Cherenkov light production from the α-emitting decay chains of 223Ra, 212Pb, and 149Tb for Cherenkov Luminescence Imaging.

Cherenkov Luminescence Imaging (CLI) is a new method to image radioactive therapeutic and diagnostic agents, primarily in preclinical studies. This study used Geant4 and Python to generate the predicted Cherenkov light production as a function of time for a set of isotopic chains of interest for targeted alpha therapy: 223Ra, 212Pb, and 149Tb. All are shown to produce substantial Cherenkov light, though time delays between initial decays and the production of Cherenkov light requires caution in interpreting CLI.

The potential for Cerenkov luminescence imaging of alpha-emitting radionuclides.

Targeted α-emitting drugs are promising for cancer therapy, but cannot be effectively imaged by conventional techniques. Cerenkov luminescence imaging (CLI) has previously been shown capable of imaging ß(+)- and ß(-)-emitting radionuclides in vivo and could have the potential to image α-emitters. Cerenkov light production from α-emitters is through Compton scattering and from farther down the decay chain. This causes the Cerenkov production to vary in time and depend on sample geometry, complicating the interpretation of CLI images. We used the simulation toolkit Geant4 to predict the Cerenkov light output from five α-emitting radionuclides that have therapeutic potential: (225)Ac, (230)U, (213)Bi, (212)Bi and (212)At. We found that (225)Ac, (213)Bi and (212)Bi produced an order of magnitude more Cerenkov light than (18)F. However, the light from (225)Ac is delayed from the initial decay, possibly decreasing the correlation of the drug and light source. This indicates that CLI will not be helpful in the development of some α-emitting drugs.

Observation of two-neutrino double-beta decay in 136Xe with the EXO-200 detector.

We report the observation of two-neutrino double-beta decay in (136)Xe with T(1/2) = 2.11 ± 0.04(stat) ± 0.21(syst) × 10(21) yr. This second-order process, predicted by the standard model, has been observed for several nuclei but not for (136)Xe. The observed decay rate provides new input to matrix element calculations and to the search for the more interesting neutrinoless double-beta decay, the most sensitive probe for the existence of Majorana particles and the measurement of the neutrino mass scale.

A simple radionuclide-driven single-ion source.

We describe a source capable of producing single barium ions through nuclear recoils in radioactive decay. The source is fabricated by electroplating (148)Gd onto a silicon α-particle detector and vapor depositing a layer of BaF(2) over it. (144)Sm recoils from the alpha decay of (148)Gd are used to dislodge Ba(+) ions from the BaF(2) layer and emit them in the surrounding environment. The simultaneous detection of an α particle in the substrate detector allows for tagging of the nuclear decay and of the Ba(+) emission. The source is simple, durable, and can be manipulated and used in different environments. We discuss the fabrication process, which can be easily adapted to emit most other chemical species, and the performance of the source.

A prospective study of change in visual function in patients treated with pegylated interferon alpha for hepatitis C in the UK.

BACKGROUND: Hepatitis C virus and interferon treatment have been associated with retinopathy. Baseline and ongoing assessment by ophthalmologists have therefore been advocated in previous studies. Our experience suggests that the incidence is low, with no or negligible impact of pegylated interferon alpha on actual visual function. This study was conducted to determine whether ophthalmic assessment is necessary in such patients. METHODS: The study was a prospective case series of 52 patients (104 eyes). Visual acuity, contrast sensitivity, colour vision, visual field by perimetry and fundal assessment were measured at baseline and at 3 and 6 months post commencement of interferon alpha treatment. RESULTS: Forty-two men and ten women were followed. No patients reported any subjective visual symptoms. The mean changes in right and left logarithmic minimal angle resolution (LogMAR) visual acuity were negligible between baseline and 6 months (0.05 (SD 0.13) and 0.10 (SD 0.12), respectively). Mean changes in contrast sensitivity and colour vision were also negligible. Of all eyes monitored by serial perimetry for the full follow-up period and deemed to have reliable tests, none developed visual field defects. One patient appeared to develop nasal field defects within 3 months of commencing treatment but failed to attend for repeat testing. No patients developed optic disc changes or permanent fundal changes over the follow-up period. CONCLUSION: In contrast to previous studies in America and south-east Asia, our findings based on a UK cohort suggest that routine ophthalmic screening is not essential for patients with hepatitis C treated with pegylated interferon alpha who have no subjective visual complaints.

Effect of acetaminophen on the accuracy of glucose measurements obtained with the GlucoWatch biographer.

BACKGROUND: Improved glycemic control significantly reduces long-term microvascular complications of diabetes mellitus associated with chronic hyperglycemia. The GlucoWatch biographer is designed to facilitate intensive diabetes management by providing automatic, frequent, and noninvasive glucose readings up to three times per hour for as long as 12 hours. METHODS: The device extracts glucose through intact skin using reverse iontophoresis and measures the extracted glucose with an electrochemical biosensor. A clinical trial was performed to assess the effect of acetaminophen, a potential interference for traditional blood glucose meters, on the accuracy of the GlucoWatch biographer in adult subjects with diabetes (n = 18). One thousand milligram doses of acetaminophen were administered to subjects in two groups: one to achieve Cmax (peak acetominophen concentration) at the time of biographer calibration and the other to achieve Cmax during the measurement period. The biographer readings were compared to serial fingerstick blood glucose measurements. RESULTS: Time profiles over 9 hours show close tracking of the biographer glucose results with fingerstick blood glucose measurements for all groups. The mean difference between the two measurements is between 8 and 12 mg/dL for all groups. The mean absolute value of the relative difference is less than 20%, and more than 93% of the points were in the clinically acceptable (A+B) region of the Clarke Error Grid. No statistically significant differences were found for any accuracy measurement across all groups. CONCLUSIONS: The GlucoWatch Biographer provides frequent measurements of glucose over a 12-hour period with high accuracy. No effect of therapeutic dosage of acetaminophen on the accuracy of the glucose readings was found.

The GlucoWatch biographer: a frequent automatic and noninvasive glucose monitor.

The GlucoWatch (Cygnus, Inc, Redwood City, CA, USA) biographer provides automatic, frequent and noninvasive blood glucose measurements for up to 12 h. The device extracts glucose through intact skin where it is measured by an amperometric biosensor. Clinical trials in a variety of environments have shown that the biographer provides accurate and precise glucose measurements when compared with serial fingerstick blood glucose measurements. Mean difference between these measurements was 0.26 mmol/L in the home environment (r = 0.80). Over 94% of biographer readings were in the clinically acceptable A+B region of the Clarke Error Grid. A slight positive bias is observed for the biographer readings at low glucose levels. Biographer precision, as measured by coefficient of variation (CV)%, is approximately 10%. The low glucose alert function of the biographer was able to detect up to 75% of hypoglycaemic episodes with a low false alert level. Skin irritation, characterized by erythema and oedema was either nonexistent or mild in over 87% of subjects and resolved in virtually all subjects without treatment in several days. The GlucoWatch biographer has been shown to be a safe and effective method to track glucose level trends and patterns, which should enable improved glycaemic control for many patients.

Correlation of fingerstick blood glucose measurements with GlucoWatch biographer glucose results in young subjects with type 1 diabetes.

OBJECTIVE: The purpose of this study was to compare measurements of glucose obtained via iontophoretic extraction with the GlucoWatch automatic glucose biographer (Cygnus, Inc., Redwood City, CA) with capillary blood glucose values that were determined 1) in a controlled outpatient clinic setting and 2) in a home setting. RESEARCH DESIGN AND METHODS: There were 76 GlucoWatch biographers used on 28 different young adults (21 women and 7 men) with type 1 diabetes (age 30.9 +/- 6.9 years and duration of diabetes 18.4 +/- 8.1 years [mean +/- SD]) in a controlled outpatient clinic setting. Some subjects participated on multiple days. Subjects wore two GlucoWatch biographers, each on the forearm (ventral aspect). Comparisons were made to HemoCue blood glucose analyzer (Aktiebolgat Leo, Helsingborg, Sweden) capillary blood glucose measurements. In addition, GlucoWatch biographers (one each day for 3 consecutive days) were used by 12 subjects (8 women, 4 men) in a home setting. Comparisons were made to capillary blood glucose values determined using the One Touch Profile meter (Johnson & Johnson, New Brunswick, NJ). RESULTS: GlucoWatch biographer glucose values correlated well with capillary blood glucose values determined using the HemoCue analyzer in the clinic setting (r = 0.90, 1,554 paired data points) and using the One Touch Profile meter in the home setting (r = 0.85, 204 paired data points). When 36 subjects wore two biographers simultaneously, the correlation between the two biographers was r = 0.94. The error grid analysis demonstrated that > 96% of biographer glucose values determined in the clinic or home setting were in the clinically acceptable A and B regions. CONCLUSIONS: This study confirms the accuracy and precision of glucose values as determined using the GlucoWatch biographer in clinic and home settings.

Effect of ebselen on IL-1-induced alterations in cartilage metabolism.

OBJECTIVE: To evaluate the effect of the antioxidant-like anti-inflammatory agent, ebselen, on cartilage proteoglycan degradation and to determine whether its cartilage protectant activity is related to its antioxidant activity. MATERIALS AND METHODS: Cartilage in organ culture was stimulated with interleukin-1 (IL-1), and proteoglycan degradation was assessed by measuring the amount of sulfated glycosaminoglycan released into the media, proteoglycan synthesis evaluated by [35S]-sulfate incorporation, and prostaglandin E2 (PGE2) release determined by radioimmunoassay (RIA). Glutathione peroxidase (GSH-Px) activity was evaluated in a coupled test system using NADPH/GSSG reductase as an indicator and cyclooxygenase activity was evaluated using sheep seminal vesicle prostaglandin synthase. RESULTS: Ebselen caused a concentration-dependent inhibition of IL-1-stimulated proteoglycan degradation with an IC50 of 4.7 microM. Cartilage PGE2 release was also reduced in the presence of ebselen (IC50 = 6.2 microM). However, at concentrations up to 100 microM, ebselen had no effect on the inhibition of proteoglycan synthesis by IL-1. Induction of proteoglycan breakdown was also inhibited by a sulfur analog of ebselen. This analog was devoid of GSH-Px activity and was 50-fold less potent in cyclooxygenase inhibitory activity, but was equipotent to ebselen in inhibiting cartilage degradation. CONCLUSIONS: Ebselen, unlike other NSAIDs, blocks cartilage proteoglycan breakdown without inhibiting proteoglycan synthesis. This effect is independent of its GSH-Px activity and its ability to inhibit cyclooxygenase and PGE2 production. Therefore, this compound may provide a new mechanism for protecting cartilage matrix from degradative factors in arthritic joints.

Nucleated erythrocyte count in newborn infants with left-sided congenital diaphragmatic hernia: relationship with the need for extracorporeal membrane oxygenation and survival.

Inadequate cardiac output in fetuses with left-sided congenital diaphragmatic hernia may cause chronic hypoxia and increased erythropoiesis. Postnatal nucleated erythrocyte counts were measured in 28 newborn infants with left-sided congenital diaphragmatic hernia who were eligible for extracorporeal membrane oxygenation (ECMO). Nucleated erythrocyte counts were lowest in infants who survived without ECMO, intermediate in survivors requiring ECMO, and highest in infants who died despite ECMO.

Spinal meningeal sarcoma in a rottweiler puppy.

An 11-week-old rottweiler puppy was presented for evaluation of progressive paraparesis, urinary and faecal incontinence. Radiography and myelography revealed widening of the vertebral canal and remodelling of several lumbar vertebrae associated with an intramedullary spinal mass. Magnetic resonance imaging revealed an extensive, heterogeneous mass involving the lumbosacral spinal cord. Histopathological examination indicated a meningeal sarcoma with very varied cytological architecture.

Focal gingival hyperplasia in a horse.

A diagnosis of gingival hyperplasia in a 22-year-old Quarter Horse gelding was confirmed by histologic examination. Clinical signs included difficulty eating hay, and a large, intraoral soft tissue mass measuring 13 x 8 x 4.5 cm. The mass was located in the mucosa on the lingual aspect of the caudal left portion of the mandible, ventral to the base of the tongue, and covered the second and third lower molars, extending rostrally along the buccal mucosa to the premolars. The left maxillary second and third molars were overgrown with sharp edges. Lateral radiography of the mandible revealed absence of the left third molar, with associated bony irregularity and sclerosis. The horse was positioned in right lateral recumbency under general anesthesia, and the entire mass was resected. It was speculated that the lesion developed secondary to chronic irritation from opposing teeth and food-packing after loss of the lower third molar; this would not be an unexpected development in a species with continuously advancing molars.

Magnetic resonance imaging in the diagnosis of degenerative lumbosacral stenosis in four dogs.

Magnetic resonance imaging was used to diagnose degenerative lumbosacral stenosis in four dogs that had physical and neurologic signs consistent with a cauda equina lesion. Nerve root displacement by protruding disc material and loss of epidural fat were identified. In all dogs, the diagnosis was confirmed by dorsal laminectomy of the lumbosacral area.

Evaluation and comparison of automated biopsy devices. Work in progress.

The performance of four automated biopsy devices (Bard Biopty, Bard Monopty, Microvasive ASAP 18, Medical Device Technologies Ultra-Cut) was compared when they were used to obtain 96 liver and 96 kidney samples from eight dogs under ultrasound guidance. There was no significant difference in the lengths of the samples obtained with the four devices. The Monopty device yielded a significantly greater mean weight of both kidney (30.8%) and liver (31.6%) samples compared with the other devices. There were no significant differences between the four devices relative to cellular and histologic preservation, crush artifact, and number of renal glomeruli or liver lobules and portal triads. Renal subcapsular hematomas were identified in most instances, and there was no difference between the devices in the amount of renal trauma resulting from their use. There was only one instance of severe injury to the liver. The choice of instrument should remain one of personal preference, since all four devices were satisfactory and none produced significantly greater renal or hepatic injury.