Search PubMed⌕ Search

Biomedical subjects

C Goodwin

Publications and source records attributed to C Goodwin.

At least 19 recordsLinked to original sources
PubMed2002

Bone cell mitogenic action of fluoroaluminate and aluminum fluoride but not that of sodium fluoride involves upregulation of the insulin-like growth factor system.

The fluoroaluminate (AlF(4)(-)) ion and sodium fluoride (NaF) have previously been shown to be bone cell mitogens. This study sought to determine whether the bone cell mitogenic action of AlF(4)(-) and/or NaF would involve the insulin-like growth factor (IGF) regulatory system. We evaluated the effect of mitogenic doses of AlF(4)(-) and NaF on the mRNA levels and the protein level (in conditioned media [CM]) of several components of the IGF system (i.e., IGF-2, IGF binding protein [IGFBP]-4, and IGFBP-5) in human TE85 osteosarcoma cells. Aluminum fluoride (AlF(3)) was included for comparison. NaF, AlF(3), and AlF(4)(-), each at 50-100 micromol/L, increased [3H]thymidine incorporation in TE85 cells. Mitogenic concentrations of AlF(3) and AlF(4)(-): (1) increased the mRNA (up to twofold after 24 h treatment) and protein (in CM) levels (up to 2.5-fold after 48 h treatment) of IGF-2; (2) increased the mRNA level (twofold) and the protein level in CM (up to threefold) of stimulatory IGFBP-5; and (3) either reduced slightly or had no effect on the mRNA and protein (in CM) levels of the inhibitory IGFBP-4. Conversely, mitogenic concentrations of NaF had no significant effects on the protein (in CM) or mRNA level of IGF-2, IGFBP-4, or IGFBP-5. The addition of an inhibitory concentration of IGFBP-4 completely abolished the bone cell mitogenic activity of AlF(3) and AlF(4)(-) but not that of NaF. The findings of this study provide strong evidence that the bone cell mitogenic activity of AlF(4)(-) and AlF(3), but not that of NaF, is mediated by the upregulation of the IGF regulatory system.

Aluminum↗
PubMed2001

Laparoscopic cholecystectomy: effective treatment for chronic abdominal pain in children with acalculous biliary pain.

BACKGROUND/PURPOSE: Acalcular biliary pain is a term used to identify patients who have significant abdominal pain related to an abnormally low gallbladder ejection fraction in the absence of cholelithiasis. Little is known about this disease in the pediatric population. The aim of this study was to determine whether laparoscopic cholecystectomy is an effective method for treatment of children with abdominal pain in the setting of acalcular biliary pain and whether one can predict the outcome preoperatively. METHODS: The charts of all children who underwent laparoscopic cholecystectomy for acalcular biliary pain in our institution from January 1991 through April 1998 were reviewed. Sixty-three patients were identified as children with acalcular biliary pain who underwent laparoscopic cholecystectomy. Forty-eight patients were contacted successfully and they all completed the questionnaire. Complete resolution of abdominal pain occurred in 72%, and another 18% had near-complete resolution of pain. Some improvement was noted by 8%, and only 2% had no improvement. In a multiple logistic model, none of the variables were significant predictors of response outcome. CONCLUSIONS: Laparoscopic cholecystectomy is an effective means of therapy for children with abdominal pain and low gallbladder ejection fraction. It is difficult to predict patients with complete response based on the preoperative clinical findings.

Abdominal Pain↗
PubMed2000

Influence of glucose kinetics on plasma lactate concentration and energy expenditure in severely burned patients.

BACKGROUND: In critically ill patients, elevation in the plasma lactate concentration has traditionally been interpreted as indicating a deficiency in oxygen availability and is often an impetus to increase oxygen delivery clinically. However, another possible basis for increased lactate concentrations may be simply a mass effect from increased pyruvate availability (i.e., accelerated glycolysis). METHODS: In six hypermetabolic burned patients, the rates of glucose production and oxidation were quantified using a tracer infusion of 6,6 d2 glucose combined with indirect calorimetry. Measurements were obtained after a 9-hour fast and after a 3-hour infusion of unlabeled glucose at 30 micromol/kg/min. No patient was overtly septic, hypoxic, or hypovolemic. RESULTS: The infusion of glucose significantly increased the arterial glucose concentration and rate of glucose oxidation, with a corresponding increase in the arterial plasma concentration of lactate and pyruvate. Resting energy expenditure and oxygen consumption were not affected by the infusion of glucose. CONCLUSIONS: These findings show that elevations in plasma lactate in severely injured patients may, in part, be related to increases in glucose flux and not entirely a reflection of any deficit in oxygen availability. Such findings highlight a potential pitfall for interpreting plasma lactate concentrations as an index of tissue oxygen availability in hypermetabolic patients.

Adult↗
PubMed1999

Selectin blockade worsened lipopolysaccharide-induced lung injury in a swine model.

BACKGROUND: Polymorphonuclear leukocytes have been reported to play an important role in various acute lung injuries. Neutrophil recruitment into tissues is a multistep process involving sequential engagement of adhesion molecules. The objective of this study was to determine the effect of selectin inactivation with Sulfo Lewis C (SO3-3betaGal1-3betaGlcNAc-O(CH2)8-COOMe) on the pulmonary response to lipopolysaccharide (LPS) infusion. METHODS: All animals (n = 11) were pretreated with an intramuscular injection of a priming dose of Escherichia coli LPS (10 microg/kg). Eighteen hours later, animals received an intravenous infusion of LPS (20 microg/kg) over 20 minutes. All animals were resuscitated with a lactated Ringer's solution. Group I (G1; n = 5) received no additional treatment. Group II (G2; n = 6) received a bolus injection of Sulfo Lewis C (10 mg/kg) 10 minutes before LPS insult followed by a continuous infusion (1 mg/kg per hour) for the rest of the study. Animals were observed for 5 hours from initiation of the LPS infusion and killed. Cardiopulmonary variables and blood gases were measured serially. The multiple inert gas elimination technique (MIGET) was used to evaluate the matching of air flow and blood flow in the lung 5 hours after LPS infusion. Histologic evaluation of the parenchymal injury was performed by using light microscopy. The number of polymorphonuclear leukocytes and red blood cells in the alveolar spaces per field at 400x magnification were counted in 10 randomly selected fields. RESULTS: Hypoxemia, indexed as Pao2/FIO2, was exacerbated by the administration of Sulfo Lewis C (G1:437+/-33 vs. G2: 241+/-63 mm Hg at 5 hours, p<0.03). This finding is supported by the multiple inert gas elimination technique analysis, which demonstrated significantly greater blood flow to true shunt in G2 (G1:4.42+/-1.75 vs. G2:23.2+/-5.69, p<0.02). There was no difference between the two groups in red blood cell counts in the alveolar spaces. However, polymorphonuclear leukocyte counts were significantly greater in G2 (G1:1.8+/-0.58 vs. G2:9.9+/-2.34, p<0.01). CONCLUSION: Selectin blockade significantly worsened lung injury induced by LPS infusion, and greater numbers of neutrophils were observed in alveolar spaces in the group treated with Sulfo Lewis C. These findings are supported by the multiple inert gas elimination technique analysis, which demonstrated significantly greater blood flow to the true shunt compartment in treated animals. Further studies are required to determine the role of selectins in sepsis-induced lung injury.

Animals↗
PubMed1998

Kinetics of CD4+ T cell repopulation of lymphoid tissues after treatment of HIV-1 infection.

Potent combinations of antiretroviral drugs diminish the turnover of CD4+ T lymphocytes productively infected with HIV-1 and reduce the large pool of virions deposited in lymphoid tissue (LT). To determine to what extent suppression of viral replication and reduction in viral antigens in LT might lead correspondingly to repopulation of the immune system, we characterized CD4+ T lymphocyte populations in LT in which we previously had quantitated viral load and turnover of infected cells before and after treatment. We directly measured by quantitative image analysis changes in total CD4+ T cell counts, the CD45RA+ subset, and fractions of proliferating or apoptotic CD4+ T cells. Compared with normal controls, we documented decreased numbers of CD4+ T cells and increased proliferation and apoptosis. After treatment, proliferation returned to normal levels, and total CD4+ T and CD45RA+ cells increased. We discuss the effects of HIV-1 on this subset based on the concept that renewal mechanisms in the adult are operating at full capacity before infection and cannot meet the additional demand imposed by the loss of productively infected cells. The slow increases in the CD45RA+ CD4+ T cells are consistent with the optimistic conclusions that (i) renewal mechanisms have not been damaged irreparably even at relatively advanced stages of infection and (ii) CD4+ T cell populations can be partially restored by control of active replication without eradication of HIV-1.

Adult↗
PubMed1998

Decrease of HIV-1 RNA levels in lymphoid tissue and peripheral blood during treatment with ritonavir, lamivudine and zidovudine. Ritonavir/3TC/ZDV Study Group.

OBJECTIVES: Triple combination treatment of HIV-1 infection using two reverse transcriptase inhibitors and a protease inhibitor can result in significant and sustained decreases in the quantity of viral RNA in peripheral blood. Lymphoid tissue, however, constitutes the major reservoir of HIV in infected patients. Study of the viral burden in these tissues has provided additional insight in the efficacy of antiretroviral treatment. DESIGN: Patients were randomized into two groups in order to study differences in the development of resistance to reverse transcriptase inhibitors. Group I started treatment with all three drugs simultaneously. Group II started with ritonavir monotherapy, aiming at initial reduction in virus production before the addition of lamivudine and zidovudine 3 weeks later. METHODS: Changes in the amount of HIV in plasma and tonsillar lymphoid tissue during 24 weeks of treatment with ritonavir, lamivudine and zidovudine were studied by reverse transcriptase polymerase chain reaction. RESULTS: Thirty-three antiretroviral-naive HIV-infected patients were included for analysis. After 24 weeks, median CD4+ cell count increased by 152 x 10(6)/l and median plasma viral RNA levels decreased by at least 2.87 log10 copies/ml. In 88% of the patients remaining on treatment, plasma RNA levels were below the quantification limit of the assay used (mean, 2.4 log10 copies/ml). The lymphoid tissue viral burden, ranging from 9.16 to 8.52 log10 copies/g at baseline, was markedly reduced with at least 2.1 log10 copies/g by week 24 in the five patients analysed. Eight patients (24%) withdrew because of side-effects. In one patient in group II, ritonavir and lamivudine resistance-associated mutations developed. CONCLUSIONS: Treatment with this triple antiretroviral drug combination produced a durable and strong decrease of HIV-1 RNA burden in both plasma and lymphoid tissue.

Adult↗
PubMed1998

Pharmacokinetics and antiretroviral activity of lamivudine alone or when coadministered with zidovudine in human immunodeficiency virus type 1-infected pregnant women and their offspring.

The safety, pharmacokinetics, and antiretroviral activity of lamivudine alone and in combination with zidovudine was studied in pregnant women infected with human immunodeficiency virus type 1 (HIV-1) and their neonates. Women received the drugs orally from week 38 of pregnancy to 1 week after delivery. Neonate therapy began 12 h after delivery and continued for 1 week. Both treatment regimens were well-tolerated in women and newborns. Lamivudine and zidovudine pharmacokinetics in pregnant women were similar to those in nonpregnant adults. Lamivudine and zidovudine freely crossed the placenta and were secreted in breast milk. Neonatal lamivudine clearance was about half that in pediatric patients; zidovudine clearance was consistent with previous reports. HIV-1 RNA could be quantified in 17 of the 20 women. At the onset of labor/delivery, mean virus load had decreased by approximately 1.5 log10 copies/mL in both treatment cohorts. Although not definitive for HIV-1 infection status, all neonates had HIV-1 RNA levels below the limit of quantification at birth and at ages 1 and 2 weeks.

Administration, Oral↗
PubMed1998

Analysis of performance measures. A veterans home case study.

The development or adaptation of a comprehensive performance measurement system is vital for the proper assessment of organizational performance. The authors describe their experience in developing and implementing a modified performance measurement questionnaire for the assessment of an existing performance measurement system in a state veterans home. Adapted for a long-term care environment, the questionnaire determines whether the organization's strategies, performance measurement system, and employees' actions match up and support each other.

Data Interpretation, Statistical↗
PubMed1996

Harry and Louise go to Washington: political advertising and health care reform.

Political advertising by interest groups trying to influence public policy has proliferated recently. Formerly the preserve of election campaigns, advertising has spread to policy arenas, such as abortion, trade, and health care. This article examines group lobbying for and against President Clinton's health care reform plan. Using a study of advertisements, a content analysis of news coverage, interviews with half a dozen leading figures in the debate during the spring of 1995, and an analysis of three national public opinion surveys designed to gauge the public response to health care ads, we investigate the media campaign on health care. Ads directed against the Clinton plan played a crucial role in the public's attaching negative connotations to some of its key elements. Grassroots campaigns can work either by mobilizing public opinion or by persuading political leaders that grassroots opposition exists to a particular program.

Advertising↗
PubMed1995

Prothrombin cleavage by human vascular smooth muscle cells: a potential alternative pathway to the coagulation cascade.

Thrombin is a potent mitogen for human vascular smooth muscle cells (HVSMC) and its enzymatic activity is required for this function. The present study demonstrates that prothrombin is also mitogenic for HVSMC due to the generation of enzymatically active thrombin which occurs upon incubation of prothrombin with the cells. Analysis by SDS-PAGE, immunoblotting, and amino acid sequencing revealed that prothrombin incubated with HVSMC undergoes limited proteolysis. Prethrombin 1 was formed through cleavage at R155-S156. Cleavage at R271-T272 generated fragment 1.2 and prethrombin 2 whilst cleavage at R284-T285 yielded truncated prothrombin 2 (prethrombin 2'). However, cleavage at R320-I321 which, during prothrombin activation produces two-chain alpha-thrombin, was not detectable. Studies on HVSMC-conditioned medium revealed that a similar pattern of prothrombin cleavage occurred by a cell-secreted factor(s). Amidolytic activity analysis indicated that 1-3% catalytically active thrombin-like activity was generated upon incubation of prothrombin with HVSMC-conditioned medium. By treating conditioned medium with various classes of proteinase inhibitors or hirudin, it was determined that prothrombin is cleaved by a cell-derived serine proteinase-like factor(s) at R271-S272 and by alpha-thrombin at R155-S156 and R284-T285. Antibodies neutralising the activity of either urokinase, tissue plasminogen activator, or factor Xa failed to alter the prothrombin cleaving activity of conditioned medium. This activity which may catalyse an alternative pathway for the generation of thrombin, was eluted from a gel filtration column as a single peak with apparent molecular mass of 30-40 kDa.

Adolescent↗
PubMed1995

Combination of ranitidine and cisapride in the treatment of reflux oesophagitis.

OBJECTIVE: To compare the efficacy of treatment for 8 or 12 weeks with a combination of 150 mg ranitidine twice daily plus 20 mg cisapride twice daily with ranitidine 150 mg twice daily alone in patients with moderate-to-severe reflux oesophagitis. DESIGN: A double-blind, randomized, parallel-group clinical trial. SETTING: Forty-two out-patient centres in the UK, Germany, Ireland, Denmark and South Africa. PATIENTS: A total of 344 symptomatic patients with endoscopically confirmed reflux oesophagitis (Hetzel grade 3 or 4) were randomly assigned to receive the study medication. INTERVENTIONS: Patients underwent a follow-up endoscopy after 8 weeks' treatment. Healing was defined as Hetzel grade 0 or 1 upon endoscopy. Patients with unhealed oesophagitis continued their allocated treatment regimen for a further 4 weeks before undergoing a repeat endoscopy. MAIN OUTCOME MEASURES: The primary efficacy analysis was based on a comparison of 12-week cumulative healing rates between the two groups. RESULTS: A statistically significant difference (P = 0.015) in the cumulative healing rate was observed between patients given ranitidine plus cisapride (82%) and those given ranitidine alone (71%). Oesophagitis in patients who received the combination was twice as likely to heal as that in patients who received ranitidine alone. CONCLUSION: A combination of 150 mg ranitidine twice daily and 20 mg cisapride twice daily is a safe and effective treatment for moderate-to-severe reflux oesophagitis and offers increased efficacy over ranitidine alone.

Administration, Oral↗
PubMed1992

Lumbar surgery in the elderly.

By virtue of modern neuroimaging, neurosurgeons are increasingly confronted by patients once deemed too old for lumbar corrective procedures. Management of these patients is problematic, as the literature is relatively mute in regard to results and complications within this elderly cohort. We, therefore, reviewed all surgical procedures for benign lumbar disease at two large metropolitan hospitals from January 1986 to June 1988 for patients greater than or equal to 70 years of age. There were 155 procedures performed on 143 patients (male:female, 48:95); the average age of the patients was 74.9 +/- 8.8 years; there were 32 cases of herniated disc, 29 cases of disc plus hypertrophic ligament/bone, and 94 cases of lateral recess/stenosis alone. Hospital stay averaged 7.5 +/- 3.5 days, and increasing age did not correlate with an extended admission. Major morbidity was low (6.9%), and there were no deaths. At follow-up, an average of 34.3 +/- 12.2 months postoperatively, 66.6% (56 of 84) of the patients reported no or minimal discomfort, whereas 15.4% (13 of 84) had not improved at all. Overall, 77.3% (65/84) were pleased with their procedure. These data represent the most comprehensive review in the literature of lumbar procedures in the elderly and indicate that these operations may be undertaken in this population with acceptable morbidity and a reasonable expectation of clinical improvement.

Aged↗
PubMed1991

Magnetic resonance evaluation of anterior cruciate ligament repair using the patellar tendon double bone block technique.

The magnetic resonance (MR) appearance of the anterior cruciate ligament reconstruction was determined in 20 clinically stable and 2 clinically unstable knees for a total of 22 examinations. All patients studied had undergone knee reconstruction using the patellar tendon as graft material. The reconstructed anterior cruciate ligament varies in appearance. It appeared as a thick, well-defined, low signal band on T1- and T2-weighted sagittal and coronal images in 14 of 22 examinations. The remaining 8 knees showed a graft having one or more thin and attenuated, low signal intensity bands in the sagittal and/or coronal plane. In 3 of these cases, the grafts appeared thicker in the coronal plane. All cases, including the two clinically unstable knees, showed no break in graft continuity. Arthroscopy confirmed an intact but lax graft in the clinically unstable knees.

Adolescent↗
PubMed1991

An Integrated International Aerospace Medical Information System.

An Integrated International Aerospace Medical Information System (IIASMIS) is proposed. Such a system is needed to allow all appropriate resources to be brought to bear on the medical problems that must be solved for safe extended manned missions. Existing medical data bases are reviewed. The suggested approach involves the formation of an international working group that would determine the scope of the problem, identify the real needs, and design the top-level architecture of the system. Participants would develop national data bases independently. A prototype system would be developed and evaluated; upon satisfactory operation, it would be expanded to include all active partners.

Aerospace Medicine↗