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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
PubMed1997

RPR 106541, a novel, airways-selective glucocorticoid: effects against antigen-induced CD4+ T lymphocyte accumulation and cytokine gene expression in the Brown Norway rat lung.

1. The effects of a novel 17-thiosteroid, RPR 106541, were investigated in a rat model of allergic airway inflammation. 2. In sensitized Brown Norway rats, challenge with inhaled antigen (ovalbumin) caused an influx of eosinophils and neutrophils into the lung tissue and airway lumen. In the lung tissue there was also an accumulation of CD4+ T lymphocytes and increased expression of mRNA for interleukin-4 (IL-4) and IL-5, but not interferon-gamma (IFN-gamma). These findings are consistent with an eosinophilia orchestrated by activated Th2-type cells. 3. RPR 106541 (10-300 microg kg[-1]), administered by intratracheal instillation into the airways 24 h and 1 h before antigen challenge, dose-dependently inhibited cell influx into the airway lumen. RPR 106541 (100 microg kg[-1]) caused a significant (P<0.01) (98%) inhibition of eosinophil influx and a significant (P<0.01) (100%) inhibition of neutrophil influx. RPR 106541 was approximately 7 times and 4 times more potent than budesonide and fluticasone propionate, respectively. 4. When tested at a single dose (300 microg kg[-1]), RPR 106541 and fluticasone each caused a significant (P<0.01) (100%) inhibition of CD4+ T cell accumulation in lung tissue. Budesonide (300 microg kg[-1]) had no significant effect. RPR 106541 and fluticasone (300 microg kg[-1]), but not budesonide (300 microg kg[-1]), significantly (P<0.05) inhibited the expression within lung tissue of mRNA for IL-4. RPR 106541 (300 microg kg[-1]) also significantly (P<0.05) inhibited expression of mRNA for IL-5. 5. The high topical potency of RPR 106541 in this model, which mimics important aspects of airway inflammation in human allergic asthmatics, suggests that this glucocorticoid may be useful in the treatment of bronchial asthma.

Androstadienes↗
PubMed1997

Sudden cardiac death in familial hypertrophic cardiomyopathy: are "benign" mutations really benign?

Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disorder characterised predominantly by left ventricular hypertrophy and sudden cardiac death. Mutations in the cardiac beta-myosin heavy chain gene have been identified in several families and designated as "benign" or "malignant". We describe a family (family L) with a "benign" mutation in which early sudden cardiac death has occurred. The family was studied by clinical, electrocardiographic and echocardiographic assessment. DNA analysis involved screening for the six most common cardiac beta-myosin heavy chain gene mutations using allele specific oligonucleotide probes and restriction enzyme analysis. The Val606Met missense mutation was found. This mutation has been described in four families as being "benign" since it was associated with low penetrance and a near normal life span. Sudden cardiac death was an infrequent finding. In contrast, family L has a more malignant clinical picture with one sudden death in three affected individuals. The proband died suddenly at age 14 years during exercise. Designating gene mutations in FHC as benign or malignant has major clinical implications. As these mutations have only been described in a limited number of families, caution needs to be taken when interpreting genotype-phenotype correlations in this disorder.

Cardiomyopathy, Hypertrophic↗
PubMed1997

Bayesian adaptive alignment and inference.

Sequence alignment without the specification of gap penalties or a scoring matrix is attained by using Bayesian inference and a recursive algorithm. This procedure's recursive algorithm sums over all possible alignments on the forward step to obtain normalizing constants essential to Bayesian inferences, and samples from the exact posterior distribution on the backward step. Since both terminal and intervening unrelated subsequences will often be excluded from an alignment, the resulting alignments may be seen as extensions of local alignments. An alignment's significance is assessed using the Bayesian evidence. A shuffling simulation shows that Bayesian evidence against the null hypothesis tends to be a conservative measure of significance compared to classical p-values. An application to proteins from the GTPase superfamily shows that the posterior distribution of the number of gaps is often flat and that the posterior distribution of the evolutionary distance is often flat and sometimes bimodal. An alignment of 1GIA with 1ETU shows good correspondence with a structural alignment.

Algorithms↗
PubMed1997

Placement of cardiac electrodes: written, simulated, and actual accuracy.

BACKGROUND: Research has shown that critical care nurses show low accuracy on written tests of placement of electrodes, yet it is unknown how this low accuracy translates into placement of electrodes on actual patients. OBJECTIVES: To determine if accuracy scores differ between three methods (written knowledge, simulated clinical practice, actual clinical practice) of evaluating placement of continuous ECG electrodes by a group of cardiac care nurses. METHODS: A standardized scoring diagram was used with three different methods of measuring the accuracy of 44 nurses who worked on a telemetry unit or medical ICU in placing continuous ECG electrodes. The three methods were (1) written knowledge--placement of stickers on a diagram of a torso, (2) simulated clinical practice--placement of electrodes on a human model, and (3) actual clinical practice--placement of electrodes on an assigned patient. RESULTS: For the total diagram score (maximum score = 11), no significant differences among groups were found. For the V1 subscale score (maximum score = 4), a significant difference among groups was found: Scheffé's test showed that the significant difference was between simulated and actual clinical practice. Percentages of nurses achieving the maximum, or accurate, score were 18% for written knowledge, 25% for simulated clinical practice, and 9% for actual clinical practice. CONCLUSIONS: Although total scores did not differ among groups, the mean scores indicate that placement of electrodes was not accurate by any method. This finding has implications for how electrode placement is taught to nurses and for the accountability of nurses for placement of electrodes on their patients.

Clinical Competence↗
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↗