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Biomedical subjects

P R Finley

Publications and source records attributed to P R Finley.

At least 19 recordsLinked to original sources

Circulating levels of tumor necrosis factor and interleukin-1 in cystic fibrosis.

To assess the role of tumor necrosis factor (TNF) and interleukin-1 (IL-1) in the pathophysiology of cystic fibrosis (CF)-associated growth failure/cachexia and lung disease we measured height, weight, triceps skin fold, forced vital capacity, forced expiratory volume in 1 second, and plasma levels of TNF, interleukin-1-alpha (IL-1 alpha), interleukin-1-beta (IL-1 beta), and alpha-1-antitrypsin (A1AT) in 12 patients with CF, and in 12 age- and gender-matched healthy controls. The patients as a group had significantly lower values for the anthropomorphic measurements and lung function parameters as compared to controls. They also had higher circulating levels of A1AT than controls. TNF, however, was detected less frequently in patients than in controls. Neither group had detectable levels of circulating IL-1 alpha or IL-1 beta, which is consistent with the observation that CF patients infrequently present with fever. Potential explanations for these findings include compartmentalization of secreted TNF/IL-1, altered regulation of TNF/IL-1 secretion as a result of the chronic inflammatory state seen in CF, or increased degradation of TNF/IL-1, also a result of chronic inflammation. The role of these cytokines in the pathophysiology of CF remains unclear, but should be explored further; however it seems unlikely that circulating TNF plays a role in the growth failure/cachexia associated with CF.

Adolescent

Plasma levels of fibronectin and prostacyclin metabolite in peripartum preeclamptic women.

Plasma fibronectin and prostacyclin levels have been reported to vary in preeclamptic women when compared with pregnant control women. Elevation of fibronectin and deficiency of prostacyclin have been postulated to be due to endothelial cell disruption or dysfunction. Eighteen preeclamptic women and 19 normal pregnant controls were evaluated for plasma levels of fibronectin and the prostacyclin metabolite 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). 6-keto-PGF1 alpha and fibronectin plasma levels in patients were significantly different from control patients, with preeclamptic patients exceeding control subjects. Five patients had serial samples of 6-keto-PGF1 alpha prior to, during, and after intravenous magnesium sulfate therapy and no consistent effect was noted. No correlation existed between fibronectin and 6-keto-PGF1 alpha levels or between either compound and platelet count or liver function tests. Despite an overall elevation of fibronectin in preeclamptic patients, two patients with the hemolysis, elevated liver tests, and low platelet count syndrome showed low normal fibronectin levels coinciding with thrombocytopenia, hemolysis, and liver dysfunction. The magnitude of fibronectin elevation may therefore not predict the severity of preeclampsia. The significance of these findings is discussed.

Adolescent

Effect of interleukin-2 on microvascular liquid and protein transport in the rat small intestine.

Interleukin-2 (IL-2), a glycoprotein lymphokine derived from activated T-lymphocytes displays potent anti-cancer properties but its therapeutic use has been limited by generalized tissue swelling. To shed light on the mechanism underlying this potentially life-threatening edematogenic syndrome, recombinant IL-2 or an equal volume of control solution (excipient or 5% dextrose) was administered to 88 adult, male Sprague-Dawley rats. Initially, rats were injected with 50,000 Cetus units (equal to 300,000 I.U.) of IL-2 intraperitoneally, either one-time ("acute" rats) or every eight hours for two or seven days ("chronic" rats). Thereafter, under pentobarbital anesthesia, the main mesenteric lymph duct was isolated, incised, and measurements made of intestinal lymph flow (JV) and the total protein content and protein fractions in lymph (L) and plasma (P) (refractometry and agarose gel electrophoresis, respectively). Final measurements were also carried out after superior mesenteric vein constriction to assess filtration-independent L/P total protein "washdown." After IL-2, JV and protein clearance (JV x L/P) were increased (p less than 0.001) while lymph and plasma total protein content and protein fractionation were unchanged. Protein washdown was also maintained. These data are not only inconsistent with bulk "plasma leak" from damaged capillaries, but in conjunction with previously demonstrated increased cardiac output and reduced systemic vascular resistance after IL-2 administration, the findings favor augmented microvascular surface exchange area from increased capillary perfusion as the primary mechanism underlying increased transcapillary liquid and protein flux. This conclusion conforms to the rapid reversal of edema in patients after cessation of IL-2 therapy.

Animals

Comparison of ultrasonically applied vs. intra-articular injected hydrocortisone levels in canine knees.

Phonophoresis of hydrocortisone is a commonly performed treatment for a wide variety of soft-tissue as well as intra-articular musculoskeletal disorders. There have been no previously reported studies indicating the degree of hydrocortisone penetration into joints achieved by means of phonophoresis. Twenty-four purebred greyhounds were used to compare intra-articular levels of hydrocortisone resulting from intra-articular injection, phonophoresis, and external application of hydrocortisone. A total of 40 samples from canine knees were analyzed by means of fluorescence polarization. Intra-articular hydrocortisone levels obtained with phonophoresis were extremely low in comparison with those obtained with intra-articular injection. There were no statistically significant differences in intra-articular hydrocortisone levels between the phonophoresis and external application treatments, or between either of these and placebo control measurements taken from knees of untreated dogs and from shoulders of treated dogs. It appears that phonophoresis is an ineffective method of obtaining hydrocortisone penetration into a joint in the canine model.

Animals

Alpha-globulins suppress human leukocyte tumor necrosis factor secretion.

The secretion of tumor necrosis factor (TNF) by human peripheral blood mononuclear cells was suppressed by either whole human plasma alpha-globulins or purified alpha 1-acid-glycoprotein, alpha 1-antitrypsin and alpha 2-macroglobulin in a concentration-dependent manner. alpha 1-Antitrypsin was found to be the most suppressive of the purified proteins tested and completely blocked TNF release at concentrations above 1.25 mg/ml. Both alpha 1-acid glycoprotein and alpha 1-antitrypsin blocked TNF secretion by leukocytes which were simultaneously stimulated with either recombinant human interferon-gamma (IFN-gamma) or lipopolysaccharide (LPS). IFN-gamma- and LPS-activated cells were also susceptible to suppression mediated by these two alpha-globulins and the inhibition produced by 5 mg/ml alpha 1-antitrypsin was greater than that caused by either 1 microM prostaglandin E2 or 10 ng/ml transforming growth factor-beta 1. The level of TNF mRNA in TNF-secreting and alpha-globulin-suppressed cells was examined and found to be equal in both groups. The suppressive effect of whole alpha-globulins was confined to the inhibition of TNF secretion and these plasma proteins had no effect on the cytolytic activity of the recombinant cytokine as measured on murine L-929 target cells. Thus the alpha-globulins, which are a major fraction of the circulating plasma proteins, may function in TNF homeostasis by controlling TNF secretion without inhibiting the biological activity of the released cytokine.

Adult

Immunochemical assays for IgG, IgA, IgM and transferrin compared.

We compared immunochemical methods for determining IgG, IgA, IgM, and transferrin in serum by studying calibrator crossover, patient comparison, and, for a newly developed technology, normal reference intervals. For the immunoglobulins, we compared radial immunodiffusion (RID), rate nephelometry using the Beckman ICS, and a new nephelometric method adapted to the Abbott TDx; for transferrin we compared the ICS, TDx, and immunoturbiditry. The methods examined for quantifying IgA and transferrin showed good agreement in calibrator crossover and patient comparison studies. In studies comparing IgG methods, the ICS and TDx demonstrated acceptable agreement, although neither showed accordance with RID. For IgM determination, crossover studies and patients having less than 4300 mg/L in this protein showed good agreement, even though more elevated samples, run on the TDx, showed a discrepancy in proportionally compared to the other two methods. Normal reference intervals (95% confidence limits) determined on the TDx agreed well with those established for the other immunochemical methods.

Adolescent

Precipitation of benzodiazepine withdrawal following sudden discontinuation of midazolam.

Midazolam hydrochloride is an ultra-short acting benzodiazepine recently approved by the Food and Drug Administration for anesthesia induction and preoperative sedation. Frequently, midazolam is also used as an injection or infusion for the treatment of agitation in ventilator-dependent patients. A 53-year-old man underwent a gastrojejunostomy and was later intubated following the development of pseudomonal pneumonia. Midazolam was initiated in an effort to resolve his agitation and the patient continued to receive frequent bolus injections, averaging 22 mg/d over 21 days. Approximately eight hours after midazolam was abruptly discontinued, the patient became increasingly anxious and developed somatic complaints felt to be consistent with benzodiazepine withdrawal syndrome. Symptoms rapidly abated upon the reintroduction of midazolam and the drug was ultimately tapered over a period of four days and discontinued without further incident. Implications derived from the association of long-term midazolam therapy with benzodiazepine withdrawal syndrome are discussed.

Anxiety

Gonadotropin deficiency in Tourette's syndrome: a preliminary communication.

Plasma baseline levels of gonadotropins and sex steroids were measured in 17 patients with Tourette's Syndrome (TS). In addition, a Gonadotropin Stimulation test, using a synthetic Gonadotropin releasing factor analogue (GnRH, 100 micrograms, i.v.), was performed in 7 patients. Plasma levels of Luteinizing Hormone (LH) were uniformly low in all patients, while those of Follicle Stimulating hormone (FSH) and sex steroids were less depressed in some patients and in the normal range in others. In all patients, stimulation with GnRH analogue produced a marked rise in LH levels, but the FSH responses were much less dramatic and did not significantly exceed that of normal controls. Our findings indicate reduced gonadotropin release in patients with TS, and support the hypothesis of hypothalamic involvement in the disease.

Adolescent

Raised serum levels of tumour necrosis factor in parasitic infections.

In a study of serum levels of endogenous tumour necrosis factor (TNF) in healthy people and patients with neoplastic or infectious disease, only patients with kala-azar (visceral leishmaniasis) and malaria were found to have a strikingly increased frequency of raised TNF levels (66.6% and 70.0%, respectively). 7.9% of samples from both healthy subjects and patients with neoplastic disease contained measurable TNF. The discovery of elevated TNF levels in the sera of patients with parasitic diseases suggests that this cytokine may play a part in host defences against parasitic infections.

Adult

Amitriptyline plasma protein binding: effect of plasma pH and relevance to clinical overdose.

Reversing ventricular ectopy with plasma alkalinization following acute tricyclic antidepressant overdose is a recognized mode of therapy. The mechanism responsible for this effect is unclear. Changes in plasma protein binding of free drug, effects of the sodium ion on the myocardium, and alterations of plasma concentrations of alpha-1-acid glycoprotein may all interact to alter toxicity of tricyclics in overdose. An in vitro investigation using equilibrium dialysis was designed to examine the effect of altering plasma pH on percentage of free amitriptyline at clinical overdose plasma concentrations. A 1973 report on this effect lacked adequate controls and was faulty in experimental protocol. The current investigation used plasma concentrations typically present in amitriptyline overdose, a sensitive gas liquid chromatographic assay to detect total and free drug, and adequate control of plasma pH. The results of two separate experiments demonstrated a significant decrease in percentage of free amitriptyline of 20% over a pH range of 7.0-7.4 (P less than 0.05) and 42% over a pH range of 7.4-7.8 (P less than 0.05). The rate of change in slope in both experiments was not significantly different (P less than 0.01) indicating similar effects of pH change on plasma protein binding of amitriptyline within the two groups.

Amitriptyline

AIDS in 1968.

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Acquired Immunodeficiency Syndrome

Alterations in creatine kinase, ornithine decarboxylase, and transglutaminase during muscle regeneration.

Creatine kinase (CK), transglutaminase (TGase) and ornithine decarboxylase (ODC), enzymes implicated in the regulation of growth processes, were studied during muscle regeneration subsequent to the injection of bupivacaine into rat tibialis anterior. Within 2 days, the percent BB isozyme of CK detected in the muscle was elevated 70-fold coincident with a marked decrease in total CK activity. The MB isozyme also increased and was 15-fold of control at 4-5 days postinjection. TGase activity was increased significantly to greater than 2-fold of control within 2 days of injection and significantly decreased at days 3 through 7 compared to controls. ODC activity was elevated significantly to 2- to 3-fold of control from 2-7 days after injection. These results suggest an early alteration in the expression of a coordinated battery of genes in this model of muscle degeneration-regeneration. The increased expression of MB and BB isozymes of CK in various human neuromuscular diseases may be a manifestation of an ongoing process of degeneration-regeneration.

Acyltransferases

Increased activities of MB and BB isozymes of creatine kinase in denervated neonatal and adult rat muscle.

Creatine kinase (CK) activity and isozyme patterns were assessed in newborn and adult rat anterior tibial muscle in response to denervation. Total CK activity was low in the control neonatal muscle, gradually increasing to the adult level within 1 month. Denervation prevented this normal increase, and, therefore, CK activity was reduced to 25% of control at 2 months. In the denervated adult muscle, total CK activity decreased to 50% of control within 3 weeks and remained at that level. Denervation of neonatal muscle resulted in a greater conservation of MB isozyme compared with controls. The alteration in BB isozyme expression was even more dramatic with a 33-fold difference expressed at 2 months in terms of percent total CK in denervated vs. control muscle. In denervated adult muscle, MB and BB isozyme activities increased gradually, attaining levels 3-fold and 13-fold, respectively, above control muscle at the end of the experimental period.

Aging

Lidocaine elimination: effects of metoprolol and of propranolol.

The effects of administration of metoprolol and propranolol on lidocaine elimination were studied in six healthy young men who did not smoke. Each received three single intravenous doses of lidocaine (2.5 to 3.0 mg/kg injected over 10 min): one alone, one after 1 day pretreatment with propranolol (40 mg orally every 6 hr), and one after 1 day pretreatment with metoprolol (50 mg orally every 6 hr). Lidocaine clearance was 0.88 +/- 0.28 l X hr-1 X kg-1 before beta blockade, 0.61 +/- 0.20 l X hr-1 X kg-1 during metoprolol dosing, and 0.47 +/- 0.16 l X hr-1 X kg-1 during propranolol dosing. There was no correlation between the change in lidocaine elimination and the steady-state concentrations of metoprolol or propranolol, nor between the change in lidocaine clearance and the change in resting heart rate produced by either beta blocker. Metoprolol and propranolol reduce lidocaine elimination significantly.

Adult

Phagocytic, lambda light chain, plasma cell myeloma.

A case of phagocytic, lambda light chain, plasma cell myeloma was characterized by its clinical, morphologic, cytochemical, immunologic, and cell kinetic features. A 40-year-old man presented with Coombs-negative hemolytic anemia, hepatosplenomegaly, lytic bone lesions, lambda light chain monoclonal gammopathy, and infiltration of the bone marrow by dysplastic plasma cells, 10% of which demonstrated phagocytosis of erythroid cells. Electron microscopy demonstrated myeloma cells with prominent cytoplasmic microfilaments and erythroid cells in intracytoplasmic vacuoles. The myeloma cells did not phagocytose staphylococci in vitro. Phagocytic and nonphagocytic myeloma cells were tartrate-sensitive, acid-phosphatase positive, alpha-napthyl butyrate esterase negative, and did not form E rosettes or EAox(IgG) rosettes. The tumor cells were Tdt, Ia antigen, and SIg negative. Immunofluorescent staining for cytoplasmic light chains showed a monoclonal lambda pattern in nonphagocytic myeloma cells, and a probable monoclonal lambda pattern in phagocytic myeloma cells. These findings characterize the neoplasm as a monoclonal proliferation of differentiated plasma cells with the capability of erythrophagocytosis. Erythrophagocytosis by myeloma cells may have been responsible for the hemolytic anemia. The tritiated thymidine labeling index (LI%) was high (8%), suggesting a poor prognosis, despite a dramatic initial response to chemotherapy.

Adult