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1.
Braz J Med Biol Res ; 56: e12576, 2023.
Article in English | MEDLINE | ID: mdl-37377306

ABSTRACT

Type 2 diabetes mellitus (T2DM) is characterized by endothelial dysfunction that causes micro- and macrovascular complications. Low intensity therapeutic ultrasound (LITUS) may improve endothelial function, but its effects have not been investigated in these patients. The aim of our study was to compare the effects of pulsed (PUT) and continuous (CUT) waveforms of LITUS on the endothelium-dependent vasodilation of T2DM patients. The present randomized crossover trial had a sample of twenty-three patients (7 men) diagnosed with T2DM, 55.6 (±9.1) years old, with a body mass index of 28.6 (±3.3) kg/m2. All patients were randomized and submitted to different waveforms (Placebo, CUT, and PUT) of LITUS and the arterial endothelial function was evaluated. The LITUS of 1 MHz was applied in pulsed (PUT: 20% duty cycle, 0.08 W/cm2 SATA), continuous (CUT: 0.4 W/cm2 SPTA), and Placebo (equipment off) types of waves during 5 min on the brachial artery. Endothelial function was evaluated using the flow-mediated dilation (FMD) technique. PUT (mean difference 2.08%, 95% confidence interval 0.65 to 3.51) and CUT (mean difference 2.32%, 95% confidence interval 0.89 to 3.74) increased the %FMD compared to Placebo. In the effect size analysis, PUT (d=0.65) and CUT (d=0.65) waveforms presented moderate effects in the %FMD compared to Placebo. The vasodilator effect was similar in the different types of waves. Pulsed and continuous waveforms of LITUS of 1 MHz improved the arterial endothelial function in T2DM patients.


Subject(s)
Diabetes Mellitus, Type 2 , Ultrasonic Therapy , Male , Humans , Vasodilation , Ultrasonic Therapy/methods , Endothelium, Vascular , Vasodilator Agents/pharmacology , Vasodilator Agents/therapeutic use , Brachial Artery/diagnostic imaging
2.
Braz. j. med. biol. res ; 56: e12576, 2023. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1447685

ABSTRACT

Type 2 diabetes mellitus (T2DM) is characterized by endothelial dysfunction that causes micro- and macrovascular complications. Low intensity therapeutic ultrasound (LITUS) may improve endothelial function, but its effects have not been investigated in these patients. The aim of our study was to compare the effects of pulsed (PUT) and continuous (CUT) waveforms of LITUS on the endothelium-dependent vasodilation of T2DM patients. The present randomized crossover trial had a sample of twenty-three patients (7 men) diagnosed with T2DM, 55.6 (±9.1) years old, with a body mass index of 28.6 (±3.3) kg/m2. All patients were randomized and submitted to different waveforms (Placebo, CUT, and PUT) of LITUS and the arterial endothelial function was evaluated. The LITUS of 1 MHz was applied in pulsed (PUT: 20% duty cycle, 0.08 W/cm2 SATA), continuous (CUT: 0.4 W/cm2 SPTA), and Placebo (equipment off) types of waves during 5 min on the brachial artery. Endothelial function was evaluated using the flow-mediated dilation (FMD) technique. PUT (mean difference 2.08%, 95% confidence interval 0.65 to 3.51) and CUT (mean difference 2.32%, 95% confidence interval 0.89 to 3.74) increased the %FMD compared to Placebo. In the effect size analysis, PUT (d=0.65) and CUT (d=0.65) waveforms presented moderate effects in the %FMD compared to Placebo. The vasodilator effect was similar in the different types of waves. Pulsed and continuous waveforms of LITUS of 1 MHz improved the arterial endothelial function in T2DM patients.

3.
Physiotherapy ; 105(1): 120-125, 2019 03.
Article in English | MEDLINE | ID: mdl-29373113

ABSTRACT

OBJECTIVE: To compare the effects of different waveforms of 1MHz and 3MHz therapeutic ultrasound on endothelial function in healthy subjects. DESIGN: Randomised placebo-controlled, crossover study with concealed allocation and assessor blinding. SETTING: Imaging Centre of the University Hospital. PARTICIPANTS: Thirty volunteers aged between 18 and 35 years were divided into two homogeneous groups (1MHz and 3MHz). INTERVENTIONS: Continuous (CUT; 0.4W/cm2SATA), pulsed (PUT; 20% duty cycle, 0.08W/cm2SATA) and placebo waveforms (equipment off) of ultrasound (1MHz and 3MHz) were randomized and applied over the brachial artery for 5minutes. MAIN OUTCOME MEASURES: Endothelial function was evaluated using the flow-mediated dilation (FMD) technique. RESULTS: Both 1MHz [CUT: mean difference 4%, 95% confidence interval (CI) 2 to 6%, P<0.001; PUT: mean difference 4%, 95% CI 2 to 6%, P<0.001] and 3MHz (CUT: mean difference 4%, 95% CI 2 to 6%, P<0.001; PUT: mean difference 4%, 95% CI 2 to 6%, P<0.001) of therapeutic ultrasound increased %FMD by approximately 4% compared with the placebo waveforms. The endothelium-dependent vasodilator responses were the same for both types of waves and frequencies. No differences in baseline diameter, hyperaemic flow, and nitroglycerin-mediated diameter and vasodilation were observed between groups. CONCLUSION: Both CUT and PUT ultrasound waveforms improved endothelial function. The 1MHz and 3MHz frequencies of therapeutic ultrasound led to similar improvement in endothelial function in healthy volunteers. Clinical trial registration number RBR-4z5z3t.


Subject(s)
Endothelium, Vascular/physiology , Ultrasonic Therapy/methods , Vasodilation/physiology , Adolescent , Adult , Cross-Over Studies , Double-Blind Method , Female , Hemodynamics , Hospitals, University , Humans , Male , Single-Blind Method , Young Adult
4.
Vet Comp Oncol ; 16(1): E123-E129, 2018 Mar.
Article in English | MEDLINE | ID: mdl-28941072

ABSTRACT

Oral melphalan has been included in multi-agent rescue protocols for canine lymphoma but its activity as a single-agent for this purpose has not been established. Inexpensive cost, ease of administration and tolerability make oral melphalan an attractive candidate for single-agent rescue therapy of canine lymphoma. Retrospective evaluation of 19 cases of relapsed canine lymphoma treated with oral melphalan was performed. Melphalan was primarily administered (n = 16) via a high dose protocol (HDM) with a median dosage of 19.4 mg m-2 . Fifteen dogs (78.9%) were treated concurrently with corticosteroids. Response evaluation was possible for all dogs with a calculated overall clinical benefit (partial response [PR] + stable disease [SD]) of 31.6% (PR 3/19; SD 3/19). Times to progression following melphalan (TTP-M) were 14, 24 and 34 days for responders and 20, 28 and 103 days for dogs experiencing SD. Twelve of 17 dogs evaluable for toxicity experienced an adverse event (AE) with only 3 dogs experiencing a grade III or higher AE. Haematologic toxicity was common (11/17) while gastrointestinal toxicity was rare (1/17). Although treatment resulted in limited clinical benefit and non-durable responses, oral melphalan was well-tolerated and may be a reasonable rescue option in cases where minimal effective agents remain.


Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Dog Diseases/drug therapy , Lymphoma/veterinary , Melphalan/therapeutic use , Administration, Oral , Animals , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/adverse effects , Dogs , Female , Lymphoma/drug therapy , Male , Melphalan/administration & dosage , Melphalan/adverse effects , Recurrence , Retrospective Studies
5.
Cancer Chemother Pharmacol ; 80(2): 421-431, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28685347

ABSTRACT

PURPOSE: Manganese porphyrins are redox-active drugs and superoxide dismutase mimics, which have been shown to chemosensitize lymphoma, a cancer which frequently occurs in dogs. This study aimed to identify critical information regarding the pharmacokinetics and toxicity of Mn(III) meso-tetrakis (N-n-butoxyetylpyridium-2-yl) porphyrin, (MnTnBuOE-2-PyP5+, MnBuOE) in dogs as a prelude to a clinical trial in canine lymphoma patients. METHODS: A single-dose pharmacokinetic (PK) study in normal dogs was performed to determine the plasma half-life (t 1/2) of MnBuOE. A dose reduction study was performed to establish the maximum tolerated dose (MTD) of MnBuOE. The safety and PK of a multi-dosing protocol was assessed. RESULTS: Peak plasma drug concentration occurred 30 min post-injection. The t 1/2 was defined as 7 h. MnBuOE induced an anaphylactic reaction and prolonged tachycardia. The MTD was defined as 0.25 mg/kg. The dogs were given MTD 3×/week for 2-3 weeks. The highest recorded tissue drug levels were in the lymph nodes (4-6 µM), followed by kidney and liver (2.5, 2.0 uM, respectively). CONCLUSIONS: We obtained critical information regarding the PK and toxicity of MnBuOE in dogs. The acute drug reaction and tachycardia post-injection have not been described in other species and may be specific to canines. The high tissue drug levels in lymph nodes have not been previously reported. MnBuOE accumulation in lymph nodes has important implications for the utility of adjuvant MnBuOE to treat lymphoma. With MnBuOE lymph node accumulation, reduction in the dose and/or administration frequency could be possible, leading to reduced toxicity.


Subject(s)
Antineoplastic Agents/administration & dosage , Kidney/metabolism , Liver/metabolism , Lymph Nodes/metabolism , Metalloporphyrins/administration & dosage , Anaphylaxis/chemically induced , Animals , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/toxicity , Dog Diseases/drug therapy , Dogs , Half-Life , Lymphoma/drug therapy , Lymphoma/veterinary , Male , Maximum Tolerated Dose , Metalloporphyrins/pharmacokinetics , Metalloporphyrins/toxicity , Species Specificity , Tachycardia/chemically induced , Tissue Distribution
6.
Vet Comp Oncol ; 15(3): 1101-1114, 2017 Sep.
Article in English | MEDLINE | ID: mdl-27402031

ABSTRACT

Acute leukaemia (AL) is a bone marrow malignancy of hematopoietic progenitors that historically is poorly responsive to treatment. With the widespread adoption of dose-intense chemotherapy, more human patients attain long-term survivals, but whether comparable progress has been made in canine AL is unknown. To investigate this question, medical records from three academic veterinary hospitals were reviewed. Fifty dogs met the criteria for AL, having excess circulating or marrow blasts, a major cytopenia(s), and no substantial lymphadenopathy. Thirty-six dogs received cytotoxic chemotherapy; 23 achieved a complete or partial response for a median of 56 days (range, 9-218). With failure or relapse, 14 dogs were rescued. Median survival with treatment was poor at 55 days (range, 1-300). Untreated (n = 6) and palliatively-treated (n = 8) dogs lived a median of 7.5 days. Most dogs developed chemoresistance within weeks of initiating treatment, and consequently, survival times for AL remain disappointingly short.


Subject(s)
Dog Diseases/drug therapy , Leukemia/veterinary , Acute Disease , Animals , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Dog Diseases/mortality , Dogs , Leukemia/drug therapy , Leukemia/mortality , Retrospective Studies , Survival Analysis , Treatment Outcome
7.
Physiotherapy ; 102(4): 377-383, 2016 Dec.
Article in English | MEDLINE | ID: mdl-26725004

ABSTRACT

OBJECTIVE: To investigate the combined effects of cryotherapy and pulsed ultrasound therapy (PUT) on oxidative stress parameters, tissue damage markers and systemic inflammation after musculoskeletal injury. DESIGN: Experimental animal study. SETTING: Research laboratory. PARTICIPANTS: Seventy male Wistar rats were divided into five groups: control, lesion, cryotherapy, PUT, and cryotherapy+PUT. INTERVENTIONS: The gastrocnemius muscle was injured by mechanical crushing. Cryotherapy was applied immediately after injury (immersion in water at 10°C for 20minutes). PUT was commenced 24hours after injury (1MHz, 0.4W/cm2SPTA, 20% duty cycle, 5minutes). All animals were treated every 8hours for 3 days. MAIN OUTCOME MEASURES: Oxidative stress in muscle was evaluated by concentration of reactive oxygen species (ROS), lipid peroxidation (LPO), anti-oxidant capacity against peroxyl radicals (ACAP) and catalase. Plasma levels of creatine kinase (CK), lactate dehydrogenase (LDH) and C-reactive protein (CRP) were assessed. RESULTS: When applied individually, cryotherapy and PUT reduced CK, LDH, CRP and LPO caused by muscle damage. Cryotherapy+PUT in combination maintained the previous results, caused a reduction in ROS [P=0.005, mean difference -0.9×10-8 relative area, 95% confidence interval (CI) -0.2 to -1.9], and increased ACAP {P=0.007, mean difference 0.34 1/[relative area with/without 2,2-azobis(2-methylpropionamidine)dihydrochloride], 95% CI 0.07 to 0.61} and catalase (P=0.002, mean difference 0.41units/mg protein, 95% CI 0.09 to 0.73) compared with the lesion group. CONCLUSIONS: Cryotherapy+PUT in combination reduced oxidative stress in muscle, contributing to a reduction in adjacent damage and tissue repair.


Subject(s)
Contusions/physiopathology , Contusions/rehabilitation , Cryotherapy/methods , Muscle, Skeletal/physiopathology , Oxidative Stress/physiology , Ultrasonic Therapy/methods , Animals , Antioxidants/physiology , Biomarkers , Inflammation Mediators/metabolism , Lipid Peroxidation/physiology , Male , Rats , Rats, Wistar
8.
J Comp Pathol ; 152(1): 22-7, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25435513

ABSTRACT

Comparative analyses of canine and human soft tissue sarcomas (STSs) are lacking. This study compared the histological and immunohistochemical (labelling for desmin, smooth muscle actin [SMA], CD31, pancytokeratin, S100 and CD34) appearance of 32 archived, formalin-fixed, paraffin wax-embedded canine STS tumour specimens by board-certified veterinary and medical pathologists, both blinded to the other's interpretations. Comparison between the veterinary and human diagnoses revealed a generally consistent pattern of interpretation with few notable variations. Most tumours (13/32) were judged to display similar histomorphological appearance to human low-grade spindle cell sarcomas, appearing non-distinctive and morphologically of a fibroblastic/myofibroblastic type. Five canine cases resembled human liposarcoma, but with atypical desmin-positive epithelioid cells present. Five canine cases resembled human spindle cell sarcoma with myxoid features and two additional cases resembled human myxofibrosarcoma. Seven canine cases were noted to resemble human undifferentiated sarcoma. Findings in the present study demonstrate that canine STSs display histological and immunohistochemical features similar to their human equivalents. Because of these cross-species similarities, a particular opportunity exists to understand the biology and treatment of human STS by potentially including dogs as clinical models.


Subject(s)
Sarcoma/pathology , Sarcoma/veterinary , Animals , Biomarkers, Tumor/analysis , Disease Models, Animal , Dogs , Humans , Immunohistochemistry
9.
Herzschrittmacherther Elektrophysiol ; 22(4): 209-13, 2011 Dec.
Article in German | MEDLINE | ID: mdl-22080419

ABSTRACT

BACKGROUND: Intraoperative testing of implantable cardioverter-defibrillators (ICDs) is time consuming and associated with risks. In the present study, we elucidated whether the initial implantation of an ICD with high energy output makes intraoperative defibrillation threshold testing (DFTT) unnecessary even though antiarrhythmic (AA) therapy is needed in the future. METHODS: A total of 111 patients (94 men, 17 women) receiving an ICD with subsequent AA therapy (mexiletine, amiodarone, sotalol, flecainide) were analyzed retrospectively. DFT was performed during ICD implantation and after AA drug therapy. In a second step, DFT results from the study cohort were analyzed for implantation of virtual ICDs with either low (≤ 30 J, LOD), intermediate (34 J, IOD), or high energy output (36 J, HOD). RESULTS: In the study cohort, all patients reached the safety margin (SM) of 10 J between DFT and maximal shock energy of the ICD. After loading of AA agents, 6 patients (12%) with a LOD, 3 patients (11%) with an IOD, and 3 (13%) patients with a HOD failed the 10 J SM. Using virtual ICDs, 6 (5.5%) patients with a LOD, 1 patient (1%) with an IOD, and no patients with a HOD would have failed the 10 J SM. After loading of AA agents, 18 patients (16%) with a virtual LOD, 12 patients (10.8%) with an IOD, and still 9 patients (8%) with a HOD would have failed the 10 J SM. CONCLUSION: Our results demonstrate that the 10 J SM would have been achieved intraoperatively in all patients with virtual HOD ICDs. Thus, determination of the DFT during implantation does not seem to be obligatory. However, in patients receiving AA agents, DFT testing is still required.


Subject(s)
Atrial Fibrillation/diagnosis , Atrial Fibrillation/prevention & control , Defibrillators, Implantable/statistics & numerical data , Differential Threshold , Electrocardiography/statistics & numerical data , Electrophysiologic Techniques, Cardiac/statistics & numerical data , Monitoring, Intraoperative/statistics & numerical data , Atrial Fibrillation/epidemiology , Electric Countershock/methods , Electric Countershock/statistics & numerical data , Electrocardiography/methods , Female , Germany/epidemiology , Humans , Male , Middle Aged , Utilization Review
10.
Vet Pathol ; 48(2): 482-5, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20974873

ABSTRACT

Stringently controlled in vitro experiments are a necessary part of translational research. Cell lines are useful for exploring the underlying biology of cancer. Very few canine soft tissue sarcoma cell lines exist. This report describes the establishment of a new canine soft tissue sarcoma cell line (MBSa1) derived from a high-grade, metastatic neurofibrosarcoma. The primary tumor tissue was obtained from a 12-year-old neutered male German Shepherd Dog and was maintained in tissue culture for a minimum of 20 passages over 7 months. MBSa1 was injected into athymic mice to determine tumorigenicity. Five million cells were injected into the subcutis of the right flank of athymic nude mice. Nine of the 10 mice grew tumors 1 cm or larger within 8 weeks of cell injection. The large number of in vitro passages coupled with solid tumor formation in athymic nude mice demonstrates that MBSa1 has been immortalized and is tumorigenic.


Subject(s)
Cell Line, Tumor , Chromosomes, Mammalian/genetics , Dog Diseases/pathology , Sarcoma/veterinary , Animals , Dogs , Immunohistochemistry/veterinary , Male , Mice , Mice, Nude , Microscopy, Fluorescence/veterinary , Sarcoma/pathology
11.
J Environ Manage ; 90(11): 3410-21, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19540036

ABSTRACT

The paper presents a geographic information system (GIS) model-based approach for analysis of potential contamination of soil and water by pyrethroids for the European continent. Pyrethroids are widely used pesticides and their chemical and toxicological characteristics suggest there may be concerns about human health and ecosystems, although so far there is no strong evidence indicating actual risk. However, little monitoring has been conducted and limited experimental information is available. We perform an assessment exercise that demonstrates how accessible information and GIS-based modeling allow to estimate the spatial distribution of chemical concentrations and fluxes at a screening level. The assessment highlights potential hot spots and the main environmental transport pathways, in a quick and simple way. By combining information on pesticide use, crop distribution and landscape and climate parameters we identify potential problem areas to help focusing monitoring campaigns. The approach presented here is simple and fast, and can be applied to virtually all pesticide classes used over a large domain, and is therefore suitable for the screening of large quantities of chemicals, of which the majority has not undergone any systematic environmental monitoring program. The method has been tested through benchmarking with other well-established models. However, further research is needed to evaluate it against experimental observations.


Subject(s)
Environmental Monitoring/methods , Geographic Information Systems , Pyrethrins/analysis , Soil Pollutants/analysis , Water Pollutants, Chemical/analysis , Europe , Insecticides
12.
J Med Genet ; 46(2): 115-22, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19181906

ABSTRACT

BACKGROUND: Reports of somatic mutations found in hearts with cardiac septal defects have suggested that these mutations are aetiologic in pathologic cardiac development. However, the hearts in these reports had been fixed in formalin for over 22 years. Because of the profound implication of this finding, we attempted to replicate it using fresh frozen tissue obtained in the current era from 28 patients with septal defects who underwent cardiac surgery and who were enrolled in our congenital heart disease tissue bank. METHODS: Our cohort included patients with atrial septal defects (ASD, n = 13), ventricular septal defects (VSD, n = 5), and atrioventricular canal defects (AVCD, n = 10). Cardiac tissue samples were collected both from diseased tissue located immediately adjacent to the defect and from anatomically normal tissue located at a site remote from the defect (right atrial appendage). Tissue samples were immediately frozen in liquid nitrogen and stored at -80 degrees C. Genomic DNA was isolated and amplified using the same methodology described in the previously published reports. 42 pathologic cardiac tissue samples were sequenced. RESULTS: One non-synonymous germline sequence variant was identified in one patient. Two synonymous germline sequence variants were identified in two separate patients. A common single nucleotide polymorphism (SNP) was identified in 16 patients. Based on the incidence of somatic mutations described in the previously published reports, our study was adequately powered to replicate the previous studies. No evidence of somatic mutations was found in this study. CONCLUSION: Somatic mutations in NKX2-5 do not represent an important aetiologic pathway in pathologic cardiac development in patients with cardiac septal defects.


Subject(s)
Heart Defects, Congenital/genetics , Homeodomain Proteins/genetics , Mutation , Transcription Factors/genetics , Base Sequence , Cohort Studies , DNA Mutational Analysis , Heart Defects, Congenital/metabolism , Heart Septal Defects, Atrial/genetics , Heart Septal Defects, Atrial/metabolism , Heart Septal Defects, Ventricular/genetics , Heart Septal Defects, Ventricular/metabolism , Homeobox Protein Nkx-2.5 , Homeodomain Proteins/metabolism , Humans , Molecular Sequence Data , Polymorphism, Single Nucleotide , Transcription Factors/metabolism
13.
Oecologia ; 158(3): 399-410, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18839214

ABSTRACT

In 2005 and 2006, air samples were collected at the base of a Douglas-fir watershed to monitor seasonal changes in the delta13CO2 of ecosystem respiration (delta13C(ER)). The goals of this study were to determine whether variations in delta13C(ER) correlated with environmental variables and could be used to predict expected variations in canopy-average stomatal conductance (Gs). Changes in delta13C(ER) correlated weakly with changes in vapor pressure deficit (VPD) measured 0 and 3-7 days earlier and significantly with soil matric potential (psi(m)) (P value <0.02) measured on the same day. Midday G (s) was estimated using sapflow measurements (heat-dissipation method) at four plots located at different elevations within the watershed. Values of midday Gs from 0 and 3-7 days earlier were correlated with delta13C(ER), with the 5-day lag being significant (P value <0.05). To examine direct relationships between delta13C(ER) and recent Gs, we used models relating isotope discrimination to stomatal conductance and photosynthetic capacity at the leaf level to estimate values of stomatal conductance ("Gs-I") that would be expected if respired CO2 were derived entirely from recent photosynthate. We compared these values with estimates of Gs using direct measurement of transpiration at multiple locations in the watershed. Considering that the approach based on isotopes considers only the effect of photosynthetic discrimination on delta13C(ER), the magnitude and range in the two values were surprisingly similar. We conclude that: (1) delta13C(ER) is sensitive to variations in weather, and (2) delta13C(ER) potentially could be used to directly monitor average, basin-wide variations in Gs in complex terrain if further research improves understanding of how delta13C(ER) is influenced by post-assimilation fractionation processes.


Subject(s)
Carbon Dioxide/metabolism , Ecosystem , Plant Transpiration , Pseudotsuga/metabolism , Carbon Isotopes/metabolism , Cell Respiration , Oregon , Photosynthesis , Plant Stomata/physiology , Seasons
15.
Vet Comp Oncol ; 6(4): 213-23, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19178681

ABSTRACT

Human oncology has clearly demonstrated the existence of hypoxic tumours and the problematic nature of those tumours. Hypoxia is a significant problem in the treatment of all types of solid tumours and a common reason for treatment failure. Hypoxia is a negative prognostic indicator of survival and is correlated with the development of metastatic disease. Resistance to radiation therapy and chemotherapy can be because of hypoxia. There are two dominant types of hypoxia recognized in tumours, static and intermittent. Both types of hypoxia are important in terms of resistance. A variety of physiological factors cause hypoxia, and in turn, hypoxia can induce genetic and physiological changes. A limited number of studies have documented that hypoxia exists in spontaneous canine tumours. The knowledge from the human literature of problematic nature of hypoxic tumours combined with the rapid growth of veterinary oncology has necessitated a better understanding of hypoxia in canine tumours.


Subject(s)
Cell Hypoxia/physiology , Dog Diseases/metabolism , Fluorocarbons/metabolism , Neoplasms/veterinary , Animals , Dogs , Hydrocarbons, Brominated , Neoplasms/metabolism
16.
Clin Res Cardiol ; 96(9): 613-20, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17593312

ABSTRACT

UNLABELLED: Arrhythmia induction during implantation of cardioverter defibrillators (ICD) is a standard procedure. However, controversy exists regarding the need for routine arrhythmia induction before discharge from hospital (pre-hospital discharge (PHD) test). In order to reduce the number of tests we identified risk factors that predict relevant ICD malfunction. METHODS AND RESULTS: 965 patients receiving a first device implantation (n=724) or device/system replacement (n=241) between 1998 and 2004 were analysed. During implantation 176 (18%) complications (intraoperative undersensing of induced arrhythmias, unsuccessful arrhythmia-therapy or low DFT safety margin) occurred. Frequent (>4 times) intraoperative lead repositioning due to low sensing values was present in 44 patients (5%). 9% of the patients with first ICD implantation, 21% with device replacement and 27% with system replacement developed complications during PHD testing with arrhythmia induction. Intraoperative complications, although corrected during implantation, were independent risk factors for malfunction during PHD testing (p<0.05). Additional predictors for malfunction were intraoperative lead repositioning (>4 times) and a history of both VF and VT (p<0.05). Patients without intraoperative complications rarely developed malfunction during PHD testing (3.7% first device, 6.25% system replacement). Only in patients undergoing device replacement was a higher risk for failure (13%) evident. No risk factors could be identified for these subgroups. CONCLUSION: Routine arrhythmia induction during PHD is recommended in ICD patients with intraoperative complications, although corrected during implantation, as well as frequent intraoperatives lead repositioning. Patients undergoing device/system replacement uncomplicated implantation are not generally at low risk for device failure.


Subject(s)
Arrhythmias, Cardiac/physiopathology , Arrhythmias, Cardiac/therapy , Defibrillators, Implantable , Equipment Failure , Equipment Failure Analysis , Equipment Safety , Female , Humans , Intraoperative Complications , Male , Middle Aged , Patient Discharge , Retrospective Studies , Risk Factors
17.
Int J Hyperthermia ; 21(1): 1-11, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15764347

ABSTRACT

Improving drug and macromolecular delivery of anti-cancer agents to tumours results in greater efficacy without increased toxicity. The current study was undertaken to assess the effects of the timing of injection of tumour specific and non-specific monoclonal antibodies (mAbs) relative to a hyperthermia treatment on tumour and normal tissue uptake. Using a local hyperthermia protocol of 45 min at 43 degrees C, uptake in tumour and normal tissues was measured at 1, 4, 12, 24, 48 and 72 h after injection. An anti-tenascin chimeric mAb, ch81C6, served as the specific mAb in a D-54 MG glioma xenograft mouse model. The chimeric mAb chTPS3.2 served as the control. A five-to-eight-fold increase in uptake of the tumour-targeted mAb was achieved in the heated tumours when compared with the non-heated tumours at 1 h. Differences in absolute tumour uptake of the specific mAb between the mice injected prior to hyperthermia and mice injected post-hyperthermia were seen only at 1 and 12 h. The median uptakes in the tumours of mice injected pre-heat were 25%ID/g at 1 h and 43.5%ID/g at 12 h, while in the animals injected post-hyperthermia the median uptakes were 45.5%ID/g and 80.2%ID/g, respectively. Blood levels of both the specific and non-specific mAbs were consistently higher over the initial 12 h period in the mice injected post-hyperthermia. Normal tissue uptake was also increased at most time points in the mice injected post-hyperthermia. The clinical importance of the differences in specific mAb uptake in tumour detected statistically at 1 and 12 h is questionable, given the highly variable nature of mAb uptake in vivo. Tumour targeting mAbs administered in combination with heat may be injected either prior to or immediately following hyperthermia treatment, with the expectation that levels of uptake in tumour will be relatively equivalent. Absolute normal tissue levels will be higher in patients receiving the mAb post-hyperthermia.


Subject(s)
Antibodies, Monoclonal/pharmacokinetics , Brain Neoplasms/therapy , Glioma/therapy , Hyperthermia, Induced/methods , Iodine Radioisotopes/pharmacology , Radioimmunotherapy/methods , Animals , Antibodies, Neoplasm/pharmacology , Cell Line, Tumor , Combined Modality Therapy , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Tenascin/immunology , Xenograft Model Antitumor Assays
18.
Int J Hyperthermia ; 21(1): 13-27, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15764348

ABSTRACT

Clinical application of local hyperthermia as a means for modulating drug and macro-molecular tumour uptake have been slow to develop, due in part to the difficulty in designing and comparing heating protocols. The thermal isodose formula developed by Sapareto and Dewey is used in cytotoxicity and radiosensitization hyperthermia protocols to compare different time/temperature combinations; however, its relevance to other end-points has not been evaluated. The current study was undertaken to determine whether heating protocols of different time and temperature, but predicted to be thermally equivalent by this formula, had similar effects on the tumour and normal tissue distribution of radiolabelled tumour-specific (anti-tenascin 81C6) and non-specific (anti-dansyl TPS3.2) monoclonal antibodies (mAbs). Two thermally equivalent heating protocols, 4 h at 41.8 degrees C and 45 min at 43 degrees C, were compared in mice with subcutaneous D54 MG human glioma xenografts. A 4-fold increase in xenograft localization of 81C6 mAb was achieved relative to that in non-heated control groups with both heating protocols. Both hyperthermia protocols also resulted in improved tumour:normal tissue ratios. However, differences in absolute tumour and normal tissue uptake were seen, suggesting that the thermal isodose formula has limited usefulness in the design and comparison of hyperthermia protocols for enhancing the tumour uptake of radiolabelled mAbs.


Subject(s)
Antibodies, Monoclonal/pharmacokinetics , Brain Neoplasms/therapy , Glioma/therapy , Hyperthermia, Induced/methods , Iodine Radioisotopes/pharmacology , Radioimmunotherapy/methods , Animals , Antibodies, Neoplasm/pharmacology , Cell Line, Tumor , Combined Modality Therapy , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Radiation Dosage , Temperature , Xenograft Model Antitumor Assays
19.
Forensic Sci Rev ; 17(1): 29-49, 2005 Jan.
Article in English | MEDLINE | ID: mdl-26257109

ABSTRACT

Fiber evidence suffers from the same misperception as many other types of trace evidence, that it is weak in its significance. Despite this pejorative perception, textiles make excellent evidence because of their presence in our daily lives and the variations they demonstrate. Fibers from the textiles in our and others' environments transfer from surface to surface and variously persist. Textile fibers are produced with specific raw materials, production methods, and postproduction alterations that create this variety. The distribution and use of the fibers add to their distinctive significance. The number of methods used in analysis helps to define and identify the fibers. Millions of color shades are possible in textiles and yet color analysis is not a universal technique in forensic laboratories. Transfer study after transfer study demonstrates the rarity of finding unrelated fibers at random that exhibit the same microscopic characteristics and optical properties. Examples from casework also demonstrate the usefulness of forensic textile fiber analysis in demonstrating probative associations in criminal investigations. Additional work needs to be done to fortify and support these conclusions and provide the verification necessary to remove the taint of "could have".

20.
Orthopade ; 32(10): 852-8, 2003 Oct.
Article in German | MEDLINE | ID: mdl-14579016

ABSTRACT

Functional diagnostics of the dorsal root are especially effective via nociceptive fibers on account of less intersegmental overlap compared to large-diameter fibers of the mechanoreceptive afferents. Laser-evoked potentials (LEP) are induced by short, painful heat stimuli. The aim of this work was to describe changes of the LEP in cases of dorsal root damage. The recorded LEP changes will be discussed with regard to their prognostic value as well as pathophysiologic aspects of dorsal root damage. Dorsal root function was tested in 21 patients suffering from clinically proven radiculopathy in one of the segments L4 to S1. Mechanosensibility and thermosensibility were clinically investigated. LEP were induced by slightly painful stimuli (80 on the affected and 80 on the contralateral unaffected dermatome). The LEP were evaluated by amplitude of the averaged electroencephalogram (EEG). In addition, a subjective pain rating was recorded after each stimulus. Investigation of dorsal root function by LEP in patients with radiculopathy yields two typical changes of the amplitude. On the one hand, there were significant reductions of amplitude, and on the other hand, a complete loss of LEP was found. LEP changes allow a graduation of patients who show no obvious differences in their clinical appearance. Which mechanisms are responsible as concerns deafferentiation and neuropathy of the dorsal root fibers are discussed. With regard to the LEP changes, a prognostic relevance in patients with dorsal root affections is likely. This question will be addressed in a prospective study soon.


Subject(s)
Electroencephalography/methods , Evoked Potentials, Somatosensory , Hot Temperature , Lasers , Radiculopathy/diagnosis , Spinal Nerve Roots/radiation effects , Adult , Back Pain/diagnosis , Back Pain/etiology , Female , Humans , Lumbosacral Region/physiopathology , Lumbosacral Region/radiation effects , Male , Middle Aged , Radiculopathy/complications , Radiculopathy/physiopathology , Reproducibility of Results , Sensitivity and Specificity , Spinal Nerve Roots/physiopathology
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