Oral melphalan pharmacokinetics — relation to dose in patients with multiple myeloma

The pharmacokinetics of melphalan have been studied after oral doses of 5,10 and 20 mg, and 10 mg i.v. Seven patients with multiple myeloma received the drug on 4 consecutive days and the concentration of melphalan was determined by liquid chromatography. Melphalan was rapidly absorbed after p.o. administration. Absorption lag-time was less than 1 h. The median time for attaining the peak concentration was 1.12 h (97% confidence interval: 0.68–1.55), 1.21 h (0.85–1.43) and 1.08 h (0.84–1.29) after doses of 5,10 and 20 mg. The bioavailability showed large interindividual variations, and was not significantly affected by the dose given. There was a significant decrease in bioavailability during the treatment course (P < 0.05). Absorption of melphalan obeys first-order kinetics in the dose interval studied. The results indicate that it might be of benefit to administrate oral melphalan for fewer days than the usually used 4 day regimen, in an attempt to achieve a higher bioavailability.     

Enzymatic detoxification of gluten by germinating wheat proteases: Implications for new treatment of celiac disease

Introduction. Currently the only treatment for celiac disease is a lifelong gluten-free diet. The diet is, however, often burdensome, and thus new treatment options are warranted. We isolated proteases from germinating wheat grain naturally meant for total digestion of wheat storage proteins and investigated whether these enzymes can diminish toxic effects of gluten in vitro and ex vivo.

Methods. Pepsin and trypsin digested (PT) gliadin was pretreated with proteases from germinating wheat, whereafter the degradation was analyzed by HPLC-MS (high-performance liquid chromatography and mass spectroscopy) and sodium dodecyl sulphate polyacrylamide gel electrophoresis. The toxicity of cleaved PT-gliadin products was assessed in Caco-2 epithelial cells, celiac patient-derived T cells, and in human small intestinal mucosal organ culture biopsies.

Results. Proteases from germinating wheat degraded gliadin into small peptide fragments, which, unlike unprocessed PT-gliadin, did not increase epithelial permeability, induce cytoskeletal rearrangement or changes in ZO-1 expression in Caco-2 cells. Pretreated gliadin did not stimulate T cell proliferation in vitro or enhance the production of autoantibodies to culture supernatants and the activation of CD25+ lymphocytes in the organ culture to the same extent as unprocessed PT-gliadin.

Discussion. Germinating wheat enzymes reduce the toxicity of wheat gliadin in vitro and ex vivo. Further studies are justified to develop an alternative therapy for celiac disease.     

IgA-class autoantibodies against neuronal transglutaminase, TG6 in celiac disease: no evidence for gluten dependency

BackgroundIt has been suggested that antibodies against transglutaminase (TG) 6 could serve as a biomarker to identify a subgroup of gluten-sensitive patients who may be at risk of developing neurological disease. We here investigated whether TG6-targeted autoantibodies are a characteristic feature of celiac patients, especially those with neurological symptoms, and further, whether such antibodies are gluten-dependent.MethodsSerum IgA-class TG6 autoantibodies were measured in untreated and treated celiac patients with and without neurological manifestions and in non-celiac controls. The results were compared to TG2 autoantibody levels.ResultsDuring a gluten-containing diet the number of TG6 autoantibody-positive celiac patients with neurological problems (25%) did not significantly differ from that of TG6-seropositive patients without neurological impairment (16%) or from non-celiac controls (15%). This was in contrast to our finding in TG2 autoantibody-positive individuals, whose numbers differed significantly between all three study groups. On a gluten-free diet the levels of TG6 autoantibodies remained unchanged.ConclusionsWe conclude that the serum IgA-class TG6 autoantibody assay is not able to distinguish gluten-sensitive patients with neurological manifestations from celiac patients without neurological problems or from control subjects, and further, that TG6 autoantibodies are not gluten-dependent.     

Prostate Cancer Recurrence in Kidney Transplant Recipient 15 Years After Radical Prostatectomy: A Case Report

Incidence of malignant tumors in kidney transplant recipients is higher than nontransplanted population due to many factors, such as immunosuppression therapy and complex donor-recipient interaction. Genitourinary malignancies have been reported as the second most common malignancy in kidney transplant recipients. In this regard, prostate cancer is the most common neoplasm. Herein, we describe a rare case of prostate cancer recurrence after 15 years in a patient who underwent kidney transplant after radical prostatectomy.     

Treatment of temporomandibular disorders with a combination of hard acrylic stabilisation appliance and a soft appliance in the opposing jaw. A retro- and prospective study

The aim of this study was to evaluate the treatment effect of a combined treatment with a stabilisation appliance and a soft appliance in the opposing jaw in patients refractory to previous TMD treatment. During a 5-year-period, 2001-2005, a total of 98 patients received the combined treatment at the Department of Stomatognathic Physiology, the Institute for Postgraduate Dental Education, J?nk?ping, Sweden. Before the patients received the combined treatment, they had already been given several different TMD treatments during a long period of time, either before referral or at the specialist clinic, with only minor or no effect on their TMD symptoms. The patients were followed prospectively (n=10), or analysed retrospectively (n=88). The data registered were gender, age, main indication for TMD treatment, number of visits to the clinic before and after the introduction of the combined treatment, as well as according to a clinical (Di) and anamnestic (Ai) dysfunction index. The most common causes for treatment in the retrospective material were problems of muscular origin and problems of both muscular and TMJ origin. In the prospective material, most of the patients had mainly muscular symptoms. Both the clinical and anamnestic dysfunction index decreased statistically significantly in the retrospective material after the introduction of the combined treatment. There was a numerical improvement of both indices also in the prospective material. In conclusion, the present investigation showed that a combined treatment with a hard acrylic stabilisation appliance and a soft appliance in the opposing jaw seems to give a remarkable improvement of TMD signs and symptoms in apparently therapy resistant TMD patients. General conclusions should, however, be made with caution due to the fact that the study did not include any control group. There is an obvious need for randomized controlled studies concerning the efficacy and effectiveness of the combined treatment presented in this study.     

Health-related effects of worksite interventions involving physical exercise and reduced workhours

OBJECTIVES: This study examined the health-related effects of two worksite interventions, physical exercise and reduced workhours, on women employed in dentistry. METHODS: Six workplaces were randomized to one of the following three conditions: (i) 2.5 hours of weekly, mandatory physical exercise of middle-to-high intensity to be performed during workhours (N=62), (ii) a reduction of full-time weekly workhours from 40 to 37.5 hours (N=50), and (iii) reference. In all, 177 women participated. Biomarkers and self-ratings in questionnaires were obtained before the intervention (T (1)), and six (T (2)) and 12 months (T (3)) after the intervention. RESULTS: The results showed increased levels of physical activity and exercise in all of the groups, the level of physical exercise being significantly greater in the physical exercise group. Repeated-measures analyses of variance using data from T (1)and T (3)for biological measures and all three time points for self-ratings produced significant interaction effects for glucose, waist-to-hip ratio, and work ability and clear trends for general symptoms and upper-extremity disorders. Posthoc analyses showed that the results of the health-related measures differed between the interventions, decreased glucose and upper-extremity disorders in the exercise group, and increased high-density lipoprotein and waist-to-hip ratio among those working reduced hours. CONCLUSIONS: These results show that the two interventions had small and varied effects on biomarkers and self-reports of different aspects of health among women. It is suggested that interventions involving a modest reduction in workhours seem to be more effective if these hours are used for physical exercise.     

CT arthrography of the wrist using a novel, mobile, dedicated extremity cone-beam CT (CBCT)

Purpose

To evaluate the feasibility and intra- and interobserver agreement of CBCT arthrography of wrist ligaments, triangular fibrocartilaginous complex (TFCC), and to assess the sensitivity (SE), specificity (SP), accuracy (ACC), and positive and negative predictive value (PPV, NPV) of CBCT arthrography in the diagnosis of scapholunate (SLL) and lunotriquetral (LTL) ligament tears, TFCC, and cartilage abnormalities of the scaphoid and lunate with their corresponding radial surfaces (scaphoid and lunate fossa) using a novel, mobile, dedicated extremity CBCT scanner.

Materials and methods

Fifty-two consecutively enrolled subjects (26 M, 26 F, mean age 38 years, range 18–66 years) with suspected wrist ligament tears underwent CBCT-arthrography before normally scheduled MR arthrography.An extremity CBCT was used for imaging with isotropic voxel size of 0.4 × 0.4 × 0.4 mm³. Subsequent routine 1.5 T MRI was performed using a dedicated wrist coil.Two observers reviewed the anonymized CBCT images twice for contrast enhancement (CE) and technical details (TD), for tears of the SLL, LTL, and TFCC. Also, cartilage abnormalities of the scaphoid and lunate with their corresponding radial surfaces (scaphoid and lunate fossa) were evaluated. Inter- and intraobserver agreement was determined using weighted kappa statistics. Since no surgery was performed, MRI served as a reference standard, and SE and SP, ACC, PPV, and NPV were calculated.

Results

Intra- and interobserver kappa values for both readers (reader 1/reader 2; first reading/second reading) with 95 % confidence limits were: CE 0.54 (0.08–1.00)/ 0.75 (0.46–1.00); 0.73 (0.29–1.00)/ 0.45 (0.07–0.83), TD 0.53 (0.30–0.88)/ 0.86 (0.60–1.00); 0.56 (0.22–0.91)/ 0.67 (0.37–0.98), SLL 0.59 (0.25–0.93)/ 0.66 (0.42–0.91); 0.31 (0.06–0.56)/ 0.49 (0.26–0.73), LTL 0.83 (0.66–1.00)/ 0.68 (0.46–0.91); 0.90 (0.79–1.00)/ 0.48 (0.22–0.74); TFCC (0.72–1.00)/ (0.79–1.00); 0.65 (0.43–0.87)/ 0.59 (0.35–0.83), radius (scaphoid fossa) 0.45 (0.12–0.77)/ 0.64 (0.31–0.96); 0.58 (0.19–0.96)/ 0.38 (0.09–0.66), scaphoid 0.43 (0.12–0.74)/ 0.76 (0.55–0.96); 0.37 (0.00–0.75)/ 0.32 (0.04–0.59), radius (lunate fossa) 0.68 (0.36–1.00)/ 0.42 (0.00–0.86); 0.62 (0.29–0.96)/ 0.51 (0.12–0.91), and lunate 0.53 (0.16–0.90)/ 0.68 (0.44–0.91); 0.59 (0.29–0.88)/ 0.42 (0.00–0.84), respectively. The overall mean accuracy was 82–92 % and specificity was 81–94 %. Sensitivity for LTL and TFCC tears was 76–83, but for SLL tears it was 58 %. For cartilage abnormalities, the accuracy and negative predictive value were high, 90–98 %.

Conclusions

A dedicated CBCT extremity scanner is a new method for evaluating the wrist ligaments and radiocarpal cartilage. The method has an overall accuracy of 82–86 % and specificity 81–91 %. For cartilage abnormalities, the accuracy and negative predictive value were high.