Search PubMed⌕ Search

Biomedical subjects

M J Chamberlain

Publications and source records attributed to M J Chamberlain.

At least 37 records · Page 2Linked to original sources

Preparation and evaluation of radioiodinated (iodophenyl)cholines and their morpholinium and piperidinium analogues as myocardial perfusion imaging agents.

A series of nine radioiodinated quaternary ammonium salts related to phenylcholine were synthesized, characterized, and radiolabeled by exchange. These compounds were evaluated as myocardial perfusion imaging agents in mice, pigs, and humans. Mice biodistribution studies showed that five of the nine compounds were taken up in the heart to the same extent as 201Tl+ at 5 min. At 60 min myocardial retention was significantly better than 201Tl+ for six of the compounds. Several of the compounds showed more favorable heart/blood and heart/liver ratios when compared to 201Tl+. Evaluation of three of the more promising compounds in pigs and humans however revealed no selective myocardial uptake.

Animals↗

Gastric emptying before and after transverse gastroplasty for morbid obesity.

Twenty-three morbidly obese patients underwent gastric emptying studies (Tc-99m egg salad sandwich--a semisolid meal) preoperatively, and at three months and 12 months postoperatively to evaluate the effect of transverse gastroplasty on gastric emptying and to determine the predictive value of this study for weight loss. At three months pouch emptying was variable with nine of 23 patients having prolonged half-times, and 14 shortened half-times compared with preoperative values, despite both groups having identical weight loss. At 12 months pouch half-times returned to baseline. The data suggests that this type of gastroplasty causes weight loss solely by reducing the gastric volume resulting in reduced meal volume. Weight loss is not related to impaired pouch emptying, which might result in a prolonged feeling of fullness. Gastric emptying studies neither preoperatively nor postoperatively have weight loss predictive value for this particular operation.

Adult↗

Zinc absorption and leukocyte zinc in alcoholic and nonalcoholic cirrhosis.

To determine if malabsorption of zinc contributes to the zinc deficiency found in cirrhosis, the absorption of an oral dose of ZnCl2, labeled with 65Zn and a nonabsorbed marker 51CrCl3, was determined from the ratio of these isotopes in a stool specimen. Average 65Zn absorption in 25 alcoholic cirrhotics, 37 +/- 17% (SD), was low compared to 55 +/- 16% in 31 healthy volunteer controls (P less than 0.01). In contrast, mean 65Zn absorption, 47 +/- 11%, in 11 nonalcoholic cirrhotics was not significantly different from the average result in healthy controls. Low 65Zn absorption was accompanied by low leukocyte zinc in a subgroup of alcoholic cirrhotics with ascites and/or ascites and encephalopathy, but not in the subgroup in which these clinical features were absent. Thus, low zinc absorption contributes to zinc deficiency in decompensated alcoholic cirrhosis. The failure to find similar abnormalities in nonalcoholic cirrhosis suggests that the long-standing consumption of alcoholic beverages contributes to the malabsorption of zinc.

Adult↗

Does the oral zinc tolerance test measure zinc absorption?

Increases in plasma zinc concentration were compared with radiozinc absorption after oral test doses. Ten healthy, fasting subjects were each given 385 mumol zinc chloride (25 mg Zn) labelled with 0.5 muCi 65ZnCl2 and a non-absorbed marker, 51CrCl3, dissolved in 100 ml of water; another 10 persons were given 354 mumol zinc chloride and 125 g of minced turkey containing 31 mumol zinc also labelled with 65Zn and 51Cr. Measurements were made of plasma zinc concentration at hourly intervals for 5 hours, radiozinc absorption by stool counting of unabsorbed radioactivity 12-36 hours later, and radiozinc retention by whole body counting at 7 days. The mean percentage of radiozinc absorbed and retained in the body from the two test meals was found to be identical (42%). In contrast the increased area under the plasma zinc curve up to 5 hours after the turkey meal, 28 +/- 9 mumol/L (mean +/- SD) was significantly less than that for zinc chloride alone, 47 +/- 15 mumol/L, p less than 0.005. Despite this difference, a good correlation was found between the area under the plasma zinc curve and 65Zn absorption in individual subjects after each meal. The discrepancy between the results of zinc absorption derived from the plasma zinc curve and 65Zn absorption for the liquid and solid test meals was most likely explained by binding of zinc to food and delayed gastric emptying of the solid meal. With a test meal of turkey meat at least this dampened the plasma appearance of zinc but did not affect its overall absorption.

Administration, Oral↗

Dual-isotope method for determination of human zinc absorption: the use of a test meal of turkey meat.

The percentage of 65Zn taken up (absorbed) from extrinsically labeled turkey meat was calculated from the amounts of 65Zn and a nonabsorbed 51Cr marker present in the body or in a single stool specimen after 1-2 d. 51CrCl3 proved to be a suitable marker for unabsorbed 65Zn and so the early determination of 65Zn absorption was possible. With stool counting, 65Zn absorption data from first stool samples after 1-2 d were accurate as judged by correlation with the amount of 65Zn in the body 7-10 d later (retention); results from subsequent stools gave lower absorption values due to the early excretion of some absorbed 65Zn. The dual-isotope method gave reproducible results when four successive tests of zinc absorption were carried out in a group of six subjects. The average (mean +/- SD) 65Zn absorption from turkey meals containing 31 mumol (2 mg) and 46 mumol (3 mg) of zinc was 39 +/- 8% and 29 +/- 6%, respectively, measured by stool counting; 65Zn absorption and retention correlated well in both studies. A series of different beverages was given in place of water with the turkey meal. Orange juice significantly reduced 65Zn absorption and milk also showed this tendency, but tea, whiskey, wine or beer had no significant effect on the absorption of 65Zn from the turkey meal. In groups of subjects the mean ratio of 65Zn absorption from extrinsically labeled turkey meat on two occasions (1.06) was not significantly different from that of the absorption of extrinsic to intrinsic 65Zn labels (1.16). The dual-isotope technique with either stool or body counting is suitable for the rapid determination of 65Zn absorption from extrinsically labeled turkey within 2 d.

Adult↗

Aminophylline and mucociliary clearance in patients with irreversible airflow limitation.

Were aminophylline to improve mucociliary function, it might prove useful in the management of irreversible airflow limitation. Eight subjects with irreversible airflow limitation due to emphysema inhaled an aerosol of 99mTc sulphur-colloid particles on each of 2 days. On day 1 aminophylline was administered intravenously, while on the other nothing was given. Particle clearance was measured by recording posterior gamma-camera images sequentially over a 24 h period. No significant differences were recorded between aminophylline and control studies, but there were marked variations in clearance between study days and between individuals. These differences were compatible with the known effects of airways obstruction and breathing pattern on the sites of particle deposition within the bronchial tree. The latter factors appeared to exert a far greater influence on the observed mucociliary clearance than did aminophylline.

Aminophylline↗

Regional deposition of particles in the lung during cigarette smoking in humans.

Studies were carried out on 11 habitual cigarette smokers to ascertain whether there was a difference in the regional deposition of particles during cigarette smoking compared with tidal breathing and also to investigate whether the ventilatory maneuvers associated with smoking influence the deposition site. A cigarette holder was constructed that permitted cigarette smoke to mix with a radioaerosol. An added resistance simulated the airflow resistance present in a filter-tipped cigarette. Respiratory patterns for the control period of tidal breathing and during smoking were monitored with a respiratory inductance plethysmograph. Smoking resulted in greater apical and central deposition than expected from the distribution of resting ventilation. The changes in the site of deposition during smoking are probably influenced mainly by the properties of the particles concerned, namely, its size, reactivity, and hygroscopicity. Changes in respiratory patterns that occur during inhalation of cigarette smoke may also have an effect but are difficult to quantify and show marked intersubject variation. In selected subjects smoking caused apical deposition to exceed that of the lower zones.

Adult↗

The effect of exercise on the deposition of an inhaled aerosol.

We investigated the regional deposition in the lungs, of an inhaled submicron aerosol at rest and during exercise in 13 normal volunteers of whom 5 were cigarette smokers. The degree of exercise (VO2 approximately 2 L/min) was chosen to simulate moderately heavy physical labour. Tracheobronchial and alveolar components of deposition were measured by comparing images immediately after inhalation of aerosol and 24 h later when mucociliary clearance was complete. At rest almost all deposition was alveolar (97%). The increase in total deposition on exercise was of similar order to the increase in ventilation. On exercise regional alveolar deposition became more even, although basal still exceeded apical deposition. Tracheobronchial deposition on exercise was increased in all zones but particularly in the upper zones, thereby contrasting with the base to apex gradient of parenchymal deposition. These changes were exaggerated in the smokers. The increased upper zone tracheobronchial deposition may have implications in regard to the pathogenesis of diseases caused by the inhalation of dusts and fumes.

Adult↗

Effects of iron, tin, and copper on zinc absorption in humans.

Zinc absorption as measured by body retention of [65Zn]zinc chloride or a turkey test meal extrinsically labeled with 65Zn was determined in human subjects by whole body counting after 7 days. Average 65Zn absorption from zinc chloride in persons with a high iron-absorbing capacity was similar to persons with a low capacity to absorb iron. Inorganic iron, 920 mumol (51 mg), or HB iron, 480 mumol (26 mg), inhibited 65Zn absorption from 92 mumol (6 mg) of zinc chloride. When 610 mumol of iron (34 mg) was added to a turkey test meal containing 61 mumol of zinc (4 mg), 65Zn absorption was not inhibited. Tin, 306 mumol (36 mg), given with zinc chloride or turkey test meals (61 mumol, 4 mg, of Zn) significantly reduced 65Zn absorption. Copper, 79 mumol (5 mg), had no significant effect on the 65Zn absorption from 7.9 mumol (0.5 mg) of zinc chloride. In summary, the capacity to absorb iron did not influence 65Zn absorption, but both inorganic iron and heme-iron inhibited 65Zn absorption from zinc chloride. Inorganic iron had no effect, however, on 65Zn absorption from the turkey test meal. Tin in a large dose also inhibited 65Zn absorption from both zinc chloride and the turkey test meal.

Adolescent↗

Radionuclide diagnosis of splenic rupture in infectious mononucleosis.

Spontaneous splenic rupture is a rare but serious complication of infectious mononucleosis. Although radionuclide spleen imaging is a well accepted method for diagnosis of traumatic rupture, interpretation can be difficult in the setting of mononucleosis, as tears may be ill-defined and diagnosis hampered by inhomogeneous splenic uptake. Four proven cases of spontaneous rupture are presented, three of which illustrate these diagnostic problems.

Adult↗

Factors influencing the regional deposition of inhaled particles in man.

1. Although ventilation in normal human lungs has been shown to decrease from apex to base, comparable observations are lacking in regard to particle deposition. 2. We compared regional ventilation and particle deposition in normal subjects by using radioactive xenon and a radioactive aerosol while sitting, lying, and while breathing at an increased rate. Both smokers and non-smokers were studied. 3. Particle deposition and ventilation were closely related, and the greater the ventilation the greater the deposition of particles, a situation which prevailed irrespective of position and breathing rate. While supine, the apex to base gradient for both ventilation and particle deposition decreased but did not entirely disappear. At higher respiratory rates, central deposition of particles, especially in smokers, increased. 4. We concluded that there are regional differences in the deposition of particles and that such differences are closely related to regional ventilation.

Adult↗

Histamine bronchial challenge: effect on regional ventilation and aerosol deposition.

We studied regional changes in ventilation and aerosol deposition after histamine challenge in six patients with asthma and two with rhinitis and a history of wheezing. All were known to have bronchial hyperreactivity and all showed an increased response to histamine. Ventilation and aerosol deposition studies, using xenon-133 and an aerosol of sulphur colloid tagged with technetium 99m, were performed while they were sitting. Before administration of histamine radioaerosol scintiscans were abnormal in five of six patients; after histamine challenge all were abnormal and central deposition was significantly greater in all of them. The decrease in aerosol penetration correlated with the percentage decrease in FEV1, indicating that the efficiency of aerodynamic filtration depends on the degree of airway narrowing. In six of the eight subjects the distribution of ventilation changed from predominantly basal to predominantly apical after histamine, which suggests the airways response was greater, at least initially, in the better ventilated regions. This indicates a close relationship between regional ventilation and the site of histamine deposition and has implications for the delivery of aerosolised agents in general.

Adult↗

Genetic and phenotypic expression of hemochromatosis in Canadians.

Twenty-three probands with idiopathic hemochromatosis were assigned the status of homozygotes: 132 of their relatives were classified as homozygotes, heterozygotes or normal individuals using the HLA haplotypes of the probands as markers of the hemochromatosis allele. Only half of the probands sought help because of symptoms or signs of iron overload. Clinical manifestations of iron loading were present, however, 95% of the probands and 67% of the discovered homozygotes. The commonest symptom was joint pain and stiffness. None of the heterozygotes had any clinical symptoms of excess body iron. High transferrin saturation and serum ferritin levels were prevalent in homozygotes: only 1 of 38 homozygotes had values for both of these measurements that were within normal limits. The level of transferrin saturation was increased in 6% of heterozygotes but only 1% had serum ferritin concns greater than 350 ng ml-1. The mean radioiron absorption levels of 27 homozygotes and 28 heterozygotes were similar to those in 44 controls. Radioiron absorption in relation to the respective serum ferritin concn was above the 95% confidence interval of controls in 65% of the homozygotes and 7% of the heterozygotes. The inverse relation between radioiron absorption and the respective serum ferritin concn observed in controls was absent in homozygotes but remained strong in the heterozygotes. Absence of the inverse relation indicates a deregulation of the iron absorptive mechanism in homozygotes which results in the size of body iron stores having no effect on the level of iron absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Diagnosing papillary stenosis by technetium-99m HIDA scanning.

The diagnosis of papillary stenosis, occasionally seen after cholecystectomy, is confirmed by endoscopic retrograde cholangiopancreatography (ERCP), which demonstrates delayed emptying of contrast material into the duodenum for more than 45 minutes. The authors assessed 2,6-dimethyl phenyl carbamoyl methyl iminodiacetic acid labelled with technetium-99m (99mTc HIDA) as a less invasive procedure in these circumstances by comparing it with the findings from ERCP. Twenty-six patients who had pain after cholecystectomy were studied by continuous 1-hour scintigraphy after injection of 99mTc HIDA. Biliary flow was estimated by measuring uptake and clearance of the entire liver and common bile duct. Volunteers who had no pain after cholecystectomy served as controls. Of the 26 study patients, all 99mTc HIDA scan findings were within the control range in 11. Of these, 10 had normal biliary drainage confirmed by ERCP. The one patient with delayed drainage did not improve after endoscopic sphincterotomy. Two patients demonstrated pooling of 99mTc HIDA in cystic dilatations of the biliary tree, while the other 13 patients had obstruction of the distal common bile duct and impaired flow demonstrated on the 99mTc HIDA scan. All 13 of these patients had papillary stenosis proven by ERCP. The authors conclude that 99mTc HIDA scanning is a valuable, minimally invasive method of diagnosing papillary stenosis.

Ampulla of Vater↗

The relationship between iron and lead absorption in humans.

Approximately 60% of an oral dose of 100 micrograms of 203Pb was retained in 85 fasting subjects with no difference noted between males and females. Body retention was proportional to dose up to 400 micrograms of lead. It was not related to the capacity to absorb iron or to the size of body iron stores, nor was it affected by the simultaneous ingestion of a 10-fold molar excess of iron. The effect of several dietary factors was also determined. Lead retention was lowered by eating food, slightly increased by ingestion of fat, but was unaffected by the administration of lactose or a 10-fold molar excess of zinc, cobalt, or calcium. One chelating agent, ascorbic acid, slightly lowered lead retention, whereas another agent ethylenediaminetetraacetic acid, produced a marked reduction. Several of these results suggest that human gastrointestinal lead absorption behaves differently to that of rodents. In particular, human lead retention was found to be unrelated to iron absorption or to body iron stores.

Absorption↗

Platelet interaction within giant intracranial aneurysms.

Turbulence within intracranial aneurysms may result in tearing of the aneurysmal wall, exposing the subendothelial matrix to circulating platelets. In this study, platelet interaction in giant intracranial aneurysms was evaluated by a dual-isotope technique employing In-labeled platelets and Tc-labeled red blood cells. The use of two isotopes allows the subtraction of the blood pool and the calculation of the ratio indium deposited:indium blood pool (In(D)/In(BP)). A ratio greater than zero indicates platelet deposition within aneurysm. Thirteen patients were evaluated in this way, with platelet deposition demonstrated in six. In these six patients, the ratio In(D)/In(BP) was found to be significantly elevated, with a mean value of 0.96 +/- 0.65. Three of these six patients has symptoms of recurrent transient neurological deficits; one of these three suffered a complete stroke following documentation of platelet deposition. In this case, the aneurysm was obtained at surgery and was found to contain intraluminal platelet aggregation when viewed by scanning electron microscopy. In the remaining seven patients, the ratio IN(D)/In(BP) was found not to be significantly elevated (mean -0.03 &/- 0.06), indicating the absence of active platelet deposition. Two of these patients had prior symptoms of cerebral ischemia; one of these was found to have an ulcer in the ipsilateral internal carotid artery which was probably responsible for thromboembolic events to the hemisphere. The authors conclude that platelet aggregation occurs more frequently than previously recognized in giant intracranial aneurysms, and their data substantiate the hypothesis that platelet metabolic products or thrombi originating from a large aneurysm may embolize to distal cerebral vessels.

Adult↗

Electrocardiography, cardioenzymes and myocardial imaging to detect perioperative myocardial infarction.

Serial electrocardiography, technetium-99m pyrophosphate scintigraphy and measurement of myocardial creatine kinase (CK2) and lactic dehydrogenase isoenzyme activity (specifically the LD1 to LD2 ratio) were evaluated prospectively in 26 patients who underwent aortocoronary bypass grafting and 11 patients who underwent valvular or other thoracic surgery, as methods of diagnosing perioperative myocardial infarction. Of the 26 patients who had aorto coronary bypass grafting, 7 (group 1) had myocardial infarction perioperatively; of these, only 2 had positive results from all four diagnostic tests. The other 19 patients (group 2) had no perioperative myocardial infarction and the only diagnostic method yielding positive results was the LD1 to LD2 ratio, in 7 of the 19. In the 11 patients who did not undergo aortocoronary bypass grafting (group 3), only 1 patient had myocardial infarction perioperatively; results from the measurement of CK2 isoenzyme activity and LD1 to LD2 ratio were positive while electrocardiography and 99mTc pyrophosphate scintigraphy yielded negative results. The respective sensitivity (%) and specificity (%) of the four diagnostic methods were as follows: electrocardiography: 38, 100; 99mTc pyrophosphate scintigraphy: 88, 100; LD1 to LD2 ratio: 100, 68; CK2: 38, 100. When the CK2 criterion was redefined, using patients in group 2 as controls, the sensitivity and specificity of this method became 100 and 90 respectively. The authors conclude that 99MTc pyrophosphate scintigraphy and measurement of myocardial creatine kinase isoenzyme are of comparable value and are the most reliable indicators of perioperative myocardial infarction.

Coronary Artery Bypass↗

Technique for determination of human zinc absorption from measurement of radioactivity in a fecal sample or the body.

The intestinal absorption of an oral dose of zinc chloride was determined from the ratio of 65Zn and a nonabsorbed radioactive marker, 51Cr, present in a single stool specimen or the body 24-72 h later. Chromic chloride had no effect on [65Zn]zinc chloride absorption and 51Cr and 65Zn had similar intestinal transit times. In 17 healthy control subjects given 92 mumol ZnCl2 labeled with 0.5 microCi 65Zn, 52 +/- 14% (SD) of the dose was taken up from the lumen. Intestinal absorption of 65Zn at 24 h correlated closely with 65Zn body retention of zinc measured by whole-body counting 7 days later, r = 0.995. Neither zinc absorption nor zinc retention correlated with blood leukocyte zinc levels. An average of 55% of 65Zn was retained in the body from doses of 18-90 mumol ZnCl2 but a progressively smaller proportion of zinc was absorbed from doses of 180-900 mumol. The average absorption and body retention of 65Zn were significantly reduced in 7 patients with mucosal disease of the proximal intestine but they were not affected by resection of the lower jejunum, ileum, and colon. Thus the absorption of ZnCl2 from a 92-mumol dose predominantly takes place by a rate-limited mechanism in the duodenum and upper jejunum.

Adolescent↗