The psychological and social impact of camp for children with chronic illnesses: a systematic review update.

Advances in medicine have reduced mortality among children with complex medical conditions, resulting in a growing number of young patients living with chronic illnesses. Despite an improved prognosis, these children experience significant psychosocial morbidity, such as depression and anxiety. Therapeutic summer recreation camps have been proposed as an intervention to enhance quality of life among these children. The purpose of this systematic review was to assess the psychosocial impact of camp for children with chronic illnesses. A systematic review of central databases was undertaken using key words, and a rating tool ­ the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for Quantitative Studies ­ was employed to rate methodological quality. 21 studies were included in this systematic review. Although overall methodological quality was weak, camp participation appeared to offer short-term psychosocial benefits on some parameters in children with a variety of chronic illnesses. There was some consistency in improved social outcomes, such as social interaction and acceptance. Based on the available evidence, it is premature to make robust claims regarding the psychosocial impact of camp as a therapeutic intervention. Theoretically informed camp programs, long-term follow-up, and incorporating camp-based messaging into routine hospital care,may enhance the utility of camp as a potential psychosocial intervention in paediatrics.

Pre-operative assessment of axillary lymph node status in patients with breast adenocarcinoma using intravenous 99mtechnetium mAb-170H.82 (Tru-Scint AD).

Immunoscintigraphy of the axilla has potential utility for the diagnostic and prognostic assessment of patients with breast adenocarcinoma. mAb-170H.82 is a murine monoclonal antibody (mAb) derived against synthetic Thomsen-Friedenreich (TF) antigen. Tru-Scint AD, a 99mTc-mAb-170H.82 immunoconjugate, has previously been shown to localize in various human adenocarcinomas. The purpose of this study was to evaluate the accuracy of this immunoconjugate in the pre-operative assessment of axillary lymph nodes in patients with known breast adenocarcinoma. Sixteen patients with documented primary breast cancer were injected intravenously with 1 mg of immunoconjugate (radioactivity 1.8 GBq) and imaged 22-24 hrs post-injection. Both planar and single photon emission computed tomographic (SPECT) images were obtained and reviewed in a blinded fashion. Imaging results were compared with surgical and pathological findings. Seven of 16 patients were found to have histologically positive axillary nodes: 5 of these sites were detected by immunoscintigraphy (sensitivity = 71%). Nine patients had pathologically disease-free axillary nodes: only 1 of these was misidentified as positive by immunoscintigraphy (specificity = 89%). These results suggest that immunoscintigraphy with 99mTc-mAb-170H.82 has promise in the detection of axillary lymph node involvement in patients with breast cancer. Further studies are warranted to define the role of immunoscintigraphy in axillary staging.

Management of the hot thyroid nodule.

BACKGROUND: Solitary hyperfunctioning nodules of the thyroid gland are usually viewed as benign. They may present with autonomous euthyroidism but are of concern for potential progression to hyperthyroidism. Various methods of treatment are worthy of consideration. PATIENTS AND METHODS: Forty-five patients with solitary hot thyroid nodules verified by radioisotope scintiscanning were selected for treatment. Thirty-one underwent surgery, usually partial thyroidectomy. Eight euthyroid patients received no treatment, 5 underwent therapy with radioactive iodine (RAI), and 1 received thyroid suppression treatment. The cases were assessed retrospectively. RESULTS: Thyroidectomy patients had no morbidity, were well, and showed 1 Hürthle cell tumor and 5 coincidental small malignancies associated with benign hot nodules, including a contralateral cancer. Untreated patients showed continuance of good health, but nodules persisted and 1 Graves' orbititis occurred. The RAI-treated patients had persistent nodularity, improved function, and 1 case of hyperparathyroidism. Thyroid feeding only caused iatrogenic toxicity and was discontinued. CONCLUSIONS: There are various techniques for managing the hot nodule. Nonsurgical methods may be effective, but can result in persistent nodularity and iatrogenic sequelae. Excision had no morbidity in this series and was effective in providing immediate relief of problems present and potential.

Problems of delivery of monoclonal antibodies. Pharmaceutical and pharmacokinetic solutions.

Monoclonal antibodies to tumour-associated antigens have great theoretical potential for the specific targeting of radioactivity and anti-neoplastic agents to tumours. The clinical success of monoclonal antibody-based cancer diagnosis and therapy depends, however, on solving a number of pharmacokinetic delivery problems. These include: (i) slow elimination of monoclonal antibodies from the blood and poor vascular permeability; (ii) low and heterogeneous tumour uptake; (iii) cross-reactivity with normal tissues; (iv) metabolism of monoclonal antibody conjugates; and (v) immunogenicity of murine forms in humans. As a result of extensive pharmaceutical and pharmacokinetic research conducted over the past 10 to 15 years, several potential solutions to these delivery problems have been identified. Blood concentrations of antibody conjugates may be reduced through regional administration, the use of antibody fragments, interventional strategies and various pre-targeting techniques. Tumour uptake may be increased through administration of higher doses, or the use of agents to increase tumour vascular permeability. Tumour retention of antibody conjugates may be improved by inhibition of metabolism, by using more stable linkage chemistry. Alternatively, normal tissue retention may be decreased through the use of metabolisable chemical linkages inserted between the antibody and conjugated moiety. Very small antigen-binding fragments and peptides that exhibit improved tumour penetration and more rapid elimination from the blood and normal tissues have been prepared by genetic engineering techniques. Chimeric (mouse/human) and human monoclonal antibodies have been developed to circumvent the problem of immunogenicity. Future research will continue to be focused on improvements in the design of monoclonal antibodies for tumour targeting, with the ultimate goal of finally uncovering the 'magic bullet' envisioned by Paul Ehrlich almost a century ago.

Scintigraphic flare in skeletal lymphoma.

The authors describe the bone scan flare phenomenon in a patient with treated skeletal lymphoma. This was confirmed by both gallium scanning and computed tomography. If serial bone scintigraphy is used for assessing the treatment response of lymphoma, the flare phenomenon must be recognized.

Immunoscintigraphy of human colon cancer xenografts in nude mice using a second-generation TAG-72 monoclonal antibody labelled with 99Tcm.

Monoclonal antibody CC83 is a second-generation high-affinity antibody directed against the TAG-72 antigen in colorectal cancer. Our objectives were to evaluate the biodistribution, pharmacokinetics and imaging properties of CC83 labelled with 99Tcm via a modified Schwartz technique. The immunological integrity of 99Tcm-CC83 was evaluated by size-exclusion FPLC and by determining the immunoreactive fraction in vitro against bovine submaxillary mucin. The biodistribution of 99Tcm-CC83 up to 24 h postinjection was evaluated in nude mice bearing subcutaneous LS174T human colon cancer xenografts. Blood radioactivity data was fitted to a one-compartment pharmacokinetic model. Images of tumour-bearing mice were obtained at 17-24 h postinjection with 99Tcm-CC83. 99Tcm-CC83 was eluted as intact immunoglobulin by FPLC analysis and the mean immunoreactive fraction was 0.49 +/- 0.15. Tumour uptake at 24 h postinjection was 11.2 +/- 4.1% i.d.g-1. Radioactivity in the blood was eliminated rapidly with a half-life of 8 h and tumour:blood ratios were > 2:1 at 24 h postinjection. LS174T tumours were successfully imaged in 3/3 mice. In vitro studies showed instability of 99Tcm-CC83 when challenged with cysteine and glutathione but not metallothionein, suggesting a metabolic route for the 99Tcm antibody in vivo. We conclude that CC83 labelled directly with 99Tcm retains its immunological integrity and capability specifically to target subcutaneous LS174T human colon cancer tumours hosted in nude mice. These results further suggest that 99Tcm-CC83 may have potential for imaging colorectal cancer in humans.

Osteopenia in patients with above knee amputation.

Using dual energy x-ray absorptiometry, we studied 16 male patients with unilateral above knee amputations (AKA) with a mean age of 48 years (range, 23 to 66 years) who were full-time prosthetic users for more than 5 years. All prostheses were ischial weight bearing. All 16 subjects were found to have normal bone density in their spines and in the normal femurs when compared to nonamputation controls. However, a significant decrease of mean femoral neck bone density was found on the amputated side (0.68g/cm2, range, 0.52 to 1.01) when compared to the normal side (1.01g/cm2, range, 0.75 to 1.20) (p < .05). The mean bone density percentage difference between the two sides was 28% (range, 4% to 48%). There was a significantly negative correlation between the patient's age at the time of amputation and the severity of osteopenia (-0.73; p < 0.05).

Pre-operative localization of 25 consecutive parathyroid adenomas: a prospective imaging/surgical correlative study.

The successful diagnosis and surgical treatment of primary hyperparathyroidism due to parathyroid adenoma benefits significantly, in our experience, from a process of pre-operative imaging localization of the parathyroid adenoma. This prospective study evaluates a window of 25 consecutive patients who underwent pre-operative imaging localization prior to successful unilateral parathyroidectomy for parathyroid adenoma. All parathyroid adenomas were successfully localized by imaging, and subsequently documented photographically in surgical correlation, and pathologically confirmed. All patients were cured biochemically. Ultrasound accurately localized 92% of adenomas (100% in the neck and extrathyroidal) while radionuclide subtraction scanning identified 60% of a smaller subset. Both DSA and CT were successful in the two cases utilized, and MRI demonstrated four of five adenomas. The high yield of these pre-operative localization studies should make them an important consideration in the routine evaluation of patients undergoing surgery for possible parathyroid adenoma. Their usefulness in directing a conservative unilateral operation may result in time and cost savings, as well as reduced surgical exposure.

Iodine-123-IBZM dopamine D2 receptor and technetium-99m-HMPAO brain perfusion SPECT in the evaluation of patients with and subjects at risk for Huntington's disease.

Huntington's disease (HD) is pathologically characterized by neuronal loss and neuroreceptor alterations in the striatum, including a reduction in dopamine receptor density. We evaluated the clinical usefulness of 123I-iodobenzamide (IBZM) D2 receptor SPECT imaging and 99mTc-hexamethylpropyleneamineoxime (HMPAO) brain perfusion SPECT imaging by studying four early symptomatic HD patients, 20 asymptomatic subjects at risk for HD and 22 controls. Striatal D2 receptor binding and perfusion were measured semiquantitatively by calculating striatum-to-frontal cortex IBZM and HMPAO uptake ratios, respectively. The control IBZM ratio (1.58 +/- 0.06) declined with age at 1.5% per decade (r = -0.58, p < 0.005), whereas the HMPAO ratio (1.15 +/- 0.05) did not. All four symptomatic patients had decreased IBZM ratios and three patients also had decreased HMPAO ratios. Five of 20 at-risk subjects had decreased IBZM ratios and two subjects also had decreased HMPAO ratios. Three of the five at-risk subjects showed subtle nonchoreic neurological abnormalities. Decreased striatal D2 receptor binding thus may be detected by IBZM-SPECT in the asymptomatic as well as symptomatic groups, and these changes were more marked than perfusion deficits detected by HMPAO-SPECT. IBZM-SPECT thus appears to be a promising method for early diagnosis and preclinical detection of HD.

Dopamine D2 receptor SPECT imaging: basic in vivo characteristics and clinical applications of 123I-IBZM in humans.

The purposes of this study are to evaluate the utility of kit formulation, the basic in vivo characteristics, and clinical usefulness of dopamine D2 receptor imaging with 123I-(S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrodinyl)m ethyl]- benzamide (123I-IBZM). We studied 22 normal controls, 3 early symptomatic Huntington's disease patients, and 1 patient with visual hallucination on and off neuroleptics. 123I-IBZM could be conveniently prepared with a high degree of purity from a kit, but with relatively low radiochemical yield. We demonstrated 123I-IBZM receptor binding equilibrium by performing serial SPECT scanning in a normal volunteer. The basal ganglia/frontal cortex (BG/FC) ratios plateaued after the specific binding reached equilibrium approximately 60 minutes after injection. The BG/FC ratio declined significantly with age. The ratios for the Huntington's disease patients were significantly lower than those for normal controls. The images of the patient off neuroleptic therapy showed dramatically increased BG activity compared with those obtained while on therapy. The BG/FC ratio provides an estimate of Bmax/Kd and hence the receptor density. It appears important to perform SPECT early in the equilibrium phase and at a fixed time after injection to obtain significantly high signal to noise ratios. 123I-IBZM is an ideal tracer for SPECT including a rotating gamma camera type which can provide estimates of the receptor density objectively by calculating the BG/FC ratio, and is a promising agent for the investigation of dopamine D2 receptors in clinical conditions.

Compartmental analysis of the pharmacokinetics of radioiodinated monoclonal antibody B72.3 in colon cancer patients.

Sixteen patients with colorectal cancer were administered 37-74 MBq (1 mg) of radioiodinated B72.3 monoclonal antibody. Pharmacokinetic analysis was carried out on plasma and urine samples. Elimination from the plasma was biexponential with a mean T1/2 alpha of 3.7 h and T1/2 beta of 62.4 h. The plasma clearance was fit to a two-compartmental model. This was combined with a previously reported model for radioiodine to construct a composite model. There was a good correlation (r = 0.952) between the model-predicted and observed excretion of radioiodine suggesting that the composite model is compatible with the pharmacokinetics of the radiolabelled antibody.

Radioimmunodetection of colorectal cancer metastases with 131I-labeled monoclonal antibody B72.3: a pilot study to determine efficacy of detection and pharmacokinetics.

We performed radioimmunoscintigraphy (RIS) and/or pharmacokinetic (PCK) studies in 12 patients with primary or metastatic colorectal carcinoma, utilizing an intravenous administration of 1-4 mCi (1 mg) of 131I-B72.3 monoclonal antibody. Metastatic lesions were correctly identified in 4/8 patients by RIS. Two patients with small lesions (> 2 cm diameter) had a false-negative RIS scan. Two patients had a true-negative RIS scan. Optimal images were obtained at 1 week postinjection. PCK studies showed that the plasma clearance of 131I-B72.3 was biexponential with an alpha-phase half-life ranging from 0.5 to 7.1 hr and a beta-phase half-life ranging from 47.5 to 85.3 hr. Systemic and renal clearance data indicated that 131I-B72.3 was cleared very slowly and almost entirely by deiodination. This pilot study was conducted to gain an understanding of the pharmacokinetics of this radiolabeled antibody. On the basis of these data, we are now studying second-generation antibodies as part of our long-range objectives to incorporate them in early detection and treatment protocols.

Comparative dual label study of first and second generation antitumor-associated glycoprotein-72 monoclonal antibodies in colorectal cancer patients.

Radiolabeled first-generation anti-tumor-associated glycoprotein-72 (TAG-72) monoclonal antibody (MAb), B72.3, has proven useful in detecting primary and secondary colorectal carcinoma. It has been anticipated that the development of second-generation, higher affinity, anti-TAG-72 MAbs, CC49 and CC83, would be of greater use in cancer detection and of value in radioimmunotherapy of human cancer. We compared the pharmacokinetics, biodistribution, and immune responses of 131I-labeled CC49 and CC83 to 125I-labeled B72.3 by preoperatively coninjecting dual-labeled MAbs into 16 colorectal cancer patients. The imaging properties of radiolabeled CC49 and CC83 were also assessed. Pharmacokinetics of all three MAbs were identical, and there were no differences in the uptake of any of three MAbs in tumor and normal tissues. Maximum tumor uptake was 0.0041% of the injected dose/g for 125I-B72.3, 0.0024% for 131I-CC49, and 0.0029% for 131I-CC83. Radiolabeled CC49 and CC83 detected most known tumor sites on scintigrams without any clear advantage for either MAb. Nonspecific splenic and testicular uptake was frequently observed. Anti-idiotypic human anti-mouse antibody responses were seen more frequently with B72.3 than with CC49 or CC83. We conclude that higher affinity, radiolabeled anti-TAG-72 MAbs can detect colorectal cancer but do not penetrate these tumors more effectively than B72.3. Improvements in tumor detection and radioimmunotherapeutic strategies will likely require the administration of smaller fragments of MAb molecules or novel delivery systems rather than the continued development of higher affinity MAbs.

Neuroanatomical localization for clinical SPECT perfusion brain imaging: a practical proportional grid method.

For the purpose of facilitating anatomical localization in interpretation of 99Tcm-hexamethylpropyleneamine oxime (HMPAO) brain single photon emission tomographic (SPECT) scans, a stereotaxic proportional grid system was applied in the form of an interactive computer program. This method takes advantage of a rotating gamma camera system which permits planar scout imaging for the determination of anatomical reference lines, and standardization of tomographic slices for brain size. Using measurements made on a lateral planar HMPAO image, proportional grids were constructed onto standardized transaxial images. This method was implemented for 33 clinical HMPAO SPECT studies. It required less than 15 min of an operator's time. This simple and practical neuroanatomical localization technique can be instrumental as an aid to the interpretation of routine clinical HMPAO SPECT images.

Assessment of regional cerebral perfusion by 99Tcm-HMPAO SPECT in chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is a severely disabling illness of uncertain aetiology. It is characterized by a chronic, sustained or fluctuating sense of debilitating fatigue without any other known underlying medical conditions. It is also associated with both somatic and neuropsychological symptoms. Both physical and laboratory findings are usually unremarkable. Regional cerebral blood flow (rCBF) was assessed in 60 clinically defined CFS patients and 14 normal control (NC) subjects using 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) single photon emission computed tomography (SPECT). Compared with the NC group, the CFS group showed significantly lower cortical/cerebellar rCBF ratios, throughout multiple brain regions (P < 0.05). Forty-eight CFS subjects (80%) showed at least one or more rCBF ratios significantly less than normal values. The major cerebral regions involved were frontal (38 cases, 63%), temporal (21 cases, 35%), parietal (32 cases, 53%) and occipital lobes (23 cases, 38%). The rCBF ratios of basal ganglia (24 cases, 40%) were also reduced. 99Tcm-HMPAO brain SPECT provided objective evidence for functional impairment of the brain in the majority of the CFS subjects. The findings may not be diagnostic of CFS but 99Tcm-HMPAO SPECT may play an important role in clarifying the pathoaetiology of CFS. Further studies are warranted.

'Reverse crescent pattern' on SPECT brain perfusion scan in chronic subdural hematoma.

A SPECT brain perfusion scan was performed on a patient who had symptoms of dementia. The SPECT scan showed marked crescentic medial displacement of the left cerebral hemisphere ("reverse crescent pattern"), and mildly decreased cortical perfusion in the affected hemisphere. Crossed cerebellar diaschisis was not present. On x-ray CT, the underlying abnormality was found to be a unilateral chronic subdural hematoma causing a significant mass effect. A reverse crescent pattern without crossed cerebellar diaschisis on SPECT brain perfusion scan in patients with dementia may suggest the diagnosis of chronic subdural hematoma.

Parotid gland and parapharyngeal space imaging--the surgical significance.

Wise head and neck surgeons, for whom parotid gland surgery constitutes a substantial portion of their case load, make full use of the radiologist and cytologist in arriving at a rational pre-operative diagnosis. They utilize the skill of these allied consultants to qualify (by histology) and quantify (by staging) diffuse and mass lesions of the parotid gland (and subjacent parapharyngeal space) in order to evolve an effective surgical, radiation or other treatment plan. They understand the basic principles of diagnostic imaging and apply them to the clinical problem at hand. They minimize diagnostic and intra-operative "surprises", reduce intra-operative and post-operative complications and generally have a more "informed" patient and patient's family. The purpose of this manuscript is to discuss a contemporary role for diagnostic imaging in neoplastic (and other) diseases of the parotid gland and subjacent parapharyngeal space. Not all lesions of the parotid gland require imaging, although a pre-operative clinical photograph, including evidence of facial nerve function, is always welcome. Other lesions may need diagnostic imaging, from simple to complex and sophisticated, depending upon the problem. Properly used, effective and selective diagnostic imaging can improve the surgeon's confidence by providing a more realistic provisional diagnosis and a better pre-operative staging process and treatment plan, thereby avoiding the surgically unexpected and facilitating prognosis.

Decision making in thyroid and parathyroid surgery: the influence of imaging.

Surgical decision making is essentially based on experience, augmented by a management philosophy. In this manuscript we review concepts of thyroid and parathyroid surgical decision making in relation to diagnostic imaging input. These two endocrine glands have crucial anatomic associations, but very different pathologic conditions; it is the specific pathologic considerations that ultimately determine the decision-making process. For us, diagnostic imaging has enabled a more effective surgical decision-making process through thorough pre-operative planning. The strategy for parathyroid surgery is based upon the pathologic localization obtained by high resolution ultrasound. Thyroid surgical strategy is more heavily influenced by experience, and our policy is total thyroidectomy for all malignant and benign tumors with airway compression.

Contribution of nuclear medicine to the diagnosis and management of extracranial head and neck diseases (excluding thyroid and parathyroid).

Nuclear medicine contributes to the diagnosis and management of extracranial head and neck diseases through the physiological information it provides. In addition to thyroid and parathyroid indications, radionuclide studies, i.e., bone and 67Gallium citrate scans are helpful in diagnosing and treating head and neck malignancies. Positron emission tomography with 18F-fluorodeoxy-glucose evaluates tumor glucose metabolism before and after treatment. Triphase bone scintigraphy enables early detection of osteomyelitis of the skull base, and its management requires 67Gallium-citrate or 111Indium-WBC scintigraphies. Salivary gland scintigraphy is the only functional imaging test of salivary tissue and should be utilized more in the diagnosis of submandibular duct obstruction and in the evaluation of preserved parenchymal function after recurrent infections.