A comparative study of the safety and efficacy of dysprosium-165 hydroxide macro-aggregate and yttrium-90 silicate colloid in radiation synovectomy--a multicentre double blind clinical trial. Australian Dysprosium Trial Group.

The aim of our study was to compare the safety and efficacy of a new preparation, Dysprosium-165 Hydroxide Macroaggregate (165Dy) with Yttrium-90 Silicate (90Y) for radiation synovectomy of the knee in patients with RA and OA. A multicentre double blind clinical trial with subjects randomized to receive 165Dy or 90Y was undertaken in Sydney, Melbourne and Perth. Seventy knees of 59 patients were studied, using as clinical end point measurements, pain in the knee on walking, pain in the knee at rest and stiffness in the knee after rest. Cytogenetic damage, knee retention and extra-articular spread of the radionuclide to regional lymph nodes, liver, urine and blood were evaluated. There was no significant difference in clinical response in the two treatment groups for either RA or OA. Chromosomal changes occurred with equal frequency and the knee retention and extra-articular leakage of radiocolloids to regional lymph nodes and liver were comparable in the two groups. For radiation synovectomy of the knee, 165Dy is at least as safe and as effective as 90Y and has the advantage of a short half-life (2.334 h) and hence requires a shorter period of post-injection immobilization and hospitalization.

Surgery for severe constipation: the use of radioisotope transit scan and barium evacuation proctography in patient selection.

Nineteen women aged 19-64 years (median 38) with intractable constipation were assessed by Indium-111 DTPA colonic transit scan and barium evacuation proctogram. Patients were classified as having an isolated (I) or predominant disorder of colonic transit (II), a mixed disorder of colonic transit and rectal evacuation (III), a predominant disorder of rectal evacuation (IV) or normal colorectal emptying (V). Twelve patients fell into categories I and II and were considered suitable for surgery. Three responded to further vigorous aperient therapy and nine (32-55 years, median 38) underwent subtotal colectomy with ileorectal anastomosis at the level of the sacral promontory. Two patients required re-operation for suspected anastomotic leak. One patient required readmission on two occasions for small bowel obstruction. Follow up has been 2-21 months (median 16). Eight of the nine patients no longer take oral aperients. Eight patients have a satisfactory stool frequency of 2-8 per 24 h; the other patient has an ileostomy and incapacitating postprandial abdominal pain. Abdominal pain is troublesome in two other patients. Two patients require antidiarrhoeal therapy but none experience faecal incontinence. In severely constipated patients with a proven disorder of colonic transit but normal or near normal rectal evacuation subtotal colectomy provides excellent symptomatic relief.

Mapping the spread of epidural phenol in cancer pain patients by radionuclide admixture and epidural scintigraphy.

This study used a radionuclide imaging technique to map the spread and density contours of phenol in glycerin injected into the epidural space of cancer patients. Correlations were made between phenol injectate volume, sequence of injection, position of patient, and resultant epidural spread and analgesic outcome. Fifteen patients with cancer pain (average age of 61 years) were treated with serial epidural phenol in glycerin injections. Phenol in glycerin is miscible with [99mTc]sulfur colloid. An assumption was made that the admixture injected epidurally was inseparable prior to absorption and the spread was recorded by continuous gamma camera observations with computer collection for 30 min postinjection. The spread of injectate volumes of 2, 3, and 4 ml were compared and further correlations made between observed spread and sequence of injections (first to fifth in series within each patient) and position of patient. Small volumes of phenol may spread extensively in the epidural space (3 ml spreads a mean 13.6 segments) with wide variation among patients. Initial phenol injections spread further than subsequent injections. Maximum spread is achieved by 15 min postinjection and epidural distribution is mostly uniform, independent of patient position. Good analgesia was obtained in 14 patients (93%). Epidural neurolysis using serial injections of small volumes of phenol in glycerin is an effective, safe technique for cancer pain relief. Injectate volumes larger than 3 ml may be unnecessary and potentially dangerous.

Comparison of two yttrium-90 regimens in inflammatory and osteoarthropathies.

Two yttrium-90 (90Y) radiosynovectomy procedures were compared. One procedure, performed at the Royal Perth Rehabilitation Hospital (RPRH) required a shorter immobilisation time than that performed at the Sir Charles Gardiner Hospital (SCGH). There were no significant differences in outcome between the two procedures for the groups with inflammatory and osteoarthropathy. Thirty two patients (45 joints) with inflammatory arthropathy were treated (25 with rheumatoid arthritis, three with psoriatic arthritis, two with ankylosing spondylitis, and two with unspecified inflammatory arthropathy) and 40 patients (58 joints) with osteoarthropathy. A separate assessment of local lymph node spread in patients treated by the RPRH showed a minor spread of 90Y in one of 37 joints assessed. A marked improvement in the patient evaluation scores in the inflammatory arthropathy group at three months persisted at 12 months. Good lasting responses were more common in patients with inflammatory arthropathy with a normal joint or early radiological disease. A marked improvement in the pain and evaluation scores occurred at three months in the group with osteoarthropathy but had disappeared by six months after treatment.

Gallium lung scanning and bronchoalveolar lavage in crocidolite-exposed workers.

Gallium lung scanning is widely used to evaluate pulmonary inflammation in patients with interstitial lung disease but has not previously been reported in crocidolite-exposed workers. In order to characterize the pulmonary inflammation caused by crocidolite inhalation, GLS and BAL findings were related to chest x-ray film changes graded according to the ILO classification of roentgenograms of pneumoconioses. In individuals with roentgenographic evidence of asbestosis (CXR greater than or equal to 1/0, n = 15), 13 had a positive GLS and 13 had an abnormal BAL. In asbestos-exposed individuals with equivocal chest x-ray film changes (CXR 0/1, n = 12), six had a positive GLS and six had BAL changes (both GLS and BAL abnormal in three). In individuals with a normal chest x-ray film (CXR 0/0 n = 8), two had a positive GLS and two BAL changes (both abnormal in 1). These data demonstrate that most subjects with crocidolite-induced asbestosis have an abnormal GLS and BAL. In addition, many individuals with asbestos exposure and equivocal or no chest x-ray film changes have an abnormal GLS and/or BAL, suggesting the presence of active subclinical pulmonary inflammation in these individuals.

Preoperative assessment as a predictor of mortality and morbidity after lung resection.

To refine the functional guidelines for operability for lung resection, we prospectively studied 55 consecutive patients with suspected lung malignancy thought to be surgically resectable. Lung function and exercise capacity were measured preoperatively and at 3 and 12 months postoperatively. Preoperative pulmonary scintigraphy was used to calculate the contribution to overall function by the affected lung or lobe and to predict postoperative lung function. Pneumonectomy was performed in 18 patients, lobectomy in 29, and thoracotomy without resection in six. No surgery was attempted in two patients who were considered functionally inoperable. Cardiopulmonary complications developed in 16 patients within 30 days of surgery, including three deaths. The predictions of postoperative function correlated well with the measured values at 3 months. For FEV1, r = 0.51 in pneumonectomy (p less than 0.05) and 0.89 in lobectomy (p less than 0.001). Predicted postoperative FEV1 (FEV1-ppo), diffusing capacity (DLCO), predicted postoperative DLCO (DLCO-ppo) and exercise-induced arterial O2 desaturation (delta SaO2) were predictive of postoperative complications including death and respiratory failure. In patients who underwent pneumonectomy, the best predictor of death was FEV1-ppo. The predictions were enhanced by expressing the value as a percentage of the predicted normal value (% pred) rather than in absolute units. For the entire surgical group a FEV1-ppo greater than or equal to 40% pred was associated with no postoperative mortality (n = 47), whereas a value less than 40% pred was associated with a 50% mortality (n = 6), suggesting that resection is feasible when FEV1-ppo is greater than or equal to 40% pred.(ABSTRACT TRUNCATED AT 250 WORDS)

Surface labelling of Strongyloides ratti: stage-specificity and cross-reactivity with S. stercoralis.

Various methods of radioiodination were compared for their efficacy in labelling the surface of Strongyloides ratti infective larvae and adult worms. The Iodogen method was chosen as the optimal technique for this parasite. The surface location of 125-iodine was confirmed with light microscope autoradiography of transverse sections of labelled worms. Stage-specific surface components were identified when the sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) profiles of infective larvae and adult worms were compared. Labelled surface molecules were solubilized with either the non-ionic detergent Triton-X-100, the anionic detergents sodium deoxycholate (DOC) or sodium dodecyl sulphate (SDS), or the cationic detergent cetyl trimethyl-ammonium bromide (CTAB). The CTAB extract yielded most labelled proteins that retained their antigenicity in an immunoprecipitation assay with hyperimmune mouse sera. Immunoprecipitation analysis with stage-specific mouse sera revealed that the surface of infective larvae is immunogenic and that there are no cross-reactions with adult worms. Adult worms resident in the intestine were not found to be immunogenic and showed a complete absence of reactivity. Antigenic determinants shared between S. ratti and S. stercoralis were identified. Patients infected with S. stercoralis precipitated bands with molecular weights 32 and 34 kD which were not reactive with normal sera. These reactions suggest the potential usefulness of the surface of S. ratti as a source of diagnostic antigens.

Comparison of "direct" and "indirect" radionuclide cystography.

Thirty children were studied using both direct (catheter) and indirect techniques of radionuclide cystography. Of 54 ureters able to be compared, six showed vesico-ureteric reflux (VUR) on the direct study but were read as negative on the indirect cystogram, and five showed no reflux on the direct cystogram but were read as positive for VUR on the indirect study. (Sensitivity of 68% and specificity of 86%). Regarding ureters read as true positives on indirect study, if that ureter has ever shown reflux at any time, or if it drained a scarred kidney specificity was improved to 97% without changing the sensitivity. Concerns about the validity of indirect cystogram results and the ease of assessment and low radiation dose from the direct cystogram has made direct cystography our preferred technique.

Isotope bone scans in the assessment of children with hip pain or limp.

Bone scans from 43 children referred with hip pain of uncertain cause were reviewed. The bone scan was abnormal in 36 patients: normal in 7. In 12 the findings were diagnostic: osteomyelitis, osteoid osteoma, osteomyelitis with septic arthritis, Perthes' Disease and juvenile chronic arthritis. Twenty-four patients had abnormal scans including diffuse peri-articular increase and of these 18 had transient synovitis. Immobilisation and trauma accounted for the remainder. Isotope bone scans have been found to be a valuable investigation in children presenting with hip pain or limp, where the x-rays may appear normal or nondiagnostic.

Loss of surface coat by Strongyloides ratti infective larvae during skin penetration: evidence using larvae radiolabelled with 67gallium.

The optimal conditions for labelling infective larvae of Strongyloides ratti with 67gallium citrate were determined. Radiolabelled larvae were injected s.c. into normal and previously infected rats. The distribution of radioactivity in these animals was compared with that in rats infected subcutaneously with a similar dose of free 67Ga by using a gamma camera linked to a computer system. Whereas free 67Ga was distributed throughout the body and excreted via the hepatobiliary system, the bulk of radioactivity in rats injected with radiolabelled larvae remained at the injection sites. Direct microscopical examination of these sites, however, revealed only minimal numbers of worms. When rats were infected percutaneously with radiolabelled larvae, it was found that most radioactivity remained at the surface, despite penetration of worms. When infective larvae were exposed to CO2 in vitro and examined carefully by light microscopy, loss of an outer coat was observed. It was concluded that infective larvae lose an outer coat on skin penetration.

The assessment of response to therapy of bone metastases in breast cancer.

Serial bone scans, x-rays and records of bone pain were reviewed in order to determine the relative contributions of these parameters in the assessment of response of bone metastases to treatment. Twenty-seven patients with abnormal bone scans due to metastatic breast cancer were studied. Ten of the patients showed an early temporary flare on bone scan including five with apparent new lesions. Confirmation that such new lesions did not denote progressive disease was provided by subsequent improvement in symptoms and reduction in intensity and number of lesions on a follow-up bone scan, without any change in systemic therapy. Serial x-rays were found to be unreliable as a sole method for assessing response to therapy or disease progression, as in only seven of the 27 patients could a definitive radiological assessment of response be made. In only one patient did x-rays improve the accuracy of the scan by distinguishing between a healing flare and progressive disease. In contrast, this distinction was made in seven of the 10 patients on the basis of improvement in bone pain at the time of the flare. The other 3 patients had no bone pain prior to therapy or at the time of the flare. Tentative response criteria incorporating bone scan, x-ray and symptoms are suggested. The criteria incorporate recognition of the fact that new lesions appearing on a bone scan within six months of initiation of therapy may comprise part of a healing flare response.

Serial bone scans in the assessment of response to therapy in advanced breast carcinoma.

Twenty-seven patients taking part in an advanced breast cancer trial in Australia and New Zealand were studied to assess the predictive value of serial bone scans as an indicator of response to therapy. The report of serial bone scans in 20 of the 27 patients correctly reflected the clinical outcome. Of the 20 patients, all had an initial subjective response and 15 had an objective response. Of the seven patients whose bone scan report did not reflect the clinical situation, five had increased uptake in known lesions and new lesions and one had increased uptake in known lesions only within six months of commencing therapy. These scan reports indicated progression of disease rather than a healing or "flare" response which was later proved to exist. One patient had clinical progression of bone metastases which was confirmed by x-ray but was not reflected in the bone scan until months later. Clinical progression of disease was accurately reflected in the bone scans of 11 of 12 patients. Recognition that a "'flare" effect in the first months of therapy may also cause new lesions to be seen should enhance the accuracy of bone scintigraphy.

Beta-adrenergic blockade and peripheral vascular disease.

Hypertension and ischaemic heart disease are common accompaniments of peripheral vascular disease, and are often treated with beta-blocking drugs. Previous reports, however, have suggested that these drugs may aggravate peripheral vascular disease. A study was designed to investigate this problem with claudication-distance and skin and muscle blood-flow studies (as determined by 133Xe clearance) as indices for assessment. In all 11 patients who presented with features of peripheral vascular disease and were found to be taking beta-blocking drugs, administration of the drug was stopped, blood pressure was controlled by other means, and the situation was reassessed four weeks later. There was a significant improvement in claudication distance and in resting and post-exercise muscle blood flow after withdrawal of the drug. This held for both cardioselective and nonselective beta-blockers. It is recommended that this group of drugs be avoided in the treatment of patients with peripheral vascular disease.

The role of bone scanning in the assessment of prostatic carcinoma.

Fifty new cases of carcinoma of the prostate were assessed prior to treatment to determine the incidence of bony metastases. The radioisotope bone scan was the most sensitive method of detecting metastases and of localising them. It was twice as accurate as the serum acid phosphatase estimation. Skeletal X-rays were the least accurate method. Forty-six per cent of patients had abnormal bone scans at presentation. The histological grade of the tumour correlated well with the bone scan. The higher the grade, the more likely was the bone scan to be abnormal. There is need for greater accuracy in detecting metastases, and the bone marrow acid phosphatase estimation, either alone or in conjunction with the bone scan, may provide this accuracy.