Quantitative MR characterization of disease activity in the knee in children with juvenile idiopathic arthritis: a longitudinal pilot study

Background The development of a quantifiable and noninvasive method of monitoring disease activity and response to therapy is vital for arthritis management. Objective The purpose of this study was to investigate the utility of quantitative dynamic contrast-enhanced MRI (DCE-MRI) based on pharmacokinetic (PK) modeling to evaluate disease activity in the knee and correlate the results with the clinical assessment in children with juvenile idiopathic arthritis (JIA). Materials and methods A group of 17 children with JIA underwent longitudinal clinical and laboratory assessment and DCE-MRI of the knee at enrollment, 3 months, and 12 months. A PK model was employed using MRI signal enhancement data to give three parameters, K^{trans ′} (min⁻¹), k_ep (min⁻¹), and V_p ^′ and to calculate synovial volume. Results The PK parameters, synovial volumes, and clinical and laboratory assessments in most children were significantly decreased (P < 0.05) at 12 months when compared to the enrollment values. There was excellent correlation between the PK and synovial volume and the clinical and laboratory assessments. Differences in MR and clinical parameter values in individual subjects illustrate persistent synovitis when in clinical remission. Conclusion A decrease in PK parameter values obtained from DCE-MRI in children with JIA likely reflects diminution of disease activity. This technique may be used as an objective follow-up measure of therapeutic efficacy in patients with JIA. MR imaging can detect persistent synovitis in patients considered to be in clinical remission.     

Ursodeoxycholic acid and F(6)-D(3) inhibit aberrant crypt proliferation in the rat azoxymethane model of colon cancer: roles of cyclin D1 and E-cadherin.

We have previously demonstrated that ursodeoxycholic acid(UDCA) and a fluorinated analogue of vitamin D(3), F(6)-D(3),inhibited colonic carcinogenesis in the azoxymethane (AOM) model. Generalized colonic mucosal hyperproliferation and aberrant crypt foci (ACF) are intermediate biomarkers of colon cancer. Using these biomarkers, in this study we examined the anticarcinogenic mechanisms of these chemopreventive agents. Rats were maintained on AIN-76A chow or supplemented with 0.4% UDCA or F(6)-D(3) (2.5 nmol/kg chow) and treated weekly with AOM 20 mg i.p./kg wt or saline x 2 weeks. F(6)-D(3) was continued for an additional 2 weeks and UDCA for the duration of the study. At 40 weeks, animals received bromodeoxyuridine (BrdUrd) i.p. 2 h before sacrifice. A portion of each tumor was fixed in formalin and the remainder flash frozen. Colons were divided longitudinally and half-fixed in formalin and half in ethanol. The size and location of methylene blue-stained ACF were recorded. Cell proliferation (BrdUrd labeling) and apoptosis (terminal deoxynucleotidyl transferase-mediated nick end labeling assay) were measured in colonic crypts and tumors. Protein expression levels of several regulators of cell proliferation were analyzed by immunostaining and Western blotting. Colonic crypt cyclin D1 and E-cadherin mRNA levels were measured by real-time PCR. In saline injected controls, neither UDCA nor F(6)-D(3) alone had any effect on cytokinetic parameters or on the expression of mitogenic regulators. AOM significantly increased the proliferation (percentage of BrdUrd-positive cells) of both ACF (23.1 +/- 1.7%) and non-ACF crypts (17.6 +/- 1.6%), compared with normal colonic crypts (4.5 +/- 0.8%; P < 0.05). This hyperproliferation was accompanied by a 5-fold increase in cyclin D1 and >50% decrease in E-cadherin protein (P < 0.05) in ACF, both of which are predicted to be growth-enhancing alterations. UDCA and F(6)-D(3) significantly (P < 0.05) inhibited AOM-induced crypt cell hyperproliferation, ACF development, and tumor burden. These chemopreventive agents also significantly blocked AOM-induced alterations in cyclin D1 and E-cadherin protein in ACF and tumors. In ACF, changes in mRNA levels of cyclin D1, but not E-cadherin, paralleled alterations in protein expression. Cyclooxygenase-2 and inducible nitric oxide synthase were increased in AOM tumors but not in ACF, and these changes were blocked by UDCA and F(6)-D(3). UDCA and F(6)-D(3) significantly inhibited ACF development and hyperproliferation, in part, by preventing carcinogen-induced alterations in cyclin D1 and E-cadherin. In established tumors, UDCA and F(6)-D(3) also limited inductions of cyclooxygenase-2 and inducible nitric oxide synthase, which together with their effects on cyclin D1 and E-cadherin, contribute to their chemopreventive actions.     

Small cell neuroendocrine carcinoma of the cervix: outcome and patterns of recurrence

OBJECTIVES: To analyze the sites of relapse and overall survival in women with neuroendocrine marker-positive small cell carcinoma of the cervix. METHODS: The records of all women who had their initial treatment for cervical cancer at The University of Texas M.D. Anderson Cancer Center between 1980 and 2000 were reviewed. Fifty-one patients had stages I-III cancers that were originally described as "small cell" or "neuroendocrine." Histological material was available for reexamination in 45 cases; of these, 21 were found to have small cell neuroendocrine carcinoma (SCNEC) as indicated by positive staining for chromogranin, synaptophysin, or CD56. Local treatment consisted of a radical hysterectomy in six patients and radiation therapy in 15. Thirteen patients received chemotherapy as part of their initial treatment. The median follow-up for surviving patients was 83 months (range, 25-209 months). RESULTS: Fourteen (66%) of the 21 patients had a relapse. The median time to first relapse from the initiation of treatment was 8.4 months (range, 3.6-28 months). Most patients developed hematogenous distant metastases before their death. Only 2 of 15 patients who were treated with radiation therapy had a recurrence within the radiation fields. However, five patients had a recurrence above the radiation fields in the paraaortic lymph nodes, and two patients had a recurrence distal to the pelvic fields in the vagina. No patient had brain metastases as the sole site of first recurrence. However, two patients developed brain metastases concurrently with lung metastases. The overall survival rate was 29% at 5 years; none of the patients who had disease more extensive than stage IB1 or clinical evidence of lymph node metastases survived their disease. CONCLUSIONS: Patients with small cell neuroendocrine cervical cancer have a poor prognosis. Their course is frequently characterized by the development of widespread hematogenous metastases; locoregional recurrence outside irradiated fields is also frequent. Brain metastases were seen only in patients who also had lung metastases, suggesting that prophylactic cranial irradiation would be of little benefit.     

Effect of Curcuma longa on vascular function in native Tamilians with type 2 diabetes mellitus: A randomized,double‐blind,parallel arm,placebo‐controlled trial

Diabetes mellitus is characterized by increased central arterial stiffness and endothelial dysfunction leading to increased risk of cardiovascular complications. The aim of this study is to evaluate the effect of Curcuma longa on arterial stiffness and endothelial dysfunction in patients with type 2 diabetes mellitus. This randomized controlled trial was conducted in 136 patients of type 2 diabetes. Among them, 114 completed at least one follow‐up visit and included for data analysis. Arterial stiffness parameters were measured at baseline and every month for 3 months and endothelial dysfunction markers at baseline and after 3 months of treatment with C. longa or placebo. These parameters were compared between the two groups. Both C. longa and placebo groups were comparable at baseline. After 3 months of treatment, C. longa produced significant reduction from baseline in carotid–femoral pulse wave velocity (p = .002), left brachial–ankle pulse wave velocity (p = .001), aortic augmentation pressure (p = .007), aortic augmentation index (p = .007), and aortic augmentation index at heart rate 75 (p = .018) as compared with the placebo group. Three months treatment with C. longa significantly decreases arterial stiffness as compared with placebo in type 2 diabetes mellitus patients.     

Assessment of perioperative transfusion therapy and complications in sickle cell disease patients undergoing surgery

BACKGROUND: Perioperative blood transfusion is usually given to sickle cell disease patients to reduce or prevent perioperative morbidity. Assessment of such a practice was the subject of our study. METHODS: A retrospective one year survey of sickle cell disease patients undergoing surgery at Salmaniya Medical Complex, Bahrain was conducted. The medical records were reviewed to characterize the surgical procedure, transfusion management and perioperative complications. RESULTS: 85 sickle cell disease patients who underwent surgery were studied. Preoperatively, 21.2% had exchange transfusion (ETX), 24.7% had simple transfusions (STX) and 54.1% had no transfusion (NTX). 14.1% of all patients had postoperative complications, and 50% of those, had complications from the laparoscopic cholecystectomy group. The incidence of sickle cell crisis postoperatively was 22.2% in ETX group, 9.5% in STX group and 4.34% in the NTX group. The incidence of acute chest syndrome postoperatively was found to be 5.55% in the ETX group, 4.76% in the STX group and 4.34% in the NTX group. No intraoperative complications were recorded in all groups. All patients who had postoperative complications had a preoperative HBSS > 40%. CONCLUSION: Exchange transfusion does not prevent perioperative complications of sickle cell disease patients. HBSS > 40% carries a higher risk of postoperative complications.     

Acute tumour lysis syndrome after oral fludarabine in a patient with chronic lymphocytic leukaemia

Acute tumour lysis syndrome (TLS) is a very rare complication of cytotoxic therapy in patients with chronic lymphocytic leukaemia (CLL). We report a patient with CLL who developed tumour lysis syndrome twice after oral fludarabine therapy. Both times TLS developed more than 2 weeks after the initiation of therapy. To our knowledge this is the first reported case of TLS in CLL precipitated by oral fludarabine.     

Identification of Tunisian Leishmania spp. by PCR amplification of cysteine proteinase B (cpb) genes and phylogenetic analysis

Discrimination of the Old World Leishmania parasites is important for diagnosis and epidemiological studies of leishmaniasis. We have developed PCR assays that allow the discrimination between Leishmania major, Leishmania tropica and Leishmania infantum Tunisian species. The identification was performed by a simple PCR targeting cysteine protease B (cpb) gene copies. These PCR can be a routine molecular biology tools for discrimination of Leishmania spp. from different geographical origins and different clinical forms. Our assays can be an informative source for cpb gene studying concerning drug, diagnostics and vaccine research.     

The influence of three acid modifications on the physicochemical characteristics of tea-waste biochar pyrolyzed at different temperatures: a comparative study

Tea-waste is an abundant feedstock for producing biochar (BC) which is considered to be a cost effective carbonaceous adsorbent useful for water remediation and soil amendment purposes. In the present study, tea-waste BC (TWBC) produced at three different temperatures were subjected to nitric, sulfuric and hydrochloric acid modifications (abbreviated as NM, SM and HM respectively). Characteristics of the raw and modified BC such as ultimate and proximate analyses, surface morphology, surface acidity and functionality, point of zero charge, cation exchange capacity (CEC) and thermal stability were compared to evaluate the influence of pyrolysis temperature and of modifications incorporated. The amount of carboxylic and phenolic surface functionalities on TWBC was seen to decrease by 93.44% and 81.06% respectively when the pyrolysis temperature was increased from 300 to 700 °C. Additionally, the yield of BC was seen to decrease by 46% upon the latter temperature increment. The elemental analysis results provided justification for high-temperature BC being more hydrophobic as was observed by the 61% increase in H/C ratio which is an indication of augmented aromatization. The CEC was the highest for the low-temperature BC and was seen to further increase by NM which is attributed to the 81.89% increase in carboxylic functionalities. The surface area was seen to significantly increase for BC700 upon NM (∼27 times). The SM led to pore wall destruction which was observed in scanning electron microscopy images. Findings would enable the rational use of these particular modifications in relevant remediation and soil amendment applications.

Tea-waste biochar produced under different pyrolysis temperatures were subjected to three acid modifications and a comparative evaluation of their key physicochemical characteristics made.