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Biomedical subjects

M Patterson

Publications and source records attributed to M Patterson.

At least 19 recordsLinked to original sources
PubMed1997

Predictive value of skull radiography for intracranial injury in children with blunt head injury.

BACKGROUND: The value of routine skull radiography as a method of predicting intracranial injury is controversial. We aimed to assess the effectiveness of skull radiography by prospectively studying head-injured children admitted to a children's hospital that serves an urban population. METHODS: Over a 2-year period, 9269 children attended our accident and emergency department with head injury, and 6011 were referred for skull radiography. All children who were admitted to hospital or had a skull fracture (n = 883) were included in the study. Computed tomography (CT) was done in children with skull fractures on radiography and in those without fractures if there were neurological indications. FINDINGS: Radiographs showed 162 fractures (2.7% of all radiographs and 18% of study group radiographs). Staff in the accident and emergency department missed 37 (23%) fractures. CT scan was done on 156 children, of whom 107 had a skull fracture. 23 children were found to have intracranial injuries on CT. The presence of neurological abnormalities had a sensitivity for identification of intracranial injury of 91% (21 of 23) and a negative predictive value of 97%. The corresponding values for skull fracture on radiography were 65% (15 of 23) and 83%. Four children died, of whom only one had a skull fracture. INTERPRETATION: In children, severe intracranial injury can occur in the absence of skull fracture. Skull radiography is not a reliable predictor of intracranial injury and is indicated only to confirm or exclude a suspected depressed fracture or penetrating injury, and when non-accidental injury is suspected, including in all infants younger than 2 years. Clinical neurological abnormalities are a reliable predictor of intracranial injury. If imaging is required, it should be with CT and not skull radiography.

Brain Injuries↗
PubMed1997

Cancer genetics.

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Cytogenetics↗
PubMed1997

Production of monoclonal antibodies against excretory-secretory products of adult male Onchocerca gibsoni.

Nine monoclonal antibodies (mabs) have been produced against excretory-secretory products (ES) of adult male Onchocerca gibsoni. These mabs fail to interact with the highly cross-reactive phosphorylcholine (PC) group and with ES of the related rodent filarial parasites Acanthocheilonema viteae and Litomosoides carinii. Eight of the mabs are of the IgG isotype: 1 is an IgM. Three of the mabs, OGMES 4, 9, and 10, were each found by immunoprecipitation/SDS-PAGE analysis of [3H] leucine-labeled ES, to recognize a triplet of polypeptides of molecular weight 120, approximately 210, and approximately 260 kDa. No recognition was observed by any mab when [3H] glucosamine was employed as the radiolabel for ES. Western blotting employing [125I] as indicator system demonstrated that OGMES 7 recognized a molecule of 27 kDa, and OGMES 1, a molecule of approximately 210 kDa, albeit faintly. These mabs may be of value to researchers working on the isolation, characterization, and detection in the bloodstream of Onchocerca volvulus ES.

Animals↗
PubMed1996

Transplantation of fetal myocardial tissue into the infarcted myocardium of rat. A potential method for repair of infarcted myocardium?

BACKGROUND: Unlike skeletal myocytes, mammalian adult cardiomyocytes cannot regenerate after injury. A possible strategy to increase viability and augment ventricular function after myocardial injury is fetal myocardial tissue transplantation. The engrafted fetal cells are a potential source of growth factors and can be used for cardiomyocyte-based gene therapy. The purpose of our study was to test the feasibility and efficiency of fetal cardiomyocyte transplantation into a model of myocardial infarction. METHODS AND RESULTS: We subjected rats after myocardial infarction to three protocols of therapy. In the first protocol, tissue fragments of cultured human fetal ventricles were injected into the scar 7 to 24 days after infarction. The rats were treated with intraperitoneal injections of 12.5 mg.kg-1.d-1 cyclosporine. In the second protocol, fragments of cultured fetal rat ventricles were injected into the scar 9 to 17 days after infarction. A third group of animals with myocardial infarction was treated with injection of saline into the scar (control). After 7 to 65 days post-transplantation, hearts were harvested and processed for electron microscopy and alpha-actin immunohistochemistry. Toluidine blue staining and electron microscopy revealed the presence of engrafted human and rat cardiomyocytes in the infarcted myocardium up to 14 and 65 days after transplantation, respectively. The morphology was similar to that of cultured fetal cardiomyocytes. The engrafted fetal tissues were also stained positive for alpha-actin, which is unusual for the adult rat myocardium. Examination of control hearts detected infarcted tissue only, and alpha-actin staining was limited to vessel walls. CONCLUSIONS: Fetal cardiomyocyte tissue can be implanted and survive in the infarcted myocardium. This experimental approach may provide a therapeutic strategy for cardiomyocyte-based gene therapy for introduction of therapeutic proteins into myocardial infarction.

Actins↗
PubMed1996

Avoidance of immune response prolongs expression of genes delivered to the adult rat myocardium by replication-defective adenovirus.

BACKGROUND: Gene delivery is a rapidly expanding field with potential applications to every human organ system. Recently, adenoviruses have been used as efficient vectors for in vivo gene transfer into the myocardium. These methods, however, have shown a sharp decline of gene expression after 1 week. To test the hypothesis that an immune-effector mechanism is involved in this decline, we compared the results after injection of adenovirus-5 carrying the beta-galactosidase gene (Ad beta-gal) into the left ventricular myocardium of athymic nude rats (NDRs) versus immunocompetent Sprague-Dawley rats (SDRs). METHODS AND RESULTS: Ad beta-gal (5.0 x 10(9) PFU/mL) was injected into the left ventricle of NDRs (n = 16) and SDRs (n = 22). Hearts were harvested, embedded in paraffin, and sectioned and stained for beta-gal activity, hematoxylin and eosin and picrosirius red at 4, 21, 35, 85, and 120 days. Representative samples were immunostained with antibodies directed at inflammatory markers. beta-gal activity was quantified by digital planimetry and expressed as area of staining (% +/- SEM). Peak beta-gal activity was highest at 4 days, with NDRs displaying significantly greater staining (83 +/- 3.0% versus 54 +/- 8.0%; P = .03). SDRs sustained a rapid drop in activity, such that at 35 (1 +/- 0.19%) and 85 (1 +/- 0.4%) days, only occasional cells stained positive and by 120 days (0.3 +/- 0.0%), activity had been extinguished. NDRs continued to show transgene expression at all time periods (35 and 85 days, 25 +/- 7.1% and 7.4 +/- 2.7%, respectively) and was still readily detected at 120 days. An inflammatory response was limited in NDRs compared with SDRs, in which there was intense mononuclear cell infiltration, with collagen deposition and scar formation. Immunostaining identified the majority of these inflammatory cells as not being of lymphocyte lineage, although small numbers of lymphocytes and phagocytic and activated plasma cells were identified. CONCLUSIONS: Our data suggest that immune-effector mechanisms can severely affect the expression of genes delivered by adenovirus. The present model provides efficient gene expression for at least 120 days without significant inflammatory reaction.

Adenoviridae↗
PubMed1996

Adenovirus-mediated gene transfer into infarcted myocardium: feasibility, timing, and location of expression.

Gene transfer as a therapeutic modality for the treatment of myocardial ischemia and/or infarction has been proposed as a revolutionary approach to improve collateral circulation, enhance myocardial viability and amplify healing. Our study was undertaken to assess the feasibility, efficiency, anatomic distribution, timing and localization of adenovirus-mediated gene transfer into the vicinity of infarcted myocardium in the adult mammalian heart. We induced myocardial infarction by subjecting rats to 60 min of coronary artery occlusion followed by sustained reperfusion. Gene transfer into the infarction area was performed using direct injection of a replication-defective adenovirus vector encoding the bacterial reporter gene, beta-galactosidase. A total of 5.0 x 10(9) plaque-forming units of virus was delivered into the left ventricular myocardium either immediately (n = 7) or at 7 (n = 6), 22 (n = 5) or 30 days (n = 5) after reperfusion of rat hearts. Control rats received either 50 microliters of saline 13 days after myocardial infarction (n = 2) or were not subjected to infarction and received Adenovirus carrying the beta-galactosidase gene as described above (n = 4). All rats were killed at 7 days after cardiac injection. Hearts were harvested, frozen and sectioned and stained for beta-galactosidase activity and with hematoxylin and eosin. Sections were evaluated by light microscopy. Relative beta-galactosidase activity was measured by digital planimetry and expressed as the ratio of the maximal area of beta-galactosidase staining relative to the total area of the section examined (% +/- S.E.M.). beta-galactosidase gene expression was limited mainly to viable myocytes at the border of the myocardial infarction. The area of transgene expression in the non-infarcted hearts (28 +/- 7%) was significantly higher (P = 0.02) than at any time point studied in infarcted tissues (3.4 +/- 1.2%, 1.4 +/- 1.0%, 2.8 +/- 0.8% and 3.4 +/- 0.9% at reperfusion and at 7, 22 and 30 days after myocardial infarction, respectively). Hearts injected 7 days after infarction had significantly less transgene activity (P = 0.03) with three of five samples displaying no macroscopically visible beta-gal activity. Following viral injection, an inflammatory response consisting of mononuclear cell infiltration was much less intense seven days following injection in non-infarcted control rat hearts than at any of the time points examined for infarcted hearts. Gene transfer into infarcted myocardium, while feasible, was limited by low transfection efficiency when compared to non-infarcted normal myocardium. Transgene expression in the infarcted myocardium appears restricted to residual cardiomyocytes in the periphery. Nevertheless, the ability to introduce genes into these viable peripheral cells might be a useful therapeutic strategy for enhancing neovascularization, collateral flow and healing.

Adenoviruses, Human↗
PubMed1996

Direct evidence that ischemic preconditioning does not cause protein kinase C translocation in rabbit heart.

OBJECTIVE: Indirect pharmacological evidence suggests that myocardial protection conferred by ischemic preconditioning in rabbit myocardium is mediated through the translocation of protein kinase C (PKC). To test this hypothesis, we performed direct biochemical measurements of subcellular distribution of PKC in rabbit hearts. METHODS: Two protocols were utilized. In Protocol I the preconditioned group (PC) underwent two 5-min episodes of brief coronary artery occlusion each followed by 5 min of reperfusion, while the control group consisted of time-matched, sham-operated (non-ischemic) animals (SO). Tissue samples were homogenized and cytosolic and particulate fractions were obtained by ultracentrifugation. In Protocol II one group of rabbits received ischemic preconditioning as in Protocol I followed by 10 min of sustained ischemia (PC + IS); a second control group was subjected to 10 min of sustained ischemia (IS); and the third group was time-matched, sham-operated (non-ischemic) animals (SO). Homogenized tissue samples were separated into cytosolic, nuclear and membrane fractions. RESULTS: In Protocol I, no differences in the subcellular distribution of PKC between the SO and PC groups were observed. In Protocol II, when samples were obtained at 10 min of sustained ischemia, no changes in the subcellular distribution of PKC were observed between SO, IS and PC + IS groups. CONCLUSION: Our results indicate that translocation of protein kinase C is not an important mediator of ischemic preconditioning in the rabbit ischemia model.

Animals↗
PubMed1996

Evaluation of Roche Amplicor PCR assay for Mycobacterium tuberculosis.

The Roche Amplicor Mycobacterium tuberculosis PCR test (RMtb-PCR) was compared with mycobacterial culture, with the BACTEC 460 system and inoculation on Lowenstein-Jensen media. Results were interpreted with an adjusted "gold standard" incorporating clinical diagnosis. A total of 1,480 clinical specimens from 1,155 patients, including tissues and fluids, as well as 141 specimens which demonstrated a positive growth index on the BACTEC 460 system were assessed. The sensitivity, specificity, and positive and negative predictive values of RMtb-PCR compared with the adjusted gold standard for clinical specimens were 79, 99, 93, and 98%, respectively. In smear-positive specimens, the sensitivity of RMtb-PCR was 98% versus 53% for smear-negative specimens. When RMtb-PCR was performed two times per week, PCR results were available an average of 21 days before the culture results. For specimens demonstrating a positive growth index on the BACTEC 460 system, RMtb-PCR had a sensitivity and specificity of 98 and 100%, respectively. This study demonstrates the value of a commercial nucleic acid amplification kit for rapid diagnosis of M. tuberculosis, particularly in smear-positive specimens or BACTEC culture-positive specimens.

Bacteriological Techniques↗
PubMed1996

Controlled trials of rG-CSF and CD11b-directed MAb during hyperoxia and E. coli pneumonia in rats.

We studied the effects of inhibiting and augmenting neutrophil function by using an immunocompetent rat model of infectious and hyperoxic lung injury. After intrabronchial Escherichia coli challenge at all fractional inspired O2 (FIO2) values studied (FIO2 = 0.21, 0.60, and 0.95) and after lethal O2 exposure alone (FIO2 = 0.90), lung injury, as measured by histological and physiological changes, was reduced by a CD11b/CD18-directed monoclonal antibody (MAb 1B6, P < 0.05 vs. controls) but was increased by recombinant granulocyte colony-stimulating factor (rG-CSF; P < 0.05 vs. control; MAb 1B6 vs. rG-CSF, P < 0.004). Pulmonary neutrophil counts were reduced by MAb 1B6 (P < 0.04) and increased by rG-CSF (P < 0.0004) compared with control animals. However, despite antibiotics, MAb 1B6 and rG-CSF both significantly increased the relative risk of death, independent of O2 concentration, during E. coli pneumonia (1.74 [symbol: see text] 1.20 and 2.39 [symbol: see text] 1.19, respectively, each P < 0.01). During lethal hyperoxia, MAb 1B6 increased the relative risk of death (1.76 [symbol: see text] 1.28, P < 0.16), whereas rG-CSF had no effect on survival (0.97 [symbol: see text] 1.28, P = 0.89). Thus inhibition of neutrophil function attenuated and enhancement worsened lung injury in response to infectious and hyperoxic challenges, supporting a pathophysiological role of the neutrophil in these processes. However, it is problematic that MAb 1B6 therapy, despite preventing lung damage, ultimately worsened host defenses and survival. Furthermore, rG-CSF also adversely affected survival during infectious lung injury, demonstrating the inherent risks of inhibiting or augmenting neutrophil function in an immunocompetent host during infection.

Animals↗
PubMed1995

Severity of beta-thalassemia due to genotypes involving the IVS-I-6 (T-->C) mutation.

Among individuals of Mediterranean or Middle Eastern descent, the IVS-I-6 (T-->C) mutation is one of the most common causes of beta-thalassemia. In this report, we describe the clinical phenotypes of a group of beta-thalassemia patients who are compound heterozygotes for the relatively mild IVS-I-6 (T-->C) beta-thalassemia mutation and more severe beta(+)- or beta (0)-thalassemia mutations. Although most of these patients are transfusion-dependent, the requirement for regular transfusions generally occurred late in childhood. A correlation between concomitant alpha-thalassemia and a mild transfusion-independent phenotype is not apparent, indicating the involvement of other ameliorating determinants.

Adult↗
PubMed1995

Properties of calcium currents and contraction in cultured rat diaphragm muscle.

The characterization of calcium currents and contraction simultaneously measured in cultured rat diaphragm muscle cells was carried out in the present study. Whole-cell patch-clamp experiments were designed to further elucidate the mechanism of excitation-contraction (E-C) coupling in diaphragm which, though generally considered a skeletal-type muscle, has been reported to exhibit properties indicative of a cardiac-like E-C coupling mechanism. Normalized current/voltage (I/V) curves for two concentrations of external calcium (2.5 and 5 mM) were obtained from diaphragm myoballs. Both curves showed peaks corresponding to the activation of a T-type calcium current and a dihydropyridine-sensitive L-type calcium current. The normalized curve for the voltage dependence of the activation of contraction in diaphragm myoballs followed a typical Boltzmann-type relationship to the peak of contraction. Thereafter, the curve declined in a manner that was more pronounced in diaphragm compared to that measured in additional experiments using cultured rat limb muscle myoballs. This effect could be interpreted in terms of a more pronounced participation of the L-type current in E-C coupling in cultured diaphragm muscle. An increased likelihood of cultured diaphragm muscle to undergo depletion of sarcoplasmic reticular calcium stores during repetitive stimulation, or a heightened propensity for the voltage sensor for E-C coupling in diaphragm to enter the inactive state could also explain this effect. Maximal contractile activity was only slightly affected when the L-type current was blocked by externally applied cadmium (2 mM) or cobalt (3 mM), suggesting that a pronounced calcium-current-dependent component of contraction is unlikely in cultured diaphragm muscle. These results show that T- and L-type calcium channels are expressed in cultured rat diaphragm muscle cells and that, in contrast to cardiac muscle, the entry of calcium ions via L-type voltage-dependent calcium channels is not a prerequisite for contraction. Differences in the voltage sensitivity of contraction, observed at depolarized membrane potentials in cultured rat diaphragm and limb muscle cells, suggest that the voltage sensor for E-C coupling in diaphragm might more readily enter an inactivated configuration - possibly by a mechanism which is dependent on the concentration of external calcium.

Animals↗
PubMed1995

A comparison of the mast cell and eosinophil responses of sheep and goats to gastrointestinal nematode infections.

The mucosal mast cell and eosinophil responses of goats and sheep to a mixed gastrointestinal nematode infection were compared. Groups of eight does and nine ewes, previously maintained on pasture and treated with anthelmintic when they were housed and five worm-free lambs were challenged with 10,000 Trichostrongylus vitrinus third stage larvae (L3) and 10,000 Teladorsagia circumcincta L3. Eleven days after challenge, the ewes had significantly (P < 0.001) lower burdens of abomasal and intestinal worms than the does or naive lambs, but significantly higher (P < 0.001) tissue concentrations of mast cell proteinase. Toluidine blue-stained sections indicated a paucity of mast cells in the does compared with the ewes, whereas the immunolocalisation of sheep mast cell proteinase revealed similar numbers of stained cells in the two species. This discrepancy was due to the relatively high proportion of globule leucocytes (77 and 91 per cent in the jejunum and abomasum, respectively) in the does compared with the ewes (7 and 24 per cent in the jejunum and abomasum, respectively). No differences were detected between the numbers of circulating or tissue eosinophils in the ewes and does.

Animals↗
PubMed1995

A complex issue.

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Animals↗
PubMed1995

Identification of a new high oxygen affinity hemoglobin variant: Hb Aurora [beta 139(H17) Asn-->Tyr].

A 73-year-old female of Dutch descent was referred for investigation of a high oxygen affinity hemoglobin variant. The beta-globin gene was amplified using the polymerase chain reaction. Direct nucleotide sequencing of the polymerase chain reaction amplified DNA revealed that she is heterozygous for a novel beta-globin gene mutation at codon 139, AAT-->TAT. The resulting hemoglobin variant has been designated Hb Aurora [beta 139 (H17) Asn-->Tyr].

Aged↗
PubMed1994

DNA diagnosis of Hb S and Hb Caribbean (alpha 2 beta 2 91 Leu-->Arg) in a Jamaican family.

We describe a Canadian infant of Jamaican descent who presented with mild anemia. Hb electrophoresis revealed Hb S and an unknown Hb variant that migrated slightly faster than Hb S on cellulose acetate. Molecular studies of the family indicated that the proband is a compound heterozygote for Hb S and Hb Caribbean. Hb Caribbean has previously been characterized as a mildly unstable hemoglobin with low oxygen affinity, due to a Leu-->Arg substitution at amino acid residue 91. The present study establishes the molecular basis for Hb Caribbean (beta 91, CTG-->CGG) and confirms that Hb S/Hb Caribbean syndrome is not associated with serious clinical manifestations.

Adult↗