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Biomedical subjects

F M Graziano

Publications and source records attributed to F M Graziano.

At least 37 records · Page 2Linked to original sources

Sulfa hypersensitivity in patients with HIV infection: onset, treatment, critical review of the literature.

Trimethoprim/Sulfamethoxazole is the most effective medication used in both the treatment and prevention of Pneumocystis carinii pneumonia (PCP) in patients with HIV/AIDS. Its use, however, is accompanied by a high incidence of adverse reactions, especially fever, myalgia and rash (sulfa hypersensitivity). In a group of our patients, we have examined the clinical parameters at the time of onset of sulfa hypersensitivity, and the success of a desensitization protocol for this adverse event. We also have performed a comprehensive review of the literature on sulfa hypersensitivity and have compared our results to those previously reported in the literature. Our findings indicate that the sulfa hypersensitivity reaction is more likely to develop in patients with advanced disease and that desensitization can restore tolerability to the drug in approximately two thirds of those who attempt it.

AIDS-Related Opportunistic Infections↗

Isolation and purification of functional bovine lung mast cells (BLMCs).

Purified pulmonary mast cells were obtained from bovine lung using a combination of enzymatic digestion of tissue, density gradient centrifugation using Percoll, and centrifugal elutriation. In the initial procedure, lung tissue was enzymatically digested with collagenase, hyaluronidase, protease and elastase in three 30 min incubations at 37 degrees C. Monodispersed cell suspensions contained between 2 and 6% mast cells. Further purification of these mast cells by Percoll gradients and elutriation consistently yielded mast cells of > 90% purity. These cells were morphologically intact, viable and functional, as determined by histamine release evoked by secretagogue challenge. Incubation of BLMCs with Pasteurella haemolytica A1 culture supernate containing leucotoxin (LCT) alone, resulted in increased histamine release compared to controls. LCT also potentiated calcium ionophore (CaI)-induced histamine release from BLMCs.

Animals↗

Optimization and validation of an ELISA to measure specific guinea pig IgG1 antibody as an alternative to the in vivo passive cutaneous anaphylaxis assay.

Assessment of the allergenic potency of enzymes involves the use of a guinea pig model in which specific IgG1 antibody titers are used as the endpoint. The in vivo passive cutaneous anaphylaxis (PCA) assay is used to measure specific IgG1 antibody. This report describes the development and validation of an enzyme-linked immunosorbent assay (ELISA) to measure guinea pig specific IgG1 antibody as an in vitro alternative to the PCA assay. Cross reactivity of various rabbit and mouse (monoclonal) anti-guinea pig IgG1 preparations were evaluated using purified IgG1 and IgG2 from serum of guinea pigs immunized with ovalbumin. The two subclasses of guinea pig IgG were purified by first using Protein A affinity chromatography, followed by anion exchange chromatography and fluid phase isoelectric focusing. Affinity-purified rabbit anti-guinea pig IgG1 was shown to have minimal cross reactivity toward IgG2, while providing a strong signal with IgG1. The ELISA was designed as an antigen capture system in which the following are added in sequence: (1) enzyme antigen (passively adsorbed to the plate), (2) diluted serum samples from guinea pigs immunized with enzyme, (3) affinity-purified rabbit anti-guinea pig IgG1, (4) alkaline phosphatase-conjugated donkey anti-rabbit IgG, and (5) p-nitrophenyl phosphate substrate. Three replicate ELISA and PCA analyses were conducted on sera samples of varying titers from guinea pigs immunized with either Alcalase (protease), BPN' (protease), and Termamyl (amylase) enzyme. The correlation coefficients (r2) between the ELISA and PCA assay for Alcalase, BPN', and Termamyl were 0.826, 0.945, and 0.755, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A comparison of the effects of isoproterenol and forskolin on immunologic and nonimmunologic release of histamine from guinea-pig superfused trachea and dispersed tracheal cells.

This study has compared the abilities of isoproterenol and forskolin to inhibit immunologic- and nonimmunologic-induced histamine release from guinea-pig superfused trachea and enzymatically dispersed tracheal cells. Contraction was also measured in the former preparation. The potency of isoproterenol was similar for inhibition of all parameters associated with immunologic (ovalbumin) challenge in the two preparations. In contrast, forskolin appeared less potent in inhibiting ovalbumin-induced histamine release from dispersed tracheal cells. Histamine release by the nonimmunologic secretagogues d-tubocurarine and compound 48/80 was not altered by either substance. However, inhibition by isoproterenol and forskolin of tracheal contraction was evident when challenge was conducted with d-tubocurarine and compound 48/80. Inhibition of contraction appears to be a result of functional antagonism at the level of the smooth muscle. The superfused trachea is a useful preparation in which to explore the effects of substances that modulate mast cell mediator release.

Animals↗

Adrenal insufficiency in the antiphospholipid antibody syndrome.

OBJECTIVE: Adrenal insufficiency (AI) is a rare complication of the antiphospholipid antibody syndrome (APS). The objective of this report is to describe a case and review the published literature to enhance recognition of this potentially fatal disorder by emphasizing its course, diagnosis, and cause. DATA SOURCES: A bibliographic database with the indexing terms adrenal insufficiency, adrenal hemorrhage, adrenal thrombosis, APS, systemic lupus erythematosus, with the constraints of human subjects only, was used. STUDY SELECTION: All 27 reports meeting the indexing terms were selected for review. DATA EXTRACTION: The specific criteria used for data extraction articles included course of the disease, causation, clinical and laboratory diagnostic criteria, and therapeutic intervention. DATA SYNTHESIS: Our patient is a previously health woman who developed a respiratory tract infection, followed by a prolonged illness with fever, hypotension, nausea, depression, and venous thromboses. She was found to have AI and APS that was alleviated with hydrocortisone and anticoagulation. Initially, her adrenal glands were normal on CT scan but subsequently became enlarged and later atrophic. Of the 27 previous case reports, a majority had thromboses and typical clinical and laboratory manifestations of AI. Hemorrhagic infarction of the adrenal gland appears to be the mechanism for AI in the APS. IgG and IgM anticardiolipin antibodies are most commonly reported in association with AI in APS. CONCLUSIONS: The hypercoagulable state in the APS may lead to adrenal vein thrombosis and subsequently to hemorrhagic necrosis of the adrenal gland. This complication of APS is important to recognize because it may be fatal if untreated.

Adrenal Glands↗

2-LTR circular viral DNA as a marker for human immunodeficiency virus type 1 infection in vivo.

The unintegrated viral DNA found in human immunodeficiency virus type 1 infection includes linear and circular forms. We targeted the circular form containing two copies of the viral long terminal repeat (2-LTR circle) and developed specific assays to detect this molecule in peripheral blood mononuclear cells from HIV-infected patients. In vitro HIV-1 infection of peripheral blood mononuclear cells showed rapid accumulation and rapid decay of 2-LTR circular viral DNA. Examination of 2-LTR circular viral DNA levels provides a view of spreading infection based on a viral DNA form that is structurally distinct and has a known, short half-life in infected cells. In patients not receiving antiviral therapy, the levels of 2-LTR circular viral DNA and total viral DNA were significantly correlated to CD4 cell counts. Similar correlations were not observed in patients receiving zidovudine (AZT), didanosine (ddA), or zalcitabine (ddC).

Base Sequence↗

Peptidoleukotriene (pLT) release from guinea pig lung mast cells.

Guinea pig lung mast cells can be isolated and purified to high purity. This has given us the opportunity to study in greater detail mediator release from these cells. Both immunologic (ovalbumin sensitized) and nonimmunologic (calcium ionophore, CaI) stimuli caused a dose-dependent release of histamine and pLT from monodispersed lung cells and highly purified lung mast cells. Examination of the time release curve for pLT revealed a 5-min lag in the release of this mediator and a peak release at 60 min after challenge with antigen. Verification of pLT release was obtained by use of the 5-lipoxygenase inhibitor A64077 (Zileuton). Pretreatment of lung mast cells with the 5-lipoxygenase inhibitor prevented release of pLT by either antigen or CaI but had no appreciable effect on histamine release (HR). The pulmonary mast cell appears to be an important contributor to pLT release in the guinea pig lung.

Animals↗

In vitro passive sensitization of guinea pig, rhesus monkey and human bladders as a model of noninfectious cystitis.

Studies of human bladder inflammation have been limited to examination of urine, bladder biopsy, or examination of autopsy material. We have developed an in vitro bladder passive sensitization technique which can measure type I responses of isolated human bladder tissue. We have compared these results using human tissue to those obtained with bladder tissue from guinea pigs and Rhesus monkeys. In our studies, bladder tissue was passively sensitized in vitro for 20 hours with immunoglobulin-containing serum. Subsequent antigen challenge of the passively sensitized tissue resulted in a time-dependent contraction that was accompanied by tissue histamine release. Contractions of guinea pig, monkey and human bladder tissue reached 79%, 100% and 78% of the maximal contraction induced by potassium chloride. In contrast, adjacent strips of unsensitized tissue had no detectable response to antigen challenge. The responses were reduced in the presence of histamine H1 receptor blockade with pyrilamine and abolished in the presence of a concomitant blockade of leukotriene synthesis with nordihydroguaiaretic acid (NDGA). Blockade of cyclooxygenase activity with indomethacin increased the contraction of the sensitized guinea pig bladder in response to antigen challenge. These findings demonstrate that in vitro passive sensitization of human bladder tissue can be used to investigate basic mechanisms of noninfectious bladder inflammation in humans.

Animals↗

Differential release of prostaglandins and leukotrienes by sensitized guinea pig urinary bladder layers upon antigen challenge.

The relative contributions of mucosal/submucosal and detrusor layers to the release of inflammatory mediators were investigated in isolated, ovalbumin (OVA) sensitized guinea pig urinary bladders. Ovalbumin challenge of sensitized mucosa induced release of prostaglandins (PG): PGE2, PGD2 and PGF2 alpha, in that order of magnitude. The total release of PGs was significantly higher from the mucosa/submucosa than from the detrusor/serosa. Under the same conditions, net release of leukotriene (LT) was observed predominantly from the detrusor. The total amount of histamine released from the mucosa was greater than that from the muscle layer. These results indicate differential production and release of inflammatory mediators from the mucosal/submucosal and detrusor smooth muscle layers. These results may have serious implications in disorders, such as interstitial cystitis, involving bladder mucosal damage. The cytoprotective effect of PGE2 is likely to be lost when the mucosa is damaged, and LT release from deeper layers may contribute significantly to symptoms of bladder inflammation.

Animals↗

Inhibition of aromatase activity in rat Sertoli cells by thyroid hormone.

Basal and FSH-induced aromatase activity in prepubertal rat Sertoli cells was inhibited by L-triiodothyronine (T3) in a time- and dose-dependent manner. The effect was evident only after 6 h of preincubation with T3 (10(-7) M) and the half-maximal dose was 0.5 +/- 0.2 nM, which correlated with the Kd of the nuclear T3 receptor of rat Sertoli cells (Kd = 1-2 nM). The effect was specific as judged by the lack of effect of the T3 analogue 3-iodo-L-tyrosine. The inhibitory effect of T3 was present over the entire range of FSH concentrations used (0.001-100 ng/ml). In T3-treated Sertoli cells, aromatase activity induced by 8-bromo-cyclic AMP was inhibited by the same order of magnitude as that of FSH, thus suggesting that the inhibitory effect of T3 was downstream from cyclic AMP formation. Furthermore, pretreatment of Sertoli cells cultures with T3 (24 h, 10(-7) M) did not affect basal or FSH-induced extracellular cyclic AMP accumulation. This effect of T3 on rat Sertoli cell aromatase activity may be regarded as a part of the integrated mechanism by which thyroid hormone modulates the functions of the seminiferous epithelium.

8-Bromo Cyclic Adenosine Monophosphate↗

[Iodine deficiency diseases and pregnancy].

Iodine is a fundamental element of diet since it is important in thyroid hormone biosynthesis. Dietary iodine deficiency can provoke not only thyroid enlargement, but also symptoms and signs of hypothyroidism of various degree, known as "iodine deficiency disorders" (IDD). Thus, the iodine supplementation is mandatory. It can be obtained, in our regions, where subendemic deficiency is frequent, by adding iodine to salt. This is the only way to avoid anatomo-functional lesions, that are dramatic in pregnancy and childhood.

Female↗

Pharmacologic modulation of the influence of the epithelium on immunologic- and nonimmunologic-induced histamine release and contraction in guinea pig superfused tracheal strips.

The influence of the epithelium on contractions and histamine release evoked by ovalbumin and d-tubocurarine has been examined in guinea pig superfused tracheal strips under several experimental conditions. Without drug pretreatment, removal of the epithelium resulted in larger (P < .05) total histamine released by ovalbumin, 10(-4) to 10(-1) mg/ml, and by d-tubocurarine, 3 x 10(-3) M. In the presence of indomethacin, 5 x 10(-6) M, epithelium removal resulted in elevated histamine release only at smaller ovalbumin concentrations, 10(-4) and 10(-3) mg/ml. Indomethacin did not change the influence of the epithelium on histamine release by d-tubocurarine. Indomethacin treatment abolished the influence of the epithelium on ovalbumin-induced tracheal contraction. With indomethacin, larger (P < .05) histamine release was seen with ovalbumin, 10(-1) and 1 mg/ml, when the epithelium was intact. The larger histamine release in response to ovalbumin, 10(-1) mg/ml, in the presence of the epithelium was unaltered by pyrilamine, 10(-6) M, cimetidine, 10(-4) M, and thioperamide, 10(-6) M, to block histamine H1, H2 and H3 receptors, respectively. Therefore, histamine released by ovalbumin does not stimulate histamine release through an action on these receptors when the epithelium is intact. In the presence, but not in the absence, of the epithelium, A64077, 10(-5) M, and ICI198615, 10(-8) and 10(-6) M, inhibitors of 5-lipoxygenase and LTD4/E4 receptors, respectively, inhibited histamine release by ovalbumin, 10(-1) mg/ml. Histamine release by ovalbumin, 10(-4) mg/ml, and d-tubocurarine, 3 x 10(-3) M, studied with or without epithelium was not altered by A64077 or ICI198615.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Rheumatoid arthritis. Importance of early diagnosis in long-term outcome.

Rheumatoid arthritis is a common disorder that does not have the favorable outcome it was once thought to have. A detailed clinical history, thorough physical examination, and judicious use of serologic tests and radiologic studies should allow accurate diagnosis, even at an early stage. Traditional therapy can successfully improve short-term functional status but may not alter long-term outcome. Early, aggressive therapy may improve prognosis, but this approach must be further studied and, if attempted, should be done in consultation with a rheumatologist.

Adult↗

Munchausen's syndrome: the importance of a comprehensive medical history.

Munchausen's syndrome was first described by Asher in 1951. Then Ireland, et al, described eight criteria that characterized these patients. These characteristics include factitious illness of a dramatic nature, factitious evidence of disease, evidence of multiple medical procedures, pathologic lying, aggressive behavior, leaving the hospital against medical advice, multiple hospitalizations with traveling and absence of any obvious secondary gain. Another form of this disease is Munchausen's syndrome by proxy which describes parental behavior that creates the appearance of, or produces, physical illness in a child with harmful consequences to the child. In this report, we present a complex case of Munchausen's syndrome in a patient who has been traveling around the country, going from one hospital to another for several years. We ask physicians to be aware of the features of this patient, bearing in mind that this was her third hospitalization at the University of Wisconsin Hospital in Madison.

Adult↗

Pharmacokinetic-interaction study of didanosine and ranitidine in patients seropositive for human immunodeficiency virus.

The potential pharmacokinetic interactions between didanosine, an acid-labile antiretroviral agent, and ranitidine, an H2-receptor antagonist, were evaluated by a crossover study of 12 male patients seropositive for the human immunodeficiency virus. Single oral doses of 375 mg of didanosine, formulated as a citrate-phosphate-buffered sachet, or of 150 mg of ranitidine were administered alone or in combination (ranitidine was given 2 h prior to didanosine). Serial blood samples and total urinary output were collected after each treatment and analyzed for didanosine and/or ranitidine by validated high-performance liquid chromatography-UV assay methods. Pharmacokinetic parameters were calculated by noncompartmental methods. There were significant increases in mean area under the curve from time zero to infinity and mean urinary recovery for didanosine given in combination with ranitidine compared with those for didanosine alone. There were no significant differences between didanosine coadministered with ranitidine and didanosine alone in the respective mean peak concentrations in plasma, times to peak, elimination half-lives, or renal clearances. The mean area under the curve for ranitidine given with didanosine was significantly less than that for ranitidine given alone. There were no significant differences between the mean peak concentrations in plasma, times to peak, elimination half-lives, renal clearances, or urinary recovery values for ranitidine coadministered with didanosine and values for ranitidine given alone. These data demonstrate that administration of didanosine 2 h after ranitidine will result in a minor increase in the bioavailability of didanosine. A modification in the dose of didanosine or ranitidine is not necessary if the dose of ranitidine precedes that of didanosine by 2 h.

Administration, Oral↗

Human synovial mast cell involvement in rheumatoid arthritis and osteoarthritis. Relationship to disease type, clinical activity, and antirheumatic therapy.

Mast cells were isolated by enzymatic digestion of synovium obtained from 48 patients with rheumatoid arthritis (RA) and 42 patients with osteoarthritis (OA). A significantly lower percentage of stainable synovial mast cells was obtained by tissue digestion from patients with clinically active RA compared with those with less active disease. The 54 patients treated with nonsteroidal antiinflammatory drugs had a significantly lower percentage of stainable synovial mast cells in cell suspension than did the other 36 patients. When anti-IgE antibody was used as a secretagogue in vitro, significantly greater histamine release was observed from synovial mast cells of RA patients compared with OA patients. Greater histamine release in response to anti-IgE was observed in the RA patients with more clinically active disease and those who were treated with prednisone, compared with RA patients without these features. Synovial mast cells of RA patients treated with a disease-modifying antirheumatic drug had a significantly lower mean histamine content than did cells from patients not receiving such treatment. Our data suggest that there are differences between synovial mast cells from tissues of patients with RA and OA and suggest that synovial mast cells may be activated in clinically active RA. In addition, the data indicate an effect of systemic antirheumatic therapy on mast cells isolated from synovium of patients with arthritis.

Adult↗

Studies of desensitization and cross-desensitization to immunologic and nonimmunologic stimuli that evoke contraction and histamine release in superfused guinea pig trachea.

This study examined the possibility that there is cross-desensitization between immunologic and nonimmunologic stimuli that evoke contraction and histamine release (HR) in the isolated guinea pig trachea. Compound 48/80 and D-tubocurarine were found to cause homologous and heterologous desensitization for both contraction and HR from superfused trachea. Specific antigen challenge of trachea obtained from animals sensitized with either IgG1 (ovalbumin [OA]) or IgE (oxazalone-human serum albumin [OX-HSA]) also resulted in homologous desensitization for both contraction and HR. However, in experiments with animals sensitized with both IgG1 and IgE antibodies, prechallenge with OA resulted in cross-desensitization to OX-HSA, whereas the reverse sequence was ineffective in eliciting this phenomenon. This may be related to the type of desensitization produced by each antigen (specific versus nonspecific) or to heterogeneity of mast cells in the tissue. Prechallenge of the trachea with compound 48/80 or D-tubocurarine failed to alter subsequent effects of antigen after active sensitization with OA or passive sensitization with either IgG1 or IgE antibodies. Small but statistically significant decreases in tracheal responses to D-tubocurarine were observed after antigen prechallenge to active both IgG1 and IgE antibodies. This is the first study to demonstrate a cross-desensitization between compound 48/80 and D-tubocurarine and the first to examine cross-desensitization with IgG1 and IgE antibodies in the guinea pig trachea. The overall conclusion is that there is no major overlap in the desensitization mechanisms between immunologic and nonimmunologic stimuli in the guinea pig trachea.

Animals↗