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Biomedical subjects

K Price

Publications and source records attributed to K Price.

At least 19 recordsLinked to original sources
PubMed2005

Bispectral index monitoring may not reliably indicate cerebral ischaemia during awake carotid endarterectomy.

BACKGROUND: Intraoperative ischaemia during carotid cross-clamping in patients undergoing carotid endarterectomy (CEA) is a major complication and prompt recognition of insufficient collateral blood supply is crucial. Electroencephalogram (EEG) is believed to be one of the useful forms of monitoring cerebrovascular insufficiency during CEA. The aim of this study was to evaluate the utility of bispectral index (BIS) monitoring, a processed EEG parameter, for the reliable detection of intraoperative cerebral ischaemia during awake CEA. METHODS: We monitored 52 patients continuously with the BIS monitor together with assessment of neurological function (contralateral upper and lower limb strength and the verbal component of the Glasgow Coma Scale for speech) in patients undergoing awake CEA. RESULTS: Overall mean BIS value in all patients was 96 (SD 2.9). In five patients who showed clinical evidence of cortical ischaemia during carotid cross-clamping, there was no change in the original range of BIS values throughout the procedure (96.7 [3.2]). In one patient BIS values decreased to 38 about 5 min after the incision and recovered within the next 10 min. The mean BIS value in the remaining 46 patients who did not develop clinical signs of ischaemia was 95.4 (2.6). Three cases are presented which demonstrate the inability of the BIS monitor to detect cerebral ischaemia. CONCLUSIONS: Lack of correlation of BIS with the signs of cerebral ischaemia during CEA makes it unreliable for detection of cerebrovascular insufficiency. We conclude that awake neurological testing is the preferred method of monitoring in these patients.

Aged↗
PubMed2005

Adolescents' and their parents' views on the acceptability and design of a new diabetes education programme: a focus group analysis.

BACKGROUND: The present study was conducted as part of an ongoing project to develop an innovative educational intervention for young people with type 1 diabetes. We aimed to seek the views of children and adolescents with type 1 diabetes and their parents regarding (i) the acceptability of the new programme and (ii) practical aspects regarding course design and delivery. METHODS: Twenty-four children and 29 parents attended one of eight separate focus groups. Semi-structured interview schedules were developed around two main areas of discussion: views on the education programme; and views on the design and delivery of current and future education. Discussions were tape-recorded and transcribed, before undergoing systematic qualitative analysis. RESULTS: Participants agreed that the proposed intervention was feasible, and were enthusiastic that it could improve quality of life and 'normality'. Potential problems included self-management during school-time and parental anxiety. In terms of course design/delivery, participants emphasized the need to maximize enjoyment on the course (e.g. integrating fun and practical sessions, holding parts of the course outside of the clinic setting), and encourage effective learning and adherence to the regimen (e.g. including separate parent education, and using IT-based reference material). CONCLUSIONS: The qualitative methodology proved an effective way of eliciting child and parent views and informing the development of the proposed intervention. These findings can now be incorporated into the development of the education programme.

Adolescent↗
PubMed2003

Risk factors for locoregional recurrence among breast cancer patients: results from International Breast Cancer Study Group Trials I through VII.

PURPOSE: To explore prognostic factors for locoregional failures (LRF) among women treated for invasive breast cancer within clinical trials of adjuvant therapies. PATIENTS AND METHODS: The study population consisted of 5,352 women who were treated with a modified radical mastectomy and enrolled in one of seven International Breast Cancer Study Group randomized trials. A total of 1,275 women with node-negative disease received either no adjuvant therapy or a single cycle of perioperative chemotherapy, and 4,077 women with node-positive disease received adjuvant chemotherapy of at least 3 months' duration and/or tamoxifen. Median follow-up is 12 to 15.5 years. RESULTS: In women with node-negative disease, factors associated with increased risk of LRF were vascular invasion (VI) and tumor size greater than 2 cm for premenopausal and VI for postmenopausal patients. Of the 1,275 patients, 345 (27%) met criteria for the highest risk groups, and the 10-year cumulative incidences of LRF with or without distant metastases were 16% for premenopausal and 19% for postmenopausal women. For the node-positive cohort, number of nodes and tumor grade were factors for both menopausal groups, with additional prediction provided by VI for premenopausal and tumor size for postmenopausal patients. Of the 4,077 patients, 815 (20%) met criteria for the highest risk groups, and 10-year cumulative incidences were 35% for premenopausal and 34% for postmenopausal women. CONCLUSION: LRFs are a significant problem after mastectomy alone even for some patients with node-negative breast cancer, as well as after mastectomy and adjuvant treatment for some subgroups of patients with node-positive disease. In addition to number of positive lymph nodes, predictors of LRF include tumor-related factors, such as vascular invasion, higher grade, and larger size.

Breast Neoplasms↗
PubMed2001

Influence of endocrine-related factors on response to perioperative chemotherapy for patients with node-negative breast cancer.

PURPOSE: We investigated tumor- and patient-related features that might influence the response to perioperative chemotherapy (PeCT) compared with no adjuvant therapy for patients with node-negative breast cancer. PATIENTS AND METHODS: A total of 1,275 patients were randomized to either no adjuvant treatment (427 patients) or PeCT (848 patients). The following variables thought to have prognostic significance were evaluated: grade, tumor size, estrogen (ER) and progesterone receptor (PgR) content (absent; low, 1 to 9 fmol/mg cytosol protein; or positive, > or = 10 fmol/mg cytosol protein), c-erbB-2 overexpression, menopausal status, and age. Cox proportional hazards regression models were used to assess the relative influence of these factors to predict the effect of PeCT on disease-free survival (DFS). Median follow-up was 13.5 years. RESULTS: The 10-year DFS percentage for 692 premenopausal patients did not significantly differ between the PeCT and no-adjuvant-treatment groups: 61% and 59%, respectively (relative risk [RR], 0.95; 95% confidence interval [CI], 0.75 to 1.20; P = .70). No predictive factors were identified. For 583 postmenopausal patients, 10-year DFS percentages for the groups were 63% and 58%, respectively (RR, 0.75; 95% CI, 0.58 to 0.93; P = .03). The absence of expression of ER, PgR, or both ER and PgR was the most important factor predicting improved outcome with PeCT among postmenopausal patients. The 10-year DFS percentages were 85% and 53% for the steroid hormone receptor-absent cohort of treated and untreated patients, respectively (RR, 0.18; 95% CI, 0.06 to 0.49; P = .0009). CONCLUSION: The role of PeCT should be explored for patients whose primary tumors do not express steroid hormone receptors, because it is likely that early initiation of treatment is exclusively relevant for such patients.

Adult↗
PubMed2001

Antigenically distinct conformations of CXCR4.

The major human immunodeficiency virus type 1 (HIV-1) coreceptors are the chemokine receptors CCR5 and CXCR4. The patterns of expression of the major coreceptors and their use by HIV-1 strains largely explain viral tropism at the level of entry. However, while virus infection is dependent upon the presence of CD4 and an appropriate coreceptor, it can be influenced by a number of factors, including receptor concentration, affinity between envelope gp120 and receptors, and potentially receptor conformation. Indeed, seven-transmembrane domain receptors, such as CCR5, can exhibit conformational heterogeneity, although the significance for virus infection is uncertain. Using a panel of monoclonal antibodies (MAbs) to CXCR4, we found that CXCR4 on both primary and transformed T cells as well as on primary B cells exhibited considerable conformational heterogeneity. The conformational heterogeneity of CXCR4 explains the cell-type-dependent ability of CXCR4 antibodies to block chemotaxis to stromal cell-derived factor 1 alpha and to inhibit HIV-1 infection. In addition, the MAb most commonly used to study CXCR4 expression, 12G5, recognizes only a subpopulation of CXCR4 molecules on all primary cell types analyzed. As a result, CXCR4 concentrations on these important cell types have been underestimated to date. Finally, while the factors responsible for altering CXCR4 conformation are not known, we found that they do not involve CXCR4 glycosylation, sulfation of the N-terminal domain of CXCR4, or pertussis toxin-sensitive G-protein coupling. The fact that this important HIV-1 coreceptor exists in multiple conformations could have implications for viral entry and for the development of receptor antagonists.

Amino Acid Sequence↗
PubMed2000

Expression and coreceptor function of APJ for primate immunodeficiency viruses.

APJ is a seven transmembrane domain G-protein-coupled receptor that functions as a coreceptor for some primate immunodeficiency virus strains. The in vivo significance of APJ coreceptor function remains to be elucidated, however, due to the lack of an antibody that can be used to assess APJ expression, and because of the absence of an antibody or ligand that can block APJ coreceptor activity. Therefore, we produced a specific monoclonal antibody (MAb 856) to APJ and found that it detected this receptor in FACS, immunofluorescence, and immunohistochemistry studies. MAb 856 also recognized APJ by Western blot, enabling us to determine that APJ is N-glycosylated. Using this antibody, we correlated APJ expression with coreceptor activity and found that APJ had coreceptor function even at low levels of expression. However, we found that APJ could not be detected by FACS analysis on cell lines commonly used to propagate primate lentiviruses, nor was it expressed on human PBMC cultured under a variety of conditions. We also found that some viral envelope proteins could mediate fusion with APJ-positive, CD4-negative cells, provided that CD4 was added in trans. These findings indicate that in some situations APJ use could render primary cell types susceptible to virus infection, although we have not found any evidence that this occurs. Finally, the peptide ligand for APJ, apelin-13, efficiently blocked APJ coreceptor activity.

Adipokines↗
PubMed2000

Expression and coreceptor activity of STRL33/Bonzo on primary peripheral blood lymphocytes.

CCR5 and CXCR4 are the major coreceptors that mediate human immunodeficiency virus 1 (HIV-1) infection, while most simian immunodeficiency virus (SIV) isolates use CCR5. A number of alternative coreceptors can also mediate infection of some virus strains in vitro, although little is known about their in vivo relevance. Therefore, we characterized the expression pattern and coreceptor activity of one of these alternative coreceptors, STRL33/Bonzo, using a newly developed monoclonal antibody. In addition to being highly expressed (approximately 1000-7000 STRL33 ABS [antibody binding sites]) on specific subsets of natural killer cells (CD3(-)/CD16(-/low)/CD56(+) and CD3(-)/CD16(low)/CD56(-)) and CD19(+) B lymphocytes (approximately 300-5000 STRL33 ABS), STRL33 was expressed at levels sufficient to support virus infection on freshly isolated, truly naive CD4(+)/CD45RA(+)/CD62L(+) cells (6000-11 000 ABS). STRL33 expression on peripheral blood mononuclear cells (PBMCs) was increased by mitogenic stimulation (OKT3/IL-2 [interleukin-2] had a greater effect than phytohemaglutinin (PHA)/IL-2), but it was dramatically decreased upon Ficoll purification. Infection of CCR5(-) human peripheral blood lymphocytes (PBLs) showed that 2 different SIV envelope (Env) proteins mediated entry into STRL33(+) cells. More importantly, the preferential infection of STRL33(+) cells in CCR5(-) PBLs by an R5/X4/STRL33 HIV-1 maternal isolate in the presence of a potent CXCR4 antagonist (AMD3100) suggests that STRL33 can be used as a coreceptor by HIV-1 on primary cells. Rhesus macaque (rh) STRL33 was used less efficiently than human STRL33 by the majority of SIV Env proteins tested despite similar levels of expression, thereby making it less likely that STRL33 is a relevant coreceptor in the rhesus macaque system. In summary, the expression pattern and coreceptor activity of STRL33 suggest its involvement in trafficking of tumor-infiltrating lymphocytes and indicate that STRL33 may be a relevant coreceptor in vivo.

Animals↗
PubMed2000

Identification and cellular localisation of voltage-operated calcium channels in immature rat testis.

Sertoli cells regulate the spermatogenic process mainly through the secretion of a complex fluid into the lumen of the seminiferous tubules behind the blood-testis barrier, containing many of the essential proteins necessary for maintenance and maturation of male germ cells. Thus, the study of Sertoli cell secretory processes is strictly correlated with the understanding of the regulatory mechanisms of spermatogenesis. In this work the authors have explored the voltage-sensitive calcium channel variety in the immature rat testis, their localisation and distribution within the seminiferous epithelium and peritubular and interstitial tissues as well as the possible role in the control of Sertoli cell secretion. The results reported in this paper, obtained by in situ hybridisation, immunohistology of rat testicular sections and Western blot analysis of Sertoli cell plasma membranes, show that mammalian Sertoli cells express mRNA encoding for several voltage-operated calcium channel subunits and express such proteins on their surface. Experiments performed on Sertoli cell monolayers cultured in the presence of specific toxins indicate that both N and P/Q-type Ca(2+) channels are involved in the regulation of protein secretion.

Animals↗
PubMed2000

Early start of adjuvant chemotherapy may improve treatment outcome for premenopausal breast cancer patients with tumors not expressing estrogen receptors. The International Breast Cancer Study Group.

PURPOSE: The proper time to commence adjuvant chemotherapy after primary surgery for breast cancer is unknown. An analysis of the International (Ludwig) Breast Cancer Study Group (IBCSG) Trial V at a median follow-up of 11 years suggested that early initiation of adjuvant chemotherapy might improve outcome for premenopausal, node-positive patients whose tumors did not express any estrogen receptor (ER). PATIENTS AND METHODS: We investigated the relationship between early initiation of adjuvant chemotherapy, ER status, and prognosis in 1,788 premenopausal, node-positive patients treated on IBCSG trials I, II, and VI. The disease-free survival for 599 patients (84 with ER-absent tumors) who commenced adjuvant chemotherapy within 20 days (early initiation) was compared with the disease-free survival for 1,189 patients (142 with ER-absent tumors) who started chemotherapy 21 to 86 days after surgery (conventional initiation). The median follow-up was 7.7 years. RESULTS: Among patients with ER-absent tumors, the 10-year disease-free survival was 60% for the early initiation group compared with 34% for the conventional initiation group (226 patients; hazard ratio [HR], 0. 49; 95% confidence interval [CI], 0.33 to 0.72; P =.0003). This difference remained statistically significant in a Cox multiple regression analysis controlling for study group, number of positive nodes, tumor size, age, vessel invasion, and institution (HR, 0.60; 95% CI, 0.39 to 0.92; P =.019). Conversely, early initiation of chemotherapy did not significantly improve disease-free survival for patients with tumors expressing ER (1,562 patients; multiple regression HR, 0.93; 95% CI, 0.79 to 1.10; P =.40). CONCLUSION: In premenopausal patients with ER-absent tumors, early initiation of systemic chemotherapy after primary surgery might improve outcome. Further confirmatory studies are required before any widespread modification of current clinical practice. In premenopausal patients with tumors expressing some ER, gains from early initiation are unlikely to be clinically significant.

Adult↗
PubMed1999

Striatal biopterin and tyrosine hydroxylase protein reduction in dopa-responsive dystonia.

OBJECTIVE: To determine the mechanism leading to striatal dopamine (DA) loss in dopa-responsive dystonia (DRD). BACKGROUND: Although mutations in the gene GCH1, coding for the tetrahydrobiopterin (BH4) biosynthetic enzyme guanosine triphosphate-cyclohydrolase I, have been identified in some patients with DRD, the actual status of brain BH4 (the cofactor for tyrosine hydroxylase [TH]) is unknown. METHODS: The authors sequenced GCH1 and measured levels of total biopterin (BP) and total neopterin (NP), TH, and dopa decarboxylase (DDC) proteins, and the DA and vesicular monoamine transporters (DAT, VMAT2) in autopsied brain of two patients with typical DRD. RESULTS: Patient 1 had two GCH1 mutations but Patient 2 had no mutation in the coding region of this gene. Striatal BP levels were markedly reduced (<20% of control subjects) in both patients and were also low in two conditions characterized by degeneration of nigrostriatal DA neurons (PD and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treated primate), whereas brain NP concentrations were selectively decreased (<45%) in the DRD patients. In the putamen, both DRD patients had severely reduced (<3%) TH protein levels but had normal concentrations of DDC protein, DAT, and VMAT2. CONCLUSIONS: The data suggest that 1) brain BH4 is decreased substantially in dopa-responsive dystonia, 2) dopa-responsive dystonia can be distinguished from degenerative nigrostriatal dopamine deficiency disorders by the presence of reduced brain neopterin, and 3) the striatal dopamine reduction in dopa-responsive dystonia is caused by decreased TH activity due to low cofactor concentration and to actual loss of TH protein. This reduction of TH protein, which might be explained by reduced enzyme stability/expression consequent to congenital BH4 deficiency, can be expected to limit the efficacy of acute BH4 administration on dopamine biosynthesis in dopa-responsive dystonia.

Adult↗
PubMed1999

Epitope mapping of CCR5 reveals multiple conformational states and distinct but overlapping structures involved in chemokine and coreceptor function.

The chemokine receptor CCR5 is the major coreceptor for R5 human immunodeficiency virus type-1 strains. We mapped the epitope specificities of 18 CCR5 monoclonal antibodies (mAbs) to identify domains of CCR5 required for chemokine binding, gp120 binding, and for inducing conformational changes in Env that lead to membrane fusion. We identified mAbs that bound to N-terminal epitopes, extracellular loop 2 (ECL2) epitopes, and multidomain (MD) epitopes composed of more than one single extracellular domain. N-terminal mAbs recognized specific residues that span the first 13 amino acids of CCR5, while nearly all ECL2 mAbs recognized residues Tyr-184 to Phe-189. In addition, all MD epitopes involved ECL2, including at least residues Lys-171 and Glu-172. We found that ECL2-specific mAbs were more efficient than NH2- or MD-antibodies in blocking RANTES or MIP-1beta binding. By contrast, N-terminal mAbs blocked gp120-CCR5 binding more effectively than ECL2 mAbs. Surprisingly, ECL2 mAbs were more potent inhibitors of viral infection than N-terminal mAbs. Thus, the ability to block virus infection did not correlate with the ability to block gp120 binding. Together, these results imply that chemokines and Env bind to distinct but overlapping sites in CCR5, and suggest that the N-terminal domain of CCR5 is more important for gp120 binding while the extracellular loops are more important for inducing conformational changes in Env that lead to membrane fusion and virus infection. Measurements of individual antibody affinities coupled with kinetic analysis of equilibrium binding states also suggested that there are multiple conformational states of CCR5. A previously described mAb, 2D7, was unique in its ability to effectively block both chemokine and Env binding as well as coreceptor activity. 2D7 bound to a unique antigenic determinant in the first half of ECL2 and recognized a far greater proportion of cell surface CCR5 molecules than the other mAbs examined. Thus, the epitope recognized by 2D7 may represent a particularly attractive target for CCR5 antagonists.

Amino Acid Sequence↗
PubMed1999

Expression and function of CXC and CC chemokines in human malignant liver tumors: a role for human monokine induced by gamma-interferon in lymphocyte recruitment to hepatocellular carcinoma.

Chemotactic cytokines (chemokines) play an important role in the recruitment of lymphocytes to tissue by regulating cellular adhesion and transendothelial migration. This study examined the expression and function of CXC (human monokine induced by gamma-interferon [HuMig], interleukin-8 [IL-8], and interferon-inducible protein-10 [IP-10]) and CC (macrophage inflammatory protein-1alpha [MIP-1alpha], MIP-1beta, regulated upon activation normal T lymphocyte expressed and secreted (RANTES), and macrophage chemoattractant protein-1 [MCP-1]) chemokines and their respective receptors on lymphocytes infiltrating human liver tumors. Chemokine and chemokine receptor expression was assessed by immunohistochemistry, flow cytometry, in situ hybridization and ribonuclease (RNAse) protection assays and function by in vitro chemotaxis of tumor-derived lymphocytes to purified chemokines and to HepG2 tumor cell culture supernatants. Tumor-derived lymphocytes showed strong chemotactic responses to both CC and CXC chemokines in vitro and expressed high levels of CXCR3 (HuMig and IP-10 receptor) and CCR5 (RANTES, MIP-1alpha, and MIP-1beta receptor). Expansion of tumor-derived lymphocytes in recombinant IL-2 increased expression of CXCR3. The corresponding chemokines were detected on vascular endothelium (HuMig, IL-8, MIP-1alpha, and MIP-1beta) and sinusoidal endothelium (HuMig, MIP-1alpha, MIP-1beta) in hepatocellular carcinoma. In vitro, HepG2 cells secreted functional chemotactic factors for tumor-derived lymphocytes that could be inhibited using anti-CCR5 or anti-CXCR3 monoclonal antibodies (MoAbs). Thus, lymphocytes infiltrating human liver tumors express receptors for and respond to both CXC and CC chemokines. The relevant chemokine ligands are expressed in hepatocellular carcinoma (HCC), particularly HuMig, which was strongly expressed by tumor endothelium, suggesting that they play a role in lymphocyte recruitment to these tumors in vivo. The ability of HepG2 cells to secrete lymphocyte chemotactic factors in vitro suggests that the tumor contributes to lymphocyte recruitment in vivo.

Aged↗
PubMed1999

The membrane-permeabilizing effect of avenacin A-1 involves the reorganization of bilayer cholesterol.

Avenacin A-1 is a member of a group of naturally occurring compounds called saponins. It is found in oat plants, where it protects against fungal pathogens. A combined electrical and optical chamber was used to determine the interaction of avenacin A-1 with Montal-Mueller planar lipid bilayers. This system allowed simultaneous measurement of the effect of avenacin A-1 on the fluorescence and lateral diffusion of a fluorescent lipid probe and permeability of the planar lipid bilayer. As expected, cholesterol was required for avenacin A-1-induced bilayer permeabilization. The planar lipid bilayers were also challenged with monodeglucosyl, bis-deglucosyl, and aglycone derivatives of avenacin A-1. The results show that the permeabilizing activity of the native avenacin A-1 was completely abolished after one, two, or all three sugar residues are hydrolyzed (monodeglucosyl, bis-deglucosyl, and aglycone derivatives, respectively). Fluorescence recovery after photobleaching (FRAP) measurements on cholesterol-containing planar lipid bilayers revealed that avenacin A-1 caused a small but significant reduction in the lateral diffusion of the phospholipid probe N-(7-nitrobenzoyl-2-oxa-1,3-diazol-4-yl)-1, 2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (NBD-PE). Similarly, with the sterol probe (22-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3beta-ol (NBD-Chol), avenacin A-1, but not its derivatives, caused a more pronounced reduction in the lateral diffusion than that observed with the phospholipid probe. The data indicate that an intact sugar moiety of avenacin A-1 is required to reorganize membrane cholesterol into pores.

4-Chloro-7-nitrobenzofurazan↗
PubMed1999

A model for the assessment and management of children with multiple disabilities.

Children with multiple disabilities present complex management problems, both for their families and for the professionals involved in their care. For any one child, the list of functional and medical problems that need to be addressed is frequently reflected in an even longer list of involved professionals, leading to conflicting advice and problems in co-ordination of care. A hierarchical model for assessment and management is proposed, which highlights the interdependency of apparently different areas of functioning. The model aims to assist both parents and professionals in determining priorities, to improve interdisciplinary working, and to underpin staff training. Illustrative case studies indicate the importance of resolving issues in areas such as visual functioning, positioning and nutrition before integrated functions such as communication skills can be addressed successfully.

Child↗
PubMed1999

The presence of melanin in genomic DNA isolated from pigmented cell lines interferes with successful polymerase chain reaction: a solution.

We have found that polymerase chain reaction (PCR) amplification of genetic material is unsuccessful when using template genomic DNA derived from certain normal melanocyte and melanoma cell lines. We demonstrated that this phenomenon only occurs with pigmented cell lines and appears to be due to the association of genomic DNA with remnants of the pigment melanin. We therefore describe a simple and rapid technique that rids genomic DNA samples of melanin, resulting in a genomic DNA template that allows successful PCR.

DNA↗
PubMed1999

Outcome for cancer patients requiring mechanical ventilation.

PURPOSE: To describe hospital survival for cancer patients who require mechanical ventilation. MATERIALS AND METHODS: A prospective, multicenter observational study was performed at five academic tertiary care hospitals. Demographic and clinical variables were obtained on consecutive cancer patients at initiation of mechanical ventilation, and information on vital status at hospital discharge was acquired. RESULTS: Our analysis was based on 782 adult cancer patients who met predetermined inclusion criteria. The overall observed hospital mortality was 76%, with no statistically significant differences among the five study centers. Seven variables (intubation after 24 hours, leukemia, progression or recurrence of cancer, allogeneic bone marrow transplantation, cardiac arrhythmias, presence of disseminated intravascular coagulation, and need for vasopressor therapy) were associated with an increased risk of death, whereas prior surgery with curative intent was protective. The predictive model based on these variables had an area under the receiver operating characteristic curve of 0.736, with Hosmer-Lemeshow goodness-of-fit statistics of 7.19; P = .52. CONCLUSION: This model can be used to estimate the probability of hospital survival for classes of adult cancer patients who require mechanical ventilation and can help to guide physicians, patients, and families in deciding goals and direction of treatment. Prospective independent validation in different medical settings is warranted.

Critical Care↗
PubMed1999

Effects of cigarette smoke on nitric oxide synthase expression in the rat lung.

To examine the effects of cigarette smoke on nitric oxide synthase (NOS) gene expression and protein production, groups of rats were exposed to smoke once only or daily and were sacrificed after 1, 2, 7, or 28 days of exposure. NOS-1, NOS-2, and NOS-3 mRNAs in whole lung were quantified using reverse transcription polymerase chain reaction (RT-PCR), and NOS protein levels were determined by Western blots. Neither NOS-1 gene expression nor protein levels changed with smoke exposure. Levels of NOS-2 expression were more than doubled in smokers at Day 1 and decreased to control values during 1 month with daily smoke exposure, while protein levels did not change. NOS-3 expression was increased approximately 35% after 2 days of smoke exposure and remained increased to 28 days, whereas protein levels were increased by approximately 60% at Day 7 and remained elevated. In situ hybridization showed that NOS-2 was diffusely expressed in the lung parenchyma, airways, and vessels, and that NOS-3 was strongly expressed in vascular endothelium. Protein distribution, as determined by immunohistochemical staining, was identical to mRNA tissue distribution, and these distributions were not changed by smoke. We conclude that smoke exposure induces a rapid but transient increase in transcription of NOS-2, and a sustained increase in transcription and translation of NOS-3; up-regulation of NOS occurs within the anatomic compartment where these genes are normally expressed. These findings indicate that cigarette smoke can directly and rapidly affect NOS expression, and thus potentially affect the function of the pulmonary vasculature.

Animals↗