Pulmonary Glue Embolism: An unusual complication following endoscopic sclerotherapy for gastric varices.

A pulmonary glue embolism is an unusual but potentially life-threatening complication following the treatment of variceal bleeding, especially in patients with large varices requiring large volumes of sclerosant. Other contributory factors include the rate of injection and ratio of the constituent components of the sclerosant (i.e. n-butyl-cyanoacrylate and lipiodol). This condition may be associated with a delayed onset of respiratory compromise. Therefore, a high degree of clinical suspicion is essential in patients with unexplained cardiorespiratory decline during or following endoscopic sclerotherapy. We report a 65-year-old man who was admitted to the Hull Royal Infirmary, Hull, UK, in 2017 with haematemesis and melaena. He subsequently developed acute respiratory distress syndrome secondary to a glue embolism following emergency sclerotherapy for bleeding gastric varices. The aetiology of the embolism was likely a combination of the large size of the gastric varices and the large volume of cyanoacrylate needed. After an endoscopy, the patient underwent transjugular intrahepatic portosystemic shunting twice to control the bleeding, after which he recovered satisfactorily.

Phase IIa randomized, placebo-controlled study of antimicrobial photodynamic therapy in bacterially colonized, chronic leg ulcers and diabetic foot ulcers: a new approach to antimicrobial therapy.

BACKGROUND: With increasing problems of antibiotic resistance, photodynamic therapy (PDT) is being developed as a novel antimicrobial treatment. Following light activation, cationic photosensitizer PPA904 [3,7-bis(N,N-dibutylamino) phenothiazin-5-ium bromide] kills a broad spectrum of bacteria in vitro and this has a variety of potential clinical applications. OBJECTIVES: To determine if PDT in bacterially colonized chronic leg ulcers and chronic diabetic foot ulcers can reduce bacterial load, and potentially lead to accelerated wound healing. METHODS: Sixteen patients with chronic leg ulcers and 16 patients with diabetic foot ulcers (each eight active treatment/eight placebo) were recruited into a blinded, randomized, placebo-controlled, single-treatment, Phase IIa trial. All patients had ulcer duration > 3 months, bacterially colonized with > 10 colony-forming units cm . After quantitatively assessing pretreatment bacterial load via swabbing, PPA904 or placebo was applied topically to wounds for 15 min, followed immediately by 50 J cm of red light and the wound again sampled for quantitative microbiology. The wound area was measured for up to 3 months following treatment. RESULTS: Treatment was well tolerated with no reports of pain or other safety issues. In contrast to placebo, patients on active treatment showed a reduction in bacterial load immediately post-treatment (P < 0·001). After 3 months, 50% (four of eight) of patients with actively treated chronic leg ulcer showed complete healing, compared with 12% (one of eight) of patients on placebo. CONCLUSIONS: This first controlled study of PDT in chronic wounds demonstrated significant reduction in bacterial load. An apparent trend towards wound healing was observed; further study of this aspect with larger patient numbers is indicated.

A phase II trial of cisplatin (C), gemcitabine (G) and gefitinib for advanced urothelial tract carcinoma: results of Cancer and Leukemia Group B (CALGB) 90102.

BACKGROUND: This phase II trial (Cancer and Leukemia Group B 90102) sought to determine the efficacy of cisplatin, standard infusion of gemcitabine and gefitinib in patients with advanced urothelial carcinoma. PATIENTS AND METHODS: Eligible patients had previously untreated measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status of zero to two and creatinine clearance >50 ml/min. Treatment consisted of cisplatin 70 mg/m(2) day 1 and gemcitabine 1000 mg/m(2) on days 1 and 8 given every 3 weeks concurrent with gefitinib 500 mg/day orally for six cycles. Maintenance gefitinib 500 mg/day was continued for responding or stable disease. RESULTS: Fifty-four of 58 patients were assessable. Twelve patients (22%) had node-only disease, and 25 (46%) had an ECOG performance status of zero. There were 23 objective responses for an overall response rate of 42.6% [95% confidence interval (CI) 29.2% to 56.8%]. The median survival time was 15.1 months (95% CI 11.1-21.7 months) and the median time to progression was 7.4 months (95% CI 5.6-9.2 months). CONCLUSIONS: The combination of cisplatin, gemcitabine and gefitinib is well tolerated and active in advanced transitional cell carcinoma. The addition of gefitinib does not appear to improve response rate or survival in comparison to historical controls of cisplatin and gemcitabine alone.

Autologous stem cell transplantation followed by consolidation chemotherapy for patients with multiple myeloma.

Although high-dose therapy and autologous stem cell transplant (ASCT) is superior to conventional chemotherapy for treatment of myeloma, most patients relapse and the time to relapse depends upon the initial prognostic factors. The administration of non-cross-resistant chemotherapies during the post-transplant period may delay or prevent relapse. We prospectively studied the role of consolidation chemotherapy (CC) after single autologous peripheral blood stem cell transplant (auto-PBSCT) in 103 mostly newly diagnosed myeloma patients (67 patients were < or =6 months from the initial treatment). Patients received conditioning with BCNU, melphalan+/-gemcitabine and auto-PBSCT followed by two cycles of the DCEP+/-G regimen (dexamethasone, cyclophosphamide, etoposide, cisplatin+/-gemcitabine) at 3 and 9 months post-transplant and alternating with two cycles of DPP regimen (dexamethasone, cisplatin, paclitaxel) at 6 and 12 months post-transplant. With a median follow-up of 61.2 months, the median event-free survival (EFS) and overall survival (OS) are 26 and 54.1 months, respectively. The 5-year EFS and OS are 23.1 and 42.5%, respectively. Overall, 51 (49.5%) patients finished all CC, suggesting that a major limitation of this approach is an inability to deliver all planned treatments. In order to improve results following autotransplantation, novel agents or immunologic approaches should be studied in the post-transplant setting.

Bacterial adhesion to bisphosphonate coated hydroxyapatite.

Staphylococcus aureus (S. aureus) is commonly associated with microbial infection of orthopaedic implants. Such infections often lead to osteomyelitis, which may result in failure of the implant due to localised bone destruction. Bacterial adhesion and subsequent colonisation of the device may occur as a consequence of contamination during surgery, or by seeding from a distant site through the blood circulation. Coating of the hydroxyapatite (HA) ceramic component of artificial hip joints with the bisphosphonates clodronate (C) and pamidronate (P) has been proposed as a means to minimise osteolysis and thereby prevent loosening of the implant. However, the effect of the bisphosphonate coating on bacterial adhesion to the HA materials must be determined before this approach can be implemented. In this study coated HA materials were incubated with the S. aureus and the number of adherent bacteria determined using the Modified Vortex Device (MVD) method. The number of bacteria adherent to the P coated HA material was significantly greater than that adherent to uncoated HA (60-fold increase) or to the C coated HA (90-fold increase). Therefore, even though earlier studies suggested that P bound to HA may improve osseointegration, the results presented would suggest that the use of this coating may be limited by the potential increased susceptibility of the coated device to infection.

DNA replication regulation protein Mcm7 as a marker of proliferation in prostate cancer.

BACKGROUND: Recent studies have shown that minichromosome maintenance (MCM) proteins (Mcm2-7) may be useful proliferation markers in dysplasia and cancer in various tissues. AIMS: To investigate the use of Mcm7 as a proliferation marker in 79 lymph node negative prostate cancers and compare it with Ki-67, a commonly used cell proliferation marker. METHODS: The percentage of proliferating cells (proliferation index; PI) was calculated for basal and luminal epithelial cells in benign prostate tissue, prostatic intraepithelial neoplasia (PIN), and epithelial cells in adenocarcinoma. The PI for each biomarker was correlated with the preoperative prostate specific antigen concentration, the Gleason score, surgical resection margin status, and the AJCC pT stage for each patient. RESULTS: The mean PIs for Ki-67 and Mcm7 were: benign luminal epithelium 0.7 and 1.2 and benign basal epithelium 0.8 and 8.2; PIN non-basal epithelium 4.9 and 10.6 and PIN basal epithelium 0.7 and 3.1; adenocarcinoma 9.8 and 22.7, respectively. Mcm7 had a significantly higher mean PI (p<0.0001) than Ki-67 for all cell categories except benign luminal epithelial cells. Mcm7 was a better discriminatory marker of proliferation between benign epithelium, PIN, and invasive adenocarcinoma (p<0.0001) than Ki-67. The drop in Mcm7 mean basal cell PI from benign epithelium to PIN epithelium was significantly larger than for Ki-67 (p<0.0001). Mcm7 had a significantly higher PI than Ki-67 at each risk level. CONCLUSION: Mcm7 may be a useful proliferation marker in prostatic neoplasia and warrants further evaluation as a complementary tool in the diagnosis of PIN and prostate carcinoma.

IAEA/NUS Distance Learning Diploma Training Course for Tissue Bank Operators - Past, Present and Future.

National University Hospital (NUH) Tissue Bank as the Regional Training Centre for Asia Pacific Region provided National University of Singapore (NUS) Diploma Course in Tissue Banking - a long distance diploma course since 1997. To date, five batches have participated - 94 tissue bank operators. Sixty-three tissue bank operators have convocated with NUS Diploma in Tissue Banking.From Regional Co-operative Agreement (RCA) Project, RAS 7/008 technology transfer was effected to Latin America and to Africa.A Memorandum of Understanding has been signed between International Atomic Energy Agency (IAEA) and NUS in July 2002 making Singapore the International Training Centre. An Internet NUS Diploma Course in Tissue Banking has been developed by IAEA and NUS. The first on-line diploma course will be launched in 2003.

A comparison of the lactate Pro, Accusport, Analox GM7 and Kodak Ektachem lactate analysers in normal, hot and humid conditions.

This study aimed to compare the performance of a new portable lactate analyser against other standard laboratory methods in three conditions, normal (20 +/- 1.3 degrees C; 40 +/- 5 % RH), hot (40 +/- 2.5 degrees C; 40 +/- 5 % RH), and humid (20 +/- 1.1 degrees C; 82 +/- 6 % RH) conditions. Seven healthy males, ([Mean +/- SE]: age, 26.3 +/- 1.3 yr; height, 177.7 +/- 1.6 cm; weight, 77.4 +/- 0.9 kg, .VO(2)max, 56.1 +/- 1.9 ml x kg x min(-1)) undertook a maximal cycle ergometry test to exhaustion in the three conditions. Blood was taken every 3 min at the end of each stage and was analysed using the Lactate Pro LT-1710, the Accusport, the Analox GM7 and the Kodak Ektachem systems. The MANOVA (Analyser Type x Condition x Workload) indicated no interaction effect (F(42,660), = 0.45, p > 0.99, Power = 0.53). The data across all workloads indicated that the machines measured significantly differently to each other (F(4,743) = 14.652, p < 0.0001, Power = 1.00). The data were moderately to highly correlated. We conclude that the Lactate Pro is a simple and effective measurement device for taking blood lactate in a field or laboratory setting. However, we would caution against using this machine to compare data from other machines.

Histopathological analysis of Leri-Weill dyschondrosteosis: disordered growth plate.

Leri-Weill syndrome (LWS) is a dominant (pseudoautosomal) skeletal dysplasia with mesomelic short stature and bilateral Madelung deformity, due to dyschondrosteosis of the distal radius. It results from the loss of one copy of the Short Stature Homeobox Gene (SHOX) from the tip of the short arm of the X or Y chromosome. SHOX molecular testing enabled us to evaluate the histopathology of the radial physis in LWS patients with a documented SHOX abnormality. A widespread disorganisation of physeal anatomy was revealed with disruption of the normal parallel columnar arrangement of chondrocytes. Tandem stacking of maturing chondrocytes within columns was replaced by a side-by-side arrangement. The presence of hypertrophic osteoid with micro-enchondromata in the radial metaphysis suggests abnormal endochondral ossification. The Vickers' ligament was confirmed to blend with the triangular fibrocartilage complex (TFCC). This histopathological study demonstrates that the zone of dyschondrosteosis in LWS is characterised by marked disruption of normal physeal chondrocyte processes and that a generalised physeal abnormality is present.

Erythrocyte glutathione deficiency in symptom-free HIV infection is associated with decreased synthesis rate.

Although several studies have documented intra- and extracellular glutathione (GSH) deficiency in asymptomatic human immunodeficiency virus (HIV) infection, the mechanisms responsible for the altered GSH homeostasis remain unknown. To determine whether decreased synthesis contributes to this alteration of GSH homeostasis, a primed-constant infusion of [2H2]glycine was used to measure the fractional and absolute rates of synthesis of GSH in five healthy and five symptom-free HIV-infected subjects before and after supplementation for 1 wk with N-acetylcysteine. The erythrocyte GSH concentration of the HIV-infected group was lower (P < 0.01) than that of the control group (1.4 +/- 0.16 vs. 2.4 +/- 0.08 mmol/l). The smaller erythrocyte GSH pool of the HIV-infected group was associated with a significantly slower (P < 0.01) absolute synthesis rate of GSH (1.15 +/- 0.14 vs. 1.71 +/- 0.15 mmol. l-1. day-1) compared with controls. Cysteine supplementation elicited significant increases in both the absolute rate of synthesis and the concentration of erythrocyte GSH. These results suggest that the GSH deficiency of HIV infection is due in part to a reduced synthesis rate secondary to a shortage in cysteine availability.

Dolomite limits acidification of a biofilter degrading dimethyl sulphide

The applicability of dolomite particles to control acidification in a Hyphomicrobium MS3 inoculated biofilter removing dimethyl sulphide (Me2S) was studied. While direct inoculation of the dolomite particles with the liquid microbial culture was not successful, start-up of Me2S-degradation in the biofilter was observed when the dolomite particles were mixed with 33% (wt/wt) of Hyphomicrobium MS3-inoculated compost or wood bark material. Under optimal conditions, an elimination capacity (EC) of 1680 g Me2S m(-3) d(-1) was obtained for the compost/dolomite biofilter. Contrary to a wood bark or compost biofilter, no reduction in activity due to acidification was observed in these biofilters over a 235 day period because of the micro environment neutralisation of the microbial metabolite H2SO4 with the carbonate in the dolomite material. However, performance of the biofilter decreased when the moisture content of the mixed compost/dolomite material dropped below 15%. Next to this, nutrient limitation resulted in a gradual decrease of the EC and supplementation of a nitrogen source was a prerequisite to obtain a long-term high EC (> 250 g Me2S m(-3) d(-1)) for Me2S. In relation to this nitrogen supplementation, it was observed that stable ECs for Me2S were obtained when this nutrient was dosed to the biofilter at a Me2S-C/NH4Cl-N ratio of about 10.

Pre-clinical evaluation of probes to detect t(8;21) AML minimal residual disease by fluorescence in situ hybridization.

The 8;21 translocation in acute myeloid leukemia (AML) results in a consistent fusion transcript, AML1/ETO. Long-term clinical remission occurs in some patients despite incomplete eradication of AML1/ETO as demonstrated by RT-PCR, thus limiting the usefulness of this assay. An important future goal will be to determine if there is a level of minimal residual disease (MRD) in patients below which relapse is unlikely. For the detection of MRD, we have developed reagents for fluorescence in situ hybridization (FISH) that identify both derivative 8 and 21 chromosomes with a high analytical sensitivity. In t(8;21) AML cells, two fused signals were detected in addition to the normal 8 and 21 alleles. The sensitivity and specificity of this probe mixture were analyzed in cell lines and patient bone marrows. One and two randomly juxtaposed signals were observed in 2.4 and 0.04% of normal cells, respectively. However, these were easily differentiated from t(8;21) cells by the absence of signals from the normal alleles. Using as criteria the presence of two fused signals plus the normal alleles, we observed no false positives among 5,000 normal cells. The probe correctly identified 20/20 patients with t(8;21) AML and 10/10 non-t(8;21) patients. In cell dilution experiments, the analytical sensitivity of this reagent was equal to that of the X chromosome and Y chromosome alpha-satellite probes. These optimized probes should facilitate the quantitative assessment and study of MRD in t(8;21) AML.

ETO and AML1 phosphoproteins are expressed in CD34+ hematopoietic progenitors: implications for t(8;21) leukemogenesis and monitoring residual disease.

To study acute myelogenous leukemia 1 (AML1) transcription factor, ETO protein, and t(8;21) AML chimeric AML1/ ETO protein in normal hematopoiesis and in leukemia, we raised rabbit antisera to a bacterially expressed polypeptide containing amino acid residues 1 to 220 of ETO and to synthetic peptides extending from residues 528 to 548 of ETO and 32 to 50 of AML1. The latter was selected to have little chance of cross-reactivity with other members of the PEBP2 alpha family. With affinity-purified reagents, we observed immunofluorescent staining for both AML1 and ETO in the nucleus of HEL, K562, and Kasumi-1 leukemic cell lines, the last from a t(8;21) AML. Biochemical analysis confirmed specificity of the antibodies and the nuclear localization of the antigens, the latter being exclusive for AML1 and primary for ETO. Immunoprecipitations of metabolically labeled 32P-proteins from Kasumi-1 cells show that AML1 and ETO are phosphorylated on serine and threonine. Investigations with normal bone marrow reveal AML1 and ETO are coexpressed in megakaryocytes and that each is expressed in a portion of the approximately 10-microns-diameter cells residing there. Using a CD34+ enriched population mobilized to peripheral blood, we found AML1 and, unexpectedly, ETO present in these cells. Because of this, we conclude that the expression of ETO in hematopoietic cells is not by itself leukemogenic. Also, because ETO would not be exclusively expressed as part of chimeric AML1/ETO in leukemic patients, its presence cannot be used to monitor t(8;21) AML residual disease.

Myofibril size variation along the length of extraocular muscle in rabbit and rat. I: orbital layer.

It is generally assumed that a muscle fiber is structurally uniform along its length. That assumption is not consistent with the observed variation of myofibrillar profile size along the length of both singly innervated fibers (SIFs) and multiply innervated fibers (MIFs) in the orbital (outer) layer of extraocular muscle (EOM). Muscle fibers were reconstructed in serial sections along the orbital layer of rabbit and rat EOM. For both the SIFs and MIFs, myofibril profile size was smallest (narrowest) near the endplate. In the SIFs of rat, for example, the myofibril profiles were 28% wider at a distance of 1.5 mm from the endplate than at the endplate itself. Measures of profile size included the mean intercept length and the mean shortest path from test points within the profile to the profile boundary. The possible effect of sarcomere length variation was controlled by normalizing the myofibrillar profile size data to a constant spacing of the myosin filament lattice. This morphometric approach was also used to quantify the further increase of profile size that occurs in the end portions of the orbital MIFs where the myobrillar organization is typically ill-defined.