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Biomedical subjects

C Lawrence

Publications and source records attributed to C Lawrence.

At least 73 records · Page 4Linked to original sources
PubMed1996

Anti-inflammatory 17beta-thioalkyl-16alpha,17alpha-ketal and -acetal androstanes: a new class of airway selective steroids for the treatment of asthma.

The synthesis and anti-inflammatory potencies of a new class of 17beta-thioalkyl-16alpha,17alpha-ketal and -acetal androstanes are described. This new class of steroids was made by fragmentation of 2-thioxo-1,2-dihydropyrid-1-yl esters of the corresponding 17-acids to the 17-radical. The radical generated was trapped using a variety of radicophilic disulfides, giving a steroidal D-ring having acetal or ketal functionality at C-16 and C-17, together with a sulfide link at C-17. Compounds from this series bind to the glucocorticoid receptor with high potency and are functional agonists as measured by their ability to induce tyrosine aminotransferase activity in a rat hepatic cell line in vitro. These 17beta-thioalkyl androstanes potently inhibit Sephadex-induced rat lung inflammation when administered directly into the airways. The high topical potency, together with a low propensity to induce systemic glucocorticoid-like side effects (rat thymus involution), provides the present compounds with a high degree of airway selectivity compared with currently available inhaled glucocorticoids. The presently described 17beta-thioalkyl-16alpha,17alpha-ketal androstanes may be useful for therapies for inflammatory diseases such as asthma.

Androstanes↗
PubMed1996

Beta-globin gene haplotype in Hb SC disease.

We asked the question, is the haplotype found with the sickle hemoglobin gene associated with different hematological characteristics in patients who were combined heterozygotes for sickle hemoglobin and hemoglobin C (Hb SC disease)? In 73 adults with Hb SC disease, a Benin haplotype chromosome was present in 56%, and Bantu (or Central African Republic; CAR), Senegal, and atypical haplotype chromosomes were found in 25%, 6%, and 12%, respectively. No significant difference were found in hematological characteristics or fetal hemoglobin levels of patients with Benin/C, CAR/C, Senegal/C, and atypical/C haplotypes. There were 71% C I, 18% C II, and 11% other beta(c) haplotypes. Fetal hemoglobin levels are lower in Hb SC disease than in sickle-cell anemia. Perhaps because haplotype has no discernible effect on fetal hemoglobin level in Hb SC disease, it does not modulate its hematological features.

Adult↗
PubMed1996

Reappraisal of Thomas Lewis's place in the history of electrocardiography.

Thomas Lewis is among the most significant figures in the history of electrocardiography. In the late 1920s, he abandoned electrocardiography for other areas that he considered to be clinical science, in spite of the fact that he had made great contributions to the then new technique and that interest in this technique was increasing worldwide. The reasons why Lewis left electrocardiography are discussed further here. Lewis's leaving of electrocardiography had as much influence on the history of electrocardiography as did his practice of it.

Electrocardiography↗
PubMed1996

Consecutive isolation of homologous strains of methicillin-resistant and methicillin-susceptible Staphylococcus aureus from a hospitalized child.

A multiply resistant, methicillin-resistant Staphylococcus aureus was repeatedly isolated from the anterior nares of a premature neonate hospitalized in an intensive-care unit and treated with multiple courses of antibiotics. Two months following cessation of antibiotic therapy, a strain of S. aureus with a similar antibiotic resistance profile, but susceptible to methicillin, was isolated from three consecutive nasal swabs. Total DNA of the methicillin-susceptible and -resistant isolates was digested with SmaI and resolved by pulsed-field gel electrophoresis. The SmaI restriction profile of the susceptible isolate was similar to that of the resistant one except for the replacement of a 207-kb fragment by a 147-kb fragment. In Southern hybridization, a mecA-specific probe hybridized to the 207-kb SmaI fragment of the methicillin-resistant strain but not to DNA of the susceptible strain. These results suggest that loss of the mecA gene can occur in vivo when antibiotic selective pressure is removed.

Base Sequence↗
PubMed1996

Use of the coagulase gene typing method for detection of carriers of methicillin-resistant Staphylococcus aureus.

Strains of Staphylococcus aureus can be typed on the basis of the polymorphism of the coagulase gene. DNA fragments generated after amplification by polymerase chain reaction (PCR) of the variable region of this gene and digested with the restriction enzyme HaeIII can be compared by their restriction fragment length polymorphism (RFLP). Seventy-nine of 86 (91.8%) methicillin-resistant S. aureus (MRSA) strains isolated in various hospitals had a characteristic RFLP pattern. This pattern differed from those of 32 methicillin-susceptible S. aureus (MSSA). Only one MSSA shared with MRSA the same RFLP pattern. After modification, we applied this method to the rapid detection of MRSA from 255 nasal swabs from patients hospitalized in intensive care units. When screened by plating on Chapman agar, 55 of these samples contained MRSA, whereas 40/55 yielded the expected restriction profile after amplification by PCR. No DNA was amplified by PCR in 9/55 samples and restriction profiles were uninterpretable in six cases. When compared to culture, the positive and negative predictive values of the PCR test were 100% and 93%, respectively. The specificity was 100% and the sensitivity was 72.7%. Since control of spread of MRSA strains in hospitals is based in part on rapid isolation of carriers, this method which allows detection of epidemic MRSA in nasal swabs within a day could be helpful, though culture would still be necessary to confirm the result.

Bacterial Typing Techniques↗
PubMed1996

Prospective, randomized trial of two antiseptic solutions for prevention of central venous or arterial catheter colonization and infection in intensive care unit patients.

OBJECTIVES: To compare the efficacy of a newly available antiseptic solution (composed of 0.25% chlorhexidine gluconate, 0.025% benzalkonium chloride, and 4% benzyl alcohol), with 10% povidone iodine, on the prevention of central venous or arterial catheter colonization and infection. DESIGN: Prospective, randomized clinical trial. SETTING: Surgical-trauma intensive care unit (ICU) in a university hospital. PATIENTS: All patients admitted to the ICU and requiring the insertion of a central venous and/or an arterial catheter from July 1, 1992 to October 31, 1993. INTERVENTIONS: Patients were randomly assigned to one of two groups according to the antiseptic solution used for insertion and catheter care. The same solution was used for skin disinfection from the time of catheter insertion to the time of removal of each catheter. MEASUREMENTS AND MAIN RESULTS: Catheter distal tips were quantitatively cultured when catheters were no longer necessary, if there was a suspicion of catheter-related infection, and routinely after 7 days of use for arterial catheters, or after 15 days of use for central venous catheters. The rate of significant catheter colonization (i.e., > or = 10(3) colony-forming units [cfu]/mL by quantitative culture), and catheter-related sepsis (as defined by sepsis abating following catheter removal per 1,000 catheter-days), were significantly lower in the chlorhexidine group (12 vs. 31 [relative risk 0.4, 95% confidence interval 0.1 to 0.9, p < .01] and 6 vs. 16 [relative risk 0.4, 95% confidence interval 0.1 to 1, p = 0.5], respectively). The rate of central venous catheter colonization and central venous catheter-related sepsis per 1,000 catheter-days were also significantly lower in the chlorhexidine group (8 vs. 31 [relative risk 0.3, 95% confidence interval 0.1 to 1, p = .03] and 5 vs. 19 [relative risk 0.3, 95% confidence interval 0.1 to 1, p = .02], respectively). Finally, the rate of arterial catheter colonization per 1,000 catheter-days was significantly lower in the chlorhexidine group (15 vs. 32 [relative risk 0.5, 95% confidence interval 0.1 to 1, p = .05]), whereas the rate of arterial catheter-related sepsis per 1,000 catheter-days was similar for the two study groups (8 in the chlorhexidine group vs. 10 in the povidone iodine group [relative risk 0.8, 95% confidence interval 0.1 to 2.2, p = .6]). The 0.25% chlorhexidine solution was superior to the 10% povidone iodine solution in preventing catheter colonizations and catheter-related sepsis due to Gram-positive bacteria (5 vs. 20 [p < .001], and 2 vs. 10 [p < .001], respectively), whereas the activity of the 0.25% chlorhexidine solution was nonsignificantly superior in preventing Gram-negative infections (7 vs. 4 [p = .5], and 4 vs. 2 [p = .8], respectively). CONCLUSIONS: The 4% alcohol-based solution of 0.25% chlorhexidine gluconate and 0.025% benzalkonium chloride was more effective than 10% povidone iodine for insertion site care of short-term central venous and arterial catheters. This effect appeared related to a more efficacious prevention of infections with Gram-positive bacteria.

Adult↗
PubMed1996

Characteristics of referrals to an inpatient hospice and a survey of general practitioner perceptions of palliative care.

In order to determine symptoms, drug prescribing and physical problems of patients referred to an inpatient hospice, case notes from 130 consecutive first admissions (95 general practitioner (GP) referrals, 35 consultant referrals) were analysed. GP referrals were more likely to be constipated, require care and be discharged to home. Consultant referrals were more gravely ill, dependent and more likely to die in the hospice. On admission 76 (58%) patients were receiving opiates with co-prescription of opiate and laxative occurring in 41% (31/76) of the cases. The prescription of laxatives with the symptoms of constipation occurred in 62% (26/42) of the cases on admission. A telephone survey of 79 referring GPs revealed that 37% had attended neither a course nor a lecture relevant to palliative care in the past 3 years. GPs experienced difficulties frequently or always in: (a) managing pain (8/79); (b) managing other symptoms (25/79); (c) helping patients and relatives cope with their emotional distress (18/79); and (d) coping with their own emotional responses to death and dying (5/79). In conclusion, the differences demonstrated between the GP and consultant referrals have implications for purchasers. The high incidence of possible opiate-induced side-effects and the difficulties with symptom control expressed by some GPs indicate a continuing need for effective educational input.

Analgesics↗
PubMed1996

Drug management in skin surgery.

Lidocaine (lignocaine) 1% with epinephrine (adrenaline) 1:200,000 (maximum dose 40mL) is the agent of choice in skin surgery. It can be used at all sites except the fingers, toes and penis, where epinephrine should be avoided. Epinephrine-induced vasoconstriction delays local anaesthetic clearance, thus prolonging its effect and, by reducing peak blood lidocaine concentrations, enables a higher maximum dose to be used. Adding epinephrine, however, introduces the possibility of a drug interaction with tricyclic antidepressants and nonselective beta-blockers. Also, injection pain is greater because of the acidic sodium metabisulphite that has to be added to prevent epinephrine oxidation. Injection pain can be reduced by buffering the solution using sodium bicarbonate. There are no drug interactions that prevent the use of plain lidocaine: injection pain is least with 0.5% solutions. Injection of large volumes of very dilute lidocaine solutions (tumescent anaesthesia) enables higher maximum doses of lidocaine to be tolerated and large areas to be anaesthetised by infiltration. Amethocaine gel is a faster acting and more effective topical anaesthetic compared with eutectic lidocaine-prilocaine cream, but is a topical sensitiser. In high risk patients, prophylactic antibiotics should be given to prevent bacterial endocarditis when operating on infected lesions and on potentially colonised crusted lesions in high-risk patients (i.e. those with prosthetic heart valves). Wound infections following surgery on infected skin lesions can be prevented by the prophylactic use of mupirocin ointment. Aspirin-induced inhibition of platelet adhesion results in bleeding complications in approximately 15% of skin surgery patients receiving aspirin. Patients whose bleeding time is > 8 minutes are particularly at risk, and aspirin should be stopped at least 7 days prior to surgery in these patients. Aspirin can be continued in other patients without serious bleeding complications.

Anesthetics, Local↗
PubMed1995

Differential sensitivity of stilbenedisulfonates in their reaction with band 3 HT (Pro-868-->Leu).

Band 3 HT (Pro-868-->Leu) is a mutant anion exchange protein which has several phenotypic characteristics, including a 2- to 3-fold larger Vmax, and reduced covalent binding of the anion transport inhibitor 4,4'-diisothiocyanodihydrostilbene-2,2'-disulfonate (H2DIDS). We have used fluorescence kinetic methods to study inhibitor binding to band 3 to determine if the point mutation in band 3 HT produces localized or wide-spread conformational changes within the membrane-bound domain of this transporter. Our results show that covalent binding of H2DIDS by band 3 HT is slower by a factor of 10 to 20 compared with the wild-type protein. In contrast, no such difference in the kinetics was observed for covalent binding of 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS). In addition, the kinetics of H2DIDS release from band 3 HT was abnormal, while the kinetics of 4,4'-dibenzamidostilbene-2,2'-disulfonate (DBDS) release showed no difference when compared with the wild-type protein. We conclude that substitution of leucine for proline at position 868 does not perturb the structure of "lysine A" in the membrane-bound domain of band 3 but rather produces an apparently localized conformational change in the C-terminal subdomain of the protein which alters H2DIDS affinity. When combined with the observation of an increased Vmax, these results suggest that protein structural changes at position 868 influence a turnover step in the transport cycle.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1995

Can Matrigel substitute for Vero cells in promoting the in-vitro development of mouse embryos?

The influences of Vero cells and the basement membrane substratum for these cells (Matrigel) on the rate of hatched blastocyst formation from mouse zygotes in vitro were compared. Zygotes obtained from C57BL/6 x BALB/c F1 females pretreated with pregnant mare's serum gonadotrophin/human chorionic gonadotrophin mated with BDF1 males were cultured (120 h) in human tubal fluid medium supplemented 0.5% with bovine serum albumin. The rates of early hatching and hatched blastocyst formation at 96 and 120 h of culture were expressed as the percentage of 2-cell embryos visualized after the initial 24 h. The rate of total blastocyst formation did not differ between treatment groups. However, < 10% of embryos cultured for 96 h in medium alone advanced to the hatching stage compared with 35-40% of blastocysts cultured with Vero cells or with Matrigel alone. Similarly, by 120 h of culture, only 20% of embryos cultured in medium alone developed to hatching or hatched blastocysts compared with > 70% for those embryos co-cultured with Vero cells or with Matrigel. In conclusion, Vero cells improved the rate of development of mouse embryos to hatched blastocysts during serum-free culture. Similar improvements were seen in the presence of Matrigel alone; Matrigel is the basement membrane substratum used for the Vero cells. Further studies on the means whereby Matrigel promotes early embryonic development (e.g. appropriate combination of basement membrane-associated growth factors) may lead to a safe, defined medium preparation for the stimulation of in-vitro development of human embryos.

Animals↗
PubMed1995

Seronegative chronic relapsing neuroborreliosis.

We report an unusual patient with evidence of Borrelia burgdorferi infection who experienced repeated neurologic relapses despite aggressive antibiotic therapy. Each course of therapy was associated with a Jarisch-Herxheimer-like reaction. Although the patient never had detectable free antibodies to B. burgdorferi in serum or spinal fluid, the CSF was positive on multiple occasions for complexed anti-B. burgdorferi antibodies, B. burgdorferi nucleic acids and free antigen.

Anti-Bacterial Agents↗
PubMed1995

Fulminating systemic capillary leak syndrome with lymphocytosis and hypogammaglobulinemia.

We report a case of fulminating systemic capillary leak syndrome which temporarily responded to verapamil, a calcium channel blocker. We noted two features of the disease not previously reported: a rise in lymphocyte count 2-3 days prior to an attack, and hypogammaglobulinemia. These findings are discussed in relation to the possible etiology of this disease.

Agammaglobulinemia↗
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↗