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Biomedical subjects

J M Mishler

Publications and source records attributed to J M Mishler.

At least 19 recordsLinked to original sources
PubMed1979

The plasma kinetics of hydroxyethyl starch 350/0.60: a potential new adjunct for centrifugal leucapheresis.

A modified species of hydroxyethyl starch (HES 350/0.60) possessing a Mw- of 350,000 daltons combined with a molar hydroxyethyl group substitution (MS) of 0.60 (60 hydroxyethyl groups.100 glucose residues) was clinically assessed in seven normal subjects to determine the influence of these chemical modifications on intravascular clearance kinetics concomitantly with effects on the suspension stability (ESR) of blood. Following a standardised intravenous dose (30 gm.m2 BSA), the concentration of HES 350/0.60 in serum fell to half its peak value in 11.8 +/- 1.3 (SD) hours, while the ESR remained elevated for up to 12 hours post-injection. By adopting a Mw- of 350,000 daltons, the critical molecular weight (Cmw) of this colloid was surpassed, while the critical concentration (Cc), below which the suspension stability of blood is not affected, was shown to range between 0.3 and 0.5 gm.dl-1. In comparison to the present species of HES (Mw- 450,000 daltons, MS: 0.70) utilised as a sedimenting agent duirng centrifugal leucapheresis, HES 350,000/0.60 appears to affect the ESR in a similar manner, but is removed from the intravascular space approximately twice as rapidly. This more rapid clearance should be useful in avoiding cumulative build-up of HES in blood concomitant with reducing the total amount of intravascular H2O bound to this colloid, in normal and CML donors undergoing multiple cell collection procedures.

Adult↗
PubMed1979

Changes in the molecular composition of circulating hydroxyethyl starch following consecutive daily infusions in man.

1 Changes in the circulating molecular composition of hydroxyethyl starch (HES) were determined in four normal men following three consecutive daily 500 ml infusions (total 1,500 ml), by passage of trichloroacetic acid filtrates of plasma through a Sepharose CL4B gel filtration column. 2 The HES recovered from the intravascular space 10 min following the injection on Days 1, 2 and 3, was of a narrower molecular size distribution than the injected material, with a noticeable shift to molecules of a low molecular weight (LMW) size. 3 The HES in the sampled plasma 24 h post-injection on Days 1, 2 and 3 consisted of molecules possessing a LMW distribution, concomitantly with a slight shift to molecules of a larger molecule size. 4 The HES recovered from the bloodstream 480 h after the third and final injection consisted of molecules possessing an intermediate size distribution, between LMW and high molecular weight (HMW) size material. 5 The results indicate that large HES molecules contained in the injected material are eliminated from the bloodstream; the HMW fraction at least partially by a alpha-amylase mediated catabolism, and the resulting LMW fraction by excretion.

Adult↗
PubMed1979

A clinical study of low molecular weight-hydroxyethyl starch, a new plasma expander.

1. The pharmacokinetics of a new plasma expander, low molecular weight-hydroxyethyl starch (LMW-HES) were examined in six normovolaemic men. 2. One hour post-infusion, 13.5% of the total dose of LMW-HES injected was excreted in the urine, 50.2% was present in the intravascular space, and 36.3% was unaccounted for. 3. Twenty-four hours post-infusion, 65.5% of the total dose of injected LMW-HES had been excreted in the urine, 4.1% remained intravascularly, and 30.4% was unaccounted for. 4. The plasma volume increased rapidly from a mean value of 45.7 ml kg-1 to a maximum value of 57.9 ml kg-1 immediately post-injection, then gradually returned to normal over 24 h. 5. The infusion of an average of 58.1 g had no effect on ESR, renal and hepatic biochemical indices. 6. LMW-HES appears to be safe and effective, and should be of value clinically when rapid and short-lived augmentation of the plasma volume is required.

Adult↗
PubMed1979

Viability of red cells stored in diminished concentration of citrate.

A comparison was made between the post-transfusion survival of red cells stored in standard ACD-A and in modified ACD-A, containing two-thirds the amount of citrate. Measurements of survival after 28 d storage in both solutions were made in each of six subjects. Mean post-transfusion survival with the two solutions was almost identical. When the results in one subject in whom survival was particularly bad with both solutions were omitted mean values at 24 h were 74.0% for standard ACD-A and 74.9% for modified ACD-A. It is concluded that viability is just as well maintained in modified ACD-A as in standard ACD-A. The results also provide further evidence of large differences between donors with respect to the maintenance of red cell viability during storage.

Adenosine Triphosphate↗
PubMed1979

Transfusion of hydroxyethylated amylopectin-protected frozen blood in man. I. Plasma clearance and renal excretion of the cryoprotectant.

In man following the autologous transfusion of blood previously frozen with 14% low molecular weight-hydroxyethylated amylopectin (cryo-HES), the clearance of this material from the intravascular space was compound, and appeared to consist of exponential components. The overall half-life -- however, was 10.6 +/- 3.0 (SD) h. Approximately 17% of the total infused cryo-HES was excreted in the urine 1 h postinjection, and 40% by 72 h. The erythrocyte sedimentation rate (ESR) was not affected by the presence of this substance in the bloodstream of the recipient. The results indicate that cryo-HES is removed rapidly following the transfusion of blood previously frozen with this material.

Adult↗
PubMed1979

The utilisation of a new strength citrate anticoagulant during centrifugal plateletpheresis. III. Assessment of in vitro platelet metabolism.

Employing the Haemonetics Blood Processor (IFC), a relatively pure platelet concentrate can be prepared by collecting only the first portion of the PRP leaving the centrifuge bowl (Fraction I). A subsequent fraction containing RBC and WBC contaminants (Fraction II) can be purified by means of a second centrifugation, using a conventional blood bank centrifuge (Fraction II), if transfusion of these contaminants would be detrimental to the recipient. Utilising the new 1.4% Na3-citrate anticoagulant, platelet metabolic parameters (ATP, ADP, AMP, lactate and pyruvate) as well as O2-uptake, were determined in Fraction I and II prepared from 10 normal healthy subjects. In contrast to previous studies reporting marked dysfunction in platelets contained in Fraction II when standard ACD-A was used during IFC, we observed no significant difference (Student's t test) in the present study between Fractions I and II, in regard to platelet metabolism, when using the new anticoagulant. It is further concluded that the second centrifugal manipulation does not exert a detrimental effect on platelet metabolism.

Anticoagulants↗
PubMed1979

Macroamylasaemia following the infusion of low molecular weight-hydroxyethyl starch in man.

In fasted normovolaemic subjects dosed with 400 ml of 14% low molecular weight-hydroxyethyl starch (LMW-HES, Mw 264,000 daltons, Mn 63,000 daltons, Mw/Mn = 4.2, MS = 0.43), an increase in the concentration of alpha-amylase was observed in blood which exceeded the upper limit of normal (190 U-1(-1), and in all cases reached twice the basal value. Concomitant with this elevated activity in the blood, the urinary excretion of this enzyme was significantly reduced. Gel filtration of serum recovered from 1 subject on a column of Sephadex G-100 revealed the presence of an LMW-HES-induced macroamylase, detectable for up to 6 h post-injection. This induced alpha-amylase-LMW-HES complex is apparently of a molecular weight that is not easily filtered at the renal glomerulus, thus accounting for the observed hyperamylasaemia concomitant with the decrease in renal excretion. By 12 h post-injection however, the high activity of alpha-amylase in the blood was returning to normal levels and this was observed to parallel the reduction in the formation of macroamylase complexes in serum.

Adult↗
PubMed1979

Catabolism of low-molecular-weight hydroxyethylated amylopectin in man. I. Changes in the circulating molecular composition.

Intravascular persistence concomitant with changes in the circulating molecular composition were determined in six fasted normal men dosed with 400 ml of 14% LMW-HES (a new plasma expander). The concentration of LMW-HES in serum fell to half its peak value in 3.9 +/- 1.1 (S.D.) hr, whereas serum levels of glucose remained elevated throughout the 12 hr postinjection fasting period. The LMW-HES recovered from the intravascular space was shown by gel filtration on a column of Sepharose CL-4B to be a narrower molecular size distribution (less polydispersion) than the injected material. The ratio of Kav . urine/Kav . injected solution was 1.34. At 30 min after injection, however, the ratio of Kav . urine/Kav . serum was 1.20, and by 24 hr, the value was 1.15. Overall, changes in the molecular distribution in the bloodstream between the end of the infusion period and 24 hr later were small. The results suggest that the intravascular catabolism of LMW-HES may occur in two distinct phases: a rapid initial degradation, followed by a more gradual elimination influenced by the MS of the injected material.

Adult↗
PubMed1979

[Mathematical decription of the human intravascular elimination of HAS after repeated infusions].

Serum concentrations of high molecular weight-hydroxyethyl starch (HMW-HES, Mw 450,000 d, Mn 71,000 d, Mw/Mn = 6.3, MS = 0.7) were determined in normovolemic subjects dosed with three consecutive daily 500 ml infusions, to mathematically calculate the influence of the two-variable (Mw and MS) HES drug design system, on elimination of this material from the intravascular space under controlled conditions. Following the initial 500 ml (6% solution) infusion, the intravascular clearance up to 24-hours post-injection, was well predicted by the exponential equation: y = 3.94 + 3.34e-0.15x. On days two and three, the clearances up to 24-hours post-injection, were described by the equations: y = 6.32 + 3.75e-0.15x and y = 9.39 + 5.41e-0.15x, respectively. From these mathematical models, it appears that up to 24-hours post-injection on each of the three infusion days, HMW-HES is cleared from the bloodstream in a similar manner. HMW-HES clearance from the blood on day three, however, exhibited a slightly faster rate of decline, as seen by the larger coefficient attributed to the exponential component. The serum concentration of HMW-HES, 480 hours (2.9 weeks) following the third and final infusion, was 2.3 +/- 0.3 (SD) mg ml-1. Thus, in the 480-hour interval following the third and final injection, the serum concentration of HMW-HES measured at 10 minutes after injection 3, had been reduced by 85%. This decline in serum concentration following the infusion of HMW-HES, appears to be greater than previously reported by other investigators.

Humans↗
PubMed1978

Whole blood storage in citrate and phosphate solutions containing half-strength trisodium citrate: cellular and biochemical studies.

The efficacy of whole blood preservation in acid citrate dextrose (ACD-A) and citrate-phosphate dextrose (CPD) anticoagulants containing half-strength trisodium citrate concentrations, was determined by biochemical and cellular assessment during 28 day storage at 4 degrees--6 degrees. Erythrocyte 2,3-DPG and ATP concentrations, serum potassium, plasma haemoglobin, and blood pH values were similar between the standard and half-strength citrate counterpart in both ACD-A and CPD series, throughout the entire storage period. Erythrocyte indices (MCV, MCH, MCHC, and osmotic fragility) and the red cell, platelet, and leucocyte counts, were also similar regardless of the final citrate concentration in both ACD-A and CPD series during the 28 day storage period. Tests of coagulation (PT, KCCT, TT, and ethanol gel) and fibrinogen levels were also similar, except for a lower quantity of clottable fibrinogen at day 28 in half-strength CPD. The formation of platelet and leucocyte aggregates during storage, as measured by changes in the SFP, were similar in magnitude whether or not the half-strength citrate formulation was used in ACD-A or CPD. Phagocytic and bactericidal capacity against Staph. aureus was normal following 24-hr storage at 4 degrees--6 degrees, in both ACD-A and CPD preserved blood, regardless of the final citrate concentration. It may now be concluded from this evaluation and those of others, that a reasonable argument can be made for reducing the citrate quantity presently used during blood storage, in order to provide a safe and effective transfusion product for routine use.

Adenosine Triphosphate↗
PubMed1978

Plasma clearance and renal excretion of erythrocyte cryoprotectant hydroxyethylated amylopectin.

The value of low molecular weight-hydroxyethylated amylopectin (cryo-HES) as an extracellular cryoprotectant has been demonstrated in vitro. It is important that details of the intravascular persistence and urinary excretion be determined to compare with data already available as other grades of HES and with data on transfusion of cryo-HES cryoprotected blood. Following a single 400 ml (14% solution) infusion in man, the intravascular clearance of cryo-HES was well described mathematically by the equation: y = 3.30+6.49e-0.15kappa. The plasma concentration of cryo-HES fell to half its peak value in approximately 9.6 h. Approximately 20% of the total infused cryo-HES was excreted in the urine during the first post-injection hour, and 50% by 72 h. The ESR was not altered significantly by the presence of this material. The present study indicates that cryo-HES is eliminated rapidly and may thus be safe for transfusion to recipients of frozen blood.

Adult↗
PubMed1977

The utilization of a new strength citrate anticoagulant during centrifugal plateletpheresis. II. Assessment of in vitro platelet function.

Platelets contained in concentrates prepared by intermittent flow centrifugation utilizing 5.0 g total ionized citrate, function normally as assessed by tests for adhesion, spreading, and ADP and collagen-induced aggregation. The ability of platelets to adhere and to aggregate following incubation with ADP is significantly reduced, in samples taken immediately after the collection procedure. Total platelet collection and platelet collection efficiency, is not compromised by use of the above citrate concentration.

Anticoagulants↗
PubMed1977

Hydroxyethyl starch. An agent for hypovolaemic schock treatment II. Urinary excretion in normal volunteers following three consecutive daily infusions.

1 Urinary hydroxyethyl starch (HES) concentrations were determined by the anthrone method, in four healthy normal male volunteers following three consecutive daily 500 ml infusions (total 1500 ml), in order to ascertain excretion rates under normal controlled conditions. 2 The HES was excreted at a rate of 2.57, 2.46, and 2.44 g/h during the first hour postinjection, on days 1, 2, and 3, respectively. 3 The rate during the interval 12-24 h postinjection, averaged 0.14, 0.21, and 0.10 g/h, on days 1,2, and 3, respectively. 4 In the intervals 24-72, 72-120, and 120-168 h after the third and final injection, the excretion rate was 0.07, 0.04, and 0.02 g/h, respectively. 5 Renal function, as assessed by serum creatinine and uric acid concentrations and 24 h void volumes, was normal during the entire period of observation. 6 The results indicate that HES is excreted at a similar rate following three consecutive daily infusions without evidence of renal injury.

Adult↗
PubMed1977

Development of Neutrophilia by serially increasing doses of dexamethasone.

Dexamethasone (4-8 mg/m2 body surface area) was given orally or intravenously to six normal volunteers. The maximum neutrophil count occurred 4-6 h after oral or intravenous administration of dexamethasone and was due almost entirely to an increase in mature neutrophils; concomitantly there was a lymphocytopenia. A second rise in the neutrophil count occurred 24 h after oral ingestion of dexamethasone, coinciding with a lymphocytosis. Neutrophil alkaline phosphatase (NAP) activity during development fell as the neutrophil count rose. Other haematological values were unchanged except for small increments in erythrocyte sedimentation rate (ESR). Sodium concentration in serum and urine remained normal but urinary potassium excretion and urine volume increased after the intravenous dose. There was a direct relationship between plasma concentration of dexamethasone and the rise in neutrophil count following intravenous but not oral administration. The concentration of dexamethasone in plasma fell to half its peak value in 2-6 h. Dexamethasone-induced neutrophilia was similar to that induced by other corticosteroids. Dexamethasone in a dose of 6 mg/m2 produced minimal discomfort while inducing an adequate neutrophilia in the volunteers.

Adult↗