Quantitation in gated perfusion SPECT imaging: The Cedars-Sinai approach

Cedars-Sinai’s approach to the automation of gated perfusion single photon emission computed tomography (SPECT) imaging is based on the identification of key procedural steps (processing, quantitation, reporting), each of which is then implemented, in completely automated fashion, by use of mathematic algorithms and logical rules combined into expert systems. Our current suite of software applications has been designed to be platform- and operating system-independent, and every algorithm is based on the same 3-dimensional sampling scheme for the myocardium. The widespread acceptance of quantitative software by the nuclear cardiology community (QGS alone is used at over 20,000 locations) has provided the opportunity for extensive validation of quantitative measurements of myocardial perfusion and function, in our opinion, helping to make nuclear cardiology the most accurate and reproducible modality available for the assessment of the human heart.     

Normal pressure hydrocephalus and cerebral blood flow: a PET study of baseline values.

Regional cerebral blood flow (CBF) was studied with O(15)-water positron emission tomography and anatomic region-of-interest analysis on co-registered magnetic resonance in patients with idiopathic (n = 12) and secondary (n = 5) normal pressure hydrocephalus (NPH). Mean CBF was compared with values obtained from healthy volunteers (n = 12) and with clinical parameters. Mean CBF was significantly decreased in the cerebrum and cerebellum of patients with NPH. The regional analysis demonstrated that CBF was reduced in the basal ganglia and the thalamus but not in white matter regions. The results suggest that the role of the basal ganglia and thalamus in NPH may be more prominent than currently appreciated. The implications for theories regarding the pathogenesis of NPH are discussed.     

Frontal versus transcorneal stimulation to induce maximal electroshock seizures or kindling in mice and rats

Frontal stimulation, i.e. electrical stimulation where electrodes are pressed on the skin of the intact frontal skull of mice or rats, may represent a more humane alternative to the widely used transcorneal stimulation to induce electroshock seizures. The aim of this work was to directly compare transcorneal and frontal stimulation in eliciting maximal electroshock-induced seizures (MES) in mice and the anticonvulsant effect of carbamazepine (CBZ) and phenytoin (PHT) on thus produced seizures. In addition, we stimulated mice and rats repeatedly via transcorneal and frontal electrodes to see whether kindling is produced by this procedure. Two electroshock tests were used in mice, i.e. maximal electroshock seizure threshold (MEST) test and MES generated by supramaximal stimulation (50 mA). Frontal stimulation resulted in lower convulsive threshold than in the case of corneal stimulation. Both CBZ and PHT produced dose-dependent increases in seizure threshold for both sites of stimulation, i.e. transcorneal and frontal. As regards type of electrodes, higher doses of PHT were required to increase seizure threshold in the case of frontal than transcorneal stimulation. Supramaximal stimulation (50 mA) yielded comparable ED₅₀ values regardless of the site of stimulation. Furthermore, once-daily stimulation of mice, regardless of the placement of electrodes, did not induce any changes in convulsive threshold. We also attempted to kindle mice and rats via corneal and frontal electrodes by repetitive electrical stimulation using currents which initially did not produce generalized clonic seizures. Mice were stimulated once daily for 2 s with 3 mA (corneal electrodes) or 2 mA (frontal electrodes) and rats were stimulated twice daily for 4 s at 8 mA (corneal electrodes) or 5 mA (frontal electrodes). With corneal stimulation in rats there was a clear progression of kindling development which was not the same in nature when compared with corneally-stimulated mice. Frontal stimulation did not produce kindling. Moreover, corneal stimulation was better tolerated by rats, while in mice high mortality was seen after either method of current delivery. Our data indicate that frontal electrodes can be used as an alternative to transcorneal stimulation to produce MES by supramaximal or threshold current intensities as screening procedures in antiepileptic drug (AED) development. Nevertheless, this type of stimulation cannot be used to produce minimal electroshock seizures and seems not to be useful to produce kindling in rats and mice.     

Surprisingly quick development of squamous cell carcinoma in chronic skin ulcer]

Malignant transformation of skin epithelium caused by chronic wound exudation in the absence of osteomyelitis is a rare event. The paper reports a case of 50 year old Caucasian male who presented with an exophytic tumor on the right hand. The tumor rapidly developed within previous area of unhealed skin wound that had existed only for about 5 months. Histological examination of the excised tumor revealed highly differentiated squamous cell carcinoma (SCC). At that time of surgery nearby lymph node biopsy didn't reveal evidence for metastatic spreading. Patient underwent the limb salvage procedure with tumor resection followed by two stage, cross-flap skin plasty. This report indicates that there is a need to expand knowledge about SCC and about the treatment of the patients with these tumor by surgeons practicing in small medical centers.     

Anionic block polymerization of β-lactones initiated by potassium solutions, 1. Synthesis of poly(4-methyl-2-oxetanone-block-2-oxetanone)

The block polymerization of 4-methyl-2-oxetanone (β-butyrolactone) with 2-oxetanone (β-propiolactone) proceeds fast with a yield of more than 90%, in the presence of potassium solutions in THF containing 18-crown-6. Poly(4-methyl-2-oxetanone-block-2-oxetanone) polymers having the expected molecular weight and composition are formed by this way. Their glass transition and melting temperatures as well as their melting enthalpies, determined by DSC, show a strict correlation with block polymer composition.     

The results of the interference of nitrates and vitamin E in the metabolism in the connective tissue of rat''s liver

We examined 72 female Wistar rats which were divided into 6 groups. The animals were administered sodium nitrate (V), vitamin E or both compounds at the same time. In order to estimate the interference of nitrates in the presence of vitamin E with the metabolism of rat's liver, we determined the composition and the amount of glycosoaminoglycans (GAGs). It was stated that the total amount of GAGs increased in livers of all rats. Basing on all fractions of the examined GAGs it was determined that the most significant differences between individual groups appeared in the amount of heparane sulphate (HS). The results obtained confirmed the fact of the changes taking place in the picture of liver GAGs in the process of ageing of the examined animals. The results obtained, however, allowed to state the normalising influence of vitamin E on the quantitative composition of GAGs of rats which drank nitrates.     

Nitric oxide mediates intestinal hyperaemic responses to intraluminal bile-oleate

It has long been recognized that intestinal blood flow increases at mealtimes. Mesenteric hyperaemia is also evoked by activation of sensory peptidergic nerves. Our studies explored the possible role of endogenous nitric oxide (NO) in the rat intestinal vasodilator response to luminal instillation of an oleic acid plus bile mixture before and after acute intrajejunal instillation of capsaicin and after chronic pretreatment with capsaicin. In anaesthetized rats we measured jejunal blood flow (BF) with an ultrasonic Doppler flowmeter and systemic arterial pressure (AP) with a pressure transducer. Intestinal perfusion with 80 mM oleic acid in bile increased BF by 98±12%. Instillation of 4 mg of capsaicin into the jejunal lumen initially increased BF by 42±9% but was followed by vasoconstriction. Inhibition of NO synthase with 25 mg/kg i.v. N-nitro-L-arginine (L-NNA) decreased BF by 27±5% and increased AP by 37±11%. After treatment with L-NNA and after acute and chronic administration of capsaicin, the bile-oleate-induced maximal increases in BF above control levels were 42±7%, 65±12%, and 58±8%, respectively. The observed inhibitory effect of L-NNA on the intestinal hyperaemic response to the bile-oleate mixture was reversed by pretreatment with L-arginine (100 mg/kg i.V.). In capsaicin pretreated rats the subsequent bile-oleate-induced hyperaemia was reduced in magnitude but the inhibitory effects of L-NNA were proportionately the same as in animals not receiving capsaicin. These findings support the hypothesis that NO is involved with bile-oleate-induced mesenteric hyperaemia.     

Visualisation of the extent of damage in a rat spinal cord injury model using MR microsopy of the water diffusion tensor

Magnetic Resonance Diffusion Tensor Imaging (DTI) of the control and traumatic injured spinal cord of a rat in vitro is reported. Experiments were performed on excised spinal cords from 10 Wistar rats, using a home-built 6.4 T MR microscope. MRI and histopathological results were compared. Presented results show that DTI of the spinal cord, perfused with formalin 10 minutes after the injury, can detect changes in water diffusion in white matter (WM) and in gray matter (GM), in areas extending well beyond the region of direct impact. Histology of neurons of the GM shows changes that can be attributed to ischemia. This is in agreement with the observed decrease of diffusion in the injured regions, which may be attributed to the cytotoxic edema due to ischemia. However, the diffusion changes in highly anisotropic WM seem to be caused by a direct action of mechanical force of impact, which significantly distorts the nerve fibers.     

Exome sequencing reveals a novel COL2A1 mutation implicated in multiple epiphyseal dysplasia

Mutations in the COMP, COL9A1, COL9A2, COL9A3, MATN3, and SLC26A2 genes cause approximately 70% of multiple epiphyseal dysplasia (MED) cases. The genetic changes involved in the etiology of the remaining cases are still unknown, suggesting that other genes contribute to MED development. Our goal was to identify a mutation causing an autosomal dominant form of MED in a large multigenerational family. Initially, we excluded all genes known to be associated with autosomal dominant MED by using microsatellite and SNP markers. Follow‐up with whole‐exome sequencing analysis revealed a mutation c.2032G>A (p.Gly678Arg) in the COL2A1 gene (NCBI Reference Sequence: NM_001844.4), which co‐segregated with the disease phenotype in this family, manifested by severe hip dysplasia and osteoarthritis. One of the affected family members had a double‐layered patella, which is frequently seen in patients with autosomal recessive MED caused by DTDST mutations and sporadically in the dominant form of MED caused by COL9A2 defect.     

A Vicious Cycle of Osteosarcopenia in Inflammatory Bowel Diseases—Aetiology,Clinical Implications and Therapeutic Perspectives

Sarcopenia is a disorder characterized by a loss of muscle mass which leads to the reduction of muscle strength and a decrease in the quality and quantity of muscle. It was previously thought that sarcopenia was specific to ageing. However, sarcopenia may affect patients suffering from chronic diseases throughout their entire lives. A decreased mass of muscle and bone is common among patients with inflammatory bowel disease (IBD). Since sarcopenia and osteoporosis are closely linked, they should be diagnosed as mutual consequences of IBD. Additionally, multidirectional treatment of sarcopenia and osteoporosis including nutrition, physical activity, and pharmacotherapy should include both disorders, referred to as osteosarcopenia.