Pulmonary mantle cell lymphoma: a rare manifestation of an uncommon condition

Herein we describe the case of a 64-year old man with a history of mantle cell lymphoma found to have evidence of pulmonary parenchymal involvement by recurrence of his lymphoma. While lung involvement is not necessarily uncommon with Non-Hodgkin's lymphomas as a group, it is very rare for mantle cell lymphoma to involve the lung parenchyma. In addition, the radiographic manifestation of his pulmonary lymphoma as a discrete FDG-avid ground-glass lesion on chest imaging was also distinctly uncommon for pulmonary lymphoma which classically appears in one of three patterns: scattered ill-defined nodules, a bronchovascular/lymphangitic process, or pneumonic/alveolar consolidation effectively indistinguishable from bacterial pneumonia. Due to significant underlying lung disease our patient was not a candidate for high-dose conditioning and autologous stem cell transplantation. He was ultimately treated with rituximab and cladribine therapy and had early signs of clinical response at last correspondence

Generic Airspace Research Phase 5 Report

Human-in-the-loop testing was completed to assess the subjective preferences, usage, and operational benefits of Integrated and Separated Controller Information Tools (CITs) in support of Generic Airspace Research. Participants controlled traffic in in a busy, high altitude sector with the aid of the CITs. When the participants were asked which CIT that they preferred to use, they overwhelmingly chose the integrated version of the CIT. The primary reason for this seemed to be that it allowed participants to remain focused on the traffic situation, whereas the Standalone CIT required them to focus their attention for short periods away from the radar presentation. In contrast to their preference, there were little or no differences in the CIT usage and the operational differences. There were similar numbers of losses of separation and participants accessed each CIT equally. Although the information accessed was the similar for the two conditions, participants actively turned off the data on the Integrated CIT, presumably to reduce the clutter on the radar scope. Further work is needed to isolate which information can and should be available to controllers in the Integrated vs. Standalone format

Endowment Advisory Panels (1976): Memorandum 01

TGF-β1 is an important multifunctional cytokine with numerous protective effects on intestinal mucosa. The influence of TGF-β1 on serotonin transporter (SERT) activity, the critical mechanism regulating the extracellular availability of serotonin (5-HT), is not known. Current studies were designed to examine acute effects of TGF-β1 on SERT. Model human intestinal Caco-2 cells grown as monolayer's or as cysts in 3D culture and ex vivo mouse model were utilized. Treatment of Caco-2 cells with TGF-β1 (10 ng/ml, 60 min) stimulated SERT activity (~2 fold, P<0.005). This stimulation of SERT function was dependent upon activation of TGF-β1 receptor (TGFRI) as SB-431542, a specific TGF-βRI inhibitor blocked the SERT stimulation. SERT activation in response to TGF-β1 was attenuated by inhibition of PI3K and occurred via enhanced recruitment of SERT-GFP to apical surface in a PI3K dependent manner. The exocytosis inhibitor brefeldin A (2.5 μM) attenuated the TGF-β1-mediated increase in SERT function. TGF-β1 increased the association of SERT with the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) syntaxin 3 (STX3) and promoted exocytosis of SERT. Caco-2 cells grown as cysts in 3D culture recapitulated the effects of TGF-β1 showing increased luminal staining of SERT. Ussing chamber studies revealed increase in 3H-5-HT uptake in mouse ileum treated ex vivo with TGF-β1 (10 ng/ml, 1h). These data demonstrate a novel mechanism rapidly regulating intestinal SERT via PI3K and STX3. Since decreased SERT is implicated in various gastro-intestinal disorders e.g IBD, IBS and diarrhea, understanding mechanisms stimulating SERT function by TGF-β1 offers a novel therapeutic strategy to treat GI disorders

Isolated HbA1c identifies a different subgroup of individuals with type 2 diabetes compared to fasting or post-challenge glucose in Asian Indians: The CARRS and MASALA studies.

AIMS: Guidelines recommend hemoglobin A1c (HbA1c) as a diagnostic test for type 2 diabetes, but its accuracy may differ in certain ethnic groups. METHODS: The prevalence of type 2 diabetes by HbA1c, fasting glucose, and 2 h glucose was compared in 3016 participants from Chennai and Delhi, India from the CARRS-2 Study to 757 Indians in the U.S. from the MASALA Study. Type 2 diabetes was defined as fasting glucose ≥ 7.0 mmol/L, 2-h glucose ≥ 11.1 mmol/L, or HbA1c ≥ 6.5%. Isolated HbA1c diabetes was defined as HbA1c ≥ 6.5% with fasting glucose < 7.0 mmol/L and 2 h glucose < 11.1 mmol/L. RESULTS: The age, sex, and BMI adjusted prevalence of diabetes by isolated HbA1c was 2.9% (95% CI: 2.2-4.0), 3.1% (95% CI: 2.3-4.1), and 0.8% (95% CI: 0.4-1.8) in CARRS-Chennai, CARRS-Delhi, and MASALA, respectively. The proportion of diabetes diagnosed by isolated HbA1c was 19.4%, 26.8%, and 10.8% in CARRS-Chennai, CARRS-Delhi, and MASALA respectively. In CARRS-2, individuals with type 2 diabetes by isolated HbA1c milder cardio-metabolic risk than those diagnosed by fasting or 2-h measures. CONCLUSIONS: In Asian Indians, the use of HbA1c for type 2 diabetes diagnosis could result in a higher prevalence. HbA1c may identify a subset of individuals with milder glucose intolerance

Utility of certain nucleophilic aromatic substitution reactions for the assay of pregabalin in capsules

<p>Abstract</p> <p>Background</p> <p>Pregabalin (PG) is an anticonvulsant, analgesic and anxiolytic drug. A survey of the literature reveals that all the reported spectrophotometric methods are either don't offer high sensitivity, need tedious extraction procedures, recommend the measurement of absorbance in the near UV region where interference most probably occurs and/or use non specific reagent that don't offer suitable linearity range.</p> <p>Results</p> <p>Two new sensitive and simple spectrophotometric methods were developed for determination of pregabalin (PG) in capsules. Method (I) is based on the reaction of PG with 1,2-naphthoquinone-4-sulphonate sodium (NQS), yielding an orange colored product that was measured at 473 nm. Method (II) is based on the reaction of the drug with 2,4-dinitrofluorobenzene (DNFB) producing a yellow product measured at 373 nm. The different experimental parameters affecting the development and stability of the reaction product in methods (I) and (II) were carefully studied and optimized. The absorbance-concentration plots were rectilinear over the concentration ranges of 2-25 and 0.5-8 μg mL^-1for methods (I) and (II) respectively. The lower detection limits (LOD) were 0.15 and 0.13 μg mL^-1and the lower quantitation limits (LOQ) were 0.46 and 0.4 μg mL^-1for methods (I) and (II) respectively.</p> <p>Conclusion</p> <p>The developed methods were successfully applied to the analysis of the drug in its commercial capsules. The mean percentage recoveries of PG in its capsule were 99.11 ± 0.98 and 100.11 ± 1.2 (n = 3). Statistical analysis of the results revealed good agreement with those given by the comparison method. Proposals of the reaction pathways were postulated.</p

Primary radiotherapy and deep inferior epigastric perforator flap reconstruction for patients with breast cancer (PRADA): a multicentre, prospective, non-randomised, feasibility study

BACKGROUND: Radiotherapy before mastectomy and autologous free-flap breast reconstruction can avoid adverse radiation effects on healthy donor tissues and delays to adjuvant radiotherapy. However, evidence for this treatment sequence is sparse. We aimed to explore the feasibility of preoperative radiotherapy followed by skin-sparing mastectomy and deep inferior epigastric perforator (DIEP) flap reconstruction in patients with breast cancer requiring mastectomy. METHODS: We conducted a prospective, non-randomised, feasibility study at two National Health Service trusts in the UK. Eligible patients were women aged older than 18 years with a laboratory diagnosis of primary breast cancer requiring mastectomy and post-mastectomy radiotherapy, who were suitable for DIEP flap reconstruction. Preoperative radiotherapy started 3-4 weeks after neoadjuvant chemotherapy and was delivered to the breast, plus regional nodes as required, at 40 Gy in 15 fractions (over 3 weeks) or 42·72 Gy in 16 fractions (over 3·2 weeks). Adverse skin radiation toxicity was assessed preoperatively using the Radiation Therapy Oncology Group toxicity grading system. Skin-sparing mastectomy and DIEP flap reconstruction were planned for 2-6 weeks after completion of preoperative radiotherapy. The primary endpoint was the proportion of open breast wounds greater than 1 cm width requiring a dressing at 4 weeks after surgery, assessed in all participants. This study is registered with ClinicalTrials.gov, NCT02771938, and is closed to recruitment. FINDINGS: Between Jan 25, 2016, and Dec 11, 2017, 33 patients were enrolled. At 4 weeks after surgery, four (12·1%, 95% CI 3·4-28·2) of 33 patients had an open breast wound greater than 1 cm. One (3%) patient had confluent moist desquamation (grade 3). There were no serious treatment-related adverse events and no treatment-related deaths. INTERPRETATION: Preoperative radiotherapy followed by skin-sparing mastectomy and immediate DIEP flap reconstruction is feasible and technically safe, with rates of breast open wounds similar to those reported with post-mastectomy radiotherapy. A randomised trial comparing preoperative radiotherapy with post-mastectomy radiotherapy is required to precisely determine and compare surgical, oncological, and breast reconstruction outcomes, including quality of life. FUNDING: Cancer Research UK, National Institute for Health Research

Endovascular control of haemorrhagic urological emergencies: an observational study

BACKGROUND: Transarterial embolisation (TAE) is an effective method in control of haemorrhage irrespective of the nature of urological emergency. As the technique and technology have evolved, it is now possible to perform highly selective embolisation. The aim of this study was to critically appraise feasibility and efficacy of therapeutic TAE in control of haemorrhagic urological emergencies using selective and non-selective embolisation. Specifically, we aimed to assess the impact of timing of embolisation on the requirement of blood transfusion and long-term morphological and functional follow-up of embolised organs. METHODS: This is a single institutional observational study carried out between March 1992 and March 2006. Records of all patients who underwent selective and non-selective angioembolisation to control bleeding in urological emergencies were reviewed. Data on success rate, periprocedural complications, timing of embolisation, requirement of blood transfusion and the long-term morphological and functional outcomes of embolised organs was recorded. RESULTS: Fourteen patients underwent endovascular control of bleeding as a result of trauma, iatrogenic injury and spontaneous perinephric haemorrhage during a period of 14 years. All these patients would have required emergency open surgery without the option of embolisation procedure. The mean time between the first presentation and embolisation was 22 hours (range 30 minutes to 60 hours). Mean pre-embolisation transfusion requirement was 6.8 units (range 0–22 units). None of the patients with successful embolisation required post-procedural blood transfusion. Permanent haemostasis was achieved in all but one patient, who required emergency nephrectomy. There were no serious procedure related post-embolisation complications. CONCLUSION: Endovascular control using transarterial angioembolisation is an effective method for managing haematuria or haemorrhage in urological emergencies. Wherever and whenever indicated, this option should be considered early in the management of these cases