Ultrasound-Guided Interstitial Brachytherapy in the Treatment of Advanced Vaginal Recurrences from Cervical and Endometrial Carcinoma

BACKGROUND: In advanced vaginal recurrences of cervical and endometrial carcinomas therapeutic options are rare because of preceding therapy. PATIENTS AND METHODS: 23 patients developing advanced vaginal recurrences of cervical and endometrial carcinomas were included. 15 patients started with external-beam therapy to the pelvis and eight patients after preceding radiotherapy underwent brachytherapy alone. All patients had ultrasound-guided implantation of transvaginal or transperineal interstitial needles for brachytherapy. Median prescribed total dose was 64 Gy. RESULTS: 18 patients (78%) achieved complete remission. Six patients are alive without tumor and one with tumor after a median follow-up of 64 months. 14 patients died of tumor and two of intercurrent disease. 5-year disease-specific survival and local control rate were 43% and 47%, respectively, in patients with complete remission. Univariate analysis found time to relapse > 2 years, initial diameter < or = 4 cm, initial volume < 15 cm(3), no extension to the pelvic side wall, volume before brachytherapy < 7.5 cm(3), brachytherapy coverage index > 0.8, and prescribed total dose > 64 Gy being positive predictors for local control and survival. CONCLUSION: The use of ultrasound guidance for placement of interstitial needles in template-based brachytherapy of advanced recurrent gynecologic malignancies is a feasible, safe, and cheap method with encouraging results. Today, ultrasound imaging can be also used to some extent for treatment planning which requires further development. Patient- and treatment-related prognostic factors can be defined.     

Ghrelin and bone: is there an association in older adults?: the Rancho Bernardo study.

Laboratory studies suggest that ghrelin is involved in bone metabolism, but studies of ghrelin and bone in humans are limited. We studied sex-specific associations of ghrelin with BMD, NTX, and bone loss. Ghrelin was not associated with BMD or bone loss in either sex. There was a significant inverse association with NTX in men but not in women. INTRODUCTION: Ghrelin is a gastric hormone recently shown to be associated with bone metabolism in animal and in vitro studies. Studies in humans are limited. We investigated the association of ghrelin with BMD, the bone resorption marker N-telopeptide (NTX), and bone loss in older men and women. MATERIALS AND METHODS: Participants were 977 community-dwelling men and non-estrogen-using postmenopausal women, 50-91 years of age. Plasma ghrelin was measured by radioimmunoassay from blood obtained between 1984 and 1987. Between 1988 and 1991, BMD was measured at the midshaft radius by single photon absorptiometry and at the femoral neck, total hip, and lumbar spine by DXA. Axial BMD measurements were repeated an average of 4 years later in 544 participants. Bone turnover was assessed by NTX in urine obtained at the same time as the initial BMD. Multiple regression analyses were used to test sex-specific associations of ghrelin with BMD, NTX, and bone loss in both sexes. RESULTS: No significant ghrelin-BMD or ghrelin-bone loss associations were observed in either sex, after adjusting for age and body mass index (BMI). Ghrelin was inversely associated with NTX in men and positively associated with NTX in women, independent of age. After adjusting for both age and BMI, this association reached statistical significance in men and was weakened in women. CONCLUSIONS: Ghrelin may be associated with bone turnover, but there is no evidence for an association with BMD or short-term change in BMD in older adults.     

Gastrointestinal failure in intensive care: a retrospective clinical study in three different intensive care units in Germany and Estonia

Background  

While gastrointestinal problems are common in ICU patients with multiple organ failure, gastrointestinal failure has not been given the consideration other organ systems receive. The aim of this study was to evaluate the incidence of gastrointestinal failure (GIF), to identify its risk factors, and to determine its association with ICU mortality.     

Valproic acid induced encephalopathy--19 new cases in Germany from 1994 to 2003--a side effect associated to VPA-therapy not only in young children.

Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously.     

Glutamate receptors in striatum and substantia nigra: Effects of medial forebrain bundle lesions

We examined NMDA-sensitive [³H]glutamate, [³H]AMPA, [³H]kainate and metabotropic-sensitive [³H]glutamate binding sites in neostriatum and substantia nigra pars reticulata (SNr) in rats after unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. One week after the lesion, NMDA, AMPA, kainate and metabotropic receptors were decreased in the ipsilateral neostriatum, whereas at three months NMDA receptors were increased while AMPA, kainate and metabotropic receptors were not changed. In the SNr at one week, only AMPA and metabotropic receptors were significantly decreased whereas three months after the lesion NMDA, AMPA and kainate binding sites were decreased. The early decrease of excitatory amino acid receptors in the striatum is likely to reflect degeneration of dopaminergic fibers, suggesting that specific subpopulations of excitatory amino acid binding sites are located on dopaminergic terminals.     

ADAMTS-4 activity on a proteoglycan vs. a polypeptide is controlled by the ancillary domains

Introduction In combination with the catalytic domain, the ancillary domains of the ADAMTS' are proposed to regulate activity via interactions with sulfated GAGs, the extracellular matrix (ECM) and cell surface. Interactions with both GAGs and the ECM have been attributed to the thrombospondin (TSP) type 1 motifs and spacer region ( Kuno and Matsushima 1998 ; Flannery et al. 2002 ). ADAMTS‐1, ‐4 and ‐5, all undergo cleavage within their respective spacer regions ( Flannery et al. 2002 ; Rodriguez‐Manzaneque et al. 2000 ; Georgiadis et al. 2002 ), an event which has been reported to increase activity towards the interglobular domain of aggrecan and decrease the heparin affinity of ADAMTS‐4 ( Flannery et al. 2002 ; Gao et al. 2002 ). Materials and methods V5‐ and His‐tagged recombinant human ADAMTS‐4 constructs terminating after the catalytic (?DTS), disintegrin‐like (?TS), TSP (?S) or spacer region (Full) were expressed in High‐Five cells. Proteoglycanase activities of the resultant proteins were assayed with solution digests of aggrecan and a polyacrylamide‐entrapped aggrecan particle assay. Proteolytic activity was measured using a novel, nonglycosylated, reporter substrate assay. Results All forms of ADAMTS‐4 were active to varying degrees in the reporter substrate assay. Digestion of aggrecan in solution digests was apparent in all proteins with the exception of the catalytic domain in isolation (?DTS). Activity towards aggrecan decreased with increasing truncation of the protein. Discussion Removal of the cysteine‐rich‐spacer domain and further C‐terminal truncations decrease the activity of ADAMTS‐4 towards aggrecan, whilst the proteolytic activity remains intact. Cleavages releasing the ancillary domains of ADAMTS' may therefore alter the catalytic activity of these enzymes against proteoglycans and also nonglycosylated polypeptides. More information is required about potential substrates for the processed forms of ADAMTS‐4.     

Gender differences in condom-related behaviors and attitudes among Mexican adolescents living on the U.S.-Mexico border.

Adolescents are at increasing risk for HIV infection in Mexico. Research on gender differences in risk behaviors and determinants is needed to develop effective HIV prevention interventions targeting Mexican adolescents. This study examined gender differences in the likelihood of unprotected sex and theoretical correlates among high school students in the border city of Tijuana. Three hundred seventy high-school students completed a face-to-face interview and a self-administered survey. Differences in sexual initiation, condom use, intentions to use condoms in the future, and attitudes towards condoms in this population were assessed. Although male students initiated sexual practices earlier than females, females were more likely to have unprotected sex. Females perceived themselves as more likely to avoid unprotected sex in the future and held more favorable attitudes about condoms. The results suggest that stereotypical gender roles and communication barriers place Tijuana female high school students at higher risk for HIV infection than their male peers.