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Biomedical subjects

M Carney

Publications and source records attributed to M Carney.

At least 19 recordsLinked to original sources

Three-dimensional graphic reconstruction of the insect exoskeleton through confocal imaging of endogenous fluorescence.

The exoskeleton of the cockroach leg was imaged via confocal microscopy to generate digital graphic reconstructions of its three-dimensional structure. The cuticle is autofluorescent and can be visualized without staining, but is maximally imaged in aldehyde-fixed preparations viewed under krypton-argon laser illumination (yellow green (568 nm) excitation, commonly used in confocal microscopes). Images of the entire trochanteral segment of the leg were constructed as montages from optical sections taken as overlapping series that were coincident in the z-axis. Reconstructions of the exoskeleton from these images showed that strain sensing mechanoreceptors are located in association with buttresses and thickenings that form a consistent internal architecture in both juvenile and adult animals. Accuracy of reconstructions was gauged by embedding specimens in Spurr's resin and histologically sectioning them perpendicular to the optical plane of section (z-axis). Comparison of plastic sections with two-dimensional images generated by "resectioning" the software model showed that reconstructed exoskeleton had a high level of accuracy. Imaging of older and larger animals was limited by the sclerotization and increased thickness of the cuticle. Surface extraction algorithms were used to generate vector graphic files in CAD format for export to software used in engineering and design. Among other potential uses, these models have been studied by Finite Element Analysis to examine the distribution of mechanical strains in the exoskeleton that occur during posture and locomotion. The advantages and limitations of the techniques are discussed. These methods may be used in studying the exoskeleton and the anatomy of cuticular mechanoreceptors of other arthropods to similar advantage.

Animals↗

Catecholamines in urine after death.

Noradrenaline, adrenaline and dopamine levels were measured using high-performance liquid chromatography (HPLC) and electrochemical detection and related to urine creatinine in 30 specimens from unselected autopsies. Values calculated from patients with essential hypertension were used as a reference and raised values of noradrenaline, adrenaline and dopamine were found in 76.6, 80 and 23.3%, respectively. Using the Mann-Whitney U test, there was no difference between the 11 patients with myocardial infarction and the seven who died from severe head injury or multiple trauma. The median values in mmol/mol creatinine for patients with myocardial infarction and trauma were 0.07 and 0.12 for noradrenaline and 0.012 and 0.024 for adrenaline, respectively. Physiological stress is common before death and urine noradrenaline values at autopsy overlap those found in some normal subjects and at autopsy in patients with phaeochromocytoma.

Adolescent↗

Microcystic adnexal carcinoma arising in the setting of previous radiation therapy.

While there are several reports of microcystic adnexal carcinoma developing in patients within sites of previous therapeutic irradiation, this relationship is not well described in the dermatologic literature. We report a case of a 42-year-old man with a remote history of therapeutic irradiation following surgical resection of periorbital rhabdomyosarcoma. Subsequently, he developed multiple basal cell carcinomas and a microcystic adnexal carcinoma within the field of irradiation. The histologic features were those of a classic microcystic adnexal carcinoma, with well differentiated nests and cords of keratinocytes displaying follicular and ductular differentiation infiltrating diffusely into the reticular dermis. Dense fibrosis was present surrounding the neoplastic keratinocytes. Nuclear atypia and mitotic figures were not identified. A carcinoembryonic antigen (CEA) stain demonstrated glandular differentiation. It is important for dermatologists to be aware of the apparent relationship between the rare microcystic adnexal carcinoma with its innocuous scar-like clinical appearance and prior local radiation therapy.

Adult↗

Human ovarian cancer of the surface epithelium.

Epidemiologic studies have shown that the risk of cancer in the ovarian surface epithelium is decreased by factors that suppress ovulation, whereas uninterrupted ovulation has been associated with increased risk. This suggests that ovulation may play a critical role in ovarian carcinogenesis. More recently, molecular studies have demonstrated alterations in specific oncogenes and tumor suppressor genes in ovarian cancers. Overexpression of the HER-2/neu oncogene occurs in approximately 30% of ovarian cancers and correlates with poor survival. Although mutation of the K-ras oncogene has been found in some mucinous ovarian cancers, mutations in this gene appear to be more common in borderline ovarian tumors. Amplification of c-myc occurs in approximately 30% of ovarian cancers and is more frequently seen in serous cancers. Mutation of the p53 tumor suppressor gene, with resultant overexpression of mutant p53 protein, occurs in 50% of stage III/IV and 15% of stage I/II ovarian cancers. Most p53 mutations in ovarian cancers are transitions, which suggests that they arise spontaneously rather than due to exogenous carcinogens. In contrast to the acquired genetic alterations described above that are a feature of sporadic ovarian cancers, 5-10% of ovarian cancers probably arise due to inherited genetic defects. Recently, the BRCA1 tumor suppressor gene has heen identified and shown to be responsible for most cases of hereditary ovarian cancer. Further studies are needed to augment our understanding of the molecular pathogenesis of ovarian cancer.

BRCA1 Protein↗

Does aggressive therapy improve survival in suboptimal stage IIIc/IV ovarian cancer? A Canadian-American comparative study.

In an effort to determine if differences exist in the treatment and outcome of patients with suboptimally debulked stage IIIc and IV epithelial ovarian cancer between two tertiary-care cancer centers in Canada and the United States, we conducted a comparative study. The records of all patients who underwent treatment for epithelial ovarian cancer at two tertiary-care cancer centers in Canada and the United States between 1987 and 1989 were abstracted onto a common datasheet which was then entered into a computerized database for analysis. Only patients with suboptimally debulked stage IIIc disease (residual tumor diameter > 1 cm) or stage IV were included in the comparative study. There was a total of 129 evaluable patients (61 Canadian, 68 American). There were no statistically significant differences between the centers in mean age, performance status, histology, grade, or stage distribution. During the period of this study there was no statistically significant difference between the two institutions in the proportion of patients in whom optimal debulking was achieved (Canadian 19%, American 26%). The American patients were heavier than the Canadian patients (Quetelet index 27.3 vs 23.8, P < 0.006). Primary chemotherapy included a platin-containing regimen in 98 and 93% of Canadian and American patients, respectively. The average number of laparotomies each patient received during her course of illness was 1.7 and 2.5 at the Canadian and the American centers, respectively (P < 0.0001). Similarly, the American patients received a higher mean number of different chemotherapy regimens and total number of courses of chemotherapy during the course of their disease (3.0 and 12.6) than did the Canadian patients (2.4 and 8.8) (P < 0.01 and P < 0.001, respectively). The median survival was 21 months and 20 months in the Canadian and the American patients, respectively (no significant difference), and the 5-year survival was 10% for the Canadian and 11% for the American patients. Despite significant differences in the overall aggressiveness of treatment between the two centers, there was no difference in the survival of these patients. Until effective salvage agents or treatment strategies are realized, "more is not necessarily better."

Actuarial Analysis↗

Efficacy of nurses suturing pediatric dermal lacerations in an emergency department.

STUDY OBJECTIVE: To assess the efficacy of nurses suturing pediatric dermal lacerations in an emergency department. DESIGN: Prospective study. SETTING: Pediatric ED. PARTICIPANTS: Suturing nurses completed a comprehensive training program provided by physicians at our institution and at a national wound management workshop; both included instruction in wound assessment, preparation, anesthesia, repair, and care after repair. A survey of physician and parent satisfaction with wound repair and for wound healing complications was performed at the time of suture removal in 61 children whose dermal laceration was repaired by suturing nurses. RESULTS: The laceration was located on the face in 40 patients, the scalp in 14, and an extremity in 7. A total of 343 sutures was required (18 lacerations required a layered closure). Pediatricians graded wound repair as "very good" in 32 cases (53%) and "excellent" in 29 cases (47%). Parents rated themselves as "very satisfied" with the wound repair procedure in 60 cases (98%) and with the wound repair outcome in 59 cases (97%). There were no wound-healing complications. Suturing nurses took a total of 72 hours to repair lacerations. In comparison, of 20 lacerations repaired by an ED attending physician, 11 (55%) were graded as "excellent" and 9 (45%) as "very good," with no wound-healing complications (P = NS). CONCLUSION: Nurses who complete a standardized training program in wound management and repair are capable of providing high-quality, definitive care for children with dermal lacerations, thus allowing physicians to use their time more effectively in managing general patient care in the ED.

Anesthesia↗

Clinical signs of pneumonia in children.

Clinical and chest radiographic findings were recorded prospectively in 185 children with cough who attended an outpatient clinic in Papua New Guinea. Children were studied if they were between 8 weeks and 6 years of age; patients with wheeze, stridor, measles, or pertussis were excluded. 56 children (30%) had radiological evidence of pneumonia. The presence of either a respiratory rate greater than or equal to 50/min or chest indrawing, or of both signs, was a good indication of pneumonia, with a predictive power of 46% for a positive test and 83% for a negative test. A more complex definition of tachypnoea, as a respiratory rate greater than or equal to 40/min in children over 12 months old and greater than or equal to 50/min in infants, showed little additional diagnostic benefit.

Child, Preschool↗

Isolation and sequencing of cDNA clones encoding the Dictyostelium discoideum 30,000-dalton actin-bundling protein.

The Dictyostelium 30,000-dalton protein is a calcium-regulated actin filament-bundling protein which has been suggested to contribute to the structure and reorganization of filopodia and pseudopodia accompanying cell movements. cDNAs encoding this protein were isolated using antibody and oligonucleotide probes to screen cDNA libraries in phage lambda. The sequence of the cDNA predicts a protein of 295 amino acids with a molecular weight of 33,355. The sequence reveals two EF-hand calcium-binding regions that provide a structural explanation for calcium regulation of the activity of this protein. The putative calcium-binding region of the 30,000-dalton protein has similarity to sequences of other calcium-regulated actin-binding proteins such as alpha-actin and fimbrin. One region of the sequence with similarity to both Dictyostelium gelation factor (ABP 120) and fructose bisphosphate aldolase is a potential actin-binding sequence. A highly charged region of the protein is similar to a sequence in human cytovillin that is repeated eight times in chicken gizzard caldesmon. No strong homology to previously identified actin-binding sequences of other actin-binding proteins is apparent. Results from Southern blot experiments indicate that the 30,000-dalton protein is encoded by a single gene in the Dictyostelium genome.

Amino Acid Sequence↗

Expression of C5a anaphylatoxin receptor in monoblastic cells involves facilitation of an adenosine 3',5'-monophosphate-dependent process.

We have previously reported a synergistic effect of 1,25-dihydroxyvitamin D [1,25-(OH)2D] and agents that elevate intracellular cAMP to induce the expression of the C5a complement receptor in U937 cells. In this report we examine the mechanism of this synergy, considering the hypothesis that the steroid hormone works by facilitating what is ultimately a cAMP-dependent process. We show that U937 cells cultured with 1,25-(OH)2D alone before culture with prostaglandin (PGE2) alone will express C5a receptor (an average of 55 +/- 4% of the receptors expressed with continuous exposure of cells to both agents; P less than 0.05). The reverse, PGE2 followed by 1,25-(OH)2D, causes very little receptor induction. This demonstrates the ability of 1,25-(OH)2D to induce changes in the state of the cell, such that activation of cAMP-dependent protein kinase has effects that are otherwise not seen, in other words 1,25-(OH)2D can prime the cell for the subsequent action of the cAMP messenger system. Furthermore, we are able to substitute, during the priming period, the protein synthesis inhibitor cycloheximide (CHX) for 1,25-(OH)2D. Cells cultured for 24 h with CHX will express C5a receptor when cultured for a second 2-day period with PGE2 at about 77 +/- 7% of the amount obtained with simultaneous exposure to 1,25-(OH)2D and PGE2. The CHX effect is time dependent and visible after 2 h. CHX is not synergistic with 1,25-(OH)2D. Other agents that can also substitute for 1,25-(OH)2D, but not for cAMP, in facilitating C5a receptor expression include retinoic acid and ionomycin, but with less potency. The 1,25-(OH)2D and PGE2 synergy is sensitive to the presence of isobutylmethylxanthine, implicating its dependence on the maintained elevation of intracellular cAMP levels. The synergy does not appear to be sensitive to changes in extracellular or intracellular calcium. We conclude from these results that 1,25-(OH)2D may promote the expression of C5a receptor in these cells in a fashion similar to that by which CHX potentiates other genes, i.e. that 1,25-(OH)2D increases levels of the mRNA encoding the C5a receptor. The mechanism of cAMP's subsequent and necessary action in the induction of C5a receptor expression is not yet clear.

1-Methyl-3-isobutylxanthine↗

The intraocular penetration and retinal toxicity of teicoplanin.

We investigated the intraocular penetration and retinal toxicity of teicoplanin, a relatively new glycopeptide antibiotic with activity similar to vancomycin when used to inhibit staphylococci and other gram positive organisms, particularly Streptococcus faecalia. Topically administered teicoplanin penetrated poorly into the aqueous and vitreous in rabbit eyes. Subconjunctival injection of the drug yielded aqueous levels above the minimum inhibiting concentration (3.1 micrograms/ml) only at one hour after injection. In the vitreous, drug levels were above the mean inhibitory concentration at 30 minutes after the subconjunctival injection, but rapidly declined thereafter. The maximum nontoxic, single-dose, intravitreal injection was 750 micrograms/0.1 ml. Rabbits received 8 micrograms/ml of teicoplanin in an intravitreal infusion solution without demonstrable retinal toxicity.

Animals↗

Intercostal artery laceration during thoracocentesis: increased risk in elderly patients.

Two cases of intercostal artery laceration following thoracocentesis are reported. Subsequent analysis of 29 thoracic aortograms demonstrated a definite trend toward increasing tortuosity of intercostal arteries with advancing age. Consequently, the amount of space available for safe insertion of the thoracocentesis needle tends to decrease with advancing age. As a result, elderly patients are more prone to intercostal artery laceration during thoracocentesis, and careful attention must be paid to the proper technique for performing this examination in such patients.

Age Factors↗

Sulfite oxidase deficiency. Biochemical and clinical investigations of a hereditary metabolic disorder in sulfur metabolism.

Study of a 4 1/2-year-old boy with the unusual combination of acute infantile hemiplegia, ectopia lentis and the absence of homocystinuria showed large amounts of abnormal sulfur-containing metabolites (sulfite, thiosulfate and S-sulfocysteine) in the urine. Sulfite and S-sulfocysteine were also present in the plasma. His inorganic sulfate excretion was only 50 per cent of total sulfur, as compared with 75 to 95 per cent by controls. Loading with L-cysteine hydrochloride and L-methionine further increased the excretion of sulfite and thiosulfate, but not inorganic sulfate excretion. Sulfite oxidase activity in skin fibroblasts average 1.07 nmol of cytochrome d reduced per milligram of protein per minute in control lines; it was not detectable (less than 5 per cent) in the patient. Activity was reduced in both parents (0.50 in the father and 0.32 in the mother)--compatible with autosomal recessive inheritance. Good biochemical responses to a low sulfur amino acid diet suggest that early treatment may benefit the patient.

Amino Acids, Sulfur↗