PubMed Health⌕ Search

Biomedical subjects

K Flaherty

Publications and source records attributed to K Flaherty.

11 recordsLinked to original sources
PubMed2001

Usual interstitial pneumonia.

Usual interstitial pneumonia (UIP) is a distinct histological lesion observed in idiopathic pulmonary fibrosis (IPF), but can be found in other etiologies. The diagnosis of UIP can be established by surgical lung biopsy or by high resolution thin section computed tomographic scans (provided the radiographic features are classical). Historically, patients labeled as "IPF'' encompassed a group of disorders including UIP as well as other idiopathic interstitial pneumonias, which differ from UIP in prognosis and responsiveness to therapy. Current recommendations from international consensus statements restrict the term IPF to patients with idiopathic UIP. The inciting cause(s) and pathogenesis of UIP have not been elucidated, but alveolar epithelial cell injury and dysregulation or altered phenotypic expression of fibroblasts are key elements. Inflammatory cells may play minor roles in initiating or propagating the fibrotic process. The prognosis of UIP is poor. Mean survival following diagnosis approximates 3 years. Current therapies are of unproven value. Corticosteroids or immunosuppressive agents have been most often used, but data affirming benefit are lacking. Single-lung transplantation is a viable option for patients failing medical therapy. Novel therapeutic strategies based upon inhibiting fibroproliferation or enhancing alveolar reepithelialization are desperately needed. In this article, we discuss diagnostic criteria for UIP (both histopathological and radiographic), natural history and clinical course, and therapeutic approaches (both current and future).

Journal Article↗
PubMed2001

Corticosteroids in idiopathic pulmonary fibrosis.

Corticosteroids were the mainstay of therapy for idiopathic pulmonary fibrosis (IPF) for more than four decades, but their efficacy is unproven and toxicities are substantial. The course of IPF is characterized by progressive respiratory insufficiency, leading to death within 3 to 8 years from the onset of symptoms. Although a subset (10-20%) of patients survives more than 10 years, there is no evidence that any form of therapy alters the natural history of the disease. Nonetheless, given the poor prognosis, a trial of corticosteroids is often given. Because of the rarity of IPF, randomized, placebo-controlled therapeutic trials have not been done. Further, no studies have compared differing dosages or duration of corticosteroid in matched patients. Interpretation of therapy efficacy is obscured by several factors including heterogeneous patient populations, inclusion of patients with histologic entities other than usual interstitial pneumonia, lack of objective, validated endpoints, different criteria for "response." We review published data regarding corticosteroid therapy for IPF and present a rationale for stratifying therapy based on host, demographic, and clinical factors that influence prognosis as well as risk for corticosteroid complications.

Adrenal Cortex Hormones↗
PubMed2001

Protecting the subrogation rights of self-insured group health plans.

As a means of controlling costs, self-insured group health plans often contain subrogation provisions that give the plan a right to recoup benefits paid to a plan participant or beneficiary who recovers damages from a third party. Such subrogation claims are frequently contested, so it is important that a plan's subrogation provisions are properly drafted.

Employee Retirement Income Security Act↗
PubMed1993

Definition and spatial location of mouse interleukin-2 residues that interact with its heterotrimeric receptor.

The high affinity receptor for interleukin-2 (IL-2) contains three subunits called IL-2R alpha, beta and gamma. A biological and receptor binding analysis based on 1393 different mutant mouse IL-2 (mIL-2) proteins was used to define the function of each of the 149 residues. By this genetic analysis, 44 residues were assigned important functions, 21 of which were structural. The remaining 23 residues consisted of 19 residues, from three separate regions, that were important for IL-2R alpha interaction; three residues, from two separate regions, that were important for IL-2R beta interaction; and a single residue important for IL-2R gamma interaction. We built a model mIL-2 structure based on the homologous human IL-2 (hIL-2) crystal structure. The roles of the 21 residues presumed to be important for structure were consistent with the model. Despite discontinuity in the primary sequence, the residues specific for each IL-2R subunit interaction were clustered and located to three disparate regions of the tertiary mIL-2 structure. The relative spatial locations of these three surfaces are different from the two receptor binding sites known for the structurally related human growth hormone and the significance of this observation is discussed.

Amino Acid Sequence↗
PubMed1991

Evolution of human immunodeficiency virus type 1 nucleotide sequence diversity among close contacts.

The degree of change in the nucleotide sequence of human immunodeficiency virus type 1 (HIV-1) that occurs when it is transmitted sexually from one individual to another or vertically from mother to child is unknown. Previous studies have shown that most cultured HIV-1 isolates from the same individuals differed in the entire envelope gene nucleotide sequence by up to 2%, although most isolates from unrelated individuals differed by 6-22%. To examine diversity among HIV-1 isolates from close contacts, we determined the nucleotide sequences of viruses from a family with a known epidemiologic profile, in which a woman transmitted HIV-1 heterosexually to her partner and vertically to her daughter. Direct DNA sequence analysis of primary HIV-1 isolates amplified by PCR was used to distinguish the major and minor viral sequences, termed quasispecies, to rapidly determine the predominant sequences and their phylogenetic relationships. The nucleotide sequence diversity of a major portion of the HIV-1 envelope gene was 3.7% between isolates from the woman and her heterosexual partner and 8.5% between isolates from this woman and her daughter, who had been infected for a longer period than the partner. The configuration of the phylogenetic tree demonstrated that the daughter's predominant isolate evolved from a progenitor of her mother's current strain. This study provides evidence of a continuous spectrum of sequence diversity between any two isolates ranging from those derived from the same person to those from close contacts and, ultimately, those from unrelated individuals. These data and methods can be applied to epidemiologic investigations of possible HIV-1 transmission between health care workers and their patients.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Long HIV-1 incubation periods and dynamics of transmission within a family.

The incubation period of human immunodeficiency virus type 1 (HIV-1) infection was studied in a family of five in which vertical and heterosexual transmission occurred from one index case. This investigation documented incubation periods of longer than 12 years in a mother and her daughter; although neither has symptoms, both are definitely infected and have very low CD4(+)-lymphocyte counts. The study confirmed the predictions of incubation periods longer than 10 years in a small proportion of infected individuals. It provides evidence that vertically HIV-1-infected teenagers can be expected to appear in the population.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Efficacy of rifabutin in the treatment of AIDS-related complex.

We performed a phase 1-2 antiviral dose escalation trial of rifabutin, a rifamycin antibiotic with anti-HIV-1 activity in vitro. We followed 16 men with AIDS-related complex (ARC) for a mean duration of 29 weeks; the maximum toxicity-limited dose of rifabutin was 2400 mg/day, which was achieved in two patients. There was some evidence of anti-HIV-1 activity in two patients, one of whom had an improvement in immune status, but 11 of the 16 patients showed a deterioration in either virologic or immunologic status. The majority of the patients under study remained clinically stable during the trial, but there was clinical deterioration in the three who entered with CD4 cell counts of less than 100 x 10(6)/l. On the basis of this trial, rifabutin as a single antiviral agent does not appear to be beneficial to ARC patients.

AIDS-Related Complex↗
PubMedDate not supplied

Nurses' perceptions of their health educator role.

A questionnaire was designed to describe and understand the role of the registered nurse in patient teaching as perceived by nurses. The questionnaire was distributed to 1355 nurses working in an acute care tertiary teaching hospital. The data indicated most nurses expressed strong agreement with the majority of items relating to their skill and educational preparation to teach patients. Selected questions relating to the nurse's role as a patient educator showed nurses viewed their patient education role as satisfying and expected by their patients. Needs relating to their patient education role included: additional time to teach patients, more educational materials, peer feedback regarding teaching effectiveness, and sufficient medical information. Additionally, the majority of nurses perceived that patients did not have sufficient knowledge to care for themselves after leaving the hospital and that too much information about their condition was withheld from them. Summary scales showed significant differences in area of work and position with the nurse's perception of the health educator role.

Clinical Competence↗