Wait times for diagnosis and treatment of lung cancer: a single-centre experience.

BACKGROUND: Multiple clinical practice guidelines recommend rapid evaluation of patients with suspected lung cancer. It is uncertain whether delays in diagnosis and management have a negative effect on outcomes. METHODS: This retrospective study included 551 patients diagnosed with lung cancer through the diagnostic assessment program at the Institut universitaire de cardiologie et de pneumologie de Québec between September 2013 and March 2015. Median wait times between initial referral, diagnosis, and first treatment were calculated and compared with recommended targets. Analyses were performed to evaluate for specific factors associated with longer wait times and for the effect of delays on the outcomes of progression-free survival (pfs), relapse-free survival (rfs) after primary surgical resection, and overall survival (os). RESULTS: Most patients were investigated and treated within recommended targets. Of the entire cohort, 379 patients were treated at our institution. Of those 379 patients, 311 (82%) were treated within recommended targets. In comparing patients within and outside target times, the only statistically significant difference was found in the distribution of treatment modalities: patients meeting targets were more likely to be treated with surgery or chemotherapy rather than with radiation. The pfs on first treatment modality was influenced by clinical stage, but not by time to therapy [hazard ratio (hr): 1.10; p = 0.65]. The os for the entire cohort was also influenced by stage, but not by delays (hr: 1.04; p = 0.87). For the 209 patients treated by surgery with curative intent, a significant reduction in rfs was associated with male sex and TNM stage, but not with delays (hr: 1.11; p = 0.83). The os after primary surgical resection was also associated with TNM stage, but not with delays (hr: 1.82; p = 0.43). CONCLUSIONS: Recommended targets for wait times in the investigation and treatment of lung cancer can be achieved within a diagnostic assessment program. Compared with radiation treatment, treatment with surgery or chemotherapy is more likely to be completed within targets. Delays in investigation and treatment do not appear to negatively affect the clinical outcomes of os, rfs, and pfs. Prospective studies are needed to evaluate whether efficient work-up and treatment influence other important variables, such as quality of life, cost of care, and access to therapies while performance status is adequate.

Autotaxin interacts with lipoprotein(a) and oxidized phospholipids in predicting the risk of calcific aortic valve stenosis in patients with coronary artery disease.

BACKGROUND: Studies have shown that lipoprotein(a) [Lp(a)], an important carrier of oxidized phospholipids, is causally related to calcific aortic valve stenosis (CAVS). Recently, we found that Lp(a) mediates the development of CAVS through autotaxin (ATX). OBJECTIVE: To determine the predictive value of circulating ATX mass and activity for CAVS. METHODS: We performed a case-control study in 300 patients with coronary artery disease (CAD). Patients with CAVS plus CAD (cases, n = 150) were age- and gender-matched (1 : 1) to patients with CAD without aortic valve disease (controls, n = 150). ATX mass and enzymatic activity and levels of Lp(a) and oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) were determined in fasting plasma samples. RESULTS: Compared to patients with CAD alone, ATX mass (P < 0.0001), ATX activity (P = 0.05), Lp(a) (P = 0.003) and OxPL-apoB (P < 0.0001) levels were elevated in those with CAVS. After adjustment, we found that ATX mass (OR 1.06, 95% CI 1.03-1.10 per 10 ng mL-1 , P = 0.001) and ATX activity (OR 1.57, 95% CI 1.14-2.17 per 10 RFU min-1 , P = 0.005) were independently associated with CAVS. ATX activity interacted with Lp(a) (P = 0.004) and OxPL-apoB (P = 0.001) on CAVS risk. After adjustment, compared to patients with low ATX activity (dichotomized at the median value) and low Lp(a) (<50 mg dL-1 ) or OxPL-apoB (<2.02 nmol L-1 , median) levels (referent), patients with both higher ATX activity (≥84 RFU min-1 ) and Lp(a) (≥50 mg dL-1 ) (OR 3.46, 95% CI 1.40-8.58, P = 0.007) or OxPL-apoB (≥2.02 nmol L-1 , median) (OR 5.48, 95% CI 2.45-12.27, P < 0.0001) had an elevated risk of CAVS. CONCLUSION: Autotaxin is a novel and independent predictor of CAVS in patients with CAD.

Impact of high-fat /low-carbohydrate, high-, low-glycaemic index or low-caloric meals on glucose regulation during aerobic exercise in Type 2 diabetes.

AIMS: A decrement in blood glucose (BG) may be observed in patients with Type 2 diabetes (T2DM) when exercise is performed after a meal, in contrast to fasting. We determined the impact of different pre-exercise meal macronutrient compositions with modulation of the glycaemic index (GI) on glucose regulation during exercise in patients with T2DM. METHODS: Using a randomized, single-blind crossover design, 10 sedentary men performed five exercise sessions, once after an overnight fast, and also after each of four test meals, consisting of a high-fat/low-carbohydrate meal, a high-GI meal, a low-GI meal, and a low-calorie meal. RESULTS: Pre-exercise BG and insulin levels were comparable for all four meals. Exercise decreased BG and insulin levels during all meal conditions (all P < 0.001) compared with the fasting state in which BG levels did not change. The magnitude of BG and insulin decrements was similar after consuming the low-calorie, the high-GI and the high-fat/low-carbohydrate meals, whereas the low-GI meal induced the lowest BG fall. Adrenaline response was higher after consumption of the high-, the low-GI and the low-caloric meals compared with the high-fat/low-carbohydrate meal and with the fasting state (P < 0.05). CONCLUSIONS: This study underlines the beneficial effect of low-GI foods and the differential impact of pre-exercise meal macronutrient composition on BG decrease. This may protect against exercise-induced hypoglycaemia, and reiterates the safety of exercising while fasting in T2DM patients.

Exploring reasons for overuse of contralateral prophylactic mastectomy in Canada.

Background: Contralateral prophylactic mastectomy (cpm) in women with known unilateral breast cancer (bca) has been increasing despite the lack of supportive evidence. The purpose of the present study was to identify the determinants of cpm in women with unilateral bca. Methods: This qualitative descriptive study used semi-structured interviews informed by the Theoretical Domains Framework. We interviewed 74 key informants (surgical oncologists, plastic surgeons, medical oncologists, radiation oncologists, nurses, women with bca) across Canada. Interviews were analyzed using thematic analysis and an analysis for shared and discipline-specific beliefs. Results: In total, 58 factors influencing the use of cpm were identified: 26 factors shared by various health care professional groups, 15 discipline-specific factors (identified by a single health care professional group), and 17 factors shared by women with unilateral bca. Health care professionals identified more factors discouraging the use of cpm (n = 26) than encouraging its use (n = 15); women with bca identified more factors encouraging use of cpm (n = 12) than discouraging its use (n = 5). The factor most commonly identified by health care professionals that encouraged cpm was lack of awareness of existing evidence or guidelines for the appropriate use of cpm (n = 44, 75%). For women with bca, the factor most likely influencing their decision for cpm was wanting a better esthetic outcome (n = 14, 93%). Conclusions: Multiple factors discouraging and encouraging the use of cpm in unilateral bca were identified. Those factors identify potential individual, team, organization, and system targets for behaviour change interventions to reduce cpm.

Impact of fasting and postprandial state on plasma carnitine concentrations during aerobic exercise in type 2 diabetes.

The effects of metabolic states of fasting and post-absorption on plasma concentrations of free carnitine (FC), acylcarnitine (AC) and total carnitine (TC) were compared during submaximal exercise in subjects with type 2 diabetes mellitus. Ten sedentary men (54+/-5 years) treated with oral hypoglycaemic agents were tested on two separate occasions: following an overnight fast and 2 h after a 395-kcal standardised breakfast. Exercise was performed at 60% of [Formula: see text]O(2peak) on a cycle ergometer for 60 min. Blood samples were drawn at rest for baseline values and following 60 min of exercise and 30 min of recovery. Our results show that: (1) baseline levels of TC, FC and AC were similar in fasted and postprandial groups, (2) TC and AC levels were increased during exercise in the fasted group only, (3) FC levels were decreased during exercise in both fasted and postprandial state and (4) the AC/FC ratio increased during exercise in the fasted group. Our results indicate that the metabolic state of the diabetic patient is associated with a different plasma carnitine status. These patterns may reflect differences in energy metabolism associated with fasting and postprandial hyperglycaemia.

Long-term nutritional impact of sleeve gastrectomy.

BACKGROUND: Sleeve gastrectomy (SG) has become a predominant bariatric procedure throughout the world. However, the long-term nutritional impact of this procedure is unknown. OBJECTIVES: To describe the nutritional deficiencies before and after SG and to analyze the influence of baseline weight on nutritional status. SETTING: University-affiliated tertiary care center. METHODS: All patients who underwent SG as a standalone procedure between 2008 and 2012 were included in this study. Patients were given multivitamin supplementation. Data were obtained from our prospectively maintained electronic database and are reported as mean ± standard deviation and percentage. Bivariate analyses were conducted to evaluate the influence of selected variables on outcomes. RESULTS: The mean age of the 537 patients was 48.0 ± 11.3 years, with an initial body mass index of 48.1 ± 8.7 kg/m2. Excess weight loss and total weight loss were 56.2% and 28.0% at 1 year and 43.0% and 21.1% at 5 years, respectively (P<.0001). Percentage of follow-up was 74% at 5 years (n = 79). The mean follow-up time was 34.3 ± 17.2 months. Hypoalbuminemia was present in 1.1% preoperatively and 4.2% at 5 years (P = .0043), low ferritin levels in 8.6% and 37.8% (P<.0001), low vitamin B12 in 30.3% and 16.4% (P<.0001), low vitamin D 63.2% and 24.3% (P<.0001), and hyperparathyroidism in 23.4% and 20.8% (P<.0001). There was no significant difference in the prevalence of anemia over time (P = 0.4301). The prevalence of vitamin A insufficiency peaked from 7.9% preoperatively to 28.7% at 3 months (P<.0001) and returned to baseline thereafter. Baseline weight was negatively correlated with vitamin B12 and vitamin D. CONCLUSION: Nutritional deficiencies are common in patients with morbid obesity before and after surgery. Preoperative supplementation and long-term nutritional follow-up are required to prevent nutritional deficiencies.

Biological profiles in subjects with recurrent acute coronary events compared with subjects with long-standing stable angina.

BACKGROUND: At one end of the clinical spectrum of coronary artery disease (CAD) are subjects who have had repeated acute ischemic events, and at the other end are those with long-standing angina who have never been unstable. This study tests the hypothesis that a specific biological profile can distinguish these 2 extreme groups and predict acute coronary events. METHODS AND RESULTS: Blood levels of lipoprotein(a), homocysteine, tissue plasminogen activator, plasminogen activator inhibitor-1, C-reactive protein (CRP), fibrinogen, and von Willebrand factor were compared in 3 groups of 50 subjects each: (1) those with previous multiple acute coronary events, (2) age-matched subjects with >/=3 years of stable angina and no prior acute coronary events, and (3) matched controls without evidence of atherosclerotic disease and a normal coronary angiogram. All subjects were followed for 4.0 years. Lipoprotein(a), homocysteine, tissue plasminogen activator, and plasminogen activator inhibitor-1 were similar in both CAD groups and significantly higher than in the control group. However, compared with subjects with long-standing stable angina, those with previous multiple coronary events had higher values of CRP (5.7+/-5.4 versus 3.0+/-5.2 mg/L, P=0.012), fibrinogen (3.38+/-0.75 versus 2.92+/-0.64 g/L, P=0.001), and von Willebrand factor (1.60+/-0.55 versus 1.25+/-0.36 U/mL, P=0.0003). On follow-up, myocardial infarction and unstable angina occurred in 42% of the group with multiple events, 4% of the stable angina group (P<0.0001), and none of the control subjects. In the 100 patients with CAD, CRP was 4.9 mg/L in those with and 1.8 mg/L in those without new instability (P<0.0001). In a multivariate analysis, only CRP distinguished those with follow-up acute coronary events (adjusted odds ratio 5.9, 95% CI 2.0 to 17.9; P=0.002). A baseline CRP >3.5 mg/L had a relative risk of 7.6 (2.6 to 21.7, P=0.0002) for subsequent acute events. CONCLUSIONS: An inflammatory biological profile distinguished patients with previous multiple acute coronary events from those with long-standing stable angina and predicted acute coronary instability.

A reappraisal of exercise electrocardiographic indexes of the severity of ischemic heart disease: angiographic and scintigraphic correlates.

OBJECTIVES: We explored how the exercise electrocardiographic (ECG) indexes generally presumed to signify severe ischemic heart disease (IHD) correlate with coronary angiographic and scintigraphic myocardial perfusion findings. BACKGROUND: In exercise testing, it is generally assumed that the early onset of ST segment depression and its occurrence at a low rate-pressure product (ischemic threshold); the amount of maximal ST segment depression; and a horizontal or downsloping ST segment and its prolonged recovery after exercise signify more severe IHD. However, the relation of these indexes to coronary angiographic and exercise myocardial perfusion findings in patients with IHD is unclear. METHODS: We prospectively carried out a symptom-limited 12-lead Bruce protocol thallium-201 single-photon emission computed tomographic (SPECT) exercise test in 66 consecutive subjects with stable angina, > or = 70% stenosis of at least one coronary artery, normal rest ECG and left ventricular wall motion and a prior positive exercise ECG. The above ECG indexes, vessel disease (VD), a VD score and the quantitative thallium-SPECT measures of the extent, maximal deficit and redistribution gradient of the perfusion abnormality were characterized. RESULTS: Maximal ST segment depression could not differentiate the number of diseased vessels; was not related to VD score, maximal thallium deficit or redistribution gradient; but was related to the extent of perfusion abnormality (r = 0.29, 95% confidence interval [CI] 0.08 to 0.52, p = 0.02). Time of onset of ST segment depression correlated inversely only with VD (r = -0.22, 95% CI -0.44 to -0.05, p < 0.05), whereas the ischemic threshold had low inverse correlation only with VD score (r = -0.25, 95% CI -0.47 to -0.01, p < 0.05) and the redistribution gradient (r = -0.33, 95% CI -0.53 to -0.10, p < 0.01). A horizontal or downsloping compared with an upsloping ST segment did not demonstrate more severe angiographic and scintigraphic disease. Recovery time did not correlate with angiographic and scintigraphic findings, and correlations between angiographic and scintigraphic findings were also low or absent. CONCLUSIONS: In this homogeneous study group, the exercise ECG indexes did not necessarily signify more severe IHD by angiographic and scintigraphic criteria. Lack of concordance between the exercise ECG, angiography and myocardial scintigraphy suggests that these diagnostic modalities examine different facets of myocardial ischemia, underscoring the need for caution in the interpretation of their results.

Attenuation of myocardial ischemia with repeated exercise in subjects with chronic stable angina: relation to myocardial contractility, intensity of exercise and the adenosine triphosphate-sensitive potassium channel.

OBJECTIVES: This study characterized the attenuation of myocardial ischemia observed with re-exercise to determine whether: 1) a differing exercise intensity modifies this attenuation; 2) it could be explained by contractile down-regulation or stunning; 3) it is mediated by activation of ATP-sensitive potassium channels (K+-ATP). BACKGROUND: Subjects with ischemic heart disease (IHD) frequently note less angina with re-exercise after a brief rest. Potential mechanisms of this 'warm-up' phenomenon have been little explored. METHODS: IHD subjects with a positive exercise test were studied. Groups I and II (12 subjects each) underwent 2 successive Naughton protocol exercise echocardiography tests (with 1 min instead of 2 min stages for Group II). Group D (10 subjects) had type II diabetes, were on > or =10 mg daily of the K+-ATP blocker, glibenclamide, and underwent the group I exercise protocol. The ischemic threshold or rate-pressure product at 1 mm ST segment depression, ST depression corresponding to the peak rate-pressure product of the first exercise (maximum ST depression equivalent), and left ventricular wall motion indexes before and immediately after each exercise were analyzed. RESULTS: Exercise-induced myocardial ischemia with re-exercise was similarly attenuated in groups I, II, and D. The ischemic threshold was raised by nearly 20% with re-exercise (p=0.001, p=0.02, and p=0.02, respectively) and the maximum ST depression equivalent was nearly halved on re-exercise (p=0.005, p=0.006, and p=0.001, respectively). Exercise-induced wall motion dysfunction was attenuated with re-exercise. In group I, wall motion returned to the initial baseline score prior to exercise 2, whereas in the more intense protocol of group II, wall motion dysfunction persisted prior to exercise 2. CONCLUSIONS: Thus, the attenuation of myocardial ischemia observed with re-exercise appears to be independent of the intensity of the exercise protocol and is not explained by down-regulation of myocardial contractility induced by the initial ischemic stimulus. Since results were similar in diabetic subjects on robust doses of glibenclamide, this phenomenon does not appear to be mediated by K+-ATP activation.

Central endotoxin induces different patterns of interleukin (IL)-1 beta and IL-6 messenger ribonucleic acid expression and IL-6 secretion in the brain and periphery.

Centrally injected endotoxin induced high levels of interleukin (IL)-6 in serum, but the mechanisms of this induction and the signal conveying the information from the brain to the periphery are not yet known. To help characterize the pathway of centrally mediated induction of IL-6 in periphery, the cytokine levels were measured in rat serum and cerebrospinal fluid at different times after intracerebro-ventricular endotoxin (LPS, 2.5 micrograms/rat). In the same experiments, IL-6 and IL-1 beta messenger RNA (mRNA) expression, measured by Northern blot analysis, were evaluated in the periphery (adrenals, lymph nodes, and mononuclear cells) and brain (hypothalamus, hippocampus and striatum). In serum, IL-6 levels were highest after 2h; then they rapidly decreased. IL-6 mRNA showed the same time-course in adrenals and lymph nodes. The pattern in the central nervous system was different: in the cerebrospinal fluid, IL-6 was detectable starting from 2h, reaching a plateaux at 4-8h and remaining detectable until 16 h. IL-6 mRNA expression in the brain areas showed a similar time-course, reaching a maximum at 4-8 h. IL-1 beta mRNA induction started at the same time in brain and periphery, i.e. 1 h after LPS, but the maximal effect was reached at 2 h in mononuclear cells, adrenals, and lymph nodes, and at 8 h in brain regions. The results indicate that circulating IL-6 induced by central LPS is produced mainly peripherally and that synthesis of IL-6 and IL-1 beta are regulated differently in the brain and periphery.

Liver pathology and the metabolic syndrome X in severe obesity.

The metabolic syndrome X, characterized by insulin resistance, dyslipidemia, hypertension, and a male, visceral distribution of adipose tissue, is associated with increased morbidity and mortality from several prevalent diseases, such as diabetes, cancers, myocardial infarction, and stroke. Because the liver has a central role in carbohydrate, lipid, and steroid metabolism, we investigated the relationships between liver pathology and the metabolic syndrome. Blood chemistry, anthropometry (waist/hip circumference ratio), and intraoperative routine knife biopsies of the liver were obtained in 551 (112 men) severely obese patients (body mass index, 47 +/- 9; mean +/- SD) undergoing antiobesity surgery. Steatosis was found in 86%, fibrosis in 74%, mild inflammation or steatohepatitis in 24%, and unexpected cirrhosis in 2% (n = 11) of the patients. The risk of steatosis was 2.6 times greater in men than in women (P < 0.0001). With each addition of 1 of the 4 components of the metabolic syndrome, elevated waist/hip ratio, impaired glucose tolerance, hypertension, and dyslipidemia, the risk of steatosis increased exponentially from 1- to 99-fold (P < 0.001). Fibrosis correlated with steatosis (r = 0.56; P < 0.0001), whereas patients with diabetes or impaired glucose tolerance had a 7-fold increased risk of fibrosis (P < 0.0001). Diabetes, steatosis, and age were all significant indicators of cirrhosis, whereas inflammation was only associated with age. We conclude that the metabolic syndrome via impaired glucose tolerance is strongly correlated with steatosis, fibrosis, and cirrhosis of the liver.

Prevalence, clinical characteristics, and risk factors for insomnia in the context of breast cancer.

STUDY OBJECTIVES: To estimate the prevalence of insomnia, describe clinical characteristics of sleep difficulties, assess the influence of cancer on the insomnia course, and identify potential risk factors involved in the development of insomnia among women who had received radiotherapy for non metastatic breast cancer. DESIGN: A sample of 300 consecutive women who had been treated with radiotherapy for non metastatic breast cancer first completed an insomnia screening questionnaire. Participants who reported sleep difficulties were subsequently interviewed over the phone to evaluate further the nature, severity, duration, and course of their insomnia. SETTING: N/A. PATIENTS OR PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Nineteen percent (n=56) of the participants met diagnostic criteria for an insomnia syndrome. In most cases (95%), insomnia was chronic. The onset of insomnia followed the breast cancer diagnosis in 33% of the patients and 58% of the patients reported that cancer either caused or aggravated their sleep difficulties. Factors associated with an increased risk for insomnia were sick leave, unemployment, widowhood, lumpectomy, chemotherapy, and a less severe cancer stage at diagnosis. Among women with insomnia symptoms, the risk to meet diagnostic criteria for an insomnia syndrome was higher in those who were separated and had a university degree. CONCLUSIONS: Insomnia is a prevalent and often chronic problem in breast cancer patients. Although it is not always a direct consequence of cancer, pre-existing sleep difficulties are often aggravated by cancer. It is therefore important to better screen breast cancer patients with insomnia and offer them an appropriate treatment.

How changes in the serial distribution of bronchoconstriction affect lung mechanics.

It is generally accepted that methacholine (MCh) acts predominantly on the central airways and histamine (H) acts on the lung periphery. We hypothesized therefore that lung mechanics would be affected differently by H and MCh aerosols. In 12 anesthetized paralyzed open-chest mongrel dogs, we obtained MCh (0.1-30 mg/ml, n = 6) and H (0.1-30 mg/ml, n = 6) concentration-response curves. The alveolar capsule technique was used to partition lung resistance (RL) into airway (Raw) and tissue (Rti) components. The degree of mechanical heterogeneity across the lung was assessed by computing the coefficient of variation for five alveolar pressures during relaxed expirations. RL increased 823 +/- 202% after H and 992 +/- 219% after MCh. Rti increased 784 +/- 192% after H and 1,014 +/- 279% after MCh. Raw increased 1,098 +/- 297% after H and 1,275 +/- 332% after MCh. Elastance increased 342 +/- 53% after H and 423 +/- 88% after MCh. The coefficient of variation increased 279 +/- 65% after H and 252 +/- 55% after MCh. The patterns of change were similar throughout the H and MCh concentration-response curves. We conclude that H and MCh have comparable effects on lung mechanics and that the degree and pattern of heterogeneity inside the lung after constriction are the same regardless of the agent used. These data support the hypothesis that H and MCh have some similar direct effect on the lung parenchyma. Parenchymal deformation after MCh-induced central airway constriction alone would be unlikely to explain increases in Rti of this magnitude or changes in lung mechanics so similar to those induced by H.

Lung tissue behavior during methacholine challenge in rabbits in vivo.

Previous studies have shown that lung challenge with smooth muscle agonists increases tissue viscance (Vti), which is the pressure drop between the alveolus and the pleura divided by the flow. Passive inflation also increases Vti. The purpose of the present study was to measure the changes in Vti during positive end-expiratory pressure- (PEEP) induced changes in lung volume and with a concentration-response curve to methacholine (MCh) in rabbits and to compare the effects of induced constriction vs. passive lung inflation on tissue mechanics. Measurements were made in 10 anesthetized open-chest mechanically ventilated New Zealand male rabbits exposed first to increasing levels of PEEP (3-12 cmH2O) and then to increasing concentrations of MCh aerosol (0.5-128 mg/ml). Lung elastance (EL), lung resistance (RL), and Vti were determined by adjusting the equation of motion to tracheal and alveolar pressures during tidal ventilation. Our results show that under baseline conditions, Vti accounted for a major proportion of RL; during both passive lung inflation and MCh challenge this proportion increased progressively. For the same level of change in EL, however, the increase in Vti was larger during MCh challenge than during passive inflation; i.e., the relationship between energy storage and energy dissipation or hysteresivity was dramatically altered. These results are consistent with a MCh-induced change in the intrinsic rheological properties of lung tissues unrelated to lung volume change per se. Lung tissue constriction is one possible explanation.

Effect of lung volume on plateau response of airways and tissue to methacholine in dogs.

We have recently shown in dogs that much of the increase in lung resistance (RL) after induced constriction can be attributed to increases in tissue resistance, the pressure drop in phase with flow across the lung tissues (Rti). Rti is dependent on lung volume (VL) even after induced constriction. As maximal responses in RL to constrictor agonists can also be affected by changes in VL, we questioned whether changes in the plateau response with VL could be attributed in part to changes in the resistive properties of lung tissues. We studied the effect of changes in VL on RL, Rti, airway resistance (Raw), and lung elastance (EL) during maximal methacholine (MCh)-induced constriction in 8 anesthetized, paralyzed, open-chest mongrel dogs. We measured tracheal flow and pressure (Ptr) and alveolar pressure (PA), the latter using alveolar capsules, during tidal ventilation [positive end-expiratory pressure (PEEP) = 5.0 cmH2O, tidal volume = 15 ml/kg, frequency = 0.3 Hz]. Measurements were recorded at baseline and after the aerosolization of increasing concentrations of MCh until a clear plateau response had been achieved. VL was then altered by changing PEEP to 2.5, 7.5, and 10 cmH2O. RL changed only when PEEP was altered from 5 to 10 cmH2O (P < 0.01). EL changed when PEEP was changed from 5 to 7.5 and 5 to 10 cmH2O (P < 0.05). Rti and Raw varied significantly with all three maneuvers (P < 0.05). Our data demonstrate that the effects of VL on the plateau response reflect a complex combination of changes in tissue resistance, airway caliber, and lung recoil.

Lung tissue resistance during contractile stimulation: structural damping decomposition.

Research in the mechanics of soft tissue, and lung tissue in particular, has emphasized that dissipative processes depend predominantly on the viscous stress. A corollary is that dissipative losses may be expressed as a tissue viscous resistance, (Rti). An alternative approach is offered by the structural damping hypothesis, which holds that dissipative processes within soft tissue depend directly more on the elastic stress than on the viscous stress. This implies that dissipative and elastic processes within lung tissues are coupled at a fundamental level. We induced alterations of Rti by exposing canines to aerosols of the constrictors prostaglandin F2 alpha, histamine, and methacholine and by changing volume history. Using the structural damping paradigm, we could separate those alterations in Rti into the product of two distinct contributions: change in the coefficient of coupling of dissipation to elastance (eta) and change in the elastance itself (Edyn). Response of Edyn accounted for most of the response of resistance associated with contractile stimulation; it accounted for almost all the response associated with differences in volume history. The eta changed appreciably with constriction but accounted for little of the response of Rti with volume history. According to the structural damping hypothesis, induced changes in eta with constriction must reflect changes in the kinetics of the stress-bearing process, i.e., differences in cross-bridge kinetics within the target contractile cell and/or differences in the influence of the target cell on other stress-bearing systems. We conclude that, regardless of underlying processes, the structural damping analysis demonstrates a fundamental phenomenological simplification: when Edyn responds, Rti is obligated to respond to a similar degree.

The Ilizarov procedure: limb lengthening and its implications.

The purpose of this article is to provide a historical and clinical perspective on the Ilizarov method of external fixation for limb lengthening and deformity correction of the lower extremity. Though relatively new in the United States, the technique has been applied for orthopedic problems with great success for over three decades in Russia and Europe. Physical therapy management is discussed from the preoperative planning phase to removal of the apparatus.

Effects of maternal surgical weight loss in mothers on intergenerational transmission of obesity.

BACKGROUND AND OBJECTIVES: By studying cardiometabolic risk factors in children born after maternal biliopancreatic diversion bariatric surgery (AMS) compared with those in children born before maternal surgery (BMS), we tested the hypothesis that significant maternal weight loss may modify obesity-related factors transmitted via the intrauterine environment. DESIGN: Anthropometry and fasting blood levels were studied in 49 mothers who had lost 36 +/- 1.8% body weight sustained for 12 +/- 0.8 yr and their 111 children (54 BMS and 57 AMS) aged 2.5-26 yr. RESULTS: AMS children had lower birth weight (2.9 +/- 0.1 AMS vs. 3.3 +/- 0.1 kg BMS, P = 0.003) associated with a reduced prevalence of macrosomia (1.8 AMS vs. 14.8% BMS, P = 0.03) with no difference in underweight. At the time of follow-up, AMS children exhibited 3-fold lower prevalence of severe obesity (11 vs. 35%, P = 0.004), greater insulin sensitivity (homeostasis model assessment of insulin resistance index 3.4 +/- 0.3 vs. 4.8 +/- 0.5, P = 0.02), improved lipid profile (cholesterol/high-density lipoprotein cholesterol 2.96 +/- 0.11 vs 3.40 +/- 0.18, P = 0.03; high-density lipoprotein cholesterol 1.50 +/- 0.05 vs. 1.35 +/- 0.05 mmol/liter, P = 0.04), lower C-reactive protein (0.88 +/- 0.17 vs. 2.00 +/- 0.34 microg/ml, P = 0.004), and leptin (11.5 +/- 1.5 vs.19.7 +/- 2.5 ng/ml, P = 0.005) and increased ghrelin (1.28 +/- 0.06 vs.1.03 +/- 0.06 ng/ml, P = 0.005) than BMS offspring (AMS vs. BMS, respectively, for all). CONCLUSIONS: This unique study of children aged 2.5-26 yr born before and after maternal antiobesity surgery demonstrated improvements in cardiometabolic markers sustained into adolescence, attributable to an improved intrauterine environment.