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Biomedical subjects

A Davis

Publications and source records attributed to A Davis.

At least 217 records · Page 12Linked to original sources

Thyroid disease in the elderly. Part 2. Predictability of subclinical hypothyroidism.

BACKGROUND: The purpose of this study was to determine how well hypothyroidism could be predicted from clinical signs and symptoms in elderly patients with no known history of thyroid disease. METHODS: This retrospective study was conducted in a primary care geriatrics clinic. Two hundred eighty-three patients (205 women, 78 men), who were between the ages of 60 and 97 years of age and had no history of thyroid disease, were included in the study. Medical records of patients were reviewed for data obtained at their first visit to the clinic: serum thyroid-stimulating hormone (TSH), free thyroxine (T4), height, weight, demographic variables, clinical signs and symptoms of hypothyroidism, previous history of thyroid disease and treatment with thyroid medications, and current medications. RESULTS: Of the 283 patients with no previous history of thyroid disease, 15.4% of men and 14.6% of women had subclinical hypothyroidism (TSH levels of 5.0 to 14.9 microU/mL, and normal free T4 levels [0.7 to 2.0 ng/dL]). Overt hypothyroidism (TSH > or = 15.0 microU/mL, low free T4 < 0.7 ng/dL) was discovered and subsequently treated in one male and two female patients. There were no significant differences (P > .05) in the frequencies of any of the clinical signs and symptoms of hypothyroidism between euthyroid and hypothyroid patients. There was no significant relationship between TSH levels and the total number of hypothyroid symptoms experienced by all patients (r = -.004, P = .99). Logistic regression analyses determined that clinical signs and symptoms were poor predictors of subclinical hypothyroidism in these elderly patients. CONCLUSIONS: Thyroid status could not be predicted from clinical signs and symptoms in this sample of elderly community-dwelling patients. This finding substantiates the difficulty of diagnosing subclinical hypothyroidism in the elderly based solely on clinical features.

Aged↗

Purification and biochemical characterization of tubulin from the budding yeast Saccharomyces cerevisiae.

We describe a method for isolating milligram quantities of assembly-competent tubulin from the budding yeast Saccharomyces cerevisiae. The tubulin is > 95% purified and free of contaminating enzyme activities. As a result, it has been possible to determine the yeast tubulin equilibrium-binding constant for Mg-GTP and the tubulin GTPase activity under nonassembling and assembling conditions. We also determined the critical concentration for yeast tubulin polymerization and found it to be significantly lower than that for bovine brain tubulin under identical conditions. Similarly, the dynamic properties both of individual yeast microtubules and of bulk microtubule suspensions were significantly different from those of bovine brain microtubules free of microtubule-associated proteins. The data suggest that the properties of the yeast tubulin may reflect the particular functional requirements of the yeast cell. With this method, it is now possible to introduce any desired tubulin gene mutation into the budding yeast and correlate the phenotypic effects of the mutation in cells with the effects of the mutation on the biochemical and polymerization properties of the tubulin.

Binding Sites↗

Cloning of a unique human homologue of the Escherichia coli DNAJ heat shock protein.

A human homologue of the bacterial DNAJ heatshock protein, HDJ-2, was isolated from a human umbilical vein endothelial cDNA library using a monoclonal antibody which reacts specifically to human endothelial cells and monocytes. This cDNA clone consists of 1469 nucleotides with an open reading frame of 1191 nucleotides. HDJ-2 shares significant homology with Escherichia coli heat shock protein DNAJ, as well as the yeast homologues Sec63, YDJ1, SCJ1 and SIS1. This homology suggests HDJ-2 may be involved in protein folding and/or transport.

Amino Acid Sequence↗

Association of casein kinase 2 with nuclear chromatin in relation to androgenic regulation of rat prostate.

Casein kinase 2 (CK-2) is a ubiquitous messenger-independent protein serine/threonine kinase that has been implicated in growth control. We have studied the activity and subcellular location of CK-2 in adult rat ventral prostate in relation to androgen withdrawal and administration. Androgen deprivation by castration results in a faster decline in CK-2 activity associated with prostatic nuclei than that in the cytosol. Nuclear CK-2 associated with chromatin is reduced at an even greater rate than that in the total nucleus. Reversal of these events by administration of a single dose of 5 alpha-dihydrotestosterone to adult rats castrated 144 hr previously was accompanied by a differential early enhancement of chromatin-associated CK-2 activity, with a concomitant decrease in the CK-2 activity present in the cytosol. Changes in the nuclear CK-2 activity correlated with the immunostainable enzyme protein in the nucleus. We propose that androgens evoke translocation of CK-2 from the cytoplasm to the nucleus (nucleoplasm) where its enhanced association with the chromatin constituents takes place. Conversely, withdrawal of circulating androgens due to castration evokes a dissociation of CK-2 from chromatin and eventual translocation of nucleoplasmic CK-2 to the cytoplasm. Modulations in the association of CK-2 with nuclear chromatin may represent an important mechanism of post-transcriptional regulation of nuclear CK-2 in relation to androgen action in the prostate.

Amino Acid Sequence↗

Mutation of N-myc in mice: what does the phenotype tell us?

Oncogenesis is manifested as uncontrolled cellular proliferation and in some situations a failure of normal differentiation in the transformed cell. This has led to speculation that the normal role of proto-oncogenes during development may be to mediate the relationship between proliferation and differentiation. The advent of gene targeting in ES cells allows the role oncogenes in development to be tested directly. Two recent studies have examined the phenotype of N-myc mutant mice generated by gene targeting. In both reports, the mutation is an embryonic lethal at 11.5 days of gestation confirming a critical role for this proto-oncogene in development and the inability of other members of the myc family to substitute functionally for N-myc. Although the phenotypes are similar in general outline, the two reports differ in the specifics of the morphological and histological abnormalities identified. The disparity may result from the mutation created, the genetic background of the mutant mice or the criteria used to determine abnormalities. Assuredly, there is valuable information to be gained about N-myc function from these mutant mice. However, these reports make it clear that morphological and histological abnormalities in N-myc mutant mice serve as a starting point rather than as an endpoint. The challenge now is to link the defect at the cellular level to the abnormalities at the physiological level.

Animals↗

Analysis of faecal neutral sterols in patients with familial adenomatous polyposis by gas chromatography-mass spectrometry.

Previous studies have suggested that patients with familial adenomatous polyposis (FAP) have increased faecal excretion of cholesterol but a reduction in cholesterol metabolites. It was consequently proposed that the degree of faecal cholesterol degradation could be used as a means of diagnosis. Developments in the extraction and analysis of faecal neutral sterols as well as the accurate means of diagnosing FAP by DNA analysis and indirect ophthalmoscopy has necessitated a re-examination of this proposal. Faecal neutral sterols were analysed in 10 patients with untreated FAP following a complete 5-day stool collection and compared with 9 healthy control subjects (including 4 siblings) closely matched for age and sex. The median [25 and 75, percentiles] stool wet weights were similar between the FAP (97.5 [69, 192] g.24 h-1) and the control (116 [61.5, 137] g.24 h-1) groups. Faecal cholesterol concentration was similar in the two groups (FAP = 2.3 [1.4, 4.2]; control = 3.5 [1.0, 6.0] mumol.g-1 dry wt) as was the concentration of total neutral sterols not including plant sterols (FAP = 17.2 [13.4, 21.0]; control = 18.2 [7.4, 21.6] mumol.g-1 dry wt). There were no significant differences in the proportions of cholesterol metabolised between the FAP (82.3 [74.2, 93.5]%) and control (72.1 [5.7, 81.3]%) groups. This study does not support the notion that faecal neutral sterol metabolism is uniquely different in patients with FAP.

Adenomatous Polyposis Coli↗

The effect of capsaicin and conventional analgesics in two models of monoarthritis in the rat.

Systemic administration of capsaicin has been shown to be antinociceptive in a number of acute nociceptive models. We present here two models of prolonged hyperalgesia in the rat induced by intra-articular injection of uric acid or Freund's complete adjuvant into the knee. The time course of hyperalgesia lasts up to 48 h with uric acid and 5 to 10 days with Freund's adjuvant. The hyperalgesia was maximal in both models after 18 h. At this time, the weight tolerated by the injected leg was reduced by 70-80% in the Freund's-treated and 50-60% in the uric-treated animals, compared to the uninjected leg. The hyperalgesia was reversed in both models by indomethacin and ibuprofen (1-100 mg kg-1 s.c.), paracetamol (50-500 mg kg-1 s.c.) and morphine (2-16 mg kg-1 s.c.) in a dose-dependent manner. The morphine reversal was blocked by coadministration with naloxone (2.5 mg kg-1 s.c.). Capsaicin (3-9 mg kg-1 s.c.) also reversed the hyperalgesia in both models.

Animals↗

Phacoemulsification during the learning curve: risk/benefit analysis.

To assess prospectively the complications and outcomes in a single-surgeon series during the phacoemulsification learning curve a prospective analysis of 400 phacoemulsification procedures in 358 patients was carried out. The main outcome measures were capsular tear, vitreous and nuclear loss, best corrected post-operative visual acuity and refractive cylinder. Capsular tears occurred in 6.3% of phacoemulsification procedures, with vitreous loss in 1.5%. One nucleus was lost into the vitreous. Best corrected visual acuity, including pre-existing pathology, was 6/9 or better in 83.6% of eyes. There was 1 dioptre or less change of astigmatism from pre-operative to 6 weeks in 91% of eyes. It is concluded that phacoemulsification with careful patient selection can be a safe procedure even during the learning curve.

Aged↗

Mutations in the PAX6 gene in patients with hereditary aniridia.

The 14 exons of the PAX6 gene have been analysed exon-by-exon using SSCP in 6 aniridia families. In each family band shifts were observed on the SSCP gels for only one exon and direct PCR-sequencing revealed mutations in each case. Two mutations involved C-->T transitions in CGAarg codons in exons 9 and 11. Another C-->T transition converted a CAG-glutamine to a TAG-stop in exon 7. Small insertions created frameshifts which produced downstream stop codons in another two patients and an A-->T mutation disrupted the splice donor site of exon 5 in the remaining family. Thus, complete inactivation of the PAX6 gene is predicted in all cases. Analysis of other affected members of the families showed that, in each case, all affected individuals carried the same family-specific mutation. One polymorphism was found in exon 7. This data strongly supports the candidature of PAX6 as the gene responsible for hereditary aniridia.

Amino Acid Sequence↗

Paraspinal soft-tissue sarcoma. Classification of 14 cases.

Fourteen patients were treated surgically for soft-tissue sarcoma arising in the paraspinal muscles. Eleven patients received adjuvant irradiation administered before or after resection. In describing the treatment and outcomes of these patients, a new classification of paraspinal soft-tissue sarcoma is introduced that is based on the anatomic relationship of the tumor to the spinal lamina and the epidural space. This classification can be used in planning combined modality treatment for paravertebral sarcomas. Lesions that extend through the lamina into the epidural space present an unanswered problem for local control.

Adult↗

New drugs in pediatric dermatology.

A number of important therapeutic agents have recently become available for the treatment of infectious and inflammatory skin diseases. Five of these drugs, calcipotriol, EMLA (eutectic mixture of local anesthetics), interferon-alpha 2a, cyclosporine, and acyclovir, are reviewed. Calcipotriol, a vitamin D analogue, has been shown to be useful but not curative in chronic stable plaque psoriasis in adults. Its use in children is being studied. EMLA is proving to be useful in the prevention of pain prior to minor procedures. The use of interferon-alpha 2a promises to be highly effective in the treatment of the complications of vascular lesions. Cyclosporine is a powerful immunomodulating agent. It has been used in the treatment of atopic dermatitis and psoriasis. Adverse effects limit its widespread use as a systemic agent. Topical cyclosporine has limited efficacy due to its poor penetration. Acyclovir has revolutionized the treatment of herpes simplex virus infections, particularly in reducing the morbidity and mortality of neonatal herpes. Whether it is indicated in varicella infection in normal children is questionable.

Acyclovir↗

A medication discharge planning program: measuring the effect on readmissions.

Repeated hospitalizations result in high costs and may occur as a result of patient errors in their medication regimen. To reduce rehospitalizations (hospitalizations within 31 days of the previous discharge), health care professionals have turned to the discharge planning process. Using Orem's theory of self-care, a medication discharge planning program was developed to provide instruction on the requisites necessary for medication self-care. The purpose of this pilot study was to examine the effects of this program on readmissions within 31 days. Five nurses implemented the program for 54 patients with an admitting diagnosis of congestive heart failure. These patients were alternately assigned to a control or an experimental group. The experimental group received the medication discharge planning program. The control group received the usual informal discharge planning provided on the nursing unit. Eight (28.6%) of the 28 patients in the control group were readmitted within 31 days of the previous discharge. Two (7.7%) of the 26 patients in the experimental group were readmitted within 31 days. These results showed a statistically significant difference using Fisher's Exact Test (p = .05). Those receiving the medication discharge planning program were less likely to be readmitted, suggesting the importance of a medication discharge planning program.

Adult↗

The impact of hearing impairment on television viewing in the UK.

Just under one in 10 of a nationally representative sample of UK television viewers said that they experienced difficulty with their hearing. These hard-of-hearing viewers were found to report much greater difficulty watching programmes (mean difficulty rating = 32%) than elderly viewers with no reported hearing difficulty (mean difficulty rating = 10%), or those viewers generally who said they had no hearing problems (mean difficulty rating = 3%). Using a similarly constructed rating for reported enjoyment of different television programmes, hard-of-hearing viewers were found to exhibit a small reduction in enjoyment across the majority of programmes types. While it might have been anticipated that a greater proportion of those with impaired hearing owned a teletext television set giving them access to subtitling, this was not found to be the case. Across the sample as a whole, teletext ownership was shown to be 45%, but was lower than this (38.5%) amongst the hard-of-hearing. The findings corroborate what has been shown in another study, namely that teletext ownership is lower among older viewers. Hearing impairment, if it is not congenital or of early childhood origin, is a condition associated with increasing age. Thus, those whose viewing and appreciation of programmes might be enhanced by subtitles, in the main, do not have access to them. Among hard-of-hearing viewers who did have access to the teletext subtitle service, two thirds of those aged 51 years and over felt that subtitles assisted their understanding of television programmes. As one might expect, of those owning teletext, hard-of-hearing viewers reported greatest use of subtitles. Thirteen per cent of those with hearing difficulty and aged over 51 years said they used subtitles for all programmes watched and a further 26% of the over fifties with hearing difficulty reported regularly using subtitles for selected programmes. These data advocate that there are many hard-of-hearing viewers whose viewing could be enhanced by subtitling. Effort should be made to promote public and professional awareness of the availability of teletext subtitling and additional resources will be needed to combat the technophobia which may hinder older people from initially purchasing a teletext television set, or making effective use of one they already own.

Adolescent↗