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Biomedical subjects

C Lawrence

Publications and source records attributed to C Lawrence.

At least 91 records · Page 5Linked to original sources
PubMed1995

Appropriate place of death for cancer patients: views of general practitioners and hospital doctors.

BACKGROUND: The majority of cancer patients in the United Kingdom die in a National Health Service hospital, a setting that is contrary to the wishes of those patients expressing a preference to die elsewhere, for example at home or in a hospice. AIM: A study was undertaken to determine clinicians' views of the appropriate place of death for cancer patients and to examine factors leading to patients being admitted to a hospital specialist services unit where they died. METHOD: A questionnaire was sent to all general practitioners and hospital doctors who had cared for cancer patients who had died between May 1991 and April 1992 in a single health district. The appropriateness of the place of death, whether the patient was terminally ill, reasons for hospital admission and effect on management had different resources been available were determined. RESULTS: A total of 1022 deaths attributable to cancer were recorded for patients registered with general practitioners in the study area. Questionnaires were returned by general practitioners for 951 of the deaths (93%); hospital doctors returned questionnaires for 216 out of 268 patients (81%) who had been admitted to hospital under the care of a consultant. For deaths which had occurred at home, in a community hospital, residential/nursing home or Marie Curie hospice, the place of death was considered appropriate by general practitioners in over 92% of cases. For deaths in the hospital specialist services unit the place of death was considered probably or definitely appropriate by general practitioners in 83% of the 212 cases, but not appropriate in 17% of cases (P < 0.001 compared with all other settings). Hospital doctors considered 27% of deaths in the unit inappropriate. Significantly fewer cases fulfilled the criteria for terminal illness (death expected and palliative treatment commenced) according to general practitioners among those dying in the specialist services unit compared with deaths elsewhere (P < 0.001). The most common main reasons for admission to the specialist services unit were for investigation, because of difficult symptom control (apart from pain) and for curative/active treatment. General practitioners reported that management of between a sixth and a quarter of patients admitted to the specialist services unit would have been affected by the availability of 24-hour home cover, community hospital beds and a city-based hospice. Among the group of patients fulfilling the study criteria for terminal illness, the effect of other services on patient management would have been considerably higher. CONCLUSION: A greater proportion of cases where patients died from cancer in settings other than a specialist services unit were considered appropriate by general practitioners compared with deaths in a specialist services unit. For a considerable minority of patients, death in a specialist services unit was not considered appropriate by the general practitioners or by the hospital doctors. Improvements in local hospice facilities, community hospitals and community support would mean that a substantial proportion of hospital admissions could be avoided and thus cancer patients could die in more appropriate settings.

Home Care Services↗
PubMed1994

The RAD6 DNA repair pathway in Saccharomyces cerevisiae: what does it do, and how does it do it?

The RAD6 pathway of budding yeast, Saccharomyces cerevisiae, is responsible for a substantial fraction of this organism's resistance to DNA damage, and also for induced mutagenesis. The pathway appears to incorporate two different recovery processes, both regulated by RAD6. The error-prone recovery process accounts for only a small amount of RAD6-dependent resistance, but probably all induced mutagenesis. The underlying mechanism for error-prone recovery is very likely to be translesion synthesis. The error-free recovery process accounts for most of RAD6-dependent resistance, but its mechanism is less clear; it may entail error-free bypass by template switching and/or DNA gap filling by recombination. RAD6 regulates these activities by ubiquitinating target proteins, but the identities of these target proteins, and the roles they play in error-free and error-prone recovery, have not yet been established.

DNA Damage↗
PubMed1994

Rate of activation and deactivation of K:Cl cotransport by changes in cell volume in hemoglobin SS, CC and AA red cells.

Red blood cells (RBC) of subjects homozygous for hemoglobin A (AA), C (CC) and S (SS) exhibit different cell volumes which might be related to differences in cell volume regulation. We have investigated how rapidly K:Cl cotransport is activated and deactivated to regulate the cell volume in these cells. We measured the time course of net K+ efflux after step changes in cell volume and determined two delay times: one for activation by cell swelling and a second for deactivation by cell shrinkage. Cell swelling induced by 220 mOsm media activated K+ efflux to high values (10-20 mmol/liter cell x hr) in CC and SS; normal AA had a threefold lower activity. The delay time for activation was very short in blood with a high percentage of reticulocytes (retics): (SS, 10% retics, 1.7 +/- 0.3 min delay, n = 8; AA, 10% retics, 4 +/- 1.5 min, n = 3; CC, 11.6% retics, 4 +/- 0.3, n = 3) and long in cells with a smaller percentage of reticulocytes: (AA, 1.5% retics, 10 +/- 1.4 min, n = 8; CC whole blood 6% retics, 10 +/- 2.0 min, n = 10, P < 0.02 vs. SS). The delay times for deactivation by cell shrinking were very short in SS (3.6 +/- 0.4 min, n = 8, P < 0.02) and AA cells with high retics (2.7 +/- 1 min, n = 3) and normal retics (2.8 +/- 1 min, n = 3), but 8-15-fold longer in CC cells (29 +/- 2.8 min, n = 9). Density fractionation of CC cells (n = 3) resulted in coenrichment of the top fraction in reticulocytes and in swelling-activated cotransport (fourfold) with short delay time for activation (4 +/- 0.3 min) and long delay for deactivation (14 +/- 4 min). The delay time for activation, but not for deactivation, increased markedly with increasing cell density. These findings indicate that all CC cells do not promptly shut off cotransport with cell shrinkage and high rates of cellular K+ loss persist after return to isotonic conditions. In summary, (i) K:Cl cotransport is not only very active in young cells but it is also very rapidly activated and deactivated in young AA and SS cells by changes in cell volume. (ii) Delay times for cotransport activation markedly increased with RBC age and in mature cells with low cotransport rates, long delay times for activation were observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Size↗
PubMed1994

Toward the unification of sequence and structural data for identification of structural and functional constraints.

The identification and characterization of local residue patterns or conserved segments shared by a set of biopolymers has provided a number of insights in molecular biology. Biopolymer sequences are observations from macro molecules that share common structural or function features. The approach taken here rests on the notion that information may be most efficiently extracted from these observations through the use of a model that faithfully represents macro-molecular characteristics. Accordingly, our efforts are focused on statistical models which attempt to capture central features of protein structure, function, and change. Here the assumptions that underlie two new methods for the analysis of protein sequence data are explicitly delineated. (1) Threading of a sequence through structural motifs seeks to determine if a protein sequence fits a known protein structure. The assumptions delineated here also generally apply to other contact based threading methods that have been recently described. (2) Multiple sequence alignment via the Gibbs sampling algorithm seeks to identify position specific empirical free energy models for residue sites in common motifs and simultaneously the align sequence observations form these motifs.

Algorithms↗
PubMed1994

Effect of aspirin and nonsteroidal antiinflammatory drug therapy on bleeding complications in dermatologic surgical patients.

BACKGROUND: Aspirin and nonsteroidal antiinflammatory drugs (NSAIDs) inhibit platelet cyclooxygenase activity, resulting in altered platelet function and thus potentially enhanced bleeding. OBJECTIVE: We examined the frequency of operative bleeding complications in dermatologic surgical patients taking these drugs and the value of template bleeding time estimates in predicting this complication. METHODS: Bleeding time was measured with and without therapy in 23 patients and was correlated to bleeding complications after skin tumor or benign lesion excision in 40 patients taking aspirin, 21 taking NSAIDs, and 20 taking neither drug. RESULTS: Bleeding time dropped significantly (p < 0.01) when patients stopped therapy for at least 5 days (median, 7 days), although bleeding time was prolonged in only 6 of 16 patients taking aspirin and 2 of 7 taking NSAID. In patients who continued antiplatelet drugs during surgery, bleeding time was prolonged in 8 of 40 patients taking aspirin and in 1 of 21 treated with NSAIDs. Excessive intraoperative bleeding occurred in three aspirin-treated patients, all of whom had a prolonged bleeding time, compared with none of those with normal bleeding times (p < 0.001, Fisher's exact probability test) and with none of those taking NSAIDs. Postoperative ooze requiring a dressing replacement occurred in one NSAID-treated patient and in three patients taking neither drug. CONCLUSION: Bleeding time is increased by aspirin and NSAID therapy but is prolonged beyond the normal range in only approximately 25% of aspirin-treated and 10% of NSAID-treated patients. Intraoperative bleeding complications occurred only in patients receiving aspirin who had a prolonged bleeding time. Postoperative oozing occurred only in NSAID-treated and in untreated patients and thus is probably unrelated to antiplatelet therapy. Patients with a normal bleeding time can continue aspirin or NSAID therapy before dermatologic surgery.

Adult↗
PubMed1994

Prediction of final height in short, normal and tall children.

Measurements of final height were made on more than 4000 children in the final grade of school in Gothenburg in 1992; at the same time, mid-parental heights were recorded. These data were combined with other information (sex, length of gestation, size at birth, estimated age at peak height velocity (PHV) and height measurements made before 8 years of age) and used in a multiple regression analysis to assess the strength of the linear relationship between attained final height and these other potentially predictive measures of adult height. The R2 value increased from 0.16 at birth to 0.64 when the child was 8 years old. The inclusion of mid-parental height in the regression analysis contributed significantly to the explained variation in final height, especially at the earlier ages; the further addition of size at birth and age at PHV provides a small increase in the explained variation. The probability that the final height of a child will be below -2 or above +2 standard deviation scores (SDS) was assessed, based on previous SDS values for height when younger and on mid-parental height SDS. As a result of the large sample size included in the analyses, considerable confidence can be placed on the accurate prediction of final height values in the range -2.5 to +2.5 SDS.

Adolescent↗
PubMed1994

The influence of general practitioner community hospitals on the place of death of cancer patients.

All deaths from cancer were identified from death certificates in the Exeter Health District for a period of one year. Place of death, age, cancer type and access to general practitioner community hospital beds and the domiciliary hospice service were recorded. There were 1022 deaths attributable to cancer (parts 1a, 1b or 1c of the death certificate) who were patients of general practitioners in the health district. The place of death for patients with access to community hospital beds were: home 173/590 (29%), community hospital 232/590 (39%), specialist services unit 102/590 (17%), nursing or residential home 32/590 (5%), Marie Curie hospice 51/590 (9%). For patients without access to community hospital beds the place of death was: home 177/427 (41%), specialist service unit 165/427 (39%), nursing or residential home 42/427 (10%), Marie Curie hospice 43/427 (10%). The presence of community hospital beds was associated with a significant reduction of deaths in the specialist service unit (p < 0.001) and with a smaller reduction in home deaths (p < 0.01). Access to the domiciliary hospice services in areas with community beds was not associated with any significant change in the place of death. General practitioners cared for 74% of cases at the time of death in areas with access to community hospital beds and for 51% of cases without such access, which was a significant difference (p < 0.001). It therefore appears that community hospitals play a major role in the terminal care of cancer patients and access to such beds is associated with a decrease in cancer deaths occurring in specialist services beds.

Aged↗
PubMed1994

Molecular basis of human band-3 mutation associated with increased anion transport.

Band 3, the anion transporter, is a ubiquitous protein. It is present in brain and all other tissues. Not only is band 3 present in cell membranes, but also in nuclear, Golgi, and mitochondrion membranes. Band 3 is involved in respiration, acid-base balance, and is the major structural protein linking the plasma membrane to the cytoskeleton. Thus, alterations/mutations in the transport segment of the band-3 molecule might be expected to be of major importance. We discovered and sequenced a mutation of band 3, high-transport band 3 (HTbd3), that exhibits anion transport that is 2-3 time above normal. Anion transport studies of the family members revealed that red cells from the proposita, one of two siblings, and both parents had abnormally increased anion transport (increased Vmax). We used synthetic peptides of band 3 to help localize the change along the band-3 molecule. Results suggest that high-transport band 3 is altered in or near residue 869-883. This places the alteration toward the carboxyl terminal of band 3. cDNA sequencing demonstrated that the mutation was a proline to leucine at residue 868. A peptide was synthesized corresponding to residues 853-870 for testing in the anion transport inhibition assay. This peptide significantly inhibited anion transport (p < or = 0.001) indicating that it is an anion transport/binding region of band 3. Thus, DNA technology confirms the validity of the anion transport inhibition assay for localizing transport regions. Glucose transport is decreased in affected individuals. The HTbd3 mutation appears benign as determined by the red cell aging panel. IgG binding, creatinine, and glyceraldehyde-3-phosphate dehydrogenase are normal. Our studies indicate that the most rapid and sensitive techniques for detecting band-3 alterations are polyacrylamide gel electrophoresis, IgG binding, and anion transport studies. This is the only mutation of band 3 discovered to date the affects the transmembrane, anion transport region of band 3.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1993

Band 3 HT, a human red-cell variant associated with acanthocytosis and increased anion transport, carries the mutation Pro-868-->Leu in the membrane domain of band 3.

1. We have studied band 3 HT, a human red-cell band 3 variant with increased M(r), which is associated with abnormal red-cell shape (acanthocytosis) and increased anion-transport activity. 2. We have shown that the increased M(r) does not result from the presence of the band 3 Memphis mutation, and that the variant band 3 is covalently labelled by 4,4'-di-isothiocyanato-1,2-diphenylethane-2,2'-disulphonic acid (H2DIDS) less readily than normal. 3. cDNA cloning studies show that band 3 HT results from the mutation Pro-868-->Leu, and the possible significance of the mutation in the altered anion-transport activity and cytoskeleton binding properties of band 3 HT is discussed.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1993

Anabolic steroid abuse and cardiac death.

OBJECTIVE: To examine the relationship between anabolic steroid abuse and cardiac death. We report the first two cases in Australia. They are the only reported cases in which the anabolic steroid oxymesterone has been detected. This compound has never been approved for use in Australia. CLINICAL FEATURES: Two footballers, aged 18 and 24, sustained fatal cardiac arrests while at training sessions. Both were considered fit and healthy. OUTCOME: Autopsy revealed features of a hypertrophic cardiomyopathy in the 18-year-old; the 24-year-old had findings of a myocarditis. In both cases the coronary arteries were normal and there was no evidence of coronary thrombosis. Urine in both subjects contained the anabolic steroid oxymesterone. CONCLUSIONS: There are limited clinical uses for anabolic steroids but they are widely abused by athletes in attempts to alter lean body mass and strength. Acute non-fatal myocardial infarction was first reported in 1988 and fatal myocardial infarction in 1990. While a causal relationship is hard to prove, it is possible that the anabolic steroid contributed to the increase in cardiac size in the first subject and may have increased his responsiveness to catecholamines causing an arrhythmogenic event. In the second, the inflammatory changes could have provided the focus for an arrhythmia. It would appear that anabolic steroid abuse should be considered in any athlete presenting with an acute vascular event.

Adolescent↗
PubMed1993

The td intron endonuclease I-TevI makes extensive sequence-tolerant contacts across the minor groove of its DNA target.

I-TevI, a double-strand DNA endonuclease encoded by the mobile td intron of phage T4, has specificity for the intronless td allele. Genetic and physical studies indicate that the enzyme makes extensive contacts with its DNA substrate over at least three helical turns and around the circumference of the helix. Remarkably, no single nucleotide within a 48 bp region encompassing this interaction domain is essential for cleavage. Although two subdomains (DI and DII) contain preferred sequences, a third domain (DIII), a primary region of contact with the enzyme, displays much lower sequence preference. While DII and DIII suffice for recognition and binding of I-TevI, all three domains are important for formation of a cleavage-competent complex. Mutational, footprinting and interference studies indicate predominant interactions of I-TevI across the minor groove and phosphate backbone of the DNA. Contacts appear not to be at the single nucleotide level; rather, redundant interactions and/or structural recognition are implied. These unusual properties provide a basis for understanding how I-TevI recognizes T-even phage DNA, which is heavily modified in the major groove. These recognition characteristics may increase the range of natural substrates available to the endonuclease, thereby extending the invasive potential of the mobile intron.

Base Sequence↗