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Biomedical subjects

David R Jones

Publications and source records attributed to David R Jones.

At least 73 records · Page 4Linked to original sources
PubMed2004

Modulation of antiapoptotic cell signaling pathways in non-small cell lung cancer: the role of NF-kappaB.

Apoptosis, or programmed cell death, is a natural phenomenon that is critical for normal embryonic development and the maintenance of homeostasis in multicellular organisms. In adults, apoptosis represents a protective strategy that limits the spread of infection and helps prevent the development of malignancies. Cells acquiring nonrepairable DNA mutations are capable of "committing suicide" to prevent propagation of acquired genetic mutations and to eliminate their own malignant potential. Although malignant cells maintain the necessary intracellular apoptotic machinery, inappropriate inhibition of apoptosis allows for continued tumor growth and metastases. The majority of nonsmall cell lung cancer (NSCLC) exhibits dysregulated antiapoptotic pathways involving the transcription factor NF-kappaB. In addition, in NSCLC both chemotherapy and radiation upregulate antiapoptotic and cell-cycle regulatory proteins through NF-kappaB-dependent signaling mechanisms. Preclinical and phase I clinical trials suggest that inhibition of NF-kappaB markedly attenuates the resistance of NSCLC to undergo apoptosis and sensitizes these cells to chemotherapy. Modulation of the antiapoptotic cascade mediated by NF-kappaB, combined with either traditional or novel chemotherapeutic agents, represents a promising treatment strategy for patients with NSCLC.

Angiogenesis Inhibitors↗
PubMed2004

Prediction of cytochrome P450 3A inhibition by verapamil enantiomers and their metabolites.

Verapamil inhibition of CYP3A activity results in many drug-drug interactions with CYP3A substrates, but the mechanism of inhibition is unclear. The present study showed that verapamil enantiomers and their major metabolites [norverapamil and N-desalkylverapamil (D617)] inhibited CYP3A in a time- and concentration-dependent manner by using pooled human liver microsomes and the cDNA-expressed CYP3A4 (+b5). The values of the inactivation kinetic parameters kinact and KI obtained with the cDNA-expressed CYP3A4 (+b5) were 0.39 min(-1) and 6.46 microM for R-verapamil, 0.64 min(-1) and 2.97 microM for S-verapamil, 1.12 min(-1) and 5.89 microM for (+/-)-norverapamil, and 0.07 min(-1) and 7.93 microM for D617. Based on the ratio of kinact and KI, the inactivation potency of verapamil enantiomers and their metabolites was in the following order: S-norverapamil>S-verapamil>R-norverapamil>R-verapamil>D617. Using dual beam spectrophotometry, we confirmed that metabolic intermediate complex formation with CYP3A was the mechanism of inactivation for all compounds. The in vitro unbound fraction was 0.84 for S-verapamil, 0.68 for R-verapamil, and 0.84 for (+/-)-norverapamil. A mechanism-based pharmacokinetic model predicted that the oral area under the curve (AUC) of a CYP3A substrate that is eliminated completely (fm=1) by the hepatic CYP3A increased 1.6- to 2.2-fold after repeated oral administration of verapamil. For midazolam (fm=0.9), a drug that undergoes extensive intestinal wall metabolism, the predicted increase in oral AUC was 3.2- to 4.5-fold. The predicted results correlate well with the in vivo drug interaction data, suggesting that the model is suitable for predicting drug interactions by mechanism-based inhibitors.

Administration, Oral↗
PubMed2004

Lack of efficacy for a cervicomandibular support collar in the management of obstructive sleep apnea.

STUDY OBJECTIVES: The effect of therapy using a cervicomandibular support collar (CMSC) to manage obstructive sleep apnea (OSA) was compared with standard therapy, nasal continuous positive airway pressure (nCPAP). DESIGN: Subjects received treatment with CMSC or nCPAP each for 1 month in random order. The study was analyzed on an intention-to-treat basis. SETTING: Tom McKendrick Sleep Laboratory, Dunedin Hospital. PARTICIPANTS: Ten adult subjects with mild-to-moderate OSA (apnea-hypopnea index [AHI], 24 +/- 13/h slept [mean +/- SD]) completed the study. INTERVENTIONS: The CMSC was designed to prevent mandibular movement and hold the head in slight extension, thus preventing the postural changes that might contribute to OSA. Positioning of the CMSC was confirmed by an externally applied cervical range of motion (CROM) instrument and by cephalometry. Subjects were carefully instructed in the use of each device and completed a symptom diary. After 1 month, subjects underwent polysomnography with each of the allocated devices in situ, and symptom questionnaires were administered. MEASUREMENTS AND RESULTS: Treatment success (AHI </= 10/h slept) with CMSC was achieved in only 2 of 10 subjects, partial success (AHI > 10/h to </= 15/h slept) was achieved in 2 subjects, and in 6 of 10 subjects there was no benefit. In contrast, treatment success was achieved in 7 of 10 subjects receiving nCPAP. Mean AHI was 29.4 +/- 13.4/h at baseline, 26.9 +/- 17.2/h slept with CMSC, and 9.9 +/- 8.0/h slept with nCPAP (p = 0.001). No significant differences in sleep architecture or sleep efficiency were achieved using nCPAP compared to CMSC. The efficacy of the CMSC in maintaining the desired head position was confirmed by cephalometry and the CROM instrument. CONCLUSIONS: Our results, although negative, provide important evidence that control of head and neck posture, perhaps adopted as a second-line treatment, is not helpful in the management of OSA. It appears that other anatomic and physiologic factors have a dynamic overriding influence on upper airway closure compared to simple skeletal relationships.

Adult↗
PubMed2004

Aeromedical regulation of aviators using selective serotonin reuptake inhibitors for depressive disorders.

This report, prepared at the request of the Aerospace Medical Association (AsMA), reviews the present status of aeromedical regulation of depressive disorders and antidepressant medications, emphasizing the role of serotonin specific reuptake inhibitors (SSRIs). Aeromedical certifying authorities (CAs) generally prohibit pilots from flying with a diagnosed depressive disorder, and also prohibit flying while taking antidepressant medications, including SSRIs. Some CAs are reassessing these prohibitions, which are based on long aeromedical practices, in view of changing medical management of depressive disorders. Many pilots choose to fly while depressed, with or without medications, because of the long grounding periods mandated by current policies. Some SSRIs have very few aeromedically significant side effects. Modern psychiatric practice calls for long-term use of medication following clinical recovery from depressive disorders in order to prevent recurrent episodes. Given these and other factors, AsMA proposes that CAs remove the current absolute prohibitions against pilots flying while taking SSRIs, and adopt aeromedical protocols that include carefully controlled follow-up and review. AsMA urges all certificatory and regulatory authorities to consider immediately instituting a policy of using study groups to manage depressed aviators who require SSRI antidepressants. Protocols designed to aggressively manage the full spectrum of adverse possibilities related to SSRI use may enable the safe use of SSRIs in formerly depressed aviators who suffer no aeromedically significant side effects. In these closely managed cases of depressive disorders, special issuances or waivers for SSRI use are justified.

Aerospace Medicine↗
PubMed2003

Role of iron (II)-2-oxoglutarate-dependent dioxygenases in the generation of hypoxia-induced phosphatidic acid through HIF-1/2 and von Hippel-Lindau-independent mechanisms.

Hypoxia-inducible factors (HIF-1/HIF-2) govern the expression of critical genes for cellular adaptation to low oxygen tensions. We have previously reported that the intracellular level of phosphatidic acid (PA) rises in response to hypoxia (1% O(2)). In this report, we have explored whether components of the canonical HIF/von Hippel-Lindau (VHL) pathway are involved in the induction of PA. We found that hypoxia induces PA in a cell line constitutively expressing a stable version of HIF-1alpha. PA induction was also found in HIF-1alpha- and 2alpha-negative CHO Ka13 cells, as well as in HIF-beta-negative HepaC4 cells. These data indicate that HIF activity is neither sufficient nor necessary for oxygen-dependent PA accumulation. PA generation was also detected in cells deficient for the tumor suppressor VHL, indicating that the presence of VHL was not required for the induction of PA. Here we show that PA accumulation also occurs at moderate hypoxia (5% O(2)), although to a lesser extent to that seen at 1% O(2), revealing that PA is induced at the same hypoxia range required to activate HIF-1. Prolyl hydroxylases (PHD) and asparaginyl hydroxylase (FIH) belong to the iron (II) and 2-oxoglutarate-dependent dioxygenase family and have been proposed as oxygen sensors involved in the regulation of HIFs. Chemical inhibition of these activities by treatment with iron chelators or 2-oxoglutarate analogs also results in a marked PA accumulation similar to that observed in hypoxia. Together these data show that PA accumulation in response to hypoxia is both HIF-1/2- and VHL-independent and indicate a role of iron (II)-2-oxoglutarate-dependent dioxygenases in the oxygen-sensing mechanisms involved in hypoxia-driven phospholipid regulation.

Cell Hypoxia↗
PubMed2003

A randomized controlled trial of adaptive ventilation for Cheyne-Stokes breathing in heart failure.

Heart failure is associated with Cheyne-Stokes breathing, which fragments patients' sleep. Correction of respiratory disturbance may reduce sleep fragmentation and excessive daytime sleepiness. This randomized prospective parallel trial assesses whether nocturnal-assist servoventilation improves daytime sleepiness compared with the control. A total of 30 subjects (29 male) with Cheyne-Stokes breathing (mean apnea-hypopnea index 19.8 [SD 2.6] and stable symptomatic chronic heart failure (New York Heart Association Class II-IV) were treated with 1 month's therapeutic (n = 15) or subtherapeutic adaptive servoventilation. Daytime sleepiness (Osler test) was measured before and after the trial with change in measured sleepiness the primary endpoint. Secondary endpoints included brain natriuretic peptide levels and catecholamine excretion. Active treatment reduced excessive daytime sleepiness; the mean Osler change was +7.9 minutes (SEM 2.9), when compared with the control, the change was -1.0 minutes (SEM, 1.7), and the difference was 8.9 minutes (95% confidence interval, 1.9-15.9 minutes; p = 0.014, unpaired t test). Significant falls occurred in plasma brain natriuretic peptide and urinary metadrenaline excretion. We conclude that adaptive servoventilation produces an improvement in excessive daytime sleepiness in patients with Cheyne-Stokes breathing and chronic heart failure. This study suggests improvements in neurohormonal activation with this treatment.

Aged↗
PubMed2003

The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor.

Phosphoinositides (PtdInsPs) play critical roles in cytoplasmic signal transduction pathways. However, their functions in the nucleus are unclear, as specific nuclear receptors for PtdInsPs have not been identified. Here, we show that ING2, a candidate tumor suppressor protein, is a nuclear PtdInsP receptor. ING2 contains a plant homeodomain (PHD) finger, a motif common to many chromatin-regulatory proteins. We find that the PHD fingers of ING2 and other diverse nuclear proteins bind in vitro to PtdInsPs, including the rare PtdInsP species, phosphatidylinositol 5-phosphate (PtdIns(5)P). Further, we demonstrate that the ING2 PHD finger interacts with PtdIns(5)P in vivo and provide evidence that this interaction regulates the ability of ING2 to activate p53 and p53-dependent apoptotic pathways. Together, our data identify the PHD finger as a phosphoinositide binding module and a nuclear PtdInsP receptor, and suggest that PHD-phosphoinositide interactions directly regulate nuclear responses to DNA damage.

1-Phosphatidylinositol 4-Kinase↗
PubMed2003

Quantification of tamoxifen and three metabolites in plasma by high-performance liquid chromatography with fluorescence detection: application to a clinical trial.

A sensitive and reproducible assay employing liquid-liquid extraction and high-performance liquid chromatography with fluorescence detection for the quantification of tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen, and Z-4-hydroxy-N-desmethyltamoxifen in human plasma is described. The compounds and internal standard, propranolol, were separated with a cyano column and a mobile phase of acetonitrile-20 mM potassium phosphate buffer (pH 3; 35:65, v/v) then detected with fluorescence using a modified version of a method originally described by Fried and Wainer [J. Chromatogr. B 655 (1994) 261]. The coefficients of variation for the midpoint of the standard curve for each compound were less than 10%. This method was applied to a pharmacokinetic study of tamoxifen disposition in breast cancer patients.

Antineoplastic Agents, Hormonal↗
PubMed2003

The cytochrome P450 2B6 (CYP2B6) is the main catalyst of efavirenz primary and secondary metabolism: implication for HIV/AIDS therapy and utility of efavirenz as a substrate marker of CYP2B6 catalytic activity.

We used human liver microsomes (HLMs) and recombinant cytochromes P450 (P450s) to identify the routes of efavirenz metabolism and the P450s involved. In HLMs, efavirenz undergoes primary oxidative hydroxylation to 8-hydroxyefavirenz (major) and 7-hydroxyefavirenz (minor) and secondary metabolism to 8,14-dihydroxyefavirenz. The formation of 8-hydroxyefavirenz in two HLMs showed sigmoidal kinetics (average apparent Km, 20.2 micro M; Vmax, 140 pmol/min/mg protein; and Hill coefficient, 1.5), whereas that of 7-hydroxyefavirenz formation was characterized by hyperbolic kinetics (Km, 40.1 micro M and Vmax, 20.5 pmol/min/mg protein). In a panel of 10 P450s, CYP2B6 formed 8-hydroxyefavirenz and 8,14-dihydroxyefavirenz from efavirenz (10 micro M) at the highest rate. The Km value for the formation of 8-hydroxyefavirenz in CYP2B6 derived from hyperbolic Eq. 12.4 micro M) was close to that obtained in HLMs (Km, 20.2 micro M). None of the P450s tested showed activity toward 7-hydroxylation of efavirenz. When 8-hydroxyefavirenz (2.5 micro M) was used as a substrate, 8,14-dihydroxyefavirenz was formed by CYP2B6 at the highest rate, and its kinetics showed substrate inhibition (Ksi, approximately 94 micro M in HLMs and approximately 234 micro M in CYP2B6). In a panel of 11 HLMs, 8-hydroxyefavirenz and 8,14-dihydroxyefavirenz formation rates from efavirenz (10 micro M) correlated significantly with the activity of CYP2B6 and CYP3A. N,N',N"-Triethylenethiophosphoramide (thioTEPA; 50 micro M) inhibited the formation rates of 8-hydroxyefavirenz and 8,14-dihydroxyefavirenz from efavirenz (10 micro M) by > or = 60% in HLMs) and CYP2B6, with Ki values < 4 micro M. In conclusion, CYP2B6 is the principal catalyst of efavirenz sequential hydroxylation. Efavirenz systemic exposure is likely to be subject to interindividual variability in CYP2B6 activity and to drug interactions involving this isoform. Efavirenz may be a valuable phenotyping tool to study the role of CYP2B6 in human drug metabolism.

Alkynes↗
PubMed2003

Ineffectiveness of histone deacetylase inhibitors to induce apoptosis involves the transcriptional activation of NF-kappa B through the Akt pathway.

Histone deacetylase (HDAC) inhibitors are emerging as a new class of anticancer agents for the treatment of solid and hematological malignancies. Although HDAC inhibitors induce cell death through an apoptotic process, little is known about the molecular events that control their effectiveness. In this study, we demonstrate that HDAC inhibitors are limited in their ability to induce apoptosis in non-small cell lung cancer (NSCLC) cell lines despite their ability to effectively inhibit deacetylase activity. Because the anti-apoptotic transcription factor NF-kappa B has been shown to be under the control of HDAC-mediated repression, we analyzed whether HDAC inhibitors activated NF-kappa B in NSCLC cells. HDAC inhibitors effectively stimulated endogenous NF-kappa B-dependent gene expression by up-regulating IL-8, Bcl-XL, and MMP-9 transcripts. The ability of HDAC inhibitors to increase NF-kappa B transcriptional activity was not associated with signaling events that stimulated nuclear translocation, but rather modulated the transactivation potential of the RelA/p65 subunit of NF-kappa B. The inhibition of HDAC activity was associated with the recruitment of the p300 transcriptional co-activator to chromatin in an Akt-dependent manner. Moreover, Akt directly phosphorylated p300 in vitro and was required for stimulating the transactivation potential of the co-activator following the addition of HDAC inhibitors. Selective inhibition of either the phosphoinositide 3-kinase/Akt pathway, or NF-kappa B itself blocked the ability of HDAC inhibitors to activate NF-kappa B and dramatically sensitized NSCLC cells to apoptosis following of the addition of HDAC inhibitors. Our study indicates that the ineffectiveness of HDAC inhibitors to induce apoptosis in NSCLC cancer cells is associated with the ability of these molecules to stimulate NF-kappa B-dependent transcription and cell survival.

Antineoplastic Agents↗
PubMed2003

T cell activation in vivo targets diacylglycerol kinase alpha to the membrane: a novel mechanism for Ras attenuation.

Diacylglycerol kinase (DGK) phosphorylates diacylglycerol to produce phosphatidic acid, leading to decreased and increased levels, respectively, of these two lipid messengers that play a central role in T cell activation. Nine DGK isoforms, grouped into five subtypes, are found in higher organisms; all contain a conserved C-terminal domain and at least two cysteine-rich motifs of unknown function. In this study, we have researched in vivo the regulation of DGK alpha, using a transgenic mouse model in which injection of an antigenic peptide activates the majority of peripheral T cells. We demonstrate that DGK alpha, highly expressed in resting T lymphocytes, is subject to complex control at the mRNA and protein levels during in vivo T cell activation. Subcellular fractionation of T lymphocytes shortly after in vivo engagement of the TCR shows rapid translocation of cytosolic DGK alpha to the membrane fraction. At early time points, DGK alpha translocation to the membrane correlates with rapid translocation of Ras guanyl nucleotide-releasing protein (RasGRP), a nucleotide exchange activator for Ras that associates to the membrane through a diacylglycerol-binding domain. To demonstrate a causal relationship between DGK alpha activity and RasGRP relocation to the membrane, we determined RasGRP translocation kinetics in a T cell line transiently transfected with constitutive active and dominant-negative DGK alpha mutants. We show that membrane localization of DGK alpha is associated with a negative regulatory signal for Ras activation by reversing RasGRP translocation. This study is the first demonstration of in vivo regulation of DGK alpha, and provides new insight into the functional role of a member of this family of lipid kinases in the regulation of the immune response.

Animals↗
PubMed2003

Pulmonary segmentectomy: results and complications.

BACKGROUND: Segmentectomy is an anatomic pulmonary parenchymal-sparing resection performed for certain benign lesions and on selected patients with lung cancer. We reviewed our experience with segmentectomy in this highly select group of patients. METHODS: We retrospectively reviewed the records of 61 patients (5% of all anatomic resections) undergoing 62 segmentectomies from 1991 to 2001. Wedge resections were excluded. The operative indications were suspected or known lung cancer (43), benign disease (12), and metastatic cancer to the lung (7). Median follow-up for patients with malignancy was 28 months (range 1 to 89 months). Actuarial survival was calculated using the Kaplan-Meier method. RESULTS: Segmentectomy was performed in 43 lung cancer patients with pathologic stages of Ia-22, Ib-14, IIa-2, IIb-1, IIIa/IIIb-2, and IV-2. All resection margins were negative for malignancy. Segmentectomy for benign diseases included granulomatous disease (5), pulmonary abscess (2), plasmacytoma (1), and others (4). Complications occurred in 39% (24/62) of patients, including atelectasis requiring bronchoscopy (10/62, 16%), pneumonia (9/62, 14%), air leak more than 7 days (5/62, 8%), and supraventricular dysrhythmias (6/62, 10%). In-hospital mortality was 3% (2 patients). Median length of hospital stay was 6 days (range 4 to 66 days). In the lung cancer patients the locoregional recurrence rate was 0% and the distant recurrence rate was 20%. The 4-year actuarial survival for patients with lung cancer was 72%. CONCLUSIONS: Pulmonary segmentectomy has acceptable morbidity and mortality in selected patients with both benign and malignant lung disease and remains a useful procedure in a thoracic surgeon's armamentarium. Distant, not locoregional recurrence, was responsible for the cancer deaths.

Adolescent↗
PubMed2003

A randomized crossover efficacy trial of oral CPAP (Oracle) compared with nasal CPAP in the management of obstructive sleep apnea.

STUDY OBJECTIVES: To determine the therapeutic efficacy and viability of a novel oral interface for continuous positive airway pressure (CPAP) compared with conventional nasal interfaces. DESIGN: A randomized single-blind crossover study. SETTING: Hospital-based sleep laboratory. PATIENTS OR PARTICIPANTS: 21 CPAP-naïve patients with obstructive sleep apnea (baseline apnea-hypopnea index, 85 +/- 36) INTERVENTIONS: Nasal CPAP and oral CPAP MEASUREMENTS AND RESULTS: Patients were each treated for two 4-week periods using nasal CPAP and oral CPAP. The CPAP titrations were undertaken at the start of each treatment arm. Outcome measures were recorded at baseline and at the end of each treatment arm. These included polysomnography variables, CPAP compliance, subjective sleepiness, obstructive sleep apnea symptom ratings, and adverse effects. There were no significant differences between oral and nasal interfaces for the on-CPAP frequency of apneas and hypopneas (mean difference, nasal-oral [95%CI] = -4.6[-10.1-1.0]/h; P = 0.06) or arousals (-3.0 [-7.8-1.8]/h; P = 0.23). There were also no statistically significant differences between interfaces for scores on the Epworth Sleepiness Scale (-0.7 [-3.1-1.7]; P = 0.20), obstructive sleep apnea symptoms (-7.7 [-17.7-2.4]; P = 0.052), CPAP compliance (0.3 [-0.5-1.1] h/night; P = 0.50), CPAP pressure (0.05 [-0.66-0.76] cmH20; P = 0.73), CPAP side effects scores (-2.0 [-5.3-1.4]; P = 0.23), or mask preference (P = 0.407). In addition, both nasal and oral interfaces significantly improved polysomnographic variables, Epworth Sleepiness Scale scores, obstructive sleep apnea symptoms, and CPAP compliance from baseline (all P < 0.05). CONCLUSIONS: This preliminary study indicates that oral CPAP has similar efficacy to traditionally applied nasal CPAP in treating obstructive sleep apnea. Additional large studies are required to determine the range of clinical situations where oral CPAP is indicated.

Administration, Oral↗
PubMed2003

Form and function of the bulbus arteriosus in yellowfin tuna (Thunnus albacares), bigeye tuna (Thunnus obesus) and blue marlin (Makaira nigricans): static properties.

The juxtaposition of heart and gills in teleost fish means that the Windkessel function characteristic of the whole mammalian arterial tree has to be subserved by the extremely short ventral aorta and bulbus arteriosus. Over the functional pressure range, arteries from blue marlin (Makaira nigricans) and yellowfin tuna (Thunnus albacares) have J-shaped pressure-volume (P-V) loops, while bulbi from the same species have r-shaped P-V loops, with a steep initial rise followed by a compliant plateau phase. The steep initial rise in pressure is due to the geometry of the lumen. The interactions between radius, pressure and tension require a large initial pressure to open the bulbar lumen for flow. The plateau is due to the unique organization of the bulbar wall. The large elastin:collagen ratio, limited amount of collagen arranged circumferentially, lack of elastin lamellae and low hydrophobicity of the elastin itself all combine to lower stiffness, increase extensibility and allow efficient recoil. Even though the modulus of bulbus material is much lower than that of an artery, at large volumes the overall stiffness of the bulbus increases rapidly. The morphological features that give rise to the special inflation characteristics of the bulbus help to extend flow and maintain pressure during diastole.

Animals↗
PubMed2003

Form and function of the bulbus arteriosus in yellowfin tuna (Thunnus albacares): dynamic properties.

The bulbus arteriosus of the teleost heart possesses a static inflation curve that is r-shaped over the in vivo pressure range. To examine the possible significance of this in living animals, we recorded arterial blood pressure from anaesthetized yellowfin tuna and utilized a video dimensional analyser to simultaneously record changes in bulbar diameter. By plotting the changes in pressure against the changes in diameter, it was possible to create dynamic pressure-diameter (P-D) loops as well as calculate the instantaneous volume changes within the bulbus. The dynamic P-D loops showed the same features exhibited by static inflation. When nearly empty, a small stroke volume caused a large increase in blood pressure, while around systolic pressure large changes in volume resulted in small changes in pressure. We conclude that these features allow the bulbus to maintain ventral aortic flows and pressures over a large range of volumes.

Animals↗
PubMed2003

Metabolic and cardiovascular adjustments of juvenile green turtles to seasonal changes in temperature and photoperiod.

We measured activity levels, oxygen consumption, metabolic enzyme activity, breathing frequency, heart rate and blood chemistry variables of juvenile green turtles exposed to a laboratory simulation of subtropical winter and summer temperatures (17-26 degrees C) and photoperiod (10.25 h:13.75 h to 14 h:10 h light:dark). The activity level of turtles had a significant effect on oxygen consumption and breathing frequency but there was no significant change in activity level between the summer and winter simulations. There was a moderate 24-27% decrease in oxygen consumption during exposure to winter conditions compared with summer conditions, but this difference was not statistically significant. Likewise, there was no statistically significant difference in breathing frequency between summer and winter simulations. Exposure to winter conditions did result in a significant decrease in activity of the aerobic enzyme citrate synthase. By contrast, activities of the glycolytic enzymes pyruvate kinase and lactate dehydrogenase were significantly higher in tissue collected during exposure to winter conditions compared with summer conditions. Citrate synthase, pyruvate kinase and lactate dehydrogenase had relatively low thermal dependence over the range of assay temperatures (15-30 degrees C; Q10=1.44-1.69). Heart rate was 46-48% lower during the winter simulation compared with the summer simulation, and this difference was statistically significant. Exposure to winter conditions resulted in a significant decrease in plasma thyroxine and plasma proteins and a significant increase in plasma creatine phosphokinase and hematocrit. Overall, our results suggest that green turtles have a relatively low thermal dependence of metabolic rate over the range of temperatures commonly experienced at tropical to subtropical latitudes, a trait which allows them to maintain activity year-round.

Animals↗
PubMed2003

Lung cancer. Special treatment issues.

This chapter of the Lung Cancer Guidelines addresses patients with particular forms of non-small cell lung cancer that require special considerations. This includes patients with Pancoast tumors, T4N0,1M0 tumors, satellite nodules in the same lobe, synchronous and metachronous multiple primary lung cancers (MPLC), and solitary metastases. For patients with a Pancoast tumor, a multimodality approach, involving chemoradiotherapy and surgical resection, appears optimal provided appropriate staging has been carried out. Patients with central T4 tumors that do not have mediastinal node involvement are uncommon. When carefully staged and selected, however, such patients appear to benefit from resection as part of the treatment as opposed to chemoradiotherapy alone. Patients with a satellite lesion in the same lobe as the primary tumor have a good prognosis and require no modification of the approach to evaluation and treatment from what would be dictated by the primary tumor alone. On the other hand, it is difficult to know how best to treat patients with a focus of the same type of cancer in a different lobe. Although MPLC do occur, the survival results after resection for either a synchronous presentation or a metachronous presentation with an interval of < 4 years between tumors are variable and generally poor, suggesting that many of these patients may have had a pulmonary metastasis rather than a second primary lung cancer. A thorough and careful evaluation of these patients is warranted to try to differentiate between patients with a metastasis and those with a second primary lung cancer, although criteria to distinguish them have not been defined. Finally, some patients with a solitary focus of metastatic disease in the brain or adrenal gland appear to benefit substantially from resection.

Adrenal Gland Neoplasms↗