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1.
PLoS One ; 15(5): e0233103, 2020.
Article in English | MEDLINE | ID: mdl-32407398

ABSTRACT

Differential migration-increased migration propensity with increasing individual size-is common in migratory species. Like other forms of partial migration, it provides spatial buffering against regional differences in habitat quality and sources of mortality. We investigated differential migration and its consequences to survival and reproductive patterns in striped bass, a species with well-known plasticity in migration behaviors. A size-stratified sample of Potomac River (Chesapeake Bay) Morone saxatilis striped bass was implanted with acoustic transmitters and their subsequent coastal shelf migrations recorded over a 4-yr period by telemetry receivers throughout the Mid-Atlantic Bight and Southern New England. A generalized linear mixed model predicted that ≥ 50% of both males and females depart the Chesapeake Bay at large sizes >80 cm total length. Egressing striped bass exited through both the Chesapeake Bay mouth and Delaware Bay (via the Chesapeake and Delaware Canal), favoring the former. All large fish migrated to Massachusetts shelf waters and in subsequent years repeatedly returned to regions within Massachusetts and Cape Cod Bays. Within this dominant behavior, minority behaviors included straying, skipped spawning, and residency by large individuals (those expected to migrate). Analysis of the last day of transmission indicated that small resident striped bass experienced nearly 2-fold higher loss rates (70% yr-1) than coastal shelf emigrants (37% yr-1). The study confirmed expectations for a threshold size at emigration and different mortality levels between Chesapeake Bay (resident) and ocean (migratory) population contingents; and supported the central premise of the current assessment and management framework of a two-contingent population: smaller Chesapeake Bay residents and a larger ocean contingent. An improved understanding of differential migration thus affords an opportunity to specify stock assessments according to different population sub-components, and tailor reference points and control rules between regions and fishing stakeholder groups.


Subject(s)
Animal Migration/physiology , Bass/physiology , Bays , Aging/physiology , Animals , Bass/anatomy & histology , Body Size , Estuaries , Female , Male , Maryland , New England , Rivers , Seasons , Telemetry
2.
Drug Test Anal ; 10(6): 961-967, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29055108

ABSTRACT

The use of filtration/pass-through extraction (FPTE) and ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-qTOF-MS) to detect tramadol (TRAM), dextromethorphan (DXM), and metabolites from skeletal remains is described. Rats (n=5) received 50 mg/kg tramadol and were euthanized by CO2 asphyxiation approximately 30 minutes post-dose. Rats (n=4) received 75 mg/kg dextromethorphan and were euthanized by CO2 asphyxiation approximately 45 minutes post-dose. Remains decomposed to skeleton outdoors and vertebral bones were collected. Bones were cleaned, dried, and pulverized to a fine powder. Bones underwent dynamic methanolic extraction followed by FPTE before analysis using UPLC-qTOF-MS. Recovery was at least 90% of maximal value within the first 10 minutes of methanolic extraction for all samples assayed. Analytical response was measured over the concentration range of 1-500 ng/mL, with precision and bias <20% in triplicate analyses of all calibrators, and a limit of detection of 1 ng/mL for TRAM, DXM, and all metabolites. The vertebral bone analyzed using this method detected TRAM, DXM, and their respective metabolites in all samples analyzed.


Subject(s)
Body Remains/chemistry , Dextromethorphan/analysis , Dextromethorphan/metabolism , Tramadol/analysis , Tramadol/metabolism , Animals , Body Remains/metabolism , Chromatography, High Pressure Liquid , Limit of Detection , Male , Rats , Tandem Mass Spectrometry
3.
J Anal Toxicol ; 40(8): 669-676, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27562970

ABSTRACT

The effects of decomposition microclimate on the distribution of dextromethorphan (DXM) and dextrorphan (DXT) in skeletonized remains of rats acutely exposed to DXM were examined. Animals (n = 10) received DXM (75 mg/kg, i.p.), were euthanized 30 min post-dose and immediately allowed to decompose at either Site A (shaded forest microenvironment on a grass-covered soil substrate) or Site B (rocky substrate exposed to direct sunlight, 600 m from Site A). Ambient temperature and relative humidity were automatically recorded 3 cm above rats at each site. Skeletal elements (vertebral columns, ribs, pelvic girdles, femora, tibiae, humeri and scapulae) were harvested, and analyzed using microwave assisted extraction, microplate solid phase extraction, and GC/MS. Drug levels, expressed as mass-normalized response ratios, and the ratios of DXT and DXM levels were compared across bones and between microclimate sites. No significant differences in DXT levels or metabolite/parent ratios were observed between sites or across bones. Only femoral DXM levels differed significantly between microclimate sites. For pooled data, microclimate was not observed to significantly affect analyte levels, nor the ratio of levels of DXT and DXM. These data suggest that microclimate conditions do not influence DXM and metabolite distribution in skeletal remains.


Subject(s)
Body Remains/chemistry , Bone and Bones/chemistry , Dextromethorphan/analysis , Dextrorphan/analysis , Microclimate , Postmortem Changes , Animals , Dose-Response Relationship, Drug , Forensic Toxicology , Gas Chromatography-Mass Spectrometry , Limit of Detection , Male , Microwaves , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Solid Phase Extraction
4.
J Anal Toxicol ; 38(8): 548-54, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25217545

ABSTRACT

The influence of body position and microclimate on ketamine (KET) and metabolite distribution in decomposed bone tissue was examined. Rats received 75 mg/kg (i.p.) KET (n = 30) or remained drug-free (controls, n = 4). Following euthanasia, rats were divided into two groups and placed outdoors to decompose in one of the three positions: supine (SUP), prone (PRO) or upright (UPR). One group decomposed in a shaded, wooded microclimate (Site 1) while the other decomposed in an exposed sunlit microclimate with gravel substrate (Site 2), roughly 500 m from Site 1. Following decomposition, bones (lumbar vertebrae, thoracic vertebra, cervical vertebrae, rib, pelvis, femora, tibiae, humeri and scapulae) were collected and sorted for analysis. Clean, ground bones underwent microwave-assisted extraction using acetone : hexane mixture (1 : 1, v/v), followed by solid-phase extraction and analysis using GC-MS. Drug levels, expressed as mass normalized response ratios, were compared across all bone types between body position and microclimates. Bone type was a main effect (P < 0.05) for drug level and drug/metabolite level ratio for all body positions and microclimates examined. Microclimate and body position significantly influenced observed drug levels: higher levels were observed in carcasses decomposing in direct sunlight, where reduced entomological activity led to slowed decomposition.


Subject(s)
Bone and Bones/chemistry , Ketamine/analogs & derivatives , Ketamine/pharmacokinetics , Microclimate , Postmortem Changes , Posture , Animals , Dose-Response Relationship, Drug , Gas Chromatography-Mass Spectrometry , Ketamine/metabolism , Male , Rats , Rats, Wistar , Reproducibility of Results , Solid Phase Extraction
5.
Article in English | MEDLINE | ID: mdl-24799069

ABSTRACT

Microwave assisted extraction (MAE) followed by microplate solid phase extraction (MPSPE) coupled with ultra high performance liquid chromatography (UHPLC) for the semi-quantitative determination of colchicine, 3-demethyl colchicine and 2-demethyl colchicine in postmortem rat bone is described. Rats (n=4) received 50mg/kg colchicine (i.p), and euthanized by CO2 asphyxiation. Remains decomposed to skeleton outdoors and vertebral bones were collected cleaned, and ground to a fine powder. Powdered bone underwent MAE using methanol in a closed microwave system, followed by MPSPE and analysis using UHPLC-PDA. MAE analyte stability was assessed and found to be stable for at least 60 min irradiation time. The majority (>95%) of each analyte was recovered after 15 min. The MPSPE-UHPLC method was linear between 10 and 2,000 ng/mL, with coefficients of variation <20% in triplicate analysis, with a limit of detection of 10 ng/mL for each of the three analytes. Following MAE for 30 min (80°C, 1200W), MPSPE-UHPLC analysis of vertebral bone of colchicine-exposed rats detected colchicine (1.8-4.1 µg/g), 3-demethyl colchicine (0.77-1.8 µg/g) and 2-demethyl colchicine (0.43-0.80 µg/g) in all samples assayed.


Subject(s)
Bone and Bones/chemistry , Chromatography, High Pressure Liquid/methods , Colchicine/analogs & derivatives , Colchicine/analysis , Solid Phase Extraction/methods , Animals , Colchicine/chemistry , Colchicine/pharmacokinetics , Microwaves , Rats , Rats, Wistar
6.
Anal Biochem ; 419(2): 345-7, 2011 Dec 15.
Article in English | MEDLINE | ID: mdl-21910964

ABSTRACT

Paraquat (PQ) is widely used in the laboratory to induce in vivo oxidative stress, particularly in the fruit fly, Drosophila melanogaster. PQ administration to the fly traditionally involves feeding in a 1% sucrose solution; however, a diet high in sucrose can itself be stressful. We examined a novel method of PQ administration: incorporation into the fly's standard cornmeal-sucrose-yeast diet. This method successfully delivers PQ to the fly at concentrations similar to those of the traditional method but with fewer possibly confounding complications.


Subject(s)
Biochemistry/methods , Drosophila melanogaster/drug effects , Drosophila melanogaster/metabolism , Oxidative Stress/drug effects , Paraquat/toxicity , Animals , Chromatography, High Pressure Liquid , Paraquat/administration & dosage
7.
Can Urol Assoc J ; 4(1): 42-6, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20165577

ABSTRACT

INTRODUCTION: We determined the status of Canadian training during senior residency in laparoscopic, robotic and endourologic surgery. METHODS: Fifty-six residents in their final year of urology residency training were surveyed in person in 2007 or 2008. RESULTS: All residents completed the survey. Most residents (85.7%) train at centres performing more than 50 laparoscopic procedures yearly and almost all (96.4%) believe laparoscopic radical nephrectomy is the gold standard. About 82% of residents participated in a laparoscopic partial nephrectomy in 2008, compared to 64.7% in 2007. Of the respondents, 66% have participated in a laparoscopic prostatectomy and 54% believe the procedure has promising potential. Exposure and training in robotic-assisted laparoscopic procedures seem to be increasing as 35.7% of 2008 residents have access to a surgical robot and 7% consider themselves trained in robotic-assisted procedures. Most residents (71.4%) train at centres that perform percutaneous ablation. However, 65% state the procedure is performed solely by radiologists. Percutaneous nephrolithotomy is widely performed (98.2%), but only 37.5% of residents report training in obtaining primary percutaneous renal access. Despite only 12.5% of residents ranking their laparoscopic experience as below average or poor, an increasing proportion of graduating residents are pursuing fellowships in minimally-invasive urology. CONCLUSION: Laparoscopic nephrectomy is commonly performed and is considered the standard of care by Canadian urology residents. Robotic-assisted surgery is becoming more common but will require continued evaluation by educators who will ultimately define its role in the urological residency training curriculum. Minimally-invasive surgical fellowships remain popular, as Canadian residents do not feel adequately trained in certain advanced procedures. Urologists must strive to learn and adapt to new technologies or risk losing them to other specialties.

8.
Proc Inst Mech Eng H ; 222(7): 1013-22, 2008 Oct.
Article in English | MEDLINE | ID: mdl-19024150

ABSTRACT

Bespak, a division of Consort Medical plc, and Queen's University Belfast have developed a viable and unique in-vitro testing capability for nasal drug delivery devices. The aim was to evaluate and optimize current and conceptual drug delivery devices by quantifying the deposition of drug in the various distinct regions of the nasal cavity. The development of this test apparatus employed computed tomography (CT) scan data of the human nasal cavity to construct an accurate representation of the human nasal airways. An investigation of suitable materials and manufacturing technologies was required, together with extensive analytical method development. It is possible for this technique to be further developed in an attempt to create a standardized apparatus based on nasal geometry that can be used to compare accurately deposition from drug delivery devices. This paper presents the issues encountered in the development of this test apparatus, including manufacturing and material limitations, investigation and choice of suitable materials, laboratory testing considerations, and the steps required to validate the analytical process.


Subject(s)
Aerosols/administration & dosage , Equipment Failure Analysis/instrumentation , Models, Anatomic , Nasal Cavity/anatomy & histology , Nasal Cavity/physiology , Nebulizers and Vaporizers , Administration, Intranasal , Equipment Failure Analysis/methods , Humans
9.
J Endourol ; 18(6): 527-30, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15333214

ABSTRACT

BACKGROUND AND PURPOSE: Shockwave lithotripsy (SWL) is widely practiced in the management of pediatric urolithiasis. However, the efficacy, need for ancillary procedures, and treatment-related complications are not as clearly defined as in the adult population. We reviewed the outcomes of SWL in the pediatric population at our lithotripsy unit. PATIENTS AND METHODS: A retrospective review of all patients

Subject(s)
Kidney Calculi/therapy , Lithotripsy , Ureteral Calculi/therapy , Adolescent , Child , Child, Preschool , Humans , Infant , Retrospective Studies
10.
J Biomech ; 35(10): 1337-46, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12231279

ABSTRACT

The development of intimal hyperplasia at arterial bypass graft anastomoses is a major factor responsible for graft failure. A revised surgical technique, involving the incorporation of a small section of vein (vein cuff) into the distal anastomosis of PTFE grafts, results in an altered distribution of intimal hyperplasia and improved graft patency rates, especially for below-knee grafts. Numerical simulations have been conducted under physiological conditions to identify the flow behaviour in a typical cuffed bypass model and to determine whether the improved performance of the cuffed system can be accounted for by haemodynamic factors. The flow patterns at the cuffed anastomosis are significantly different to those at the conventional end-to-side anastomosis. In the former case, the flow is characterised by an expansive, low momentum recirculation within the cuff. Separation occurs at the graft heel, and at the cuff toe as the blood enters the recipient artery. Wall shear stresses in the vicinity of the cuff heel are low, but high shear stresses and large spatial gradients in the shearing force act on the artery floor during systole. In contrast, a less disturbed flow prevails and the floor shear stress distribution is less adverse in the conventional model. In conclusion, aspects of the anastomotic haemodynamics are worsened when the cuff is employed. The benefits associated with the cuffed grafts may be related primarily to the presence of venous material at the anastomosis. Therefore, caution is advised with regard to the use of PTFE grafts, pre-shaped to resemble a cuffed geometry.


Subject(s)
Anastomosis, Surgical/methods , Blood Vessel Prosthesis Implantation/methods , Blood Vessel Prosthesis , Computer Simulation , Femoral Artery/physiopathology , Femoral Artery/surgery , Models, Cardiovascular , Blood Flow Velocity , Equipment Failure Analysis/methods , Finite Element Analysis , Hemodynamics , Humans , Pulsatile Flow , Sensitivity and Specificity , Stress, Mechanical , Veins/transplantation
11.
Med Eng Phys ; 24(6): 393-401, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12135648

ABSTRACT

Intimal hyperplasia at arterial bypass graft anastomoses is a major factor responsible for graft failure. A revised surgical technique, incorporating a Taylor vein patch into the distal anastomosis of PTFE grafts, results in a decrease in intimal hyperplasia and improved patency rates. Numerical simulations of pulsatile, non-Newtonian blood flow through life-like femorodistal bypass models have been performed to determine whether haemodynamic benefits arise from the modified geometry of the Taylor anastomosis. In a conventional bypass, the distal anastomotic flow exhibited considerable spatial and temporal variations. Steep spatial gradients in the shearing force acted along the floor during systole. The effect of the Taylor geometry was to reduce gradually the momentum of the blood approaching the junction. Thus, flow disturbances were abated, undesirable flow separation at the toe was diminished, and a less adverse floor shear stress distribution prevailed in that case. Intimal thickening should be alleviated at the toe in the Taylor model where separation is reduced, and where the thrombogenic graft surface is replaced with a vein patch. Intimal hyperplasia on the floor may be inhibited in the Taylor model due to more favourable shear stresses. The improved flow through the patched anastomosis should contribute to its enhanced performance.


Subject(s)
Femoral Artery/physiopathology , Femoral Artery/surgery , Models, Cardiovascular , Systole/physiology , Veins/physiopathology , Veins/surgery , Anastomosis, Surgical/methods , Blood Vessel Prosthesis , Computer Simulation , Hemodynamics/physiology , Polytetrafluoroethylene , Regional Blood Flow , Reproducibility of Results , Sensitivity and Specificity , Stress, Mechanical
12.
Proc Inst Mech Eng H ; 216(2): 135-43, 2002.
Article in English | MEDLINE | ID: mdl-12022420

ABSTRACT

The development of intimal hyperplasia at arterial bypass graft anastomoses is a major factor responsible for graft failure. A revised surgical technique, involving the incorporation of a small section of vein (vein cuff) into the distal anastomosis of polytetrafluoroethylene (PTFE) grafts, alters the distribution of intimal hyperplasia and improves graft performance. Numerical and in vitro flow visualization experiments have been conducted to identify the flow behaviour in the cuffed bypass model and to determine whether the improved performance of the cuffed system can be accounted for by haemodynamic factors. The flowfield at the cuffed anastomosis is characterized by an expansive recirculation. Separation occurs at the graft heel, and at the cuff toe as the blood enters the recipient artery. Wall shear stresses in the vicinity of the cuff heel are low, but high shear stresses and large spatial gradients in the shearing force act for a time on the artery floor. In the conventional model, a less disturbed flow prevails while the gradients of shear stress on the floor are smaller. Aspects of the anastomotic haemodynamics are worsened when the cuff is employed. The superior patency rates of cuffed bypasses may not be explained purely on the basis of local haemodynamic factors.


Subject(s)
Arteries/physiopathology , Blood Vessel Prosthesis , Computer Simulation , Hemodynamics/physiology , Models, Cardiovascular , Anastomosis, Surgical/methods , Arteries/surgery , Blood Flow Velocity , Reproducibility of Results , Stress, Mechanical
13.
Pediatrics ; 108(5): E93, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11694677

ABSTRACT

OBJECTIVE: Eosinophil-associated proteins, especially eosinophil-derived neurotoxin, may be important contributors to the neurologic pathology and symptoms caused by Baylisascaris procyonis infection. METHODS: Two cases of severe B procyonis encephalitis with evidence of marked eosinophil degranulation in the central nervous system are presented. Serial cerebrospinal fluid (CSF) specimens were collected from each patient during the course of their illness. Antibodies against B procyonis were measured in the patients' serum and CSF. Levels of the eosinophilopoietin interleukin-5 (IL-5) and 2 important eosinophil proteins, eosinophil-derived neurotoxin and major basic protein, were assayed in the CSF. RESULTS: Both patients had rapidly progressive central nervous system disease with evidence of eosinophilic meningoencephalitis. Both tested positive for antibodies to B procyonis in serum and CSF and had progressively worsening deep white matter changes on magnetic resonance images of the brain. CSF levels of IL-5, eosinophil-derived neurotoxin, and major basic protein were markedly elevated over controls. CONCLUSIONS: This is the first report of the measurement of IL-5, eosinophil-derived neurotoxin, and major basic protein in human CSF. In addition to traumatic damage and necrosis caused by migrating larvae, eosinophil-derived neurotoxin from associated eosinophilic inflammation may be an important contributory factor in the pathogenesis of B procyonis encephalitis. parasite, eosinophil-derived-neurotoxin, major basic protein, eosinophilia, hypereosinophilia, interleukin-5, encephalitis, child.


Subject(s)
Ascaridida Infections/complications , Ascaridoidea , Encephalitis/parasitology , Eosinophilia/complications , Raccoons/parasitology , Animals , Ascaridida Infections/cerebrospinal fluid , Ascaridida Infections/drug therapy , Biomarkers/cerebrospinal fluid , Blood Proteins/cerebrospinal fluid , Encephalitis/cerebrospinal fluid , Encephalitis/drug therapy , Eosinophil Granule Proteins , Eosinophil-Derived Neurotoxin , Eosinophilia/cerebrospinal fluid , Fatal Outcome , Humans , Infant , Male , Ribonucleases/cerebrospinal fluid
14.
Mol Endocrinol ; 15(10): 1758-67, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11579208

ABSTRACT

Immunosuppressants such as FK506 (tacrolimus), the primary cellular target of which is calcineurin, decrease beta-cell insulin content and preproinsulin mRNA expression. This study offers an explanation for this effect by establishing that calcineurin is an important regulator of insulin gene expression through the activation of a transcription factor, nuclear factor of activated T cells. Three putative nuclear factor of activated T cells binding sites were located within the proximal region of the rat insulin I gene promoter (-410 to +1 bp). Expression of nuclear factor of activated T cells in both clonal (INS-1) and primary (islet) beta-cells was confirmed by immunoblot and immunocytochemical analyses. Moreover, nuclear factor of activated T cells DNA-binding activity was detected in INS-1 and islet nuclear extracts by EMSAs. Activation of the insulin gene promoter by glucose or elevated extracellular K(+) (to depolarize the beta-cell) was totally prevented by FK506 (5-10 microM). K(+)-induced promoter activation was suppressed (>65%) by a 2-bp mutation of a single nuclear factor of activated T cells binding site in -410 rInsI. Both stimulants also activated a minimal promoter-reporter construct containing tandem nuclear factor of activated T cells consensus sequences. The effects of FK506 on K(+)-induced nuclear factor of activated T cells reporter or insulin gene promoter activity were not mimicked by rapamycin, indicating specificity toward calcineurin. These findings suggest that the activation of calcineurin by beta-cell secretagogues that elevate cytosolic Ca(2+) plays a fundamental role in maintenance of insulin gene expression via the activation of nuclear factor of activated T cells.


Subject(s)
Calcineurin/pharmacology , Calcium/pharmacology , DNA-Binding Proteins/pharmacology , Gene Expression Regulation , Insulin/genetics , Nuclear Proteins , Transcription Factors/pharmacology , Binding Sites , Cell Line , Cyclic AMP Response Element-Binding Protein/metabolism , DNA/metabolism , DNA-Binding Proteins/analysis , DNA-Binding Proteins/genetics , Glucose/pharmacology , Humans , Islets of Langerhans/chemistry , Islets of Langerhans/metabolism , Jurkat Cells , Mutagenesis , NFATC Transcription Factors , Plasmids/genetics , Polymerase Chain Reaction , Potassium/pharmacology , Promoter Regions, Genetic , Tacrolimus/pharmacology , Transcription Factors/analysis , Transcription Factors/genetics , Transcription, Genetic/drug effects , Transfection
16.
Mod Pathol ; 14(7): 720-6, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11455006

ABSTRACT

We describe a case of desmoplastic infantile ganglioglioma (DIG) arising in the ventral diencephalon of a 3-1/2-month-old boy. On biopsy, the tumor featured a desmoplastic, S-100 protein and GFAP immunoreactive stromal element, as well as a variable spectrum of ganglion cells. Electron microscopy demonstrated astrocytes, and morphologically fibroblasts, as well as neurons containing 120-nm dense core granules. In addition, tubular structures composed of tightly apposed cells with features of astrocytes and of Schwann-like cells were also noted. Devoid of fibroblasts, the tubular structures were surrounded by a single basal lamina. At autopsy 6 years later, the multinodular, cystic mass had replaced the diencephalon, extended into both temporal lobes as well as the optic nerves, and showed marked leptomeningeal involvement. Microscopically, superficial portions of the tumor consisted of typical DIG, whereas deep, nondesmoplastic portions exhibited pattern variation ranging from pilocytic astrocytoma to ganglioglioma and gangliocytoma. There was also a minor element of small, 'primitive-appearing' neuroepithelial cells. Dysplastic ganglion cells variously reactive for neurofilament protein and synaptophysin were present throughout the tumor. Our study not only confirms DIG as a variant of ganglioglioma, one capable of slow growth, infiltration, and fatal progression but suggests that its differentiating potential includes elements of both the central and peripheral nervous systems. If so, their derivation may be from multipotential cells of the neural plate.


Subject(s)
Brain Neoplasms/pathology , Ganglioglioma/pathology , Autopsy , Brain Neoplasms/ultrastructure , Child , Child, Preschool , Fatal Outcome , Follow-Up Studies , Ganglioglioma/ultrastructure , Humans , Infant , Male , Microscopy, Electron
17.
Pediatrics ; 107(5): E82, 2001 May.
Article in English | MEDLINE | ID: mdl-11331732

ABSTRACT

Lymphomatoid granulomatosis, a rare condition in children, affects the lungs primarily but may have significant extrapulmonary manifestations, especially in the central nervous system. We report a case of lymphomatoid granulomatosis with onset after the completion of chemotherapy for childhood acute lymphoblastic leukemia. Two months after treatment ended, the 7-year-old girl developed splenomegaly, cervical adenopathy, and bilateral interstitial pulmonary infiltrates. She improved on cefotaxime but experienced a seizure 1 month later. A computed tomography scan of the head was normal, but her pulmonary infiltrates had become nodular. A computed tomography-guided biopsy of 1 of the nodules revealed cellular interstitial pneumonitis. One month later, she had persistent pulmonary infiltrates, marked splenomegaly, and new seizures. Magnetic resonance imaging of the head revealed cerebral nodules. Itraconazole was begun, and the pulmonary infiltrates resolved. Five months after her initial symptoms, she developed tonic pupil and a decreased level of consciousness. Dexamethasone was initiated. Needle biopsies of the brain were carried out, yielding the diagnosis of severe chronic inflammatory changes focally consistent with granuloma. The child redeveloped splenomegaly and fever, and then suffered an acute decompensation with hypoxemia, tachypnea, splenomegaly, and cardiac gallop. Open-lung biopsy revealed lymphomatoid granulomatosis. Lymphoma-directed therapy was initiated, and the patient had complete resolution of pulmonary and cerebral nodules 5 months later. No intrathecal chemotherapy was administered, and radiation therapy was not necessary. Neuropsychological testing obtained after completion of therapy revealed an improvement in attention, coordination, and fine motor speed over time. She is now in good health and attending school.


Subject(s)
Brain Neoplasms/diagnosis , Lung Neoplasms/diagnosis , Lymphomatoid Granulomatosis/diagnosis , Neoplasms, Second Primary/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biopsy , Brain Neoplasms/drug therapy , Child, Preschool , Female , Humans , Lung Neoplasms/drug therapy , Lymphomatoid Granulomatosis/drug therapy , Magnetic Resonance Imaging , Neoplasms, Second Primary/drug therapy
18.
Fresenius J Anal Chem ; 369(7-8): 601-8, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11371056

ABSTRACT

The immobilization of oligonucleotides to solid surfaces can provide a platform of chemistry that is suitable for the development of biosensor and microarray technologies. Experiments were performed using a fiber optic nucleic acid biosensor based on total internal reflection fluorescence to examine the effects of the presence of non-complementary DNA on the detection of hybridization of complementary target DNA. The work has focused on the rates and extent of hybridization in the presence and absence of non-selective adsorption using fluorescein-labeled DNA. A stop-flow system of 137 microL volume permitted rapid introduction and mixing of each sample. Response times measured were on the order of seconds to minutes. Non-selective adsorption of non-complementary oligonucleotides (ncDNA) was found to occur at a significantly faster rate than hybridization of complementary oligomers (cDNA) in all cases. The presence of ncDNA oligonucleotides did not inhibit selective interactions between immobilized DNA and cDNA in solution. The presence of high concentrations of non-complementary genomic DNA had little effect on the extent of hybridization of complementary oligonucleotides, but actually reduced the response times of sensors to cDNA oligonucleotides.


Subject(s)
Biosensing Techniques , DNA, Bacterial/genetics , DNA, Complementary/analysis , Escherichia coli/genetics , Oligodeoxyribonucleotides , DNA, Bacterial/analysis , DNA, Single-Stranded/analysis , Fiber Optic Technology , Nucleic Acid Hybridization , Optical Fibers
19.
J Am Acad Orthop Surg ; 8(5): 277-84, 2000.
Article in English | MEDLINE | ID: mdl-11029555

ABSTRACT

Viscosupplementation by means of intra-articular injections of hyaluronic acid has been used to treat osteoarthritis of the knee. The proposed mechanisms of action result from the physical properties of hyaluronic acid, as well as from its anti-inflammatory, anabolic, local analgesic, and chrondroprotective effects. Adverse reactions from hyaluronic acid injections into the knee occurred in 8.3% of the 336 patients treated in one study, but at a rate of less than 3% per injection. Reactions were almost always local and generally resolved over 1 to 2 days. Hyaluronic acid injections were approved by the US Food and Drug Administration as a medical device; thus, the level of efficacy demonstrated is less than might have been required for approval as a drug. Several studies have failed to show statistically significant benefit compared with placebo. Furthermore, the treatment is relatively expensive; the cost of the drug for a series of injections is more than $500 per knee. Therefore, widespread use of these agents should be limited until more convincing data on their efficacy are available from well-designed clinical trials.


Subject(s)
Hyaluronic Acid/therapeutic use , Osteoarthritis, Knee/drug therapy , Analgesics/administration & dosage , Animals , Cartilage, Articular/drug effects , Costs and Cost Analysis , Humans , Hyaluronic Acid/administration & dosage , Hyaluronic Acid/analogs & derivatives , Hyaluronic Acid/economics , Injections, Intra-Articular
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