Induction of cyclin-dependent kinase 5 in the hippocampus by chronic electroconvulsive seizures: role of [Delta]FosB.

The transcription factor DeltaFosB is induced in the hippocampus and other brain regions by repeated electroconvulsive seizures (ECS), an effective antidepressant treatment. The unusually high stability of this protein makes it an attractive candidate to mediate some of the long-lasting changes in the brain caused by ECS treatment. To understand how DeltaFosB might alter brain function, we examined the gene expression profiles in the hippocampus of inducible transgenic mice that express DeltaFosB in this brain region by the use of cDNA expression arrays that contain 588 genes. Of the 430 genes detected, 20 genes were consistently upregulated, and 14 genes were downregulated, by >50%. One of the upregulated genes is cyclin-dependent kinase 5 (cdk5). On the basis of its purported role in regulating neuronal structure, we studied directly whether cdk5 is a true target for DeltaFosB. Upregulation of cdk5 immunoreactivity in the hippocampus was confirmed by Western blotting in the DeltaFosB-expressing transgenic mice as well as in rats treated chronically with ECS. Chronic ECS treatment also increased, in the hippocampus, the phosphorylation state of tau, a microtubule-associated protein that is a known substrate for cdk5. A 1.6 kb fragment of the cdk5 promoter was cloned, and activity of the promoter was found to be increased after overexpression of DeltaFosB in cell culture. Moreover, mutation of the single consensus activator protein-1 site contained within the cdk5 promoter fragment completely abolished activation of the promoter by DeltaFosB. Together, these results suggest that cdk5 is one target by which DeltaFosB produces some of its physiological effects in the hippocampus and thereby mediates certain long-term consequences of chronic ECS treatment.

99Tcm-(tin) colloid scans in the evaluation of renal transplant rejection.

Technetium-99m-(tin) colloid uptake in renal transplants was quantified to evaluate rejection. A dynamic acquisition following i.v. injection of 110 MBq of this radiopharmaceutical enabled quantification of 15 to 20 min transplant uptake (PU), in terms of percentage of an injected dose after allowing for attenuation in the patient. An uptake ratio (UR) i.e. the ratio of 15 to 20 min uptake over the 0 to 5 min uptake was also derived. Normal values were obtained in 20 stable functioning transplants (normal PU less than or equal to 1%, normal UR less than or equal to 0.7). In 66 patients, PU and UR were compared with clinical, biochemical, histological and radiological, evidence of rejection. A sensitivity of 70% and specificity of 85% was obtained for this 99Tcm-(tin) colloid study in the diagnosis of renal transplant rejection.

99Tcm-polyclonal IgG and 99Tcm nanocolloid scans in orthopaedics: a comparison with conventional bone scan.

The bone scan is sensitive in detection of active bone/joint lesions. A normal bone scan virtually excludes the presence of an inflammatory process with high precision, but the poor specificity of bone scans is well known. In recent years, various new agents including 99Tcm-hexamethylpropylene amine oxime (HMPAO)-labelled white blood cells, nanocolloid, polyclonal IgG, anti-granulocyte antibody, 111In-labelled IgG, leucocytes, chemotactic peptides etc. have been widely evaluated in inflammatory imaging, especially in the orthopaedic context. This study was undertaken to compare the usefulness of 99Tcm-nanocolloid and 99Tcm-polyclonal IgG in the detection of focal bone/joint inflammation. Twenty-seven patients with a common presentation of bone/joint pain resulting from various pathologies were included in the study. A total of 47 lesions were imaged. The overall sensitivity and specificity of both nanocolloid scan and IgG scan were identical with 95% sensitivity and 100% specificity, in detecting inflammatory foci. However, specificity dropped to 18% with nanocolloid scans and 16% with IgG scans when an attempt was made to distinguish noninfective from infective inflammatory processes; thus neither type of scan permits differentiation between septic and nonseptic inflammatory processes with sufficient accuracy. As both nanocolloid and IgG scans are equally sensitive and specific in detecting inflammation, the choice of type of scan will depend on cost, imaging time and availability of the radiopharmaceutical.

Massive bleeding from a Dieulafoy-like lesion of the rectum in a burns patient.

Gastrointestinal haemorrhage is a rare but well-recognised complication of extensive burns, the site of haemorrhage usually being in the upper gastrointestinal tract. The case of an 18-year old female patient who developed sudden massive rectal bleeding 1 month after suffering 45% body surface area burns is presented. The source of the haemorrhage was a Dieulafoy-type lesion at the anorectal junction associated with mucosal ulceration, a cause of bleeding not previously described in a patient with major burns. Angiographic embolisation failed to control the haemorrhage and surgical arrest was required, following which the patient made a complete recovery with no recurrence of bleeding. Haemorrhage from the lower gastrointestinal tract is rarely associated with major burns but may be significant when it occurs. The aetiology is unclear but sepsis, mucosal ischaemia and ulceration may be implicated.

Severe gastrointestinal bleeding resulting in total gastrectomy in a patient with major burns--a case report.

Gastrointestinal hemorrhage is a known but rare complication of major burns. This case report describes the management of this potentially life threatening problem in a young adult with 45% body surface area burns who developed massive gastrointestinal-tract bleeding. The patient required a total gastrectomy that was complicated by a burst abdomen. Despite undergoing a series of major insults. the patient survived and was eventually discharged from hospital with an acceptable level of morbidity. The problems faced by the burn centre team and the issues involved in the decision making process are discussed in the management of this unusually devastating complication.

Reconstructive challenges in the management of a rare case of sphenoid osteosarcoma--a case report.

Primary osteosarcoma of the sphenoid bone is an extremely rare condition. This paper presents a case of a lady with recurrent oesteosarcoma of the sphenoid bone who had resection of the tumour via a combined neurosurgical and craniofacial procedure and reconstruction with a free flap and bone graft. It details the diagnosis, treatment and follow-up of this unusual condition.

Radionuclide imaging in primary hyperparathyroidism using 99mTc sestamibi--four case reports.

Radionuclide imaging using the 99mTc sestamibi either singly or as a subtraction technique with pertechnetate is a recent and reliable method in localising parathyroid adenomas prior to surgery. This is of use in pre-operative planning, as well as in failed first neck exploration. Four local patients with primary hyperparathyroidism whose parathyroid adenomas were localised by this scintigraphy are presented. The value and limitations of this imaging modality are discussed.

Intermediate probability lung scans (IPLS): retrospective review of 82 cases.

OBJECTIVE: In the light of a reported 30-40% prevalence of pulmonary embolism (PE) in intermediate probability lung scans (IPLS) based on results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study, we examined the frequency of documented PE in 82 patients with IPLS, the management strategy employed in these patients with regards to additional imaging (e.g. further evaluation with venous sonography or spiral computed tomographic angiography (CTA)), anticoagulation therapy, and subsequent follow-up outcomes. METHOD: Retrospective review of the medical records of 82 patients with intermediate probability ventilation-perfusion (V/Q) lung scans from January 1998 to July 1999. RESULTS: 14.1% of V/Q scans were reported as having an intermediate probability of PE. 72% of IPLS were subject to further evaluation with venous Doppler ultrasound and/or CTA, and 39% of these patients had evidence of thrombo-embolic disease. All patients with imaging evidence of thromboembolic disease were started on anticoagulation therapy. In addition, 19 patients were treated based on clinical judgement. Amongst the 35 patients who were not treated, 17 (49%) were based on clinical findings without further imaging. There was no mortality on follow-up of 28 cases of untreated IPLS. CONCLUSION: The majority of IPLS will have further imaging, out of which over one-third will have thrombo-embolic disease. Approximately half of IPLS cases will receive anticoagulation therapy. No mortality or PE was found on follow-up of patients who were not treated.

Effect of lithium and oral thyrotrophin-releasing hormone (TRH) on serum thyrotrophin (TSH) and radioiodine uptake in patients with well differentiated thyroid carcinoma.

Oral thyrotrophin-releasing hormone (TRH) and lithium were given to patients on follow-up for well-differentiated thyroid carcinoma to see their effect on serum thyrotrophin level (TSH) and radioiodine (I-131) uptake (RAIU). The study was randomised and doubled-blinded and consisted of a total of 19 patients in 3 groups. Group 1 received placebo and TRH, group 2 received lithium and placebo, and group 3 received lithium and TRH. Serum TSH and RAIU at 24 hours were measured before, and after treatment, with TRH, lithium, and/or placebo. In group 1, mean (+/-SEM) TSH increased from 48.9 (+/-15.2) mU/l to 148.2 (+/-48.0) mU/l (p < 0.05); in group 2, the change of 24.9 (+/- 15.9) mU/l to 31.7 (+/-14.1) mU/l in TSH was not statistically significant; and in group 3, TSH increased from 108.1 (+/-13.8) mU/l to 187.0 (+/-39.1) mU/l (p < 0.05). However, despite the significant change in TSH, there was no significant increase in I-131 uptake in any group: 7.70% to 10.43%, 7.15% to 7.43% and 2.49% to 2.61%, in groups 1, 2 and 3 respectively (p > 0.05). We conclude that while oral TRH will increase endogenous serum TSH significantly, there is no significant increase in I-131 uptake. Lithium was not an useful adjunct in increasing serum TSH or I-131 uptake in these patients.

Prospects for tumour imaging with radiolabelled antibodies.

An ideal diagnostic imaging method in cancer management should be one which surveys the entire body for occult or small tumour foci in a single procedure. Imaging with radiolabelled antibodies appears to have such potential if the limiting factors which we have encountered in the last 40 years can be completely eliminated. These factors include antibody-dependent factors, radionuclide-dependent factors, host-dependent factors and imaging modality-dependent factors. Advances in immunology and bio-genetic engineering have enabled production of various antibody fragments and genetically engineered antibody molecules (i.e. chimeric/humanized antibodies and the single-chain antigen binding protein), giving a promise of overcoming the problem of cross-reactivity and host immuno-response. The rapid development in radiopharmacy and labelling chemistry has led to the establishment of various pre-targetted methods which are aimed to improve the tumour to non-tumour ratio. The recent success of producing Tc99m labelled monoclonal antibodies preparation in a kit form has certainly encouraged its clinical applications and made antibody imaging a less tedious task. The progression in computer technology has made "image fusion" possible and hence improve the accuracy of anatomical localization of tumour foci in antibody imaging. It would appear possible to overcome most, if not all, of the limiting factors mentioned above in the near future. The prospect of radiolabelled antibodies in tumour imaging is promising and the dream of a "magic bullet" will soon be fulfilled.

Eccrine porocarcinoma: a case report.

We report a 58-year-old Chinese female who presented with a pigmented skin lesion on the right thigh, associated with a single ipsilateral inguinal lymph node without distant metastases detected. A wide excision of the tumour, split skin graft coverage and an en-bloc ipsilateral superficial groin dissection was performed. Histopathology revealed malignant skin adnexal tumour or porocarcinoma, with nodal metastases. She is presently at six months follow-up without any recurrence.

Role of technetium-99m sestamibi in localisation of thyroid cancer metastases.

Technetium-99m sestamibi (MIBI) is a routinely used myocardial perfusion imaging agent. We have studied groups of patients with differentiated thyroid carcinoma, in order to evaluate the usefulness of this agent in localising regional neck and nodal disease and metastases. There are three groups of patients. Group 1 consisted of patients with known nodal disease or metastases (22 patients) and with raised serum thyroglobulin levels (Tg). Group 2 comprised patients with normal I-131 scans and normal Tg levels (nine patients). Non-thyroid malignancies (six patients) comprised an additional group 3. In group 1, the MIBI scan showed 47 sites of metastases, while the I-131 scan revealed 49 sites. The MIBI scan was positive in two patients where the I-131 scan was negative, while in two other patients, the MIBI study was negative whereas the I-131 scan was positive. In group 2, 6/9 patients had no disease, 2/9 had thyroid remnants, and 1/9 had a fresh primary lung tumour, unrelated to the earlier thyroid cancer. All of them had normal MIBI scans. In group 3, two patients with lung cancer and two with breast cancer and metastases had normal MIBI scans. A further two patients with nasopharyngeal cancer (NPC) had mildly increased MIBI localisation in neck nodes and bone metastases. In summary, Tc-99m sestamibi appears to be as good as I-131 in search for thyroid carcinoma metastatic spread, especially nodal disease and this tracer does not localise well in the primary or metastases of other cancers.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatobiliary scintigraphy in the diagnosis of biliary atresia--a Singapore experience.

In recent years, 99mTechnetium IDA hepatobiliary scintigraphy has been widely accepted as a highly sensitive and fairly accurate test in the diagnosis of biliary atresia and evaluation of neonatal jaundice. Over a period of 4 years from 1982 to 1986, a total of 110 paediatric patients had undergone 99mTechnetium IDA hepatobiliary scans in our department for prolonged neonatal jaundice. Their scans were reviewed to evaluate the role of this nuclear imaging technique in the diagnosis of biliary atresia. There were 43 true positive and 49 true negative scans. No false negative scan was encountered in our study. Hence the sensitivity was 100%. However, out of the 110 scans, there was misdiagnosis of biliary atresia in 18 cases. This gave a specificity of 73% with an accuracy of 84%. From this study we concluded that 99mTechnetium IDA imaging is a highly sensitive test in the screening of biliary atresia. However, its specificity is possibly limited by the short half life of the radioisotope 99mtechnetium in delayed 24 hr imaging and we feel that this could be improved by using slightly higher doses than what we are presently using.

Radionuclide measurement of liquid and solid gastric emptying in normal subjects in Singapore.

Scintigraphic methods for liquid and solid gastric emptying were utilised to study normal patterns in 21 volunteers. Of these, 19 had solid emptying studies and 14 had liquid emptying studies. The liquid study lasted 1/2 hour, while the solid study was for 1 hour. The gastric emptying half-time (T 1/2), as well as percentage retention at 15 minutes (liquids), and at 60 minutes (for solids) were noted. The time-activity curves were also corrected for tissue attenuation. Results indicated normal average liquid emptying T 1/2 to be 14.2 minutes, while that for solids was 116 minutes.

Radionuclide detection of dialysate leakage in patients on continuous ambulatory peritoneal dialysis.

While continuous ambulatory peritoneal dialysis (CAPD) offers several advantages over haemodialysis in patients with end-stage renal disease, several complications have been recognised. The intraperitoneal instillation of dialysate increases intra-abdominal pressure and consequently predisposes to leaks and herniations through defects in the abdominal wall. This can lead to disruption of CAPD therapy. Peritoneal scintigraphy with Tc99m colloid has been used to identify such leaks of dialysate. This report analyses the clinical role of peritoneal scintigraphy in patients on the CAPD programme in the Singapore General Hospital. The results of 25 scans performed over a two-and-a-half year period were correlated with clinical and surgical findings. The clinical presentations of suspected dialysate leakage were varied, but can be broadly classified into three subsets for this analysis: (A) swellings confined to the inguinal and genital region, (B) peri-catheter, umbilical and incisional swellings, and (C) diffuse pattern of swellings in the abdominal wall, pelvic and genital region. In group A, the scan proved to be clearly helpful, correctly identifying 10/10 inguinal hernias, all of which resolved after herniorrhaphy. In group B, the scan correctly identified 7/9 leaks and hernias in the ventral abdominal wall. There was one false negative scan in a patient with a peri-catheter leak, and an equivocal result in another with fluid leakage in the lower anterior abdominal wall. In group C, which presented the greatest difficulty in clinical diagnosis, 2/3 cases were correctly diagnosed by scintigraphy. An equivocal result was seen in a patient who had had multiple operations for recurrent incisional hernias.(ABSTRACT TRUNCATED AT 250 WORDS)

Technetium-99m (Tc-99m) diphosphono-propanedicarboxylic acid bone tracer uptake and Tc-99m sestamibi distribution in cardiac amyloidosis--a case report.

It has long been recognised that significant bone tracer localisation in the myocardium is a good indicator for amyloid involvement of the heart in the clinical context of systemic amyloidosis. In this case report, although myocardial tissue diagnosis of amyloidosis was not made, the massive myocardial uptake of bone tracer strongly suggested the presence of amyloid infiltration in the heart, and this finding eventually led to the histological diagnosis of familial amyloid polyneuropathy by skin and sural nerve biopsy. Interesting findings were noted in the single photon emission computerised tomography (SPECT) studies of the myocardium with Technetium-99m diphosphono-propanedicarboxylic acid bone agent and Technetium-99m sestamibi myocardial perfusion agent. Such findings suggest that there is a lack of correlation between the intensity of myocardial uptake of bone tracer and viability of the myocardium, and that amyloid will not deposit in infarcted myocardial tissue.

Evaluation of technetium-99m ciprofloxacin (Infecton) in the imaging of infection.

INTRODUCTION: The aim of this study was to evaluate the usefulness of technetium-99m (Tc-99m) ciprofloxacin in imaging inflammation/infection. The ciprofloxacin for labelling, as a kit, was obtained from St Bartholomew's Hospital in London. MATERIALS AND METHODS: Patients were injected intravenously with Tc-99m ciprofloxacin and imaging was done at 10 minutes, 4 hours and 24 hours if necessary. Tomographic images (SPECT) were obtained in a few patients. Ninety-six patients were studied using Tc-99m ciprofloxacin. Forty-eight patients had bone scans and 22 had Tc-99m IgG scans. Eight patients were imaged using Tc-99m HMPAO labelled white blood cell, and bacteriological culture results were available in 24 patients. Organisms cultured included Acinetobacter baumanii, Streptococcus, Staphylococcus aureus, Pseudomonas, Klebsiella, Blastococidia, Methicillin-resistant S. aureus, Salmonella and Candida. RESULTS: Findings were evaluated against microbiology, alternative imaging modalities and clinical outcome. There were 47 true positives, 33 true negatives, 5 false positives and 11 false negatives, giving a sensitivity of 81% and specificity of 87%. The positive and negative predictive values were 90% and 75%, respectively. There were no side effects and the scan was particularly useful in the evaluation of painful joint prosthesis to exclude infection. Repeat studies on 8 patients given antibiotics over a long period were very useful in deciding on termination of the antibiotic treatment.

Tomographic thallium-201 stress scintigraphy in the evaluation of coronary artery disease.

57 patients with chest pain, had tomographic thallium-201 stress scintigraphy (TTSS), and coronary angiography within three months of the TTSS. The exercise images were compared with delayed images obtained at 3 hours post-exercise. The sensitivity and specificity of locating individual coronary artery disease was 88% and 100% for disease of left anterior descending artery (LAD), 89% and 83% for right coronary artery disease (RCA), and 24% and 96% for left circumflex artery (LCX) disease. Other than for LCX disease, our results compare favourably with other reports. The overall accuracies are 91%, 86% and 60% for LAD, RCA and LCX disease respectively.

The role of alternative therapy in the management of partial thickness burns of the face--experience with the use of moist exposed burn ointment (MEBO) compared with silver sulphadiazine.

INTRODUCTION: Conventional management of partial thickness facial burn wounds includes the use of silver sulphadiazine dressings. Silver sulphadiazine forms an overlying slough that makes wound healing assessment difficult. Moist exposed burn ointment (MEBO) has been proposed as the ideal burn wound dressing both for burns of the face and other sites. Proponents of MEBO claim that it accelerates wound healing and results in scarless wound healing and at the same time reduce bacterial colonisation and the need for analgesics. We present here our experience with MEBO in the management of partial thickness burns of the face. MATERIALS AND METHODS: One hundred and fifteen patients with partial thickness burns were randomly assigned to conventional treatment or MEBO. Out of this, 112 were analysed. Thirty-nine patients sustained facial burns; 17 received MEBO and 22 received silver sulphadiazine. Patients were followed up daily until the burn wounds were reduced by 75% of original body surface area (BSA). RESULTS: In patients with facial burns, MEBO was similar to silver sulphadiazine therapy with respect to rate of wound healing. Minimal slough was present over the wounds in MEBO-treated wounds resulting in clearer assessment of healing progression. CONCLUSIONS: Advantages of MEBO as compared to silver sulphadiazine in the management of partial thickness burns of the face include convenient change of dressing and easier assessment of healing progression. This suggests that MEBO is a useful alternative therapy for partial thickness burns of the face.

Technetium-99m sestamibi for the assessment of myocardial salvage following reperfusion therapy in acute myocardial infarction.

INTRODUCTION: Reperfusion therapy with either thrombolysis or angioplasty has been shown to be beneficial in acute myocardial infarction. Tc-99m sestamibi is a myocardial tracer that can be used to assess myocardial salvage because of its property of very limited redistribution. MATERIALS AND METHODS: To assess the feasibility of this technique locally, Tc-99m sestamibi was injected before and after reperfusion therapy with angioplasty (n = 11) or streptokinase (n = 18) in 29 patients with acute myocardial infarction (anterior = 25, inferior = 4). Single-photon emission computed tomography (SPECT) was performed within 4 hours of reperfusion and repeated 5 to 7 days later. RESULTS: Initial perfusion defect size ranged from 6% to 78% (mean 36.3 +/- 18.7%), and final defect size from 0% to 50% of the left ventricle (mean 23.7 +/- 14.8%, P < 0.001). Patients with proximal left anterior descending artery (LAD) lesions had larger defects compared to those with mid LAD lesions (mean defect size 52% for pLAD versus 28% for mLAD, P < 0.013). However, there were wide variations in initial defect size (myocardium at risk) for a given infarct-related artery location. The mean decrease in defect size was 12% in the 28 patients with patent arteries compared to only 2% in the patient with an occluded artery (47% to 45%). There was no significant difference in amount of salvage between patients who had thrombolysis (mean 13%, P = 0.0003) and patients who had percutaneous transluminal coronary angioplasty (PTCA) (mean 12%, P = 0.005). CONCLUSIONS: Assessment of myocardial salvage is feasible using Tc-99m sestamibi SPECT imaging. It allows for quantitation of myocardium at risk and the amount of myocardial salvage, which is not possible by angiography alone.