PubMed HealthSearch

Biomedical subjects

R Summers

Publications and source records attributed to R Summers.

At least 19 recordsLinked to original sources

Impact of unified procedures as implemented in the Canadian Quality Assurance Program for T lymphocyte subset enumeration. Participating Flow Cytometry Laboratories of the Canadian Clinical Trials Network for HIV/AIDS Therapies.

The objective of the Canadian Quality Assurance Program (CQAP) is to provide the most reproducible and accurate T-cell subset enumeration for individuals living with HIV who are enrolled in the Canadian Clinical Trial Network for Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS) Therapies (abbreviated as CTN). The Canadian National Laboratory for Analytical Cytology, within the Laboratory Centre for Disease Control, is part of the Health Protection Branch of Health Canada. For the past eight years, the Laboratory for Analytical Cytology has been responsible for delivering a bilingual quality assurance program for CD4 T-cell enumeration. This federal program, which integrates biotechnology transfer with quality assessment, was achieved through the organization of workshops focused on technology transfer and essential skill-building techniques. Two training sessions were conducted for the CTN flow cytometer operators. The first introduced the concept of window of analysis, to demonstrate the practical benefits of unified quantitative fluorescent measurement. As a follow-up to the first workshop, participants performed a series of quantitative assays that monitored the expression of CD69, an early activation marker. This quantitative fluorescence protocol was performed with acceptable inter-laboratory variation using modified commercial kits. The second workshop focused on a absolute count method based on a single platform. Four preserved whole-blood preparations were tested with this approach. The combined effort reduced inter-laboratory variation. The direct impact was monitored as related to the frequency of participation. Over the years, the standard deviation of average accumulated variation decreased dramatically with increased frequency of participation, from 10% to <4%.

Canada

Differential roles for disulfide bonds in the structural integrity and biological activity of kappa-Bungarotoxin, a neuronal nicotinic acetylcholine receptor antagonist.

kappa-Bungarotoxin, a kappa-neurotoxin derived from the venom of the banded Krait, Bungarus multicinctus, is a homodimeric protein composed of subunits of 66 amino acid residues containing five disulfide bonds. kappa-Bungarotoxin is a potent, selective, and slowly reversible antagonist of alpha3 beta2 neuronal nicotinic acetylcholine receptors. kappa-Bungarotoxin is structurally related to the alpha-neurotoxins, such as alpha-bungarotoxin derived from the same snake, which are monomeric in solution and which effectively antagonize muscle type receptors (alpha1 beta1 gamma delta) and the homopentameric neuronal type receptors (alpha7, alpha8, and alpha9). Like the kappa-neurotoxins, the long alpha-neurotoxins contain the same five conserved disulfide bonds, while the short alpha-neurotoxins only contain four of the five. Systematic removal of single disulfide bonds in kappa-bungarotoxin by site-specific mutagenesis reveals a differential role for each of the disulfide bonds. Removal of either of the two disulfides connecting elements of the carboxy terminal loop of this toxin (Cys 46-Cys 58 and Cys 59-Cys 64) interferes with the ability of the toxin to fold. In contrast, removal of each of the other three disulfides does not interfere with the general folding of the toxin and yields molecules with biological activity. In fact, when either C3-C21 or C14-C42 are removed individually, no loss in biological activity is seen. However, removing both produces a polypeptide chain which fails to fold properly. Removal of the C27-C31 disulfide only reduces the activity of the toxin 46.6-fold. This disulfide may play a role in specific interaction of the toxin with specific neuronal receptors.

Alanine

Adenoma characteristics at first colonoscopy as predictors of adenoma recurrence and characteristics at follow-up. The Polyp Prevention Study Group.

BACKGROUND & AIMS: All patients with colorectal adenomas may not require identical follow-up. We aimed to determine if adenoma characteristics at initial colonoscopy could predict adenoma recurrence or characteristics at follow-up. METHODS: The number of adenomas and the size, type, and degree of atypia in 479 patients in a polyp prevention trial were evaluated as predictors of the same characteristics at follow-up using odds ratios (ORs) with 95% confidence intervals (CIs). Multiple logistic regression analysis was performed to determine if several baseline characteristics were simultaneously associated with outcome. RESULTS: Although several characteristics were significant predictors of recurrence univariately, by multivariate analysis, multiple adenomas at follow-up were more likely when patients had > or = 3 baseline adenomas (OR, 2.25; 95% CI, 1.20-4.21) or at least 1 tubulovillous adenoma (OR, 2.12; 95% CI, 1.12-4.02). No specific characteristic was associated with recurrence of high-risk polyps (> or = 1 cm, villous, severe atypia). Seventy percent of patients with 1 or 2 baseline adenomas had no recurrence, and only 3.3% had any adenomas of clinical concern. CONCLUSIONS: Number and type of baseline adenomas predict recurrent adenomas, but the recurrence is rarely of clinical concern. Patients with 1 or 2 tubular adenomas constitute a low-risk group for whom follow-up might be extended beyond 3 years.

Adenoma

Does retrograde warm blood cardioplegia provide equal protection to both ventricles? A magnetic resonance spectroscopy study in pigs.

BACKGROUND: The degree of protection provided to the right ventricle during retrograde continuous normothermic blood cardioplegia (RCNBC) remains controversial. The purpose of this study was to determine whether RCNBC is able to provide "adequate" nutritive flow to both ventricles to prevent ischemic metabolism in normal swine hearts. Localized 31P magnetic resonance spectroscopy (MRS) was used to monitor the changes in energy metabolism and intracellular pH (pHi) in each ventricle separately. METHODS AND RESULTS: Isolated normal swine hearts received 20 minutes of antegrade continuous normothermic blood cardioplegia (ACNBC) for collection of control (baseline) data, followed by 20 minutes of RCNBC. This protocol was repeated four times in five hearts and twice in two hearts. Perfusion pressure was maintained between 70 to 85 and 38 to 43 mm Hg during ACNBC and RCNBC, respectively. pHi, creatine phosphate (PCr), inorganic phosphate (Pi), and ATP were measured continuously in each ventricle during ACNBC and RCNBC, using localized 31P MRS with two surface coils. RCNBC resulted in a significant increase in Pi (LV 222% and RV 244% of the baseline levels, respectively) and a decrease in PCr (left ventricle [LV] to 68% and right ventricle [RV] to 31% of the baseline levels, respectively) in both ventricles relative to ACNBC. The PCr level was significantly lower in the RV than in the LV (31% versus 68%, P<.001) during RCNBC. In one series of experiments (n=5) where ACNBC and RCNBC were alternated every 20 minutes (ACNBC, RCNBC, ACNBC, RCNBC, ACNBC) for a total of 100 minutes, Pi and PCr recovered completely. A continuous and significant decrease in ATP was observed in the RV, and no recovery of ATP was found when switching from RCNBC to ACNBC. No significant decrease in ATP was observed in the LV. pHi remained unchanged in both ventricles during alternate ACNBC and RCNBC. CONCLUSIONS: Energy metabolism in the RV is less well preserved than in the LV during RCNBC. A combination of ACNBC and RCNBC seems to provide good cardiac protection as measured by the recovery of cardiac energetics and pHi.

Adenosine Triphosphate

Nucleotide sequence of the ermE distal flank of the erythromycin biosynthesis cluster in Saccharopolyspora erythraea.

A 7023 nucleotide BamHI fragment immediately upstream of the eryK gene of the erythromycin (Er) biosynthesis cluster in Saccharopolyspora erythraea was sequenced. Computer-assisted analysis of this sequence reveals the existence of seven ORFs that display the codon preferences typical of actinomycete genes. Six of these show homology to known genes: an esterase, a transposase, a peptidyl-prolyl cis-trans isomerase, a subtilisin inhibitor-like protein, and two genes involved in bacterial cell wall biosynthesis. All the ORFs are transcribed toward the Er biosynthetic gene cluster (in the same direction as eryK). From the predicted functions of the putative ORF products none of these genes appear to be involved in the biosynthesis of Er. The eryK gene thus most likely defines one end of the Er biosynthetic gene cluster.

Amino Acid Sequence

The effect of circulatory arrest and retrograde cerebral perfusion on microtubule-associated protein 2: an immunohistochemical study in pig hippocampus.

Microtubule-associated protein 2 (MAP2) immunohistochemical labeling in the hippocampus was studied to assess the protective effect of brain perfusion during surgery requiring hypothermic circulatory arrest in 24 pigs exposed to anesthesia alone (control), 120 min of complete circulatory arrest at 15 degrees C, min of retrograde cerebral perfusion at 15 degrees C, or 120 min of anterograde cerebral perfusion at 15 degrees C. Pigs were reperfused for 60 min and sacrificed. In the control anterograde perfusion groups, the intensity of MAP2 labeling was similar in all regions of the hippocampus. Circulatory arrest and retrograde perfusion resulted in significant reduction of MAP2 labeling (28% and 38% respectively of control, P < 0.001) of neurons in the CA1 region. MAP2 labeling may be useful for assessing early damage in the hippocampus in this model.

Animals

Beyond hyperkalemia: beta-blocker-induced cardiac arrest for normothermic cardiac operations.

BACKGROUND: Four experimental protocols were carried out to assess the ability of esmolol to induce and maintain reversible cardiac arrest under continuous normothermic (37 degrees C) perfusion. METHODS AND RESULTS: In the first protocol, 8 perfused rat hearts were subjected to 20, 60, 90, and 120 minutes of esmolol arrest, after which positive and negative first derivative of pressure, heart rate, left ventricular developed pressure, and left ventricular end-diastolic pressure were evaluated. Arrest was achieved 45 to 60 seconds after beginning the infusion of esmolol. Mechanical arrest was achieved before electrical arrest. In the second protocol, dose-response curves were obtained using isolated (Langendorff) rat and rabbit (n = 6) hearts. The concentrations of esmolol varied from 0.084 to 6.7 mmol/L and from 0.12 to 1.45 mmol/L in the rat and rabbit heart experiments, respectively. In the third protocol, the effects of 20 minutes of normothermic (37 degrees C) ischemia on the function of isolated rat hearts perfused with esmolol-containing Krebs solution were compared with those using high-potassium (25 mmol/L) Krebs solution. Group A subjects (n = 9) received the ischemic injury after being perfused (and arrested) for 20 minutes with either esmolol or potassium (KCl, 25 mmol/L). Group B subjects (n = 10) received the same ischemic insult before being perfused with either esmolol or potassium. Esmolol-treated hearts showed better recovery than those receiving potassium, in terms of +/- dP/dt (p < 0.01), left ventricular systolic pressure (p < 0.01), and left ventricular developed pressure (p < 0.009). Finally, the fourth protocol was done to evaluate the effects of esmolol in a clinically relevant experimental model. Pigs were divided into esmolol (n = 6) and potassium (n = 5) groups and subjected to normothermic cardiopulmonary bypass and a 1-hour period of cardiac arrest. Twenty minutes after stopping infusion of the cardioplegic agents, all animals were weaned off bypass. There were no statistically significant differences between the groups. CONCLUSIONS: Esmolol hydrochloride can be used as effectively as potassium for inducing and maintaining predictable and reversible cardiac arrest during normothermic cardiac operations.

Adrenergic beta-Antagonists

Retrograde cerebral perfusion provides limited distribution of blood to the brain: a study in pigs.

OBJECTIVE: The objective of this study was to investigate flow distribution during retrograde and antegrade cerebral perfusion with India ink as a marker. METHODS: Ten pigs received cerebral perfusion with a solution containing 50% filtered India ink for 5 minutes either antegradely through both internal carotid arteries at a flow of 180 to 200 ml/min (n = 5) or retrogradely via the superior vena cava at a flow of 300 to 500 ml/min (n = 5). The brains were then fixed for quantitative measurement of the density of ink-filled capillaries (reported as a percentage of the total selected area). The assessment was done with the use of an in-house software program. RESULTS: In the antegrade cerebral perfusion group, the intracranial arterial and venous systems were completely filled with ink. The gray matter was colored uniformly black, and light coloring was observed in the white matter. During retrograde cerebral perfusion, the majority of ink was returned to the inferior vena cava, and only a small amount of ink was found in the innominate artery draining from the brain. Massive ink filling was observed in the sagittal sinus and other venous sinuses in all the pigs. Vessels on the surface of the brain and large vessels in the brain were also well filled with ink. However, only 10% of capillaries were filled with ink during retrograde cerebral perfusion relative to the number observed with antegrade cerebral perfusion. CONCLUSIONS: Retrograde cerebral perfusion supplies a limited amount of blood to brain tissue, which flows mainly through superficial and large deep cerebral vessels.

Animals

Feeding mechanism and functional morphology of the jaws of the lemon shark Negaprion brevirostris (Chondrichthyes, Carcharhinidae)

This study tests the hypothesis that preparatory, expansive, compressive and recovery phases of biting behavior known for aquatically feeding anamniotes are conserved among extant elasmobranch fishes. The feeding mechanism of the lemon shark Negaprionbrevirostris is examined by anatomical dissection, electromyography and high-speed video analysis. Three types of feeding events are differentiated during feeding: (1) food ingestion primarily by ram feeding; (2) food manipulation; and (3) hydraulic transport of the food by suction. All feeding events are composed of the expansive, compressive and recovery phases common to aquatically feeding teleost fishes, salamanders and turtles. A preparatory phase is occasionally observed during ingestion bites, and there is no fast opening phase characteristic of some aquatically feeding vertebrates. During the compressive phase, palatoquadrate protrusion accounts for 26% of the gape distance during jaw closure and is concurrent with muscle activity in the dorsal and ventral preorbitalis and the levator palatoquadrati. Hydraulic transport events are shorter in duration than ram ingestion bites. Prey ingestion, manipulation and hydraulic transport events are all found to have a common series of kinematic and motor components. Individual sharks are capable of varying the duration and to a lesser extent the onset of muscle activity and, consequently, can vary their biting behavior. We propose a model for the feeding mechanism in carcharhinid sharks, including upper jaw protrusion. This study represents the first electromyographic and kinematic analysis of the feeding mechanism and behavior of an elasmobranch.

Journal Article

A new technique of coronary artery ligation: experimental myocardial infarction in rats in vivo with reduced mortality.

In vivo models of myocardial infarction following coronary artery ligation in the rat still suffer from high early mortality and a low rate of success of myocardial infarction. This study investigated the possibility of reducing early mortality and increasing the rate of myocardial infarction by modifications of surgical techniques. Eighteen rats were divided into two groups: normal control (3 rats) and ligation (15 rats). The major modifications of surgical techniques used in this study include: (1) no exteriorization of the heart, (2) ligation of the origins of the branches rather than the main trunk of the left coronary artery, (3) removal of air from the chest after closure, (4) supplying oxygen immediately after extubation. Following surgery, the rats recovered uneventfully and 11 rats were alive after 16 weeks. One rat, with a large myocardial infarction, died 2 h after surgery. Early mortality (during surgery and 1 week after surgery) was 6.7% with a success rate of myocardial infarction of 85%. The left ventricle in the ligation group showed significant dilation relative to normal and sham-operated control hearts (317% of control hearts, p < 0.001). However, myocardial mass did not increase. The average infarct size was 33%. These results demonstrate that a reduction in early mortality and an increased success rate of myocardial infarction can be achieved by modifications of surgical techniques.

Analysis of Variance

Neuronal damage after hypothermic circulatory arrest and retrograde cerebral perfusion in the pig.

BACKGROUND: Antegrade and retrograde cerebral perfusion during hypothermic circulatory arrest (HCA) has been reported to provide better brain protection during operation than hypothermic circulatory arrest alone. However, the efficacy of these techniques remains to be fully determined, especially when used for prolonged periods. We used a pig model to evaluate the histopathologic consequences of HCA and the potential benefit of cerebral perfusion during HCA. METHODS: Twenty-two pigs were divided into four groups and exposed to either anesthesia alone, 120 minutes of HCA (15 degrees C), 120 minutes of retrograde cerebral perfusion at 15 degrees C during HCA, or 120 minutes of antegrade cerebral perfusion at 15 degrees C during HCA, and then reperfused for 60 minutes under cardiopulmonary bypass at 37 degrees C. The brains were perfusion fixed at the end of the experiments and examined by light microscopy. RESULTS: There were no morphologic changes in any areas of the brains in the anesthesia group, and very minor changes in some areas of the brains in the antegrade cerebral perfusion. group. Varying severity of neuronal damage was found in the brains of all the pigs in the HCA and retrograde cerebral perfusion groups. The severity of ischemic damage in the brain showed the following descending order: hippocampus (CA4), caudate nucleus, cerebral cortex, putamen, thalamus, Purkinje cells of the cerebellum, pons, and mesencephalic gray matter. In the hippocampus the order of damage was CA4, CA3, polymorphous layer of the dentate gyrus, prosubiculum, CA2, CA1, and granule cell layer of the dentate gyrus. The damage in the retrograde cerebral perfusion group was less severe relative to the HCA group in many areas (no significance except mesencephalic gray matter). CONCLUSIONS: These results demonstrate that the pattern of neuronal damage in pigs subjected to HCA and retrograde cerebral perfusion differs from the traditional pattern in that the caudate nucleus and hippocampal CA4 region are the most vulnerable to ischemia-hypoxia. Our results also suggest that antegrade cerebral perfusion prevented ischemic damage to the brain and retrograde cerebral perfusion provided some protection but moderately severe damage occurred.

Animals

Acid-base chemistry of the blood--a general model.

This paper describes a general model of acid-base chemistry of the blood which can be used to simulate physiological perturbation of acid-base chemistry on addition or removal of any buffer acid or base. In particular, it is shown how this model can be used to estimate the concentrations of buffer acid or base. In particular, it is shown how this model can be used to estimate the concentrations of buffer acids and bases when blood is equilibrated to a new pCO2, when hydrogen ions H+ are added to the blood, or when two pools of blood with different concentrations of buffer acids and bases are mixed. The ability of the model to represent the addition or removal of any acid or base is a significant increase in functionality above the Siggaard-Andersen nomogram which is limited to simulating the effects of equilibrating the blood to a new pCO2. When used to represent the situation where blood is equilibrated at a new pCO2 the model enables calculation of the amount CO2 removed during equilibration, a further increase in functionality above the Siggaard-Andersen nomogram. In two experimental situations, equilibrating blood to a new pCO2 and addition of H+ ions, the model predictions are shown to be consistent with existing experimental data in the form of the Siggaard-Andersen nomogram.

Acid-Base Equilibrium

Cerebral protection during moderate hypothermic circulatory arrest: histopathology and magnetic resonance spectroscopy of brain energetics and intracellular pH in pigs.

OBJECTIVE: We evaluated the effect of antegrade and retrograde brain perfusion during moderate hypothermic circulatory arrest at 28 degrees C. METHODS: Phosphorus 31-magnetic resonance spectroscopy was used to follow brain energy metabolites and intracellular pH in pigs during 2 hours of ischemia and 1 hour of reperfusion. Histopathologic analysis of brain tissue fixed at the end of the experimental protocol was performed. Fourteen pigs were divided into two experimental groups subjected to antegrade (n = 6) or retrograde (n = 8) brain perfusion. Anesthesia (n = 8) and hypothermic cardiopulmonary bypass groups (15 degrees C, n = 8) served as control subjects. In the antegrade and retrograde brain perfusion groups, the initial bypass flow rate was 60 to 100 ml x kg(-1) x min(-1). In the antegrade group, the brain was perfused through the carotid arteries at a flow rate of 180 to 210 ml x min(-1) during circulatory arrest at 28 degrees C. In the retrograde group, the brain was perfused through the superior vena cava at a flow rate of 300 to 500 ml x min(-1) during circulatory arrest at 28 degrees C. RESULTS: The intracellular pH was 7.1 +/- 0.1 and 7.2 +/- 0.1 in the anesthesia and hypothermic bypass groups, respectively. Brain intracellular pH and high-energy metabolites (adenosine triphosphate, phosphocreatine) did not change during the course of the 3.5-hour study. In the antegrade group, adenosine triphosphate and intracellular pH were unchanged throughout the protocol. In the retrograde perfusion group, the intracellular pH level decreased to 6.4 +/- 0.1, and adenosine triphosphate and phosphocreatine levels decreased within the first 30 minutes of circulatory arrest and remained at low levels until the end of reperfusion. High-energy phosphates did not return to their initial levels during reperfusion. Histopathologic analysis of nine regions of the brain showed good preservation of cell structure in the anesthesia, hypothermic bypass, and antegrade perfusion groups. The retrograde perfusion group showed changes in all the regions examined. CONCLUSIONS: The study shows that moderate hypothermic circulatory arrest at 28 degrees C with antegrade brain perfusion during circulatory arrest protects the brain but that retrograde cerebral perfusion at 28 degrees C does not protect the brain.

Adenosine Triphosphate

Morphing radiologic images: applications on a desktop computer.

OBJECTIVE: Morphing is an image processing technology that transforms one image into another by generating a series of intermediate synthetic images. The ability to perform morphing, once restricted to high-end graphics workstations, is now widely available for desktop computers. We investigated the potential use of morphing for displaying radiographic images. MATERIALS AND METHODS: Morphing was performed with commercially available software (Morph 2.5; Gryphon Software, San Diego, CA) on a Macintosh (Apple Computer, Cupertino, CA) computer. Images from 26 patients with serial radiologic studies were selected, digitized, and morphed. Key points and key surfaces were identified on the images to improve the quality of the morph movie, a process that took approximately 15 min. The images were then morphed into a continuous Quick Time (Apple) movie lasting 5-7 sec. When a sequence contained more than two images, a single movie incorporating all the images was created. The intervals between segments of the movie were made proportional to the actual time elapsed between the images. Images obtained with different techniques (positron emission tomography and MR imaging) were also morphed. Three observers judged the quality of the morph movies as satisfactory, good, or excellent. RESULTS: Twenty of the 26 movies were judged to be of good or excellent quality. The movie format allowed the rapid display of multiple images in a concise 5- 7-sec time frame. Moreover, the movie allowed the recognition of several simultaneous processes more easily than was possible with static images. Morphing two images of the same anatomic site using different techniques (MR imaging and positron emission tomography) proved to be a simple method of superimposing images. CONCLUSION: Morphing is a readily available and easily learned technique for displaying serial studies. The movie format is a more interesting, intuitive, and concise summary of events than can be provided by serial static images. Morphing may be useful for displaying large numbers of serial images in a short time for occasions such as clinical conferences or teaching purposes.

Humans

Calcium supplementation and rectal mucosal proliferation: a randomized controlled trial.

BACKGROUND: Data from studies using rodents suggest that dietary calcium inhibits bile acid-induced mucosal damage and experimental carcinogenesis in the large bowel. However, in humans, the effect of dietary calcium and calcium supplementation on proliferation and carcinogenesis in the large bowel has been unclear. PURPOSE: To assess the effect of calcium supplementation on rectal mucosal proliferation in humans, we conducted a multicenter, randomized, placebo-controlled, double-blinded trial. METHODS: Participants were part of a larger multicenter chemoprevention trial; all were at high risk for large-bowel neoplasia, with at least one large-bowel adenoma removed endoscopically within the 3 months before study entry but with no known polyps remaining. Subjects were randomly assigned to receive daily either 3000 mg of calcium carbonate (providing 1200 mg elemental calcium) or an identical-appearing placebo tablet. During a scheduled endoscopy 6-9 months after random assignment (approximately 1 year after the qualifying endoscopy), rectal mucosal samples were obtained from 333 patients (173 assigned to calcium and 160 assigned to placebo). Proliferating cell nuclear antigen (PCNA) labeling indices (LIs) were computed as the measure of proliferation in specimens from 146 patients receiving calcium and 129 patients receiving placebo. Bromodeoxyuridine (BrdU) labeling was used to measure proliferation in a smaller number of specimens (27 calcium-receiving and 31 placebo-receiving participants). For each scorable crypt having at least one labeled cell (or surrounded by crypts with at least one labeled cell), a crypt LI was calculated as the number of labeled cells divided by the total number of crypt cells. Crypt LIs were averaged to produce a participant's average LI. RESULTS: The overall unadjusted mean PCNA LIs (+/- SE) were similar in the calcium and placebo groups (3.85% +/- 0.08% versus 3.92% +/- 0.08%, respectively, P = .30). The overall unadjusted mean BrdU LIs (+/- SE) were 3.88% +/- 0.30% in the calcium group and 3.54% +/- 0.21% in the placebo group (P = .54). PCNA labeling indices in the most luminal 40% of the crypt were small but, if anything, were higher in the calcium group. There was no patient subgroup within which calcium had an antiproliferative effect; the overall findings persisted among patients with high and low calcium intake, high and low fat intake, and high and low fiber intake. CONCLUSIONS: Calcium supplementation does not decrease rectal mucosal proliferation, as measured by PCNA (and BrdU) immunohistochemistry, in patients with previous large-bowel adenomas. This study, therefore, does not provide evidence for an anticarcinogenic effect of calcium.

Adenoma