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Biomedical subjects

R Fredericks

Publications and source records attributed to R Fredericks.

8 recordsLinked to original sources
PubMed2000

A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse.

A randomized, multicentre, open-label, phase II study compared temozolomide (TMZ), an oral second-generation alkylating agent, and procarbazine (PCB) in 225 patients with glioblastoma multiforme at first relapse. Primary objectives were to determine progression-free survival (PFS) at 6 months and safety for TMZ and PCB in adult patients who failed conventional treatment. Secondary objectives were to assess overall survival and health-related quality of life (HRQL). TMZ was given orally at 200 mg/m(2)/day or 150 mg/m(2)/day (prior chemotherapy) for 5 days, repeated every 28 days. PCB was given orally at 150 mg/m(2)/day or 125 mg/m(2)/day (prior chemotherapy) for 28 days, repeated every 56 days. HRQL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 [+3]) and the Brain Cancer Module 20 (BCM20). The 6-month PFS rate for patients who received TMZ was 21%, which met the protocol objective. The 6-month PFS rate for those who received PCB was 8% (P = 0.008, for the comparison). Overall PFS significantly improved with TMZ, with a median PFS of 12.4 weeks in the TMZ group and 8.32 weeks in the PCB group (P = 0.0063). The 6-month overall survival rate for TMZ patients was 60% vs. 44% for PCB patients (P = 0.019). Freedom from disease progression was associated with maintenance of HRQL, regardless of treatment received. TMZ had an acceptable safety profile; most adverse events were mild or moderate in severity.

Adult↗
PubMed1999

Studies in calf venous pump function utilizing a two-valve experimental model.

OBJECTIVES: to explore the hydrodynamic mechanisms involved in the regulation of ambulatory venous pressure. DESIGN: an experimental model of calf venous pump was constructed with collapsible tubes and valves. MATERIAL: the model consisted of a conduit and a pump with an intervening competent valve. Another valve that could allow reflux into the pump was mounted above the pump. METHODS: conduit pressure and recovery times were monitored under conditions of different degrees of ejection fraction and reflux into the pump. Model variables included using poorly compliant tubes for the pump, the conduit and for both the pump and conduit. RESULTS: the latex tube exhibited a non-linear volume-pressure relationship and a bi-modal regimen of compliance. This bestowed pressure-buffering properties. Ambulatory venous hypertension resulted when reflux beyond buffering capacity occurred. Substituting less compliant PTFE for latex at the pump had a relatively minor effect on post-ejection pressure and recovery times. Using PTFE at the conduit had a profound but divergent effect on both of these parameters. Conduit capacitance reduction had a similar effect. CONCLUSION: conduit elastance plays a significant role in the regulation of ambulatory venous pressure in this experimental model. The hydrodynamic principles illustrated by the model may enhance our understanding of the human calf venous pump.

Blood Pressure Determination↗
PubMed1993

Observations on the calf venous pump mechanism: determinants of postexercise pressure.

PURPOSE: We investigated the factors determining postexercise pressure and the relationship of venous valve closure and venous column segmentation to ambulatory venous pressure changes. METHODS: Valve closure and venous segmentation were observed during dynamic ascending phlebography in 40 nonrefluxive limbs and by duplex imaging in 25 normal limbs in healthy volunteers. Simultaneous volume (air plethysmography) and pressure studies during calf exercise were also carried out. Some studies used a simple mechanical model comprised of a collapsible latex tube ("calf pump") and a graduated "popliteal" valve. RESULTS: The femoropopliteal venous column above the popliteal valve remains unsegmented and continuous during ambulatory venous pressure changes in response to calf muscle contraction. Therefore ambulatory venous pressure changes cannot be explained purely on the basis of hydrostatic column pressure changes. Postexercise pressure appears to be determined by a complex set of factors: (1) physical segmentation of the venous column below the popliteal valve (i.e., tibial valve closure); (2) tube collapse below the closed valve, which further aids in the breakup of the hydrostatic column pressure and dampens the effect of any reflux through or around the closed valve; (3) ejection fraction, which influences the degree of tube collapse; and (4) the interaction of the resultant pressure forces with the wall properties of the venous pump. CONCLUSIONS: The mechanism of ambulatory venous pressure reduction is complex and multifactorial. The importance of venous wall characteristics as a determinant of postexercise pressure has not been previously appreciated. Changes in venous wall property after a thrombotic process, for example, could conceivably influence ambulatory venous pressure and recovery time in the absence of reflux.

Exercise↗
PubMed1991

Hemodynamic basis of stasis ulceration--a hypothesis.

Approximately 25% of patients with stasis ulceration have normal or below normal ambulatory venous pressures. A reflux index was calculated by multiplying postexercise pressures by Valsalva-induced foot venous pressure elevation. In patients with stasis ulceration, reflux index was found to have an excellent negative predictive value with a clear discriminant line between normal limbs and those with ulcers. Increasing incidence of stasis ulceration was demonstrated with increasing reflux index value. Even when ambulatory venous pressure was within the normal range, the index was found to be abnormal in ulcerated limbs because Valsalva-induced foot venous pressure was elevated in these limbs. Conversely, some patients with stasis ulceration and normal Valsalva foot venous pressure elevation were found to have abnormal ambulatory venous pressure values, yielding an elevated reflux index. Preliminary analysis indicates that reflux index may be a better predictor of surgical outcome after valve reconstruction procedures than either ambulatory venous pressure or Valsalva-induced foot venous pressure elevation. The concept of reflux index is a hypothesis that attempts to explain inconsistencies observed in implicating ambulatory venous hypertension as the sole determinant of venous reflux.

Chronic Disease↗
PubMed1991

Venous obstruction: an analysis of one hundred thirty-seven cases with hemodynamic, venographic, and clinical correlations.

One hundred thirty-seven limbs with venous obstruction were analyzed. The arm/foot venous pressure differential and reactive hyperemia tests were found to be useful techniques to diagnose and grade venous obstruction. Traditional techniques including venography and ambulatory venous pressure are inferior in this regard. The newer techniques have provided newer insights in venous obstruction which are detailed herein. The hand-held Doppler was surprisingly very sensitive in grade I as well as in more severe forms of obstruction. Neither anatomic locale of obstruction nor its extent determined hemodynamic severity. Extensive proximal lesions could be hemodynamically mild, and conversely distal crural obstructions and single segment lesions could be hemodynamically severe. Phlebographic appearance was a poor index of collateralization. The paradoxical venous pressure response to the reactive hyperemia test in grade IV obstruction was found to be due to suppression or delay of the reactive hyperemia response itself in the presence of severe venous obstruction. The pain of venous claudication may be related to this phenomenon. Skin ulceration in the presence of venous obstruction was related to the associated reflux rather than the hemodynamic severity of the obstruction itself. The Linton procedure was found to be useful in treating such skin ulcerations. After perforator disruption, obstruction did not become hemodynamically worse, but reflux as measured by the Valsalva test improved with ulcer healing. The improvement in reflux related to Valsalva offers for the first time a hemodynamic rationale for the Linton procedure.

Arm↗
PubMed1990

Evaluation of methods for detecting venous reflux. Perspectives in venous insufficiency.

Using 793 limbs with nonobstructive venous reflux, we evaluated a number of techniques used for the assessment of venous reflux. The venous Doppler examination was found to be a reliable screening tool with excellent sensitivity and good specificity. Photoplethysmography was 97% sensitive in patients with ambulatory venous hypertension; however, in milder forms of reflux, it was less sensitive. The major drawback of photoplethysmography was the large number of false-positive results obtained. Ambulatory venous pressure measurement and another pressure-based technique, Valsalva-induced foot venous pressure measurement, defined overlapping but different normal and abnormal limbs. Descending venography, when performed as described by Kistner et al, was found to be a reliable tool to assess reflux with more than a 90% sensitivity. The horizontal technique of performing descending venography and nucleotide descending venographies had unacceptably low sensitivity and were abandoned. Features of venous reflux as outlined by these modern technical tools are described.

Evaluation Studies as Topic↗
PubMed1988

Valve reconstruction procedures for nonobstructive venous insufficiency: rationale, techniques, and results in 107 procedures with two- to eight-year follow-up.

Among 211 limbs with nonobstructive chronic venous insufficiency, valve reflux of the deep system was the predominant (more than 70%) pathologic condition. Superficial venous or perforator incompetence when present invariably occurred in combination with valve reflux of the deep veins, suggesting that the latter is a common denominator for symptom production. Single level-single system reflux was only occasionally symptomatic (10%), whereas the incidence of single level-multisystem reflux (25%) and multilevel-multisystem reflux (65%) in symptomatic limbs was much higher. Our experience with 107 venous valve reconstructions with a 2- to 8-year follow-up is described. Different techniques of valve reconstruction employed are detailed. The most common pathologic feature is a redundant valve with malcoaptation probably of nonthrombotic origin. Valsalva foot venous pressure elevation is a useful hemodynamic technique for assessing surgical results. Valvuloplasty may be superior to other reconstruction techniques in relieving symptoms of stasis, including stasis ulceration.

Axillary Vein↗