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Biomedical subjects

K McCarthy

Publications and source records attributed to K McCarthy.

At least 55 records · Page 3Linked to original sources
PubMed1997

Antigen presentation by autoreactive proteolipid protein peptide-specific T cell clones from chronic progressive multiple sclerosis patients: roles of co-stimulatory B7 molecules and IL-12.

To assess the role of T cell antigen (Ag) presentation in multiple sclerosis (MS), proteolipid protein (PLP) peptide reactive CD4+ T cell clones (TCCs) from MS patients and normal subjects were studied. TCCs derived from chronic progressive (CP) MS patients were able to proliferate and secret cytokines in response to PLP peptide stimulation in the absence of professional antigen presenting cells (APCs), suggesting that these T cells can simultaneously present and respond to Ags. However, they did not respond to total PLP protein, suggesting that PLP-peptide TCCs were unable to process and present the whole PLP molecule. The ability of the different TCCs to act as APCs in response to Ag stimulation did not correlate with expression of HLA-class II molecules. However, the degree of expression of B7-1 and B7-2 co-stimulatory molecules showed a significant correlation with APC capacity. Furthermore, a combination of anti-B7-1 and anti-B7-2 mAbs effectively inhibited proliferative responses as well as secretion of IL-10, IFN gamma and TGF beta induced by antigen presenting T cells. By contrast, IL-4 secretion was not affected. Finally, IL-12 significantly enhanced the efficiency of T cell Ag presentation by a pathway independent of Ag processing, suggesting that IL-12 might act as an additional co-stimulatory signal for T cell activation during T-T cell interactions. Together, these observations suggest that Ag presentation by T cells might amplify and perpetuate an autoimmune response previously initiated by professional APCs. These properties may account for progression of MS into a CP phase.

Adult↗
PubMed1997

Is kidney length a good predictor of kidney volume?

Kidney length is commonly used to determine kidney size; however, its relationship to kidney volume is not well established. This study evaluated the association between kidney length and kidney volume. Eighteen healthy adults (9 men and 9 women) consented to take part in this prospective study; all 18 underwent spiral computerized tomography (CT) of the kidneys, 14 of 18 also underwent kidney ultrasound. Kidney volume was measured by totaling the areas of the CT scan cuts, and kidney length was measured both on the kidney ultrasound and on the CT scan. Each independent variable, CT length (CTL) and ultrasound length (USL), was regressed against the dependent variable, kidney volume. Kidney length explained only 10% of the variability of the volume, although length x width was a better predictor of kidney volume (r = 0.72, P < 0.001). It was concluded that kidney length does not reliably predict kidney volume and that other methods, both clinical and radiologic, should be considered when a more exact determination of renal volume is clinically relevant.

Adult↗
PubMed1997

Quality control of spirometry testing in the registry for patients with severe alpha1-antitrypsin deficiency. alpha1-Antitrypsin Deficiency Registry Study Group.

As part of the multicenter National Heart, Lung, and Blood Institute registry of patients with severe deficiency of alpha1-antitrypsin with 1,129 enrollees, this report describes measures undertaken to achieve high-quality FEV1 measurements, the rates of satisfying reproducibility and acceptability criteria, and clinical features of participants unable to achieve reproducible FEV1 values at baseline. Spirograms were performed both before and after an inhaled bronchodilator in enrollees followed up at 37 participating clinical centers. Using a reproducibility criterion of < 100 mL or 5% (whichever greater), high reproducibility rates for FEV1 measurements at baseline were observed for both prebronchodilator (95.0% of 1,090 sessions) and postbronchodilator measurements (95.7% of 1,077 sessions). Using the more recently published reproducibility criterion of < or = 200 mL, reproducibility rates were even higher. Eighty-four percent of clinical centers submitted FEV1 values that satisfied reproducibility criteria for at least 90% of spirograms. Also, the mean coefficient of variation for prebronchodilator FEV1 values measured over serial visits separated by up to 9 months was 5.6% for participants with baseline FEV1 55 to 90% predicted. This degree of reproducibility is similar to that observed in the Lung Health Study. Rates of satisfying acceptability criteria for prebronchodilator spirograms were lower, almost universally (98% of tests) due to failure to achieve end-of-test criteria (which usually required 15 s of expiration in this population with mean FEV1 = 42.6+/-29.6% [SD] predicted). Multivariate logistic regression models show that clinical correlates of failure to achieve reproducible prebronchodilator FEV1 efforts include symptoms of chronic wheeze, chronic cough, and chronic phlegm, and the degree of airflow obstruction. We conclude that highly reproducible FEV1 measurements are achievable in a population with severe airflow obstruction despite the additional challenges posed by testing in multiple centers on a variety of spirometers. Furthermore, the difficulty of satisfying end-of-test criteria in a large cohort with severe airflow obstruction did not preclude achieving high rates of reproducibility for FEV1 measurements. Finally, our study confirms prior observations that failure to achieve reproducible efforts is associated with the presence of pulmonary symptoms and the degree of airflow obstruction. Thus, excluding patients with nonreproducible FEV1 efforts from epidemiologic studies would bias results by including only healthier participants.

Female↗
PubMed1997

Is direct collection of pleural fluid into a heparinized syringe important for determination of pleural pH? A brief report.

INTRODUCTION: It has long been believed that pleural fluid must be directly aspirated into a heparinized syringe to obtain an accurate value. Many operators aspirate 30 to 60 mL of pleural fluid into a syringe without heparin, and then place 1 mL into a heparinized syringe from which the pH is determined. We postulated that this technique does not cause a clinically significant difference in pleural pH values. METHODS: Patients undergoing thoracentesis in the outpatient clinic, general ward, and medical ICU were eligible. After the initial entry of the needle into the pleural space, a heparinized syringe was used to obtain pleural fluid for pH determination. A 60-mL syringe was then used to aspirate additional pleural fluid for biochemical analysis and culture. At the end of the procedure, a second aliquot of pleural fluid was placed into a heparinized syringe for pH determination. A difference of 0.1 in pH was taken as clinically important. RESULTS: Twenty-one pleural fluid samples were obtained from 20 patients. Pleural fluid pH determinations were within 0.1 in all but one patient. The mean pH for the directly collected group was 7.39 (25%: 7.35; 75%: 7.45). The mean for the indirectly collected group was 7.41 (25%: 7.35; 75%: 7.45). The difference between the two means (0.02; 95% confidence interval, 0.0368 to 0.00131) was statistically significant but clinically unimportant (p=0.037). CONCLUSIONS: Pleural fluid can be collected in a large syringe and then placed into a heparinized syringe to assess pH. This is useful information because the use of just one syringe saves time and reduces the risk of iatrogenic complications.

Aged↗
PubMed1997

Metastatic carcinoid tumor imaged with CT and a radiolabeled somatostatin analog: a case report.

Radiolabeled somatostatin analogs have shown uptake in a variety of tumors. These include carcinoid, Merkel cell carcinoma, pheochromocytoma, islet cell tumor, and other tumors with somatostatin receptors. Radiolabeled somatostatin analog imaging with Indium-111-DTPA-pentetreotide permits whole body imaging, providing a new safe and effective means for detection of primary tumors and metastatic foci in neoplasms with somatostatin receptors. This imaging modality is helpful in screening the entire body as well as evaluating questionable foci of disease identified by conventional imaging modalities. This case report demonstrates the utility of computed tomography (CT) and radiolabeled somatostatin imaging as complementary modalities in the workup of a patient with metastatic carcinoid tumor.

Aged↗
PubMed1996

Infertility among human immunodeficiency virus-positive women: incidence and treatment dilemmas.

The increasing demand for fertility advice among human immunodeficiency virus (HIV)-positive women under our care led us to review the incidence of infertility and the ethical problems associated with its management. All HIV-positive women who attended the HIV outpatients clinic from October 1990 to the end of January 1996 were studied. The main outcome measures were: the number of women undergoing infertility investigations before and after HIV diagnosis, their demographic and social details, and the outcome of these investigations. Most of the 183 women studied were in their reproductive years (mean age 32.7 +/- 6.7 years). Nine women had undergone infertility investigations, and/or treatment before HIV diagnosis, three of whom were diagnosed with HIV during routine testing prior to IVF treatment. Six declined further infertility treatment after discovering their HIV status. Eight women have undergone infertility investigations after HIV diagnosis but none have achieved pregnancy to date. Management decisions may have been hampered by ethical uncertainties in several cases. In conclusion therefore, as requests for infertility treatment from HIV-infected women occur and may become more common as the prevalence of HIV infection in women continues to rise, the ethical issues associated with the management of this problem demand urgent attention so that clear guidelines are available to aid treatment decisions.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Patterns of cytokine secretion by autoreactive proteolipid protein-specific T cell clones during the course of multiple sclerosis.

To determine whether cytokine secretion patterns change with disease status in patients with multiple sclerosis (MS), we measured IFN-gamma, TNF-alpha beta, IL-4, IL-6, IL-10 and TGF-beta secretion in a panel of T cell clones (TCCs) specific for proteolipid protein (PLP) after stimulation with PLP peptides or polyclonal activators. During acute attack, the predominant pattern of cytokine secretion resembled that of murine Th1 cells; i.e, IFN-gamma and TNF-alpha beta, and appeared to be restricted to PLP-reactive TCCs. None of the TCCs isolated during acute attack produced TGF-beta in response to PLP, Con A, or anti-CD3 Ab. Half of these TCCs were, however, capable of TGF-beta secretion and mRNA expression upon stimulation with PMA and the calcium inonphore A23187, suggesting a possible defect in activation through the TCR/CD3 pathway. During remission in the same patients all but two PLP-TCCs showed patterns of cytokine secretion resembling that of murine Th0, Th1, and Th2 subsets. The levels of IL-10 secreted by these TCCs were significantly higher than those of TCCs isolated during acute attacks and those derived from normal subjects and patients with other noninflammatory neurologic diseases. Furthermore, 50% of these TCCs were capable of producing TGF-beta after Ag-specific or polyclonal stimulation. All TCCs isolated from control subjects exhibited a Th0 like secretion profile. These data indicate that different stages of disease in MS are characterized by different patterns of cytokine secretion by PLP-specific TCCs, suggesting a role for cytokines in clinical events during the course of MS.

Autoantigens↗
PubMed1995

Mr. Smith goes to Washington?. Interview by Renee Blankenau.

The five freshman congressmen we're profiling in this issue have a lot more going for them than Mr. Smith did; most importantly, all bring strong community health and welfare concerns to Capitol Hill. A look at representatives of a sometimes surprising new crop of citizen-lawmakers.

Health Care Reform↗
PubMed1995

Efficacy and tolerance of Menorest compared to Premarin in the treatment of postmenopausal women. A randomised, multicentre, double-blind, double-dummy study.

Two-hundred and fourteen (214) menopausal women with moderate to severe vasomotor symptoms, aged 40-65 years, were randomised. After a 4-week treatment-free period, each women received a continuous regimen of Menorest 50 twice weekly or Premarin 0.625 mg daily, for 12 weeks. Didrogesterone 10 mg was also given to all women for 12 days of every 28-day cycle. The objectives were to compare the efficacy and safety profiles of Menorest and an oral estrogen. A statistically significant reduction in the mean number of hot flushes occurred in each group compared to baseline with a decrease from 7.1 at baseline to 0.9 at 12 weeks in the Menorest group, and from 6.7 to 0.5 in the oral estrogen group; there was no statistically significant difference between the two groups (P = 0.36). With each successive treatment cycle, there was a continuous improvement in the number of hot flushes. The incidence and severity of menopausal symptoms were reduced in the same manner in both groups. There were no statistically significant differences in the mean plasma estradiol and estrone concentrations between the two treatment groups after 10 weeks of therapy. The mean estradiol to estrone ratio was similar in both groups, as was the number of adverse events observed. In summary, Menorest was as effective as an oral estrogen in alleviating menopausal symptoms.

Administration, Cutaneous↗
PubMed1995

Hepatosplenic gamma delta T-cell lymphoma. A distinctive aggressive lymphoma type.

The T-cell receptor (TCR) expressed on the surface of most T-lymphocytes is of alpha beta type, and only a minority bear the gamma delta-TCR. Similarly, postthymic T-cell lymphomas rarely express gamma delta-TCR. Hepatosplenic gamma delta T-cell lymphoma is an uncommon entity that has so far not been widely recognized. We report one such case that has been comprehensively studied by multiple modalities and showed the unique occurrence of leukemic picture at presentation. The 39-year-old man presented with fever, marked weight loss, and massive splenomegaly. Peripheral blood showed thrombocytopenia and a white cell count of 5.8 x 10(9)/l, with 66% medium-sized lymphoid cells that had a round or folded nucleus, condensed chromatin and a moderate amount of pale blue cytoplasm. Splenectomy was performed and histologic examination of the spleen, bone marrow, liver, and abdominal lymph nodes demonstrated lymphoma infiltration with a predominantly sinusoidal pattern. Immunohistochemical studies of the lymphoma cells showed a T-cell phenotype: CD2+ CD3+ CD5+ CD7+ gamma delta-TCR+ alpha beta-TCR- CD56+ CD4- CD8- CD16- CD57-. Cytogenetic studies showed complex clonal chromosomal abnormalities of 44,X, -Y, -11, -22, + mar in 3/16 cells. Rearrangement of the TCR gamma chain gene was demonstrated by polymerase chain reaction; the TCR beta chain gene was partially chain reaction; the TCR beta chain gene was partially rearranged. The patient did not respond to single agent chemotherapy, but achieved clinical remission with combination chemotherapy. Based on the available data in the literature, hepatosplenic gamma delta T-cell lymphoma exhibits distinctive clinicopathologic features, and probably represents the neoplastic counterpart of splenic gamma delta T-lymphocytes. This disease is associated with a poor prognosis and usually relapses despite initial response to chemotherapy.

Adult↗
PubMed1995

Isolation and characterization of autoreactive proteolipid protein-peptide specific T-cell clones from multiple sclerosis patients.

During the course of multiple sclerosis (MS), myelin proteins are likely antigenic targets for autoreactive T cells. Although most studies have implicated myelin basic protein as a potent encephalitogenic myelin component, proteolipid protein (PLP) appears also to be a possible target antigen in the autoimmune response in MS. In this report, we investigated the human T-cell responses to PLP by using PLP104-117 and PLP142-153 synthetic peptides as target antigens in limiting dilution. One hundred twenty-five CD4+, T-cell receptor (TCR) alpha beta+ T-cell clones (TCCs) were established from the peripheral blood of seven MS patients and five control subjects. Despite the use of enriched cultures no gamma delta TCCs were obtained. Recognition of both PLP epitopes occurred in the context of multiple HLA-DR alleles. We found no differences in restriction element usage between MS patients and control subjects. TCR variable beta-region (V beta) usage was assessed by flow cytometry using a panel of monoclonal antibodies defining different V beta elements. In both MS patients and control subjects, there was a marked heterogeneity in the TCR V beta repertoire. Furthermore, sequential evaluation of MS patients during acute attacks and clinical remissions showed even more broadening of the TCR V beta repertoire. These data demonstrate that a heterogeneous T-cell response to PLP concerning HLA restriction and TCR usage is present in both MS patients and normal subjects.

Adult↗