Spatially-distinct redox conditions and degradation rates following field-scale bioaugmentation for RDX-contaminated groundwater remediation.

In situ bioaugmentation for cleanup of an hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX)-contaminated groundwater plume was recently demonstrated. Results of a forced-gradient, field-scale cell transport test with Gordonia sp. KTR9 and Pseudomonas fluorescens strain I-C cells (henceforth "KTR9" and "Strain I-C") showed these strains were transported 13 m downgradient over 1 month. Abundances of xplA and xenB genes, respective indicators of KTR9 and Strain I-C, approached injection well cell densities at 6 m downgradient, whereas gene abundances (and conservative tracer) had begun to increase at 13 m downgradient at test conclusion. In situ push-pull tests were subsequently completed to measure RDX degradation rates in the bioaugmented wells under ambient gradient conditions. Time-series monitoring of RDX, RDX end-products, conservative tracer, xplA and xenB gene copy numbers and XplA and XenB protein abundance were used to assess the efficacy of bioaugmentation and to estimate the apparent first-order RDX degradation rates during each test. A collective evaluation of redox conditions, RDX end-products, varied RDX degradation kinetics, and biomarkers indicated that Strain I-C and KTR9 rapidly degraded RDX. Results showed bioaugmentation is a viable technology for accelerating RDX cleanup in the demonstration site aquifer and may be applicable to other sites. Full-scale implementation considerations are discussed.

Attachment representations, patterns of emotion regulation, and social exclusion in patients with chronic and episodic depression and healthy controls.

BACKGROUND: The experience of social exclusion (ostracism) is linked to the etiology and maintenance of depression. Most individuals experience emotional stress in states of social exclusion. Insecurely attached individuals, especially with an unresolved trauma, show maladaptive coping in response to social stress. The present study examines (a) the differences with regards to attachment representations in episodic (ED) and chronic depressive (CD) inpatients and (b) how ostracism affects their emotional reactions. METHODS: Patients with CD (n=29) and ED (n=23) and healthy control subjects (n=29) were interviewed using the Adult Attachment Projective Picture System (AAP), a valid measure to assess attachment representation; and played a virtual ball tossing game simulating social exclusion (Cyberball). Multiple depression-related risk and protective factors were considered. We hypothesized that CD patients show the most severe attachment disorganization and are emotionally most affected by the social exclusion situation. Moreover, we explored the interaction between ostracism and attachment. RESULTS: Contradicting our hypotheses, ED and CD individuals were almost akin with regards to their attachment insecurity/disorganization and reactions to Cyberball. An emotionally altered reaction to social exclusion was identified in the insecure-disorganized depressive subgroup. LIMITATIONS: Small sample size hampering further subgroup analyses. The ED sample may include single CD subjects with recent manifestation. CONCLUSIONS: The pattern of emotion regulation in the depressive groups matches with findings from clinical studies, including attachment research. The relationship between attachment representations and ostracism should be further investigated in larger samples of depressive individuals.

Measurement of DNA cross-linking in patients on ifosfamide therapy using the single cell gel electrophoresis (comet) assay.

The single cell gel electrophoresis comet assay has become established as a sensitive technique for measuring DNA strand breaks. The technique has been modified to allow the sensitive detection and quantitation of DNA interstrand cross-linking at the single cell level. Cells are irradiated immediately before analysis to deliver a fixed level of random strand breakage. After embedding of cells in agarose and lysis, the presence of cross-links retards the electrophoretic mobility of the alkaline denatured cellular DNA. Cross-links are, therefore, quantitated as the decrease in the comet tail moment compared with irradiated controls. Using this method, a linear response of cross-linking versus dose of chlorambucil over a wide dose range was demonstrated in human lymphocytes after drug treatment ex vivo. The method was also sensitive enough to determine cross-linking in clinical samples after chemotherapy. For example, crosslinking was observed in the lymphocytes of patients receiving ifosfamide (3 g/m2/day) as a continuous infusion for 3-5 days or as a 3-h infusion daily for 3 days. Cross-links were detected in all patients within 3 h, with no evidence of DNA single strand break formation. In patients receiving continuous infusion, a plateau of cross-linking was reached by 24 h. In the patients receiving ifosfamide over 3 h, a clear decrease in the peak level of cross-linking was observed before subsequent infusions.

Pharmacokinetics of temozolomide in association with fotemustine in malignant melanoma and malignant glioma patients: comparison of oral, intravenous, and hepatic intra-arterial administration.

PURPOSE: Depletion of the DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (AT) has been shown to increase tumor sensitivity to chloroethylnitrosoureas. Temozolomide (TMZ), an analogue of dacarbazine, can deplete AT, suggesting that it may be used to sensitize tumors to chloroethylnitrosoureas. However, the influence of nitrosoureas on the pharmacokinetics of TMZ is unknown, and a pilot study was performed to assess the pharmacokinetics of TMZ given via, various routes to 29 patients (27 malignant melanomas, 2 gliomas) with or without sequential administration of i.v. fotemustine. METHODS: On day 1, TMZ was given intravenously (i.v.), orally (p.o.), or by intra-hepatic arterial infusion (h.i.a.) at four ascending dose levels (150 to 350 mg/m2 per day). On day 2 the same dose of TMZ was given by the same route (or by another route in six patients for determination of its bioavailability), followed 4 h later by fotemustine infusion at 100 mg/m2. Plasma and urinary levels of TMZ were determined on days 1 and 2 by high-performance liquid chromatography after solid-phase extraction. RESULTS: The pharmacokinetics of i.v. TMZ appeared linear, with the area under the curve (AUC) increasing in proportion to the dose expressed in milligrams per square meter (r = 0.86 and 0.91 for days 1 and 2, respectively). The clearance after i.v. administration was 220 +/- 48 and 241 +/- 39 ml/min on days 1 and 2, respectively. The apparent clearance after p.o. and h.i.a. administration was 290 +/- 86 and 344 +/- 77 ml/min, respectively. The volume of distribution of TMZ after i.v., p.o., and h.i.a. administration was 0.4, 0.6, and 0.6 l/kg on day 1 and 0.5, 0.5, and 0.6 l/kg on day 2, respectively. The absolute bioavailability of TMZ was 0.96 +/- 0.1, regardless of the sequence of the i.v.-p.o. or p.o.-i.v. administration, confirming that TMZ is not subject to a marked first-pass effect. A comparison of TMZ pharmacokinetics after i.v. and h.i.a. treatment at the same infusion rate revealed little evidence of hepatic extraction of TMZ. However, the systemic exposure to TMZ (AUC) appeared to decrease at a lower infusion rate. TMZ excreted unchanged in the urine accounted for 5.9 +/- 3.4% of the dose, with low within-patient and high interpatient variability. TMZ crosses the blood-brain barrier and the concentration detected in CSF amounted to 9%, 28%, and 29% of the corresponding plasma levels (three patients). The equilibrium between plasma and ascitic fluid was reached after 2 h (assessed in one patient). CONCLUSION: The sequential administration of fotemustine at 4 h after TMZ treatment had no clinically relevant influence on the pharmacokinetics of TMZ. The potential clinical effect of TMZ given by h.i.a. or by locoregional administration has yet to be established, as has the impact of the infusion duration on patients' tolerance and response rate.

Intracellular Localization and intercellular heterogeneity of the human DNA repair protein O(6)-methylguanine-DNA methyltransferase.

O(6)-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein that removes alkyl adducts from DNA and may be important in tumor resistance to alkylation chemotherapy. MGMT was visualized in human cells and tumor tissues with monoclonal antibodies against MGMT and immunofluorescence microscopy, and fluorescent signals were quantified by digital image analysis. MGMT was found both in the cytoplasm and the nucleus, and in either locale the protein reacts with alkylated DNA bases and becomes inactivated and lost from the cell. Cell lines in culture and xenografts showed a broad normal distribution of nuclear MGMT levels, but human brain tumors often showed a skewed distribution, with a significant fraction of cells with high levels of MGMT. O(6)-Benzylguanine, a suicide substrate inactivator for MGMT activity, reduced MGMT in human cells and in a mouse xenograft to levels undetectable by antibody assay 1 h post-treatment. In melanoma specimens taken from a patient 3 h post-treatment with temozolomide, MGMT levels were reduced by 70%. This quantitative immunofluorescence assay can be used to monitor MGMT and it depletion in human tumors to improve the use of alkylating agents in cancer chemotherapy.

Two successful pregnancies in a patient with single ventricle and transposition of the great arteries.

A 29-year-old female with transposition of the great arteries, single ventricle, a small open ductus arteriosus and a mild aortic incompetence experienced two successful pregnancies without major complications. The benign course of pregnancy is attributed to the relatively low pulmonary vascular resistance and to the fact that the patient has not yet developed an Eisenmenger syndrome.

[Coronary fistulae (author's transl)]. / Beitrag zur Kenntnis der Koronarfisteln

Three patients with coronary fistulae are described, including one patient with a rare coronary-pulmonary double fistula. The clinical features, diagnostic aspects and radiological signs are reviewed.

[Echinococcus of the heart. Infundibular pulmonary stenosis due to a large solitary cyst of the ventricular septum (author's transl)]. / Beitrag zur Echinokokkuserkrankung des Herzens. Infundubuläre Pulomnalstenose durch grosse solitäre Zyste im Ventrikelseptum

An echinococcus cyst in the ventricular septum is described, which produced an infundibular pulmonary stenosis. Following angiography, surgical intervention could be accurately planned and proved successful. The incidence, course, radiological features and diagnosis of cardiac echinococcus are reviewed.

[Large solitary aneurysm of the left coronary artery. Plain films and angiography (author's transl)]. / Grosses solitäres Aneurysma der linken Koronararterie Thoraxröntgenbild und Angiographie

The diagnosis of coronary aneurysms has for a long time been made at autopsy. After a general review of coronary artery aneurysms, a large aneurysm of the circumflex branch of the left coronary is described; this was diagnosed by selective coronary angiography and successfully treated by surgery. The results are compared with six other reported cases of pre-operatively diagnosed coronary artery aneurysms. Since complications, such as rupture, embolisation or infarction, are common in large coronary aneurysms, early diagnosis is desirable. An abnormal bulge of the cardiac contour or circular calcification within or at the edge of the cardiac shadow may be suggestive of the diagnosis.

[Correlation the laevocardiogram and plain chest films in the presence of myocardial insufficiency (author's transl)]. / Die Korrelation zwischen Lävokardiogramm und Nativthoraxröntgenbild bei der Herzmuskelinsuffizienz.

A correlation was attempted in 106 patients with myocardial insufficiency between linear and volume parameters of the laevocardiogram and the corresponding parameters on plain chest films, as well as between pressure measurements and the degree of pulmonary congestion. Measurements on the plain radiograph provide only limited information on the function of the myocardium and the severity of myocardial lesion respectively. Nevertheless, they are of some value during the course of the disease.

[Chronic right-sided pain-associated nondermatomal somatosensory deficit following an accident]. / Halbseitenstörung nach Unfall.

We present the case of a 48-year old man who, eight years after an industrial accident, presents with chronic right-sided nondermatomal pain and hypaesthesia to heat and touch. During symmetric peripheral touch functional magnetic resonance imaging revealed hypometabolism in the left thalamus, somatosensory cortex, and anterior cingulate cortex. Pain-associated nondermatomal somatosensory deficits (NDSDs) localizing to one side of the body are a frequent clinical entity, which are often triggered by an accident. The tendency of NDSDs to extend to adjunct ipsilateral body parts and to become chronic points to maladaptive adjustment of pain-processing areas in the central nervous system. Psychological stress prior to or around the triggering event seems an important risk factor for NDSDs.