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Biomedical subjects

R Wilcox

Publications and source records attributed to R Wilcox.

At least 19 recordsLinked to original sources
PubMed2006

Truncated form of VACM-1/cul-5 with an extended 3' untranslated region stimulates cell growth via a MAPK-dependent pathway.

We have sequenced a 4.9kb clone (KLB22) which shares 99% sequence homology with the rabbit vasopressin-activated calcium mobilizing (VACM-1) protein. The 5' terminus sequence of KLB22 cDNA (nucleotides 1-1961) is continuous and overlapping with nucleotides 1226-3186 of the VACM-1 cDNA sequence. The 3'UTR of KLB22 cDNA extends beyond the 3'UTR of VACM-1 by 2999nt. KLB22 cDNA encodes a 497 amino acid protein, which putatively begins at Met 284 of the 780 amino acid VACM-1 protein. The in vitro translation of KLB22 cDNA yields a 59kDa protein. When expressed in cos-1 cells, the truncated VACM-1 protein localizes to the nucleus. KLB22 cDNA transfected cells show increased growth rates and increased levels of phosphorylated MAPK when compared to the vector or to VACM-1 cDNA transfected cells. Finally, in vivo, KLB22 protein expression is tissue specific and can be detected in kidney and in heart atrium. These results suggest that truncated VACM-1 cDNA (KLB22) increases cell proliferation through a MAPK pathway.

3' Untranslated Regions↗
PubMed2006

Lower extremity control and dynamics during backward angular impulse generation in forward translating tasks.

Observation of complex whole body movements suggests that the nervous system coordinates multiple operational subsystems using some type of hierarchical control. When comparing two forward translating tasks performed with and without backward angular impulse, we have learned that both trunk-leg coordination and reaction force-time characteristics are significantly different between tasks. This led us to hypothesize that differences in trunk-leg coordination and reaction force generation would induce between-task differences in the control of the lower extremity joints during impulse generation phase of the tasks. Eight highly skilled performers executed a series of forward jumps with and without backward rotation (reverse somersault and reverse timer, respectively). Sagittal plane kinematics, reaction forces, and electromyograms of lower extremity muscles were acquired during the take-off phase of both tasks. Lower extremity joint kinetics were calculated using inverse dynamics. The results demonstrated between-task differences in the relative angles between the lower extremity segments and the net joint forces/reaction force and the joint angular velocity profiles. Significantly less knee extensor net joint moments and net joint moment work and greater hip extensor net joint moments and net joint moment work were observed during the push interval of the reverse somersault as compared to the reverse timer. Between-task differences in lower extremity joint kinetics were regulated by selectively activating the bi-articular muscles crossing the knee and hip. These results indicate that between-task differences in the control of the center of mass relative to the reaction force alters control and dynamics of the multijoint lower extremity subsystem.

Adult↗
PubMed2005

Lower extremity control and dynamics during backward angular impulse generation in backward translating tasks.

Observation of complex whole-body movements suggests that the nervous system coordinates multiple operational subsystems using some type of hierarchical control. When comparing two backward translating tasks performed with and without backward angular impulse, we have learned that task-specific modifications in trunk-leg coordination contribute to the regulation of total-body center of mass (CoM) position relative to the reaction force (RF). In this study, we hypothesized that task-specific differences in trunk-leg coordination would affect the control of the lower extremity joints during the impulse-generation phase of the tasks. Eight highly skilled performers executed a series of backward translating jumps with and without backward rotation (back somersault and back timer, respectively). Sagittal plane kinematics, RFs and electromyograms of lower extremity muscles were acquired during the take-off phase of both tasks. Lower extremity joint kinetics was calculated using inverse dynamics. The results indicate that between-task differences in the relative angles between the lower extremity segments and the net joint forces/RF contributed to significant reductions in knee-extensor net joint moments and increases in hip-extensor net joint moments during the push interval of the back somersault as compared to the back timer. Between-task differences in backward trunk angular velocity also contributed to the re-distribution of work done by the lower extremity net joint moments. Between-task differences in lower extremity joint kinetics were associated with synergistic activation of the bi-articular muscles crossing the knee and hip. These results indicated that task-specific control of CoM relative to the RF in order to regulate the backward angular-impulse-involved modification in the control and dynamics of the knee and hip joints. These results indicate that between-task differences in the control objectives at the total-body level (position of CoM relative to the RF) alters the control and dynamics of the multi-joint lower extremity subsystem.

Adult↗
PubMed2004

British Cardiac Society Working Group on the definition of myocardial infarction.

The British Cardiac Society commissioned this report to help address inconsistencies in the terminology for acute coronary syndromes and wide variations in the threshold for the diagnosis of myocardial infarction (MI) depending on the assay performed, the precision, and the sensitivity. In addition, several publications have highlighted potential problems with the application of the European Society of Cardiology(ESC)/American College of Cardiology (ACC) consensus document published in 2000. A revision process has been initiated under the guidance of the ESC, the ACC, and the American Heart Association (AHA). The purpose of this report is to help inform the next revision of the ESC/ACC/AHA guidelines for the diagnosis of MI.

Acute Disease↗
PubMed2004

British Cardiac Society Working Group on the definition of myocardial infarction.

The British Cardiac Society commissioned this report to help address inconsistencies in the terminology for acute coronary syndromes and wide variations in the threshold for the diagnosis of myocardial infarction (MI) depending on the assay performed, the precision, and the sensitivity. In addition, several publications have highlighted potential problems with the application of the European Society of Cardiology (ESC)/ American College of Cardiology (ACC) consensus document published in 2000. A revision process has been initiated under the guidance of the ESC, the ACC, and the American Heart Association (AHA). The purpose of this report is to help inform the next revision of the ESC/ACC/AHA guidelines for the diagnosis of MI.

Cardiology↗
PubMed2001

Resident and faculty perceptions of a surgical residency program merger.

To evaluate resident and faculty perceptions of a residency merger process.Survey of faculty and residents of a recently merged general surgical residency. Nineteen separate program characteristics were evaluated via a numerical scoring system, and additional written commentary regarding dominant perceived benefits and detriments of the merger was solicited. Statistical significance was evaluated on numerically scored items by applying the Mann-Whitney U test to median values expressed with interquartile ranges, comparing resident and faculty responses.Scoring system responses from faculty and residents were generally similar. The merger was seen as neutral to positive in its impact on academic issues, but it had more negative effects on issues related to overall program atmosphere and morale. Statistically significant differences between resident and faculty responses were noted in 2 areas: teaching conference timing and overall program effectiveness in preparing for practice. Both of these areas were more favorably impacted by the merger from the residents' perspective, and more negatively as judged by the faculty (p < 0.05). Written commentary by both groups similarly emphasized areas of academic strengthening as a positive effect of the merger, and relationship and morale issues as being more negatively impacted.As reflected by resident and faculty perceptions, program mergers may provide opportunities to strengthen and enhance the academic and clinical foundation of residency. This may, however, occur at the expense of morale and relational issues, which may be negatively impacted by program administrative and geographic expansion.

Journal Article↗
PubMed2000

Survival outcomes 1 year after reperfusion therapy with either alteplase or reteplase for acute myocardial infarction: results from the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) III Trial.

BACKGROUND: New recombinant plasminogen activators have been developed to simulate the fibrinolytic action of the physiological serine protease tissue plasminogen activator (alteplase, t-PA), and have prolonged half-life features permitting bolus administration. One such activator, reteplase (r-PA), was compared with t-PA in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-III Trial. METHODS AND RESULTS: At 1-year follow-up, survival status was ascertained in 97.4% of the 15 059 patients enrolled in the GUSTO-III trial. At 1 year, the mortality rate for the t-PA-assigned group was 11.06%, and for r-PA it was 11.20% (P:=0. 77). The absolute mortality difference of 0.14% has 95% CIs of -1. 21% to 0.93%. There were no significant differences in outcome by intention-to-treat for the 2 different plasminogen activators in the prespecified groups (age, infarct location, time-to-treatment). The absolute difference in mortality rates between t-PA and r-PA progressively narrowed over the predetermined observation times after random assignment; it was 0.31% at 24 hours, 0.26% at 7 days, 0.23% at 30 days, and 0.14% at 1 year. Of note, mortality rate in the trial between 30 days and 1 year in 13 883 patients was 4.02% and did not differ between the treatment groups. However, this mortality rate was substantially greater than in GUSTO-I, in which mortality rate for t-PA versus streptokinase between 30 days and 1-year was 2.97% (heart rate 1.36, 95% CI 1.23, 1.50, P:<0.001). CONCLUSIONS: The r-PA and t-PA strategies yielded similar survival outcomes after 30 days in this trial. The increase in mortality rate during extended follow-up compared with previous trials may reflect higher-risk patients and highlights the need for improved secondary prevention strategies.

Acute Disease↗
PubMed1999

Frequency and clinical outcome of cardiogenic shock during acute myocardial infarction among patients receiving reteplase or alteplase. Results from GUSTO-III. Global Use of Strategies to Open Occluded Coronary Arteries.

AIMS: Reteplase has been reported to achieve better patency of the infarct artery than alteplase. As infarct artery patency is strongly associated with survival among patients with cardiogenic shock, we postulated that treatment with reteplase would improve outcomes among shock patients. METHODS: We compared 30-day mortality rates among patients in GUSTO-III who either presented with shock or developed shock after enrollment; all patients received either front-loaded alteplase or reteplase (two bolus doses of 10 MU, 30 min apart). RESULTS: Shock occurred in 260 (5.3%) of 4921 patients randomized to alteplase and 560 (5.5%) of 10,138 patients randomized to reteplase. Of these patients, 28 (10.8%) and 55 (9.8%) randomized to alteplase and reteplase, respectively, presented with shock. In-hospital, 35% and 37% of shock patients assigned to alteplase or reteplase, respectively, underwent coronary angiography, with similar rates of percutaneous (approximately 11-13%) or surgical (approximately 2-3%) revascularization procedures subsequently performed. Death within 30 days occurred in 169 (65%) and 353 (63%) shock patients randomized to alteplase and reteplase, respectively (P = 0.59). Of patients presenting with shock, 64% and 58% of patients randomized to alteplase or reteplase died within 30 days (P = 0.59). CONCLUSION: Compared with alteplase, reteplase did not improve outcome among patients who presented with shock or developed shock after receiving thrombolytics. The newer-generation thrombolytic agents remain of limited efficacy in the treatment and prevention of shock.

Aged↗
PubMed1996

Marked bone marrow eosinophilia at the time of relapse of acute myeloblastic leukaemia in association with the appearance of translocation t(12;20)(q24;q11).

We report a case of acute myeloblastic leukaemia (AML), FAB type M2, with karyotype t(8;21)(q22;q22), who at the time of relapse showed marked eosinophilia of the bone marrow. Karyotype analysis showed the appearance of an additional clone t(8;21)(q22;q22),t(12;20)(q24;q11). To the best of our knowledge, marked eosinophilia has not been reported in association with this particular chromosomal translocation.

Adult↗
PubMed1990

Comparative trial of nifedipine retard and atenolol in the treatment of elderly patients with mild to moderate hypertension.

Forty-one elderly patients with mild to moderate hypertension (resting diastolic blood pressure 100-130 mmHg after an eight week placebo run-in phase) were randomised to a double-blind parallel group comparison of nifedipine retard 10 mg twice daily or atenolol 50 mg once daily. If the resting diastolic pressure exceeded 95 mmHg after four weeks of treatment the dose(s) were doubled for a further four weeks. Initial sitting blood pressures were 187 +/- 21/105 +/- 5 mmHg in the nifedipine group and 181 +/- 19/106 +/- 6 in the atenolol group. At four weeks, eight patients given nifedipine and nine given atenolol had their doses doubled. At eight weeks sitting blood pressures were 159 +/- 19/85 +/- 7 and 162 +/- 21/87 +/- 8 respectively, with 18/20 patients given nifedipine and 16/21 given atenolol having a sitting diastolic pressure equal to or less than 95 mmHg. One patient given nifedipine was withdrawn because of unacceptable ankle oedema and one given atenolol withdrawn because of worsening angina. Both drugs were equally acceptable to the patients and neither caused a change in their sense of well-being.

Aged↗
PubMed1989

The relationship between anticonvulsant activity and receptor affinity of N-methyl-D-aspartate antagonists in epileptic fowl.

The N-methyl-D-aspartate (NMDA) receptor antagonists [(3-(+/-)2-carboxypiperazin-4-yl)-propyl-l-phosphonic acid (CPP), +/- 2-amino-7-phosphonoheptanoic acid (2AP7), +/- 2-amino-5-phosphonovaleric acid (2AP5), D-alpha-aminoadipic acid (alpha AA), and +/- alpha, epsilon-diaminopimelic acid (DAP)] were tested for anticonvulsant activity in epileptic chickens. There was a high correlation between anticonvulsant potencies (ED50) and the affinity for the NMDA receptor measured by displacement of L-[3H]glutamate from synaptosomal membranes. The high seizure susceptibility is not due to abnormalities in the NMDA receptor as comparison of KD, Bmax and Ki values in synaptosomal preparations from epileptic and non-epileptic chickens indicated no differences in NMDA receptor binding receptor characteristics.

Animals↗
PubMed1987

Benzodiazepine antagonist Ro 15-1788 (flumazepil) attenuates the anticonvulsant activity of diazepam in epileptic fowl.

The ability of the imidazobenzodiazepine Ro 15-1788 to displace diazepam from brain membranes in vitro and to antagonize the anticonvulsant activity of diazepam in vivo was determined in epileptic fowl. At doses of 1.0 mg/kg and higher, Ro 15-1788 significantly attenuated the anticonvulsant action of diazepam (1.0 mg/kg) in epileptic chickens. Ro 15-1788 alone exerted no anticonvulsant activity even in doses as high as 10 mg/kg. Specific binding of 10 nM [3H]diazepam to whole homogenate fractions prepared from cerebral hemispheres of epileptic fowl was inhibited by Ro 15-1788 with an IC50 of 8.5 nM and the Ki was determined to be 4.25 nM. These results suggest that Ro 15-1788 competes directly with diazepam for a binding site involved in producing anticonvulsant activity.

Animals↗