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Biomedical subjects

D Richardson

Publications and source records attributed to D Richardson.

At least 19 recordsLinked to original sources

Microsatellite instability in colorectal adenocarcinoma cell lines that have full-length adenomatous polyposis coli protein.

Almost 20% of colon cancers are characterized by genomic instability at simple repeated sequences. This instability is the result of a deficient DNA mismatch repair system. Sporadic, as well as hereditary carcinomas of the proximal colon display this effect. In this study, we examined colorectal adenocarcinoma cell lines, with or without wild-type adenomatous polyposis coli (APC) protein, for the presence of microsatellite instability. The three cell lines that maintained full-length APC protein also displayed the highest level of instability, suggesting a negative correlation between APC mutations and microsatellite instability. This data, in addition to other studies that show a negative correlation between microsatellite instability and mutations in p53 and K-ras, support the idea of a second pathway for colorectal cancer development.

Adenocarcinoma

Mandibular reconstruction and rehabilitation in childhood.

The management of a case of osteosarcoma of the mandible in an 7-year-old girl is presented. A variety of reconstructive techniques were used following surgical ablation of the tumour, including the use of a revascularised free bone flap and osseointegrated endosseous implants.

Child

Postoperative symptomatic internal thoracic artery stenosis and successful treatment with PTCA.

From 1988 to 1992, 4,182 coronary bypass grafting procedures were performed at the University of Ottawa Heart Institute. The left internal thoracic artery (ITA) was used in 2,913 patients, the right ITA in 79, and bilateral ITAs in 61 for a total of 3,053 patients with ITAs. This study assessed patients requiring angioplasty for symptomatic ITA stenosis after operation. A total of 29 patients (0.95%) with a mean age of 55.3 +/- 1.9 years underwent angioplasty for ITA stenosis from 4 days to 34 months after operation (mean, 6.5 +/- 1.6 months). Internal thoracic artery stenosis was identified in 18 patients (62.1%) within 3 months after operation. Angina was present in 26 patients (89.7%), a positive stress test in 8 (27.6%), and myocardial infarction in 1 (3.4%). At angiography, a total of 34 stenotic sites were identified in ITA grafts. Angioplasty was successful (< 50% residual stenosis) in 31 sites (91.2%). Follow-up was available for 28 of 29 patients (96.6%) at 24.6 +/- 2.3 months. Four patients (14.3%) returned with restenosis within 3 months, 2 of whom had successful repeat angioplasty, and 1 required reoperation. Canadian Cardiovascular Society anginal class after angioplasty was less than class II in 84.6% of patients. In conclusion, symptomatic postoperative ITA stenosis is uncommon, occurs most frequently at the site of distal anastomosis, and generally presents within 3 months of operation. It may be safely and effectively treated with angioplasty with a low recurrence rate.

Adult

Suspensory ligament desmitis.

The gross and functional anatomy of the suspensory ligament (SL) and its ultrasonographic variability are described. Injuries of the suspensory apparatus are divided into lesions confined to the proximal one third of the metacarpus or metatarsus (proximal suspensory desmitis and avulsion fractures), lesions of the body, and branch lesions. Complete breakdown injuries are also discussed. In view of the close association of the SL, the second, third, and fourth metacarpal or metatarsal bones, and the proximal sesamoid bones, associated bony lesions are also considered.

Animals

Percutaneous anterior discectomy under ultrasound guidance.

The object of this experiment was to demonstrate that, by using a peritoneal fluid infusion coupled with ultrasound guidance, a safe anterior entry into the L5-S1 disc of the pig could be made. The goal was to develop a procedure with the advantages of a laparoscopic approach to the disc which has been published to allow removal of extruded herniations, that a neurosurgeon could perform without a general surgeon in attendance. The procedure was carried out under general anesthesia and fluoroscopic control. One liter of normal saline was then infused into the abdomen of a pig. Under ultrasound guidance and laparoscopic confirmation, a Nucleotome was placed into the L5-S1 disc and the disc was aspirated. The results showed that the disc was safely entered in all 5 pigs. The disc was successfully removed in 4 of 5 pigs. In all animals the bowel floated out of the pelvis, obviating the need for bowel manipulation. Laparoscopic ultrasound was needed for visualization in 3 pigs, while external ultrasound was used in two. Our conclusion is that peritoneal fluid infusion and ultrasound guidance, when applied to laparoscopic anterior discectomy, eliminates the need for retroperitoneal dissection and bowel manipulation, significantly simplifying the laparoscopic discectomy procedure.

Animals

Posttraumatic stress disorder in peers of adolescent suicide victims: predisposing factors and phenomenology.

OBJECTIVE: To examine the factors predisposing to posttraumatic stress disorder (PTSD) in peers of adolescent suicide victims. METHOD: One hundred forty-six adolescents who were the friends of 26 suicide victims were studied. Five percent (n = 8) developed PTSD after exposure to suicide. These 8 subjects with PTSD were compared to the remainder of the exposed subjects (n = 138). RESULTS: Subjects with PTSD were more likely than those without PTSD to have had a history of substance abuse, agoraphobia, and suicide attempts. Subjects who developed PTSD were more likely to have developed a new-onset depression, to have more severe grief, and to have been closer to the suicide victim. Subjects with PTSD tended to have more severe exposure to suicide and came from discordant households with a history of disruptions in key relationships. The 8 subjects who developed PTSD were compared to 38 subjects who developed new-onset depression but not PTSD. Those with PTSD were more likely to have had past substance abuse, prior suicide attempts, family history of panic disorder, a history of parent-child disruption, and a history of loss. Symptoms of intrusive visual images, hypervigilance, and avoidance of reminders discriminated subjects who had PTSD from new-onset depressives without PTSD. CONCLUSIONS: PTSD is an expectable outcome in youth exposed to suicide. Further work is required to differentiate symptoms of depression from PTSD.

Adolescent

Teaching physiology by combined passive (pedagogical) and active (andragogical) methods.

Pedagogy and andragogy are models of education based, respectively, on passive and active learning. This project compared two balanced sections of an undergraduate course in physiology. Both sections used the pedagogical method of didactic lectures to present basic material. Students in section 01 were given multiple-choice examinations, a pedagogical procedure, over the lecture content for the purpose of performance evaluation. In section 02 the lectures were used as an information source, which students combined with other information researched in the library to draft essays on assigned topics, i.e., an andragogical approach. Grading of the essays constituted 75% of a student's performance evaluation, with participation in class discussions making up the remaining 25%. There was no significant difference in overall performance outcome between the two sections (P > 0.47). Students from both sections valued the lectures, even though they served a different purpose in each section. However, overall the student rating of section 02 was significantly higher than that of section 01 (P < or = 0.05). This reflected different teaching methods rather than different teachers, because the ratings of the two instructors were virtually identical (P > 0.98). These results suggest that a combined pedagogical and andragogical approach is an acceptable model for teaching introductory physiology.

Analysis of Variance

Psychiatric emergencies.

Psychiatric emergencies can arise during pregnancy and the puerperium. When faced with a gravida presenting with the symptoms of an acute psychiatric illness, the obstetrician must consider the possibilities of organic disorders and substance abuse before initiating psychotropic therapy with the consulting psychiatrist. Generally, patients with psychiatric illness have difficulty caring for themselves and hospitalization may be indicated at least initially. Emotional support, a quiet environment, and psychotherapy are often the most important aspects of treatment. Suicide gestures should always be taken seriously. Immediate psychiatric consultation is imperative. Finally, anyone caring for pregnant women should be aware of the possibility of domestic violence. Pregnant women are unlikely to volunteer information about an abusive situation. Detection hinges on willingness of the physician to ask probing questions.

Anxiety Disorders

Role of nitric oxide in the response of capillary blood flow in the rat tail to body heating.

This study tested whether or not nitric oxide (NO) is involved in mediating the response of cutaneous capillary blood flow to an indirect heat stress. Blood cell velocity (BCV) in capillaries within the subepidermal plexus of the tail of anesthetized Sprague-Dawley rats was measured by videomicroscopy while the animals' trunk was exposed to a 35 degrees environment. Vascular conductance, estimated as the ratio of BCV to mean arterial pressure (MAP), increased by 259% in saline (placebo)-treated rats. Intravenous administration of 32 mg/Kg of the NO synthesis inhibitor NG-nitro-L-arginine (NNA) attenuated the response of vascular conductance (BCV/MAP) to body heating regardless of whether NNA was given before or during the heat stress procedure. In a subset of NNA-treated animals, infusion of the NO substrate L-arginine restored the BCV/MAP response to heat stress. In summary, the results of this study support the hypothesis that NO is involved in the response of cutaneous capillary blood flow to heat stress. Possible mechanisms mediating the local release of NO are discussed.

Animals

Estrogen antibodies reduce vulnerability to stress-induced failure of intrauterine implantation in inseminated mice.

In Experiment 1, inseminated mice were randomly assigned to either an undisturbed control condition or four conditions involving exposure to restraint stress on days 1 through 5 of pregnancy. Restrained animals received one of three doses of estrogen antibodies or just vehicle injections on each day of restraint. Restrained animals receiving vehicle only showed significantly fewer uterine implantation sites than did unrestrained controls, while restrained animals given estrogen antibodies showed more implantation sites than did vehicle-treated restrained animals. In Experiment 2, varied dosages of refined estrogen antibodies were administered to inseminated females concurrent to restraint-stress on days 1 through 5 of pregnancy. More females receiving the higher dosages of antibodies produced litters than did restrained females with just vehicle injections, and at the highest dose the number of litters was similar to that produced by undisturbed control females. These results converge with other evidence to suggest that stress-induced pregnancy blocks are mediated by estrogens.

Animals

Auditory M100 component 1: relationship to Heschl's gyri.

This study was designed to localize the neuroanatomic generator of the 100 ms latency magnetic auditory evoked field (EF) component (M100) activated by an unattended tone pip. Magnetic EFs in response to 25 ms duration, 90 dB, 1 kHz tone pips were recorded from both hemispheres of nine normal adults, five males and four females, using a seven-channel second-order gradiometer. The source of the M100 was estimated, with confidence intervals, by a least squares based inverse solution algorithm. Magnetic resonance (MR) images of the brain were acquired with a 1.5 T system using a standard head coil. The superior temporal gyri (STG) were manually segmented from 1.7 mm thick coronal images, and the superior surfaces were then rendered from the 3-D volume data. Translation and rotation matrices were identified to locate the magnetoencephalography (MEG) determined sources within the reconstructed STGs. This population of 18 STGs in 9 individuals demonstrated two transverse gyri in 4 of 9 left hemispheres, and 5 of 9 right hemispheres. All 9 left hemisphere M100 sources were in or included Heschl's gyrus(i) in the confidence intervals. Seven of the 9 included Heschl's gyrus(i) on the right: the remaining two, both males, had sources slightly anterior to Heschl's gyrus(i). We conclude that all M100 source location estimates were compatible with an auditory koniocortex source in or adjacent to Heschl's gyri.

Adult

A predictive model for fetal lung maturity employing gestational age and test results.

Most laboratory tests for fetal lung maturity (FLM) are optimized to exclude false-negative predictions of absence of respiratory distress syndrome (RDS), with a reciprocal low predictive value for maturity. The authors employed FLM Surfactant/Albumin Ratio (FLM S/A) test results to construct a predictive model for FLM that included the obstetric estimates of gestational age. The charts of 388 newborns were abstracted and reviewed. The clinical outcome was the gold standard of the multivariate logistic analysis. Both the obstetric estimates of gestational age and the test result were significant predictors of the clinical outcome (P values of < .0002 and .001, respectively). The prediction rule for RDS as a function of both of these variables allows for adjustment of the test cutoffs, so that there is a consistent probability of RDS at the cutoff FLM S/A result for different gestational ages. Fetal lung maturity probability reporting may facilitate clinical decision-making.

Albumins

Prospective evaluation of extracranial carotid stenosis: MR angiography with maximum-intensity projections and multiplanar reformation compared with conventional angiography.

OBJECTIVE: The purpose of this prospective study was to compare MR angiography of the carotid artery from the aortic arch through the circle of Willis using maximum-intensity projection (MIP) and multiplanar reformation (MPR) images with intraarterial angiography in the depiction of extracranial carotid atherosclerosis. SUBJECTS AND METHODS: The carotid arteries in 20 patients were studied with MR and intraarterial angiography. MR angiography included two-dimensional (2D) time-of-flight (TOF) sequences from the aortic arch through the skull base and three-dimensional (3D) TOF sequences centered at the carotid bifurcation and multiple overlapping thin slab acquisition (MOTSA) from the skull base to above the circle of Willis. Targeted MIP images of the 2D and 3D TOF MR angiograms through each carotid bifurcation were obtained. Last, MPR images of the 3D TOF MR angiograms at the obliquity that showed the greatest stenosis were obtained. All studies were reviewed in a double-blinded fashion by two neuroradiologists. Caliper measurements of MR angiograms and intraarterial angiograms were made by using North American Symptomatic Carotid Endarterectomy Trial criteria. Global MIPs of the aortic arch and common carotid arteries from the 2D TOF MR angiograms and targeted MIPs of the intracranial carotid arteries from the MOTSA MR angiograms were compared with the intraarterial angiogram and graded as normal, mild, moderate, severely stenotic, or occluded. RESULTS: MPR of the 3D TOF MR angiograms was highly correlated with intraarterial angiograms for both observers 1 and 2 (0.94/p < .001, 0.96/p < .001 [Pearson correlation/p value]). No statistically significant difference between 3D TOF MPR and intraarterial angiography was seen with a paired t-test. With an alpha = 0.05 (5% probability of type 1 error), the power to detect a difference as small as +/- 5% stenosis between 3D TOF MPR and intraarterial angiogram was 80% for observer 1 and 90% for observer 2. Although both MIPs of the 2D and 3D TOF MR angiograms showed high Pearson correlation coefficients (0.83, 0.90) with intraarterial angiography, the paired t-test revealed a statistically significant difference in the estimation of carotid stenosis. Both observers thought the global MIPs of the 2D TOF MR angiogram allowed good to excellent visualization of the common carotid arteries. The aortic arch was seen in 70% of patients; most of the missed cases occurred early in our experience, when the 2D axial images were not placed sufficiently inferior to include the arch. No stenosis of the great vessel origins was seen in this study. All four stenoses of the intracranial internal carotid artery identified with intraarterial angiography were seen with the MOTSA MR angiogram but with a tendency to overestimate stenosis. Only one carotid siphon was thought to show severe stenosis on the MR angiogram. Intraarterial angiography showed a 50% stenosis. CONCLUSION: It is possible to image the entire carotid artery from the aortic arch through the circle of Willis with MR angiography in a clinically acceptable time. MPR of the 3D TOF MR angiogram reliably shows the percentage of carotid stenosis with no statistically significant difference compared with intraarterial angiography. The role of MR angiography in showing lesions in the circle of Willis or the aortic arch is promising, but the limited number of tandem lesions in this study makes it difficult to draw any conclusions.

Aged

A comparison of HIV risk between women and men who inject drugs.

Although there is growing evidence of differences between women and men who inject drugs (IDUs) in terms of level of risk for HIV infection, very little research has been conducted specifically addressing the risk practices of women IDUs. This study formed part of a national study of HIV infection risks in IDUs and the purpose of the present analysis was an exploration of gender differences in HIV risk practices, focusing on the HIV risk practices of IDU women. 1,245 IDUs from the inner city area of Sydney took part in this study. Of these, 908 were men and 331 were women. Notable results were that female respondents were more likely to report sharing needles, they injected heroin more times in a typical using month and were more likely to have shared with someone they later found out was HIV seropositive. Female respondents also reported more sexual partners than men, were more likely to engage in prostitution, and were more likely to have sexual partners who were themselves IDUs. The results provide support for the proposition that women who inject drugs may be at greater risk of HIV infection through both their drug taking and their sexual practices. Further research is needed to explore the reasons underlying the risk practices of women who inject drugs and an understanding of these factors needs to be incorporated into HIV risk-reduction and drug harm-reduction policies and programs.

Adolescent

Two mechanisms of iron uptake from transferrin by melanoma cells. The effect of desferrioxamine and ferric ammonium citrate.

The effects of ferric ammonium citrate (FAC) and desferrioxamine (DFO) on iron (Fe), and transferrin (Tf) uptake have been investigated using SK-MEL-28 human melanoma cells, which express the Tf homologue, melanotransferrin, in high concentrations. Previously we demonstrated two separate Fe uptake mechanisms from Tf, viz. a specific process mediated by the transferrin receptor (TfR) and a nonspecific process (Richardson, D. R., and Baker, E. (1990) Biochim. Biophys. Acta 1053, 1-12). Cells exposed to DFO demonstrated up-regulation of the TfR with a concurrent increase in the rate of Fe uptake. Desferrioxamine also stimulated the nonspecific process of Fe uptake, resulting in a further increase in accumulation of Fe over Tf after saturation of the specific TfR. Ferric ammonium citrate had two effects. First, it resulted in down-regulation of the TfR. Second, and paradoxically, it markedly stimulated the rate of Fe uptake from Tf by the nonspecific process without increasing the rate of nonspecific Tf uptake. These data conclusively demonstrate that two entirely different mechanisms of iron uptake from Tf exist in melanoma cells and that ferric ammonium citrate may be a useful experimental tool to further characterize the specific and nonspecific mechanisms of Fe uptake from Tf.

Biological Transport

Evaluation of the iron chelation potential of hydrazones of pyridoxal, salicylaldehyde and 2-hydroxy-1-naphthylaldehyde using the hepatocyte in culture.

A range of new analogues of the promising iron chelator pyridoxal isonicotinoyl hydrazone was prepared and assessed for activity in reducing hepatocyte iron, mechanism of action and potential in iron-chelation therapy. A total of 45 compounds were synthesized by condensation of aromatic aldehydes (pyridoxal, salicylaldehyde and 2-hydroxy-1-naphthylaldehyde) with various acid hydrazides prepared by systematic substitutions on the benzene ring or by the replacement of the ring with an acetyl, pyridyl, furoyl or thiophene moiety. The effects of these compounds on 59Fe uptake and intracellular distribution in hepatocytes in culture and on 59Fe mobilization from prelabeled hepatocytes were assessed. Toxicity, lipophilicity and the ability to chelate plasma transferrin-bound 59Fe were also evaluated. Several compounds were much more active than pyridoxal isonicotinoyl hydrazone and may have clinical potential. These included pyridoxal benzoyl hydrazone, pyridoxal p-methoxybenzoyl hydrazone, pyridoxal m-fluorobenzoyl hydrazone and pyridoxal 2-pyridyl hydrazone. All were more effective at reducing iron uptake than mobilizing hepatocyte iron; they also may act primarily on the transit iron pool rather than on storage iron. Other compounds (e.g., salicylaldehyde p-t-butyl-benzoyl hydrazone) redistributed ferritin-59Fe to different intracellular sites but had little net effect on hepatocyte iron levels.

Animals