Crohn's Disease in Transvaal Blacks: A REPORT OF THREE CASES WITH A REVIEW

Crohn's disease is rarely seen in Transvaal Blacks. Three cases are presented. The pathology and radiological features are discussed. The difficulty of diagnosing the extent of the disease in the acute stage both clinically and radiologically is emph,!lsised. The acute case should be recognised at operation and nothing further done. The case presenting with intestinal obstruction should have conservative excision of the organically narrowed segment. Azathioprine may be of some use in the treatment of the acute episode. Its probable chief mode of action is by its antiphlogistic effect.S. Afr. Med. J., 48, 580 (1974)

Percutaneous radiofrequency ablation of HCC: reduced ablation duration and increased ablation size using single, internally cooled electrodes with an optimized pulsing algorithm

Purpose To assess the use of optimized radiofrequency (RF) to achieve larger, spherical ablation volumes with short application duration for hepatocellular carcinoma (HCC). Materials and methods Twenty-two patients (M:F = 17:5, median age 69.6 year, range 63–88) with 28 HCCs due to HCV + liver cirrhosis underwent RFA. 20/28 (71.4%) were tumors ≤3cm diameter, and 8/28 (28.6%) ranged from 3.2 to 4.2 cm. RF was applied using up to 2500mA via an optimized pulsing algorithm with real-time ultrasound monitoring to detect hyperechogenic changes. Single insertions of an internally cooled electrode were performed using exposed tips of 2 or 3 cm for 13 HCCs and 4 cm for 15 HCCs. All patients were followed-up for a minimum of 5 years with contrast-enhanced computed tomography (CECT). Results Technical success was achieved without adverse events in all cases. The mean ablation time was 8.5 ± 2.6 min. In 21/28 (75%), ablation duration ranged from 3 to 9 min, with 12 min duration applied in only 7/28 (25%). Mean coagulation diameters were 2.4 ± 0.14, 3.3 ± 0.62, and 4.4 ± 1.0, for 2, 3 and 4 cm electrodes, respectively (p 3 cm tumors developed local progression. One patient had multifocal disease with no local progression. Conclusion Efficient delivery of RF energy can considerably decrease the ablation time in many instances while achieving larger, relatively spherical, and reproducible areas of ablation with extremely low rates of local tumor progression and adverse events

Comparison of BMD changes and bone formation marker levels 3 years after bisphosphonate discontinuation: FLEX and HORIZON-PFT Extension I trials

An ASBMR task force recommends a drug holiday for certain women treated for ≥5 years with oral alendronate or ≥3 years with intravenous zoledronic acid, with reassessment 2-3 years later. It is not known whether changes in BMD or bone turnover markers differ after oral or intravenous therapy. Our goal was to compare changes in BMD and procollagen type I N propeptide, PINP, after oral or intravenous bisphosphonate use. In the Fracture Intervention Trial Long-term Extension (FLEX), women who received a mean 5 years of alendronate were randomized to placebo or continued treatment. In the Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial Extension I (HORIZON-PFT E1), women who received 3 years of zoledronic acid were randomized to placebo or continued treatment. We examined the proportion of participants with BMD loss or PINP gain ≥least significant change (LSC), and those whose values exceeded a threshold (T score ≤-2.5 or PINP ≥36.0 ng/mL, a premenopausal median value). After 3 years of placebo, the FLEX group had greater mean total hip BMD decreases (-2.3% versus -1.2% in the HORIZON-PFT E1 group, p < 0.01), and greater rises in PINP (+11.6 ng/mL versus +6.7 ng/mL, p < 0.01). There was a greater proportion of individuals in FLEX with total hip BMD loss and PINP increases that exceeded LSC, and PINP values ≥36.0 ng/mL. In contrast, there were small changes in the proportion of women with femoral neck T scores ≤-2.5 in both groups. In conclusion, 3 years after bisphosphonate discontinuation, a considerable proportion of former alendronate and zoledronic acid users had meaningful declines in total hip BMD and elevations in PINP. Despite a longer treatment course, alendronate may have a more rapid offset of drug effect than zoledronic acid

Application of NMR Methods to Identify Detection Reagents for Use in the Development of Robust Nanosensors

Nuclear Magnetic Resonance (NMR) spectroscopy is a powerful technique for studying bi-molecular interactions at the atomic scale. Our NMR lab is involved in the identification of small molecules, or ligands that bind to target protein receptors, such as tetanus (TeNT) and botulinum (BoNT) neurotoxins, anthrax proteins and HLA-DR10 receptors on non-Hodgkin's lymphoma cancer cells. Once low affinity binders are identified, they can be linked together to produce multidentate synthetic high affinity ligands (SHALs) that have very high specificity for their target protein receptors. An important nanotechnology application for SHALs is their use in the development of robust chemical sensors or biochips for the detection of pathogen proteins in environmental samples or body fluids. Here, we describe a recently developed NMR competition assay based on transferred nuclear Overhauser effect spectroscopy (trNOESY) that enables the identification of sets of ligands that bind to the same site, or a different site, on the surface of TeNT fragment C (TetC) than a known ''marker'' ligand, doxorubicin. Using this assay, we can identify the optimal pairs of ligands to be linked together for creating detection reagents, as well as estimate the relative binding constants for ligands competing for the same site

Syringobulbia and syringomyelia in a case with Chiari 0 malformation successfully treated by posterior fossa reconstruction: Case presentation and literature review

“Chiari zero malformation” is a rare and a relatively new described condition which associates syringohydromyelia without caudal displacement of the cerebellar tonsils through the foramen magnum. We present a case of a 40 years old woman with Chiari zero malformation with both syringomyelia and syringobulbia and a good clinical and radiological outcome after posterior fossa decompression. The presence of associated syringomyelia and syringobulbia in this condition is less frequent and it usually occurs in younger patients. In our case we considered syringobulbia as being an extension of syringomyelia

Early changes in biochemical markers of bone turnover and their relationship with bone mineral density changes after 24 months of treatment with teriparatide

Summary We report the changes in biochemical markers of bone formation during the first 6 months of teriparatide therapy in postmenopausal women with osteoporosis according to previous antiresorptive treatment. Prior therapy does not adversely affect the response to teriparatide treatment. Similar bone markers levels are reached after 6 months of treatment. Introduction The response of biochemical markers of bone turnover with teriparatide therapy in subjects who have previously received osteoporosis drugs is not fully elucidated. We examined biochemical markers of bone formation in women with osteoporosis treated with teriparatide and determined: (1) whether the response is associated with prior osteoporosis therapy, (2) which marker shows the best performance for detecting a response to therapy, and (3) the correlations between early changes in bone markers and subsequent bone mineral density (BMD) changes after 24 months of teriparatide. Methods We conducted a prospective, open-label, 24-month study at 95 centers in 10 countries in 758 postmenopausal women with established osteoporosis (n = 181 treatment-naïve) who had at least one post-baseline bone marker determination. Teriparatide (20 μg/day) was administered for up to 24 months. We measured procollagen type I N-terminal propeptide (PINP), bone-specific alkaline phosphatase (b-ALP), and total alkaline phosphatase (t-ALP) at baseline, 1 and 6 months, and change in BMD at the lumbar spine, total hip and femoral neck from baseline to 24 months. Results Significant increases in formation markers occurred after 1 month of teriparatide regardless of prior osteoporosis therapy. The absolute increase at 1 month was lower in previously treated versus treatment-naïve patients, but after 6 months all groups reached similar levels. PINP showed the best signal-to-noise ratio. Baseline PINP correlated positively and significantly with BMD response at 24 months. Conclusions This study suggests that the long-term responsiveness of bone formation markers to teriparatide is not affected in subjects previously treated with antiresorptive drugs

Do trauma cue exposure and/or PTSD symptom severity intensify selective approach bias toward cannabis cues in regular cannabis users with trauma histories?

Trauma cue-elicited activation of automatic cannabis-related cognitive biases are theorized to contribute to comorbid posttraumatic stress disorder and cannabis use disorder. This phenomenon can be studied experimentally by combining the trauma cue reactivity paradigm (CRP) with cannabis-related cognitive processing tasks. In this study, we used a computerized cannabis approach-avoidance task (AAT) to assess automatic cannabis (vs. neutral) approach bias following personalized trauma (vs. neutral) CRP exposure. We hypothesized that selective cannabis (vs. neutral) approach biases on the AAT would be larger among participants with higher PTSD symptom severity, particularly following trauma (vs. neutral) cue exposure. We used a within-subjects experimental design with a continuous between-subjects moderator (PTSD symptom severity). Participants were exposed to both a trauma and neutral CRP in random order, completing a cannabis AAT (cannabis vs. neutral stimuli) following each cue exposure. Current cannabis users with histories of psychological trauma (n = 50; 34% male; mean age = 37.8 years) described their most traumatic lifetime event, and a similarly-detailed neutral event, according to an established interview protocol that served as the CRP. As hypothesized, an AAT stimulus type x PTSD symptom severity interaction emerged (p = .042) with approach bias greater to cannabis than neutral stimuli for participants with higher (p = .006), but not lower (p = .36), PTSD symptom severity. Contrasting expectations, the stimulus type x PTSD symptoms effect was not intensified by trauma cue exposure (p = .19). Selective cannabis approach bias may be chronically activated in cannabis users with higher PTSD symptom severity and may serve as an automatic cognitive mechanism to help explain PTSD-CUD co-morbidity.</p

Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G

Background: The activating immunoreceptor NKG2D is expressed on Natural Killer (NK) cells and subsets of T cells. NKG2D contributes to anti-tumour and anti-viral immune responses in vitro and in vivo. The ligands for NKG2D in humans are diverse proteins of the MIC and ULBP/RAET families that are upregulated on the surface of virally infected cells and tumours. Two splicing variants of ULBP5/RAET1G have been cloned previously, but not extensively characterised. Methodology/Principal Findings: We pursue a number of approaches to characterise the expression, trafficking, and function of the two isoforms of ULBP5/RAET1G. We show that both transcripts are frequently expressed in cell lines derived from epithelial cancers, and in primary breast cancers. The full-length transcript, RAET1G1, is predicted to encode a molecule with transmembrane and cytoplasmic domains that are unique amongst NKG2D ligands. Using specific anti-RAET1G1 antiserum to stain tissue microarrays we show that RAET1G1 expression is highly restricted in normal tissues. RAET1G1 was expressed at a low level in normal gastrointestinal epithelial cells in a similar pattern to MICA. Both RAET1G1 and MICA showed increased expression in the gut of patients with celiac disease. In contrast to healthy tissues the RAET1G1 antiserum stained a wide variety or different primary tumour sections. Both endogenously expressed and transfected RAET1G1 was mainly found inside the cell, with a minority of the protein reaching the cell surface. Conversely the truncated splicing variant of RAET1G2 was shown to encode a soluble molecule that could be secreted from cells. Secreted RAET1G2 was shown to downregulate NKG2D receptor expression on NK cells and hence may represent a novel tumour immune evasion strategy. Conclusions/Significance: We demonstrate that the expression patterns of ULBP5RAET1G are very similar to the well-characterised NKG2D ligand, MICA. However the two isoforms of ULBP5/RAET1G have very different cellular localisations that are likely to reflect unique functionality