The role of bone scintigraphy in the investigation of patients with low back pain.
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Biomedical subjects
Publications and source records attributed to M Critchley.
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249 patients with well differentiated thyroid cancer attended the Nuclear Medicine Department of the Royal Liverpool Hospital (formerly housed at the Liverpool Clinic) from 1967 to 1990. Papillary carcinoma was histologically evident in 68% of patients and follicular carcinoma in 32%. Fifteen percent of all patients died of their cancer. The extent of initial surgery did not appear to influence the recurrence of disease, nor the patient survival. Univariate analysis showed that males had a worse survival rate than females during the 5 years after diagnosis but thereafter survival rates were similar. Multivariate analysis indicated that unfavourable survival factors were "age over 45 years at diagnosis" and "presence of distal metastases". Survival was not significantly different with or without 131I ablation where there were no distal metastases. Outcome of pregnancy after 131I ablation gave no cause for concern. No serious complications were observed following 131I therapy. Serum thyroglobulin tests were introduced only half way through the review period and were helpful in predicting the presence of tumour recurrence but these data are to be discussed in another communication.
To establish the normal pattern of postoperative tracer uptake we performed 73 99mtechnetium methylene diphosphonate scans following primary Charnley hip replacements for arthrosis in 68 patients without clinical, hematological and radiographic complications. The patients were divided into 7 subgroups according to the period, 6-24 months, between surgery and scan. There were 10-12 patients in each subgroup. A high-resolution gamma camera with a large field of view was used. Ratios of uptake in each of 10 peri-prosthetic zones to normal bone were calculated. Femoral uptake was found to decrease in linear fashion from 6 to 12 months after surgery. Thereafter the uptake remained unaltered at levels nearly twice the normal ones in the greater trochanter and nearly 1.5 times in the lesser trochanter, returning to almost normal levels in other zones. Acetabular uptake remained elevated throughout.
1. The novel method recently developed to measure renal tubular degradation of filtered proteins in man using radiolabelled aprotinin (Trasylol) has been modified to allow the fate and the significance of the renal catabolism of radiolabelled aprotinin to be determined beyond 24h. 2. Ten renal patients with normal kidney function and variable proteinuria each received two separate intravenous injections of radiolabelled aprotinin, 5.0 mg of 99mTc-labelled aprotinin (40MBq) and 0.5mg of 131I-labelled aprotinin (5MBq). Chromatography (Sephadex-G-25-M) was used to separate undegraded radiolabelled aprotinin from the free isotope in urine and plasma. Renal uptake from gamma-camera images (24h for 99mTc-labelled aprotinin and up to 96h for 131I-labelled aprotinin) and urinary activity (48 and 96h, respectively) were measured. 3. The renal handling of radiolabelled aprotinin was similar with the two isotopes. Chromatography showed that all plasma activity was undegraded radiolabelled aprotinin, and urine activity was only the free isotopic label. 4. Kidney uptake of 131I-labelled aprotinin was prompt, reaching a cumulative maximum of 37.1 +/- 3.0% of dose at 24h, but falling exponentially thereafter to 5.6 +/- 1.0% of dose at 96h. 5. The rate of excretion of the free label in urine, i.e. the metabolic rate of radiolabelled aprotinin, was relatively constant over the first 24h (1.6 +/- 0.09% of dose/h), but then fell in parallel with the diminishing activity over the kidney, i.e. to 1.0 +/- 0.1% of dose/h over 24-48h and to only 0.4 +/- 0.08% of dose/h over 72-96h.(ABSTRACT TRUNCATED AT 250 WORDS)
1. The new method developed to measure renal tubular degradation of small filtered proteins in patients with normal renal function, using radiolabelled aprotinin (Trasylol) (R. Rustom, J. S. Grime, P. Maltby, H. R. Stockdale, M. Critchley, J. M. Bone. Clin Sci 1992; 83, 289-94), was evaluated in patients with chronic renal failure. 2. Aprotinin was labelled with either 99mTc (40 MBq) or 131I (0.1 MBq), and injected intravenously in nine patients, with different renal pathologies. 51Cr-EDTA clearance (corrected for height and weight) was 40 +/- 5.4 (range 11.2-81) ml min-1 1.73 m-2. Activity in plasma and urine was measured over 24-48 h, and chromatography on 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 volume of distribution was 20.2 +/- 2.3 litres. Chromatography showed all plasma activity as undegraded aprotinin, and urine activity only as the free labels (99mTcO4- or 131I-). 4. As in patients with normal renal function, activity in the kidney appeared promptly, with 5.7 +/- 2.5% of the dose detected even at 5 min. Activity rose rapidly to 9.4 +/- 1.6% of dose after 1.5 h, then more slowly to 15.0 +/- 0.5% of dose at 4.5 h, and even more slowly thereafter, reaching 24.1 +/- 2.8% of dose at 24 h. Extra-renal uptake was again insignificant, and both 99mTcO4- and 131I- appeared promptly in the urine, with similar and uniform rates of excretion over 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)
A comparative study of neutrophil pharmacokinetics and distribution between normal volunteers and patients with rheumatoid arthritis (RA) is presented. White cell viability was confirmed by prominent localization of activity in the spleen with minimal liver uptake and lack of retention in the lungs in both normal volunteers and RA patients. There were no significant differences between both groups in granulocyte clearance from the lungs and their subsequent distribution in the spleen, bone marrow and liver. The results of this study demonstrate that the behaviour of granulocytes in RA patients is essentially unchanged from that of normal volunteers.
Tests of gastric emptying with modern scintigraphic methods are recommended in the clinical management of gastric disorders. An audit of 472 gastric emptying tests carried out over a 10 year period was performed to discover the reasons for requests from consultant clinicians, their anticipation of the results of tests, and the influence of the results upon the subsequent management of their patients. Excluding control (n = 47) and research (n = 50) studies, there were 375 clinical referrals that could be grouped under the headings: non-ulcer dyspepsia (n = 72), suspected diabetic gastroparesis (n = 18), peptic ulcer (n = 15), suspected delayed gastric emptying after surgery (n = 154), dumping and diarrhoea (= 107), and other indications (n = 9). Although the results were abnormal for 55 (48%) of the 'medical' patients, they did not seem to influence clinical management. Delayed gastric emptying after surgery was confirmed in only 20% of patients referred with this clinical diagnosis. Conversely, most (79%) o the patients referred with dumping and diarrhoea exhibited abnormally rapid emptying. Isotope gastric emptying studies may be useful in clinical practice. The results are often at variance with the clinical diagnosis. Clinicians must take into account the nature of the test meal used when results are correlated with clinical features.
AIMS: To develop and validate an analytical procedure for the quantitation of pepsins and gastricsin in human gastric juice and to assess its potential in a controlled gastric secretory study. METHODS: High performance ion-exchange chromatography was used to separate human pepsin 1, 3a, 3b, 3c and gastricsin from gastric juice. Computed chromatographic areas for each enzyme were quantified by relation to a known amount of a secondary standard porcine pepsin. The assay procedure was validated by recovery and analytical precision studies. Gastric secretions after pentagastrin and insulin stimulation from 10 patients with portal hypertension were used to assess the potential of the analytical procedure. RESULTS: The assay precision varied from 1.5 to 9.0% within batch and 7.5 to 18.1% between batch, with about 100% recoveries of porcine pepsin A from human gastric juice over the assay range 0.025-0.5 mg/ml. A fourfold increase in combined pepsin and gastricsin concentration was observed following pentagastrin and insulin stimulation. The mean percentage content of pepsins 3a, 3b, 3c, and 1 in non-stimulated gastric juice were 4%, 72%, 12% and 1.4%, respectively, and did not change significantly after gastric stimulation. An approximate doubling of the percentage of gastricsin (10% to 20%) relative to the pepsins was observed, however, after both insulin and pentagastrin stimulation. CONCLUSIONS: This procedure for quantifying individual human pepsins and gastricsin in gastric juice is simple and reliable. It may be of considerable importance in determining the mechanisms involved in the control and secretion of these digestive enzymes in man, including the effect of anti-ulcer drugs and our understanding of the pathophysiology of peptic ulcer disease.
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)
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 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.
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.
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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.
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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.
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.