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Biomedical subjects

M O'Neill

Publications and source records attributed to M O'Neill.

At least 19 recordsLinked to original sources

Diagnosis of vertical human immunodeficiency virus type 1 infection by whole blood culture.

The qualitative and quantitative performance of a human immunodeficiency virus type 1 (HIV-1) whole blood culture method was assessed for use in the diagnosis of vertical HIV-1 infection. This method requires < 1 mL of whole blood and allows for the quantification of blood virus load. HIV-1 was isolated from 36 (95%) of 38 whole blood specimens from 27 HIV-1-infected children compared with 0 of 16 whole blood specimens from 16 uninfected children. HIV-1 titers were significantly higher in severely symptomatic children (2450 TCID/mL) than in less symptomatic children (179 TCID/mL). This simple quantitative culture assay may be useful for the early diagnosis of vertical HIV-1 infection, the assessment of blood virus load, and the evaluation of antiretroviral therapies.

Acquired Immunodeficiency Syndrome

Schizophrenics and social judgement. Why do schizophrenics get it wrong?

Videotaped social interactions were shown to a population of schizophrenics and controls who were asked to comment on the emotional state of the principal protagonist. Their free responses were subjected to a content analysis to examine which of three possible explanations of known schizophrenic inaccuracies on this task were responsible: formal thought disorder, selective avoidance of psychological factors, or perceptual/attentional deficits. Neither selective avoidance nor marked thought disorder were found to explain these errors. The schizophrenics as a group rated much the same, irrespective of clinical profile. Their judgements of personality were less clear-cut than the controls.

Adult

Community participation in Quebec's health system: a strategy to curtail community empowerment?

Since the beginning of the 1970s, the province of Quebec has undergone a major reform of its health and social services system. Following this reform, the state has become a major protagonist, and the participation of the population is a built-in element in the system, guaranteed by law. Now, about 20 years later, there is a major effort to reorganize health services, in the wake of a "dewelfarization" mood that has reached Canada and Quebec. This article reviews the successes and pitfalls of public participation in Quebec's health system, presents the way in which participation is dealt with in current reform proposals, and draws lessons for people in many countries who have recently been encouraged to jump onto the bandwagon of participation as a strategy to promote the health of populations.

Community Health Centers

Enamel microabrasion: a microscopic evaluation of the "abrosion effect".

Enamel surfaces have been found to acquire a glasslike luster and an exceptionally smooth texture following enamel microabrasion procedures. A commercially available enamel microabrasion compound containing abrasive particles and a mild concentration of hydrochloric acid, when applied by rotary compression, simultaneously abrades and erodes (abrosion) the enamel surface. Human enamel surfaces were evaluated microscopically after routine enamel microabrasion procedures. The results show distinct evidence of enamel surface changes that have been described as the abrosion effect.

Complex Mixtures

Structural analysis of the glycoprotein allergen Art v II from the pollen of mugwort (Artemisia vulgaris L.).

The glycoprotein allergen Art v II, from the pollen of mugwort (Artemisia vulgaris L.) was treated with peptide:N-glycosidase F (PNGase F) to release asparagine-linked oligosaccharides. The oligosaccharides were isolated by gel permeation chromatography and their structures determined by 500-MHz 1H NMR spectroscopy, fast atom bombardment-mass spectrometry, and high-pH anion-exchange chromatography. The high-mannose oligosaccharides Man5GlcNAc2, Man6GlcNAc2, Man7GlcNAc2, Man8GlcNAc2, and Man9GlcNAc2 were present in the ratios 2:49:19:24:6 and accounted for all the asparagine-linked oligosaccharides released from Art v II by PNGase F. The NH2-terminal amino acid sequences of Art v II and of four peptides generated by cyanogen bromide (CNBr) cleavage of deglycosylated Art v II were determined. The first 30 amino acid residues of Art v II did not contain any potential N-glycosylation sites. One potential N-glycosylation site was identified in one of the CNBr fragments. The native protein conformation was shown by enzyme-linked immunosorbent assay inhibition assays to be essential for the binding of rabbit IgG to Art v II and for the binding of human IgE to the major IgE-binding epitope(s) in this allergen. At least one minor IgE-binding epitope still bound IgE after denaturation of the allergen. Removal of the high-mannose chains from denatured Art v II had no significant effect on the binding of human IgE to the minor IgE-binding epitope(s).

Allergens

Pulmonary hemorrhage and necrotizing glomerulonephritis without glomerular immune deposits: report of two cases.

Two children with a syndrome of pulmonary hemorrhage and necrotizing, nonimmune glomerulonephritis are reported. A boy and girl, both of East Indian descent, developed recurrent lung infiltrates from the age of 3 months and 2 years, respectively. Both subsequently presented with pulmonary hemorrhage, fever, arthritis, hematuria, and nephrotic range proteinuria at 1.5 and 6 years of age, respectively. Renal biopsy in each case showed acute, severe, focal and segmental, necrotizing and crescentic glomerulonephritis without immune deposits. Subsequent renal biopsies revealed severe glomerular and tubulointerstitial scarring. No vasculitis or granulomas were seen on renal, skin, or lung biopsies. Antineutrophil cytoplasmic antibodies (ANCA) were not detected in sera taken 1.5 years in the boy and 3.5 years in the girl after the onset of renal disease. The boy was treated with prednisone, azathioprine, and plasmapheresis, but developed progressive renal impairment and commenced dialysis within 4 years. Subsequent to renal transplantation, he developed an immunoblastic lymphoma and died. The girl was treated initially with prednisone and later with cyclophosphamide. After 4 years, she had a normal glomerular filtration rate (GFR). While necrotizing nonimmune glomerulonephritis associated with pulmonary hemorrhage is rare, and cases are characteristically difficult to classify because of many overlapping features, it is possible that these children had a unique illness.

Child

Hurler's disease with diastematomyelia.

A case of Hurler's disease is reported in a child with a gibbous deformity of the lumbar vertebrae L1/L2 and a localized diastematomyelia of the spinal cord at L1/L3. The association of an enzyme disorder affecting connective tissue with spinal cord dysraphism has not been reported before, and may be fortuitous. However, as each condition is rare, the occurrence of both gibbous deformity due to Hurler's and diastematomyelia in the same child, makes it unlikely to be a chance association. We suggest that defective neurulation in this case may be related to mesodermal damage associated with mucopolysaccharidosis.

Brain

Familial infantile oesophageal achalasia.

Oesophageal achalasia is uncommon in children and in its familial form it is a rarity. The presentation and management of two male siblings who presented with oesophageal achalasia as infants are reported. A high degree of consanguinity in the parents of the children existed, suggesting autosomal recessive transmission.

Esophageal Achalasia

Effects of experimental context, demand characteristics, and situational cues: new data.

When in 1964 stress induced by Restricted Environmental Stimulation (REST) was publicized, Orne and Scheibe showed "sensory deprivation" effects could be produced merely by manipulating contextual cues. Since REST is now widely regarded as beneficial, it seemed appropriate to reexamine these early findings. Stringently replicating Orne and Scheibe's procedures, 10 subjects were exposed to conditions designed to generate expected REST effects. Conditions for 10 controls suggested that nothing was expected to happen. Analyses did not confirm earlier findings as no significant difference was found between experimental and control groups on any measure. A postexperimental inquiry identified positive attitudes toward REST. The specific experimental context, demand characteristics, and situational cues did not elicit responses inconsistent with the general sociopsychological context. Researchers are cautioned about attributing causality to contextual cues because context exists merely at a correlative level with data collection.

Adaptation, Psychological

Prevention of hypothyroidism related to mantle irradiation for Hodgkin's disease: preparative phantom study.

To decrease the incidence of hypothyroidism related to mantle irradiation for Hodgkin's disease, we initiated a study designed to protect the thyroid gland using a phantom. A thyroid phantom was filled with technetium-99m. The thyroid phantom was placed inside of its corresponding anterior neck position in a whole body phantom. An anterior scintiscan of the head and neck region demonstrated the radioactivity in the simulated thyroid. A mantle port included a focused block that would shield the thyroid from the anterior port. The phantom was exposed (4 MeV) to 180 cGy (AP-PA) at midplane with lithium fluoride dosimeters in the position of the thyroid. The thyroid received an average of 12 cGy from the anterior field and 48 cGy from the posterior field for a total of 60 cGy per treatment or 30% of the prescribed dose. A complete mantle field course of radiation of 4000 cGy would lead to a thyroid dose of 1200 cGy at a daily fractional dose of 60 cGy. We elected not to block the thyroid from the posterior field to prevent shielding and potential underdosage of involved nodal sites. The present study suggests a method of safe and effective thyroid shielding which needs to be tested clinically to determine whether it would reduce the incidence of chemical and clinical hypothyroidism or simply extend the period until occurrence.

Hodgkin Disease

A century of home parenteral nutrition for Crohn's disease.

During an 11-year period, 41 patients with Crohn's disease were placed on home parenteral nutrition (HPN) for a mean of 1,083 days (range: 33 to 3,258 days). Data were retrospectively analyzed to determine whether HPN had an effect on the course of their disease, i.e., on the number of operative procedures performed and the intensity of required medical therapy. Data represented information obtained during a total of 121 patient-years of HPN for Crohn's disease. The main indications for HPN were short bowel syndrome (66%) and high stoma output. Twenty-four of 41 patients (59%) underwent surgery for Crohn's disease during the course of HPN. There was no significant difference between the number of procedures performed per patient per year of Crohn's disease during pre-HPN and HPN periods (p greater than 0.25). Although there was no significant change in body weight, both serum albumin and transferrin levels increased during HPN (p less than 0.01 and p less than 0.01, respectively). Twenty-nine percent of patients were taking prednisone while on HPN, compared with 54% of patients during the pre-HPN period (p less than 0.01). HPN appeared to result in a significant improvement in the numerically assessed quality of life. During the HPN period, 24 patients had 1 or more HPN-related complications that required 1 to 13 hospital admissions (mean: 1.8). These complications included catheter sepsis in 19 patients, blocked or damaged catheters in 15 patients, and dehydration and/or electrolyte imbalance in 5 patients. Eight patients died, with 7% of deaths secondary to catheter-related sepsis. Although permanent HPN is associated with an identifiable morbidity and mortality and is not associated with a reduction in the frequency of surgery for Crohn's disease, benefits include a decrease in the intensity of medical therapy, an improvement in patients' nutritional state, and a significant perceived improvement in patients' quality of life. Without HPN, we believe all patients would have died secondary to malnutrition and/or dehydration.

Adult

The value of CT scans for children with headaches.

We studied the value of CT scans for all children referred because of headache to one secondary and one tertiary pediatric centre during a 1 year period. Of 117 children who were seen by the Pediatric Neurology Service, at the I.W.K. Children's Hospital, 4 had CT scans and only 1 of these was abnormal. The consultant Pediatrician saw 40 children because of headache. CT scans were done on 3 of these patients and all were normal. None of the children who had a clinical assessment alone had unrecognized neurological disease during 20 months of follow-up. Therefore only 1 of 157 children had significant intracranial pathology. We conclude that CT scans have a limited role in the management of children with headache.

Adolescent

Myocyte structure, function, and calcium kinetics in the cardiomyopathic hamster heart.

The hereditary cardiomyopathic strain of the Syrian hamster has been studied extensively as a model of cardiomyopathy and heart failure. However, the primary defect underlying the cascade of events leading to heart failure has not been identified. In the present study, isolated cardiac cells were obtained for study from 8-mo-old cardiomyopathic (Bio 14.6) and age-matched normal hamsters (F1B). We examined the relationships among structure, contractile function, and calcium kinetics in these isolated cardiomyocytes. The cardiomyopathic myocytes were wider and longer than controls, and myopathic cells were less calcium tolerant. The sarcoplasmic reticulum and T-tubule systems from myopathic hearts were more abundant as determined by electron microscopy. The amplitude and velocity of contraction was decreased in cardiomyopathic cells, whereas diastolic relaxation velocity was not different between the two groups. The size of the rapidly exchangeable calcium pool determined by 45Ca2+ uptake was significantly increased in cardiomyopathic myocytes. Time-averaged cytosolic Ca2+ in these cells (472 +/- 60 nM) was significantly higher than control (260 +/- 15 nM) as measured by the fura-2 fluorescence ratio. When extracellular Ca2+ ([Ca2+]o) was increased to greater than 1.2 mM, the resulting increase in intracellular calcium concentration was less than that in normal control cells. The corresponding [Ca2+]o-induced increase in amplitude of cell motion was significantly attenuated in the cardiomyopathic cells compared with normal control myocytes. We conclude that distinct abnormalities of contractile function and calcium homeostasis can be identified in single cells isolated from cardiomyopathic hamster hearts.

Animals

Inotropic and calcium kinetic effects of calcium channel agonist and antagonist in isolated cardiac myocytes from cardiomyopathic hamsters.

The mechanism by which heart cells of cardiomyopathic (CM) hamsters become calcium overloaded is not known. We examined the number of slow calcium channels, calcium uptake via slow calcium channels, calcium pool sizes, and the contractile response to Bay K 8644, verapamil, and nifedipine using isolated cardiac myocytes from 8-9-month-old CM hamsters (BIO 14.6) and age-matched normal controls. The number of dihydropyridine binding sites as assessed by specific binding of [3H]PN200-110 was similar in the two groups (control hearts: Bmax = 333 +/- 89 [mean +/- SD] fmol/mg; CM hearts: Bmax = 357 +/- 75 fmol/mg; n = 5 experiments, p = 0.6). Current density through L-type calcium channels was determined using the whole-cell clamp technique (at -50 mV holding potential and -10 mV test potential) and was the same in CM myocytes (17.8 +/- 1.5 [mean +/- SD] pA/pF) and control myocytes (18.6 +/- 2.1 pA/pF) (n = 5 experiments, p = 0.5). The current-voltage relation (test potentials varied from -40 to +50 mV) was also the same in CM and control cells, as was apparent threshold, peak current, and reversal potential. However, the initial rate of 45Ca influx as well as the size of the rapidly exchangeable calcium pool was significantly greater in myocytes obtained from CM than from normal hamsters. In both myocyte preparations, Bay K 8644 increased the rate of 45Ca uptake by 25% at 60 seconds; verapamil decreased 45Ca uptake at 60 seconds by 16% and 17% in normal and CM hamsters, respectively. A similar inhibitory effect was observed with nifedipine. The amplitude of cell motion in cells driven at 1.5 Hz as assessed by an optical-video system increased progressively with increasing concentrations of extracellular calcium or Bay K 8644 in cardiac myocytes from normal or CM hamsters. However, the concentration-effect curves for the two effectors were shifted to the left in CM cells compared with cells from normal hamsters. Both preparations demonstrated similar contractile responses to verapamil and nifedipine. These findings demonstrate that single enzymatically dissociated cardiac myocytes from CM hamsters have impaired contractile properties analogous to those seen in the intact heart and thus provide a useful experimental system in which to study underlying cellular mechanisms operative in this model of heart failure. Our results further indicate that calcium overload in CM hamster cardiac myocytes may not be due to increased calcium influx via dihydropyridine-sensitive calcium channels, as suggested previously, but rather to abnormalities of intracellular calcium homeostasis.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

Endothelin enhances the contractile responsiveness of adult rat ventricular myocytes to calcium by a pertussis toxin-sensitive pathway.

It has long been assumed that the primary influences regulating cardiac contractility are the extent of mechanical loading of muscle fibers and the activity of the autonomic nervous system. However, the vasoactive peptide endothelin, initially found in vascular endothelium, is among the most potent positively inotropic agents yet described in mammalian myocardium. In isolated adult rat ventricular cells, endothelin's action was slow in onset but very long lasting with an EC50 of 50 pM that approximates the reported KD of the peptide for its receptor in rat heart. When the calcium activity of the buffer superfusing isolated single fura-2-loaded myocytes paced at 1.5 Hz was varied from 0.1 to 0.9 mM [Ca2+]o, 100 pM endothelin increased contractile amplitude with no significant change in diastolic or systolic [Ca2+]i, thus appearing to sensitize the myofilaments to intracellular calcium. Pertussis toxin, or prior exposure to a beta-adrenergic agonist, reduced or abolished the increase in myocyte contractility induced by endothelin. This novel and potent pharmacologic action of endothelin points to the potential importance of local, paracrine factors, perhaps derived from microvascular endothelium or endocardium, in the control of the contractile function of the heart.

Animals

tctex-1: a candidate gene family for a mouse t complex sterility locus.

The t complex of the mouse has an important role in male germ cell development and function. Multiple mutations in the t complex interact to alter profoundly the transmission ratio of t complex-bearing sperm or to cause complete sterility or semisterility. We have isolated a multigene family, tctex-1, by screening a testicular cell cDNA library with two reciprocally subtracted testicular cDNA probes. The tctex-1 gene family produces an abundant, virtually germ cell-specific transcript that is 8-fold overexpressed in t homozygotes. The aberrant expression of tctex-1 is solely dependent on the t haplotype genes and occurs only in germ cells. The chromosomal location and pattern of expression of tctex-1 make it a candidate for involvement in male sterility.

Amino Acid Sequence

Length changes in dendritic networks of cerebellar Purkinje cells of old rats after chronic ethanol treatment.

Dendritic networks of cerebellar Purkinje neurons from aging ethanol-treated Fisher 344 rats were analyzed for metric changes in terminal and internal segments of the networks. Mean lengths of three categories of dendritic segments were determined. No significant metric changes in segment lengths were detectable immediately at the termination of 24 weeks of ethanol treatment, but significant changes were apparent after 8 weeks of recovery from ethanol treatment. Return to a diet of standard laboratory chow was associated with a period of dendritic extension in networks from pair-fed control rats but not in those from the ethanol-treated rats. The resulting significant differences in mean segment length were restricted to the paired terminal segments at the peripheral tips of the bifurcating networks. Unpaired terminal segments and internal segments of the networks showed no significant changes in length during the recovery period.

Age Factors