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Biomedical subjects

J Nettleton

Publications and source records attributed to J Nettleton.

10 recordsLinked to original sources
PubMed2000

Junior doctors' views on clinical audit--has anything changed?

A postal questionnaire survey of junior doctors' views was conducted in a large acute hospital in the south-east of England, amongst 146 junior medical staff recorded as being employed by the Trust across 21 specialities. It profiled their level of participation in audit and the quality of current audit programmes within their specialities and assessed their knowledge and understanding of clinical governance. Our findings suggest: a high level of involvement in activities labelled audit, but that these activities did not necessarily conform to robust audit methodologies; that junior doctors' professional attitudes towards clinical audit are influenced by negative experience of undertaking audit within their specialities; and that there was a variety of understanding about the principles and meaning of clinical governance. It concluded that the conditions for coherent strategy aimed at promoting effective audit programmes which could support the use of clinical audit as a tool for continuous professional development are not yet in place across the Trust.

Attitude of Health Personnel↗
PubMed1998

Facilitating effective learning during clinical placement.

The aim of this pilot study was to employ a qualitative research methodology to explore students' perceptions of learning and assessment of that learning whilst on clinical placement. The students' perceptions were sampled by questionnaire both pre- and post-placement (ten weeks block placement). The analysis of the data was undertaken using principles from Grounded Theory (Strauss and Corbin 1990). The analysis yielded a number of categories and bipolar paradigms relating to learning and assessment. However little change was seen between comments made pre and post-placement. The implications of this analysis are discussed.

Educational Measurement↗
PubMed1996

Breast cancer during pregnancy: quantifying the risk of treatment delay.

OBJECTIVE: To quantify the risk of axillary nodal metastases due to delayed treatment of breast cancer during pregnancy. METHODS: A mathematical model using recently published data was developed to correlate primary breast tumor size with the percentage of pathologically positive axillary lymph nodes. Using this relationship obtained from pathologic data and the accepted relationship of tumor growth and time, Y2 = Y1e(In2)n/DT, an equation estimating the increased risk of axillary metastases due to each day of treatment delay was derived: delta X = 3.7 n/DT, where X = percent positive axillary lymph nodes, n = number of days delay in treatment, and DT = tumor doubling time. RESULTS: A 1-month delay in treatment for an early-stage primary breast cancer with a 130-day doubling time increases the risk of axillary lymph node involvement by 0.9%. A 3-month delay increases the risk by 2.6%, and a 6-month delay by 5.1%. For breast cancer with a 65-day doubling time, a 1-month delay increases the risk by 1.8%, a 3-month delay by 5.2%, and a 6-month delay by 10.2%. CONCLUSION: Axillary lymph nodes are the most important prognostic indicator for survival in breast cancer. Our mathematical model suggests the daily increased risk of axillary metastases due to treatment delay is 0.028% for tumors with moderate doubling times of 130 days and 0.057% for tumors with rapid doubling times of 65 days. This minimal maternal risk may be acceptable to some third-trimester pregnant women with early breast cancer, who prefer organ-sparing treatment with radiation after delivery to a mastectomy during pregnancy. This model further quantitates the increased risk of mortality borne by pregnant women whose breast cancer diagnosis is delayed.

Axilla↗
PubMed1993

Proteus mirabilis biofilms and the encrustation of urethral catheters.

Bacterial biofilms were observed on 69 of 75 catheters taken from patients undergoing long-term bladder management. Ten catheters were colonized by pure cultures of Proteus mirabilis. In each of these cases the bacteria formed layers on the catheter surface, underlying encrustations of struvite and hydroxyapatite which partially or completely occluded the catheter lumen. Encrustation was also apparent on catheters colonized by P. mirabilis plus other species, but was rarely seen on catheters colonized by non-urease-producing species. These observations support the hypothesis that catheter encrustation is brought about by the activity of urease-producing biofilms and confirms that the main target in the control of catheter encrustation should be P. mirabilis.

Catheterization↗
PubMed1993

Flexural rigidity of microtubules and actin filaments measured from thermal fluctuations in shape.

Microtubules are long, proteinaceous filaments that perform structural functions in eukaryotic cells by defining cellular shape and serving as tracks for intracellular motor proteins. We report the first accurate measurements of the flexural rigidity of microtubules. By analyzing the thermally driven fluctuations in their shape, we estimated the mean flexural rigidity of taxol-stabilized microtubules to be 2.2 x 10(-23) Nm2 (with 6.4% uncertainty) for seven unlabeled microtubules and 2.1 x 10(-23) Nm2 (with 4.7% uncertainty) for eight rhodamine-labeled microtubules. These values are similar to earlier, less precise estimates of microtubule bending stiffness obtained by modeling flagellar motion. A similar analysis on seven rhodamine-phalloidin-labeled actin filaments gave a flexural rigidity of 7.3 x 10(-26) Nm2 (with 6% uncertainty), consistent with previously reported results. The flexural rigidity of these microtubules corresponds to a persistence length of 5,200 microns showing that a microtubule is rigid over cellular dimensions. By contrast, the persistence length of an actin filament is only approximately 17.7 microns, perhaps explaining why actin filaments within cells are usually cross-linked into bundles. The greater flexural rigidity of a microtubule compared to an actin filament mainly derives from the former's larger cross-section. If tubulin were homogeneous and isotropic, then the microtubule's Young's modulus would be approximately 1.2 GPa, similar to Plexiglas and rigid plastics. Microtubules are expected to be almost inextensible: the compliance of cells is due primarily to filament bending or sliding between filaments rather than the stretching of the filaments themselves.

Actin Cytoskeleton↗
PubMed1991

Block of single batrachotoxin-activated Na+ channels by clofilium.

The effects of clofilium on single batrachotoxin-activated Na+ channels from rabbit skeletal muscle, incorporated into planar bilayers, were studied under symmetrical 200 mM NaCl conditions. Internally applied clofilium (0.3-30 microM) induced long lasting closures, with a mean duration of approximately 450 msec at +50 mV. The fraction of time spent in the clofilium-induced closed state was concentration dependent, with an equilibrium dissociation constant (Kd) of 3.4 microM at +50 mV. Kinetic analysis showed that both open and closed time distributions were well described by single exponentials, with respective time constants of tau o and tau C. As expected for an open channel blocker, 1/tau o increased linearly with increasing clofilium concentration, whereas 1/tau c remained relatively constant. Inhibition of batrachotoxin-activated Na+ channels by clofilium exhibited a strong voltage dependence. The binding affinity of clofilium increased about 10-fold upon depolarization from -50 mV to 50 mV. Competition studies using quaternary and tertiary local anesthetics showed that clofilium and local anesthetics probably share a common receptor site located about halfway across the membrane electrical field. Together, our results demonstrate that clofilium is a potent Na+ channel blocker in bilayers and its action is similar to that of other local anesthetics characterized previously.

Animals↗
PubMed1990

pH-dependent binding of local anesthetics in single batrachotoxin-activated Na+ channels. Cocaine vs. quaternary compounds.

The effects of internal and external pH on the binding kinetics of local anesthetics (LAs) were studied in single batrachotoxin-activated Na+ channels incorporated into planar bilayers. With internal quaternary QX-314 and RAC421-II drugs, the binding interactions were little affected by either external or internal pH. With tertiary cocaine, the binding kinetics were drastically altered by pH. A decrease in the internal pH from 9.3 to 6.2 decreased the apparent equilibrium dissociation constant (Kd) of internal cocaine by more than 100-fold. This increase in the binding affinity was mostly accounted for by an increase in the apparent cocaine on-rate constant (kon) of approximately 80-fold. The cocaine off-rate constant (koff) was little changed (between 3-4 s-1). These results demonstrate quantitatively that the charged form of cocaine is the active form for BTX-activated Na+ channels. Surprisingly, the apparent pKa of cocaine near its binding site was estimated to be 1.4 units lower than that in bulk solution (7.1 vs. 8.5), indicating that the LA drug encounters a relatively hydrophobic environment. Opposite to the internal pH effect, a decrease of external pH from 8.4 to 6.2 increased the Kd value of internally and externally applied cocaine by approximately 8- and approximately 25-fold, respectively. External pH effect was primarily mediated by modulation of kon; koff was again relatively unaffected. Our findings support a model in which neutral cocaine can readily cross the membrane barrier, but needs to be protonated internally to bind to its binding site.

Anesthetics, Local↗
PubMed1981

A novel human T cell antigen preferentially expressed on mature T cells and shared by both well and poorly differentiated B cell leukemias and lymphomas.

A new lymphocyte differentiation antigen shared by all normal T cells and some malignant B cells was defined by a monoclonal antibody designated 12.1. This antibody reacted with all peripheral blood T cells but not with normal B cells and B cell lines. Analysis with a fluorescence activated cell sorter showed that the expression of 12.1 antigen changes during T cell maturation. Most thymocytes, blasts of acute T cell leukemia, and cells from established leukemic T cell lines bear a small amount of 12.1 antigen. In contrast the majority of peripheral blood T cells, activated T cells, and leukemic T cells of the Sezary syndrome bear a large amount of 12.1 antigen. Unexpectedly, antibody 12.1 reacted with leukemic cells from most patients with B-type chronic lymphocytic leukemia (CLL) and some patients with lymphosarcoma cell leukemia (LSCL). Among these leukemias, expression of the 12.1 antigen was not correlated with the stage of B cell maturation, with the amount of surface immunoglobulin on the cells, or with the presence or absence of monoclonal gammapathy. In a comparative serologic analysis the antigen defined by antibody 12.1 was distinct from the p67 T cell antigen (defined by monoclonal antibody 10.2) that is also known to be expressed by B-type CLL cells.

Acute Disease↗