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1.
J Environ Manage ; 183(Pt 3): 794-805, 2016 Dec 01.
Article in English | MEDLINE | ID: mdl-27658655

ABSTRACT

Worldwide the renewable energy sector is expanding at sea to address increasing demands. Recently the race for space in heavily used areas such as the North Sea triggered the proposal of co-locating other activities such as aquaculture or fisheries with passive gears in offshore wind farms (OWFs). Our interdisciplinary approach combined a quantification of spatial overlap of activities by using Vessel Monitoring System and logbook data with a stakeholder consultation to conclude and verify on the actual feasibility of co-location. In the German Exclusive Economic Zone (EEZ) of the North Sea up to 90% of Danish and 40% of German annual gillnet fleet landings of plaice overlapped with areas where OWFs are developed. Our results indicated further that the international gillnet fishery could lose up to 50% in landings within the North Sea German EEZ when OWF areas are closed entirely for fisheries. No spatial overlap was found for UK potters targeting brown crab in the German EEZ. We further identified a number of key issues and obstacles that to date hinder an actual implementation of co-location as a measure in the marine spatial planning process: defining the legal base; implementation of safety regulations; delineation of minimum requirements for fishing vessels such as capacities, quotas, technical equipment; implementation of a licensing process; and scoping for financial subsidies to set up business. The stakeholder consultation verified the scientific findings and highlighted that all those points need to be addressed in a planning process. In the German EEZ we have shown that the socio-economic importance of spatial overlap varies within planning boundaries. Therefore we recommend an interdisciplinary bottom-up approach when scoping for suitable areas of co-location. Hence, an informed marine spatial planning process requires comprehensive and spatial explicit socio-economic viability studies factoring in also ecological effects of OWFs on target species.


Subject(s)
Fisheries , Renewable Energy , Wind , Animals , Germany , North Sea , Public Opinion , Socioeconomic Factors
2.
Methods Enzymol ; 572: 193-213, 2016.
Article in English | MEDLINE | ID: mdl-27241755

ABSTRACT

Cell communications are essential to the organization, development, and maintenance of multicellular organisms. Much of this communication involves changes in RNA transcription and is dynamic. Most methods for studying transcription require interrupting the continuity of cellular function by sacrificing the communicating cells and capturing gene expression information by periodic sampling of individual cells or the population. The IMAGEtag technology to quantify RNA levels in living cells, demonstrated here in yeast, allows individual cells to be tracked over time as they respond to different environmental cues. IMAGEtags are short RNAs consisting of strings of a variable number of tandem aptamers that bind small-molecule ligands. The aptamer strings can vary in length and in configuration of aptamer constituents, such as to contain multiples of the same aptamer or two or more different aptamers that alternate in their occurrence. A minimum effective length is about five aptamers. The maximum length is undefined. The small-molecule ligands are enabled for imaging as fluorophore conjugates. For each IMAGEtag, two fluorophore conjugates are provided, which are FRET pairs. When a cell expresses an RNA containing an IMAGEtag sequence, the aptamers bind their ligands and bring the fluorophores into sufficiently close proximity to allow FRET. The background fluorescence of both fluorophores is minimal in the FRET channel. These features endow IMAGEtags with the sensitivity to report on mRNA expression levels in living cells.


Subject(s)
Aptamers, Nucleotide/chemistry , Fluorescence Resonance Energy Transfer/methods , Fluorescent Dyes/analysis , RNA, Messenger/genetics , Transcription, Genetic , Yeasts/genetics , Aptamers, Nucleotide/genetics , Base Sequence , Cloning, Molecular/methods , Ligands , Optical Imaging/methods , RNA, Messenger/analysis
3.
J Oral Rehabil ; 43(4): 286-90, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26440476

ABSTRACT

Removable dentures are a non-invasive, cost-effective prosthodontic solution for the reduced dentition. Their intended purpose is the rehabilitation of harmonious oral function and aesthetics on a long-term basis. The prevalence of removable dentures among patients of advanced age is high and the quality of the dentures is often poor. The aim of this study was to find the most important shortcomings of removable dentures and address the main targets for improving the quality of prosthodontic rehabilitation. The records from dental check-ups in Austrian residential homes were analysed retrospectively. Dental anamnesis questionnaires and data from the clinical examinations of 105 denture wearers were analysed. The functional condition and retention of 192 dentures had been assessed, as well as the impact of the dentures on the intra-oral tissues. Insufficient denture retention was very common, particularly in the lower jaw (56·0%). Problems with the masticatory function were reported by 26.7% of the denture wearers, 11·4% were dissatisfied with the denture aesthetics, and 4·8% had difficulties with phonetics. Traumatic ulcers were found in 18·1%. Cracks, broken pieces (6·3%) or missing denture teeth (2·1%) were rare. It may be assumed that the findings of the present study also apply to a great percentage of community-dwelling seniors. The most important issues in prosthodontic rehabilitation with removable dentures are denture retention and masticatory function. Regular dental check-ups, denture adjustment and, when necessary, relining can maintain the primary denture quality and prevent damages of the oral tissues caused by ill-fitting dentures.


Subject(s)
Denture, Complete , Denture, Partial, Removable , Jaw, Edentulous, Partially/rehabilitation , Mastication/physiology , Prosthodontics , Aged , Aged, 80 and over , Austria/epidemiology , Dental Restoration Wear , Esthetics, Dental/psychology , Female , Humans , Jaw, Edentulous, Partially/psychology , Jaw, Edentulous, Partially/therapy , Long-Term Care , Male , Middle Aged , Oral Health , Patient Outcome Assessment , Patient Satisfaction/statistics & numerical data , Prosthodontics/economics , Quality of Life
4.
Orthopade ; 41(9): 742-8, 2012 Sep.
Article in German | MEDLINE | ID: mdl-22825055

ABSTRACT

The frequency of infectious diseases of the spine and associated spinal cord injury are constantly increasing. Affected are multimorbid and elderly patients, mostly after prolonged medical treatment. An acute spinal cord injury due to infection is an emergency. A rapid decision for treatment strategy and if at all possible subtle debridement of the infected tissue with decompression of the spinal cord is paramount. Additionally spinal cord injury necessitates specialized treatment and care of the infection. Spinal cord injured patients in general and these patients in particular are prone to complications and need especially trained nursing personnel. It is therefore recommended that patients with vertebral osteomyelitis associated with spinal cord injury should be transferred to dedicated centres of treatment as soon as possible.Just as in cases of spondylodiscitis without spinal cord injury inconsistent surgical or insufficient antibiotic treatment worsens the prognosis significantly. If it is possible to remit the infection, the prognosis for recovery of motor and sensory function is better than in cases with traumatic spinal cord injury. In many cases at least partial recovery can be observed.


Subject(s)
Osteomyelitis/therapy , Paraplegia/therapy , Spinal Cord Injuries/therapy , Spondylitis/therapy , Humans , Osteomyelitis/complications , Paraplegia/etiology , Spinal Cord Injuries/complications , Spondylitis/complications
5.
J Virol ; 83(18): 9512-20, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19587054

ABSTRACT

The requirement for multiple mutations for protease inhibitor (PI) resistance necessitates a better understanding of the molecular basis of resistance development. The novel bioinformatics resistance determination approach presented here elaborates on genetic profiles observed in clinical human immunodeficiency virus type 1 (HIV-1) isolates. Synthetic protease sequences were cloned in a wild-type HIV-1 background to generate a large number of close variants, covering 69 mutation clusters between multi-PI-resistant viruses and their corresponding genetically closely related, but PI-susceptible, counterparts. The vast number of mutants generated facilitates a profound and broad analysis of the influence of the background on the effect of individual PI resistance-associated mutations (PI-RAMs) on PI susceptibility. Within a set of viruses, all PI-RAMs that differed between susceptible and resistant viruses were varied while maintaining the background sequence from the resistant virus. The PI darunavir was used to evaluate PI susceptibility. Single sets allowed delineation of the impact of individual mutations on PI susceptibility, as well as the influence of PI-RAMs on one another. Comparing across sets, it could be inferred how the background influenced the interaction between two mutations, in some cases even changing antagonistic relationships into synergistic ones or vice versa. The approach elaborates on patient data and demonstrates how the specific mutational background greatly influences the impact of individual mutations on PI susceptibility in clinical patterns.


Subject(s)
Drug Resistance, Viral/genetics , HIV Protease/genetics , HIV-1/physiology , Mutation/physiology , Amino Acid Sequence , Cloning, Molecular , Computational Biology , HIV Protease Inhibitors/pharmacology , HIV-1/enzymology , Humans , Peptide Fragments/chemical synthesis , Peptide Fragments/genetics
6.
Poult Sci ; 85(10): 1795-7, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17012171

ABSTRACT

Based on evidence from rodent models, it was hypothesized that furan fatty acids found in corn would inhibit reproduction in the laying hen. An isomeric mixture of furan fatty acids [9, (12)-oxy-10,13-dihydroxystearic acid and 10, (13)-oxy-9,12-dihydroxystearic acid] was administered for a period of 3 wk via the diet (1 and 3 ppm) at levels greater than those in corn to 20-wk-old pullets. There were no overt indications of acute or chronic toxicity (no effects on mortality, feed intake, or average daily gain). Similarly, there was no dose-dependent effect on reproductive parameters [egg production, egg weight, shell thickness, ovarian weight, number or weight of large yolky preovulatory follicles, and number of small yellow follicles (4-8 mm in diameter)]. The present data do not suggest that furan fatty acids are a cause of concern to the poultry industry.


Subject(s)
Chickens/physiology , Fatty Acids/chemistry , Fatty Acids/toxicity , Reproduction/drug effects , Stearic Acids/chemistry , Stearic Acids/toxicity , Zea mays/chemistry , Animal Feed , Animals , Body Weight , Diet/veterinary , Dose-Response Relationship, Drug , Drug Administration Schedule , Fatty Acids/administration & dosage , Female , Organ Size , Ovary/anatomy & histology , Ovary/drug effects , Oviposition/drug effects , Reproduction/physiology , Stearic Acids/administration & dosage
7.
Photochem Photobiol ; 81(4): 924-33, 2005.
Article in English | MEDLINE | ID: mdl-15884972

ABSTRACT

Hydroxy and methoxy perylene quinones are synthesized in an attempt to isolate the essential spectroscopic and biological features of light-induced antiviral agents such as hypericin and hypocrellin. Unlike their naturally occurring counterparts, these synthetic quinones bear the carbonyl, hydroxyl, and methoxy groups in the "bay region." The hydroxy and methoxy compounds have rich absorption spectra with broad features in the visible (approximately 450-800 nm) and relatively more intense and narrow features at wavelengths < or = 350 nm. High-level ab initio quantum mechanical calculations assign the features in the absorption spectra to electronic transitions from S0 to S2 and to higher-lying electronic states. The calculations indicate that in the ground state the trans dihydroxy isomer is 12.5 kcal/mol lower in energy than the cis dihydroxy isomer and is thus the only species present. The lowest-energy trans methoxy ground state isomer and the lowest-energy cis methoxy ground state isomer are found to be degenerate. An additional cis methoxy isomer 6.3 kcal/mol higher in energy than the global minimum is assumed to contribute to the spectrum and is also considered. Finally, the synthetic compounds exhibit similar light-induced antiviral activity to each other, but significantly less than that of hypericin.


Subject(s)
Antiviral Agents/pharmacology , Perylene/analogs & derivatives , Quinones/chemical synthesis , Antiviral Agents/chemistry , Perylene/pharmacology , Quinones/pharmacology , Spectrometry, Fluorescence , Spectrophotometry , Structure-Activity Relationship
8.
Br J Radiol ; 78(928): 355-7, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15774600

ABSTRACT

In patients with suspected liver disease, ultrasound is the most commonly performed initial imaging modality. We report a patient who had previously undiagnosed liver cirrhosis with target-shaped lesions interspersed throughout the liver parenchyma on ultrasound seen as multiple uniform round shaped lesions with varying isoechoic to hyperechoic centres surrounded by a hyperechoic rim. We have termed this the "reverse" target sign as there is inversion of the typical echoic pattern that is normally seen in metastatic liver disease. We suggest this ultrasound sign may represent a method for differentiating cirrhotic liver nodules from other nodular liver lesions.


Subject(s)
Liver Cirrhosis/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Diagnosis, Differential , Humans , Male , Middle Aged , Tomography, X-Ray Computed , Ultrasonography, Doppler, Color
9.
Neurol India ; 52(1): 91-3, 2004 Mar.
Article in English | MEDLINE | ID: mdl-15069248

ABSTRACT

We describe functional imaging findings using MRI, 1H-Magnetic resonance spectroscopy and positron emission tomography in a case of radiation-induced medulloblastoma following radiotherapy for pineal gland tumor. MRS showed a prominent choline peak; FDG, 11C-Met and 11C-Choline PET showed a minimal glucose, increased methionine and choline uptake.


Subject(s)
Brain Neoplasms/pathology , Medulloblastoma/pathology , Neoplasms, Radiation-Induced/pathology , Adult , Brain Neoplasms/diagnostic imaging , Fatal Outcome , Humans , Image Interpretation, Computer-Assisted , Magnetic Resonance Imaging , Male , Medulloblastoma/diagnostic imaging , Neoplasms, Radiation-Induced/diagnostic imaging , Pinealoma/complications , Pinealoma/radiotherapy , Positron-Emission Tomography
10.
Crop Sci ; 44(3): 861-869, 2004.
Article in English | MEDLINE | ID: mdl-17047728

ABSTRACT

Because of expanding markets for high-value niche crops, opportunities have increased for the production of medicinal herbs in the USA. An experiment was conducted in 2001 and 2002 near Gilbert, IA, to study crop performance, weed suppression, and environmental conditions associated with the use of several organic mulches in the production of two herbs, catnip (Nepeta cataria L.) and St. John's wort (Hypericum perforatum L. 'Helos'). Treatments were arranged in a completely randomized design and included a positive (hand-weeded) control, a negative (nonweeded) control, oat straw, a flax straw mat, and a nonwoven wool mat. Catnip plant height was significantly greater in the oat straw than the other treatments at 4 wk through 6 wk in 2001; at 4 to 8 wk in 2002, catnip plant height and width was significantly lower in the negative control compared with the other treatments. Catnip yield was significantly higher in the flax straw mat than all other treatments in 2001. In 2002, St. John's wort yields were not statistically different in any treatments. All weed management treatments had significantly fewer weeds than the non-weeded rows in 2002. Total weed density comparisons in each crop from 2 yr showed fewer weeds present in the flax straw and wool mat treatments compared with positive control plots. There was no significant weed management treatment effect on the concentration of the target compounds, nepetalactone in catnip and pseudohypericin-hypericin in St. John's wort, although there was a trend toward higher concentrations in the flax straw treatment.

11.
J Neurooncol ; 64(3): 227-37, 2003 Sep.
Article in English | MEDLINE | ID: mdl-14558598

ABSTRACT

OBJECTIVES: Despite being in use for nearly two decades, the utility of [18F]2-fluoro-2deoxy-D-glucose positron emission tomography (FDG PET) in the evaluation and treatment of brain tumors remains controversial. We retrospectively analyzed all patients with histologically proven gliomas, between the years 1990 and 2000, who underwent FDG PET studies at various stages of their treatment and who were followed till either death or for a minimum period of 1 year in an attempt to bring resolution to this controversy. METHODS: All PET scans prior to 1997 were acquired on an ECAT 951/31 scanner in 2D. Scans since 1997 were obtained on a Siemens HR+ scanner in 3D mode. The majority of FDG PET scans were co-registered with the magnetic resonance imaging (MRI) scans to aid in diagnosis and therapy. Based on independent visual inspection, two board certified nuclear medicine physicians graded the highest activity level of the tumor using the metabolic grading: 0 = no uptake; 1 = uptake less or equal to normal white matter; 2 = uptake greater than normal white matter and less than gray matter; 3 = uptake equal to or greater than gray mater. The measure of association of lambda (lambda) was used to measure the strength of predictive ability of FDG PET for pathological grading of the gliomas. The Cox proportional hazards regression model was used to assess the significance of grade of uptake on survival. RESULTS: A total of 331 patients were analyzed of which 137 had a PET scan prior to histological diagnosis and therapeutic intervention (mean age = 46.5 years; M:F = 1.7:1). Eighty six percent (143/166) of the patients with low uptake (metabolic scores 0,1) had low-grade gliomas (grade I,II) and 14% (23/166) high-grade gliomas (grade III,IV) on histologic examination. Ninety four percent (154/165) of the patients with high uptake (metabolic scores 2,3) on PET had high-grade gliomas and 7% (11/165) had low-grade gliomas on histologic examination. The grade of uptake had increasing significance on survival as the level increased from 'low' to 'high' (P = 0.0009). Ninety four percent (156/166) of the patients with low uptake survived for > 1 year (median survival of 28 months) and 19% survived for > 5 years. Only 29% (48/165) of patients with high uptake survived for > 1 year, (median survival of 11 months) and none survived for > 5 years. Irrespective of when the scan showed a high uptake of FDG, before or after intervention, the prognosis following that scan was poor. CONCLUSIONS: Our observations confirm the utility of FDG PET as a prognostic tool for the histological grading and survival in patients with gliomas and appears to more than complement pathological grading.


Subject(s)
Brain Neoplasms/diagnostic imaging , Brain Neoplasms/mortality , Fluorodeoxyglucose F18 , Glioma/diagnostic imaging , Glioma/mortality , Radiopharmaceuticals , Tomography, Emission-Computed , Adolescent , Adult , Aged , Aged, 80 and over , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Child , Child, Preschool , Female , Fluorodeoxyglucose F18/metabolism , Follow-Up Studies , Glioma/metabolism , Glioma/pathology , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Radiopharmaceuticals/metabolism , Retrospective Studies , Statistics as Topic , Survival Rate
12.
Photochem Photobiol ; 76(2): 153-7, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12194210

ABSTRACT

The synthesis of a molecule containing hypericin and luciferin moieties joined by a tether is reported. The light-induced (in vitro) antiviral activity as well as the photophysical properties of this new compound are measured and compared with those of the parent compounds, hypericin and pseudohypericin. This tethered molecule exhibits excited-state behavior that is very similar to that of its parent compounds and antiviral activity that is identical, within experimental error, to that of its more closely related parent compound, pseudohypericin. The implications for a photodynamic therapy that is independent of external light sources are discussed.


Subject(s)
Firefly Luciferin/radiation effects , Perylene/analogs & derivatives , Perylene/radiation effects , Photosensitizing Agents/radiation effects , Anthracenes , Firefly Luciferin/chemical synthesis , Firefly Luciferin/chemistry , Perylene/chemical synthesis , Perylene/chemistry , Photochemistry , Photochemotherapy , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/chemistry
13.
Phytopathology ; 92(5): 456-63, 2002 May.
Article in English | MEDLINE | ID: mdl-18943019

ABSTRACT

ABSTRACT This study explored the possibilities that changes in the egg shell/lipid layer electrical potential or pH communicate external hatching conditions to the Heterodera glycines second-stage juvenile (J2) within the mature egg and that electrophysiology could measure effects of chemicals on emergence. Potentials were measured following application of the emergence inducers (ZnSO(4) and ZnCl(2)), ions that do not affect emergence, or synthetic emergence inhibitors. Results were compared with pH measurements and emergence bioassays. Healthy appearing eggs had negative resting potentials. Application of ZnSO(4) caused a smooth depolarization. However, eggs containing J2 and immature eggs depolarized to a similar degree when ZnSO(4) was added. In addition, ZnSO(4), synthetic emergence inhibitors, and CaCl(2) caused similar depolarization, and some depolarization was measured in dye-permeable eggs and empty shells. Results suggest that change in cation surface charge contributed to depolarization and that Cl penetrated the egg shell/lipid layer without causing potential changes. In bioassays, zinc consistently stimulated emergence to a greater degree than H(2)O, other cations, or buffers, and counteracted emergence inhibitors. Zinc-caused emergence stimulation was independent of pH. In summary, it is concluded that depolarization and pH are not emergence signals and electrophysiology is unlikely to measure effectiveness of emergence stimulators or inhibitors.

14.
Photochem Photobiol ; 74(2): 157-63, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11547549

ABSTRACT

Using time-resolved infrared spectroscopy, ab initio quantum mechanical calculations and synthetic organic chemistry a region in the infrared spectrum of triplet hypericin has been found between 1400 and 1500 cm-1 corresponding to the translocation of the hydrogen atom between the enol and the keto oxygens, O...H...O. This result is discussed in the context of the photophysics of hypericin and of eventual measurements to observe directly the excited-state H-atom transfer.


Subject(s)
Perylene/analogs & derivatives , Perylene/chemistry , Anthracenes , In Vitro Techniques , Perylene/pharmacology , Photochemistry , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Spectrophotometry, Infrared
15.
Photochem Photobiol ; 74(2): 216-20, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11547558

ABSTRACT

A series of hypericin analogs were found to differ in their cytotoxic activity induced by ambient light levels. These analogs vary in their ability to partition into cells, to generate singlet oxygen as well as in other photophysical properties. The data suggest that the biological activity of hypericin is due to a combination of factors whose roles may vary under different circumstances.


Subject(s)
Antineoplastic Agents/pharmacology , Perylene/analogs & derivatives , Perylene/pharmacology , Anthracenes , Antineoplastic Agents/chemistry , Humans , Oxygen/metabolism , Perylene/chemistry , Photochemotherapy , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Singlet Oxygen , Tumor Cells, Cultured
16.
Mol Cell Probes ; 15(3): 169-75, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11352598

ABSTRACT

Real-time PCR and fluorogenic probes were combined in a simple, rapid and sensitive method to genotype murine breeding stocks and their progeny for a point mutation. DNA from tail biopsies of newborn mice was mixed with amplification primers and fluorogenic hybridization probes in a PCR mixture. The primers were designed to amplify a region of the Fas-Ligand gene including the site for the gld natural point mutation. The fluorogenic hybridization probes overlaid this target sequence and were used to detect amplification of the PCR fragment as well as determine the presence of the point mutation using fluorescence resonance energy transfer (FRET). Both mutated and wild-type forms of the gene fragment were amplified as detected with real-time PCR. Melting curve profiles completed on each amplified sample revealed the genotype for each mouse. These genotypes were confirmed by sequencing the amplified fragments. These results suggest real-time spectrofluorometric PCR techniques incorporating FRET-based hybridization probes may be used for rapid, sensitive, inexpensive and reliable genotyping.


Subject(s)
DNA/metabolism , Fluorescent Dyes/metabolism , Genotype , Nucleic Acid Hybridization/methods , Polymerase Chain Reaction/methods , Animals , Animals, Newborn , Mice , Mice, Inbred C57BL , Models, Genetic , Mutation , Sequence Analysis, DNA , Spectrometry, Fluorescence/methods , Temperature
17.
Clin Psychol Rev ; 21(3): 345-73, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11288605

ABSTRACT

This article is a summary of some of the more recent research on the diagnosis, etiology, and treatment of Cluster B personality disorders (antisocial, histrionic, borderline, and narcissistic). Research on psychological, psychosocial, and biological perspectives of these disorders is presented. Individual psychotherapy, group psychotherapy, and other forms of multi-person therapies are also discussed. Finally, perspectives on issues of countertransference when treating these personality-disordered patients are addressed.


Subject(s)
Personality Disorders , Psychotherapy , Countertransference , Diagnosis, Differential , Humans , Personality Disorders/diagnosis , Personality Disorders/etiology , Personality Disorders/therapy , Psychotherapy, Group
18.
Int J Radiat Oncol Biol Phys ; 49(3): 665-71, 2001 Mar 01.
Article in English | MEDLINE | ID: mdl-11172947

ABSTRACT

BACKGROUND: In locally advanced pancreatic cancer, the combination of chemotherapy with radiotherapy is gaining increasing importance; although, in view of the reported long-term results of several contemporary trials, further improvements are certainly warranted. The aim of the present study was to evaluate the effectiveness and safety of a combined-treatment modality consisting of systemic chemotherapy with 24-h continuous infusional gemcitabine and mitomycin C, plus external beam radiotherapy in patients with localized unresectable adenocarcinoma of the pancreas. METHODS AND MATERIALS: Systemic chemotherapy consisted of mitomycin C 8 mg/m2 given as i.v. bolus injection on day 1 and gemcitabine administered as a 24-h continous infusion once weekly for 3 of 4 weeks. The starting dose of gemcitabine was 100 mg/m2 and dose levels were escalated in consecutive cohorts of 3-6 patients to 130 and 160 mg/m2, utilizing an escalating-dose Phase I trial design. Radiation therapy using megavolt irradiation (total dose, 45 Gy, 1.8 Gy/day) of 6 MV photons or greater with a 3- or 4-field technique was delivered concurrently for 5-6 weeks. RESULTS: Between January 1997 and August 1998, a total of 15 patients were enrolled in this trial, all of whom were assessable for toxicity, response, and survival. The dose-limiting toxicities at the 160 mg/m2 gemcitabine level were myelosuppression, specifically neutropenia +/- thrombocytopenia, and gastrointestinal symptoms, including stomatitis, vomiting, and diarrhea. Only 1 partial response was observed (7%), and disease was stabilized in 10 additional patients (67%). The median time to progression was 5.5 months (range, 2-12 months). Whereas all patients developed distant metastases, locoregional failure occurred in only 3. The median survival time was 8.3 months (range, 2.5 to 22.0+ months), and the 1-year survival rate was 13.3%. CONCLUSION: The MTD of gemcitabine when given as prolonged infusion in combination with mitomycin C and radiation therapy was 130 mg/m2/week. Therapeutic results suggest that combined chemoradiation with this regimen is feasible and effective for local control of pancreatic cancer, but essentially ineffective in counteracting metastatic tumor growth.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/radiotherapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/radiotherapy , Adenocarcinoma/pathology , Aged , Combined Modality Therapy , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Female , Humans , Injections, Intravenous , Leukopenia/etiology , Male , Middle Aged , Mitomycin/administration & dosage , Neoplasm Staging , Neutropenia/etiology , Pancreatic Neoplasms/pathology , Survival Analysis , Thrombocytopenia/etiology , Gemcitabine
19.
J Neurooncol ; 55(1): 39-44, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11804281

ABSTRACT

Leptomeningeal metastases (LM) is often an elusive disease frequently diagnosed at an advanced clinical stage. Early diagnosis may allow for prompt initiation of treatment with minimal tumor burden and maximal chance of survival, especially in solid tumors such as breast cancer. Although the method of choice for imaging LM currently is by gadolinium enhanced magnetic resonance imaging (MRI), the technique has a high sensitivity but low specificity. We report the first case of Carbon 11-labelled methionine (Cmet) positron emission tomography (PET) imaging of leptomeningeal metastases in a patient with primary breast cancer. This patient presented with clinical features suggestive of LM, but had inconclusive cerebrospinal fluid (CSF) findings. Although, the contrast enhanced MRI revealed calvarial and meningeal lesions, it is known that meningeal enhancement on MRI does not always indicate metastases. In this clinical dilemma the strong methionine uptake on PET helped steer the diagnosis in favor of cancerous infiltration even before the CSF cytology became positive for malignancy.


Subject(s)
Breast Neoplasms/pathology , Meningeal Neoplasms/diagnostic imaging , Meningeal Neoplasms/secondary , Methionine , Carbon Isotopes , Female , Fluorodeoxyglucose F18 , Humans , Magnetic Resonance Imaging , Middle Aged , Tomography, Emission-Computed , Tomography, X-Ray Computed
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