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1.
Article in English | MEDLINE | ID: mdl-38616765

ABSTRACT

OBJECTIVE: Provide benchmarks for the rates of complications by type of surgery performed. STUDY DESIGN: Prospective multicenter database. BACKGROUND: We have previously examined overall construct survival and complication rates for ASD surgery. However, the relationship between type of surgery and construct survival warrants more detailed assessment. METHODS: Eight surgical scenarios were defined based on the levels treated, previous fusion status (primary [P] vs. revision [R]), and 3-column osteotomy use [3CO]: Short Lumbar fusion, LT-Pelvis with 5-12 levels treated (P, R or 3CO), UT-Pelvis with  13 levels treated (P, R or 3CO), and Thoracic to Lumbar fusion without pelvic fixation, representing 92.4% of the case in the cohort. Complication rates for each type were calculated and Kaplan Meier curves with multivariate Cox regression analysis was used to evaluate the effect of the case characteristics on construct survival rate, while controlling for patient profile. RESULTS: 1073 of 1494 patients eligible for 2-year follow-up (71.8%) were captured. Survival curves for major complications (with or without reoperation), while controlling for demographics differed significantly among surgical types (P<0.001). Fusion procedures short of the pelvis had the best survival rate, while UT-Pelvis with 3CO had the worst survival rate. Longer fusions and more invasive operations were associated with lower 2-year complication-free survival, however there were no significant associations between type of surgery and renal, cardiac, infection, wound, gastrointestinal, pulmonary, implant malposition or neurologic complications (all P>0.5). CONCLUSION: This study suggests that there is an inherent increased risk of complication for some types of ASD surgery independent of patient profile. The results of this paper can be used to produce a surgery-adjusted benchmark for ASD surgery with regard to complications and survival. Such a tool can have very impactful applications for surgical decision making and more informed patient counseling.

2.
Spine (Phila Pa 1976) ; 49(12): 829-839, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38375636

ABSTRACT

OBJECTIVE: Provide benchmarks for the rates of complications by type and timing. STUDY DESIGN: Prospective multicenter database. BACKGROUND: Complication rates following adult spinal deformity (ASD) surgery have been previously reported. However, the interplay between timing and complication type warrants further analysis. METHODS: The data for this study were sourced from a prospective, multicenter ASD database. The date and type of complication were collected and classified into three severity groups (minor, major, and major leading to reoperation). Only complications occurring before the two-year visit were retained for analysis. RESULTS: Of the 1260 patients eligible for two-year follow-up, 997 (79.1%) achieved two-year follow-up. The overall complication rate was 67.4% (N=672). 247 patients (24.8%) experienced at least one complication on the day of surgery (including intraoperatively), 359 (36.0%) between postoperative day 1 and six weeks postoperatively, 271 (27.2%) between six weeks and one-year postoperatively, and finally 162 (16.3%) between one year and two years postoperatively. Using Kaplan-Meier survival analysis, the rate of remaining complication-free was estimated at different time points for different severities and types of complications. Stratification by type of complication demonstrated that most of the medical complications occurred within the first 60 days. Surgical complications presented over two distinct timeframes. Operative complications, incision-related complications, and infections occurred early (within 60 d), while implant-related and radiographic complications occurred at a constant rate over the two-year follow-up period. Neurological complications had the highest occurrence within the first 60 days but continued to increase up to the two-year visit. CONCLUSION: Only one-third of ASD patients remained complication-free by two years, and 2 of 10 patients had a complication requiring a reoperation or revision. An estimation of the timing and type of complications associated with surgical treatment may prove useful for more meaningful patient counseling and aid in assessing the cost-effectiveness of treatment. LEVEL OF EVIDENCE: 3.


Subject(s)
Postoperative Complications , Humans , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Male , Female , Middle Aged , Adult , Prospective Studies , Aged , Time Factors , Follow-Up Studies , Reoperation/statistics & numerical data , Spinal Curvatures/surgery , Young Adult , Databases, Factual
3.
Biochim Biophys Acta Mol Cell Res ; 1864(2): 336-344, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27888098

ABSTRACT

Maspin is a non-inhibitory member of the serpin family that affects cell behaviours related to migration and survival. We have previously shown that peptides of the isolated G α-helix (G-helix) domain of maspin show bioactivity. Migration, invasion, adhesion and proliferation of vascular smooth muscle cells (VSMC) are important processes that contribute to the build-up of atherosclerotic plaques. Here we report the use of functional assays of these behaviours to investigate whether other maspin-derived peptides impact directly on VSMC; focusing on potential anti-atherogenic properties. We designed 18 new peptides from the structural moieties of maspin above ten amino acid residues in length and considered them beside the existing G-helix peptides. Of the novel peptides screened those with the sequences of maspin strand 4 and 5 of beta sheet B (S4B and S5B) reduced VSMC migration, invasion and proliferation, as well as increasing cell adhesion. A longer peptide combining these consecutive sequences showed a potentiation of responses, and a 7-mer contained all essential elements for functionality. This is the first time that these parts of maspin have been highlighted as having key roles affecting cell function. We present evidence for a mechanism whereby S4B and S5B act through ERK1/2 and AMP-activated protein kinase (AMPK) to influence VSMC responses.


Subject(s)
Muscle, Smooth, Vascular/physiology , Peptide Fragments/physiology , Serpins/physiology , Amino Acid Sequence , Cell Proliferation/physiology , Cells, Cultured , Humans , Integrin beta1/physiology , MAP Kinase Signaling System , Muscle, Smooth, Vascular/chemistry , Serpins/chemistry , Signal Transduction
4.
World Neurosurg ; 98: 603-613, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27789321

ABSTRACT

The purpose of this paper is to propose and qualify a novel funding mechanism for international neurosurgical nonprofits. The article first identifies and explains neurosurgeons' means for practicing in the developing world through a literature review. After this examination of the current funding methods for surgical care in low-income regions, the work transitions to an explanation of the applications and limitations of a new resource: the internal wealth of a developing country. This wealth may be leveraged by way of a for-profit hospital to create sustainable and domestic funding for nonprofit neurosurgical training. The applicability of the proposed mechanism extends beyond the field of neurosurgery to nonprofits in any health-related discipline. Factors influencing the viability of this mechanism (including local disease burden, economic trajectory, and political stability) are examined to create a baseline set of conditions for success.


Subject(s)
Financing, Organized/economics , Neurosurgery/economics , Charities/economics , Developing Countries/economics , Equipment and Supplies/economics , Financial Support , Financing, Organized/methods , Gift Giving , Global Health , Humans , Income , International Cooperation , Marketing of Health Services/economics , Neurosurgery/education , Organizations, Nonprofit/economics
5.
J Theor Biol ; 388: 37-49, 2016 Jan 07.
Article in English | MEDLINE | ID: mdl-26497917

ABSTRACT

Most cancer treatments efficacy depends on tumor metastasis suppression, where tumor suppressor genes play an important role. Maspin (Mammary Serine Protease Inhibitor), an non-inhibitory serpin has been reported as a potential tumor suppressor to influence cell migration, adhesion, proliferation and apoptosis in in vitro and in vivo experiments in last two decades. Lack of computational investigations hinders its ability to go through clinical trials. Previously, we reported first computational model for maspin effects on tumor growth using artificial neural network and cellular automata paradigm with in vitro data support. This paper extends the previous in silico model by encompassing how maspin influences cell migration and the cell-extracellular matrix interaction in subcellular level. A feedforward neural network was used to define each cell behavior (proliferation, quiescence, apoptosis) which followed a cell-cycle algorithm to show the microenvironment impacts over tumor growth. Furthermore, the model concentrates how the in silico experiments results can further confirm the fact that maspin reduces cell migration using specific in vitro data verification method. The data collected from in vitro and in silico experiments formulates an unsupervised learning problem which can be solved by using different clustering algorithms. A density based clustering technique was developed to measure the similarity between two datasets based on the number of links between instances. Our proposed clustering algorithm first finds the nearest neighbors of each instance, and then redefines the similarity between pairs of instances in terms of how many nearest neighbors share the two instances. The number of links between two instances is defined as the number of common neighbors they have. The results showed significant resemblances with in vitro experimental data. The results also offer a new insight into the dynamics of maspin and establish as a metastasis suppressor gene for further molecular research.


Subject(s)
Computer Simulation , Models, Biological , Neoplasms/metabolism , Serpins/metabolism , Algorithms , Apoptosis , Cell Adhesion , Cell Line, Tumor , Cell Movement , Cell Proliferation , Extracellular Matrix/metabolism , Humans , Neoplasm Metastasis , Neoplasms/pathology , Protein Binding , Protein Interaction Maps , Signal Transduction , Tumor Microenvironment
6.
J Theor Biol ; 337: 150-60, 2013 Nov 21.
Article in English | MEDLINE | ID: mdl-23988797

ABSTRACT

Cancer metastasis is a complex multistep process which allows cancer cells to establish new tumours in distant organs. The process of metastasis involves cell migration and invasion; it is what makes cancer a fatal disease. The efficiency of most cancer treatments depends on metastasis suppression. Maspin is a type II tumour metastasis suppressor which has multiple cellular effects. It has been described as a key regulatory protein in both the intracellular and extracellular environments. Maspin has been shown to reduce cell migration, invasion, proliferation and angiogenesis, and increase apoptosis and cell-cell adhesion in in vitro and in vivo experiments. The clinical data regarding the predictive effects of maspin expression are variable. To date, the whole cellular mechanisms that maspin uses to influence tumour cell behaviours have not been clearly defined. The diversity of the effects of maspin motivated us to develop an intelligent model to investigate its effects on cellular proliferation and migration. This paper reports a hybrid model of solid tumour growth in order to investigate the impact of maspin on the growth and evolutionary dynamics of the cancer cell. A feed-forward neural network was used to model the behaviours (proliferation, quiescence, apoptosis and/or movement) of each cell, which has been suggested as a suitable model of cell signalling pathways. Results show that maspin reduces migration by 10-40%, confirmed by published in vitro data. The model also shows a reduction in cell proliferation by 20-30% in the presence of maspin. So far, this is the first attempt to model the effect of maspin in a computational model to verify in vitro data. This will provide new insights into the tumour suppressive properties of maspin and inform the development of novel cancer therapies.


Subject(s)
Computer Simulation , Models, Biological , Neoplasms/pathology , Serpins/pharmacology , Animals , Apoptosis/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Humans , Neoplasm Invasiveness , Neoplasms/drug therapy , Neoplasms/metabolism , Neural Networks, Computer , Serpins/therapeutic use
7.
J Theor Biol ; 313: 142-52, 2012 Nov 21.
Article in English | MEDLINE | ID: mdl-22974970

ABSTRACT

The potential for the use of in-silico models of disease in progression monitoring is becoming increasingly recognised, as well as its contribution to the development of complete curative processes. In this paper we report the development of a hybrid cellular automaton model to mimic the growth of avascular tumours, including the infusion of a bioreductive drug to study the effects of protein binding on drug transportation. The growth model is operated within an extracellular tumour microenvironment. An artificial Neural Network based scheme was implemented that modelled the behaviours of each cell (proliferation, quiescence, apoptosis and/or movement) based on the complex heterogeneous microenvironment; consisting of oxygen, glucose, hydrogen ions, inhibitory factors and growth factors. To validate the growth model results, we conducted experiments with multicellular tumour spheroids. These results showed good agreement with the predicted growth dynamics. The outcome of the avascular tumour growth model suggested that tumour microenvironments have a strong impact on cell behaviour. To address the problem of cellular proteins acting as resistive factors preventing efficient drug penetration, a bioreactive drug (tirapazamine) was added to the system. This allowed us to study the drug penetration through multicellular layers of tissue after its binding to cellular proteins. The results of the in vitro model suggested that the proteins reduce the toxicity of the drug, reducing its efficacy for the most severely hypoxic fractions furthest from a functional blood vessel. Finally this research provides a unique comparison of in vitro tumour growth with an intelligent in silico model to measure bioreductive drug availability inside tumour tissue through a set of experiments.


Subject(s)
Antineoplastic Agents/metabolism , Models, Biological , Neoplasms/blood supply , Neoplasms/pathology , Antineoplastic Agents/pharmacology , Biological Transport/drug effects , Cell Hypoxia/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Diffusion/drug effects , HT29 Cells , Humans , Neural Networks, Computer , Protein Binding/drug effects , Reproducibility of Results , Spheroids, Cellular/drug effects , Spheroids, Cellular/pathology , Tirapazamine , Triazines/metabolism , Triazines/pharmacology
8.
Opt Lett ; 37(12): 2328-30, 2012 Jun 15.
Article in English | MEDLINE | ID: mdl-22739897

ABSTRACT

We demonstrate a novel method to spectroscopically detect and identify trace gases. Micromechanical photothermal spectroscopy (MPS) with functionalized sorbent materials provides trace gas spectra in an optical interaction length of only a few micrometers. We use microcavity interferometry to read out displacements as low as 25 fm/√Hz, heating as low as 200 pW/√Hz, and analyte concentrations as low as 65 parts-per-billion for the nerve agent simulant DMMP. MPS integrated with functional materials represents an important new tool in chip-scale optical sensing.


Subject(s)
Gases/analysis , Mechanical Phenomena , Polymers/chemistry , Spectrum Analysis/methods , Gases/chemistry , Interferometry , Light , Optical Phenomena , Spectrum Analysis/instrumentation , Volatilization
9.
Opt Express ; 16(4): 2423-30, 2008 Feb 18.
Article in English | MEDLINE | ID: mdl-18542321

ABSTRACT

We describe a new class of micro-opto-mechanical chemical sensors: A photonic microharp chemical sensor is an array of closely spaced microbridges, each differing slightly in length and coated with a different sorbent polymer. They are optically interrogated using microcavity interferometry and photothermal actuation, and are coupled directly to an optical fiber. Simultaneous measurements of the fundamental flexural resonant frequency of each microbridge allow the real-time detection and discrimination of a variety of vapor-phase analytes, including DMMP at concentrations as low as 17 ppb.

10.
Biochem Soc Trans ; 35(Pt 3): 583-7, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17511657

ABSTRACT

Pericellular proteolytic activity affects many aspects of cellular behaviour, via mechanisms involving processing of the extracellular matrix, growth factors and receptors. The serine proteases have exquisitely sensitive regulatory mechanisms in this setting, involving both receptor-bound and transmembrane proteases. Receptor-bound proteases are exemplified by the uPA (urokinase plasminogen activator)/uPAR (uPAR receptor) plasminogen activation system. The mechanisms initiating the activity of this proteolytic system on the cell surface, a critical regulatory point, are poorly understood. We have found that the expression of the TTSP (type II transmembrane serine protease) matriptase is highly regulated in leucocytes, and correlates with the presence of active uPA on their surface. Using siRNA (small interfering RNA), we have demonstrated that matriptase specifically activates uPAR-associated pro-uPA. The uPA/uPAR system has been implicated in the activation of the plasminogen-related growth factor HGF (hepatocyte growth factor). However, we find no evidence for this, but instead that HGF can be activated by both matriptase and the related TTSP hepsin in purified systems. Hepsin is of particular interest, as the proteolytic cleavage sequence of HGF is an 'ideal substrate' for hepsin and membrane-associated hepsin activates HGF with high efficiency. Both of these TTSPs can be activated autocatalytically at the cell surface, an unusual mechanism among the serine proteases. Therefore these TTSPs have the capacity to be true upstream initiators of proteolytic activity with subsequent downstream effects on cell behaviour.


Subject(s)
Cell Membrane/enzymology , Serine Endopeptidases/metabolism , Animals , Hepatocyte Growth Factor/metabolism , Humans , In Vitro Techniques , Integrins/metabolism , Kangai-1 Protein/metabolism , RNA, Small Interfering/genetics , Receptors, Cell Surface/genetics , Receptors, Cell Surface/metabolism , Receptors, Urokinase Plasminogen Activator , Serine Endopeptidases/chemistry , Serine Endopeptidases/genetics , Urokinase-Type Plasminogen Activator/genetics , Urokinase-Type Plasminogen Activator/metabolism
11.
Br J Cancer ; 92(12): 2171-80, 2005 Jun 20.
Article in English | MEDLINE | ID: mdl-15928670

ABSTRACT

Extracellular proteases of the matrix metalloproteinase (MMP) and serine protease families participate in many aspects of tumour growth and metastasis. Using quantitative real-time RT-PCR analysis, we have undertaken a comprehensive survey of the expression of these enzymes and of their natural inhibitors in 44 cases of human prostate cancer and 23 benign prostate specimens. We found increased expression of MMP10, 15, 24, 25 and 26, urokinase plasminogen activator-receptor (uPAR) and plasminogen activator inhibitor-1 (PAI1), and the newly characterised serine proteases hepsin and matriptase-1 (MTSP1) in malignant tissue compared to benign prostate tissue. In contrast, there was significantly decreased expression of MMP2 and MMP23, maspin, and the protease inhibitors tissue inhibitor of metalloproteinase 3 (TIMP3), TIMP4 and RECK (reversion-inducing cysteine-rich protein with Kazal motifs) in the cancer specimens. The expression of MMP15 and MMP26 correlated positively with Gleason score, whereas TIMP3, TIMP4 and RECK expression correlated negatively with Gleason score. The cellular localisation of the expression of the deregulated genes was evaluated using primary malignant epithelial and stromal cell cultures derived from radical prostatectomy specimens. MMP10 and 25, hepsin, MTSP1 and maspin showed predominantly epithelial expression, whereas TIMP 3 and 4, RECK, MMP2 and 23, uPAR and PAI1 were produced primarily by stromal cells. These data provide the first comprehensive and quantitative analysis of the expression and localisation of MMPs and their inhibitors in human prostate cancer, leading to the identification of several genes involved in proteolysis as potential prognostic indicators, in particular hepsin, MTSP1, MMP26, PAI1, uPAR, MMP15, TIMP3, TIMP4, maspin and RECK.


Subject(s)
Matrix Metalloproteinases/genetics , Prostatic Neoplasms/genetics , Serine Endopeptidases/genetics , Tissue Inhibitor of Metalloproteinases/genetics , Aged , Disease Progression , GPI-Linked Proteins , Gene Expression Profiling , Humans , Male , Matrix Metalloproteinases/biosynthesis , Membrane Glycoproteins/biosynthesis , Membrane Glycoproteins/genetics , Middle Aged , Prognosis , Prostate/metabolism , Prostate/pathology , Prostatectomy , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , RNA, Messenger , Reverse Transcriptase Polymerase Chain Reaction , Serine Endopeptidases/biosynthesis , Tissue Inhibitor of Metalloproteinases/biosynthesis
12.
BJU Int ; 91(4): 315-23; discussion 323-4, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12603403

ABSTRACT

OBJECTIVE: To describe the establishment, methods, validation and use of a bank of fresh-frozen human prostate tissue. MATERIALS AND METHODS: On obtaining informed patient consent, protocols were followed for banking prostate tissue from any type of prostatectomy or cystoprostatectomy. A pseudobanking procedure was devised to determine the accuracy of assessing the histopathological status of the banked tissue. RNA was extracted, its quality assessed and used for quantitative real-time reverse transcription-polymerase chain reaction for the serine protease hepsin. RESULTS: To date prostate tissue from 112 patients has been banked, with pseudobanking in 58. The histopathological assessment showed pseudobanked tissue matched adjacent unbanked tissue in 98% of cases for benign vs malignant diagnoses, and in 92% of carcinomas for the Gleason score. Hepsin expression was significantly higher in malignant than in benign tissues (P < 0.0001). CONCLUSION: We established a validated method for banking human fresh-frozen prostate tissue and applied it successfully. Hepsin expression can be used to differentiate malignant and benign prostate tissue, and as an indicator of tissue heterogeneity.


Subject(s)
Cryopreservation/methods , Prostate , Prostatic Diseases/pathology , Tissue Banks/standards , Gene Expression , Humans , Immunohistochemistry/methods , Immunohistochemistry/standards , Informed Consent , Male , Prostatectomy , Quality Control , RNA/analysis , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction/methods , Serine Endopeptidases/analysis , Tissue Banks/organization & administration , Tissue Banks/statistics & numerical data
13.
Hum Reprod ; 17(7): 1918-24, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12093861

ABSTRACT

BACKGROUND: Estradiol exerts a number of biological effects that support extensive observational data suggesting a protective role for estrogen in cardiovascular disease prevention. These include effects on lipid and carbohydrate metabolism, coagulation/fibrinolysis as well as a possible effect on vascular reactivity. It has been proposed that this might be mediated by vascular endothelial nitric oxide (NO) production. Accordingly, we designed complementary in-vivo and in-vitro studies to investigate this hypothesis further. METHODS: Firstly, in a group of 10 healthy post-menopausal women, bilateral venous occlusion plethysmography was used to examine forearm vasoconstrictor responses to intrabrachial N(G)-monomethyl-l-arginine (l-NMMA; a substrate inhibitor of nitric oxide synthase) both before and after 4 weeks of treatment with transdermal 17beta-estradiol (E(2)) (80 microg/day). Secondly, we examined the direct effects of acute (24 h) and chronic (7 days) treatment with E(2) (10 pmol/l and 10 nmol/l) on endothelial nitric oxide synthase (eNOS) gene expression in cultured human aortic endothelial cells. RESULTS: No significant differences were observed between the vasoconstrictor responses to l-NMMA (2, 4, 8 micromol/min) before and after E(2) treatment. Comparison of E(2)-treated endothelial cells with control cells showed no significant increase in eNOS mRNA expression following either acute or chronic estradiol treatment. CONCLUSIONS: The present studies do not provide evidence for an eNOS-mediated cardioprotective response to estrogen and therefore suggest that additional mechanisms other than the endothelial NO system may have an important role in the cardiovascular effects of estrogen.


Subject(s)
Cardiotonic Agents/pharmacology , Estradiol/pharmacology , Nitric Oxide/physiology , Administration, Cutaneous , Adult , Aorta/cytology , Aorta/metabolism , Brachial Artery , Cardiotonic Agents/administration & dosage , Cells, Cultured , Drug Synergism , Endothelium, Vascular/cytology , Endothelium, Vascular/metabolism , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/pharmacology , Estradiol/administration & dosage , Estrogen Receptor alpha , Estrogen Receptor beta , Female , Forearm/blood supply , Humans , Injections, Intra-Arterial , Middle Aged , Nitric Oxide/genetics , RNA, Messenger/biosynthesis , Receptors, Estrogen/genetics , Vasoconstriction , omega-N-Methylarginine/administration & dosage , omega-N-Methylarginine/pharmacology
14.
Biochem Soc Trans ; 30(2): 189-94, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12023849

ABSTRACT

A variety of proteases have the potential to degrade the extracellular matrix (ECM), thereby influencing the behaviour of cells by removing physical barriers to cell migration, altering cell-ECM interactions or releasing ECM-associated growth factors. The plasminogen activation system of serine proteases is particularly implicated in this pericellular proteolysis and is involved in pathologies ranging from cancer invasion and metastasis to fibroproliferative vascular disorders and neurodegeneration. A central mechanism for regulating plasmin generation is through the binding of the two plasminogen activators to specific cellular receptors: urokinase-type plasminogen activator to the glycolipid-anchored membrane protein uPAR, and tissue plasminogen activator to a type-II transmembrane protein recently identified on vascular smooth muscle cells. These binary complexes interact with membrane-associated plasminogen to form higher order activation complexes that greatly reduce the K(m) for plasminogen activation and, in some cases, protect the proteases from their cognate serpin inhibitors. Various other proteins that are involved in cell adhesion and migration also interact with these complexes, modulating the activity of this efficient and spatially restricted proteolytic system. Recent observations demonstrate that certain forms of the prion protein can stimulate tissue plasminogen activator-catalysed plasminogen activation, which raises the possibility that these proteases may also have a role in the pathogenesis of the transmissible spongiform encephalopathies.


Subject(s)
Fibrinolysin/biosynthesis , Animals , Hemostasis/physiology , Humans , Membrane Proteins/metabolism , Mice , Models, Biological , Muscle, Smooth, Vascular/metabolism , Neurodegenerative Diseases/metabolism , Plasminogen/metabolism , Receptors, Cell Surface/metabolism , Receptors, Urokinase Plasminogen Activator , Urokinase-Type Plasminogen Activator/metabolism
15.
Clin Oncol (R Coll Radiol) ; 14(1): 23-7, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11899903

ABSTRACT

BACKGROUND: SRL172 is a suspension of heat killed Mycobacterium vaccae, that has been found to be a potent immunological adjuvant when used with autologous cells in animal models. This is a phase II study to test the clinical activity, feasibility and safety of combining SRL172 with chemotherapy to treat patients with small cell lung cancer (SCLC). METHODS: Patients were randomized to receive chemotherapy with (n=14) or without (n=14) SRL172. The chemotherapy was either platinum-based (MVP, n=10) or anthracycline-based (ACE, n=18). SRL172 was given intradermally on day 0, weeks 4, 8 and then 3-6 monthly. RESULTS: The treatment arms were well balanced for disease extent (43% with limited stage in each arm). The toxicity of chemotherapy and overall response at 12-15 weeks (57%) was the same for both treatment regimens. Median survival was 8.6 months and 12.9 for patients treated with chemotherapy alone and with the combination respectively (P=0.10). The survival trend was similar for both disease extent and chemotherapy regimen employed in favour of combination chemotherapy with SRL172. CONCLUSIONS: There is a trend to improved median survival in SCLC with the combination of chemotherapy and SRL172 with no increased toxicity and irrespective of drug regimen. A phase III study examining chemotherapy in combination with SRL172 in SCLC is now underway.


Subject(s)
Bacterial Vaccines/therapeutic use , Carcinoma, Small Cell/drug therapy , Lung Neoplasms/drug therapy , Mycobacterium , Aged , Feasibility Studies , Female , Humans , Male , Middle Aged , Pilot Projects
16.
Diagn Cytopathol ; 25(4): 253-7, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11599111

ABSTRACT

We report on a case of invasive lobular carcinoma of the breast with a previously undescribed cytologic feature. Diff-Quik-stained cytologic preparations showed uniform single cells with prominent coarse cytoplasmic granules. Ultrastructurally, the granules showed features suggestive of autophagosomes and/or degenerative mitochondria. The cytologic differential diagnosis included granulocytic sarcoma, metastatic melanoma, extramedullary hematopoiesis, large granulocytic leukemia/lymphoma, and mast-cell tumor. Adjunctive studies were helpful in the diagnosis of carcinoma. Histologic study of the mastectomy specimen showed classic type of invasive lobular carcinoma.


Subject(s)
Breast Neoplasms/diagnosis , Carcinoma, Lobular/diagnosis , Cytoplasmic Granules/pathology , Aged , Biopsy, Needle , Breast Neoplasms/chemistry , Breast Neoplasms/surgery , Breast Neoplasms/ultrastructure , Carcinoma, Lobular/chemistry , Carcinoma, Lobular/surgery , Carcinoma, Lobular/ultrastructure , Cytoplasmic Granules/ultrastructure , Diagnosis, Differential , Female , Flow Cytometry , Humans , Microscopy, Electron
17.
Am J Clin Pathol ; 116(4): 550-9, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11601140

ABSTRACT

We describe 35 peripheral lymph nodes classified as mantle cell/marginal zone B-cell hyperplasia with clear cells using morphologic and immunologic findings. For the purpose of this study, we obtained clinical follow-up information and performed immunoglobulin gene rearrangement studies on paraffin sections by polymerase chain reaction. Architecturally, the nodes were suggestive of a benign process: no pericapsular infiltration, sinuses readily identified, scattered reactive follicles present, and paracortical nodular hyperplasia present. No monocytoid B cells were present. Focally, small lymphoid cells with round nuclei and clear cytoplasm (clear cells) formed monomorphic nodular, inverse follicular, and/or marginal zone patterns. Flow cytometry and immunohistochemical analysis revealed neither light chain restriction nor an aberrant B-cell phenotype. Immunoglobulin gene rearrangement studies showed a clonal band in 1 of 26 cases in which DNA was amplified. To ascertain the clinical relevance of this positive case, follow-up information was obtained 30 months after the initial biopsy; the 83-year-old woman was alive without treatment but had splenomegaly and bone marrow involvement by marginal zone B-cell lymphoma. The morphologic and immunologic criteria used for diagnosis of mantle cell/marginal zone B-cell hyperplasia with clear cytoplasm are valid; however, to rule out the possibility of occult lymphoma, immunoglobulin gene rearrangement studies and clinical follow-up are necessary.


Subject(s)
B-Lymphocytes/pathology , Cytoplasm/pathology , Lymph Nodes/pathology , Adult , Aged , Aged, 80 and over , Axilla , Biopsy , Bone Marrow/pathology , Cell Nucleus/pathology , Cervix Uteri , Female , Flow Cytometry , Gene Rearrangement , Groin , Humans , Hyperplasia , Immunohistochemistry , Immunophenotyping , Lymphoma, B-Cell/pathology , Lymphoma, Mantle-Cell/pathology , Middle Aged , Splenomegaly , Tongue Neoplasms/pathology
18.
Am J Clin Pathol ; 116(2): 211-6, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11488067

ABSTRACT

We identified 3 patients with autoimmune myelofibrosis (AM) lacking American Rheumatism Association criteria for systemic lupus erythematosus (SLE). They had 1 or 2 cytopenias and lacked serologic evidence for SLE. Autoimmune features included psoriatic arthritis and positive direct Coombs test (DCT) result, DCT-positive autoimmune hemolytic anemia, and synovitis with polyclonal hypergammaglobulinemia. Bone marrow biopsy specimens from each patient were evaluated by routine morphologic and immunohistochemical examination. They demonstrated marked hypercellularity (2 cases) or hypocellularity (1 case), moderate erythroid hyperplasia (all cases) with left-shifted maturation (2 cases), intrasinusoidal hematopoiesis (all cases), slightly to moderately increased megakaryocytes (2 cases), and grade 3 to 4 reticulin fibrosis (all cases). All lacked basophilia, eosinophilia, bizarre megakaryocytes, clusters of megakaryocytes, and osteosclerosis. Mild to moderate bone marrow lymphocytosis was noted in all cases. In 2 cases, increased small T cells and B cells formed nonparatrabecular, loose aggregates. AM is a clinicopathologic entity that may lack features of SLE. Loose aggregates of bone marrow T and B lymphocytes and the absence of morphologic and clinical features of myeloproliferative disease or low-grade lymphoproliferative disease are clues that distinguish AM from better known causes of bone marrow fibrosis.


Subject(s)
Autoimmune Diseases/pathology , Primary Myelofibrosis/immunology , Primary Myelofibrosis/pathology , Adult , Aged , Anemia, Hemolytic/immunology , Anemia, Hemolytic/pathology , Antigens, CD20/analysis , Arthritis, Psoriatic/immunology , Arthritis, Psoriatic/pathology , B-Lymphocytes/immunology , B-Lymphocytes/pathology , Biopsy , Bone Marrow/pathology , CD3 Complex/analysis , Coombs Test , Female , Humans , Hypergammaglobulinemia/immunology , Hypergammaglobulinemia/pathology , Immunohistochemistry , Leukocyte Count , Male , Middle Aged , Platelet Count , Synovitis/immunology , Synovitis/pathology , T-Lymphocytes/immunology , T-Lymphocytes/pathology
19.
Am J Vet Res ; 62(6): 921-7, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11400851

ABSTRACT

OBJECTIVE: To determine effects of breed and oral vitamin E supplementation during late gestation on serum vitamin E and IgG concentrations in beef cows that calved in late winter and late summer and in neonatal calves. ANIMALS: 73 Angus and 43 Hereford primiparous and multiparous cows and their calves. PROCEDURE: Cows in groups that were homogeneous regarding breed and age distribution were randomly allotted to groups that were orally supplemented (n = 59) or not supplemented (57) with vitamin E beginning 30 days prior to onset of 65-day calving seasons. Supplemental vitamin E was provided in a vitamin-mineral mix offered free-choice until parturition. RESULTS: Cows that calved in late winter and were supplemented orally with vitamin E had higher serum vitamin E concentrations at calving and after calving than did unsupplemented cows; differences between groups before calving were not significant. Calves from supplemented multiparous cows had higher vitamin E concentrations than did calves from unsupplemented cows. Winter-born calves from supplemented Hereford cows had heavier 205-day adjusted weaning weights than did winter-born calves from unsupplemented Hereford cows. Supplementation did not affect vitamin E or IgG concentrations in the herd that calved in late summer and did not affect calf growth. CONCLUSIONS AND CLINICAL RELEVANCE: Oral vitamin E supplementation during late gestation may be economically beneficial in certain cow-calf operations in which late-gestation cows are consuming stored forages.


Subject(s)
Cattle/physiology , Dietary Supplements , Pregnancy, Animal/drug effects , Vitamin E/administration & dosage , Animals , Animals, Newborn , Birth Weight/physiology , Cattle/blood , Cattle/metabolism , Colostrum/metabolism , Female , Immunoglobulin G/analysis , Immunoglobulin G/blood , Pregnancy , Pregnancy, Animal/blood , Random Allocation , Seasons , Vitamin E/blood
20.
Arch Surg ; 136(3): 324-7, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11231854

ABSTRACT

BACKGROUND: Previous studies have suggested that patients transported by emergency medical services (EMS) following major trauma had a longer injury-to-treatment interval and a higher mortality rate than their non-EMS-transported counterparts. HYPOTHESIS: There is little actual benefit of thoracolumbar immobilization for patients with torso gunshot wounds (GSW). DESIGN: Retrospective analysis of prospectively gathered data from the Maryland Institute for Emergency Medical Service Systems State Trauma Registry from July 1, 1995, through June 30, 1998. SETTINGS: All designated trauma centers in Maryland. PATIENTS: All patients with torso GSW. MAIN OUTCOME MEASURES: (1) A patient was considered to have benefited from immobilization if he or she had less than complete neurologic deficits in the presence of an unstable vertebral column, as shown by the need for operative stabilization of the vertebral column; (2) mortality. RESULTS: There were 1000 patients with torso GSW. Among them, 141 patients (14.1%) had vertebral column and/or spinal cord injuries. Two patients (0.2%) (95% confidence interval, -0.077% to 0.48%) required operative vertebral column stabilization, while 6 others required other spinal operations for decompression and/or foreign body removal. The presence of vertebral column injury was actually associated with lower mortality (7.1% vs 14.8%, P<.02). CONCLUSIONS: This study suggests that thoracolumbar immobilization is almost never beneficial in patients with torso GSW, and that a higher mortality rate existed among those GSW patients without vertebral column injury vs those with such injuries. The role of formal thoracolumbar immobilization for patients with torso GSW should be reexamined.


Subject(s)
Emergency Medical Services , Immobilization , Lumbar Vertebrae/injuries , Spinal Cord Injuries/therapy , Spinal Injuries/therapy , Thoracic Vertebrae/injuries , Transportation of Patients , Wounds, Gunshot/therapy , Adult , Female , Humans , Male , Maryland/epidemiology , Retrospective Studies , Spinal Cord Injuries/mortality , Spinal Injuries/mortality , Survival Analysis , Survival Rate , Wounds, Gunshot/mortality
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