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Biomedical subjects

A M Peters

Publications and source records attributed to A M Peters.

At least 181 records · Page 10Linked to original sources

A specific thromboxane receptor blocking drug, AH23848, reduces platelet deposition on vascular grafts in man.

The antithrombotic effect of a specific thromboxane A2 receptor blocking drug, AH23848, on radio-labelled platelet deposition in mature Dacron aorto-bifemoral grafts has been evaluated in patients. Thirty patients were randomly allocated to AH23848 70 mg, aspirin 300 mg plus dipyridamole 75 mg or placebo 8-hourly for 9 days. AH23848 inhibited platelet aggregation induced by the thromboxane A2 mimetic U-46619; no such effect was observed with aspirin plus dipyridamole. 111In-platelet uptake was measured as the thrombogenicity index (TI) which is a measure of the daily rate of accumulation of platelets by the graft. The mean (s.e. mean) value of 0.193 (0.029) on placebo was significantly reduced to 0.115 (0.022) by AH23848 (p less than 0.05) but only to 0.175 (0.028) by aspirin plus dipyridamole. There was no difference in mean platelet life span between the three treatment groups. The pronounced antithrombotic effect of AH23848 implicates thromboxane A2 in the process of platelet deposition in arterial prostheses and demonstrates the considerable promise of thromboxane receptor blocking drugs as antithrombotic therapy.

Aged↗

Quantification of radiolabelled granulocyte migration in vivo.

Quantification of the tissue localisation of granulocytes is difficult, particularly in man. With the aim of facilitating such quantification, a technique is described which combines the micropore filter skin window technique with the infusion of autologous 111In-labelled granulocytes. The radioactivity in the removable micropore filters, placed on small forearm skin window abrasions, was compared with peripheral blood radioactivity following injection of 111In-labelled 'pure' granulocytes in normal subjects. Radioactivity in filters from abrasions which were made 8 h or more before injection of labelled cells followed the same time course as the cell-associated radioactivity in whole blood, but radioactivity in filters from abrasions made nearer to the time of labelled granulocyte injection increased to reach a peak 3-8 h after cell injection, at a time when cell-associated blood radioactivity had fallen to about 50% of its initial value. Exercise appeared to induce a transient decrease in radiolabelled granulocyte migration into the filters. This technique offers a means of studying the kinetics of granulocyte migration in vivo.

Cell Movement↗

Imaging of bone infection with labelled white blood cells: role of contemporaneous bone marrow imaging.

The uptake of white blood cells (WBC) into normal bone marrow may lead to difficulty in detecting bone infection. Twenty-one patients in whom the WBC scan was equivocal or positive underwent a technetium 99m colloid scan to show the distribution of bone marrow. Six patients had a positive WBC scan, and in five of them a discordant colloid scan confirmed infection. However, in one the colloid scan was concordant, indicating that the WBC activity was not due to infection but the result of normal bone marrow uptake. Fifteen patients had an equivocal WBC scan. In 14, infection was excluded by a concordant scan, and 1 patient with a discordant scan was lost to follow-up. We conclude that the combination of a WBC scan and a colloid scan is an effective method to distinguish infection from normal bone marrow activity and, in particular, reduces the number of incorrect diagnoses of infection.

Bone Marrow↗

Indirect radionuclide cystography: a sensitive technique for the detection of vesico-ureteral reflux.

The detection or exclusion of vesico-ureteral reflux (VUR) has classically been by micturating cystourethrography (MCUG). Radionuclide cystography will detect VUR but fails to provide the same detailed anatomical informations as MCUG. This study allowed a comparison of indirect radionuclide cystography (IRC) and MCUG in 65 children. Renal reflux was detected by IRC in 32% of renal units, while VUR was seen in 36% by MCUG. When a comparison was made with MCUG, IRC had a sensitivity of 74.1% and a specificity of 90.5%. The markedly reduced radiation dose, avoidance of a bladder catheter plus the ability to monitor the urinary tract constantly during the entire procedure should ensure that IRC is the examination of choice in follow-up studies for VUR in all toilet-trained children.

Adolescent↗

Quantitation of vesico-ureteral reflux by radionuclide cystography and urodynamics.

A method is described for the quantitation of vesico-ureteral reflux by synchronous combined direct radionuclide cystography and urodynamics. Intravesical pressures and volumes are co-ordinated with volumes of reflux. Peak reflux volumes in 11 children diagnosed as having severe (grades 3-4) reflux on conventional contrast cystography ranged from 1 to 50 ml/kidney. A number of different patterns of reflux were observed. Reflux may occur progressively throughout low pressure filling or incrementally with unstable bladder contractions. Reflux during voiding may be maximal as detrusor pressure falls. The method requires wider application to explore the potential for a functional classification of the reflux problem.

Child↗

Indium labelled leucocyte scanning in pyrexia of unknown origin.

Pyrexia of unknown origin (PUO), the commonest cause of which is occult infection, represents a difficult diagnostic problem. Radiolabelled white cell scanning provides a non-invasive and potentially useful diagnostic tool in this condition, but its efficacy remains controversial. In a retrospective study, we analysed 30 111In white cell scans, performed between 1983 and 1988 in 25 patients with PUO, strictly defined as a fever of at least 3 weeks duration reaching 38.3 degrees C on more than three occasions and investigated in hospital for a minimum of 7 days. Eleven studies were on post-operative patients who, although developing fever within 1 week of surgery, satisfied the above criteria. Overall, the diagnostic sensitivity and specificity were 55% and 74% respectively, with an overall accuracy of 67%. This improved to 91% in the post-operative patients compared to an accuracy of 52% in spontaneous PUO. Accuracy did not correlate with duration of symptoms, leucocytosis or index of clinical suspicion. In conclusion, although 111In white cell scanning is not particularly useful for the investigation of spontaneous PUO, it does have a role in post-operative PUO.

Adult↗

Indirect radionuclide cystography demonstrates reflux under physiological conditions.

Indirect radionuclide cystography (IRC) is a useful technique for the detection and quantification of vesico-ureteric reflux (VUR). Its principal advantage over micturating contrast cysto-urethrography (MCU) is its ability to demonstrate VUR under physiological conditions. Three children (age range 6-9 years) reported here illustrate some physiological features of micturition readily seen only on IRC. The most important of these was uretero-ureteric reflux which, because of bladder activity, is not usually identifiable on IRC or MCU but is probably more common than previously thought and misinterpreted as VUR.

Child↗

Measurement of microvascular permeability to small solutes in man: limitations of the technique.

STUDY OBJECTIVE: The aim was to evaluate the limitation on the measurement of the clearance rate of a small solute, 99mTc DTPA, from intravascular to extravascular spaces imposed by diffusion of the solute back into blood during the period of measurement. DESIGN: The technique for measuring clearance also generates the regional plasma volume from which the solute is cleared. Back diffusion would result in an overestimation of this plasma volume. By applying the same technique to 99mTc labelled human serum albumin, which is not cleared over the period of measurement, a separate estimate of plasma volume can be made. SUBJECTS: The subjects were eight patients undergoing routine 99mTc DTPA renography for suspected outflow obstruction. MEASUREMENTS AND RESULTS: The ratio of plasma volumes based respectively on 99mTc DTPA and human serum albumin in a region of interest below the kidney was 1.04 (SD 0.09). The technique requires a region of interest over the cardiac blood pool from which the blood level of 99mTc DTPA is continuously monitored. When a correction was made for extravascular 99mTc DTPA in this cardiac region of interest, the ratio was unchanged: 0.97 (0.12). CONCLUSION: The technique is capable of measuring the clearance of 99mTc DTPA although, because of its small molecular size, the transfer rate is blood flow dependent, ie, its PS product is greater than its clearance.

Capillary Permeability↗

Labelling autologous platelets with 111In tropolonate for platelet kinetic studies: limitations imposed by thrombocytopenia.

An in vitro method of radiolabelling platelets with 111In tropolonate in plasma has been devised enabling imaging and cell kinetic studies to be performed in patients with thrombocytopenia (TP) using autologous, rather than donor, platelets. Platelets from 10 TP patients, with platelet counts ranging from 4-91 x 10(9)/l, were labelled in 50% plasma with 111In tropolonate, containing the optimum tropolone concentration of 2 x 10(-4) mol/l, at platelet concentrations ranging from 0.08-4.5 x 10(9)/ml resulting in labelling efficiencies (LE) between 51 and 86%. In 4 patients, red cells contaminated the platelets but this was corrected for by measuring the proportion of 111In on the platelets prior to injection and in the post-injection blood samples. Platelet recovery (PR), mean platelet life-span (MPLS) and platelet production rate (PPR) were calculated and splenic and hepatic images were taken. The results clearly show that useful clinical data can be obtained by this method even in patients with severe TP.

Adult↗

Indium-111 labelled granulocyte scanning to detect inflammation in the lungs of patients with chronic sputum expectoration.

Thirty eight patients with chronic sputum expectoration underwent indium-111 labelled granulocyte lung scanning and measurement of whole body loss of indium-111 labelled granulocytes. Twenty four patients had radiologically proved bronchiectasis and 14 had mucus hypersecretion without radiological evidence of bronchiectasis. None was having an acute exacerbation at the time of the scan. The median 24 hour volume of sputum expectorated was 17 (range 2-175) ml. The 24 hour volume of purulent sputum was 5 (0-142) ml; six patients expectorated mucoid sputum only. Twenty one of the 38 patients had a positive granulocyte lung scan. All nine patients expectorating more than 20 ml purulent sputum in 24 hours had positive lung scans and all had lost more than 19% of the indium-111 from the body after five to seven days. Of the six patients with mucoid sputum, only one had a positive scan and these subjects lost only 6-11% of the indium-111 in five to seven days. The percentage loss of indium-111 from the body correlated with 24 hour purulent sputum volume (r = 0.41, n = 38, p less than 0.001) and total elastolytic activity in 24 hour sputum (r = 0.54, n = 14, p less than 0.01). The loss of indium-111 was not related to the extent of bronchiectasis when purulent sputum volume was allowed for. Indium-111 labelled granulocyte scanning provides a sensitive and objective method for detecting inflammation in the lungs and should help to improve understanding of chronic bronchial sepsis and possibly treatment in selected cases.

Adult↗

Noninvasive measurement of renal blood flow with technetium-99m-DTPA in the evaluation of patients with suspected renovascular hypertension.

If a hypertensive patient with renal artery stenosis (RAS) is to benefit from percutaneous transluminal renal angioplasty (PTRA) in terms of a sustained improvement in blood pressure control, one may postulate a demonstrable reduction in renal blood flow (RBF) to that kidney, reversible by PTRA. In a population of 32 hypertensive patients, RAS was present in 23 of 62 kidneys. Eleven of the 32 patients underwent renal revascularization, of whom 6 showed improvement in blood pressure control at 6 mo, i.e., had renovascular hypertension (RVH). There was no correlation between RBF and angiographic appearances of the renal artery. Furthermore, there was no significant difference between RBF in the stenosed kidneys of the patients with RVH compared with the stenosed kidneys of patients without RVH. Individual kidney RBF was 22% (s.d. 11) higher 1-3 wk after PTRA but the increase did not correlate with clinical outcome. Angiotensin converting enzyme (ACE) inhibition increased RBF by 25% (s.d. 25) of baseline flow before PTRA but the increase did not correlate with clinical outcome. Measurement of RBF is of limited value for the prediction of the long-term blood pressure response following PTRA.

Angiography, Digital Subtraction↗

Skeletal assessment in neuroblastoma--the pitfalls of iodine-123-MIBG scans.

This study was carried out to compare iodine-123 metaiodobenzylguanidine ([I123I]MIBG) and technetium-99m-methylene diphosphonate bone scans (99mTc-MDP) in the detection of skeletal involvement by neuroblastoma. Forty-four children with neuroblastoma underwent both [123I] MIBG and 99mTc-MDP scans within a 4-wk period; bone marrow examination also was performed; all these investigations were done both at diagnosis and at follow-up. At diagnosis, four children with Stage 4 disease had normal [123I]MIBG scans but abnormal 99mTc-MDP scans, while at follow-up there were four children with negative [123I]MIBG studies who later died from disseminated neuroblastoma. All eight scans are considered false-negative. In 24 children, the [123I]MIBG revealed more extensive disease with 161 positive sites while the 99mTc-MDP scan showed only 100 positive sites; 34 of these sites were common to both studies. This study shows that underassessment of skeletal involvement by neuroblastoma occurred using [123I]MIBG scans and that one cannot therefore substitute [123I]MIBG for 99mTc-MDP bone scans in the staging of neuroblastoma.

3-Iodobenzylguanidine↗

Monoclonal antibody-mediated tumor regression by induction of apoptosis.

To characterize cell surface molecules involved in control of growth of malignant lymphocytes, monoclonal antibodies were raised against the human B lymphoblast cell line SKW6.4. One monoclonal antibody, anti-APO-1, reacted with a 52-kilodalton antigen (APO-1) on a set of activated human lymphocytes, on malignant human lymphocyte lines, and on some patient-derived leukemic cells. Nanogram quantities of anti-APO-1 completely blocked proliferation of cells bearing APO-1 in vitro in a manner characteristic of a process called programmed cell death or apoptosis. Cell death was preceded by changes in cell morphology and fragmentation of DNA. This process was distinct from antibody- and complement-dependent cell lysis and was mediated by the antibody alone. A single intravenous injection of anti-APO-1 into nu/nu mice carrying a xenotransplant of a human B cell tumor induced regression of this tumor within a few days. Histological thin sections of the regressing tumor showed that anti-APO-1 was able to induce apoptosis in vivo. Thus, induction of apoptosis as a consequence of a signal mediated through cell surface molecules like APO-1 may be a useful therapeutic approach in treatment of malignancy.

Animals↗

Cyclosporin in juvenile dermatomyositis.

Juvenile dermatomyositis in fourteen children who had not responded fully to steroids and other immunosuppressants and who had had chronic active disease for an average of 3 years was successfully treated with cyclosporin. Twelve patients had serious complications of the disease or of previous treatment. The response to cyclosporin included recovery of muscle strength and function and resolution of complications. It was possible to stop steroids or to reduce the steroid dose, which had previously been difficult, in all fourteen patients. In general, a low dose of cyclosporin (2.5-7.5 mg/kg daily) was sufficient and no serious side-effects were seen.

Child↗