Biomedical subjects
M Critchley
Publications and source records attributed to M Critchley.
A new method to measure renal tubular degradation of small filtered proteins in man using radiolabelled aprotinin (Trasylol).
1. A method has been developed to measure the renal tubular degradation of small filtered proteins in man using radiolabelled aprotinin (Trasylol), a 6500 Da cationic polypeptide. 2. Aprotinin (0.5 or 5.0 mg) was labelled with either 99mTc (40 MBq) or 131I (1 MBq) and injected intravenously in 19 renal patients (10 with normal renal function and nine on haemodialysis). Activity in plasma and urine was measured over 48 h, and chromatography with Sephadex-G-25-M was used to separate labelled aprotinin from free 99mTcO4- or 131I-. Renal uptake was measured for 99mTc-labelled aprotinin only. 3. The volumes of distribution were similar in all patients: 18.2 +/- 0.4 litres in those with normal renal function and 20.2 +/- 0.1 litres in the others. Chromatography showed all plasma activity as undegraded aprotinin and urine activity only as the free labels (99mTcO4- or 131I-). 4. In patients with normal renal function, activity in the kidneys rose rapidly to 24.2 +/- 2.8% of dose after 90 min and to 42.2 +/- 3.4% of dose after 24 h. In the dialysis patients, activity over the kidneys was only 2.7 +/- 0.8% of dose at 24 h. Extra-renal uptake was insignificant in all patients with normal kidney function. 5. Both 99mTcO4- and 131I- appeared in the urine promptly after injection, and the rates of excretion of the two isotopes were similar, varying little over 24 h (1.8 +/- 0.04% of dose/h and 1.7 +/- 0.04% of dose/h for 99mTc and 131I, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of lysine infusion on the renal metabolism of aprotinin (Trasylol) in man.
1. Aprotinin (Trasylol) is a cationic 6500 Da polypeptide that inhibits proteolytic enzymes, and when labelled with 99mTc it is a reproducible marker for the renal tubular turnover of small filtered proteins in man. Lysine potently inhibits tubular peptide uptake, and may thus depress the uptake and metabolism of aprotinin. This was investigated in 14 glomerulonephritic patients with normal renal function and variable proteinuria and in one healthy subject. 2. 99mTc-labelled aprotinin was given intravenously alone, and again 3 days later, immediately after the intravenous administration of 3-6 g of lysine, followed by an infusion over 1 h of 0.3-1.9 g of lysine/kg in individual patients. Activity over kidneys and in urine was measured over 24 h and chromatography was used to separate the undegraded peptide from free isotope. 3. At the low dosage of lysine (< 0.8 g/kg) given to six patients, kidney activity (representing tubular uptake) was unchanged, but early urine samples contained some undegraded aprotinin. Urinary excretion of free isotope, representing tubular metabolism, fell from 1.6 +/- 0.2% of dose/h with no lysine to 0.9 +/- 0.1% of dose/h in the 24 h after lysine, suggesting suppression of tubular aprotinin degradation. Corrected fractional degradation was calculated from the mean urinary excretion of free isotope over a given interval, determined by chromatography, divided by the mean cumulative kidney counts over this same interval, and this also fell after lysine from 0.06 +/- 0.006 to 0.03 +/- 0.006 h-1 (P < 0.005) between 3.75 and 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)
The response of 99Tcm-methylene diphosphonate and 99Tcm-hexametazime-labelled neutrophils to intra-articular steroid injection in rheumatoid arthritis.
The synovial and bone uptake of tracer in the knees of patients with rheumatoid arthritis (RA) was quantified using 99Tcm-hexamethyl propylene amine oxime-labelled leucocytes and 99Tcm-methylene diphosphonate (MDP), respectively. Significant neutrophil migration and MDP uptake occurred in the knees of patients with RA irrespective of the disease duration. In all but one patient neutrophil migration was reduced after intra-articular steroid injection. The change in MDP uptake after steroid injection was variable. There was a significant correlation between the percentage reduction in neutrophil migration and pain score, while the latter correlated poorly with the change in MDP uptake. The quantification of the neutrophil component of the inflammatory process is a sensitive index for monitoring RA activity and response to pharmacological interventions, while quantitative bone scintigraphy should not be employed to monitor changes in joint inflammation in patients with RA.
Sumatriptan and cerebral perfusion in healthy volunteers.
1. The effect of sumatriptan on regional cerebral perfusion was studied in healthy volunteers. 2. Intravenous sumatriptan (2 mg) had no detectable effect on regional cerebral perfusion as measured using a SPECT system with 99technetiumm labelled hexemethylpropyleneamineoxime. 3. Sumatriptan had no effect on pulse, blood pressure or ECG indices. 4. All six volunteers experienced minor adverse effects during the intravenous infusion.
Outcome of pregnancy following treatment of well-differentiated thyroid cancer with 131iodine.
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Tubular metabolism of aprotinin 99mTc and urinary ammonia: effects of proteinuria.
Increased renal ammoniagenesis is pathogenic in animals. Thus, tubular degradation of filtered proteins to ammonia might link proteinuria to disease progression. The tubular uptake, metabolism and fractional degradation of aprotinin 99mTc (Trasylol), were measured in 26 glomerulonephritic patients with normal renal function, 10 with proteinuria > 5 g/24 h. In addition, urinary ammonia pH, and titratable acidity were measured. Patients with heavy proteinuria had a higher tubular metabolism, a lower uptake and a higher fractional degradation of aprotinin. Urinary ammonia and titratable acidity were also increased. Fractional degradation and urinary ammonia were strongly correlated as were urinary ammonia and proteinuria.
Osteomalacia mimicking metastases: a treatable cause of bone pain.
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Radioleucoscintigraphy in osteoarthritis. Is there an inflammatory component?
The possible contribution of an inflammatory component in osteoarthritis was investigated. There was no correlation between the percentage uptakes of 99Tcm-hexamethylpropyleneamine oxime (HMPAO)-labelled white blood cells and 99Tcm-methylene diphosphonate (MDP) and between the former and pain scores. A significant correlation was found between the percentage uptake of 99Tcm-MDP and pain scores (0.002 > P > 0.01). In osteoarthritis, 99Tcm-HMPAO-labelled white cell imaging may or may not show a positive localization in the synovial membrane. Positive white cell localization appears to be limited to the area that corresponds to the radiological evidence of the condition and the positive uptake of the skeletal imaging agent.
Arterial oxygen saturation in patients undergoing perfusion lung scanning with 99Tcm-labelled macroaggregates of human serum albumin.
Radionuclide imaging of the lungs with 99Tcm-labelled macroaggregates of human serum albumin (99Tcm-MAA) is a safe, reliable and non-invasive method of diagnosing pulmonary embolism. It has been suggested that following intravenous injection of 99Tcm-MAA, arterial oxygen saturation falls significantly. Oxygen saturation was measured in 101 patients who had received an intravenous injection of 99Tcm-MAA prior to a perfusion lung scan. Readings were taken using a pulse oximeter at rest, immediately following injection, 10, 30 and 60 min post-injection. Twenty-five normal volunteers who were not injected acted as controls. Forty patients showed no change in oxygen saturation throughout the study. A fall of 1% was seen in 32 patients and 2-3% in 26 patients. Of the three patients who demonstrated a reduction in saturation of 6, 7 and 13%, two had chronic airways disease and one had left ventricular failure. Twenty out of 25 normal controls showed no change in saturation over the period of observation. Five showed a fluctuation of 1-2% between the measurements. All patients and controls remained asymptomatic with almost all readings returning to the initial values after 1 h. It was the patients with chest or heart disease who showed a fall in saturation. The study shows that the majority of patients undergoing a perfusion scan with 99Tcm-MAA show no significant fall in oxygen saturation. If a fall occurs, it may be related to the underlying disease process rather than to 99Tcm-MAA.
Radiolabelled white blood cell imaging in arthritis. Is it a blood pool effect?
The aim of this study is to determine whether white blood cell imaging in inflammatory conditions is due to a blood pool effect as a result of an increased vascularity and vascular permeability, or whether cellular migration is the major contributing factor. It will be shown that white cell uptake is a specific phenomenon in the rheumatoid knee joint and not just a blood pool effect.
A study of depression in old age using single-photon emission computerised tomography.
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Relationship between gastric emptying of liquid and postvagotomy diarrhoea.
Gastric emptying of liquid was studied in 10 normal volunteers and in 27 patients previously treated with truncal vagotomy and drainage. Thirteen of the twenty-seven patients complained of persistent postvagotomy diarrhoea. For each study 300 ml 15 per cent dextrose, labelled with 99mTc-diethylene triamine penta-acetic acid (DTPA), was ingested at a standard rate by subjects who sat facing a gamma camera. Imaging proceeded for 30 min. Gastric area activity curves were corrected for emptying of the test meal during ingestion, and for movement using a new image alignment technique. Gastric emptying at 15 min was 10 +/- 2.6 per cent (mean +/- s.e.m.) in healthy volunteers, 48 +/- 7.3 per cent in patients without diarrhoea, and 84 +/- 2.3 per cent in those with diarrhoea (P less than 0.001, ANOVA). Gastric emptying from 15 min onwards was slower than normal in both patient groups (P less than 0.001). These results show that initial gastric emptying is rapid following truncal vagotomy and drainage, and this change is greater in patients with postvagotomy diarrhoea. No patient with diarrhoea had normal initial gastric emptying.
Preduodenal mechanisms in initiating gallbladder emptying in man.
The existence of preduodenal phases of gallbladder emptying in normal volunteers was investigated by evaluating the effect of sham feeding a sandwich (chew and spit) (n = 15), the sight and smell of food followed by sham feeding a cooked meal (n = 15), and gastric distension (intragastric balloon tube) (n = 9) on gallbladder emptying and comparing these responses with those after ingestion of a standard meal (n = 14). A control group given no intestinal stimuli were studied to determine the frequency of spontaneous emptying during fasting (n = 18). 99mTc-EHIDA (2,6 diethylphenylcarbamoylmethyliminodiacetic acid) was used as the biliary tracer. The frequency of gallbladder emptying during fasting was 0.0045/min. Thus, in any 20 min period emptying occurred spontaneously in only about 1 in 11 volunteers. Significant emptying (greater than 5 per cent over 20 min) occurred in 8 out of 15 volunteers after sham feeding a sandwich (P less than 0.001 versus control), in 8 out of 15 volunteers after sham feeding a cooked meal (P = 1.0 versus sandwich sham feed, n.s.), in 6 out of 9 volunteers after gastric distension (P less than 0.001 versus control) and in 14 out of 14 volunteers after meal ingestion. The rate of emptying was significantly greater in the gastric distension and meal ingestion groups compared with other groups (P less than 0.05). However, the emptying rate after sham feeding was not significantly different from spontaneous gallbladder emptying (P greater than 0.05, n.s.). There was no significant difference in time to onset of emptying between the four stimulus groups (P greater than 0.05, n.s.). These results suggest that pre-duodenal stimuli can evoke gallbladder emptying in man, although the precise physiological significance of this phenomenon remains to be established.
Remembering Kinnier Wilson.
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Comparison between the cellobiose/mannitol and 51Cr-labelled ethylenediaminetetra-acetate absorption tests in the detection of coeliac disease.
1. The cellobiose/mannitol and 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA) absorption tests have been compared with respect to their ability to detect altered intestinal permeability in coeliac disease. 2. In patients with clinically proven coeliac disease, 13 out of 14 (93%) had abnormal urinary cellobiose/mannitol ratios, while only five out of 12 (42%) had abnormal urinary recoveries of 51Cr-EDTA. Thus, the cellobiose/mannitol absorption test is more sensitive in recognizing coeliac disease and this difference was significant (P less than 0.02). 3. Possible reasons for this difference in the sensitivity of the two absorption tests are discussed.
Mechanisms governing the biphasic pattern of gastric emptying after truncal vagotomy and pyloroplasty.
The pattern of gastric emptying after truncal vagotomy and drainage is usually biphasic. An early rapid phase is followed by a characteristically abrupt transition to slow emptying. The mechanisms responsible for this pattern were studied in six dogs with truncal vagotomy and pyloroplasty, fitted with a proximal duodenal cannula. Gastric emptying was measured using gamma camera imaging of a radiolabelled 15% dextrose test meal. Sixty one hour studies were done using five designs. (1) With the cannula closed gastric emptying was initially rapid, followed by stasis (emptying at 15 min - 32% (5.3), 60 min - 34% (4.8); mean (SE)). (2) With the cannula open emptying was very rapid (15 min - 76% (4.2) p less than 0.001, 60 min - 88% (2.6) p less than 0.001 ANOVA). (3) Distal duodenal instillation of isotonic saline, at a rate equivalent to gastric emptying with the cannula closed, did not retard this rapid emptying (15 min - 78% (10.6), 60 min - 90% (5.4)). (4) With duodenal instillation of 15% dextrose, gastric emptying remained faster than in studies without diversion (15 min - 50% (7.0) NS, 60 min - 65% (6.8) p less than 0.01), but was slower than during diversion alone (p less than 0.05). (5) Finally, duodenal instillation of 15% dextrose before administration of the test meal produced slower initial emptying without subsequent stasis (15 min - 24% (4.5), 60 min - 47% (10.6)), although the amounts emptied were not significantly different from those with the cannula closed. These results indicate that after truncal vagotomy and pyloroplasty small bowel resistances play a significant role in controlling gastric emptying. Osmoreceptor responses persist after truncal vagotomy, but sympathetic inhibitory responses to small bowel distension are not involved in the regulatory process.