In vivo tumour imaging employing regional delivery of novel gallium radiolabelled polymer composites.

BACKGROUND: Understanding the regional vascular delivery of particles to tumour sites is a prerequisite for developing new diagnostic and therapeutic composites for treatment of oncology patients. We describe a novel imageable 67Ga-radiolabelled polymer composite that is biocompatible in an animal tumour model and can be used for preclinical imaging investigations of the transit of different sized particles through arterial networks of normal and tumour-bearing organs. RESULTS: Radiolabelling of polymer microspheres with 67Ga was achieved using a simple mix and wash method, with tannic acid as an immobilising agent. Final in vitro binding yields after autoclaving averaged 94.7%. In vivo stability of the composite was demonstrated in New Zealand white rabbits by intravenous administration, and intrahepatic artery instillations were made in normal and VX2 tumour implanted rabbit livers. Stability of radiolabel was sufficient for rabbit lung and liver imaging over at least 3 hours and 1 hour respectively, with lung retention of radiolabel over 91%, and retention in both normal and VX2 implanted livers of over 95%. SPECT-CT imaging of anaesthetised animals and planar imaging of excised livers showed visible accumulation of radiolabel in tumours. Importantly, microsphere administration and complete liver dispersal was more easily achieved with 8 µm diameter MS than with 30 µm MS, and the smaller microspheres provided more distinct and localised tumour imaging. CONCLUSION: This method of producing 67Ga-radiolabelled polymer microspheres is suitable for SPECT-CT imaging of the regional vascular delivery of microspheres to tumour sites in animal models. Sharper distinction of model tumours from normal liver was obtained with smaller MS, and tumour resolution may be further improved by the use of 68Ga instead of 67Ga, to enable PET imaging.

99mTc-radiolabeled composites enabling in vivo imaging of arterial dispersal and retention of microspheres in the vascular network of rabbit lungs, liver, and liver tumors.

PURPOSE: Selective internal radiation therapy (SIRT) is an effective treatment option for liver tumors, using Y-90-loaded polymer microspheres that are delivered via catheterization of the hepatic artery. Since Y-90 is a beta emitter and not conveniently imaged by standard clinical instrumentation, dosimetry is currently evaluated in each patient using a surrogate particle, 99mTechnetium-labeled macroaggregated albumin (99mTc-MAA). We report a new composite consisting of 99mTc-labeled nanoparticles attached to the same polymer microspheres as used for SIRT, which can be imaged with standard SPECT. METHODS: Carbon nanoparticles with an encapsulated core of 99mTc were coated with the polycation protamine sulfate to provide electrostatic attachment to anionic polystyrene sulfonate microspheres of different sizes (30, 12, and 8 µm). The in vivo stability of these composites was determined via intravenous injection and entrapment in the capillary network of normal rabbit lungs for up to 3 hours. Furthermore, we evaluated their biodistribution in normal rabbit livers, and livers implanted with VX2 tumors, following intrahepatic artery instillation. RESULTS: We report distribution tests for three different sizes of radiolabeled microspheres and compare the results with those obtained using 99mTc-MAA. Lung retention of the radiolabeled microspheres ranged from 72.8% to 92.9%, with the smaller diameter microspheres showing the lowest retention. Liver retention of the microspheres was higher, with retention in normal livers ranging from 99.2% to 99.8%, and in livers with VX2 tumors from 98.2% to 99.2%. The radiolabeled microspheres clearly demonstrated preferential uptake at tumor sites due to the increased arterial perfusion produced by angiogenesis. CONCLUSION: We describe a novel use of radiolabeled carbon nanoparticles to generate an imageable microsphere that is stable in vivo under the shear stress conditions of arterial networks. Following intra-arterial instillation in the normal rabbit liver, they distribute in a distinct segmented pattern, with the smaller microspheres extending throughout the organ in finer detail, while still being well retained within the liver. Furthermore, in livers hosting an implanted VX2 tumor, they reveal the increased arterial perfusion of tumor tissue resulting from angiogenesis. These novel composites may have potential as a more representative mimic of the vascular distribution of therapeutic microspheres in patients undergoing SIRT.

Induction of chronic migraine phenotypes in a rat model after environmental irritant exposure.

Air pollution is linked to increased emergency department visits for headache and migraine patients frequently cite chemicals or odors as headache triggers, but the association between air pollutants and headache is not well understood. We previously reported that chronic environmental irritant exposure sensitizes the trigeminovascular system response to nasal administration of environmental irritants. Here, we examine whether chronic environmental irritant exposure induces migraine behavioral phenotypes. Male rats were exposed to acrolein, a transient receptor potential channel ankyrin-1 (TRPA1) agonist, or room air by inhalation for 4 days before meningeal blood flow measurements, periorbital cutaneous sensory testing, or other behavioral testing. Touch-induced c-Fos expression in trigeminal nucleus caudalis was compared in animals exposed to room air or acrolein. Spontaneous behavior and olfactory discrimination was examined in open-field testing. Acrolein inhalation exposure produced long-lasting potentiation of blood flow responses to a subsequent TRPA1 agonist and sensitized cutaneous responses to mechanical stimulation. C-Fos expression in response to touch was increased in trigeminal nucleus caudalis in animals exposed to acrolein compared with room air. Spontaneous activity in an open-field and scent preference behavior was different in acrolein-exposed compared with room air-exposed animals. Sumatriptan, an acute migraine treatment blocked acute blood flow changes in response to TRPA1 or transient receptor potential vanilloid receptor-1 agonists. Pretreatment with valproic acid, a prophylactic migraine treatment, attenuated the enhanced blood flow responses observed after acrolein inhalation exposures. Environmental irritant exposure yields an animal model of chronic migraine in which to study mechanisms for enhanced headache susceptibility after chemical exposure.

Isolated Left Trochlear Nerve Palsy Caused by Sphenoid Sinus Mucocele / 대한이비인후과학회지

Paranasal sinus mucoceles are an uncommon cause of isolated palsies of cranial nerves III, IV, and VI. The trochlear nerve has been reported to be less frequently affected than the abducens and oculomotor nerves. Isolated sphenoid sinus diseases may cause serious complications by involving adjacent vital structures such as the optic nerve, cavernous sinus, internal carotid artery, and cranial nerves III–VI. We report a case of a 76-year-old woman who presented to our emergency department with a chief complaint of acute double vision and headache. Her diplopia was diagnosed as left trochlear nerve palsy. Brain CT and MRI revealed expanding cystic lesions in both sphenoid sinuses with bony erosion of the left sinus wall. The patient underwent an endoscopic intranasal sphenoidotomy and recovered completely from diplopia at postoperative 2 months. The relationship between the trochlear nerve palsy and its anatomy is also discussed.

Formal plan for self-disclosure enhances supported employment outcomes among young people with severe mental illness.

AIM: Young people with mental illness experience high levels of unemployment, which can be related to stigma and discrimination. This may result from poor choices in disclosing personal information, such as their mental illness diagnosis, in the workplace. The aim of this study was to investigate the predictive validity of a formal plan to manage personal information (PMPI) during the early stages of supported employment. The focal question was: does the use of a brief structured PMPI lead to more employment outcomes for young people with a mental illness? METHODS: A sample of 40 young unemployed mental health service users (mean age 23.9 years), who were also attending employment services on the Gold Coast, was asked about their disclosure preferences. If they preferred not to disclose at all, they did not complete a plan for managing personal information. If they preferred to disclose some personal information, they were provided with assistance to complete a PMPI. Baseline information was gathered from two equal groups of 20 individuals. Employment status was ascertained at a 6-week follow-up interview. RESULTS: Those who completed a plan to manage their personal information had 4.9 times greater odds of employment at 6 weeks than those who preferred not to disclose any personal information. CONCLUSIONS: A formal PMPI has promising predictive validity with respect to job seekers not opposed to pragmatic forms of self-disclosure. Further research is needed to examine other properties of this decision-making tool.

Laryngeal Verruca Vulgaris: A Case Report and Review of Literature

Verruca vulgaris of the larynx (VVL) is an extremely rare disease that can be easily misdiagnosed as papillary keratosis, squamous papilloma or verrucous carcinoma, which would have led to needless operation. We experienced a case of VVL in a 66-year-old man with 1-year history of progressive hoarseness. Whitish lesions in both vocal cords were observed by using indirect laryngoscopy and completely removed via microlaryngeal surgery with CO2 laser.

Forming implementation intentions improves prospective memory in early psychosis.

The study examined whether individuals with early psychosis are impaired in prospective memory (PM), that is, remembering to execute a planned intention in the future, and whether implementation intentions can improve their PM performance. Thirty participants with early psychosis and 33 healthy controls were randomly allocated to either an implementation intentions or control condition and completed a computerised event-based PM task. Participants were also administered two standardised tests of PM and an abbreviated IQ test. Results demonstrated that individuals with early psychosis showed PM deficits relative to healthy controls on the computerised PM task and on some standardised measures of PM. The PM performance of the early psychosis group benefited from forming implementation intentions. Implementation intentions was concluded to be an effective strategy for improving PM performance in individuals with early psychosis.

Implementing evidence-based practices in supported employment on the Gold Coast for people with severe mental illness.

AIM: The aim of this project was to evaluate program outcomes following the implementation of an evidence-based approach to supported employment on the Gold Coast, Queensland, Australia. METHOD: A prospective observational design was used to evaluate employment outcomes and fidelity to the evidence-based principles and practices of a specialised form of supported employment. The cohort was defined as all those (n = 114) that entered the program at each of three sites within a 21-month period. Each participant was followed up for a minimum of six months. All three sites implemented the employment program by establishing a partnership between a non-government organisation and the Gold Coast community mental health service. RESULTS: The primary outcome variable was the proportion commencing competitive employment during the follow-up period from among those that commenced receiving assistance (the denominator). This ranged from 12% at Site C to 33.3% at Site A, and 37% at Site B. Fidelity to evidence-based principles was fair at Sites A and C and good at Site B. These results were below expectations based on international-controlled trials. The variation in site effectiveness appeared related to both fidelity to evidence-based principles and to other factors at each site, which could not be clearly identified. CONCLUSIONS: Delivering an effective supported employment program using an inter-agency partnership method is challenging. There are several roles in which occupational therapists can be involved that facilitate improving both the implementation and the effectiveness of supported employment for people with severe mental illness in Australia.

The uptake of soluble and nanoparticulate imaging isotope in model liver tumours after intra-venous and intra-arterial administration.

Delivery of chemotherapeutic drugs to tumours by reformulation as nanoparticles has often been proposed as a means of facilitating increased selective uptake, exploiting the increased permeability of the tumour vasculature. However realisation of this improvement in drug delivery in cancer patients has met with limited success. We have compared tumour uptake of soluble Tc99m-pertechnetate and a colloid of nanoparticles with a Tc99m core, using both intra-venous and intra-arterial routes of administration in a rabbit liver VX2 tumour model. The radiolabelled nanoparticles were tested both in untreated and cationised form. The results from this tumour model in an internal organ show a marked advantage in intra-arterial administration over the intra-venous route, even for the soluble isotope. Tumour accumulation of nanoparticles from arterial administration was augmented by cationisation of the nanoparticle surface with histone proteins, which consistently facilitated selective accumulation within microvessels at the periphery of tumours.

Clinical Experience of Kidney Transplantation in the Hallym University Hospital / 대한이식학회지

Renal transplantation has been adopted as the treatment of choices for most patients with a end stage renal disease. This is the presentation of our experience of renal transplantation at Hallym University Hospital. From March 1984 to July 1998, 207 cases of renal transplantations were performed, 15 cases out of which were lost during follow-up period and excluded from the study. The mean age of recipients was 37.1 years. The male to female ratio was 1.5:1. Eighty nine renal allografts (46.4%) were from living unrelated donors, 59 (30.7%) from living donors and 44 (22.9%) from cadaveric donors. As an immunosuppression theray, a triple regimen was used in 104 cases (54.2), a double regimen in 86 (44.8%) and a single regimen in one (0.5%). The overall rejection developed in 87 cases (45.3%). The rejection rate was 59.3% in renal allografts from living related donors, 37.1% from living unrelated donors and 43.2% from cadavaric donors. The OKT3 and the antilymphocyte globulin (ALG) were used for steroid resistent rejection in 8 and 2 cases, respectively. Post-transplant diabetes mellitus were noticed in 22 cases (11.5). The most common complication was infection (28.1%), and 11 recipeints (5.7%) died during follw-up period. Infection was the leading cause of mortality. The overall graft survival was 92.2% at 1 year span and 83.1% at 3 year span. The overall patient survival was 95.6% at 1 year span and 92.5% at 3 year span.

Relationship of Renal Implantation Biopsies and Acute Rejection during Immediate Posttransplantation Period / 대한이식학회지

Many factors can be recognized for the acute rejection such as: degree of HLA mismatching, cytokine gene expression, ischemic time, etc. Some authors have suggested the importance of early routine biopsy of renal allograft to predict acute rejection. This prospective study on renal implantation biopsies was performed to evaluate the relationship between the implantation biopsies and the acute rejection during the immediate post-transplantation period. From December 1996 to February 1998 implantation biopsies were performed on 46 renal allografts within 40~60 minutes after vascular anastomosis using tru-cut needle (18G). Two samples were obtained from transplanted kidney in each patient. Serial sections were stained for the light microscopic examination. The slides were evaluated for histologic features such as interstitial cellular infiltration, nephrosclerosis, tubular damage, glomerular neutrophil count (GL-PMN), and peritubular neutrophil count (PTC-PMN). Forty six biopsies were grouped into acute rejection group (R group, n=10) and non-rejection group (N group, n=36) during immediate posttransplantation period (1 month). Acute rejections were confirmed by ultrasonography guided biopsy. Histologic findings were classified according to Banff schema. The statistical analysis was performed by using Chi-Square Test and Spearman Rank Sum Test. During the immediate post-transplantation period, acute rejection developed in 10 cases (21.7%) of which 9 cases were the biopsy-proven rejection. The male to female ratio was 21:25. Recipients were ranged from 22 to 54 years old with a mean age of 38.2+/- 9.1. Original disease of recipient were chronic glomerulonephritis in 15 cases (32.6%), hypertension in 8 cases, diabetes mellitus in 3 cases, RPGN in 2 cases. Fifteen cases (32.6%) were of unknown etiology. The mean number of HLA mismatches was 4.6+/- 0.9 in R group, 4.7+/- 1.2 in N group, and the mean number of HLA-B & DR mismatches was 2.2+/- 0.4 in R group, 2.3+/- 0.7 in N group. The ratio of the living vs. cadaveric donors was 34:12. No statistical difference was observed between two groups in interstitial cellular infiltration, nephrosclerosis and tubular damage. The GL-PMN was 0.6 0.9 in R group, while 0.1 +/- 0.4 in N group. The PTC-PMN was 5.3+/- 3.3 in R group and 0.3+/- 1.1 in N group (p<0.05). The presence of more than five PTC-PMN count was related with the occurrence of acute rejection (p<0.01). In conclusion, the PTC-PMN of renal implantation biopsies is a possible predicting factor for acute rejection in this preliminary report.