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Biomedical subjects

R C Allen

Publications and source records attributed to R C Allen.

At least 127 records · Page 7Linked to original sources
PubMed1984

Insulin removal in man: in vivo evidence for a receptor-mediated process.

To evaluate the in vivo participation of insulin receptors in both hepatic and extrahepatic removal of insulin, compartmental kinetic analysis of insulin behavior was performed in a patient with blocked receptors due to endogenous antiinsulin receptor antibodies. Using the standard three-compartment simulation of insulin behavior, the responses to both a 5-U injection of exogenous insulin and a 4.2-U secretion of endogenous insulin subsequent to tolbutamide injection were examined. In response to both exogenous and endogenous insulin, hepatic removal of insulin was reduced to less than 18% of the insulin exposure (normal, 40-60%). The metabolic clearance of insulin was reduced from the normal level of 520 ml/min to less than 120 ml/min, consistent with a reduction in receptor-mediated removal of insulin from the blood. These studies propose quantitative parameters for insulin receptor function in hepatic and extrahepatic removal of insulin in man.

Adult↗
PubMed1984

Direct stimulation of neutrophil oxygenation activity by serum from patients with systemic lupus erythematosus: a relationship to disease activity.

Sera from patients with systemic lupus erythematosus (SLE) directly stimulate polymorphonuclear leukocyte (PMNL) oxygenation activity as measured by luminol dependent chemiluminescence (CL). The stimulatory capacity of a serum, expressed as percent PMNL chemiluminescence (%CL), was calculated by dividing the integral CL response to the serum by the integral CL response to a standard stimulus, opsonified zymosan. Testing was performed on 50 sera obtained serially from 8 SLE patients and on 14 sera from 11 controls. Sera from SLE patients in remission and controls were nonstimulatory with mean %CL +/- SE values of 3.1 +/- 0.7 and 3.5 +/- 0.9, respectively. Sera obtained from the SLE patients during active disease yielded a mean %CL value of 26.6 +/- 9.0. The stimulatory capacity of SLE serum was concentration dependent and enhanced by adding normal serum complement. The CL response correlated with serological measures of SLE activity such as antibodies to double stranded DNA (p less than .0001) and Clq binding immune complexes (p less than .001). Thus, during active SLE, PMNL may become metabolically activated by exposure to serum containing immune complexes and possibly other factors. PMNL activation may contribute to the development of vasculitis, leukopenia, and susceptibility to infection. Our CL approach allows sensitive in vitro assessment of the phlogistic properties of serum to monitor SLE disease activity.

Adolescent↗
PubMed1983

Gliadin subfraction skin test for the diagnosis of coeliac disease.

Skin hypersensitivity to a gliadin subfraction (Fraction 3) was tested in patients with coeliac disease, patients with inflammatory bowel disease, and controls. Those with coeliac disease showed substantially greater hypersensitivity than controls, but there was no significant difference between the frequency of hypersensitivity in patients with coeliac disease and in those with inflammatory bowel disease. Fraction 3 did not provide a sufficiently specific skin reaction to be of use in the diagnosis of coeliac disease.

Adolescent↗
PubMed1983

Heterocyclic oxyacetic acid diuretics: indazole, benzisothiazole, and benzisothiazole 1,1-dioxide analogues of [[7-chloro-3-(2-fluorophenyl)-1,2-benzisoxazol-6-yl]oxy]acetic acid.

The indazole, benzisothiazole, and benzisothiazole 1,1-dioxide analogues of [[7-chloro-3-(2-fluorophenyl)-1,2-benzisoxazol-6-yl]oxy]acetic acid were synthesized and tested for diuretic activity in saline-loaded mice. Each analogue was found to be less active than the parent benzisoxazole: the diuretic activity followed the order O greater than S greater than N = SO2 in regard to the heteroatom in the 1-position of the ring.

Animals↗
PubMed1983

Hepatic removal of insulin in normal man: dose response to endogenous insulin secretion.

The hepatic extraction of insulin in normal man was evaluated by kinetic analysis of peripheral insulin behavior in the plasma following stimulation of endogenous insulin secretion. Prehepatic insulin production was determined by deconvolution of plasma connecting peptide behavior (C-peptide) and hepatic extraction of the secreted insulin determined with a three-compartment model for hepatic, vascular, and extravascular plasma spaces. Three dosages of oral glucose (10, 25, and 100 g) administered to normal volunteers resulted in 1.8 +/- 0.5, 2.7 +/- 1.1, and 7.2 +/- 1.6 U endogenous insulin secretion, respectively. Total hepatic exposure to insulin exceeded the endogenous secretion due to recycling to the liver from the systemic circulation. Decreasing insulin extraction by the liver (67-53-42%) in the presence of increasing insulin exposure (2.6-4.4-13.2 U) was observed during the dose-response to glucose. The rates of hepatic insulin extraction observed with arginine (58 +/- 9% with 3.2 U), and a normal meal (50 +/- 9% with 7.6 U) were intermediate between the extremes seen with the 10- and 100-g glucose challenge. These results quantitate hepatic exposure of insulin in man during differing stimuli of endogenous insulin secretion, and demonstrate reduced fractional hepatic extraction with increasing insulin exposure.

Adult↗
PubMed1983

Argon laser trabeculoplasty for open angle glaucoma. A retrospective study of 380 eyes.

Three hundred and eighty eyes of 300 patients which were treated with argon laser trabeculoplasty for medically uncontrolled open angle glaucoma were studied retrospectively. Among the 334 eyes having at least six weeks follow up, the mean overall pressure drop was 8.1 mm Hg. In 19.2 per cent of eyes, pressure was inadequately controlled by laser treatment and subsequent glaucoma surgery was required. Phakic primary chronic open angle glaucoma (COAG), aphakic COAG, pseudoexfoliation, pigmentary, and low tension glaucoma eyes all had a significant drop in pressure. Eyes with juvenile glaucoma or inflammatory glaucoma had a much poorer response in terms of mean pressure drop and number requiring later operation. There was no statistically significant difference in response between aphakic and phakic coag eyes, between pseudoexfoliation and phakic COAG eyes, or between eyes treated over the full 360 degrees and eyes treated over half the angle with treatment over the second half later if needed. A higher initial pressure usually resulted in a greater lowering of pressure. Medication was reduced after treatment in 28.7 per cent of eyes. The data suggest that the effect of laser trabeculoplasty generally persists for at least one year. Complications were few, the most serious being elevated intraocular pressure, which rose 10 mm Hg or more in 2.1 per cent of all eyes.

Follow-Up Studies↗
PubMed1983

Overproduction of a kinetic subclass of VLDL-apoB, and direct catabolism of VLDL-apoB in human endogenous hypertriglyceridemia: an analytical model solution of tracer data.

To investigate the participation of the major apoprotein involved in triglyceride transport in the pathogenesis of endogenous hypertriglyceridemia, five kinetic studies of apoprotein B were conducted in volunteer normolipidemic subjects and six studies in four patients with endogenous hypertriglyceridemia. The transport of apoprotein B within four kinetic subclasses of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) was studied by injection of [75Se]selenomethionine. A 24-fold increase in the entry of newly synthesized apoprotein B at the initial kinetic subclass of the four-compartment VLDL delipidation sequence characterized the hypertriglyceridemic studies relative to normal subjects. Moreover, approximately 75 mg/kg per day of VLDL-B turnover reflected direct catabolism independent of conversion to IDL and/or to LDL, in contrast to the 8 mg/kg per day observed in controls. IDL-B was derived from VLDL-B in both normal and hypertriglyceridemic subjects, and was responsible for greater than 70% of all LDL-B synthesis. LDL-B pool size and turnover were indistinguishable in hypertriglyceridemic subjects from that observed in normal subjects. These studies suggest that two kinetic phenomena may characterize the pathophysiology of endogenous hypertriglyceridemia: a) over-production of apoB within a kinetic subclass of VLDL and b) preferential catabolism of hypertriglyceridemic VLDL without prior conversion to IDL/LDL.

Adult↗
PubMed1982

Humoral-phagocyte axis of immune defense in burn patients. Chemoluminigenic probing.

Both serum opsonic capacity and granulocyte oxygenation activity were measured in 35 burn patients during their course of therapy. The microbicidal action of granulocytes is effected via the metabolic generation of oxygenating agents; introduction of chemoluminigenic substrates, such as luminol or dimethyl biacridinium dinitrate, allows ultrasensitive measurement of phagocyte oxygenation activity. Serum opsonic capacity can also be assayed by measuring the rate of activation of phagocyte oxygenation activity. Alterations in granulocyte oxygenation activity were observed in individuals patients in temporal association with changes in clinical condition, and sepsis was associated with a marked decrease in activity. An initial depression in opsonic capacity was noted at the time of admission of patients with major burns, more than 40% total body surface. Thereafter, depression of opsonic capacity was temporally associated with sepsis in individual patients. Chemoluminigenic probing provides a rapid, sensitive, and objective method for assessing the status of the humoral-phagocyte axis, and as a clinical laboratory technique is particularly applicable for monitoring patient populations in which sepsis is prevalent.

Acridines↗
PubMed1982

Filtration surgery in the treatment of neovascular glaucoma.

The disappointing visual acuity results following cyclocryotherapy for neovascular glaucoma have prompted us to consider filtration surgery as a reasonable alternative in the treatment of selected patients. All cases of surgically treated neovascular glaucoma were reviewed. There were 26 operations in 24 eyes with a follow-up ranging from six months to seven years and a mean of 22.8 months. Adequate pressure control was obtained in 16 of the 24 eyes (67%). In the eyes with successful control of intraocular pressure, vision was 20/400 or better in eight of the 16 eyes (50%). Four patients (17%) lost light perception. Approximately one half of the operations were trabeculectomies, and the others were posterior lip sclerectomies. There seemed to be no significant difference in the final intraocular pressure levels, number or degree of complications, or successes within the two subgroups. Panretinal photocoagulation, topical steroids, cycloplegics, and time for these measures to have their effect are important preoperative adjuncts to surgical treatment. We are encouraged by the long-term preservation of vision and control of intraocular pressure in many of these eyes.

Adult↗
PubMed1982

[(3-aryl-1,2-benzisoxazol-6-yl)oxy]acetic acids. A new diuretic series.

A series of [(3-aryl-1,2-benzisoxazol-6-yl)oxy]acetic acids was synthesized and tested for diuretic activity in saline-loaded mice and in conscious, water-loaded dogs. The structural requirements for good diuretic activity in both mice and dogs were found to be very specific. In summary, the compounds with the best diuretic activity (13i, 13q, and 13ff) were substituted with a 2-fluorophenyl group at the 3 position and chlorine or bromine at the 7 position. Compound 13ff, [(7-bromo-3-(2-fluorophenyl)-1,2-benzisoxazol-6-yl]oxy]acetic acid (HP 522), was found to be moderately uricosuric in chimpanzees and was selected for further development.

Animals↗
PubMed1982

Effects of ethinyl estradiol on pharmacokinetics of meperidine and pentobarbital in the rat.

Effects of estrogen administration on in vivo hepatic microsomal drug metabolism have been frequently assessed, but there has been little study of the effects of estrogen treatment on in vivo drug pharmacokinetics. After administration of ethinyl estradiol (5 mg/kg daily for 5 days), meperidine and pentobarbital pharmacokinetics were determined both in vivo and in the isolated perfused rat liver. Estrogen pretreatment caused a 45% reduction in systemic meperidine clearance in vivo and perfusate disappearance of both meperidine and its major metabolite, normeperidine, was slower in isolated liver experiments from ethinyl estradiol-treated animals as compared with propylene glycol-treated controls. In contrast to meperidine, clearance of pentobarbital was not decreased by estrogen treatment. These studies demonstrate that estrogen treatment singularly can alter drug pharmacokinetics in the rat and raise the question as to whether clinically important alterations in drug pharmacokinetics occur in humans receiving estrogen therapy.

Animals↗
PubMed1982

Metabolic heterogeneity of low density lipoprotein-apoB production in familial hypercholesterolemia: an analytical model solution of tracer data.

Six subjects with heterozygous familial hypercholesterolemia (FH) (three males, three females) formed the basis for an investigation of the pathways of production of apoprotein B within plasma low-density-lipoprotein (LDL-apoB). Following the intravenous injection of [75Se]selenomethionine as an amino acid tracer, incorporation of the radioactive isotope into the putative precursor of LDL, intermediate density lipoprotein (IDL-apoB), was examined over a 9-day period. The resulting tracer data provided the precursor profile for both the IDL catabolic conversion of LDL as well as for direct synthesis of LDL from amino acids. The fractional conversion rates, (beta) for IDL and (alpha) for amino acids to LDL-apoB, were determined utilizing the two-compartment model for LDL involving both the intravascular and the extravascular pools of apoB. This LDL model was resolved analytically and the parameters alpha and beta were determined so as to give the least squares fit to the LDL tracer data. In this solution, the fractional conversion rates of IDL and of amino acids to LDL-apoB were resolved with a mean fractional residual of 20 +/- 6%, which was randomly distributed within the LDL-apoB data throughout the 216 hours of the studies. The steady-state determination of the pathways of LDL-apoB synthesis, based upon this tracer analysis, indicate that IDL accounts for 46%, and amino acids account for 54% of total apoB production within plasma LDL in heterozygous FH. In contrast, in normal subjects, IDL accounts for 86% of total LDL-apoB production. Since the IDL catabolic pathway represents the predominant if not exclusive source of LDL in normal man, this demonstration of a major non-IDL source of LDL in FH broadens the understanding of the pathophysiology of human familial hypercholesterolemia.

Adult↗
PubMed1981

Fendosal.

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Animals↗
PubMed1981

Role of myeloperoxidase and bacterial metabolism in chemiluminescence of granulocytes from patients with chronic granulomatous disease.

Phagocytosis of catalase-positive microbes by normal polymorphonuclear neutrophils results in increased metabolism as required for microbicidal action. Chemiluminescence is a product of the associated oxygenation reactions. Neutrophils from patients with chronic granulomatous disease are capable of phagocytizing catalase-positive microbes, but there is no associated respiratory burst, microbicidal action is greatly decreased, and chemiluminescence is not detected. However, these defective neutrophils can kill catalase-negative, H2O2-generating bacteria. In the present study, chemiluminescence by neutrophils from patients with chronic granulomatous disease after phagocytosis of H2O2-generating streptococci was detected. Acid extracts of myeloperoxidase from either control or patient neutrophils also yielded chemiluminescence in the presence of streptococci, but not in the presence of catalase-positive microbes.

Female↗
PubMed1981

Shigella sonnei phase I and phase II: susceptibility to direct serum lysis and opsonic requirements necessary for stimulation of leukocyte redox metabolism and killing.

The synthesis of the lipopolysaccharide O-specific repeat polymer by Shigella sonnei phase I is a clearly defined bacterial virulence factor necessary for penetrating epithelial cells; S. sonnei phase II does not synthesize this antigen and is uniformly avirulent. The serum opsonic requirements, relative to differences in gross lipopolysaccharide structure, were investigated by quantification and comparison of polymorphonuclear leukocyte (PMNL) metabolism and PMNL-mediated microbicidal action to phase I and phase II organisms, using normal and immune serum. The stimulation of PMNL O2-redox metabolism, as required for oxidative killing, was quantified by a chemiluminescent technique, using luminol as a chemilumigenic substrate. Susceptibility to direct serum or serum PMNL-mediated killing was evaluated by serum and serum-phagocytic killing assays. Stimulation of PMNL metabolism and phagocytic killing of S. sonnei phase I required opsonification by specific phase I antibody plus the classical pathway of complement. S. sonnei phase II was susceptible to direct complement-mediated serum killing. Likewise, opsonification of the phase II microbe, as measured by PMNL-associated chemiluminescence, was effected by complement in the absence of immune antibody. These data demonstrate the importance of the O-specific repeat polymer in protecting the microbe from the microbicidal action of PMNL and the bacteriolytic action of serum.

Animals↗
PubMed1981

Allergic bronchopulmonary aspergillosis (ABPA) caused by Aspergillus terreus: specific lymphocyte sensitization and antigen-directed serum opsonic activity.

A 16-year-old male presented with a history of asthma and recurrent pneumonia. A diagnosis of ABPA was based upon the typical clinical presentation, peripheral eosinophilia, elevated IgE and positive immediate skin tests to Aspergillus. Sputum cultures grew A. terreus, a rare cause of human disease. Soluble and particulate antigens were prepared from this organism. Precipitins against A. terreus, but not against A. fumigatus, were detected in the patient's serum. His lymphocytes proliferated markedly in vitro when exposed to soluble A. terreus but not A. fumigatus antigen. The lymphocyte responses correlated with disease activity. Functional serum opsonic activity was measured using the technique of stimulated polymorphonuclear leucocyte chemiluminescence. The nonspecific opsonic activity of the patient's serum was within high normal range when zymosan was employed as an alternative pathway activator. Specific opsonic activity against particulate Aspergillus antigen was significantly increased in the patient's serum when compared with control sera. Despite the presence of specific antibody and opsonic activity against A. terreus, the patient's serum levels of C3, C4, and total hemolytic complement were normal. These findings are consistent with in vivo sequestration of the organism.

Adolescent↗