The discovery of chaperonins.
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Chaperonin 60↗
Biomedical subjects
T Smith
Publications and source records attributed to T Smith.
First molecular explanation of disease.
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Anemia, Sickle Cell↗
The impact of spinal cord injury on men's time use.
BACKGROUND: Despite evidence of the relationship between time use and health and well-being, and the World Health Organization's recognition of activity limitation as a measure of dis-ability, there has been limited investigation into the activity patterns of persons with disabilities. METHODS: Interviews and time diaries to provide preliminary descriptive and analytical information about the daily time use patterns of men with a spinal cord injury (SCI) living in the community (n=312) compared with the time use data of able-bodied men (n=3617) collected as part of the 1992 Canadian General Social Survey. The study also examined relationships between time use by men with SCI and selected factors (severity of disability and socioeconomic status). FINDINGS: Statistically different time use patterns between the SCI and able-bodied subjects. The men with spinal cord injury spent on average 7.2 h in leisure activities (able-bodied men=6.0 h); 4.7 (7.7) h in productivity; 3.7 (2.3) h in personal care; and 8.5 (8.0) h sleeping. The SCI men's lesser productivity time was accounted for largely by the lack of time spent in paid work. The average time use of the SCI sample showed the most time spent in passive leisure pursuits such as watching TV and listening to the radio. The sample rated their satisfaction with their time use as mediocre, but levels of adjustment to disability were moderate to high. Regression analysis revealed that severity of disability (lesion level, functional independence, environment) did not predict the amount of time spent in personal care, productivity, leisure, or sleep. Socioeconomic status had a mild predictive relationship with time allocation. IMPLICATIONS: The findings suggest men with SCI are socially isolated relative to their able-bodied peers. Recommendations are made and include both methodological considerations for further time use studies with persons with SCI, and policy recommendations. The latter focus on the need for rehabilitation, education and resources that go beyond functional independence such that persons with SCI can expand both their leisure and productivity roles and become better socially and economically integrated into society.
Activities of Daily Living↗
Antibodies against Plasmodium falciparum vaccine candidates in infants in an area of intense and perennial transmission: relationships with clinical malaria and with entomological inoculation rates.
Serum immunoglobulin (Ig)G1, IgG3 and total IgG were assessed by immunoabsorbent assay in 198 infants from a Tanzanian village highly endemic for Plasmodium falciparum. Antibodies were measured against epitopes of the circumsporozoite protein (the repetitive epitope (NANP)50 and a construct of the flanking regions (CS27IC)), the malaria vaccine SPf66, and two constructs of the merozoite surface protein-1 (MSP-1), a 19-kDa fragment from the C-terminal domain (MSP-119) and an N-terminal fragment spanning blocks 1-6 (H6-p190 M-1/6-H6). IgG1 and total IgG titres showed similar age profiles, all decreasing for the first 2 months of life. Anti-(NANP)50 titres remained very low throughout the first year of life, while anti-CS27IC antibody appeared to peak around 7 months of age. Only a slight tendency to increase with age was observed for levels of the other antibodies studied. IgG3 titres except for H6-p190(1/6), were very low initially and remained very low throughout the first year of life. Clinical malaria incidence at the village dispensary was analysed prospectively in relation to antibody. No IgG1 or total IgG titre showed protective effects, but low IgG3 against p190(1/6) appeared to be a risk factor in some age groups. Given the large number of antibodies tested, this single indication of possible protection could merely be chance. There were no strong associations between antibody titres and entomologically assessed sporozoite exposure suggesting that transmission-reducing interventions may have little effect on antibody levels in such children.
Aging↗
Malaria infection and morbidity in infants in relation to genetic polymorphisms in Tanzania.
To investigate the effects of host polymorphisms on malaria morbidity and infection, the frequency distributions of TNF alpha promotor gene and sickle cell trait were studied in infants in an area highly endemic for Plasmodium falciparum transmission in Tanzania. Differences in parasite prevalence, density, febrile episodes with and without parasitaemia, PCV levels and the frequencies of different MSP-2 parasite infections were assessed by genotype. The frequency of the TNF alpha promotor allele 2 was 0.09, and the trait was in Hardy-Weinberg equilibrium. There were no differences in malariametric indices between infants with the normal TNF alpha promoter gene and those who were heterozygous for this trait. Infants heterozygous for the TNF alpha promotor gene appeared to have fewer febrile episodes when they were free of parasites. The two infants homozygous for the TNF alpha promoter allele 2 had both a much higher incidence of fever, independently of parasitaemia, than the average for the other genotypes. The frequency of the sickle cell allele S was 0.06 and the trait was also in Hardy-Weinberg equilibrium. Infants heterozygous for the sickle cell trait had significantly lower parasite densities, but similar prevalence, and MSP-2 infections compared to infants with normal haemoglobin. PCV levels, and the incidence of febrile episodes both with and without parasitaemia were also similar. In contrast to the sickle cell trait, the TNF alpha promotor polymorphism appeared not to have any protective effect on malaria in this study, and its importance in other unspecified fever-causing diseases in this population needs further investigation.
Alleles↗
Vibrotactilometry as a diagnostic tool in ulnar nerve entrapment at the elbow.
Vibrotactilometry with testing of the thresholds of the vibration sense at seven frequencies between 8-500 Hz in different intensities has been correlated with nerve conduction studies of the ulnar nerve to evaluate its diagnostic power in neuropathies at the elbow. Thirty-nine patients with entrapment symptoms were studied. Vibrotactilometry was abnormal in 33 patients (85%) and nerve conduction studies were abnormal in 19 (49%). The sensitivity of vibrotactilometry in relation to nerve conduction studies was 89%, and in relation to the patients' symptoms was 85%. We conclude that vibrotactilometry is a sensitive test that correlates well with the patients' symptoms, while nerve conduction studies are less sensitive (49%) in relation to the patients' symptoms. Vibrotactilometry in the frequency area of 8-500 Hz is recommended in the screening of ulnar nerve entrapment. Nerve conduction studies are recommended in clinically doubtful cases to localise the entrapment to the elbow region.
Electrophysiology↗
Exposure assessment of laboratory students.
The Massachusetts Institute of Technology (MIT) has two kinds of laboratories, teaching for undergraduate students and research laboratories for graduate students and research staff. The objective of this study is to determine chemical exposures during teaching and research activities. There are three hypotheses in this study: (1) Exposures in academic laboratories are well below health standards; (2) Students in undergraduate teaching laboratories have less chemical exposure compared to students in graduate research laboratories; and (3) Students in different disciplines are expected to have different exposures. From September 1996 to December 1996, 132 air samples were collected from both teaching and research laboratories in the departments of Material Sciences and Engineering, Chemical Engineering, and Biology. The most frequently sampled chemicals in these three departments were cobalt, styrene, and formaldehyde, respectively. A total of 23 different agents were measured. In this study, the American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value (TLV)-short-term exposure limit (STEL) is used as the health-effect standard for exposure time less than four hours. The ACGIH TLV-TWA (time-weighted average) is used as the standard for exposure times equal to or greater than four hours. The ratio of measured concentrations to the appropriate ACGIH standard was then calculated. The geometric mean of the ratio for the total samples was 0.34 percent of the standards. There were 70 samples from teaching laboratories (geometric mean = 0.38% of the standards), and 62 samples from research laboratories (geometric mean = 0.08% of the standards). The chemical exposures relative to the standards in teaching laboratories were statistically higher than in research laboratories (p-value < 0.001). Information about personal protective equipment and the use of laboratory chemical hoods was also collected. The differences in use of personal protective equipment (PPE) among these departments was not statistically significant. From the air sampling results, we concluded that (1) Chemical exposures in the academic laboratories in this study were all well below the health standards; (2) Undergraduate students in teaching laboratories had higher chemical exposures than graduate students in research laboratories; (3) Chemical exposures among departments were not significantly different; and (4) Hazard communication, safety training, and laboratory rules enforcement are important for protection and may be the reason that the results from this study indicate that chemical exposures in this academic institution are well below the health standards under normal operations.
Adolescent↗
Failure of treatment of pneumonia associated with highly resistant pneumococci in a child.
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Anti-Bacterial Agents↗
Respiratory symptoms, sensitization and dust exposure in small bakeries.
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Bread↗
Pre-conception diabetes care in insulin-dependent diabetes mellitus.
Prospective studies of pre-conception diabetes care have confirmed its positive impact on the incidence of malformations by improving glycaemic control. Less information is available on the impact of pre-conception care on maternal and neonatal morbidity. This audit addresses its impact on timing and mode of delivery, incidence of macrosomia and rate of admission to neonatal unit care in addition to sociodemographic factors which may influence attendance at such a service. Attenders were more likely to be in a stable relationship and be non-smokers. They were more likely to book for antenatal care earlier and with a lower glycated haemoglobin. There were no early deliveries (i.e. < 30 weeks) or small for gestational age (SGA) babies in those who attended for pre-conception care and no neonatal deaths. Admission to NNU care was reduced by 50% in those who attended for pre-conception care. Although the rate of macrosomia was reduced, there was no impact on the Caesarian section rate. A pre-conception diabetes clinic may have a positive impact on neonatal morbidity.
Cesarean Section↗
Pregnancy outcome in women with insulin-dependent diabetes mellitus complicated by nephropathy.
We retrospectively analysed pregnancy complicated by diabetic nephropathy in patients attending a University teaching hospital (1990-97), to examine fetal/maternal outcomes. Fetal outcomes included early intrauterine deaths, stillbirths, neonatal/perinatal mortality, size for gestational age, malformations, and need for neonatal unit care. Maternal outcomes included change in frequency of hypertension or severe proteinuria, serum creatinine data, and caesarean section rate. There were 21 pregnancies in 18 women, resulting in 21 live infants. Neonatal mortality (RR 10, 95% CI 0-3.9), perinatal mortality (RR 5, 95% CI 0-3.3) and congenital malformations (RR 5.0, 95% CI 0.3-26.3) were greater than in the background population. At delivery, 76% of babies were appropriate in size for gestational age; 57% were preterm, all of whom required neonatal unit care. The caesarean section rate was 90.5% vs. 20% in the background population (RR 4.5, 95% CI 3.4-5.0) (p < 0.05). Hypertension frequency (p < 0.001) and high-grade proteinuria (p < 0.05) increased from booking to delivery. Although the take-home baby rate was 90%, perinatal/neonatal mortality, congenital malformations and caesarean sections, in addition to maternal morbidity, were significantly higher in women with diabetic nephropathy than in the background population.
Adult↗
Jetting lidocaine through the atomizer.
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Anesthesia, Local↗
Brain injury after cerebral arterial air embolism in the rabbit as determined by triphenyltetrazolium staining.
BACKGROUND: Microscopic cerebral arterial air embolism (CAAE) occurs commonly during cardiac surgery and causes acute and chronic nonfocal neurologic dysfunction. Nevertheless, most neuroimaging studies do not detect brain injury after cardiac surgery. Using a rabbit model, the authors hypothesized they could detect and quantitate severe brain injury and infarction 24 h after microscopic CAAE using the vital stain triphenyltetrazolium chloride. METHODS: Experiments were conducted in methohexital anesthetized New Zealand white rabbits. Surgical shams (n = 5) underwent surgery but had no neurologic insult. Positive controls (n = 3) received 200 microl/kg of intracarotid air. Other animals were randomized to receive either 50 microl/kg intracarotid air, which produces microscopic CAAE (n = 18), or 300 microl intracarotid saline (control, n = 18). Outcomes included somatosensory evoked potential amplitude at 90 min, neurologic impairment score at 4 and 24 h (0 [normal] to 99 [coma]), and percentage of nonstaining brain at 24 h using color-discrimination image analysis. Severely injured or infarcted brain does not stain with triphenyltetrazolium chloride. RESULTS: Surgical shams had little neurologic impairment and a small amount of nonstaining brain at 24 h (5.2 +/- 2.4%; mean +/- SD). Positive controls had profound neurologic impairment and large amounts of nonstaining brain (40-97%). Ninety-minute somatosensory evoked potential amplitude was less in animals receiving 50 microl/kg air versus saline: 38 +/- 28% versus 102 +/- 32%, respectively, P < 1 x 10(-7). Neurologic impairment scores were greater in animals receiving 50 microl/kg air versus saline: at 4 h, 43 +/- 16 versus 23 +/- 9, P < 1 x 10(-7); at 24 h, 24 +/- 12 versus 15 +/- 8, P = 0.013. Nevertheless, there was no difference between 50 microl/kg air and saline in nonstaining brain: 5.5 +/- 2.9% versus 6.8 +/- 5.4%, P = 0.83. CONCLUSIONS: Neurologic injury after CAAE is dose-dependent. Although microscopic CAAE causes somatosensory evoked potential abnormalities and neurologic dysfunction, severe cerebral injury or infarction is not present at 24 h. The author's findings are consistent with clinical imaging studies that suggest microscopic CAAE causes neurologic dysfunction even though overt infarction is absent.
Animals↗
Histologic and physiologic effects of electrocautery, CO2 laser, and radiofrequency injury in the porcine soft palate.
OBJECTIVES: This study was undertaken to compare the effects of electrosurgery, CO2 laser, and radiofrequency on the histological structure and physiological properties of the soft palate. These surgical techniques are used for stiffening and reducing the soft palate in the treatment of snoring and mild sleep apnea. STUDY DESIGN: Fifteen pigs were divided into five groups. METHODS: group 1 underwent electrosurgery incision of the lateral soft palate and excision of the uvula. Group 2 underwent the same procedure with the CO2 laser. Group 3 underwent CO2 laser ablation of the midline soft palate mucosa. Group 4 underwent radiofrequency volumetric reduction. Group 5 served as control. After 5 weeks the animals were sacrificed. Soft palate mucosa and muscle were subjected to tensiometric and histological analysis. Statistical analysis of tensiometric measurements was done with an ANOVA using a Bonferroni-Dunn correction. RESULTS: Tensiometric measurements of the mucosa were increased over normal controls when the surgical technique resulted in mucosal disruption. When the surgical technique resulted in primarily muscle disruption (radiofrequency) tensiometric measurements of the muscle were increased over controls. Histological analysis demonstrated normal remucosalization in all specimens, with fibrosis increased at the site of the primary injury. CONCLUSIONS: The type of injury produced resulted in identifiable patterns of physiological and histological change. Understanding of the effects of available surgical techniques is important in guiding our choice of surgical approach and allows us to better counsel our patients on their surgical options.
Animals↗
Osteoinductive response in the dorsal aspect of the carpus of young thoroughbreds in training occurs within months.
Bone mineral density (BMD) was measured by dual x-ray absorptiometry (DXA) in the carpus of 6 Thoroughbreds age 24 months that were exercised on the treadmill for 4.5 months, and of 6 matched control horses. A sagittal slab of known thickness was sawn from one or more of radius, radial carpal (Cr), third carpal (C3), and third metacarpal (Mc3) bones. After the 4.5 month treadmill exercise, there was a significantly greater volumetric BMD in the dorsal aspect of C3 (P = 0.006). Treadmill-exercised horses also had higher BMD in the dorsodistal aspect of the radius (P = 0.03), the dorsal half of Mc3 (P = 0.012), and the dorsal aspect of Cr (P = 0.04). In other areas of interest (AOI) studied on the palmar aspect of the bones, significant increases in exercised horses did not occur. These sizeable changes in bone mass occurred within a few months of initiation of exercise. With technical development, DXA could be applied in vivo for investigation of changes in bone mass of horses which are growing and exercising under various regimes. The data are also relevant to the development of scientifically based training protocols.
Absorptiometry, Photon↗
BRCA1/BRCA2 germline mutations in locally recurrent breast cancer patients after lumpectomy and radiation therapy: implications for breast-conserving management in patients with BRCA1/BRCA2 mutations.
PURPOSE: Breast cancer patients treated conservatively with lumpectomy and radiation therapy (LRT) have an estimated lifetime risk of local relapse (ipsilateral breast tumor recurrence [IBTR]) of 10% to 15%. For breast cancer patients carrying BRCA1 or BRCA2 (BRCA1/2) mutations, the outcome of treatment with LRT with respect to IBTR has not been determined. In this study, we estimate the frequency of BRCA1/2 mutations in a study of breast cancer patients with IBTR treated with LRT. PATIENTS AND METHODS: Between 1973 and 1994, there were 52 breast cancer patients treated with LRT who developed an IBTR within the prior irradiated breast and who were willing to participate in the current study. From our database, we also identified 52 control breast cancer patients treated with LRT without IBTR. The control patients were individually matched to the index cases with respect to multiple clinical and pathologic parameters. Lymphocyte DNA specimens from all 52 locally recurrent patients and 15 of the matched control patients under age 40 were used as templates for polymerase chain reaction amplification and dye-primer sequencing of exons 2 to 24 of BRCA1, exons 2 to 27 of BRCA2, and flanking intron sequences. RESULTS: After LRT, eight (15%) of 52 breast cancer patients had IBTR with deleterious BRCA1/2 mutations. By age, there were six (40%) of 15 patients with IBTR under age 40 with BRCA1/2 mutations, one (9.0%) of 11 between ages 40 and 49, and one (3.8%) of 26 older than age 49. In comparison to the six (40%) of 15 of patients under age 40 with IBTR found to have BRCA1/2 mutations, only one (6.6%) of 15 matched control patients without IBTR and had a BRCA1/2 mutation (P =.03). The median time to IBTR for patients with BRCA1/2 mutations was 7.8 years compared with 4.7 years for patients without BRCA1/2 mutations (P =.03). By clinical and histologic criteria, these relapses represented second primary tumors developing in the conservatively treated breast. All patients with BRCA1/2 mutations and IBTR underwent successful surgical salvage mastectomy at the time of IBTR and remain alive without evidence of local or systemic progression of disease. CONCLUSION: In this study, we found an elevated frequency of deleterious BRCA1/2 mutations in breast cancer patients treated with LRT who developed late IBTR. The relatively long time to IBTR, as well as the histologic and clinical criteria, suggests that these recurrent cancers actually represent new primary breast cancers. Early onset breast cancer patients experiencing IBTR have a disproportionately high frequency of deleterious BRCA1/2 mutations. This information may be helpful in guiding management in BRCA1 or BRCA2 patients considering breast-conserving therapy.
Adult↗