, it was 97%. CONCLUSIONS: Air-contrast barium enema accurately detects colon cancer and diverticula. Its sensitivity for detection of polypoid lesions or adenomas is poor and was confounded by the presence of diverticula.

Adenomatous Polyps↗
PubMed1999

Barium swallows after free jejunal transfer: should they be performed routinely?

Fistula formation after free jejunal transfer for pharyngoesophageal reconstruction is a serious complication with potentially critical consequences. Barium swallow is used postoperatively to check for anastomotic competence before feeding but has been unreliable as a predictor of leak at our institution. The objective of this study was to evaluate the role of routine postoperative barium swallow in 41 consecutive jejunal transfers. Thirty-nine patients who underwent 41 consecutive free jejunal transfers had a routine barium swallow performed between postoperative days 12 and 17. Radiologic findings and clinical outcome were evaluated and correlated. All barium swallows were reviewed by a single experienced radiologist in a blinded fashion. One total and one partial flap failure necessitated a second free jejunal transfer. Pharyngocutaneous fistulae developed after nine free jejunal transfers, of which the barium swallow was normal in four (44 percent) and showed a leak in five (56 percent). In the 32 free jejunal transfers with no clinical leaks, 6 (19 percent) had radiologic leakage of contrast. Thus, barium swallow was normal in 30 patients and showed leakage in 11 patients. Normal barium swallow correlated with uncomplicated clinical course in 26 of 30 cases. In the remaining four cases (13 percent), however, a delayed fistula developed, which was secondary to flap necrosis in one case (negative predictive value 87 percent). On the other hand, radiologic leaks corroborated clinical fistula in 5 of 11 cases (45 percent), whereas no fistula developed in 6 cases (positive predictive value 46 percent). Of the five patients with clinical fistulae, four had early leaks (within 1 week), and the barium swallow did not provide additional information. The fifth patient developed a delayed leak 2 weeks after the barium swallow. Review of these barium swallows at the time of this study reversed the initial report of leakage in three patients, improving the predictive value to 63 percent. These patients had an uncomplicated clinical course. The positive predictive value of clinical assessment alone was 63 percent. We conclude that barium studies following free jejunal transfers can be difficult to interpret, but an experienced radiologist can improve their accuracy. A normal barium swallow, however, does not ensure an uneventful clinical course. Similarly, radiologic leaks do not imply a clinical complication of fistula. Clinical judgment should therefore be exercised in initiating oral intake after free jejunal transfer. Barium swallow should be used only as an adjunct to aid in patient management.

Adolescent↗
PubMed2002

Colorectal cancer screening with double-contrast barium enema: a national survey of diagnostic radiologists.

OBJECTIVE: This article describes diagnostic radiologists' colorectal cancer screening activities and beliefs about screening effectiveness and future capacity for screening with double-contrast barium enema, and compares radiologists' opinions about colorectal cancer screening with those of primary care physicians. MATERIALS AND METHODS: We surveyed a nationally representative sample of diagnostic radiologists. Of 381 eligible radiologists, 312 (82%) responded. Descriptive statistics and chi-square tests were used to assess radiologists' opinions about double-contrast barium enema volume and capacity and to compare radiologists' beliefs about colorectal cancer screening with those of primary care physicians. Logistic regression was used to identify characteristics of radiologists who receive referrals for or perform a higher volume of screening double-contrast barium enema and of those who expect the volume of double-contrast barium enemas to increase. RESULTS: Seventy-five percent of radiologists said that double-contrast barium enema is a "very effective" colorectal cancer screening procedure compared with 33% of primary care physicians. Although 86% of radiologists reported performing one or more screening double-contrast barium enema procedures during a typical month, only 27% indicated that they did so 11 or more times. Fifteen percent of radiologists said that their double-contrast barium enema volume had increased over the past 3 years, and 50% expect an increase over the next 3 years. Only 8% said that the capacity of facilities and personnel to meet the demand for double-contrast barium enemas in their geographic area of practice is inadequate. Geographic region and belief in double-contrast barium enema efficacy were predictors of double-contrast barium enema volume and referrals. CONCLUSION: Most diagnostic radiologists perform colorectal cancer screening with double-contrast barium enema, but procedure volumes are modest. Because primary care physicians view double-contrast barium enema less positively than do radiologists, radiologists' expectations for an increased volume of double-contrast barium enemas over the next few years may not be realized.

Adult↗
PubMed1985

Cardiovascular dysfunction and hypersensitivity to sodium pentobarbital induced by chronic barium chloride ingestion.

Barium-supplemented Long-Evans hooded rats were characterized by a persistent hypertension that was evident after 1 month of barium (100 micrograms/ml mineral fortified water) treatment. Analysis of in vivo myocardial excitability, contractility, and metabolic characteristics at 16 months revealed other significant barium-induced disturbances within the cardiovascular system. The most distinctive aspect of the barium effect was a demonstrated hypersensitivity of the cardiovascular system to sodium pentobarbital. Under barbiturate anesthesia, virtually all of the myocardial contractile indices were depressed significantly in barium-exposed rats relative to the corresponding control-fed rats. The lack of a similar response to ketamine and xylazine anesthesia revealed that the cardiovascular actions of sodium pentobarbital in barium-treated rats were linked specifically to this anesthetic, and were not representative of a generalized anesthetic response. Other myocardial pathophysiologic and metabolic changes induced by barium were manifest, irrespective of the anesthetic employed. The contractile element shortening velocity of the cardiac muscle fibers was significantly slower in both groups of barium-treated rats relative to the control groups, irrespective of the anesthetic regimen. Similarly, significant disturbances in myocardial energy metabolism were detected in the barium-exposed rats which were consistent with the reduced contractile element shortening velocity. In addition, the excitability of the cardiac conduction system was depressed preferentially in the atrioventricular nodal region of hearts from barium-exposed rats. Overall, the altered cardiac contractility and excitability characteristics, the myocardial metabolic disturbances, and the hypersensitivity of the cardiovascular system to sodium pentobarbital suggest the existence of a heretofore undescribed cardiomyopathic disorder induced by chronic barium exposure. These experimental findings represent the first indication that life-long barium ingestion may have significant adverse effects on the mammalian cardiovascular system.

Anesthetics↗
PubMed2005

Limitations of barium enema performed as an adjunct to incomplete colonoscopy.

PURPOSE: Colonoscopy is believed to be inadequate in 4 to 24 percent of procedures. Barium enema often is utilized to complete the examination. In radiology literature, a successful barium enema in this setting requires only that the cecum has been reached. In this study, completion barium enema was assessed for both completeness and quality of proximal visualization. METHODS: The charts of 16,216 patients undergoing colonoscopy at Saint Vincent Health Center from July 1995 to July 2003 were reviewed to identify patients who underwent barium enema within six months of an incomplete colonoscopy. Incomplete colonoscopies were audited for history of previous abdominal/pelvic surgery, level of colon attained, and apparent reasons for failure. Corresponding barium enema reports were evaluated in a similar fashion. RESULTS: In 485 patients (2.9 percent), colonoscopy was incomplete. One hundred eighteen patients underwent barium enema after incomplete colonoscopy. In these patients, sharp angulation (42 percent) or redundancy/looping (31 percent) most often limited endoscopy. Among the barium enema studies, 91 (77 percent) were technically adequate. Twenty-seven studies were suboptimal (poor preparation/intolerance = 7, redundancy = 6, poor filling = 6, stricture/narrowing = 6, severe diverticulosis = 2). Two patients demonstrated additional polyps. There was no correlation between reasons for endoscopic failure and inadequacy of barium enema. Completeness of barium enema was not affected by previous pelvic surgery. Immediate barium enema was no less complete than a delayed study. CONCLUSIONS: The reliability of barium enema after incomplete colonoscopy is less than previously reported.

Adult↗