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Biomedical subjects

K Beach

Publications and source records attributed to K Beach.

At least 19 recordsLinked to original sources

New ultrasound approaches to dialysis access monitoring.

The failure of dialysis access is a frequent source of morbidity and hospitalization. Traditional methods of graft surveillance include: (1) clinical examination, (2) venous line pressure measurements during dialysis, (3) urea or tracer recirculation measurement, (4) continuous wave (CW) Doppler methods, (5) duplex ultrasonography, and (6) radiograph angiography. All these methods require special training and/or laboratory tests. The purpose of this study was to test a simple continuous-wave Doppler method that could be applied to measure the flow rate in dialysis access every time the patient undergoes dialysis. Twenty dialysis patients, 15 with polytetrafluoroethylene grafts and 5 with arteriovenous fistulae, were studied. Two hundred fifty-three examinations were performed over an 8-month period. Doppler waveforms of the access flow were obtained with the pump on, with the pump off, and with the pump on again. Systolic and diastolic Doppler frequency measurements were made, and the pump-on and pump-off measurements were compared. In an access functioning normally, the Doppler frequencies are higher with the pump off than with the pump on. In 22% of the cases, there were abnormal findings in which the Doppler frequencies were lower with the pump off than with the pump on. This occurs if the needles are incorrectly placed, suggesting that recirculation is occurring. Recirculation also occurs if there is stenosis of the access. Examining the hemodialysis access during each dialysis session with an inexpensive directional Doppler may identify a significant stenosis and improve the efficiency of dialysis by detecting those patients in whom the arterial and venous needles are reversed.

Adult↗

Granulocyte colony-stimulating factor given to donors before apheresis does not prevent aplasia in patients treated with donor leukocyte infusion for recurrent chronic myeloid leukemia after bone marrow transplantation.

We conducted 2 sequential studies of donor leukocyte infusion (DLI) in 26 patients with chronic myeloid leukemia in hematologic relapse after unmodified allogeneic bone marrow transplantation. In the first study, cells for DLI were collected from 13 donors who were not treated with granulocyte colony-stimulating factor (G-CSF) (group 1). In the second study, cells were collected from 13 donors who received G-CSF before apheresis (group 2) in an attempt to avoid aplasia after DLI. Patients in group 2 received 550-fold more CD34+ cells than those in group 1. We found no significant difference in the incidence (31% versus 22%), onset time (41 vs. 48 days), or duration (15 vs. 14 days) of cytopenia after DLI in the 2 groups. G-CSF given to donors before collection of cells did not prevent aplasia. These findings support the hypothesis that the pathogenesis of aplasia after DLI is not restricted to the destruction of recipient hematopoietic cells but also involves failure of donor hematopoiesis by undefined mechanisms.

Adolescent↗

Hemostasis of punctured vessels using Doppler-guided high-intensity ultrasound.

The use of Doppler ultrasound was investigated to determine if it would aid in guiding the application of high-intensity focused ultrasound (HIFU) to stop bleeding from punctured vessels. Major vessels (abdominal aorta, illiac, carotid, common femoral and superficial femoral arteries and the jugular vein) were surgically exposed, punctured and treated in anesthetized pigs. Treatment was applied when the Doppler sounds indicated the focus coincided with the bleeding site. In 89 treatment trials, the average time to achieve major hemostasis (a point where bleeding was reduced to a level of only oozing) was 8 s, and for complete hemostasis was 13 s. These times were significantly shorter than those of an identical former study in which only visual guidance was used. In that study, the average times for major and complete hemostasis were 40 and 62 s, respectively. The advantage of Doppler guidance in applying HIFU in treating bleeding vessels was demonstrated.

Animals↗

Isolation of CD34+ cells from blood stem cell components using the Baxter Isolex system.

The CD34 antigen is expressed by human hematopoietic progenitor and stem cells. These cells are capable of reconstituting marrow function after marrow-ablative chemo-radiotherapy. Several different technologies have been developed for the separation of CD34+ cells from bone marrow or peripheral blood stem cell (PBSC) components. We used an immunomagnetic separation technique to enrich CD34+ cells from PBSC components in anticipation of autologous transplantation for patients with B lymphoid malignancies. Twenty-nine patients enrolled on this study and received mobilization chemotherapy followed by G-CSF. Of these, 21 achieved a peripheral blood CD34+ cell level of at least 2.0 x 10(4)/l required by protocol for separation of the stem cell components. A median of three components per patient was collected for processing. The average CD34+ cell concentration in the components after apheresis was 1.0 +/- 1.2%. After the CD34+ cell selection, the enriched components contained 0.6 +/- 0.6% of the starting nucleated cells. The recovery of CD34+ cells, however, averaged 58.4 +/- 19.2% of the starting cell number, with a purity of 90.8 +/- 6.5%. Overall depletion of CD34- cells was 99.96 +/- 0.06%. Nineteen patients were treated with marrow-ablative conditioning regimens and received an average of 6.2 +/- 2.0 x 10(6) CD34+ cells/kg body weight. These patients recovered to an ANC >0.5 x 10(9)/l at a median of 11 days (range 8-14), and platelet transfusion independence at a median of 9 days (range 5-13). Four patients died of transplant-related complications or relapse before 100 days after transplantation. No patient required infusion of unseparated cells because of failure of sustained bone marrow function. These data demonstrate that peripheral blood-derived CD34+ cells enriched by use of an immunomagnetic separation technique are capable of rapid engraftment after autologous transplantation.

Adult↗

Platelet serotonin transporter in depressed children and adolescents: 3H-paroxetine platelet binding before and after sertraline.

OBJECTIVE: To evaluate serotonin transporter protein (5HTPR) binding in platelets from children and adolescents with major depression (MDD) compared to normal controls using the selective ligand 3H-paroxetine. METHOD: Children and adolescents with MDD (n = 24) defined by DSM-III-R criteria and normal controls (n = 22) were compared by platelet 5HTPR kinetic analysis with the hypothesis that 5HTPR is reduced in MDD. A subset of MDD subjects (n = 18) continued to participate in a fixed-dose, open-label sertraline trial for 6 weeks followed by drug-free washout and repeated 5HTPR analysis. RESULTS: Sex, prepubertal status, and age had no effect on 5HTPR. Medication-free MDD subjects differed from controls in reduced binding capacity (Bmax) (p < .001). Sertraline therapy decreased binding affinity from baseline non-selectively (p < .05), and Bmax elevation from baseline was associated with nonresponse and suicide attempt history. CONCLUSION: Earlier literature in this population is replicated with regard to reduced platelet 5HTPR Bmax in MDD. Findings support a continuum of 5HTPR involvement in MDD across the developmental spectrum.

1-Naphthylamine↗

Liver hemostasis using high-intensity focused ultrasound.

Liver hemorrhage, the major cause of death in hepatic trauma, is notoriously difficult to control. We report on the use of high-intensity focused ultrasound (HIFU) to arrest the bleeding from incisions made in rabbit livers. A HIFU transducer, with a spherically curved aperture of 6.34 cm2 area, a focal length of 4 cm and a frequency of 3.3 MHz was used. In approximately 94% of the incisions, the hemorrhage was reduced to a slow oozing of blood in less than 2 min. The maximum temperature of liver tissue around the incision area, during HIFU application, was measured to be 86 degrees C. The mechanism of hemostasis, confirmed by histological examination, appears to be coagulative necrosis of a volume of liver tissue around the incision. We believe that acoustic hemostasis, with the unique characteristic of "volume cauterization," offers a novel method for the management of liver hemorrhage and, thus, has major clinical implications.

Animals↗

Phase I trial of interleukin-2 after unmodified HLA-matched sibling bone marrow transplantation for children with acute leukemia.

Allogeneic bone marrow transplantation (BMT) for advanced acute leukemia is associated with a high risk of relapse. It is postulated that interleukin-2 (IL-2) administered after BMT might induce or amplify a graft-versus-leukemia effect and thereby reduce the relapse rate. To identify an IL-2 regimen for testing this hypothesis, a phase I trial of IL-2 (Roche) was performed in children in complete remission (CR) without active graft-versus-host disease (GVHD) off immunosuppressive agents after unmodified allogeneic matched-sibling BMT for acute leukemia beyond first remission. Beginning a median of 68 days after BMT, 17 patients received escalating doses of induction IL-2 (0.9, 3.0, or 6.0 x 10(6) IU/m2/d representing levels I, II, and III) for 5 days by continuous intravenous infusion (CIV). After 6 days of rest, they received maintenance IL-2 (0.9 x 10(6) IU/m2/d) for 10 days by CIV infusion. Levels I and II were well-tolerated, but, of 6 patients at level III, 1 developed pulmonary infiltrates, 1 developed hypotension (both resolved), and 1 died of bacterial sepsis and acute respiratory distress syndrome. Grade II acute GVHD developed in 1 patient at level I and 1 at level III. The maximum tolerated dose of induction IL-2 was level II. IL-2 induced lymphocytosis, with an increase in CD56+ and CD8+ cells. Ten patients remain in CR at 5+ to 67+ months. Thus, a regimen of IL-2 has been identified that did not induce a high incidence of acute GVHD when administered to children after unmodified allogeneic BMT. Its clinical activity will be assessed in a phase II trial.

Acute Disease↗

Platelet serotonin transporter in children and adolescents with obsessive-compulsive disorder or Tourette's syndrome.

UNLABELLED: Previous studies of serotonin transporter protein (5HTPR) indexed in platelets by 3H-imipramine demonstrate reduction in children with comorbid obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS). OBJECTIVE: To use the 5HTPR selective ligand 3H-paroxetine and homogeneous diagnostic groups to reevaluate these findings. METHOD: Platelet Kinetic binding parameters were evaluated using standard techniques from medication-free child and adolescent patients with OCD (n = 18), with TS (n = 10), and normal controls (n = 19). RESULTS: Baseline binding capacity (Bmax) was significantly reduced in patients with OCD (1,342 +/- 952 fmol/mg; protein p < .01) compared with normal controls (2,486 +/- 1309 fmol/mg) and TS patients (2,420 +/- 1,069 fmol/mg; p < .05). Among OCD patients who were subsequently treated on an open-label basis with selective serotonin reuptake inhibitor (SSRI), Bmax values at baseline differentiated between responders (1,718 +/- 1,041 fmol/mg) and nonresponders (802 +/- 713 fmol/mg protein; p < .05). Response to SSRI was greatest in patients with a positive family history of OCD. Among responders (n = 10), baseline Yale-Brown Obsessive Compulsive Scale and Bmax were positively correlated (r = .76, p = .01), as was Clinical Global Impression (r = .67, p = .03). CONCLUSIONS: Platelet 5HTPR capacity (Bmax) is reduced in children and adolescents with OCD, but not in those with TS. 5HTPR may be an indirect measure of basal serotonergic tone.

1-Naphthylamine↗

A toxicity study of trimetrexate used in combination with cyclosporine as acute graft-versus-host disease prophylaxis in HLA-mismatched, related donor bone marrow transplants.

This study evaluated the acute toxicity of trimetrexate (TMTX) used in combination with cyclosporine (CsA) for prevention of acute graft-versus-host disease (GVHD) in patients undergoing allogeneic marrow transplantation from HLA-mismatched, related donors. TMTX has a mechanism of action similar to that of methotrexate (MTX); however, unlike MTX, TMTX is not primarily dependent on renal excretion. Patients were conditioned for transplant with cyclophosphamide, anti-thymocyte globulin, and total body irradiation. TMTX, 10 mg/m2 i.v., was administered on days 1, 3, 6, 11, 18, 25, 32, and 39 after transplant. CsA, 1.5 mg/kg i.v., was administered every 12 hr beginning on day-1. Eleven patients with hematologic malignancies or aplastic anemia (median age = 34 yr) received TMTX. Toxicity assessed included nausea, vomiting, fever, rash, time to myeloid and platelet engraftment, mucositis, and hepatic and renal dysfunction. Toxicity of TMTX was not different from that observed with MTX in a similar patient population. One patient died on day 16 before engraftment. The other 10 patients all engrafted and all developed acute GVHD at a median time of 11 days after transplant. The major manifestation of acute GVHD was in the skin, and all but one patient responded to primary therapy with corticosteroids. Seven patients have survived a median of 447 days after transplant. No significant toxicity from TMTX was observed. Further trials are warranted to define the role of TMTX in marrow transplantation.

Adolescent↗

Status of the valves in the superficial and deep venous system in chronic venous disease.

The relationship between the functional status of the venous valves in the superficial and deep veins and ulceration was evaluated in 42 patients. Twenty-five patients had ulcers, 12 of these patients had a history of previous deep venous thrombosis and 13 of these patients denied such an event. Seventeen patients had normal ankle skin, 10 of these patients had a documented history of deep vein thrombosis and seven of these patients had varicose veins only. An ultrasonic duplex scanner was used to document the presence of reflux in all segments of the superficial and deep system. In the entire group of 25 limbs with ulceration, valvular incompetence was noted in 22 limbs at levels involving segments that communicated with the ulcer-bearing area. Of the 17 limbs with normal ankle skin, in only two instances was a single segment of posterior tibial vein in midcalf found to be incompetent. For those patients with normal ankle skin and a history of varicose veins, the deep veins below the common femoral vein level were always competent.

Age Factors↗

The mechanism of venous valve closure. Its relationship to the velocity of reverse flow.

Venous valves will close when the reversal of the normal pressure gradient generates a sufficient reverse flow velocity. By testing 20 healthy subjects with ultrasonic duplex scanning and controlled limb compression. It was found that the velocity of reflux is related to the external compression pressure. Valve closure is an abrupt cessation of reverse flow. In this study, with subjects in a supine position, valve closure was achieved only after reverse velocities exceeded 30 cm/s. This velocity was not generated by manual compression of the limb. With a Valsalva maneuver, this velocity is achieved only in the common femoral vein in 90% of the tested individuals. The reflux velocities in response to a Valsalva maneuver are progressively lower in more distal veins--the profunda femoris, the superficial femoral vein, and the popliteal vein. With reverse velocities lower than 30 cm/s, the valves will not close and reflux can persist. Valsalva's maneuver only allows a diagnosis of valvular competence at the most proximal level in the venous tree.

Blood Flow Velocity↗

Functional status of the deep venous system after an episode of deep venous thrombosis.

An episode of deep venous thrombosis is often followed by the opening of collaterals, fibrinolysis, recanalization and valvular dysfunction. The effect of these processes on the peak flow velocity in the superficial femoral and popliteal veins after simulated contraction of the calf muscles was tested in a group of normal subjects and three groups of patients who had deep venous thrombosis. There were 12 patients followed less than two years with no skin changes. The second group consisted of 12 patients followed for 8-15 years without ulceration. The third group of 12 patients had active or healed ulcers. The peak flow velocity in the superficial femoral and popliteal veins was assessed by rapidly inflating cuffs about the calf and ankle to 100 mmHg. The velocities generated by cuff compression were lower in patients than in normal subjects. This was particularly true in the superficial femoral vein. This change in velocity may be secondary to incomplete recanalization with resulting stenosis or valvular incompetence in the calf.

Adolescent↗

Quantitative segmental evaluation of venous valvular reflux with duplex ultrasound scanning.

The duration of deep venous valvular reflux was studied in 192 venous segments of the legs of 32 patients in good health. Three methods were used to elicit reflux in the supine and upright positions--Valsalva's maneuver, proximal limb compression, and release of distal limb compression. Standardized compressions were achieved with pneumatic cuffs. When this approach was used to study valve function, the time to complete closure of the valve and cessation of retrograde flow was found to be shorter than that for conventional methods of closure. The distal cuff deflation method is the only one that permits a quantitative and reproducible method to measure duration of venous reflux at all levels of the lower limb. Normal values obtained with this test are presented for the common femoral, deep femoral, and superficial femoral veins and for the popliteal and posterior tibial veins midway between knee and ankle level and the posterior tibial vein at the ankle. In the popliteal vein, median duration of reflux is 0.19 second; 95% of the values in the popliteal vein are less than 0.66 second. In distal areas, duration of reflux is short and uniform. The advantage of the cuff deflation test over the Valsalva method is that the cuff method is not hindered by the presence of ileofemoral valves. A better understanding of the relative importance of deep valve dysfunction at different levels and the expected benefit of valve repair may be obtained with this test.

Adolescent↗

Asymptomatic high-grade internal carotid artery stenosis: is stratification according to risk factors or duplex spectral analysis possible?

High-grade (80% to 99% diameter reduction) asymptomatic internal carotid artery stenoses are associated with an increased neurologic event rate (transient ischemic attack, stroke, asymptomatic internal carotid artery occlusion) compared to less severe asymptomatic lesions. However, many do remain free of associated events. To determine which are most dangerous, we compared risk factors and duplex scan results in two groups with asymptomatic high-grade internal carotid artery stenoses. Group A included 31 patients with 33 unoperated high-grade lesions that remained asymptomatic for at least 12 months (mean 30 months). Group B included 25 patients with 26 initially asymptomatic lesions that subsequently were associated with a neurologic event (mean time to event 7.4 months). The groups did not differ significantly in average age, sex, aspirin use, smoking, or prevalence of hypertension, diabetes, or cardiac disease. With respect to the index high-grade lesion, there was no difference in the frequency of a greater than 50% contralateral internal carotid artery stenosis or greater than 50% ipsilateral external carotid stenosis. However, on duplex scanning, high-grade stenoses with greater than 6.5 kHz end-diastolic frequencies were more frequently associated with an event than high-grade lesions with lower end-diastolic frequency (p = 0.0004). Similarly, seven of 23 lesions (30%) with end-diastolic frequency greater than 6.0 kHz were associated with subsequent internal carotid artery occlusion compared to only one of 29 (3.5%) with end-diastolic frequency less than or equal to 6.0 kHz (p = 0.025). Analysis of internal carotid artery end-diastolic frequency may help select a subgroup of patients with asymptomatic high-grade lesions who are at greatest risk for subsequent neurologic symptoms or ICA occlusion or both.

Aged↗

Duplex ultrasound assessment of venous diameters, peak velocities, and flow patterns.

Duplex ultrasound was used to study the diameters, flow patterns, and peak blood flow velocities of the common femoral vein (CFV) in 12 normal subjects (mean age 35 years). Each subject was supine and non-weight-bearing on a tilt table and rotated in 10-degree increments from -10 degrees (head down) to +30 degrees (head up). Cross-sectional B-mode image was used to monitor continuously CFV diameter for 5 minutes in each position. Doppler flow patterns were recorded in longitudinal axis; heart rate and respiratory movements were also noted. CFV flow was affected by respiratory and cardiac events. At -10 degrees flow was primarily related to cardiac events, with flow increasing during diastole. At +30 degrees flow varied minimally with the cardiac cycle and was primarily respiration dependent, stopping at peak inspiration. Proceeding from -10 to +30 degrees the mean maximal CFV diameter corrected for body surface area increased 92% (0.47 +/- 0.11 cm/m2 to 0.90 +/- 0.16 cm/m2, p less than 0.001), whereas peak flow velocity decreased from 41 +/- 10 cm/sec to 13 +/- 5 cm/sec, p less than 0.001. There was a linear, inverse relationship between mean peak velocity and mean corrected diameter, r = -0.99. The study confirms the multiple influences on venous flow patterns and establishes a quantitative relationship between venous diameters and flow velocities.

Adult↗

Cluster analysis to determine headache types.

Cluster analysis was used to separate 726 headache patients into clusters of patients with similar symptoms. This was done to answer two questions: what "naturally occurring' groups of patients can be found? And how do these groups correspond to traditional headache types? When only two clusters were required, the best two clusters were tension and migraine-like. However, eight clusters could also be distinguished, and the migraine group then became very small. The clusters were tested for clinical interpretability by having 12 physicians name and prescribe treatment for the clusters. The suggested treatment was similar to what patients had actually received in about 2/3 of the cases but was rather different for the remainder. Further, the outcomes associated with different treatments appeared to vary by cluster. This suggests that the current method for classifying and treating headaches may not be optimal.

Adult↗

Computer based pattern recognition of carotid arterial disease using pulsed Doppler ultrasound.

A minicomputer based system has been developed for studying carotid artery blood flow data obtained for a combined B-mode, pulsed Doppler ultrasound scanner. The goals of this work are to devise and improve techniques for estimating the extent of atherosclerosis at the carotid artery bifurcation. Features are automatically extracted from spectrum analyzed Doppler blood flow data. Five statistical pattern recognition algorithms are compared, with cross validation being used to improve the estimate of classification accuracy. A data collection protocol has been devised in which four sites are studied along each carotid arterial system. Classification of unknowns is done using a hierarchy of three decisions.

Adult↗

Pitfall of venous occlusion plethysmography.

The supposition that the lower limb expands uniformly in circumference during venous occlusion has been investigated. The 3 compartments of the calf were found to be expand to differing degrees depending on the volume of muscle within the compartment. The effect of this phenomenon on the measurement of venous outflow and capacitance using an overlapping strain gauge was assessed. When using an overlapping strain gauge, the anatomical site of overlap was found to alter the measured values of outflow and capacitance by as much as 50%. These errors do not arise with strain gauges designed to fit a small range of limb circumferences, so that no overlap occurs. The reproducibility of plethysmography may be enhanced by attention to the site and degree of overlap of gauges which are designed to fit all sizes of limb. Technicians performing venous occlusion plethysmography should be aware of these variations, so that the examination technique can be standardized.

Acute Disease↗