Metabolic bone disease is present at diagnosis in patients with inflammatory bowel disease.

AIM: To establish whether bone disease is present at diagnosis in inflammatory bowel disease and to identify contributory metabolic abnormalities. METHODS: Newly diagnosed patients with inflammatory bowel disease (19 males, 15 females; mean age, 44 years; range, 17-79 years; 23 ulcerative colitis, 11 Crohn's disease) were compared against standard reference ranges and a control group with irritable bowel syndrome (eight males, 10 females; mean age, 40 years; range, 19-64 years). Bone mineral density (g/cm2, dual-energy X-ray absorptiometry: lumbar spine and femoral neck) and biochemical bone markers were measured. RESULTS: Femoral neck bone mineral density, T- and Z-scores (mean +/- s.d., respectively) were lower in inflammatory bowel disease patients than in irritable bowel syndrome controls (0.78 +/- 0.12 vs. 0.90 +/- 0.16, P = 0.0046; - 0.88 +/- 0.92 vs. 0.12 +/- 1.17, P = 0.0018; - 0.30 +/- 0.89 vs. 0.61 +/- 1.10, P = 0.0030). Lumbar spine bone mineral density and T-scores were also significantly lower in patients than controls (0.98 +/- 0.15 vs. 1.08 +/- 0.13, P = 0.0342; - 1.05 +/- 1.39 vs. - 0.14 +/- 1.19, P = 0.0304). Compared with controls, the urinary deoxypyridinoline : creatinine ratio was increased (7.66 vs. 5.70 nmol/mmol, P = 0.0163) and serum 25-hydroxy vitamin D was decreased (18.7 vs. 28.5 micro g/L, P = 0.0016); plasma osteocalcin and serum parathyroid hormone did not differ (P > 0.05). CONCLUSIONS: The bone mineral density is reduced at diagnosis, prior to corticosteroid treatment, in both Crohn's disease and ulcerative colitis. Our data suggest that this is attributable to increased resorption rather than decreased bone formation.

Imaging of abdominal infection using 99m Tc stannous fluoride colloid labelled leukocytes.

Radiolabelling of leukocytes using labelled phagocytosed technetium-99m (99mTc) colloidal radiopharmaceuticals has been reported as a method for imaging infection. This in vivo study compares the use of leukocytes labelled using 99mTc stannous fluoride colloid with leukocytes labelled using indium-111 (111In) oxinate. A total of 26 patients (10 male, 16 female; mean age 52 years, range 23-88 years) referred for the investigation of possible infection were studied using both leukocyte labelling methods simultaneously. Images were acquired 4h and 24h after re-injection of the labelled cells. The images were evaluated qualitatively by two nuclear medicine physicians. The results show a high degree of concordance between the techniques: 11 of the 28 images showed a focus of leukocyte accumulation with both techniques at 24h, and 13 out of 28 showed a normal appearance at 24h with both methods. In four cases the results were discordant; the 99mTc stannous fluoride colloid labelled leukocytes gave a false positive appearance at 24h in three patients and a false negative in one. In conclusion, colloid labelling of leukocytes offers a sensitive method for the detection of infective foci coupled with the high resolution imaging offered by 99mTc. It has the advantage over other in vitro labelling methods of being a simpler, non-labour-intensive procedure employing whole blood, and its use should be considered by departments that have limited facilities for in vitro leukocyte labelling.

Pulmonary disease and smoking: a case for health promotion.

Emphasis on smoking cessation for patients with chest diseases, especially those with chronic obstructive pulmonary disease (COPD), is not new, but the latest guidelines from the British Thoracic Society highlight the necessity of helping patients to stop smoking. Health professionals do not seem ready to take on this role. Smoking cessation needs to become a priority of health promotion for all patients with COPD. A recent training needs assessment underlined the fact that training and support for those undertaking this role require urgent attention.

Helping patients to master correct inhaler techniques: nursing role.

The use of inhalers is widespread for asthma and conditions such as chronic obstructive pulmonary disease and yet many people have difficulties in mastering correct inhaler technique. Elderly people and children have specific problems with inhaler use and require both targeted and appropriate help in order to improve their inhaler technique and minimize waste of inhaled medication and therefore lack of therapeutic effect. Nurses need to be able to not only demonstrate correct inhaler technique themselves, but also identify what is going wrong and be knowledgeable concerning the various options available. Frequent assessment of inhaler technique needs to become a regular feature of health promotion for all patients using these devices.

99mTc(V)DMSA quantitatively predicts 188Re(V)DMSA distribution in patients with prostate cancer metastatic to bone.

Rhenium-188 dimercaptosuccinic acid complex [188Re(V)DMSA], a potential therapeutic analogue of the tumour imaging agent 99mTc(V)DMSA, is selectively taken up in bone metastases in patients with prostate cancer. It would be helpful in planning palliative radionuclide therapy if 99mTc(V)DMSA could be used to predict tumour and kidney retention of 188Re(V)DMSA. The aim of this study was to determine the correlation between tumour-to-normal tissue ratios and kidney-to-soft tissue ratios of 99mTc(V)DMSA and 188Re(V)DMSA. This would determine whether a scan with 99mTc(V) DMSA could be used to identify patients for whom 188Re(V)DMSA treatment would be contra-indicated, and enable prediction of relative kidney and tumour radiation absorbed dose in 188Re(V)DMSA treatment. Ten patients with prostate carcinoma were recruited following observation of disseminated bone metastases on a recent 99mTc-hydroxydiphosphonate bone scan. Whole-body planar scans were obtained at ca. 4 h and 24 h after hydration and injection of 600 MBq 99mTc(V)DMSA, and a week later, at similar times after hydration and injection of 370 MBq 188Re(V)DMSA. A triple-energy window (TEW) scatter correction was applied to the 188Re scans. Counts per pixel were determined in regions of interest drawn over metastatic sites, kidneys and normal soft tissue. Tumour-to-soft tissue ratios were significantly lower (by a factor of approximately 0.8 after the TEW was applied) on 188Re scans than on 99mTc scans, but the two were highly linearly correlated both in all individual patients and in tumours pooled from all patients together both at 4 h and at 24 h. Kidney-to-soft tissue ratios were similarly correlated and were lower for 188Re than for 99mTc by a similar factor. Both tumour- and kidney-to-soft tissue ratios increased between 4 and 24 h but the latter increased more. In conclusion, only minor differences were seen between 99mTc and 188Re scans, and kidney-to-background ratios on 188Re scans were not higher than on 99mTc scans. These differences are insufficient to infer that they are due to a real difference in biodistribution, and they may be due only to different physical imaging characteristics. Thus 99mTc(V)DMSA scans are predictive of 188Re(V)DMSA biodistribution and could be used to estimate tumour and renal dosimetry and assess suitability of patients for 188Re(V)DMSA treatment.

Leukotrienes: new therapies and their influence on asthma.

Leukotriene receptor antagonists (LTRAs) are new therapies in asthma management which act to block the naturally occurring leukotrienes and improve lung function. It is clear from past research that many asthmatics dislike taking both oral and inhaled steroids and may probably welcome these new drugs simply because they are not steroid preparations. The oral route of LTRAs may be helpful for particular groups of patients, although LTRAs will not be suitable for all asthmatics. Their use so far has been largely as 'add-on' therapies for mild-to-moderate asthma with results that are promising in some patients but have been disappointing in others. Fewer side-effects may well improve medication compliance which has caused both unnecessary morbidity and has been linked to mortality in the past.

(99m)Tc(V)DMSA quantitatively predicts (188)Re(V)DMSA distribution in patients with prostate cancer metastatic to bone.

Rhenium-188 dimercaptosuccinic acid complex [(188)Re(V)DMSA], a potential therapeutic analogue of the tumour imaging agent (99m)Tc(V)DMSA, is selectively taken up in bone metastases in patients with prostate cancer. It would be helpful in planning palliative radionuclide therapy if (99m)Tc(V)DMSA could be used to predict tumour and kidney retention of (188)Re(V)DMSA. The aim of this study was to determine the correlation between tumour-to-normal tissue ratios and kidney-to-soft tissue ratios of (99m)Tc(V)DMSA and (188)Re(V)DMSA. This would determine whether a scan with (99m)Tc(V)DMSA could be used to identify patients for whom (188)Re(V)DMSA treatment would be contra-indicated, and enable prediction of relative kidney and tumour radiation absorbed dose in (188)Re(V)DMSA treatment. Ten patients with prostate carcinoma were recruited following observation of disseminated bone metastases on a recent (99m)Tc-hydroxydiphosphonate bone scan. Whole-body planar scans were obtained at ca. 4 h and 24 h after hydration and injection of 600 MBq (99m)Tc(V)DMSA, and a week later, at similar times after hydration and injection of 370 MBq (188)Re(V)DMSA. A triple-energy window (TEW) scatter correction was applied to the (188)Re scans. Counts per pixel were determined in regions of interest drawn over metastatic sites, kidneys and normal soft tissue. Tumour-to-soft tissue ratios were significantly lower (by a factor of approximately 0.8 after the TEW was applied) on (188)Re scans than on (99m)Tc scans, but the two were highly linearly correlated both in all individual patients and in tumours pooled from all patients together both at 4 h and at 24 h. Kidney-to-soft tissue ratios were similarly correlated and were lower for (188)Re than for (99m)Tc by a similar factor. Both tumour- and kidney-to-soft tissue ratios increased between 4 and 24 h but the latter increased more. In conclusion, only minor differences were seen between (99m)Tc and (188)Re scans, and kidney-to-background ratios on (188)Re scans were not higher than on (99m)Tc scans. These differences are insufficient to infer that they are due to a real difference in biodistribution, and they may be due only to different physical imaging characteristics. Thus (99m)Tc(V)DMSA scans are predictive of (188)Re(V)DMSA biodistribution and could be used to estimate tumour and renal dosimetry and assess suitability of patients for (188)Re(V)DMSA treatment.

The search for strategies to reduce nurse wastage.

Potential nurse candidates lack realistic information about the profession. The way nurses are interviewed for entry to the pre-registration diploma programme needs restructuring. The bursary system causes problems, especially for mature students with children.

A one-hour walk-in service for wrist trauma imaging.

We investigated the feasibility of rapid imaging of wrist trauma following casualty presentation and any subsequent effect on image quality and interpretability. All patients referred for wrist imaging were injected with 370 MBq 99Tcm-hydroxymethyl diphosphonate (HDP) and imaged 1, 2 and 3 h later. Palmar images were acquired on a 256 x 256 x 16 matrix using a high-resolution collimator, 140 keV photopeak and a 20% window. The images were scored qualitatively by four qualified observers in three categories: image quality, lesion detection and lesion localization. Statistical analysis indicated a significant improvement in scan quality with time, the mean difference (+/- standard error of the mean) between the 1 and 3 h scans being 0.81 +/- 0.07 (P = 0.001). No significant differences were seen in lesion detection (0.05 +/- 0.08; P = 0.51) or localization (0.14 +/- 0.08; P = 0.10). We conclude that imaging of wrist trauma is possible as early as 1 h post-injection of 99Tcm-HDP, although negative studies at 1 h require a 3 h image to maintain diagnostic accuracy.

Therapeutic implications of thymic uptake of radioiodine in thyroid carcinoma.

The management of 38 consecutive patients with differentiated thyroid carcinoma in the period 1991-1996, who each received at least one therapy dose of iodine-131, was reviewed, looking in particular at those in whom anterior mediastinal uptake was demonstrated on scans taken 3 and 7 days post-therapy. Such activity was noted in ten patients. On the basis of clinical follow-up, thyroglobulin measurement and radiological and other scintigraphic imaging, in nine of the ten patients the anterior mediastinal activity was attributed to physiological thymic uptake. Of those nine, all were under 50 years of age; seven were considered disease free, one had residual disease in the neck and one had distant metastases. Physiological uptake by the thymus was more prominent on the 7-day scans and in patients with low tumour volumes. For appropriate patient management it is essential to recognise that physiological uptake of 131I by the thymus in patients under 50 years of age is a potential cause of false-positive therapy scans.

Pentavalent rhenium-188 dimercaptosuccinic acid for targeted radiotherapy: synthesis and preliminary animal and human studies.

Pentavalent rhenium-188 dimercaptosuccinic acid [188Re(V)DMSA] is a beta-emitting analogue of 99mTc(V)DMSA, a tracer that is taken up in a variety of tumours and bone metastases. The aim of this study was to develop the kit-based synthesis of the agent on a therapeutic scale, to assess its stability in vivo, and to obtain preliminary biodistribution and dosimetry estimates, prior to evaluation of its potential as a targeted radiotherapy agent. The organ distribution of 188Re in mice was determined 2 h after injection of 3 MBq 188Re(V)DMSA prepared from eluate from a 188W/188Re generator. Three patients with cancer of the prostate and three with cancer of the bronchus, all with bone metastases confirmed with a standard 99mTc-hydroxymethylene diphosphonate (99mTc-HDP) scan, were given 370 MBq 188Re(V)DMSA and imaged at 3 h and 24 h using the 155-keV gamma-photon (15%). Blood and urine samples were collected to determine clearance and to analyse the speciation of 188Re. Organ residence times were estimated from the scans, and used to estimate radiation doses using MIRDOSE 3. In mice, 188Re(V)DMSA was selective for bone and kidney. In patients, it showed selectivity for bone metastases (particularly those from prostate carcinoma) and kidney, but uptake in normal bone was not significantly greater than in surrounding soft tissues. Of the normal tissues the kidneys received the highest radiation dose (0.5-1.3 mGy/MBq). The images were strongly reminiscent of 99mTc(V)DMSA scans in similar patients. High-performance liquid chromatography analysis of blood and urine showed no evidence of 188Re in any chemical form other than 188Re(V)DMSA up to 24 h. In conclusion, 188Re(V)DMSA and its 186Re analogue warrant further clinical assessment as generator/kit-derived agents for treatment of painful bone metastases. These agents should also be assessed in medullary thyroid carcinoma and other soft tissue tumours which have been shown to accumulate 99mTc(V)DMSA.

Drug therapy alternatives in the treatment of thyroid cancer.

Therapy of thyroid cancers is based on the removal of the primary disease by surgery, replacement of the hormonal deficiencies and subsequent therapy of the recurrent and metastatic disease. The metabolic characteristics of many thyroid tumors mean that radionuclide techniques have been used in the identification of sites of tumour and their subsequent therapy. Differentiated thyroid cancers, papillary, follicular and mixed papillary follicular, are treated by surgery--usually a total or subtotal thyroidectomy. Postoperatively, patients have thyroxine as a replacement therapy and to suppress thyroid-stimulating hormone production. Radioiodine therapy is often given to ablate the thyroid remnant. This allows (a) adequate follow-up of patients using thyroglobulin measurements and assessment scans as necessary, and (b) further therapy with radioiodine for metastatic disease. Patients with a short effective half-life of radioiodide may require higher activities or pharmacological methods of prolonging the retention half-times of iodine. The use of chemotherapy in this group of tumors is limited and at best provides palliation. The overall prognosis is good for differentiated thyroid cancer; papillary carcinomas have an 80 to 90% 10-year survival, whereas follicular tumors are associated with a 65 to 75% 10-year survival. Medullary carcinomas may be sporadic or familial, and some of the latter form part of a multiple endocrine neoplasia syndrome (MEN). Primary treatment is surgery, and total thyroidectomy is usually recommended since tumours are often multifocal. The use of radiolabelled metaiodobenzylguanidine (MIBG) and 111In octreotide as potential therapeutic agents has been explored and may be potentially useful in palliative care. Chemotherapy is of limited benefit. The 10-year survival for medullary carcinomas is 60 to 70%. Anaplastic tumours of the thyroid are usually aggressive, with a high mortality. Treatment is palliative by surgical debulking; some patients may benefit from local radiotherapy or occasionally chemotherapy. The use of therapeutic doses of radionuclides is well tolerated, although it may be associated with a variety of mostly transient adverse effects, including gastritis, thyroiditis and sialadenitis. Therapy with high activities of radioiodine require radiation protection precautions. Despite retreatment with radioiodine there appear to be no long term effects on the fertility of patients, and healthy children are born to women receiving this treatment. 131I remains perhaps the most specific cancer therapy available today and has few adverse effects. It is difficult to see any marked improvement being developed for differentiated thyroid cancer, with the possible exception of targeted gene therapy.

Plasmodium falciparum: effect of chemical structure on efficacy and specificity of antisense oligonucleotides against malaria in vitro.

Antisense oligodeoxynucleotides (AS ODNs) have shown promise both as potential anti-malarial chemotherapeutic agents and as a means for identifying genes critical for parasite survival. Because conventional ODNs containing phosphodiester (PO) groups are subject to rapid nuclease degradation, ODNs with phosphorothioate (PS) groups are commonly used. However, at high concentration, these lose target specificity, and in some animal models, they become toxic. We compared a variety of chemical modifications (PO, PS, PO-PS hybrids, 2'-O-methyl-2'-deoxy chimeras) and structural modifications (sequence alterations favoring self-stabilizing loop formation) for their ability to inhibit Plasmodium falciparum malaria cultured in vitro. All modifications were done using an AS ODN sequence targeted against dihydrofolate reductase thymidylate synthase (DHFR). Inhibition by PO-PS hybrids containing as few as three PS groups at the 3'- and 5'-ends did not differ significantly from that obtained using compounds containing all-PS groups. Similarly, inhibition by PS chimeric compounds containing 2'-O-methyl modifications did not differ significantly from that of conventional PS compounds. In contrast, while inhibition by PO-PS hybrid chimeras did not differ significantly from that of all-PS compounds at low concentrations, at 1 microM they inhibited parasite growth 25% less (P < 0.001) than all-compounds or PS 2'-O-methyl-2'-deoxy chimeras. Extension of the nucleotide sequence to increase stem-loop formation yielded two compounds which inhibited parasite growth about 20% more than unmodified compounds, though this difference was not significant. Furthermore, most of this increase appears to correlate with the greater number of PS groups associated with the increased ODN length. We conclude that limiting the number of PS groups and inclusion of PO 2'-O-methyl groups may yield compounds with high antisense activity but low non-sequence-dependent effects. Such compounds are currently being tested in vivo.

Health promotion in a hospital ward; reality or asking the impossible?

The hospital ward environment poses challenges for health promotion which will require not only increased multiprofessional collaboration, but a new appreciation of the capabilities of each member of the ward team. This paper discusses the application of one model of health promotion suitable for use in this setting and highlights the advantages of utilising such an approach.

Pentavalent 99Tcm-DMSA imaging in patients with bone metastases.

Pentavalent 99Tcm-dimercaptosuccinic acid (99Tcm-(V)DMSA) has an established role in imaging medullary thyroid carcinoma. There have been case reports of uptake in bone metastases. Our aims were to compare 99Tcm-(V)DMSA with 99Tcm-hydroxymethylene diphosphonate (99Tcm-HDP) in bone metastases, to assess its value in imaging of bone metastases, and to assess the prospects of the beta-emitting analogues 186/188Re-(V)DMSA as palliative agents for painful bone metastases. Ten patients confirmed by a 99Tcm-HDP bone scan to have bone metastases secondary to carcinoma of the prostate, lung or breast were injected with 99Tcm-(V)DMSA (600 MBq). Whole-body scans acquired at 3 and 24 h were compared with the 99Tcm-HDP bone scans. 99Tcm-(V)DMSA showed high soft tissue background, kidney retention and avid uptake in most bone metastases: 86% of bone lesions identified on bone scans were detected with 99Tcm-(V)DMSA. The lesion-to-normal ratios were comparable to or lower than those for 99Tcm-HDP at 3 h, but increased by 24 h. Instances of abnormal uptake in liver, primary lung tumour, lymph nodes and pleural effusion were observed. We conclude that 99Tcm-(V)DMSA is a tracer for bone metastases (with lower sensitivity than 99Tcm-HDP) and soft tissue tumours. If 186/188Re-(V)DMSA behave similarly, they may find use in therapy for soft tissue tumours and bony metastases.

Nurse education: attrition rates in the UK.

Student attrition is not a new phenomenon, and for many years governments have examined ways to avoid losing nurses from the profession. This article examines the problem from a historical perspective, seeks out examples of good practice and discusses their relevance to the present situation.