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Biomedical subjects

C Williams

Publications and source records attributed to C Williams.

At least 127 records · Page 7Linked to original sources
PubMed2000

Tethered blockers as molecular 'tape measures' for a voltage-gated K+ channel.

The propagation of electrical signals in excitable cells is orchestrated by a molecular family of voltage-dependent ion channel proteins. These K+, Na+, and Ca++ channels are all composed of four identical or similar units, each containing six transmembrane segments (S1-S6) in a roughly four-fold symmetric structure. The S5-S6 sequences fold into a central pore unit, which is surrounded by a voltage-gating module composed of S1-S4. The recent structure of KcsA, a two-transmembrane bacterial K+ channel, illuminates the physical character of the pore unit, but little is known about the arrangement of the surrounding S1-S4 sequences. To locate regions of this gating module in space, we synthesized a series of compounds of varying length that function as molecular 'tape measures': quaternary ammonium (QA) pore blockers that can be tethered to specific test residues. We show that in a Shaker K+ channel, the extracellular ends of S1 and S3 are approximately 30 ¿ from the tetraethylammonium (TEA) blocking site at the external opening of the pore. A portion of the S3-S4 loop is, at 17-18 ¿, considerably closer.

Amino Acid Substitution↗
PubMed2000

A surgical career? The views of junior women doctors.

OBJECTIVE: To explore female pre-registration house officers (PRHOs) views of surgery as a possible career choice. DESIGN AND PARTICIPANTS: In this qualitative study in-depth semistructured interviews were carried out with 15 female PRHOs. They were part of a larger sample of 24 PRHOs (15 women and nine men) who were being interviewed primarily to explore their ways of learning in both hospital and general practice settings. This paper focuses on the responses of the 15 women in relation to surgery as a possible career choice. METHODS: Interviews incorporated a checklist of topics to encourage participants to discuss their experiences of learning and working as PRHOs, including factors which had impacted on future career choices. Common themes were identified by comparing narratives. RESULTS: Only three of the 15 women PRHOs were considering a career in surgery. The importance of positive surgical placements and contact with female surgical registrars and consultants during undergraduate training was highlighted. The changing nature of the surgical PRHO job with its lack of surgical exposure was unlikely to change the future career plans of female PRHOs. Factors such as the perceived difficulties of combining a family with a surgical career and the lack of women in particular surgical specialties were of considerable concern. CONCLUSIONS: Strategies for ensuring that female medical students receive a more positive view of surgery need to be implemented. Surgical PRHO jobs should be re-evaluated to assess the surgical experience being gained by doctors, particularly in light of the reduction in junior doctors' hours. Despite policy initiatives, many newly qualified women doctors have already decided against a surgical career.

Attitude of Health Personnel↗
PubMed2000

Pre-registration rotations into general practice: the concerns of pre-registration house officers and the views of hospital consultants.

AIMS: To explore the concerns of pre-registration house officers (PRHOs) and the views of hospital consultants in relation to pre-registration rotations with a general practice component. METHOD: As part of a larger qualitative study evaluating how a group of 24 PRHOs learn in hospital and primary care settings, face-to-face semistructured interviews were conducted with the PRHOs, and semistructured telephone interviews with the PRHOs' educational supervisors were carried out. RESULTS: The interviews with the PRHOs highlighted their concerns about how consultants might view PRHO rotations into general practice. However, the majority of consultants interviewed recognized and valued specific aspects of the experience to be gained by PRHOs in general practice, including the relationship between primary and secondary care; communications skills; specific clinical skills, and an understanding of the natural course of illnesses. The experience was seen as valuable for PRHOs considering either a general practice or a hospital career. Of the 17 consultants, 10 were also confident that 4-month placements in surgery and medicine would give PRHOs adequate experience in either specialty, providing the placements were sufficiently busy. CONCLUSIONS: Medical school deans and medical students considering PRHO rotations with a general practice component can be encouraged by the fact that, in this small study, the majority of hospital consultants interviewed valued the specific experience offered by these rotations, and felt that adequate medical and surgical experience could be gained in busy 4-month hospital placements.

Attitude of Health Personnel↗
PubMed2000

Omeprazole, Helicobacter pylori status, and alterations in the intragastric milieu facilitating bacterial N-nitrosation.

BACKGROUND & AIMS: Omeprazole produces greater acid inhibition in Helicobacter pylori-positive than -negative subjects. We investigated whether this is accompanied by more profound changes in the intragastric milieu that facilitates bacterial synthesis of N-nitroso compounds. METHODS: Gastric juice pH; nitrite, ascorbic acid, and total vitamin C concentrations; and colonization by other bacteria were examined before and during omeprazole treatment in subjects with and without H. pylori infection. Studies were performed in the fasting state and after consumption of 2 mmol nitrate (equivalent to a salad meal). RESULTS: Before omeprazole, H. pylori-positive and -negative subjects were similar for all parameters. During omeprazole, H. pylori-positive subjects had a higher intragastric pH (7.8 vs. 3.0; P < 0.00001) and greater colonization with non-H. pylori species (5 x 10(7) vs. 5 x 10(5) CFU/mL; P < 0.05). These bacteria included nitrosating species. During omeprazole treatment, H. pylori-positive subjects had higher intragastric nitrite levels after the nitrate meal (median area under the concentration/time curve, 12,450 vs. 4708 micromol/L. min; P = 0.04). Omeprazole lowered intragastric vitamin C levels in H. pylori-positive but not -negative subjects (1.8 vs. 3.4 microg/mL, respectively; P = 0.02). CONCLUSIONS: In H. pylori-positive subjects, omeprazole produces disturbances in intragastric nitrite, vitamin C, and bacterial colonization that facilitate bacterial N-nitrosation. This may place them at increased risk of mutagenesis and carcinogenesis.

Adult↗
PubMed2000

Flexor tendon grafting to the hand: an assessment of the intrasynovial donor tendon-A preliminary single-cohort study.

We report the results of a pilot study using intrasynovial donor tendons for flexor tendon reconstruction in 8 patients (10 digits) at a mean follow-up time of 3.8 years for neglected or failed primary repair of zone 2 lacerations and for neglected flexor digitorum profundus avulsions. The flexor digitorum longus to the second toe was used as the donor tendon graft. Four patients (4 digits) underwent single-stage reconstruction and 4 patients (6 digits) had multistage reconstruction. The overall patient satisfaction using a standardized visual analog reporting scale was excellent. There was 1 excellent, 1 good, 1 fair, and 1 poor result in the single-stage reconstruction group, including 1 repair site rupture and 1 digit requiring tenolysis. In the multistage reconstruction group there was 1 excellent, 3 good, 1 fair, and no poor results, including 1 digit requiring tenolysis. One patient was lost to follow-up. There was no donor site morbidity. The average active motion recovery was 64% and 56% for single-stage and multistage reconstructions, respectively, and was 73% overall for single digit reconstructions. The results of this pilot study suggest that intrasynovial tendon grafting may offer an improved alternative for tendon grafting to the synovial spaces of the digit.

Adolescent↗
PubMed2000

Influence of different amounts of carbohydrate on endurance running capacity following short term recovery.

This study examined the effect of ingesting different amounts of carbohydrate (CHO) during 4 h recovery (REC) from prolonged running, on subsequent endurance running capacity when subjects were fully rehydrated. Nine men ran at 70% VO2max on a treadmill for 90 min (T1), followed by the REC and a run to exhaustion at the same speed (T2) on two occasions. Thirty minutes into REC, subjects ingested 50 g of CHO from a 6.5% CHO-electrolyte solution (CE) on both occasions. Thereafter, subjects ingested either the same CE or a placebo (PL) every 30 min for the first 3 h of REC. The total volume ingested was equal to 150% of the body mass lost during T1 which achieved rehydration during REC in both trials. Higher blood glucose and serum insulin concentrations (P<0.05) were observed during REC in the CE trial. Nevertheless, similar run times were achieved during T2 in both trials (CE: 56.9+/-8.1 min and PL: 65.4+/-7.8 min) (+/- S.E.M) (NS). Therefore, these results suggest that ingestion of 50 g of CHO immediately after prolonged exercise, and rehydration with a placebo solution, results in a similar endurance capacity, after a 4 h recovery, as ingesting 3 times more CHO (approximately 167 g CHO) over the same period.

Adult↗
PubMed2000

The Loughborough Intermittent Shuttle Test: a field test that simulates the activity pattern of soccer.

The aims of this study were to describe and determine the test-retest reliability of an exercise protocol, the Loughborough Intermittent Shuttle Test (the LIST), which was designed to simulate the activity pattern characteristic of the game of soccer. The protocol consisted of two parts: Part A comprised a fixed period of variable-intensity shuttle running over 20 m; Part B consisted of continuous running, alternating every 20 m between 55% and 95% VO2max, until volitional fatigue. Seven trained games players (age 21.5+/-0.9 years, height 182+/-2 cm, body mass 80.1+/-3.6 kg, VO2max 59.0+/-1.9 ml x kg(-1) x min(-1); mean +/- s(x)) performed the test on two occasions (Trial 1 and Trial 2), at least 7 days apart, to determine the test-retest reliability of the sprint times and running capacity. The physiological and metabolic responses on both occasions were also monitored. The participants ingested water ad libitum during the first trial, and were then prescribed the same amount of water during the second trial. The 15 m sprint times during Trials 1 and 2 averaged 2.42+/-0.04 s and 2.43+/-0.04 s, respectively. Run time during Part B was 6.3+/-2.0 min for Trial 1 and 6.1+/-1.3 min for Trial 2. The 95% limits of agreement for sprint times and run times during Part B were -0.14 to 0.12 s and -3.19 to 2.16 min respectively. There were no differences between trials for heart rate, rating of perceived exertion, body mass change during exercise, or blood lactate and glucose concentrations during the test. Thus, we conclude that the sprint times and the Part B run times were reproducible within the limits previously stated. In addition, the activity pattern and the physiological and metabolic responses closely simulated the match demands of soccer.

Adult↗
PubMed2000

Temporal patterning of competitive emotions: a critical review.

An interactional model of stress that integrates current research on competitive affects and emphasizes the temporal dimensions of the stress process is forwarded. The literature reveals that the study of athletes' affective responses to competition has been narrowly focused on pre-competitive anxiety. Equivocal findings on temporal patterning of competitive anxiety suggest that a fundamental change in the empirical approach is needed because the current conceptualization of anxiety and other complex emotions is imprecise. The analysis of secondary emotions as patterns of discrete basic emotions, as suggested by differential emotions theorists, is proposed for consideration in future research. In this view, competitive anxiety is considered as a set of patterns of emotions rather than a unitary affect. The adoption of this approach could result in better operationalization of competitive anxiety as well as other secondary performance-related emotions. We propose that research on competitive affects should follow two parallel lines. The first should focus on the description of complex emotional states that reflect the idiosyncratic emotional experience and vocabulary of the athlete. The second should examine the sets of basic emotions experienced throughout competition, and focus on individual differences and factors determining those differences. The integration of the two approaches could lead to a better understanding of whether, how and why individuals differ in the interpretation of specific secondary emotions and their effect on performance. Moreover, it would permit the analysis of intra-individual variations in labelling secondary emotions with respect to different competitive contexts and temporal aspects.

Anxiety↗
PubMed2000

Effects of ingesting a large volume of carbohydrate-electrolyte solution on rehydration during recovery and subsequent exercise capacity.

This randomized, double-blind study examined the effects of rehydration per se and rehydration plus carbohydrate (CHO) ingestion during recovery (REC) on subsequent endurance running capacity. Nine men ran at 70% VáO2max on a level treadmill for 90 min (T1) on two occasions, followed by a 4 hour REC and a further exhaustive run at the same speed (T2). During the first 3 hours of REC, subjects drank either a 6.9% CHO-electrolyte solution (CE) or a CHO- and electrolyte-free sweetened placebo (PL) every 30 min. Volumes prescribed were 200% of the fluid lost after T1, but the actual volume of fluid ingested during the REC ranged from 113-200% and 88. 5-200% of the body mass lost for the CE and PL trials (NS). However, positive fluid balance was found in both trials after REC. During T2, run time was 24.3 +/- 4.4 min longer in the CE trial (69.3 +/- 5.5 vs. 45.0 +/- 4.2 min; p <.05). Higher blood glucose concentrations were observed throughout REC in the CE trial. These results suggest that ingesting a CHO-electrolyte solution is more effective in restoring endurance capacity compared to the same large volume of placebo, even though complete rehydration was achieved in both trials.

Adult↗
PubMed2000

Conserved and exposed epitopes on intact, native, primary human immunodeficiency virus type 1 virions of group M.

We have examined the exposure and conservation of antigenic epitopes on the surface envelope glycoproteins (gp120 and gp41) of 26 intact, native, primary human immunodeficiency virus type 1 (HIV-1) group M virions of clades A to H. For this, 47 monoclonal antibodies (MAbs) derived from HIV-1-infected patients were used which were directed at epitopes of gp120 (specifically V2, C2, V3, the CD4-binding domain [CD4bd], and C5) and epitopes of gp41 (clusters I and II). Of the five regions within gp120 examined, MAbs bound best to epitopes in the V3 and C5 regions. Only moderate to weak binding was observed by most MAbs to epitopes in the V2, C2, and CD4bd regions. Two anti-gp41 cluster I MAbs targeted to a region near the tip of the hydrophilic immunodominant domain bound strongly to >90% of isolates tested. On the other hand, binding of anti-gp41 cluster II MAbs was poor to moderate at best. Binding was dependent on conformational as well as linear structures on the envelope proteins of the virions. Further studies of neutralization demonstrated that MAbs that bound to virions did not always neutralize but all MAbs that neutralized bound to the homologous virus. This study demonstrates that epitopes in the V3 and C5 regions of gp120 and in the cluster I region of gp41 are well exposed on the surface of intact, native, primary HIV-1 isolates and that cross-reactive epitopes in these regions are shared by many viruses from clades A to H. However, only a limited number of MAbs to these epitopes on the surface of HIV-1 isolates can neutralize primary isolates.

Amino Acid Sequence↗
PubMed2000

Immunoreactivity of intact virions of human immunodeficiency virus type 1 (HIV-1) reveals the existence of fewer HIV-1 immunotypes than genotypes.

In order to protect against organisms that exhibit significant genetic variation, polyvalent vaccines are needed. Given the extreme variability of human immunodeficiency virus type 1 (HIV-1), it is probable that a polyvalent vaccine will also be needed for protection from this virus. However, to understand how to construct a polyvalent vaccine, serotypes or immunotypes of HIV must be identified. In the present study, we have examined the immunologic relatedness of intact, native HIV-1 primary isolates of group M, clades A to H, with human monoclonal antibodies (MAbs) directed at epitopes in the V3, C5, and gp41 cluster I regions of the envelope glycoproteins, since these regions are well exposed on the virion surface. Multivariate analysis of the binding data revealed three immunotypes of HIV-1 and five MAb groups useful for immunotyping of the viruses. The analysis revealed that there are fewer immunotypes than genotypes of HIV and that clustering of the isolates did not correlate with either genotypes, coreceptor usage (CCR5 and CXCR4), or geographic origin of the isolates. Further analysis revealed distinct MAb groups that bound preferentially to HIV-1 isolates belonging to particular immunotypes or that bound to all three immunotypes; this demonstrates that viral immunotypes identified by mathematical analysis are indeed defined by their immunologic characteristics. In summary, these results indicate (i) that HIV-1 immunotypes can be defined, (ii) that constellations of epitopes that are conserved among isolates belonging to each individual HIV-1 immunotype exist and that these distinguish each of the immunotypes, and (iii) that there are also epitopes that are routinely shared by all immunotypes.

Antibodies, Monoclonal↗
PubMed2000

Effect of endurance training on oxygen uptake kinetics during treadmill running.

The purpose of this study was to examine the effect of endurance training on oxygen uptake (VO(2)) kinetics during moderate [below the lactate threshold (LT)] and heavy (above LT) treadmill running. Twenty-three healthy physical education students undertook 6 wk of endurance training that involved continuous and interval running training 3-5 days per week for 20-30 min per session. Before and after the training program, the subjects performed an incremental treadmill test to exhaustion for determination of the LT and the VO(2 max) and a series of 6-min square-wave transitions from rest to running speeds calculated to require 80% of the LT and 50% of the difference between LT and maximal VO(2). The training program caused small (3-4%) but significant increases in LT and maximal VO(2) (P<0.05). The VO(2) kinetics for moderate exercise were not significantly affected by training. For heavy exercise, the time constant and amplitude of the fast component were not significantly affected by training, but the amplitude of the VO(2) slow component was significantly reduced from 321+/-32 to 217+/-23 ml/min (P<0.05). The reduction in the slow component was not significantly correlated to the reduction in blood lactate concentration (r = 0. 39). Although the reduction in the slow component was significantly related to the reduction in minute ventilation (r = 0.46; P<0.05), it was calculated that only 9-14% of the slow component could be attributed to the change in minute ventilation. We conclude that the VO(2) slow component during treadmill running can be attenuated with a short-term program of endurance running training.

Adult↗
PubMed2000

Psychiatric practice variations in the diagnosis and treatment of major depression.

OBJECTIVE: Practice variations in the diagnosis, treatment, and outcomes of patients with major depression were examined within six psychiatric practices participating in a national outcomes-management project. METHODS: Six of 20 psychiatric clinics met selection criteria for this study and provided a database of 5, 106 patients. Patients completed the BASIS-32, the Short-Form-36 Health Survey, and a Beginning Services Survey. Treatment information was also obtained directly from the clinician or through a medical record review. RESULTS: Although 73.1 to 77 percent of patients screened positive for a depressive disorder, only 18.5 to 36.8 percent were diagnosed with major depression (p<.001). Between 39 and 72 percent of patients received psychotropic medications, a significant difference across sites (p<.001). In addition, the number of psychotherapy sessions was significantly different across sites (p<.001). CONCLUSIONS: Patient care varies considerably across psychiatric practices, a finding that is particularly relevant for developers of performance indicators and risk-adjustment strategies for mental health.

Adult↗
PubMed2000

Impaired regulation of brain serotonin function during dieting in women recovered from depression.

BACKGROUND: Amino acid mixtures that lower brain availability of the serotonin (5-HT) precursor tryptophan produce acute depressive relapse in women with a history of major depression. Dieting also lowers brain tryptophan availability, but its effects on brain 5-HT function in recovered depressed women have not been studied. AIM: To test the hypothesis that women with a history of major depression would show impaired regulation of brain 5-HT function during a period of dieting-induced tryptophan depletion. METHOD: Women with and without a history of major depression were placed on a daily 1000 kcal (approximately 4200 kj) diet for three weeks. Before the diet and in the final week we measured fasting plasma tryptophan levels and the prolactin response to an intravenous tryptophan challenge. RESULTS: Dieting lowered plasma tryptophan levels equivalently in women with and without a history of depression. In women without a history of depression, dieting also increased the prolactin response to tryptophan. This increase did not occur in women with a history of depression. CONCLUSIONS: Women with a history of depression showed impaired regulation of brain 5-HT function in response to dieting.

Adult↗
PubMed2000

PRHOs in primary care: what is happening out there?

Preregistration house officer (PRHO) placements in general practice were introduced throughout Britain in August 1998. This paper describes an evaluation of PRHOs in primary care rotations in South Thames during 1998-99. There are important messages for both educational supervisors and undergraduates considering a PRHO in primary care rotation.

Education, Medical, Graduate↗