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Biomedical subjects

S Hartnett

Publications and source records attributed to S Hartnett.

8 recordsLinked to original sources
PubMed2001

Heparin-induced thrombocytopenia as the cause of gluteus muscle necrosis: a case study describing the benefits of multidisciplinary physical and psychosocial interventions.

Heparin-induced thrombocytopenia, an increasingly recognized aspect of heparin therapy, occurs in 0.6% to 30% of patients receiving heparin. Approximately 1% of those patients develop the more severe heparin-induced thrombocytopenia II, also called white clot syndrome, in which synchronous venous and arterial thrombi impede blood flow in central vessels. Mortality (as high as 25%) and morbidity are related to the site and extent of thrombi formation. Following vascular surgery, one patient manifested an unusual consequence of heparin-induced thrombocytopenia II when thrombotic blockage of the vessels supplying the bilateral gluteus maximus and minimus muscles resulted in tissue ischemia and death. Supporting the patient through numerous complications and managing the extensive wound healing process required multidisciplinary skills and innovative technology, including use of vacuum-assisted closure therapy, platelet-derived growth factors, parenteral and enteral nutritional support, and spirit-restoring favorite foods. This article describes the patient's life-threatening and long-lasting effects from an allergic reaction to heparin therapy. In addition to information about the diagnosis of heparin-induced thrombocytopenia, this article also describes management of the wound and other aspects of care and comforting that occurred over a 9-month hospitalization.

Anticoagulants↗
PubMed2000

Maturation and lineage-specific expression of the coxsackie and adenovirus receptor in hematopoietic cells.

Adenovirus vectors have been used to transfer genes into both hematopoietic progenitor cells and tumor cells, including carcinoma cells that have metastasized to bone marrow (BM). However, the relative susceptibility of different subsets of hematopoietic cells is unknown. In permissive cells adenoviral-mediated gene transfer is mediated by the coxsackievirus and adenovirus receptor (CAR) protein and alpha(v) integrins expressed on the cell surface of the target cells. This prompted us to investigate the expression of CAR on subpopulations of hematopoietic cells, determine whether this protein played a role in adenovirus-mediated gene transfer of hematopoietic cells and whether we could modulate CAR to enhance gene transfer efficiency. In this report we show that CAR is expressed on approximately 40% of all human BM cells, including erythroid and myeloid cells, but not lymphoid cells. Of the CD34(+) cells, 10%-15% expressed CAR, but this did not include most colony-forming progenitor cells, nor the most primitive CD38(-) subpopulation. The presence of CAR correlated well with gene transfer efficiency, but we were unable to induce CAR expression on immature, noncommitted progenitor cells. In conclusion, our results show that primitive hematopoietic progenitor cells lack CAR expression, but that expression is acquired during erythroid and myeloid differentiation.

Adenoviridae↗
PubMed1999

Essential role for the p55 tumor necrosis factor receptor in regulating hematopoiesis at a stem cell level.

Hematopoietic stem cell (HSC) self-renewal is a complicated process, and its regulatory mechanisms are poorly understood. Previous studies have identified tumor necrosis factor (TNF)-alpha as a pleiotropic cytokine, which, among other actions, prevents various hematopoietic progenitor cells from proliferating and differentiating in vitro. However, its role in regulating long-term repopulating HSCs in vivo has not been investigated. In this study, mice deficient for the p55 or the p75 subunit of the TNF receptor were analyzed in a variety of hematopoietic progenitor and stem cell assays. In older p55(-/-) mice (>6 mo), we identified significant differences in their hematopoietic system compared with age-matched p75(-/-) or wild-type counterparts. Increased marrow cellularity and increased numbers of myeloid and erythroid colony-forming progenitor cells (CFCs), paralleled by elevated peripheral blood cell counts, were found in p55-deficient mice. In contrast to the increased myeloid compartment, pre-B CFCs were deficient in older p55(-/-) mice. In addition, a fourfold decrease in the number of HSCs could be demonstrated in a competitive repopulating assay. Secondary transplantations of marrow cells from primary recipients of p55(-/-) marrow revealed impaired self-renewal ability of p55-deficient HSCs. These data show that, in vivo, signaling through the p55 subunit of the TNF receptor is essential for regulating hematopoiesis at the stem cell level.

Animals↗
PubMed1999

One-day ex vivo culture allows effective gene transfer into human nonobese diabetic/severe combined immune-deficient repopulating cells using high-titer vesicular stomatitis virus G protein pseudotyped retrovirus.

Retrovirus-mediated gene transfer into long-lived human pluripotent hematopoietic stem cells (HSCs) is a widely sought but elusive goal. A major problem is the quiescent nature of most HSCs, with the perceived requirement for ex vivo prestimulation in cytokines to induce stem cell cycling and allow stable gene integration. However, ex vivo culture may impair stem cell function, and could explain the disappointing clinical results in many current gene transfer trials. To address this possibility, we examined the ex vivo survival of nonobese diabetic/severe combined immune-deficient (NOD/SCID) repopulating cells (SRCs) over 3 days. After 1 day of culture, the SRC number and proliferation declined twofold, and was further reduced by day 3; self-renewal was only detectable in noncultured cells. To determine if the period of ex vivo culture could be shortened, we used a vesicular stomatitis virus G protein (VSV-G) pseudotyped retrovirus vector that was concentrated to high titer. The results showed that gene transfer rates were similar without or with 48 hours prestimulation. Thus, the use of high-titer VSV-G pseudotyped retrovirus may minimize the loss of HSCs during culture, because efficient gene transfer can be obtained without the need for extended ex vivo culture.

Animals↗
PubMed1993

Samarium-153-EDTMP biodistribution and dosimetry estimation.

Fifty-two patients were treated with single doses of 153Sm-EDTMP in a Phase I escalating dose protocol for palliation of bone pain from metastatic prostate carcinoma. Samarium-153 (T1/2 46.3 hr), maximum beta-particle energies 810 keV (20%), 710 keV (30%), 640 keV (50%), gamma photon 103 keV (28%), was complexed to the tetraphosphonate chelate, EDTMP. Five groups of patients were treated at doses of 1.0, 1.5, 2.0, 2.5, and 3.0 mCi/kg to evaluate toxicity from treatment. Patients were screened prior to treatment and followed after treatment with 99mTc-MDP bone scans. Biodistribution data on this group of patients were acquired and showed rapid uptake of 153Sm-EDTMP into bone with complete clearance of nonskeletal radiotoxicity by 6-8 hr. Also included are complete sets of dosimetry estimations on an additional seven patients who received 0.5 mCi/kg 153Sm-EDTMP Ca++ as part of a multiple dose therapy trial. Estimated radiation absorbed doses to bone surfaces averaged 25,000 mrad/mCi (6686 Gy/MBq), and urinary bladder doses averaged 3600 mrad/mCi (964 Gy/MBq).

Bone Neoplasms↗
PubMed1989

Septic shock in the oncology patient.

Septic shock is an infrequent but not uncommon oncologic emergency. An understanding of the risk factors, pathophysiology, and current issues in the management of septic shock can contribute to better patient care through early recognition and prompt and knowledgeable intervention. This article reviews the epidemiology, predisposing risk factors, causative organisms, and pathophysiology of septic shock. Medical and nursing interventions illustrate the necessary teamwork involved in managing this life-threatening problem. Investigational approaches are discussed as well as the importance of identifying at-risk patients and initiating preventative measures.

Emergencies↗