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Biomedical subjects

P A Fitzgerald

Publications and source records attributed to P A Fitzgerald.

16 recordsLinked to original sources
PubMed1992

HB Al-Ain Abu Dhabi [alpha 18(A16)Gly----Asp]: a new hemoglobin variant discovered in an Emiratee family.

During a routine program of hemoglobin screening performed in the United Arab Emirates, we observed an electrophoretically fast-moving variant in a 9-month-old girl and in several members of her family. The structural determination, performed by reversed phase high performance liquid chromatography and amino acid sequencing, revealed a new variant that we named Hb Al-Ain Abu Dhabi [alpha 18(A16) Gly----Asp]. Its functional properties were normal.

Amino Acid Sequence↗
PubMed1989

Human pituitary tumors secrete chromogranin-A.

Chromogranin-A (CgA) has emerged as a serum and tissue marker for a number of endocrine tumors. We studied 15 patients with pituitary tumors to evaluate the clinical value of CgA as a serum and tissue marker for such tumors. One third of the patients had elevated serum CgA levels; 2 of these patients had nonsecreting pituitary tumors, and the other 3 had corticotroph adenomas. CgA-positive cells were detected in 9 of the 11 anterior pituitary tumors that were immunostained; in these 9 tumors at least half of the cells were CgA positive. We conclude that CgA production is common in pituitary tumors and that immunohistochemical studies for CgA may aid in their classification. In addition, serum CgA measurements may help to identify patients with pituitary tumors, especially those that do not secrete a known pituitary peptide.

Biomarkers, Tumor↗
PubMed1988

Cushing's syndrome due to bilateral adrenal macronodular hyperplasia with undetectable ACTH: cell culture of adenoma cells on extracellular matrix.

A 59-year-old man developed Cushing's syndrome with massive bilateral adrenal macronodular hyperplasia. Plasma ACTH levels were undetectable both peripherally and in the inferior petrosal sinus. Computed tomography scans of his pituitary were normal. Hypercortisolism was not suppressed by high doses of dexamethasone. His adrenal cells were successfully isolated and grown on bovine corneal extracellular matrix. The cultured cells displayed strikingly rapid growth and hypersecretion of cortisol during incubation with control serum. Addition of the patient's serum to cultured fetal adrenal cells did not accelerate their growth. This was the first experience with our in vitro system in this rare clinical condition. The techniques described here may be used for future in vitro adrenal studies. These in vivo and in vitro data indicate that this patient's bilateral adrenal hyperfunction and growth were independent of ACTH.

Adrenal Glands↗
PubMed1986

Natural killer cell function and interferon generation in patients with primary immunodeficiencies.

Patients with primary immunodeficiency disorders were evaluated for three aspects of natural defense: natural killer (NK) cells which lyse HSV-infected fibroblasts [NK(HSV-FS)], NK cells which lyse K562 tumor targets [NK(K562)], and interferon-alpha generation. In addition, capacity to make interferon upon challenge with other commonly used inducers was also evaluated. Most patients with severe combined immunodeficiency disease (SCID) and deficits of both T- and B-cell function demonstrated normal NK function with one or both targets. Six of eight SCID patients generated interferon-alpha at or below the lower limit of normal while only two made clearly normal levels. Six of 10 patients with Wiskott-Aldrich syndrome (WAS) had normal NK(K562) and five of 10 generated normal levels of interferon-alpha but all had severely deficient NK(HSV-FS). Patients with Bruton's agammaglobulinemia demonstrated normal NK and interferon generation, as did patients with common variable immunodeficiency, even when subdivided into patients with T-cell proliferative deficiencies and those with only hypogammaglobulinemia. Natural defense parameters may help categorize patients with SCID and WAS and help define these heterogeneous diseases.

Agammaglobulinemia↗
PubMed1986

Opportunistic infections in acquired immune deficiency syndrome result from synergistic defects of both the natural and adaptive components of cellular immunity.

We evaluated the cellular immunity of 408 clinically stratified subjects at risk for acquired immune deficiency syndrome (AIDS), to define the role of interferon-alpha production deficits in the pathogenesis of opportunistic infections (OI). We followed 115 prospectively for up to 45 mo. Onset of OI was associated with, and predicted by, deficiency both of interferon-alpha generation in vitro, and of circulating Leu-3a+ cells. Interferon-alpha production is an index of the function of certain non-T, non-B, large granular lymphocytes (LGL) that are independent of T cell help. Leu-3a+ cell counts are a marker of T cell function. OI did not usually develop until both of these mutually independent immune functions were simultaneously critically depressed, leading to a synergistic interaction. These data suggest that the AIDS virus affects a subset of LGL, and that cytokine production by these cells is an important component of the host defense against intracellular pathogens that becomes crucial in the presence of severe T cell immunodeficiency.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Cerebral salt wasting after pituitary exploration and biopsy: case report.

We report a case of hyponatremia associated with volume depletion after pituitary exploration and biopsy. The presence of clinical dehydration precluded diagnosis of the syndrome of inappropriate secretion of antidiuretic hormone. The absence of a hypoadrenal state and the patient's response to volume reexpansion were consistent with a diagnosis of primary cerebral salt wasting.

Adult↗
PubMed1986

An overnight high-dose dexamethasone suppression test for rapid differential diagnosis of Cushing's syndrome.

We have developed a high-dose dexamethasone suppression test that can be administered overnight with a single 8-mg dose and used the new procedure in the differential diagnosis of 83 patients with Cushing's syndrome. In 76 patients with surgically or pathologically proven cause--60 with Cushing's disease, 7 with the ectopic adrenocorticotrophic hormone syndrome, and 9 with adrenal tumors--suppression of plasma cortisol levels to less than 50% of baseline indicated a diagnosis of Cushing's disease. The test had a sensitivity of 92%, a specificity of 100%, and a diagnostic accuracy of 93%. These values equal or exceed those of the standard 2-day test whether based on suppression of urinary 17-hydroxycorticosteroids or plasma cortisol. We conclude that this overnight, high-dose dexamethasone suppression test is practical and reliable in the differential diagnosis of Cushing's syndrome.

17-Hydroxycorticosteroids↗
PubMed1985

Human natural killer cells limit replication of herpes simplex virus type 1 in vitro.

Studies were undertaken to determine whether natural killer (NK) cells could inhibit the replication of herpes simplex virus type 1 (HSV-1) in culture. In the absence of effector cells, HSV-1 was found to replicate in fibroblasts with up to a 100-fold increase in virus titer from 4 to 16 hr after incubation at 37 degrees C. Human peripheral blood mononuclear cells were found to limit virus replication in a dose-dependent manner, with the greatest inhibition being observed at the highest concentration evaluated: i.e., an effector:target ratio of 800:1. The antiviral effect was not observed when nonactivated or virus-activated mononuclear cells were added to the virus preparations at the end (instead of the beginning) of the assay period, indicating that the observed effect was not due to a nonspecific toxicity of soluble factors released from freeze-thawed effectors. Neither was inhibition of HSV-1 replication due to the generation of interferon (IFN) during the NK assay, because the addition of anti-IFN did not abrogate the antiviral effect. Thus, the inhibition of viral replication was most likely due to a cytotoxic effector rather than to release of soluble factors. The effector cells responsible for limiting HSV-1 replication were shown to be NK cells by a number of criteria. Mononuclear cells from both HSV-1 seropositive and seronegative donors limited virus replication; their activity could be boosted by pretreatment of effector cells with IFN; the effector cells which limited virus replication were found in Percoll gradient fractions enriched for large granular lymphocytes; and the effector cells shared the cell surface phenotype of NK cells--they were enriched in populations depleted of T cells by panning with Leu-4 and were depleted of activity by treatment with the anti-NK antibody Leu-11b plus complement. We conclude that human NK cells are capable of recognizing and lysing HSV-1-infected target cells before infectious virus progeny are generated. These results suggest that NK cells, acting early in the course of an infection, might serve to limit HSV-1 replication and therefore reduce the virus load in the host before the development of the adaptive immune response and clearance of the infection.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1978

Cushing's disease. Selective trans-sphenoidal resection of pituitary microadenomas.

We undertook trans-sphenoidal microsurgical pituitary exploration in 20 consecutive patients with Cushing's disease, eight of whom had normal sellar polytomography. Pituitary adenomas were selectively resected in 17 and histologically confirmed in 14. In one patient total hypophysectomy revealed a 1.5-mm basophilic adenoma, and in two patients vascular anomalies prevented sellar exploration. Hypercortisolism was corrected in 17 patients (i.e., in 16 of the 17 undergoing selective tumor removal and in the one with total hypophysectomy). Panhypopituitarism occurred only in this patient, and transient diabetes insipidus occurred in five. Most patients became glucocorticoid deficient and required replacement therapy. We conclude that pituitary tumors are present in the great majority of patient with Cushing's disease, even in the absence of demonstrable tomographic changes in the sella turcica, and that selective removal corrects hypercortisolism with little morbidity.

Adenoma↗
PubMed1977

Surgical management of hyperhidrosis.

Sixty-five patients with severe disabling hyperhidrosis were subjected to operation. Eighty-nine sympathectomies and 42 axillary skin excisions were performed to abolish sweating. Almost 90% of these patients were extremely satisfied with the outcome of surgery which resulted in a change for the better in their social and working lives. When conservative therapy fails, we recommend these procedures, which often alleviate this most distressing symptom.

Adolescent↗