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1.
Fortschr Neurol Psychiatr ; 84(6): 363-7, 2016 Jun.
Article in German | MEDLINE | ID: mdl-27391986

ABSTRACT

Radiation-induced tissue damage is caused by ionizing radiation mainly affecting the skin, vascular, neuronal or muscle tissue. Early damages occur within weeks and months while late damages may occur months or even decades after radiation.Radiation-induced paresis of the spine or the trunk muscles with camptocormia or dropped-head syndrome are rare but have already been described as long-term sequelae after treatment of Hodgkin's lymphoma. The differential diagnosis includes limb-girdle muscular dystrophy, fascioscapulohumeral muscular dystrophy (FSHD) or lysosomal storage diseases (e. g. Acid Maltase Deficiency). We present the case of a patient with long lasting diagnostics over many months due to different inconclusive results.


Subject(s)
Back Muscles/innervation , Hodgkin Disease/radiotherapy , Muscular Atrophy, Spinal/diagnosis , Muscular Dystrophies/diagnosis , Neck Muscles/innervation , Paresis/diagnosis , Polyradiculopathy/diagnosis , Radiation Injuries/diagnosis , Radiculopathy/diagnosis , Spinal Curvatures/diagnosis , Spinal Nerve Roots/radiation effects , Adult , Comorbidity , Diagnosis, Differential , Dose Fractionation, Radiation , Electromyography , Hodgkin Disease/pathology , Humans , Lymph Nodes/radiation effects , Male , Neoplasm Staging , Neurologic Examination/radiation effects , Particle Accelerators , Photons/adverse effects , Photons/therapeutic use , Radiotherapy Dosage , Spleen/radiation effects
3.
J Fish Biol ; 86(4): 1251-70, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25727098

ABSTRACT

Microsatellite DNA and mitochondrial DNA control-region sequence analyses were used to determine the population and distinct population segment (DPS) origin of 173 Atlantic sturgeon Acipenser oxyrinchus oxyrinchus encountered from the Gulf of Maine to Cape Hatteras, North Carolina, in NOAA's Northeast Fisheries Observer Program. It was found that the Hudson River was by far the greatest contributor to this coastal by-catch, with 42·2-46·3% of specimens originating there. Generally, specimens represented the geographic province of the river in which they were spawned, but some specimens, particularly those originating in the South Atlantic DPS, moved to great distances. Genetic mixed-stock analyses provide an accurate approach to determine the DPS and population origin of A. o. oxyrinchus by-catch in coastal waters, but most informative management requires that these results be partitioned by locale, season, target fishery and gear type.


Subject(s)
Fishes/genetics , Genetics, Population , Animals , Atlantic Ocean , DNA, Mitochondrial/genetics , Fisheries , Microsatellite Repeats , Sequence Analysis, DNA , United States
4.
West Indian Med J ; 63(1): 29-33, 2014 Jan.
Article in English | MEDLINE | ID: mdl-25303191

ABSTRACT

OBJECTIVES: To evaluate the usefulness of the Forrest classification and the complete Rockall score with customary cut-off values for assessing the risk of adverse events in patients with upper gastrointestinal bleeding (UGI-B) subject to after-hours emergency oesophago-gastro-duodenoscopy (E-EGD) within six hours after admission. METHODS: The medical records of patients with non-variceal UGI-B proven by after-hours endoscopy were analysed. For 'high risk' situations (Forrest stage Ia-IIb/complete Rockall score > 2), univariate analysis was conducted to evaluate odds ratio for reaching the study endpoints (30-day and one-year mortality, re-bleeding, hospital stay ≥ 3 days). RESULTS: During the study period (75 months), 86 cases (85 patients) met the inclusion criteria. Patients' age was 66.36 ± 14.38 years; 60.5% were male. Mean duration of hospital stay was 15.21 ± 19.24 days. Mortality rate was 16.7% (30 days) and 32.9% (one year); 14% of patients re-bled. Univariate analysis of post-endoscopic Rockall score ≥ 2 showed an odds ratio of 6.09 for death within 30 days (p = 0.04). No other significant correlations were found. CONCLUSION: In patients with UGI-B subject to after-hours endoscopy, a 'high-risk' Rockall score permits an estimation of the risk of death within 30 days but not of re-bleeding. A 'high-risk' Forrest score is not significantly associated with the study endpoints.

5.
West Indian med. j ; West Indian med. j;63(1): 29-33, Jan. 2014. tab
Article in English | LILACS | ID: biblio-1045783

ABSTRACT

OBJECTIVES: To evaluate the usefulness of the Forrest classification and the complete Rockall score with customary cut-off values for assessing the risk of adverse events in patients with upper gastrointestinal bleeding (UGI-B) subject to after-hours emergency oesophago-gastro-duodenoscopy (E-EGD) within six hours after admission. METHODS: The medical records of patients with non-variceal UGI-B proven by after-hours endoscopy were analysed. For 'high risk' situations (Forrest stage Ia-IIb/complete Rockall score > 2), univariate analysis was conducted to evaluate odds ratio for reaching the study endpoints (30-day and one-year mortality, re-bleeding, hospital stay > 3 days). RESULTS: During the study period (75 months), 86 cases (85 patients) met the inclusion criteria. Patients' age was 66.36 ± 14.38 years; 60.5% were male. Mean duration of hospital stay was 15.21 ± 19.24 days. Mortality rate was 16.7% (30 days) and 32.9% (one year); 14% of patients re-bled. Univariate analysis of post-endoscopic Rockall score > 2 showed an odds ratio of 6.09 for death within 30 days (p = 0.04). No other significant correlations were found. CONCLUSION: In patients with UGI-B subject to after-hours endoscopy, a 'high-risk'Rockall score permits an estimation of the risk of death within 30 days but not of re-bleeding. A 'high-risk'Forrest score is not significantly associated with the study endpoints.


OBJETIVOS: Evaluar la utilidad de la clasificación de Forrest y la puntuación de Rockall completa con los valores límites habituales a fin de evaluar el riesgo de eventos adversos en los pacientes con hemorragia gastrointestinal alta (HGIA) sometidos a una esofagogastroduodenoscopia (EGD) de urgencia dentro de seis horas después del ingreso. MÉTODOS: Se analizaron las historias clínicas de pacientes con HGIA de origen no varicoso comprobada por endoscopia de urgencia. Para las situaciones de 'alto riesgo' (etapa Forrest Ia- IIb/puntuación de Rockall completa >2), se realizó un análisis univariado para evaluar las probabilidades de riesgo (oddsratio) y llegar a los criterios de valoración del estudio (mortalidad de 30 días y un año, resangrado, estancia hospitalaria > 3 días). RESULTADOS: Durante el periodo de estudio (75 meses), 86 casos (85 pacientes) cumplieron los criterios de inclusión. La edad de los pacientes fue de 66.36 ± 14.38 años; 60.5% eran varones. La duración promedio de estancia hospitalaria fue de 15.21 ± 19.24 días. La tasa de mortalidad fue de 16.7% (30 días) y 32.9% (1 año); el 14% de los pacientes volvió a tener sangramiento. El análisis univariado de la puntuación Rockall postendoscópica > 2 mostró un odds-ratio de 6.09 por muerte en 30 días (p = 0.04). No se encontraron otras correlaciones significativas. CONCLUSIÓN: En pacientes con HGIA sometidos a endoscopía de urgencia, una puntuación Rockall de 'alto riesgo'permite una estimación del riesgo de muerte dentro de 30 días, pero no de resangrado. Una puntuación Forrest de 'alto riesgo' no es significativa con respecto a los criterios de valoración del estudio.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Endoscopy, Gastrointestinal/methods , Gastrointestinal Hemorrhage/surgery , Retrospective Studies , Treatment Outcome , Emergency Service, Hospital , Length of Stay
6.
Dtsch Med Wochenschr ; 138(21): 1096-101, 2013 May.
Article in German | MEDLINE | ID: mdl-23677503

ABSTRACT

BACKGROUND AND OBJECTIVES: To evaluate the predictive value of pre-endoscopic risk scores in patients with upper gastrointestinal bleeding (UGI-B). PATIENTS AND METHODS: The medical records of patients evaluated by emergency esophago-gastro-duodenoscopy (E-EGD) for suspected UGI-B outside regular working hours were retrospectively analysed. RESULTS: During the 75 months of the study period 112 E-EGDs met the inclusion criteria. Mean age was 65.5 ± 14.7 years. 38.4 % of patients were female. Endoscopy revealed 41 gastro-duodenal ulcers, 16 Mallory-Weiss, 13 varices, 4 neoplasia. 72 patients received transfusions, 39 had endoscopic interventions. 2 patients were surgically treated, 16 had recurrent bleeding. 16 of the 110 patients died during hospitalisation. The following sensitivities were found for the Blatchford score (cut-off > 1), the clinical Rockall score (cut-off > 0) and the Adamopoulos score (cut-off > 2) in predicting need for clinical intervention (endoscopic or surgical intervention or transfusion): 100/97.7/93%, recurrent bleeding: 100/100/93.8%, in-hospital mortality: 100/93.8/93.8%, respectively. CONCLUSIONS: The Blatchford score is a suitable tool in determining the need for clinical intervention and the risk of recurrent bleeding and death in patients with UGI-B. The clinical Rockall score and the Adamopoulos score (the latter had originally been developed to predict active UGI-B at endoscopy and was used with a lower cut-off in our study) are inferior alternatives.


Subject(s)
After-Hours Care , Emergencies , Endoscopy, Digestive System , Gastrointestinal Hemorrhage/classification , Gastrointestinal Hemorrhage/etiology , Severity of Illness Index , Aged , Aged, 80 and over , Erythrocyte Transfusion , Female , Gastrointestinal Hemorrhage/mortality , Gastrointestinal Hemorrhage/therapy , Germany , Hemostasis, Surgical , Hospital Mortality , Humans , Male , Middle Aged , Predictive Value of Tests , Recurrence , Retrospective Studies , Risk Assessment/statistics & numerical data , Survival Analysis
7.
Pharmazie ; 66(2): 98-104, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21434570

ABSTRACT

A series of thiazepines has been studied as new ligands for the benzodiazepine binding site of the GABAA receptor. Compounds with high affinity and weak selectivity regarding alpha beta3gamma2, alpha2beta3gamma2, alpha3beta3gamma2, and alpha5beta3gamma2 subtypes were found. The pharmacophore is discussed based on experimental and theoretical results. The thiazepine sulfur atom was found to be able to act as hydrogen bond acceptor.


Subject(s)
GABA Agents/chemical synthesis , GABA Agents/pharmacology , Pyrans/chemistry , Receptors, GABA-A/drug effects , Thiazepines/chemistry , Chromatography, High Pressure Liquid , HEK293 Cells , Humans , Indicators and Reagents , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Conformation , Recombinant Proteins/chemistry , Reference Standards , Spectrophotometry, Ultraviolet , Stereoisomerism , Structure-Activity Relationship
8.
Vasa ; 39(4): 319-24, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21104621

ABSTRACT

BACKGROUND: Endovascular treatment is an increasingly used therapeutic option in patients with chronic atherosclerotic occlusive mesenteric disease. Purpose of this study was evaluation of patency and mortality in patients treated with visceral artery percutaneous transluminal angioplasty (PTA) or stenting including follow-up. PATIENTS AND METHODS: A retrospective review of 17 consecutive patients (4 women, 13 men) with endovascular treatment for symptomatic chronic mesenteric ischemia from 1998 to 2004 was performed. Mean follow-up period was 42 months. Patient demographics, interventional details, primary and/or secondary patency and mortality were recorded. Cumulative mortality and patency rates were determined using Kaplan-Meier life table analysis. RESULTS: Twenty-six interventions (PTA alone n=13, PTA and stenting n=13) were performed in 17 patients. Interventions were performed in the superior mesenteric artery (n=13) and celiac artery (n=13). The re-intervention rate was 30% (6/26). Re-interventions were performed for the superior mesenteric artery (n=4) and celiac artery (n=2). Cumulative overall 1-year results were primary patency rate 81%, secondary patency rate 94%, and survival rate 82%. Cumulative 10-year results were primary patency rate 73%, secondary patency rate 94%, and survival rate 65%. The 10-year secondary patency rate was 100% in patients post initial stenting and 86% in patients post initial PTA. CONCLUSIONS: Long-term follow-up post endovascular treatment for chronic mesenteric ischemia demonstrated a considerable overall secondary patency rate of 94%. However, the long-term secondary patency rate was higher in patients post initial stenting compared to PTA alone.


Subject(s)
Angioplasty, Balloon/instrumentation , Atherosclerosis/therapy , Endovascular Procedures/instrumentation , Mesenteric Vascular Occlusion/therapy , Stents , Adult , Aged , Aged, 80 and over , Angioplasty, Balloon/adverse effects , Angioplasty, Balloon/mortality , Atherosclerosis/complications , Atherosclerosis/diagnostic imaging , Atherosclerosis/mortality , Constriction, Pathologic , Endovascular Procedures/adverse effects , Endovascular Procedures/mortality , Female , Humans , Kaplan-Meier Estimate , Life Tables , Male , Mesenteric Vascular Occlusion/diagnostic imaging , Mesenteric Vascular Occlusion/etiology , Mesenteric Vascular Occlusion/mortality , Middle Aged , Radiography , Recurrence , Retrospective Studies , Severity of Illness Index , Switzerland , Time Factors , Treatment Outcome , Vascular Patency
9.
Chem Commun (Camb) ; (3): 260-2, 2006 Jan 21.
Article in English | MEDLINE | ID: mdl-16391727

ABSTRACT

Fully functional lipid-modified Ras proteins suitable for the study of Ras-membrane interactions and embodying exclusively native amide bonds can be synthesized in preparative amounts by means of Expressed Protein Ligation.


Subject(s)
Inteins/physiology , Lipids/chemistry , Lipoproteins/chemical synthesis , Protein Engineering/methods , Protein Interaction Mapping/methods , ras Proteins/chemistry , Amides/chemistry , Binding Sites , Membrane Proteins/chemistry , Models, Chemical
10.
Mol Ecol ; 11(10): 1885-98, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12296933

ABSTRACT

Shortnose sturgeon is an anadromous North American acipenserid that since 1973 has been designated as federally endangered in US waters. Historically, shortnose sturgeon occurred in as many as 19 rivers from the St. John River, NB, to the St. Johns River, FL, and these populations ranged in census size from 10(1) to 10(4), but little is known of their population structure or levels of gene flow. We used the polymerase chain reaction (PCR) and direct sequence analysis of a 440 bp portion of the mitochondrial DNA (mtDNA) control region to address these issues and to compare haplotype diversity with population size. Twenty-nine mtDNA nucleotide-substitution haplotypes were revealed among 275 specimens from 11 rivers and estuaries. Additionally, mtDNA length variation (6 haplotypes) and heteroplasmy (2-5 haplotypes for some individuals) were found. Significant genetic differentiation (P < 0.05) of mtDNA nucleotide-substitution haplotypes and length-variant haplotypes was observed among populations from all rivers and estuaries surveyed with the exception of the Delaware River and Chesapeake Bay collections. Significant haplotype differentiation was even observed between samples from two rivers (Kennebec and Androscoggin) within the Kennebec River drainage. The absence of haplotype frequency differences between samples from the Delaware River and Chesapeake Bay reflects a probable current absence of spawning within the Chesapeake Bay system and immigration of fish from the adjoining Delaware River. Haplotypic diversity indices ranged between 0.817 and 0.641; no relationship (P > 0.05) was found between haplotype diversity and census size. Gene flow estimates among populations were often low (< 2.0), but were generally higher at the latitudinal extremes of their distribution. A moderate level of haplotype diversity and a high percentage (37.9%) of haplotypes unique to the northern, once-glaciated region suggests that northern populations survived the Pleistocene in a northern refugium. Analysis of molecular variance best supported a five-region hierarchical grouping of populations, but our results indicate that in almost all cases populations of shortnose sturgeon should be managed as separate units.


Subject(s)
DNA, Mitochondrial/genetics , Fishes/genetics , Genetics, Population , Animals , Conservation of Natural Resources , Genetic Variation , Haplotypes , Molecular Sequence Data , Sequence Analysis, DNA
11.
Drug Metab Dispos ; 27(5): 613-22, 1999 May.
Article in English | MEDLINE | ID: mdl-10220491

ABSTRACT

Retigabine (D-23129, N-(2-amino-4-(4-fluorobenzylamino)-phenyl) carbamic acid ethyl ester) is a potent anticonvulsant in a variety of animal models. Rats metabolized [14C]retigabine mainly through glucuronidation and acetylation reactions. Glucuronides were detected in incubates with liver microsomes or slices, in plasma, and in bile and feces but were absent in urine (0-24 h) that contained about 2% of the dose as retigabine and approximately 29% of the dose in > 20 metabolites, which are derived mainly from acetylation reactions. About 67% of the radioactivity was excreted into feces, approximately 10% of the dose as glucuronide. The metabolite pattern in the urine (0-24 h) of dogs was comparatively simple in that retigabine (13%), retigabine-N-glucuronide (5%), and retigabine-N-glucoside (1%) were present. In the same 24-h interval, about 39% of unchanged retigabine was excreted into feces. Plasma profiling and spectroscopic analysis (liquid chromatography with tandem mass spectrometry NMR) of two isolated urinary metabolites obtained after single oral dosing of 600 mg retigabine in healthy volunteers indicated that both acetylation and glucuronidation are major metabolic pathways of retigabine in humans. We found that in vitro assays with liver slices from rat and humans reveal the major circulating metabolites in vivo.


Subject(s)
Anticonvulsants/metabolism , Carbamates/metabolism , Phenylenediamines/metabolism , Animals , Bile/metabolism , Carbon Radioisotopes , Chromatography, High Pressure Liquid , Dogs , Glucuronates/metabolism , Humans , Male , Microsomes, Liver/metabolism , Nuclear Magnetic Resonance, Biomolecular , Radiometry , Rats , Rats, Wistar
12.
Arch Biochem Biophys ; 322(1): 204-13, 1995 Sep 10.
Article in English | MEDLINE | ID: mdl-7574676

ABSTRACT

Atlantic tomcod (Microgadus tomcod) from the cancer-prone Hudson River population exhibit a genetic polymorphism in the cytochrome P4501A (CYP1A) gene which is evidenced in Northern blot analyses by a truncated transcript and in Southern blot analyses by a deletion in the variant allele. To initially evaluate the functional significance of this polymorphism, we sought to characterize the molecular basis for this polymorphism and to determine its frequency in tomcod from other populations in which the prevalence of neoplasia is low. The common CYP1A allelic sequence was determined from beta-naphthoflavone-induced tomcod cDNA and from tomcod genomic DNA. A sequence of the variant CYP1A allele was obtained by direct sequence analysis of the amplicons of variant tomcod cDNA and genomic DNA. CYP1A exon and intron structure is highly conserved between tomcod and all other teleost and mammalian species compared. Similarity of the deduced tomcod, rainbow trout, and plaice amino acid sequences was 72%, whereas similarity between tomcod and mammalian sequences was approximately 50%. The variant tomcod CYP1A allele results from a 606-bp deletion in the 7th exon of the 3' untranslated region (UTR) of the cDNA. Polymerase chain reaction and Northern blot analyses revealed an absence of this CYP1A polymorphism in tomcod from other rivers. Studies in humans suggest that variation in CYP1A1 cDNA may impact on genetic susceptibility to environmentally induced neoplasia. Furthermore, studies in in vitro mammalian models indicate the importance of 3' UTRs on gene expression by impacting on the stability of transcript. These results suggest that the 3' UTR CYP1A polymorphism in tomcod may have consequences for the genetic susceptibility of Hudson River fish to hepatic neoplasia.


Subject(s)
Carcinoma, Hepatocellular/veterinary , Cytochrome P-450 Enzyme System/genetics , Fish Diseases/genetics , Fishes/genetics , Liver Neoplasms/veterinary , Polymorphism, Genetic , Alleles , Amino Acid Sequence , Animals , Base Sequence , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/genetics , DNA Primers/genetics , DNA, Complementary/genetics , Fish Diseases/etiology , Fresh Water , Humans , Liver Neoplasms/etiology , Liver Neoplasms/genetics , Molecular Sequence Data , North America , Sequence Homology, Amino Acid , Species Specificity , Water Pollutants, Chemical/adverse effects
13.
Thromb Haemost ; 73(4): 597-600, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7495065

ABSTRACT

Insufficiency of epifascial veins promotes venous ulceration and increases thromboembolic risk in general surgery patients. Epifascial varicose vein stripping is therefore considered the most effective prophylactic procedure. Thromboembolic risk of patients undergoing this surgical procedure has not yet been prospectively evaluated but appears to be lower than in general surgery patients. The gold standard of preoperative assessment of varicose surgery patients is ascending pressure phlebography, but this technique is invasive, time consuming and costly. We prospectively investigated 100 consecutive varicose vein surgery patients for postoperative thrombosis. Ascending pressure phlebography (APP) and colour coded duplex sonography (CCDS) were performed before and 10 to 21 days after the stripping operation in 100 and 70 patients, respectively. APP revealed no postoperative deep vein thrombosis in all 100 limbs investigated (0 percent; 95 percent confidence interval: 0 to 2.95). With regard to epifascial vein reflux there was good agreement between APP and CCDS (quadratic weighted kappa: 0.76). In 67 out of 73 superficial veins investigated excellent agreement of diagnostic accuracy was found for both diagnostic procedures (91.78 percent; 95 percent confidence interval: 82.96 to 96.92). We conclude that thrombotic risk of varicose vein surgery is low in properly selected patients. CCDS provides a high degree of accuracy in diagnosis of reflux and regular vein morphology and should therefore replace APP; however, APP does remain essential in the preoperative workup of atypical anatomical variants.


Subject(s)
Postoperative Complications/diagnosis , Thrombosis/diagnosis , Varicose Veins/surgery , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Phlebography , Postoperative Complications/prevention & control , Prospective Studies , Risk Factors , Thrombosis/prevention & control , Ultrasonography, Doppler, Color
14.
Environ Health Perspect ; 102 Suppl 12: 85-90, 1994 Dec.
Article in English | MEDLINE | ID: mdl-7713041

ABSTRACT

CYP1A gene expression has been implicated in the processing of environmental procarcinogens and levels of variation in CYP1A mRNA expression are high in both environmentally exposed and chemically treated Atlantic tomcod. The objective of this study was to evaluate the effects of physical and biological parameters such as temperature, sex, and reproductive state on within-group variation in CYP1A mRNA induction. Levels of variation in CYP1A mRNA expression were directly correlated with mean levels of gene induction. Our results indicate that sex and reproductive state, but not temperature, had significant effects on CYP1A mRNA inducibility in tomcod; however, these parameters did not account for all interindividual variation in CYP1A inducibility. Other intrinsic biological factors, such as genetic polymorphisms in molecular pathways leading to CYP1A induction, may contribute to the high levels of interindividual variation in CYP1A inducibility in Atlantic tomcod.


Subject(s)
Cytochrome P-450 Enzyme System/biosynthesis , Fishes/metabolism , RNA, Messenger/biosynthesis , Water Pollutants, Chemical/toxicity , Animals , Cytochrome P-450 Enzyme System/genetics , DNA Adducts , Enzyme Induction , Female , Fishes/genetics , Gene Expression Regulation, Enzymologic/drug effects , Male , Mutagens/toxicity , Polymorphism, Genetic , Sex Factors , Temperature , Transcriptional Activation
15.
Immunology ; 83(2): 262-7, 1994 Oct.
Article in English | MEDLINE | ID: mdl-7835945

ABSTRACT

Pentoxifylline (PTX) is a methylxanthine compound known to inhibit the production of tumour necrosis factor-alpha (TNF-alpha), which is an important inflammatory mediator. There is also recent evidence that PTX may influence other inflammatory cytokines, such as interleukin-1 (IL-1) and IL-6. Due to the therapeutic implications, the present study addressed the in vivo effects of PTX on the release of TNF-alpha, IL-1 beta, IL-6 and IL-8 by human peripheral blood mononuclear cells (PBMC). When PBMC were obtained from healthy volunteers ingesting 5 x 400 mg PTX orally for 2 days, the ability of PBMC cultured for 24 hr to release TNF-alpha was significantly reduced, while secretion of IL-1 beta, IL-6 and IL-8 was not affected. However, when PBMC were obtained from the same individuals 5 days after PTX had been stopped, the release of all four cytokines was significantly suppressed. This effect appeared to be exerted at the transcriptional level, since Northern blot analysis revealed reduced cytokine transcripts. In order to gain more insight into the effect of PTX on cytokine release, PBMC were obtained from normal volunteers, either stimulated with lipopolysaccharide (LPS) or left unstimulated, and subsequently incubated in vitro with PTX for 48 hr. Under these conditions, only TNF-alpha was found to be reduced by PTX, while IL-1 beta and IL-8 were not affected, IL-6 was even enhanced. However, when PBMC were incubated with PTX for 24 hr, PTX removed thereafter by medium change and cells further cultured, the production not only of TNF-alpha but also of IL-1 beta, IL-6 and IL-8 was reduced, demonstrating that PTX exerts diverse (inhibitory) effects on cytokine release by PBMC.


Subject(s)
Interleukins/biosynthesis , Leukocytes, Mononuclear/drug effects , Pentoxifylline/pharmacology , Tumor Necrosis Factor-alpha/biosynthesis , Blotting, Northern , Cells, Cultured , Cytokines/genetics , Down-Regulation/drug effects , Humans , Interleukin-1/biosynthesis , Interleukin-6/biosynthesis , Interleukin-8/biosynthesis , Leukocytes, Mononuclear/immunology , RNA, Messenger/genetics
16.
Environ Health Perspect ; 102(9): 764-70, 1994 Sep.
Article in English | MEDLINE | ID: mdl-9657708

ABSTRACT

We determined levels of hepatic cytochrome P4501A (CYP1A) mRNA, hepatic DNA adducts, and fluorescent aromatic compounds (FACs) in bile, a measure of exposure to polyaromatic hydrocarbons, in Atlantic tomcod from six river systems ranging from highly polluted to relatively pristine on the northeast North American coast (the Hudson River, New York; the St. Lawrence River, Quebec; the Miramichi River, New Brunswick; the Saco and Royal rivers, Maine; and the Margaree River, Nova Scotia). Hudson River tomcod showed the greatest response for all parameters, and tomcod from the Margaree River exhibited the least response. Tomcod from the Miramichi River exhibited marked induction of CYP1A mRNA but low levels of hepatic DNA adducts and biliary FACs, whereas fish from the St. Lawrence River showed no induction of CYP1A mRNA and moderately elevated levels of DNA adducts and biliary FACs. In tomcod from the Hudson and Miramichi rivers, the levels of CYP1A mRNA were 28 times and 14 times, respectively, as great as the levels in fish from the St. Lawrence, Saco/Royal, and Margaree rivers. Mean levels of DNA adducts varied from 120 nmol adducts/mol bases in Hudson River tomcod to < 3 nmol adducts/mol bases in fish from the Miramichi and Margaree rivers. Concentrations of FACs in the bile of tomcod from the Hudson and St. Lawrence rivers were 8 and 1.8 times, respectively, as great as the concentrations in tomcod from the Miramichi River and Margaree River. In tomcod from the Hudson River, all three biomarkers were markedly elevated; in the St. Lawrence River two biomarkers were elevated, in the Miramichi River one was elevated, but no biomarker was substantially elevated in fish from the Saco/Royal and Margaree rivers. Elevated levels of hepatic DNA adducts and biliary FACs in tomcod from the Hudson River suggest increased exposure to PAHs, consistent with previous studies.


Subject(s)
Cytochrome P-450 Enzyme System/analysis , Environmental Monitoring/methods , Fishes , Liver/enzymology , Water Pollutants, Chemical/analysis , Xenobiotics/analysis , Animals , Atlantic Ocean , Biomarkers/analysis , Canada , United States
17.
Circ Shock ; 38(4): 219-21, 1992 Dec.
Article in English | MEDLINE | ID: mdl-1292886

ABSTRACT

We describe a case of a 38-year-old female accident victim who was admitted to the trauma hospital with an ISS of 66. Successful emergency treatment (including amputation of the left leg) and 4 weeks of intensive care led to an overall improvement so that the patient was extubated on day 29. Throughout this period neopterin was measured routinely 3 times a week and correlated well with the clinical course. At the end of the fifth week massive lung impairment and all clinical signs of sepsis appeared. Neopterin values increased dramatically up to 200 nmol/L. However, no abnormal findings were revealed by X-ray, contrast fluoroscopy, or sonographic imaging. To examine the amputation site more closely, simultaneous determination of neopterin in samples from the vena and arteria femoralis was performed. We found a 50% higher level in the venous blood (300 vs. 200 nmol/L). This was regarded as evidence for a hidden focus. Immediate surgical intervention revealed an abscess, which proved to be Pseudomonas aeruginosa positive. After adequate treatment the patient recovered quickly. In this case neopterin was not only helpful in monitoring the septic episodes of the patient, but proved essential for the detection of a septic focus and the risk of explorative relaparotomy could be omitted.


Subject(s)
Abscess/blood , Biopterins/analogs & derivatives , Postoperative Complications/blood , Pseudomonas aeruginosa , Sepsis/blood , Abscess/microbiology , Adult , Amputation, Surgical , Biopterins/blood , Blood Chemical Analysis , Female , Femoral Artery , Femoral Vein , Humans , Leg/surgery , Neopterin , Pseudomonas aeruginosa/pathogenicity
19.
Schweiz Rundsch Med Prax ; 80(33): 826-31, 1991 Aug 13.
Article in German | MEDLINE | ID: mdl-1871486

ABSTRACT

In secondary osteoporosis, amazing etiologies can be found: We report on two cases of nonsecretory myeloma, which had been diagnosed by investigations for osteoporosis. In this connection the diagnostic value of bone-density evaluation by densitometry and high-resolution tomography is discussed and illustrated.


Subject(s)
Fractures, Spontaneous/etiology , Osteoporosis/complications , Spinal Fractures/etiology , Female , Fractures, Spontaneous/diagnostic imaging , Humans , Male , Middle Aged , Osteoporosis/physiopathology , Radiography , Radionuclide Imaging , Spinal Fractures/diagnostic imaging , Technetium
20.
Biochem Genet ; 28(9-10): 459-75, 1990 Oct.
Article in English | MEDLINE | ID: mdl-1982207

ABSTRACT

It has been reported that Atlantic tomcod (Microgadus tomcod) from the Hudson River exhibit an extremely high incidence of liver tumors. More than 90% of spawning 2-year-old fish display hepatocellular carcinomas. In contrast, representatives of this species from a relatively pristine environment show a much lower incidence of tumors. Genomic DNA and mitochondrial DNA (mtDNA) were isolated from tomcod from the Hudson River, New York, and the Saco River and Royal River, Maine. We found a statistically significant difference in the frequency of PstI-generated restriction fragment length polymorphisms in the abl cellular oncogene between Hudson and Maine tomcod. Allelic variation was observed at two of the three abl domains scored. A single composite genotype seen in approximately 40% of Hudson River fish was seen in only one Maine fish. This polymorphism enabled us to differentiate a Hudson River population from that encountered in the Maine rivers. This is the first demonstration of a population-specific polymorphism at a cellular oncogene locus in any species. In contrast, no restriction site polymorphisms were seen in mtDNA between the populations. The lack of mtDNA diversity in these fish is consistent with the geological history of the area. In combination, these results suggest that the genetic diversity observed at the c-abl oncogene locus must have been a fairly recent event and that oncogene loci may be particularly sensitive to mutational change.


Subject(s)
DNA, Mitochondrial/genetics , Fishes/genetics , Genes, abl , Animals , Biological Evolution , Fish Diseases/genetics , Genetic Variation , Genetics, Population , Liver Neoplasms/genetics , Liver Neoplasms/veterinary , Maine , New York , Polymorphism, Restriction Fragment Length , Restriction Mapping
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