OBJECTIVE: To develop recommendations for practising physicians on the advisability of screening for human papillomavirus (HPV) infection in asymptomatic women. OPTIONS: Visual inspection, Papanicolaou testing, colposcopy or cervicography, use of HPV group-specific antigen, DNA hybridization, dot blot technique, Southern blot technique or polymerase chain reaction followed by physical or chemical therapeutic intervention. OUTCOMES: Evidence for a link between HPV infection and cervical cancer, sensitivity and specificity of HPV screening techniques, effectiveness of treatments for HPV infection, and the social and economic costs incurred by screening. EVIDENCE: MEDLINE was searched for articles published between January 1966 to June 1993 with the use of the key words "papillomavirus," "cervix neoplasms," "mass screening," "prospective studies," "prevalence," "sensitivity," "specificity," "human" and "female." VALUES: Proven cost-effective screening techniques that could lead to decreased morbidity or mortality were given a high value. The evidence-based methods and values of the Canadian Task Force on the Periodic Health Examination were used. BENEFITS, HARMS AND COSTS: Potential benefits are to prevent cervical cancer and eliminate HPV infection. Potential harmful effects include the creation of an unnecessary burden on the health care system and the labelling of otherwise healthy people as patients with a sexually transmitted disease for which therapy is generally ineffective. Potential costs would include expense of testing, increased use of colposcopy and treatment. RECOMMENDATIONS: There is fair evidence to exclude HPV screening (beyond Papanicolaou testing for cervical cancer) in asymptomatic women (grade D recommendation). VALIDATION: The report was reviewed by members of the task force and three external reviewers who were selected to represent different areas of expertise. SPONSORS: These guidelines were developed and endorsed by the task force, which is funded by Health Canada and the National Health Research and Development Program. The principal author (K.J.) was supported in part by the National Health Research and Development Program through a National Health Fellowship (AIDS).

DNA, Viral↗

PubMed1995

Plasma and red blood cell thiamine deficiency in patients with dementia of the Alzheimer's type.

OBJECTIVES: To determine the prevalence of plasma thiamine deficiency in patients referred to a memory disorder clinic and to compare plasma thiamine levels with red blood cell (RBC) thiamine levels. To determine if patients with senile dementia of the Alzheimer's type (SDAT) differ from those without SDAT in either plasma or RBC thiamine levels. DESIGN: Case-control study. SETTING: Ambulatory care referral center. PATIENTS: Consecutive sample of 34 patients; 17 patients who met the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer's disease and 17 patients with other forms of dementia. METHODS: Plasma and RBC thiamine levels were determined in all patients with the use of a microbiologic assay known for its specificity to biological forms of thiamine. Vitamin supplementation was determined by chart review. OUTCOME MEASURES: Plasma and RBC thiamine levels. RESULTS: Patients with SDAT were found to have significantly lower plasma thiamine levels than patients without SDAT. Low plasma thiamine levels were detected in a significantly larger proportion of patients with SDAT than in patients without SDAT. Red blood cell thiamine levels did not correlate with the clinical diagnosis of SDAT. Vitamin supplementation did not correlate with diagnosis and plasma or RBC thiamine levels. CONCLUSIONS: A significant proportion of patients with SDAT may have a thiamine deficiency, which may have an impact on cognitive function. Currently used assays may not be adequate to assess thiamine status.

Aged↗

PubMed1995

The genetic basis of the circadian clock: identification of frq and FRQ as clock components in Neurospora.

Genetic approaches to the identification of clock components have succeeded in two model systems, Neurospora and Drosophila. In each organism, genes identified through screens for clock-affecting mutations (frq in Neurospora, per in Drosophila) have subsequently been shown to have characteristics of central clock components: (1) mutations in each gene can affect period length and temperature compensation, two canonical characteristics of circadian systems; (2) each gene regulates the timing of its own transcription in a circadian manner; and (3) in the case of frq, constitutively elevated expression will set the phase of the clock on release into normal conditions. Despite clear genetic and molecular similarities, however, the two genes are neither molecular nor temporal homologues. The timing of peak expression is distinct in the two genes, frq expression peaking after dawn and per expression peaking near midnight. Also, although expression of per from a constitutive promoter can rescue rhythmicity in a fly lacking the gene, constitutive expression of frq will not rescue rhythmicity in Neurospora frq-null strains, and in fact causes arrhythmicity when expressed in a wild-type strain. These data suggest that frq is and/or encodes a state variable of the circadian oscillator. Recent molecular genetic analyses of frq have shed light on the origin of temperature compensation and strongly suggest that this property is built into the oscillatory feedback loop rather than appended to it. It seems plausible that clocks are adjusted and reset through adjustments in central clock components such as frq, and, by extension, per.

Animals↗

PubMed1995

Women's health and enhancing generalism in internal medicine.

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Curriculum↗

PubMed1995

Temporal changes in permeability and structure of piglet ileum after site-specific infection by Cryptosporidium parvum.

BACKGROUND/AIMS: Cryptosporidiosis is an important enteric infection associated with diarrhea in humans. The structural and functional basis for diarrhea is poorly understood. The aim of the study was to determine the structural and functional basis of diarrhea in cryptosporidiosis during evolving host cell-parasite interactions in the intestine. METHODS: We used the piglet model for temporal studies of alterations in intestinal epithelial structure and function that occurred 12-48 hours postinoculation. Segments of intestine were directly inoculated in vivo, harvested, and studied in vitro using Ussing chamber techniques. RESULTS: Villus architectural alterations corresponded to the extent of infection. Increased numbers of lamina propria inflammatory cells were evident at 36 hours postinoculation. Solute and macromolecular permeability was not increased. Glucose-responsive short-circuit current was diminished at 48 hours postinoculation. The short-circuit current response to theophylline was the same in control and infected tissues. CONCLUSIONS: We conclude that passive solute and macromolecular permeability in infected tissues is not significantly increased during parasite-host cell interactions 12-48 hours postinoculation. Electrogenic glucose stimulated Na+ absorption, a function principally of villus absorptive cells, is impaired, and electrogenic Cl- secretion, a function of crypt epithelial cells, remains the same. These findings parallel structural observations that include loss of the Na+/glucose-transporting villus epithelium without loss of crypt epithelium.

Animals↗

PubMed1995

Environment-driven responses in progressive supranuclear palsy.

The neurological signs and behaviors that accompany degenerative diseases associated with fronto-striatal dysfunction are incompletely described. We observed several novel environmentally-driven behaviors in seven patients with progressive supranuclear palsy (PSP). All patients had cognitive deficits with greatest impairments on tests of frontal lobe function, and frontal lobe cerebral perfusion was significantly reduced in 4 of the 5 who had single photon emission computed tomography (SPECT) brain scans. Visual grasping, in which a patient's gaze was attracted to an incidental object in the environment such as a TV set or mirror, was preeminent. Once fixed, there was inability to release the gaze and shift to another object. In other instances, removing a table placed in front of a patient or unbuckling of his seat belt would make him stand up, which was impossible on command. Similarly, playing music would induce rhythmic foot beating, which was never obtained on command. There were compulsive utilization behaviors, such as repetitively picking up and replacing the telephone for no apparent reason. As expected, there were signs of heightened facial reflexes, grasp reflexes, apraxia of eyelid opening, echolalia and echopraxia. We postulate that these stimuli-oriented behaviors stem from parietal lobe disinhibition due to fronto-striatal dysfunction.

Aged↗

PubMed1995

Drug transport across nylon 610 films: influence of synthesis variables.

Nylon 610 is a hydrophilic polymer with considerable potential as a membrane for drug microencapsulation. To better understand drug transport through such membrane, the influence of the solvents and monomers used in the synthesis of nylon films were examined using a full factorial study. Nylon 610 films were synthesized by an interfacial polycondensation reaction using hexamethylenediamine (HD) in the water phase and sebacoyl chloride (SC) in the organic phase, which was a solvent blend of chloroform and trichlorotrifluoroethane at ratios of 1:1, 1:4, and 4:1. Monomer concentrations studied were 0.2, 0.4, and 0.6 M with respect to their appropriate phase, while the monomer ratios were 1:1, 3:1, and 1:3. The molecular weight, porosity, thickness, and crystallinity of the films were characterized. The transport of potassium chloride, hydrocortisone, and m-cresol was studied at 25 degrees C as a function of the synthesis variables. Potassium chloride was selected to measure the porosity of the membrane. Hydrocortisone and m-cresol, a known solvent for nylon 610, were used to study pore and solution-diffusion transport, respectively. The molecular weight of the films was proportional to the chloroform concentration. As the molecular weight increased, film thickness, porosity, and hydrocortisone permeability increased. As the molecular weight decreased, film thickness and porosity decreased, while m-cresol permeability increased. These results can be explained on the basis of HD ability to readily partition into a good solvent such as chloroform permitting high molecular weight polymer to form before precipitation.

Cresols↗

PubMed1995

Induction of mutations by replication of malondialdehyde-modified M13 DNA in Escherichia coli: determination of the extent of DNA modification, genetic requirements for mutagenesis, and types of mutations induced.

The mutagenicity of the lipid peroxidation product, malondialdehyde (MDA), was measured in the lacZ alpha forward mutation assay using a recombinant M13 phage, M13MB102. Single-stranded M13MB102 DNA was reacted with MDA at neutral pH and the modified DNA was transformed into strains of Escherichia coli induced for the SOS response. Increasing concentrations of MDA led to an increase in lacZ alpha-mutations coincident with an increase in the level of the major MDA-deoxyguanosine adduct. Spontaneous and MDA-induced M13MB102 mutants were collected and the lacZ alpha target region was subjected to automated DNA sequence analysis. The most common sequence changes induced by MDA were base-pair substitutions (76%). Of these, 43% (29/68) were transversions, most of which were G-->T (24/29). Transitions account for 57% of the base-pair substitutions (39/68) and were comprised exclusively of C-->T (22/39) and A-->G (17/39). Frameshift mutations were identified in 16% of the induced mutants and were comprised of mainly single base additions occurring in runs of reiterated bases (11/14). The diversity of base-pair substitution and frameshift mutations induced by MDA at low levels of adduction suggests it may be an important contributor to endogenous mutagenesis and carcinogenesis in aerobic organisms.

Bacteriophage M13↗

PubMed1995

Liquid ventilation improves pulmonary function, gas exchange, and lung injury in a model of respiratory failure.

OBJECTIVE: The authors evaluated gas exchange, pulmonary function, and lung histology during perfluorocarbon liquid ventilation (LV) when compared with gas ventilation (GV) in the setting of severe respiratory failure. BACKGROUND: The efficacy of LV in the setting of respiratory failure has been evaluated in premature animals with surfactant deficiency. However, very little work has been performed in evaluating the efficacy of LV in older animal models of the adult respiratory distress syndrome (ARDS). METHODS: A stable model of lung injury was induced in 12 young sheep weighing 16.4 +/- 3.0 kg using right atrial injection of 0.07 mL/kg of oleic acid followed by saline pulmonary lavage and bijugular venovenous extracorporeal life support (ECLS). For the first 30 minutes on ECLS, all animals were ventilated with gas. Animals were then ventilated with either 15 mL/kg gas (GV, n = 6) or perflubron ([PFC], LV, n = 6) over the ensuing 2.5 hours. Subsequently, ECLS was discontinued in five of the GV animals and five of the LV animals, and GV or LV continued for 1 hour or until death. MAIN FINDINGS: Physiologic shunt (Qps/Qt) was significantly reduced in the LV animals when compared with the GV animals (LV = 31 +/- 10%; GV = 93 +/- 4%; p < 0.001) after 3 hours of ECLS. At the same time point, pulmonary compliance (CT) was significantly increased in the LV group when compared with the GV group (LV = 1.04 +/- 0.19 mL/cm H2O/kg; GV = 0.41 +/- 0.02 mL/cm H2O/kg; p < 0.001). In addition, the ECLS flow rate required to maintain the PaO2 in the 50- to 80-mm Hg range was substantially and significantly lower in the LV group when compared with that of the GV group (LV = 14 +/- 5 mL/kg/min; GV = 87 +/- 15 mL/kg/min; p < 0.001). All of the GV animals died after discontinuation of ECLS, whereas all the LV animals demonstrated effective gas exchange without extracorporeal support for 1 hour (p < 0.01). Lung biopsy light microscopy demonstrated a marked reduction in alveolar hemorrhage, lung fluid accumulation, and inflammatory infiltration in the LV group when compared with the GV animals. CONCLUSION: In a model of severe respiratory failure, LV improves pulmonary gas exchange and compliance with an associated reduction in alveolar hemorrhage, edema, and inflammatory infiltrate.

Animals↗

PubMed1995

Pion inelastic scattering to low-lying positive-parity states in 20Ne.

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Journal Article↗

PubMed1995

Comparison of CTG repeat length expansion and clinical progression of myotonic dystrophy over a five year period.

Myotonic dystrophy (DM) is associated with an underlying CTG trinucleotide repeat expansion at a locus on chromosome 19q13.3. We have determined the repeat length in 23 DM patients with varying clinical severity of symptoms and various sizes of repeat amplification. We confirm that as in previous studies there is no strong correlation between repeat length and clinical symptoms but find that the repeat length in peripheral blood cells of patients increases over a time span of five years indicating continuing mitotic instability of the repeat throughout life. Repeat length progression does not appear to be indicative of clinical progression but age probably is. The degree of expansion correlates with the initial repeat size and 50% of the patients with continuing expansions showed clinical progression of their disease symptoms over the five year study period.

Adolescent↗

PubMed1995

Direct molecular analysis of myotonic dystrophy in the German population: important considerations in genetic counselling.

Myotonic dystrophy (DM) is associated with the expansion and instability of a trinucleotide (CTG) repeat at the DM locus on chromosome 19. Direct genomic analysis in the German population was carried out on 18 DM families, six families with equivocal diagnosis, 69 subjects with equivocal clinical diagnosis, and 100 controls using the polymerase chain reaction (PCR) and a refined Southern protocol. In the majority of the cases molecular analysis confirmed the clinical diagnosis. These included seven cases of congenital DM (CDM) with widely differing gene expansions and instabilities. In most DM families the expanded fragment became larger in successive generations, but we also identified four families with contractions and two families that showed stability of the enlarged fragment during transmission. In four clinically defined DM patients we were unable to detect enlarged CTG repeats. Sequencing of each exon of the DM gene in two of these patients failed to show any mutations. Our cases have important implications for genetic counselling of DM families, highlighting both the diagnostic value of direct genomic analysis and its limitations.

Adult↗

PubMed1995

Report on MDA workshop on myotonic dystrophy, 10 October 1994, Montreal, Quebec, Canada.

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Humans↗

PubMed1995

Parental perceptions of procedure-related distress and family adaptation in childhood leukemia.

Child and parental distress related to lumbar punctures and bone marrow aspirates and general family adaptation are evaluated in a cross-sectional study of children currently in treatment with leukemia in first remission (N = 70). A parental self-report measure developed for this study--the Perception of Procedures Questionnaire (PPQ)--yielded three factors: (a) parental satisfaction, (b) parental distress or involvement, and (c) child distress. Data from the PPQ showed high levels of both satisfaction and distress in the context of invasive procedures. Data from standardized measures of family adaptation demonstrated a range of functioning. Analyses by length of time since diagnosis indicated that parental distress remains stable over the course of treatment. The data are discussed with respect to the newly developed measure of parental procedures (the PPQ) and the need for research in this field that provides an integration of procedural distress with parent and family perceptions and adjustment.

Adolescent↗