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Biomedical subjects

H McConnell

Publications and source records attributed to H McConnell.

14 recordsLinked to original sources
PubMed2001

Rheumatoid arthritis (RA)-associated HLA-DR alleles form less stable complexes with class II-associated invariant chain peptide than non-RA-associated HLA-DR alleles.

Certain HLA-DR alleles confer strong susceptibility to the autoimmune disease rheumatoid arthritis (RA). We compared RA-associated alleles, HLA-DR*0401, HLA-DR*0404, and HLA-DR*0405, with closely related, non-RA-associated alleles, HLA-DR*0402 and HLA-DR*0403, to determine whether they differ in their interactions with the class II chaperone, invariant chain (Ii). Ii binds to class II molecules in the endoplasmic reticulum, inhibits binding of other ligands, and directs class II-Ii complexes to endosomes, where Ii is degraded to class II-associated Ii peptide (CLIP). To evaluate the interaction of Ii and CLIP with these DR4 alleles, we introduced HLA-DR*0401, *0402, and *0404 alleles into a human B cell line that lacked endogenous HLA-DR or HLA-DM molecules. In a similar experiment, we introduced HLA-DR*0403 and *0405 into an HLA-DM-expressing B cell line, 8.1.6, and its DM-negative derivative, 9.5.3. Surface abundance of DR4-CLIP peptide complexes and their susceptibility to SDS-induced denaturation suggested that the different DR4-CLIP complexes had different stabilities. Pulse-chase experiments showed CLIP dissociated more rapidly from RA-associated DR molecules in B cell lines. In vitro assays using soluble rDR4 molecules showed that DR-CLIP complexes of DR*0401 and DR*0404 were less stable than complexes of DR*0402. Using CLIP peptide variants, we mapped the reduced CLIP interaction of RA-associated alleles to the shared epitope region. The reduced interaction of RA-associated HLA-DR4 molecules with CLIP may contribute to the pathophysiology of autoimmunity in RA.

Alleles↗
PubMed1998

Antidepressant interactions with warfarin.

The interactions between warfarin and antidepressants can have potentially serious consequences resulting from enhanced or reduced anticoagulant activity. Information about such interactions was obtained from a Medline and hand search of the published literature, and by directly contacting manufacturers. The different classes of antidepressants are discussed in turn. The possible mechanisms are considered with particular reference to the cytochrome p450 system. From currently available data on the newer antidepressants our conclusions are that citalopram, nefazodone and sertraline may be relatively less likely to interact with warfarin. Fluoxetine, fluvoxamine, paroxetine and moclobemide appear to have the highest potential of the antidepressants for interactions. There is insufficient data on venlafaxine to make a prediction. The clinical implications of these findings are discussed and specific recommendations for International Normalized Ratio monitoring are suggested.

Animals↗
PubMed1997

Charging for intensive care using direct nursing hours as the cost marker.

The hypothesis that direct nursing hours correlate with the cost of a patient stay in intensive care was tested. One hundred and thirty-nine patients were studied and the data collected included: (a) direct nursing hours applied to each patient; (b) a daily TISS score: (c) a detailed costing of each patient (all costs are shown in N.Z.$). There was a strong correlation between the direct nursing hours and the total cost per patient (r2 = 0.98) (total cost = 54 x direct nursing hours + 344). Also a strong correlation existed between the total TISS scores and the total costs per patient (r2 = 0.96) (total cost = 67.13 x TISS). Direct nursing hours offer a relatively simple and logical method of allocating costs per patient.

Direct Service Costs↗
PubMed1996

In situ monitoring with the Tradescantia bioassays on the genotoxicity of gaseous emissions from a closed landfill site and an incinerator.

A dual monitoring system composed of the Tradescantia-Micronucleus (Trad-MCN) and Tradescantia-Stamen-Hair-Mutation (Trad-SHM) bioassays was utilized to monitor directly the genotoxicity of the gaseous emission at a closed landfill site and around an incinerator. Four of the commonly emitted gaseous agents from the landfill flare pipes, i.e. toluene, ethylbenzene, trichloroethylene and ethyltoluene were also evaluated for their genotoxicity in the laboratory. The in situ monitoring trips (360 km one way) were carried out by transporting the plant cuttings in a clean air box or in an air-tight plastic bag to the site and exposing these test cuttings for 5-7 h. The exposed plant samples were examined for micronuclei frequencies or the pink mutation rate after the appropriate recovery periods (24 h for MCN, 7-11 days for SHM). A total of 20 monitoring trips were made to the landfill, and 8 to the nearby surroundings (100-500 m from the chimney) of the incinerator site in a two year period. The major findings of the Trad-MCN test on the clastogenicity of the gaseous emission from the flare pipe of the landfill site showed positive responses or toxic effects in 6 out of 20 trips, and that from the incinerator showed positive responses in 5 out of the 8 trips. These positive responses were closely associated with the weather, i.e. low wind velocity, high temperature and relative humidity, and especially the distance from the chimney of the incinerator. The MCN frequencies and mutation rates of the Elementary School site (E. Sch) which is about 200 m from the fence of the landfill site were mostly negative, except the test results of three trips. Trad-SHM tests on the mutagenicity of gaseous emissions from the flare pipe of the landfill showed 12 positive responses out of 20 trials and 2 positives out of 4 trials from the incinerator gaseous emissions. The average mutation rate from 20 Trad-SHM monitoring trips is positive when the ANOVA and Dunnett's t-statistic were applied to the consolidated data. There is a significant (0.01) difference between the lab control and the gas exposed groups, and between the field control and gas exposed groups. Results of the Trad-SHM test at the E. Sch. site were mostly negative except for one trip. In general, micronuclei frequencies and mutation rates of the field control groups were relatively higher than those of the lab controls. The Trad-MCN test on pure gases showed positive responses in all 3 repeated tests on toluene (50-892 ppm). The test results of ethylbenzene yielded positive responses at 172 ppm/min and 1549 ppm/min dosages and exhibited toxicity at higher concentrations. Trad-MCN tests on trichloroethylene and ethyltoluene yielded positive responses at around 100-200 ppm/min level. Three repeated Trad-SHM tests on toluene yielded no positive response at low concentrations (4.3-12.9 ppm).

Air Pollutants↗
PubMed1996

Characterization of major depression symptoms in multiple sclerosis patients.

Retrospective review of affective disturbances in 238 patients with multiple sclerosis (MS) seen over a 6-month period revealed: 1) 51 patients (22%) received pharmacologic treatment for depressive symptoms during or within 4 years of the study period, and 17 (7%) received treatment for rapid mood swings; 2) among the 51 depressed patients, response rate to medication was extremely high; 3) relapse of depressive symptomatology after discontinuation of medication was also high (17/29); 4) first episodes of major depression frequently occurred during periods of MS progression or exacerbation, but first episodes also occurred during periods of relative clinical stability; 5) suicidal ideation was common (12 patients), but only 1 patient had a history of attempted suicide; and 6) side effects were tolerable in most patients.

Adult↗
PubMed1996

Neuropsychiatric side effects related to treatment with felbamate.

Seven patients with refractory seizure disorders and neuropsychiatric symptoms believed secondary to felbamate are presented. Five were on concomitant valproic acid (and other agents). Anergia, apathy, bradyphrenia, and increased irritability were prominent. One patient on felbamate monotherapy had a new-onset psychosis. Felbamate's NMDA receptor antagonism and GABA potentiation (perhaps enhanced by valproic acid use) are discussed as possible mechanisms of these side effects.

Adult↗
PubMed1996

The use of community nurses for home peritoneal dialysis: is it cost-effective?

In the late 1970s, continuous ambulatory peritoneal dialysis was first introduced as a mode of treatment for patients with end-stage renal disease. Since that time many patients, themselves or with the help of family members, have routinely performed the therapy at home. There are now 2935 home peritoneal dialysis patients in Canada (36% of the total dialysis population). Today, however, the average patient on dialysis is likely to be older and have other complicating illnesses; moreover, patients may live alone, or have family members who are working. Over the past three years, through the use of innovative assistive devices and strong educational links with community nursing agencies, we have been able to manage peritoneal dialysis patients with complex needs in the home. We performed a retrospective analysis of 18 patients, with severe comorbid conditions, who were managed in the home with the help of community nurses. We will show that this is an economic, efficient, and effective method of caring for home dialysis patients with severe disabilities. Home care agencies need our support so that they can continue to help us manage the complex peritoneal dialysis patient in the 1990s.

Adult↗
PubMed1995

The improved Allium/Vicia root tip micronucleus assay for clastogenicity of environmental pollutants.

The meristematic mitotic cells of plant roots are appropriate and efficient cytogenetic materials for the detection of clastogenicity of environmental pollutants, especially for in situ monitoring of water contaminants. Among several cytological endpoints in these fast dividing cells, such as chromosome/chromatid aberrations, sister-chromatid exchanges and micronuclei, the most effective and simplest indicator of cytological damage is micronucleus formation. Although the Allium cepa and Vicia faba root meristem micronucleus assays (Allium/Vicia root MCN) have been used in clastogenicity studies about 12 times by various authors in the last 25 years, there is no report on the comparison of the efficiency of these two plant systems and in different cell populations (meristem and F1) of the root tip as well as under adequate recovery duration. In order to maximize the efficiency of these bioassays, the current study was designed to compare the Allium and the Vicia root MCN assays on the basis of chromosome length, peak sensitivity of the mitotic cells, and the regions of the root tip where the MCN are formed. The total length of the 2n complement of Allium chromosomes is 14.4 microns and the total length of the 2n complement of Vicia is 9.32 microns. The peak sensitivity determined by serial fixation at 12-h intervals after 100 R of X-irradiation is 44 h. The slope of the X-ray dose-response curve of Allium roots derived from the meristematic regions was lower than that derived from cells in the F1 region. Higher efficiency was also demonstrated when the MCN frequencies were scored from the F1 cells in both Allium and Vicia treated with formaldehyde (FA), mitomycin C (MMC), and maleic hydrazide (MH). The results indicated that scoring of MCN frequencies from the F1 cell region of the root tip was more efficient than scoring from the meristematic region. The X-ray linear regression dose-response curves were established in both Allium and Vicia cell systems and the coefficients of correlations, slope values were used to verify the reliability and efficiency of these two plant cell systems. Based on the dose-response slope value of 0.894 for Allium and 0.643 for Vicia, the Allium root MCN was a more efficient test system. The greater sensitivity of the Allium roots is probably due to the greater total length of the diploid complement and the higher number of metacentric chromosomes.(ABSTRACT TRUNCATED AT 400 WORDS)

Allium↗
PubMed1995

Prenuptial seizures: a report of five cases.

The cases of 5 patients with seizures occurring the day of or shortly before their weddings are presented. Major life events may precipitate or exacerbate epileptic or nonepileptic seizures as a result of 1) missed medications, 2) sleep deprivation, 3) alcohol or concomitant medications, 4) hyperventilation, or 5) the emotional state directly or stress indirectly. Seizures occurring at times of psychological stress may be either neurological or psychiatric in origin. The physician treating patients with a new onset or exacerbation of seizures around a major life event must consider all of these factors in the evaluation.

Adult↗
PubMed1995

Measurement of treatment response to sertraline in depressed multiple sclerosis patients using the Carroll scale.

We studied 11 patients with stable multiple sclerosis (MS) with major depression in terms of response to Sertraline at 100 mg q.d. in an open label trial. Patients were evaluated with self assessment measurements (Carroll scale) prior to and during treatment. Only one patient discontinued the drug during the three month treatment trial, and this was due to perceived lack of efficacy by the patient. The remainder of the patients completed at least three months of treatment and had significant improvement in depressive symptoms by self assessment measurements. No patients experienced side effects. Sertraline appears to be well tolerated and effective in treatment of major depression in MS. The Carroll scale is an easily administered means of assessing treatment response, and correlated highly with our clinical impressions.

1-Naphthylamine↗
PubMed1992

Chronic low back pain patients around the world: cross-cultural similarities and differences.

OBJECTIVE: The current study sought to determine whether there were any significant cross-cultural differences in medical-physical findings, or in psychosocial, behavioral, vocational, and avocational functioning, for chronic low back pain patients. DESIGN: Partially double-blind controlled comparison of six different culture groups. SETTING: Subjects were selected from primarily ambulatory care facilities specializing in treating chronic pain patients. PATIENTS-SUBJECTS: Subjects consisted of 63 chronic low back pain patients and 63 healthy controls. Low back pain patients were randomly selected from six different culture groups (American, Japanese, Mexican, Colombian, Italian, and New Zealander). Ten to 11 were gathered per culture from a pool of patients treated at various pain treatment programs. Likewise, 10 or 11 control group subjects were obtained from each culture from a pool of healthy support staff. MAIN OUTCOME MEASURES: The Sickness Impact Profile and the Medical Examination and Diagnostic Information Coding System were used as primary outcome measures. RESULTS: Findings showed that (a) low back pain subjects across all cultures had significantly more medical-physical findings and more impairment on psychosocial, behavioral, vocational, and avocational measures than controls did; (b) Mexican and New Zealander low back pain subjects had significantly fewer physical findings than other low back pain groups did; (c) the American, New Zealander, and Italian low back pain patients reported significantly more impairment in psychosocial, recreational, and/or work areas, with the Americans the most dysfunctional; and (d) findings were not a function of working class, age, sex, pain intensity, pain duration, previous surgeries, or differences in medical-physical findings. CONCLUSIONS: It was concluded that there were important cross-cultural differences in chronic low back pain patients' self-perceived level of dysfunction, with the American patients clearly the most dysfunctional. Possible explanations included cross-cultural differences in social expectation; attention; legal-administrative requirements; financial gains; attitudes-expectations about usage, type, and availability of health care; and self-perceived ability and willingness to cope.

Adult↗
PubMed1985

Catecholamine metabolism in the attention deficit disorder: implications for the use of amino acid precursor therapy.

The use of catecholamine precursors and agonists in the attention deficit disorder and various biochemical studies have implicated deficient catecholamine metabolism in the pathogenesis of this illness. The amino acid L-tyrosine, a catecholamine precursor, is capable of augmenting central dopamine norepinephrine. Study of its use in the treatment of the attention deficit disorder as a safer alternative to stimulant therapy is thus warranted.

Attention Deficit Disorder with Hyperactivity↗
PubMed1975

Phase separations in phospholipd membranes.

Phase diagrams representing lateral phase separations in the plane of lipid bilayer membranes have been determined for binary mixtures containing dielaidoylphosphatidylcholine together with dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, dioleoylphosphatidylcholine, and dipalmitoylphosphatidylethanolamine. The phase diagrams were deduced from observations of the temperature dependence of the paramagnetic resonance spectra of low concentrations of spin-labels incorporated in these bilayer membranes. In one case, the binary mixture of dipalmitoylphosphatidylethamine and dielaidoylphosphatidylcholine, evidence has been obtained for fluid-fluid immiscibility, in specified temperature and compoistion ranges. This immiscibility could give a lateral phase separation into fluid domains in the plane of the membrane, and/or a transverse phase separation into an asymmetrical bilayer membrane, and/or possibly disco ntinuous bilayer membranes of different composition. An asymmetrical bilayer membrane can be expected on theoretical grounds to form a nonplanar membrane.

Electron Spin Resonance Spectroscopy↗