Biomedical subjects

M Rendell

Publications and source records attributed to M Rendell.

At least 37 records · Page 2Linked to original sources

PubMed1992

Red cell filterability determined using the cell transit time analyzer (CTTA): effects of ATP depletion and changes in calcium concentration.

Cell transit time analysis (CTTA) is a new filtrometric technique for assessing red blood cell deformability by measuring the conductivity change caused by passage of erythrocytes through a polycarbonate filter. Most reported studies to date using CTTA have focused on the transit time (TT), the duration of passage of an individual red cell through a micropore. Bulk flow rate has not been previously measured via CTTA. The use of new enzyme based cleaning solutions make it possible to reduce clogging in micropore filters. Therefore, valid measures of the number of red cell transits per unit time (counts/s: C/S) can now be obtained. We evaluated both parameters, TT and C/S, as indicators of red cell filterability. Our goal was to evaluate the effect of metabolic changes shown by alternative techniques to affect red cell deformability. The two best established factors are changes in intracellular [ATP] and [Ca2+]. ATP depletion produces a very small increase in TT but a very marked decrease in C/S. In contrast, the addition of low concentrations of calcium produces an increase in TT with minimal decrease in C/S. The effects of calcium appear to be complex. The substantial changes in intracellular calcium induced by the ionophore A23187 result in a curvilinear pattern of increase in transit times and reduction in counts per s. Lanthanum, which inhibits egress of intracellular calcium, causes an increase in TT with a drop in C/S. We conclude that CTTA demonstrates the same changes in red cell deformability measurable by alternative filtrometric techniques; however, CTTA furnishes two separate and independent parameters which may be used to evaluate red cell deformability.

Adenosine Triphosphate↗

PubMed1992

Diabetic cutaneous microangiopathy.

PURPOSE: To determine a potential relationship between skin blood flow changes and the duration of diabetes and the presence of other microvascular complications. PATIENTS AND METHODS: Skin blood flow was measured by laser Doppler techniques at the finger and toe pulps, areas of predominant arteriovenous anastomotic (AVA) flow, and on the finger and toe dorsums, which have a greater nutritive microvascular contribution, in 83 diabetic patients and 39 nondiabetic control subjects. The average duration of diabetes was 14 +/- 1 years. Thirty-four patients had retinopathy. Eighteen patients had proteinuria. Forty patients had definite signs and symptoms of neuropathy, whereas 11 had no detectable neuropathy. RESULTS: There was little difference between diabetic and nondiabetic skin blood flow at normal body temperatures. However, at an elevated skin temperature of 44 degrees C, significant reductions in skin blood flow versus control were demonstrated in the diabetic group. Skin blood flow at finger and toe dorsums showed a decrease as a function of the duration of diabetes. In contrast, there was little, if any, relationship between the duration of diabetes and skin blood flow at the finger and toe pulps. Diabetic patients with retinopathy had significantly lower blood flow at both finger and toe dorsums than those without retinopathy. Even excluding patients with recent onset of diabetes from the analysis, flows at finger (18.6 +/- 2.0 mL/min/100 g) and toe dorsums (11.2 +/- 1.4 mL/min/100 g) in the patients with retinopathy were significantly lower than in diabetic patients without retinopathy [finger: 28.6 +/- 2.7 mL/min/100 g (p < 0.01) and toe: 15.1 +/- 1.5 mL/min/100 g (p < 0.05)]. The presence of proteinuria was also associated with lower blood flow at the toe dorsum. There were no differences between patients with or without clinical diabetic neuropathy. At finger and toe pulps, there were no significant differences between diabetic patients with or without retinopathy, proteinuria, or neuropathy. CONCLUSIONS: There appears to be a diabetic cutaneous microangiopathy that coexists with diabetic retinal and renal microvascular disease. This process is expressed primarily at sites of nutritive microvasculature. The ability to use the skin as a model for diabetic microangiopathy would have great practical importance, both experimentally and in clinical practice.

Adult↗

PubMed1992

Skin blood flow and current perception in pentoxifylline-treated diabetic neuropathy.

There are several anecdotal reports of improvement in diabetic sensory neuropathy following a course of pentoxifylline therapy. Pentoxifylline theoretically could improve skin blood flow, thus reducing ischemia at axonal endings. The authors used laser Doppler techniques to measure skin blood flow and measured sine wave current perception thresholds (CPTs) in pentoxifylline-treated diabetic patients with sensory neuropathy. Twenty-four patients completed a six-month course of treatment. These patients had a predominantly "stocking" neuropathy; all the major abnormalities on clinical, laser Doppler, and current perception testing were found on the lower extremity. Seventeen of the 24 patients reported symptomatic improvement. A careful, graded neurologic examination confirmed that improvement, with a decrease in symptom score on the lower extremity (SSDW) from a baseline of 5.0 +/- 0.7 to 3.5 +/- 0.7 (p < 0.01) and of physical score (PSDW) from baseline 22.0 +/- 2.0 to 16.0 +/- 1.9 (p < 0.01) after six months. On the lower extremity, there was an increase in laser Doppler measured flow score (FS) both at 35 degrees and at 44 degrees C. FSDW (35 degrees) increased from 10 +/- 2 to 14 +/- 3 at six months (p < 0.05). FSDW (44 degrees) increased from 58 +/- 5 to 77 +/- 7 at six months (p < 0.01). There was an improvement in sine wave current perception measured by current perception threshold score (TS). TSDW dropped from 150 +/- 32 to 84 +/- 28 at six months (p < 0.03). In patients with diabetic sensory neuropathy, pentoxifylline appears to improve skin blood flow. Current perception thresholds improve in tandem, corroborating improvement in clinical neurologic findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1991

Effects of glycemic control on red cell deformability determined by using the cell transit time analyzer.

There is considerable evidence that blood viscosity is greater than normal in diabetes, and decreased red blood cell deformability has been suggested as the cause. However, viscosity can be influenced by changes in the properties of blood proteins in addition to red cells. Direct interpretation of red cell filtrometry data in terms of deformability has been complicated by the interfering effect of white cells and platelets and clogging of micropores. We have thus used the cell transit time analyzer, a new filtrometric procedure that eliminates these complications and produces an individual red cell micropore transit time profile, to reassess diabetic red cell deformability. Samples from 26 patients with diabetes and an equal number of subjects without diabetes who served as controls were assayed by the cell transit time analyzer at 2 and at 4 cm hydrostatic pressure. Samples from patients with diabetes and controls were sex and age matched for daily runs. At 2 cm H2O, red blood cell transit time for the patients with diabetes was 2.73 +/- 0.05 milliseconds as compared with 2.67 +/- 0.05 milliseconds for controls (p not significant). The ratio of transit time for patients with diabetes to that of controls (Td/Tnd) was 1.03 +/- 0.01 (p less than 0.05, Wilcoxon) at 2 cm H2O and 1.02 +/- 0.01 (p not significant) at 4 cm H2O.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Microvascular blood flow, volume, and velocity measured by laser Doppler techniques in IDDM.

A laser Doppler device with the capability to simultaneously measure skin blood flow, microvascular volume, and erythrocyte velocity was used to assess blood flow changes in 35 insulin-dependent diabetes mellitus (IDDM) subjects, mean age 33 +/- 1 yr, with average duration of diabetes 14 +/- 1 yr, and in a nondiabetic control group. Blood flow was determined at 35 and 44 degree C at several sites on the upper and lower extremities with a temperature-regulated probe. Blood flow was highest at both temperatures on the pulps of the index finger and the first toe, regions of high density of arteriovenous anastomoses. There was significantly greater blood flow at most locations for the nondiabetic than the diabetic group at 35 degree C, and the differences between the two groups were substantially larger at 44 degree C. At 44 degree C, blood flow in the control group was approximately 40% greater in the upper extremity and 50% greater in the lower extremity than it was in the diabetic subjects. The differences were attributed to decreases of both microvascular volume and velocity in the diabetic group. In the upper extremity, volumes in the diabetic patients were 10-15% lower and velocities 10-40% lower than in the nondiabetic subjects. In the lower extremity, volumes were 20-25% lower and velocities 40-50% lower. We conclude that laser Doppler techniques can be used to assess microvascular changes in the skin of diabetic patients. This approach may be useful to evaluate and model diabetic microangiopathy.

Adult↗

PubMed1986

Comparison and contrast of affinity chromatographic determinations of plasma glycated albumin and total glycated plasma protein.

Techniques for affinity measurement of glycated albumin and for glycated total plasma protein have been developed. The two techniques were contrasted. Both techniques are linear over a 100-fold range of sample concentrations. There appears to be a non-specific early glucose binding phase to non-albumin plasma proteins. Although this phase is detected by radioactive incorporation and thiobarbituric acid, it does not interfere with the affinity determination, which does not appear to detect the early binding species. The correlation of glycated albumin levels with glycated hemoglobin levels is much stronger than that of glycated globulin levels with glycated hemoglobin levels. Due to the large contribution of glycated albumin levels to total glycated serum protein levels, the correlation of the latter with glycated hemoglobin levels is sufficiently strong to allow the use of either technique as an adequate index of glycation.

Boronic Acids↗

PubMed1986

Clinical use and time relationship of changes in affinity measurement of glycosylated albumin and glycosylated hemoglobin.

Simple techniques for measurement of glycosylated hemoglobin and glycosylated albumin by affinity chromatography on m-aminophenylboronic acid agarose columns have recently been developed. This study explored the time course of changes in glycoalbumin versus those of glycohemoglobin in response to rapid changes in ambient glucose concentration. One would predict that glycoalbumin levels would change more rapidly than glycohemoglobin levels due to the shorter half-life of albumin than hemoglobin. This was found to be the case in a group of rabbits rendered diabetic with alloxan. Glycoalbumin levels plateaued 4 weeks after alloxan administration, while glycohemoglobin levels were still rising. In a group of diabetic patients in whom glucose levels were initially poorly controlled, strict diet or intensive insulin management were used to rapidly bring glucose levels under control. In this group of patients, the glycoalbumin values entered the normal range and plateaued, while glycosylated hemoglobin levels were still falling. Glycoalbumin determination by affinity chromatography is a valuable adjunct to glycosylated hemoglobin determination in evaluating near term control of blood sugar values.

Animals↗

PubMed1986

New screening device for assessment of peripheral neuropathy.

Screening for the onset of toxic and entrapment neuropathy is a major concern in occupational medicine today. Current perception thresholds may be used as a measure of the integrity of the peripheral nervous system. A new transcutaneous nerve stimulator was used to evaluate current perception thresholds in 54 normal persons and 33 diabetic subjects. Current perception thresholds in the normal volunteers with no evidence of peripheral neuropathy were found to vary significantly with the frequency and location of the stimulation, as well as age. The test identified the diabetic peripheral neuropathy with an overall sensitivity of 94%. This new diagnostic technique is quick, simple to perform, noninvasive and nonaversive and provides a sensitive quantitative measure of sensory function. This diagnostic stimulator will be useful for screening occupationally related toxic and entrapment neuropathies in which sensory impairment is an early finding.

Adult↗

PubMed1986

Inhibition of glycation of albumin and hemoglobin by acetylation in vitro and in vivo.

Aspirin (acetylsalicylic acid or ASA) is known to inhibit glycosylation (glycation) of albumin in vitro. The mechanism has been presumed to be acetylation, but this has never been validated. The new affinity aminophenylboronic acid procedure for determination of glycosylated albumin was used to demonstrate inhibition of glycosylation by aspirin. ASA, but not salicylic acid, inhibited glycation. The inhibition of glycation by equimolar acetic anhydride was greater than that by ASA. Pretreatment of albumin with ASA in the absence of glucose demonstrated that inhibition was extremely rapid, occurring in a matter of minutes. However, the inhibition by ASA could not be prevented by massive acceleration of glycation induced by borohydride reduction. Glycation of hemoglobin was also inhibited by ASA, but the dose requirement was considerably higher. Various analogues of ASA were evaluated for inhibition of glycation. Only acetyl-5-ethylsalicylic acid was more effective than ASA in inhibiting albumin glycation. None of these agents was more potent than ASA in inhibiting glycation of hemoglobin. ASA was fed to diabetic rats in a long-term experiment. Glycohemoglobin and glycoalbumin levels were decreased by ASA administration. We conclude that ASA inhibits glycation by a very rapid acetylation process. This process is apparently quite selective in terms of the protein involved, presumably because of the local environment of affected lysine groups. The phenomenon can be produced in vivo by administration of ASA.

Acetylation↗

PubMed1985

An interspecies comparison of normal levels of glycosylated hemoglobin and glycosylated albumin.

Aminophenylboronic acid affinity chromatography was used to measure glycosylated hemoglobin and glycosylated albumin levels in a variety of species. The highest glycosylated hemoglobin levels were found in man, the lowest in the chicken and the pig. The highest glycosylated albumin levels were found in avian species, the lowest in the mouse and the rat. A simple kinetic model was used to analyze the rates of formation of glycosylated hemoglobin and albumin in the various species. Rates of glycosylated albumin formation were very similar across the species while rates of glycosylated hemoglobin formation were quite different, presumably reflecting wide differences in erythrocyte permeability to glucose among the species.

Animals↗

PubMed1985

'Chemical hyperthyroidism': the significance of elevated serum thyroxine levels in L-thyroxine treated individuals.

We have previously reported that L-thyroxine treated patients may often have elevated serum T4 concentrations and yet show no clinical signs of hyperthyroidism. We found that such patients had normal serum T3 concentrations. The present study explored the relationship between serum T3 and T4 and dosage of L-thyroxine. Retrospective analysis of 99 patient records was performed. There was an increase of serum T4, serum T3 resin uptake (T3R), and T3 with increasing dose of L-thyroxine. The T3/T4 ratio decreased with increasing dose of L-thyroxine and with increasing T4. This phenomenon was analysed prospectively by starting 23 individuals on L-thyroxine and progressively incrementing the dose until either symptoms of hyperthyroidism developed or T4 levels exceeded the upper unit of the normal range. Once again, there was a progressive increase in serum T4, T3R, and T3 with increasing dose of L-thyroxine. At even the lowest dose of L-thyroxine (0.05 mg), there was a marked fall in T3/T4 ratio as compared to untreated individuals. The T3/T4 ratio fell further with increasing dose but with a fairly weak correlation. The decrease in T3/T4 ratio showed a much stronger correlation with serum T4. Of the 23 individuals, all exceeded the upper limit of the normal range of serum T4. No individual with elevated T4 developed clinical signs of hyperthyroidism unless serum T3 was also elevated beyond the normal range. Of eight individuals who reached elevated T3 levels, six demonstrated clinical signs of hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

PubMed1985

Aminophenylboronic acid affinity chromatography and thiobarbituric acid colorimetry compared for measuring glycated albumin.

Two techniques originally developed for measurement of glycated ("glycosylated") hemoglobin but also applicable to determination of glycated albumin are the thiobarbituric acid colorimetric technique (I) and the aminophenylboronic acid affinity chromatographic procedure (II). The latter reliably distinguishes diabetics from nondiabetics, and concentrations of glycated hemoglobin and glycated albumin are linearly correlated. I is nonspecific; it neither correlates with diabetic status nor with values derived via the affinity technique. Most of the chromogenic material is present in the fraction of albumin that does not bind to aminophenylboronic acid. Glucose interferes significantly with I but only slightly with II. Prolonged incubation of plasma with glucose dramatically increases the II-determined glycated albumin. Reactivity with thiobarbituric acid increases much less, and mainly in the II-bound fraction. This fraction contains a high proportion of nonspecifically reactive material. The percentage of glycated albumin determined in crude plasma samples by II differs only slightly from the value determined by purifying the albumin from the plasma. This technique appears more promising than I for eventual clinical applications.

Blood Glucose↗

PubMed1985

Use of aminophenylboronic acid affinity chromatography to measure glycosylated albumin levels.

A simple technique for the measurement of glycosylated albumin by affinity chromatography on m-aminophenylboronic acid agarose columns is presented. The technique relies on bromcresol green determination of albumin in the nonbound and bound fractions. There is a linear correlation between albumin concentration of the bound fraction and glycohemoglobin values in individuals. A control nondiabetic plasma pool with a glycohemoglobin value of 7.10% +/- 0.05% (mean +/- SEM) had a glycoalbumin value of 1.64% +/- 0.06%, while a diabetic control plasma pool with a glycohemoglobin value of 13.63% +/- 0.07% had a glycoalbumin value of 4.02% +/- 0.12%. Compared with results from the affinity technique, the preponderance of colorimetric reaction determined with the thiobarbituric acid procedure is nonspecific, in that it does not correlate with diabetic status or with values derived by the affinity procedure. The bulk of thiobarbituric acid-reactive material is present in the fraction of albumin that does not bind to aminophenylboronic acid. This nonbound fraction contains plasma glucose, which significantly interferes with thiobarbituric acid determinations but only very slightly interferes with the affinity procedure. Prolonged incubation of plasma with 500 mg/dl glucose dramatically increases affinity-determined glycosylated albumin. Thiobarbituric acid reactivity increases much less, the increase being mainly in the fraction bound to aminophenylboronic acid. The percentage glycosylated albumin determined by the affinity technique in crude plasma samples differs very slightly, if at all, from that determined by purification of the albumin from plasma. The affinity technique appears very promising for eventual clinical applications in the management of diabetes.

Blood Glucose↗

PubMed1983

A pharmaceutical profile of diabetic patients.

Although there have been innumerable studies documenting various aspects of the morbidity caused by diabetes mellitus in the population, very little attention has been paid to patterns of therapeutic management of diabetic patients. The United States Public Health Service Ambulatory Care Data System (USPHS ACDS), a computerized patient information entry and recording system with a complete pharmaceutical record for each patient, was used to compare patterns of pharmaceutical consumption among diabetic patients as opposed to non-diabetic patients in a population of approximately 90,000 individuals. Drug use by diabetics was significantly higher than by non-diabetics. Cardiovascular drug use, in particular, was considerably higher. Substantially higher consumption of anti-lipemic agents, anti-gout drugs, anti-hypertensives, sedatives and tranquilizers was also found in the diabetic population. The higher use of all drugs by diabetics could be partially explained by a demonstrably higher frequency of out-patient visits by diabetics. However this factor alone could not account for very much higher use of certain selective drug groups by the diabetics. In most cases, these selective increases among the diabetics paralleled expected patterns of disease for which those drug groups are prescribed. The investigation of pharmacotherapeutic profiles of the diabetic population adds a new dimension to the epidemiological study of this disease.

Adult↗

PubMed1983

C-peptide levels as a criterion in treatment of maturity-onset diabetes.

C-Peptide levels, both basal and glucose-stimulated, were contrasted in diet-controllable vs. nondiet-controllable maturity-onset diabetic patients. Fasting and glucose-stimulated plasma C-peptide values in diet-controlled diabetics were similar to those in normal subjects. Diabetic patients who were not solely diet controllable could be differentiated into two subgroups. One diet failure subgroup was truly insulin dependent, in that insulin treatment could not be stopped for even a brief period. In these patients, fasting C-peptide levels were very low, in the same range as in the majority of juvenile-onset diabetic patients. In the second diet failure subgroup, it was possible to manage patients without insulin therapy for varying periods of time, although most patients eventually needed insulin. Fasting C-peptide levels in this second subgroup were also in the same range as those in normal subjects. However, their C-peptide responses to glucose were significantly blunted. Measurement of C-peptide may furnish a useful criterion for the categorization of maturity-onset diabetic patients. Furthermore, C-peptide levels help considerably in the selection of treatment modalities for these patients. Low C-peptide levels identify those patients who require insulin treatment, whereas high C-peptide levels in insulin-treated patients suggest the possibility of discontinuing insulin.

Adult↗

PubMed1982

Chemical hyperthyroidism: serum triiodothyronine levels in clinically euthyroid individuals treated with levothyroxine.

We have observed many patients treated with levothyroxine sodium who have elevated serum thyroxine (T4) levels but appear clinically euthyroid. Such patients generally have normal serum triiodothyronine (T3) values. A retrospective review at The Johns Hopkins Hospital, Baltimore, comparing the correlation of T3 and T4 values in levothyroxine-treated patients with that in patients not so treated was carried out from 1977 to 1979. Mean free thyroxine index (FTI) value in 104 levothyroxine-treated patients was 4.70 +/- 0.2 and mean T3 value was 177 +/- 9 ng/dL. In a group of 50 hyperthyroid patients, mean FTI value was 7.26. +/- 0.5, with a mean T3 value of 389 +/- 26 ng/dL. In 71 euthyroid patients, mean FTI value was 2.36 +/- 0.1, with a T3 value of 137 +/- 3 ng/dL. Computed ratios of T3 to FTI and T3 to T4 were significantly lower in the group treated with levothyroxine than in either the hyperthyroid or euthyroid nontreated groups. Levothyroxine-treated patients with high T4 levels but normal T3 levels were clinically euthyroid. Patients not treated with levothyroxine with similarly elevated T4 levels had elevated T3 levels and were clinically hyperthyroid. It is concluded that lower relative T3 levels in levothyroxine-treated patients may explain why these patients appear clinically euthyroid despite elevated T4 values. Serum T3 determination is the procedure of choice for evaluation of levothyroxine-treated individuals. Furthermore, an elevated FTI value in such an individual does not, in itself, dictate need to reduce dosage.

Drug Administration Schedule↗

PubMed1982

Estimation of the secretion rate of insulin from the urinary excretion rate of C-peptide. Study in obese and diabetic subjects.

Direct methods for measuring the secretion rate of insulin are too cumbersome for clinical application. Since C-peptide is secreted in an equimolar ratio with insulin and is excreted into the urine, measuring the urinary excretion rate of C-peptide (U-C) could serve as an indicator of its secretion rate (SR-C) if its urinary clearance (UCI-C) is constant and unaffected by plasma C-peptide concentration, body mass, or diabetes. We measured clearance ratios of C-peptide/creatinine (CR) in the fasting state and integrated 0-1, 1-3, and 3-5 h after 100 g of glucose p.o. as well as over a full 24-h in eight obese, eight lean, and six maturity-onset diabetic subjects. CR did not differ significantly when values in the fasting state were compared with those in the postprandial periods and was therefore unaffected by plasma C-peptide concentration. Furthermore, CR was similar in the lean, obese, and diabetic subjects. SR-C, determined as the product of the metabolic clearance rate of C-peptide and its fasting or integrated plasma concentrations, correlated significantly with U-C in all the subjects (r = 0.87, P less than 0.0001). The correlation of U-C with SR-C in the diabetic subjects alone was also significant (r = 0.88, P less than 0.0001). In conclusion, our data support the use of U-C as an indirect measure of SR-C and therefore of SR-I.

Adult↗

PubMed1981

Ligand binding to multiple equivalent sites with steric hindrance.

A general model is developed for the binding of ligands to multiple receptor sites in which steric blockage of sites is taken into account. Analytical expressions for extent of ligand binding as a function of ligand concentration are derived employing a stochastic matrix approach. Using simple numerical techniques to evaluate these expressions it is possible to obtain the inherent affinity of each site for a ligand, the number of sites available and the number of sites excluded when a ligand binds to any site. The expressions derived here are contrasted with other expressions based on simple equilibrium considerations in which there are no interactions between sites and no interactions between ligands in different sites. It is shown that the expressions derived here predict significant departures from linearity in Scatchard plots and a strong negative cooperatively, especially toward the saturation limit.

Binding Sites↗