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Biomedical subjects

T McGovern

Publications and source records attributed to T McGovern.

16 recordsLinked to original sources
PubMed1998

Phase I trial of sequential high-dose chemotherapy with escalating dose paclitaxel, melphalan, and cyclophosphamide, thiotepa, and carboplatin with peripheral blood progenitor support in women with responding metastatic breast cancer.

A single high-dose cycle of chemotherapy with stem cell support can produce disease-free survival of 15-20% for at least 3 years in women with responding stage IV breast cancer. North American Autologous Bone Marrow Transplant Registry data suggest that a complete response (CR) is the single most important prognostic factor associated with prolonged disease-free survival. Therefore, if sequential high-dose chemotherapy can increase the CR rate, then perhaps an increased proportion of patients will remain disease free. Women with at least a partial response (PR) to induction chemotherapy received three separate high-dose cycles of chemotherapy with peripheral blood progenitor support and granulocyte colony-stimulating factor. The first intensification was a dose escalation of paclitaxel (400-825 mg/ m2), the second intensification was melphalan (180 mg/m2), and the third intensification consisted of 6000 mg/m2 cyclophosphamide (1500 mg/m2/day), 500 mg/m2 thiotepa (125 mg/m2/day), and 800 mg/m2 carboplatin (200 mg/m2/day; CTCb). Thirty-six women were enrolled and 31 completed all three cycles. After the paclitaxel infusion most patients developed reversible predominantly sensory neuropathy. Of the 19 patients with measurable disease, 6 converted to CR, 7 converted to a PR* (the complete resolution of all soft tissue or visceral disease with sclerosis of prior lytic bone lesions), and 2 had a further PR for an overall response rate of 79%. Two patients had no further response and disease in two patients progressed, and thus they were taken off the study before CTCb. Seventy-eight percent are progression-free at a median follow-up of 14 months (range, 3-24+). Three sequential cycles of high-dose chemotherapy are feasible and were administered in this study with no mortality. Single agent paclitaxel at doses up to 825 mg/m2 were well tolerated with moderate reversible toxicity.

Adult↗
PubMed1997

Human keratinocytes maintain reversible anti-apoptotic defenses in vivo and in vitro.

Human keratinocytes proliferate and differentiate in an epidermal environment where induction of apoptosis can be triggered by ultraviolet radiation (UVR), activated lymphocytes and cytokines. The purpose of this study was to determine whether keratinocytes were susceptible to apoptosis induced by ionophore, ultra-violet radiation, cytokines or crosslinking of CD95 (Fas/APO-1). In normal human skin exposed to two minimal erythema doses of ultraviolet radiation, suprabasal cells were the first keratinocytes to demonstrate apoptotic nuclei, and by 48 h apoptotic cells were identified throughout the mid to upper epidermis. However, most keratinocytes resisted apoptosis and UVR-induced apoptosis was not observed in basal cells, or in the most differentiated epidermis. Human keratinocytes and keratinocyte cell lines cultured in vitro developed maximal apoptosis 48 h after radiation. Human keratinocytes cultured in full growth factor supplements were resistant to UVR-induced apoptosis compared to keratinocyte cell lines or to a lymphoid cell line (HL60) susceptible to apoptosis. Keratinocyte cell lines were completely resistant to apoptosis induced by interferon-gamma, interferon-alpha, IL-2, IL-6, TNF-alpha, IL-1Ra, and GM-CSF. A subset of the cells in cultures of keratinocytes and transformed keratinocyte cell lines died by apoptosis in response to anti-Fas, IL-1alpha and TNF-alpha plus IFN-gamma and ionophore. Second passage freshly isolated human keratinocytes were much more resistant to apoptosis induced by ionophore, anti-Fas and cytokines than were transformed keratinocyte cell lines. Calcium shift to induce differentiation in second-passage keratinocyte cultures made keratinocytes even more resistant to UVR-induced apoptosis. This parallels the lack of UVR-induced apoptosis observed in the most differentiated keratinocytes in irradiated human skin. Both keratinocytes and keratinocyte cell lines express rather low levels of the anti-apoptotic proteins bcl-2 and bcl-x compared to other apoptosis-resistant cell types. The differences between keratinocytes and keratinocyte cell lines in susceptibility to apoptosis are not explained by difference in expression of bcl-2 or bcl-x. Finally, withdrawal of growth factors from keratinocytes decreased cell survival following UVR and increased the induction of apoptosis. Inhibition of protein synthesis with cyclo-heximide also made keratinocytes more susceptible to UVR-induced apoptosis, indicating that anti-apoptotic defences in cultured keratinocytes are dependent on active protein synthesis. These experiments show that the strong keratinocyte defences against apoptosis are stratified within the epidermis, and can be altered by differentiation and growth factor withdrawal.

Journal Article↗
PubMed1996

Biomarkers of lung inflammation in recreational joggers exposed to ozone.

Humans exhibit an acute inflammatory response in the lungs after controlled laboratory exposure to ozone. The present study was designed to test whether biomarkers of inflammation are detectable in humans exposed to ozone and associated copollutants under natural conditions outdoors. Bronchoscopy with bronchoalveolar lavage (BAL) was carried out on 19 normal volunteer joggers from Governors Island, NY, who exercised in the afternoon during the 1992 summer (S1) season. Fifteen subjects were retested during the following, low ozone, winter season (W). The BAL protocol involved an initial instillation of 20 ml saline followed by four sequential 50-ml saline washes carried out in both the right middle lobe and the lingula. The eight 50-ml samples were pooled as the 'alveolar' sample. Analyses performed on the alveolar lavage samples included cell differentials, release of IL-8, TNF-alpha, and reactive oxygen species (ROS) by pooled cells, and levels of IL-8, protein, LDH, fibronectin, alpha1-antitrypsin (alpha1-AT), complement fragment 3a (C3a), and prostaglandin E2 (PGE2) in lavage fluids. Release of ROS by stimulated BAL cells was lower in S1 than in W (p = 0.03). In contrast, LDH levels in BAL fluids were 2-fold higher in S1 than in W (p = 0.02), as were IL-8 (p = 0.12) and PGE2 (p = 0.06). These results suggest a possible ongoing inflammatory response in the lungs of recreational joggers exposed to ozone and associated copollutants during the summer months.

Adult↗
PubMed1996

Reducing alcohol-impaired driving in Massachusetts: the Saving Lives Program.

OBJECTIVES: The purpose of this study ws to assess whether a community program begun in March 1988 that organized multiple city departments and private citizens could reduce alcohol-impaired driving, related driving risks, and traffic deaths and injuries. METHODS: Trends in fatal crashes and injuries per 100 crashes were compared in Saving Lives Program cities and the rest of Massachusetts from March 1984 through February 1993. In annual roadside surveys conducted at randomly selected locations, safety belt use among occupants of 54577 vehicles and travel speeds of 118442 vehicles were observed. Four statewide telephone surveys (n = 15188) monitored self-reported driving after drinking. RESULTS: In program cities relative to the rest of Massachusetts during the 5 program years in comparison with the previous 5 years, fatal crashes declined 25%, from 178 to 120, and fatal crashes involving alcohol decreased 42%, from 69 to 36. Visible injuries per 100 crashes declined 5%, from 21.1 to 16.6. The proportions of vehicles observed speeding and teenagers who drove after drinking were cut in half. CONCLUSIONS: Interventions organized by multiple city departments and private citizens can reduce driving after drinking, related driving risks, and traffic deaths and injuries.

Accidents, Traffic↗
PubMed1996

The Otto Aufranc Award. Skeletal response to well fixed femoral components inserted with and without cement.

Previous studies evaluating femoral remodeling after total hip arthroplasty have used clinical radiographs and dual energy xray absorptiometry. Limitation of these techniques make it impossible to quantify the magnitude of bone loss in terms of cortical thinning and cortical bone area and bone mineral density changes. Femoral cortical bone remodeling after cemented and cementless replacement was quantified and possible determinants of bone remodeling in terms of clinical and radiographic variables were evaluated. Forty-eight anatomic specimen femora from 24 patients with unilateral cemented and cementless hip replacements were analyzed. Cortical thickness, cortical bone area, and bone mineral density was assessed in 4 quadrants at 5 discrete levels. The maximum cortical bone loss by level was at the middle section for the cemented femurs and at the midproximal and middle sections for the cementless femurs. However, if one examines individual quadrants, the proximal medial cortex still represents the specific region of maximal bone loss for both types of implant fixation. The posterior cortex had substantially more bone loss, even in the diaphyseal levels, than had been previously appreciated. A strong correlation was noted between the bone mineral density of the control femur and the percentage decrease of bone mineral density in the remodeled femur. Based on this data, it seems that the less dense the bone is before hip replacement surgery, the greater the extent of bone loss after total hip arthroplasty regardless of the fixation type.

Adult↗
PubMed1994

Normalization of retinal blood flow in diabetic rats with primary intervention using insulin pumps.

PURPOSE: Prior results have demonstrated a significant reduction in retinal blood flow in streptozotocin (STZ)-induced diabetic rats. These studies were extended to investigate whether retinal blood flow changes, in the diabetic rat model, could be prevented with strict glycemic control using insulin pumps. Retinal blood flow changes also were measured during hyperoxia and after intravitreal histamine infusion to validate the methodology. METHODS: Retinal blood flow changes were measured using video-based fluorescein angiography and computer-assisted image analysis. A total of 48 male Sprague-Dawley and 9 Brown Norway rats were used in these experiments. Retinal blood flow after primary insulin intervention was evaluated in diabetic rats implanted with mini-osmotic insulin pumps within 24 hours of STZ-induced diabetes. Diabetic rats, not treated with insulin, were used for comparison. RESULTS: Hyperoxia caused a significant (P = 0.001) reduction (54%) in retinal blood flow, whereas intravitreal infusion of 10(-3) M histamine caused a significant (P = 0.009) increase (108%) in retinal blood flow. Retinal blood flow in the primary insulin intervention group, after 1 week of diabetes, was not statistically different from retinal blood flow of nondiabetic controls as measured at baseline from the animals used in the hyperoxia and histamine infusion experiments. In contrast there was a significant (P = 0.0001) retinal blood flow reduction in the untreated diabetic group. CONCLUSIONS: The results showed that the local effect of histamine and hyperoxia on the retina produced the expected responses in retinal blood flow, further confirming the validity of the methodology. Primary insulin intervention demonstrated that strict glycemic control initiated immediately after induction of diabetes was sufficient to maintain normal retinal blood flow in STZ-induced diabetic rats.

Animals↗
PubMed1987

The measurement of C-reactive protein and immune complexes in endocarditis caused by coagulase-negative staphylococci.

Coagulase-negative staphylococci are a major cause of early endocarditis following the insertion of prosthetic heart valves but rarely cause endocarditis in natural valves. From a 2-year prospective study we report seven cases: six with endocarditis related to prosthetic valves and one with endocarditis related to a natural valve. Each isolate of coagulase-negative staphylococcus was identified biochemically (six Staphylococcus epidermidis; one Staphylococcus hominis) and characterised by bacteriophage typing. Six isolates were also examined for slime production and for extracellular toxins and enzymes: all produced toxin but enzyme and slime production was variable. Concentrations of immune complexes and C-reactive protein in the serum were measured in six of the patients. Our results suggest that measuring C-reactive protein may be useful but measuring immune complexes is not helpful and takes more time.

Antigen-Antibody Complex↗
PubMed1976

Child-rearing attitudes of subjects who vary in guilt.

The present study sought to determine whether high- and low-guilt Ss differ in their child-rearing attitudes. High-guilt Ss were found to be more likely to prefer an overprotective orientation combined with harsh punitive control. In general, attitudes of the high-guilt Ss were seen as more likely to produce psychological disturbance in their children.

Attitude↗
PubMedDate not supplied

Nonspecific bronchial responsiveness assessed in vitro following acute inhalation exposure to ozone and ozone/sulfuric acid mixtures.

Air pollution may play some role in the recent increase in severity and prevalence of asthma, but the specific chemical components with the ambient pollutant mix that may be responsible have not been delineated. Since ambient exposures involve mixtures, it is essential to examine airway responses to realistic pollutant mixtures. This study examined the ability of single (3-h) inhalation exposures to ozone and to mixtures of ozone plus sulfuric acid to induce nonspecific airway hyperresponsiveness in healthy rabbits. Airway responsiveness was assessed using an in vitro assay involving administration of increasing doses of acetylcholine to bronchial rings obtained from animals exposed to 0.1-0.6 ppm ozone or to mixtures of ozone and 50-125 micrograms/m3 sulfuric acid aerosol; results were compared to those reported previously for sulfuric acid alone. Bronchial hyperresponsiveness to ozone was noted following exposure at all concentrations, but the combination of pollutants results in antagonism. The results support the potential for ozone to induce airway hyperresponsiveness in healthy animals and suggest that interaction with sulfuric acid may reduce the effectiveness of both pollutants.

Acetylcholine↗
PubMedDate not supplied

Inclusion of women in AIDS clinical research: a political and legal analysis.

Thirteen years into a devastating epidemic that is having a serious impact on women of color, we are only a few steps closer to genuine participation by women in AIDS clinical trials. Those who depend most heavily on research settings not only for the promise of an accessible cure, but also for life-prolonging therapies and state-of-the-art medical care are hurt most by exclusionary policies. Restrictive and contradictory federal policies, pharmaceutical company reluctance to complete animal toxicology and reproductive studies, inadequate informed consent, and unfounded industry fear of liability all play a part in keeping women with AIDS from participating in clinical research.

Acquired Immunodeficiency Syndrome↗