Respiratory modulation of sympathetic transduction to blood pressure in health and type 2 diabetes.

Type 2 diabetes (T2D) is often accompanied by hypertension, exaggerated blood pressure (BP) responses to sympatho-excitatory stressors, and raised cardiovascular disease risk. Appropriate respiratory-sympathetic coupling and sympathetic transduction to BP are important for short- and longer-term BP control. We tested the hypotheses that respiratory modulation of muscle sympathetic nerve activity (MSNA) and its transduction to BP would be impaired in T2D and associated with higher BP and respiratory-coupled BP variability. Resting MSNA, respiration and beat-to-beat BP were recorded in 20 T2D (49.1 ± 7.4 years; mean ± SD) and 13 healthy control (46.3 ± 9.4 years) participants. MSNA and the transduction of sympathetic bursts (signal-averaging) to mean arterial pressure (MAP) were compared at low and high lung volume phases. The peak MAP response following a sympathetic burst was lower during the high lung volume than low lung volume phase in controls (P = 0.005), whereas it was unchanged with phase in T2D participants (P = 0.522). Respiratory modulation of MSNA was impaired in T2D participants, who had an attenuated reduction in burst incidence from low to the high lung volume phase, versus controls (27.8 ± 38.4% vs. 49.4 ± 24.6%, respectively; P = 0.043). The T2D participants were grouped into unimpaired respiratory modulators (burst incidence modulation median or above) or impaired respiratory modulators (below median). Impaired modulators had higher systolic BP (133 ± 14 vs. 121 ± 11 mmHg, P = 0.046), greater Traube-Hering wave amplitudes (6.3 ± 2.4 vs. 4.6 ± 1.1 mmHg; P = 0.028) and higher BP variability (MAP average real variability, 2.0 ± 0.7 vs. 1.4 ± 0.3, P = 0.033). Respiratory modulation of MSNA and sympathetic transduction to BP are altered in T2D patients and may contribute to their increased hypertension and cardiovascular risk. KEY POINTS: Respiratory-sympathetic coupling and sympathetic transduction to blood pressure (BP) contribute to short- and longer-term BP control. Our understanding of these processes in health and type 2 diabetes (T2D), a condition with high prevalence of hypertension and cardiovascular risk, is incomplete. We found that respiration and sympathetic transduction to BP are coupled in healthy individuals. The mean arterial pressure response to a sympathetic burst was reduced during the high lung volume compared to the low lung volume phase. This coupling was absent in T2D. Respiratory modulation of muscle sympathetic nerve activity (MSNA) is impaired in T2D, with a blunted reduction of MSNA observed during the high lung volume phase. T2D patients with impaired respiratory MSNA modulation had augmented systolic BP, respiratory-related BP excursions (Traube-Hering waves) and BP variability. Abnormal respiratory modulation of MSNA and sympathetic transduction to BP in T2D may contribute to altered blood pressure control and cardiovascular risk in this population.

Comparative Performance of Pulmonary Ultrasound, Chest Radiograph, and CT Among Patients With Acute Respiratory Failure.

OBJECTIVES: The study goal was to concurrently evaluate agreement of a 9-point pulmonary ultrasound protocol and portable chest radiograph with chest CT for localization of pathology to the correct lung and also to specific anatomic lobes among a diverse group of intubated patients with acute respiratory failure. DESIGN: Prospective cohort study. SETTING: Medical, surgical, and neurologic ICUs at a 670-bed urban teaching hospital. PATIENTS: Intubated adults with acute respiratory failure having chest CT and portable chest radiograph performed within 24 hours of intubation. INTERVENTIONS: A 9-point pulmonary ultrasound examination performed at the time of intubation. MEASUREMENTS AND MAIN RESULTS: Sixty-seven patients had pulmonary ultrasound, portable chest radiograph, and chest CT performed within 24 hours of intubation. Overall agreement of pulmonary ultrasound and portable chest radiograph findings with correlating lobe ("lobe-specific" agreement) on CT was 87% versus 62% (p < 0.001), respectively. Relaxing the agreement definition to a matching CT finding being present anywhere within the correct lung ("lung-specific" agreement), not necessarily the specific mapped lobe, showed improved agreement for both pulmonary ultrasound and portable chest radiograph respectively (right lung: 92.5% vs 65.7%; p < 0.001 and left lung: 83.6% vs 71.6%; p = 0.097). The highest lobe-specific agreement was for the finding of atelectasis/consolidation for both pulmonary ultrasound and portable chest radiograph (96% and 73%, respectively). The lowest lobe-specific agreement for pulmonary ultrasound was normal lung (79%) and interstitial process for portable chest radiograph (29%). Lobe-specific agreement differed most between pulmonary ultrasound and portable chest radiograph for interstitial findings (86% vs 29%, respectively). Pulmonary ultrasound had the lowest agreement with CT for findings in the left lower lobe (82.1%). Pleural effusion agreement also differed between pulmonary ultrasound and portable chest radiograph (right: 99% vs 87%; p = 0.009 and left: 99% vs 85%; p = 0.004). CONCLUSIONS: A clinical, 9-point pulmonary ultrasound protocol strongly agreed with specific CT findings when analyzed by both lung- and lobe-specific location among a diverse population of mechanically ventilated patients with acute respiratory failure; in this regard, pulmonary ultrasound significantly outperformed portable chest radiograph.

Facial flushing on upper limb exertion: a rare presentation of superior vena cava obstruction.

Infection remains a significant problem for patients with cardiac-implantable electronic devices (CIEDs) but can be difficult to diagnose. We describe an unusual presentation of CIED infection in a patient with abandoned pacemaker leads. A 27-year-old male presented with facial flushing on upper but not lower limb exertion due to superior vena cava (SVC) obstruction, as well as pleuritic chest pain due to septic emboli. This was successfully treated with antibiotics and complete endovascular extraction of the pacemaker leads. Upper limb exertional facial flushing may be a useful clinical sign for the diagnosis of SVC obstruction. This case report also describes a rare presentation of CIED infection.

The Oregon Dental Market A Case Study.

This case study examines changes taking place in the Oregon dental care system. Data were obtained from interviews with senior executives from several delivery organizations. Conducted by the senior author (HB), the summarized interviews were reviewed by informants. Oregon Medicaid enrollees now receive medical! dental care in capitated managed care organizations. Several dental group practices that provide care to privately and publicly insured patients are growing rapidly.The largest local dental insurer has diversified into other health products, including management services for affiliated dental practices. The Oregon dental market is undergoing a major reorganization: (a) large dental group practices are expanding and solo practices are declining; (b) all Medicaid patients receive their care in state-regulated Coordinated Care Organizations and their contracted Dental Care Organizations; and (c) more dental graduates are seeking employment in group practices. Longer term, the dental group practice companies are expected to undergo some consolidation.Two key features of the Oregon dental market are the growth of large dental group practices and the reorganization of the dental Medicaid system.

Colorectal adenocarcinoma cancer in New Zealand in those under 25 years of age (1997-2007).

INTRODUCTION: Colorectal cancer is common and primarily a disease of older people. Colorectal cancer in patients aged 25 years and under is infrequent and may represent a unique subgroup of patients. This study aimed to describe the population of young people in New Zealand diagnosed with colorectal cancer, their tumour characteristics, management and outcomes. METHODS: A retrospective clinical study was conducted via review of medical records for all patients 25 years of age and under, diagnosed with colorectal adenocarcinoma in New Zealand between 1 January 1997 and 31 December 2007. RESULTS: Fifty patients with colorectal adenocarcinoma were identified from the New Zealand Cancer Registry. Seven had a positive family history of colorectal cancer, while eight had predisposing factors (hereditary nonpolyposis colorectal cancer, familial adenomatous polyposis, ulcerative colitis, Crohn's disease, regional enteritis). The most common presenting symptoms were abdominal pain and weight loss. Twenty-eight cases presented acutely. Eighteen presented with stage IV disease at diagnosis. Eighteen were referred to a genetics service. Five-year overall survival was 49%. DISCUSSION: Those aged 25 years and under that develop colorectal cancer tend to present acutely and move through the secondary care pathway swiftly, being diagnosed at a more advanced stage, and have a poorer prognosis than their adult counterparts. Familial cancers form a more significant component of youth colorectal cancers compared to the older population and input from genetic service should be considered.

Multiple domains in MtENOD8 protein including the signal peptide target it to the symbiosome.

Symbiotic nitrogen fixation occurs in nodules, specialized organs on the roots of legumes. Within nodules, host plant cells are infected with rhizobia that are encapsulated by a plant-derived membrane forming a novel organelle, the symbiosome. In Medicago truncatula, the symbiosome consists of the symbiosome membrane, a single rhizobium, and the soluble space between them, called the symbiosome space. The symbiosome space is enriched with plant-derived proteins, including the M. truncatula EARLY NODULIN8 (MtENOD8) protein. Here, we present evidence from green fluorescent protein (GFP) fusion experiments that the MtENOD8 protein contains at least three symbiosome targeting domains, including its N-terminal signal peptide (SP). When ectopically expressed in nonnodulated root tissue, the MtENOD8 SP delivers GFP to the vacuole. During the course of nodulation, there is a nodule-specific redirection of MtENOD8-SP-GFP from the vacuole to punctate intermediates and subsequently to symbiosomes, with redirection of MtENOD8-SP-GFP from the vacuole to punctate intermediates preceding intracellular rhizobial infection. Experiments with M. truncatula mutants having defects in rhizobial infection and symbiosome development demonstrated that the MtNIP/LATD gene is required for redirection of the MtENOD8-SP-GFP from the vacuoles to punctate intermediates in nodules. Our evidence shows that MtENOD8 has evolved redundant targeting sequences for symbiosome targeting and that intracellular localization of ectopically expressed MtENOD8-SP-GFP is useful as a marker for monitoring the extent of development in mutant nodules.

Multidetector computed tomographic characteristics of nonabsorbable polymer versus titanium ligature clips in a vascular model.

OBJECTIVE: Multidetector cardiac computed tomography is commonly performed to evaluate coronary bypass grafts, but titanium clips result in significant image artifact. Multidetector cardiac computed tomographic characteristics of newly developed nonabsorbable polymer clips are unknown. This study was undertaken to compare the image characteristics of polymer clips and titanium clips applied to a vascular model. METHODS: A vascular model was created with two porcine internal thoracic arteries. Branches were ligated with 5 titanium clips on one vessel and 6 polymer clips on the other. Vessels were imaged under pressure with normal saline solution in a 16-detector computed tomographic scanner. Image intensity was quantified in absolute Hounsfield units for clips and adjacent lumen and then normalized to the average lumen intensity. RESULTS: No difference in absolute intensity was found between polymer clips and adjacent lumen (polymer clip 1021.2 +/- 19.0 absolute Hounsfield units, adjacent lumen 1001.7 +/- 15.7 absolute Hounsfield units, P = .095). A statistically significant difference was noted between titanium clips and adjacent lumen (titanium clips 3408.8 +/- 177.3 absolute Hounsfield units, adjacent lumen 1072.7 +/- 52.1 absolute Hounsfield units, P < .0001). A statistically significant difference was also noted between titanium and polymer clips (P < .0001). CONCLUSION: The use of polymer clips in coronary bypass grafts should result in significantly improved multidetector cardiac computed tomographic image quality.

Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer.

The Lung Screening Study (LSS) was a pilot study designed to assess the feasibility of conducting a large scale randomized controlled trial (RCT) of low radiation dose spiral computed tomography (LDCT) versus chest X-ray (CXR) for lung cancer screening. Baseline results of LSS have been previously reported. Here, we report on the findings at the year one screen and on the final results of the LSS study. A total of 1660 subjects were randomized to the LDCT arm and 1658 to the CXR arm. Compliance with screening declined from 96% at baseline to 86% at year one in the LDCT arm and declined from 93% at baseline to 80% at year one in the CXR arm. Positivity rates for the year one screen were 25.8% for LDCT and 8.7% for CXR. Cancer yield was significantly less at year one for LDCT, 0.57%, than at baseline, 1.9%; cancer yield for CXR increased from 0.45% at baseline to 0.68% at year one. Forty lung cancers in the LDCT arm and 20 in the CXR arm were diagnosed over the study period. Stage I cancers comprised 48% of cases in the LDCT arm and 40% in the CXR arm. A total of 16 stage III-IV cancers were observed in the LDCT arm versus nine in the CXR arm. The LSS has established the feasibility of a RCT comparing annual spiral CT to chest X-ray for lung cancer screening.

Feasibility and value of video-assisted thoracoscopic surgery wedge excision of small pulmonary nodules in patients with malignancy.

PURPOSE: Advances in CT scanning have presented physicians with the challenge of diagnosing small (< 10 mm) or deep (> 5 mm) pulmonary nodules (SmPNs) in patients with known malignancies during workup or follow-up. Wedge excision of SmPNs is difficult with video-assisted thoracoscopic surgery (VATS) and often requires the performance of a thoracotomy. The value of the early detection of metastatic disease must be weighed against the morbidity (ie, thoracotomy) that is necessarily involved in obtaining the information. Little is known about the incidence of metastases in this subset of patients. We describe a VATS technique that allows the reliable excisional biopsy of SmPNs and present our findings in this patient population. METHODS: Using CT scan localization, 150 micro Ci technetium sulfur colloid is injected into the area of the pulmonary nodule. Additional blue dye is injected at the lung surface. During VATS, a sterile gamma probe is used to identify the area of radioactivity and plan placement of staple lines performed by an endostapling instrument. Palpation and the presence of radioactivity in the specimen supported the resection of the correct nodule, and CT scan findings confirmed the procedure. Between March 2000 and January 2001, 17 patients with known malignancies and SmPNs underwent VATS excisional biopsies. Six patients received a new diagnosis of malignancy, and 11 patients were in follow-up of a previously treated malignancy. The malignancies included the following: breast (four patients), head and neck (four patients), pancreas (two patients), lymphoma (two patients), lung (one patient), prostate (one patient), rectal (one patient), seminoma (one patient), and urethral (one patient). RESULTS: All lesions were successfully resected on the first try. Nodules were removed from 10 segments and all lobes. The mean (+/-/SD) nodule size was 9.2 +/- 3.6 mm, and the mean depth was 9.4 +/- 5.2 mm. Fourteen of 17 nodules (82.4%) could be neither seen nor felt using standard VATS techniques. Diagnoses included metastatic (four patients), new primary lung cancer (one patient), acid-fast bacillus (one patient), granuloma (seven patients), carcinoid (two patients), and inflammatory pseudotumor (two patients). Among these lesions, 29.4% were malignant, and 35.3% of patients received a diagnosis that altered their therapy. Five of 12 SmPNs (41.7%) < 10 mm in size were malignant. The median length of hospital stay was 2 days. Patients returned to full activity within 1 week. CONCLUSION: VATS excision of SmPNs after CT scan localization with radiolabeled technetium is reliable, reproducible, and associated with minimal morbidity. The technique prevented thoracotomies in 82.4% of patients. Despite the small size of these lesions, malignancy was found 29.4% of the time. This technique allows the early diagnosis of SmPNs, with low morbidity, in patients with known malignancies. CLINICAL IMPLICATIONS: The reliability of this technique, the high incidence of malignancy, and the reduction in morbidity from undergoing excisional biopsy procedures will encourage the clinician to strive for earlier and more aggressive diagnoses of SmPNs.