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D M Duffy

Publications and source records attributed to D M Duffy.

13 recordsLinked to original sources

Characterization of the beta-adrenergic receptor in isolated human fetal lung type II cells.

Functioning of the beta-adrenergic response system is important for successful transition of the neonate from fetal life to breathing air. We characterized the beta-adrenergic receptors on human fetal lung type II cells, the cell type responsible for many pulmonary responses sensitive to beta-adrenergic stimulation. Type II cells were isolated from human fetal lung explants, and membrane particulates prepared from these cells were used for radioligand binding studies. 125I-iodocyanopindolol, a specific beta-adrenergic antagonist, bound to a single class of saturable, high-affinity binding sites on type II cell membranes with a receptor concentration of 78 +/- 9 fmol receptor/mg membrane protein, a kd of 79 +/- 18 nM, and 958 +/- 120 receptors per cell. Binding was stereoselective with l-propranolol binding with higher affinity than the inactive d-isomer. The binding site had the characteristics of a beta 2-adrenergic receptor. The order of potency of beta-adrenergic agonists was isoproterenol greater than epinephrine much greater than norepinephrine. The beta 2-selective antagonist ICI 118,551 competed for a single class of high-affinity sites. Agonist binding affinity was reduced in the presence of guanyl nucleotides, consistent with receptors coupled to guanine nucleotide binding proteins. beta-Adrenergic agonists also stimulated adenylyl cyclase in these membrane preparations. 125I-iodocyanopindolol binding to membranes prepared from human fetal lung fibroblasts indicated fewer receptors (404 +/- 68) than were present on type II cells. Work by others has suggested a difference in lung function and lung beta-adrenergic receptor concentration between males and females.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases

Cyclic adenosine 3',5'-monophosphate increases beta-adrenergic receptor concentration in cultured human fetal lung explants and type II cells.

cAMP regulates the maturation of many biochemical processes that occur during normal lung development, including the changing levels of surfactant proteins and phospholipids. We examined the effect of cAMP on the beta-adrenergic receptor concentration in the developing human lung. Isobutylmethylxanthine, a cAMP phosphodiesterase inhibitor, increased both the tissue cAMP content and beta-adrenergic receptor concentration in treated explants above those in untreated explants. 8-Bromo-cAMP treatment also elevated the beta-adrenergic receptor concentration of lung explants compared to that in untreated controls. These data indicate the ability of elevated cAMP to increase the beta-adrenergic receptor concentration. Both lung cAMP and beta-adrenergic receptor concentrations increase spontaneously in culture. To test for a possible causal relationship, we cultured explants with protein kinase inhibitors. We found that H-8, a preferential inhibitor of the cAMP-dependent protein kinase [protein kinase-A (PKA)], but not H-7, which inhibits PKA and protein kinase-C with similar potency, blocked the spontaneous rise in beta-adrenergic receptor concentration in human fetal lung explants, indicating that PKA activity is required for this rise in beta-adrenergic receptor concentration. Type II cells isolated from cultured lung treated with H-8 had fewer beta-adrenergic receptors than cells isolated from untreated explants. These studies show that cAMP increases the beta-adrenergic receptor concentration in human fetal lung and specifically in type II cells through a PKA-dependent mechanism, consistent with a role for cAMP in beta-adrenergic receptor regulation during normal lung development.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Determination of incidence and risk factors for postsclerotherapy telangiectatic matting of the lower extremity: a retrospective analysis.

Telangiectatic matting are vessels less than 0.2 mm in diameter that may appear after sclerotherapy treatment of varicose or telangiectatic leg veins. It is a complication about which very little epidemiologic data have been formally accrued. Therefore, a retrospective analysis was conducted by reviewing the records of 2120 patients in a private practice setting. The overall incidence of telangiectatic matting in our patient population was 16%. To identify risk factors, in-depth comparative analysis of the databases of 160 of the patients who developed telangiectatic matting and a control group of 160 nonmatting patients was performed. Significantly more patients in the matting group were overweight, on hormones during treatment, and had both a family history and a longer duration of spider veins (p less than 0.05). Additionally, the matting group had a significantly higher proportion of people noting onset of their veins after excess hormonal states, relative to before excess hormonal states, than the nonmatting group. Age and excessive standing did not differ significantly between the two groups. The results of this study provide objective, predictive risk factors for the development of telangiectatic matting.

Adult

Silicone: a critical review.

The response of biologic systems to implanted foreign materials is subject to a lesion of variables. Each type of implant must be individually evaluated in a specific application and host. Pure DMPS polymer injected into subcutaneous tissues behaves in a specific and characteristic way. An analysis of the behavior of other types of implants in other applications will not necessarily reveal insights applicable to the behavior of liquid silicone. Most adverse case reports relate to injected fluids of unknown purity or identity used in inappropriate volumes in poorly chosen anatomical sites. It is ironic that pure DMPS in small volumes, a theoretically ideal combination, is so mistrusted. However, liquid silicone's sinful potential was easy to predict. It was cheap, available, easy to use, and, when injected in large volumes, produced instant and financially profitable results. Moreover, a welter of confusing titles, "authorized investigators" and "medical grade silicone" coupled with sensationally adverse reports detailing a criminal misuse of this modality led to draconian measures banning its use and made a meaningful analysis of true incidence and type of side effects following its use nearly impossible to assess. The advocates' position that liquid silicone is safe when used properly cannot be refuted. Only a handful of serious adverse reactions can be documented following its use; however, the concept that pure DMPS polymer can, even in expert hands, occasionally produce immunologically mediated adverse effects is equally irrefutable. This concept is supported by the following evidence: 1. Minor idiosyncratic and granulomatous reactions occurring in 1 in 10,000 are reported in association with a nidus of infection or as a consequence of allergic events. 2. At least one serious inflammatory reaction occurred in a patient afflicted with both autoimmune disease and concurrent infection. These reactions are best understood in the broader context of tissue responses to all classes of implanted foreign material, and they are most easily understood in the narrow context of autoimmune disease after injection of implantable paraffin, silicone, and possibly "silicone polymers." "Certain authors speculate that silicone acting as a primary antigen is not likely," however, silicone acting as an adjuvant associated with a subclinical infection as an antigen source may be the cause of adjuvant disease. A careful review of published anecdotal and personal experience involving the use of 350 centistoke pure dimethypolysiloxane fluid (liquid silicone) for soft-tissue augmentation in small volumes (and in large volumes for facial hemiatrophy) suggests that the bias against its proper use is unfounded.(ABSTRACT TRUNCATED AT 400 WORDS)

Dermatologic Surgical Procedures

Informed consent for chemical peels and dermabrasion.

Clinicians have an obligation to make sure that patients are adequately informed and understand, first, the general risks involved in any elective procedure, and, second, whether there are any features in their medical profiles that pose greater risks or pose the possibility of greater benefits than the average patient. Patients must understand the concepts of general risk, the possibility of unpredictable events happening randomly, and their own personal risk of having this happen. The remainder of the article deals with the information regularly provided to patients who show an interest in dermabrasions or chemical peels.

Chemexfoliation

Postsclerotherapy hyperpigmentation: a histologic evaluation.

Linear or macular pigmentation occurs in 10-30% of patients following sclerotherapy of vessels between 0.1 and 5 mm in diameter. Its occurrence is related to solution strength, vessel fragility, injection pressure, and the type of solution used. This adverse sequela of treatment has been assumed, by some, to represent post-inflammatory hyperpigmentation (incontinence of melanin pigment), and has been said to occur in individuals with this tendency. Histologic data presented in this paper suggest that this phenomenon does not represent melanocytic alteration, but is secondary to extravasation of red blood cells into the dermis following rupture of fragile vessels with resulting deposition of hemosiderin. Therapy has included bleaching agents (hydroquinones), trichloroacetic acid, and phenolic peeling agents with variable success. Eighty percent of patients who experience this adverse sequela will clear spontaneously within 6-24 months. The remaining patients will have persistence of pigmentation for up to 5 years, with a small number of patients having pigmentation persisting 5 years after therapy.

Biopsy

Meeting the challenge of multiple academic roles through a nursing center practice model.

Filling the multiple requirements of academic life--to teach, to conduct research, and to give service to the community--can be difficult for any academician. When the educator is also a nurse, meshing academic life with that of a practicing professional adds to the difficulties. Maintaining control and managing resources for practice can be time consuming and wearisome. The authors use quotes from the sociologist Paul Starr to describe and examine this professional dilemma. The process they followed in implementing a practice model in a community nursing center is described. Using this approach teaching, research, and service requirements were blended with practice for greater professional control and more productive scholarly endeavors.

Community Health Centers

Lymphangiosarcoma arising from lymphangioma circumscriptum.

A lymphangiosarcoma arose at the site of a preexisting lymphangioma circumscriptum on the skin of the anterior part of the abdominal wall. To our knowledge, this is only the second such case to be reported, and in both patients, the preexisting lymphangioma circumscriptum had been exposed to substantial x-ray therapy. Since it is possible that x-irradiation may play a role in the development of this unusual malignant neoplasm, it seems advisable that lymphangioma circumscriptum not be exposed to substantial amounts of such radiation, if feasible.

Adult

Sclerotherapy.

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Female