Evaluating risk factors for re-exploration due to postoperative neck hematoma after thyroid surgery: a nested case-control study.

PURPOSE: Postoperative bleeding after thyroid surgery remains a potentially lethal complication. Outpatient thyroidectomy is an increasing trend in the high volume centers. There is a need to identify risk factors for postoperative bleeding in order to select proper patients for outpatient thyroidectomy. This study aimed to investigate this issue using a national population-based register. MATERIAL AND METHOD: A nested case-control study on patients registered in the Swedish national register for endocrine surgery (SQRTPA) was performed. Patients with postoperative bleeding were matched 1:1 by age and gender to controls. Additional information on cases and controls was obtained from attending surgeons using a questionnaire. Risk factors for postoperative bleeding were evaluated with logistic regression and are presented as odds ratios (ORs) with 95% confidence intervals (CIs). The time of bleeding in relation to surgery was also investigated. RESULTS: There were 9494 operations, and 174 (1.8%) of them involved postoperative bleeding. In the whole cohort, patients with postoperative bleeding were older, 58 (46-69) vs. 49 (37-62) years, than patients without, p < 0.01. Male patients had a higher risk of bleeding, OR 2.18 (95% CI 1.58-2.99). In the case-control cohort, drain was an independent risk factor for bleeding, OR 1.64 (1.05-2.57). Two-thirds of patients bled within 6 h after surgery. The incidence of bleeding after 24 h was 10%. CONCLUSION: High age, male gender, and drain are independent risk factors for bleeding after thyroid surgery. Even with careful patient selection, prolonged observation might be necessary in thyroid surgery.

A Nested Case-Control Study on the Risk of Surgical Site Infection After Thyroid Surgery.

INTRODUCTION: It is unclear if antibiotic prophylaxis reduces the risk of surgical site infection (SSI) in thyroid surgery. This study assessed risk factors for SSI and antibiotic prophylaxis in subgroups of patients. METHOD AND DESIGN: A nested case-control study on patients registered in the Swedish National Register for Endocrine Surgery was performed. Patients with SSI were matched 1:1 by age and gender to controls. Additional information on patients with SSI and controls was queried from attending surgeons using a questionnaire. Risk factors for SSI were evaluated by logistic regression analysis and presented as odds ratio (OR) with 95% confidence interval (CI). RESULTS: There were 9494 operations; 109 (1.2%) patients had SSI. Patients with SSI were older (median 53 vs. 49 years) than patients without SSI p = 0.01 and more often had a cancer diagnosis 23 (21.1%) versus 1137 (12.1%) p = 0.01. In the analysis of patients with SSI versus controls, patients with SSI more often had post-operative drainage 68 (62.4%) versus 46 (42.2%) p = 0.01 and lymph node surgery 40 (36.7%) versus 14 (13.0%) p < 0.01, and both were independent risk factors for SSI, drain OR 1.82 (CI 1.04-3.18) and lymph node dissection, OR 3.22 (95% CI 1.32-7.82). A higher number of 26(62%) patients with independent risk factors for SSI and diagnosed with SSI did not receive antibiotic prophylaxis. Data were missing for 8 (31%) patients. CONCLUSION: Lymph node dissection and drain are independent risk factors for SSI after thyroidectomy. Antibiotic prophylaxis might be considered in patients with these risk factors.

Impact of genomic stability on protein expression in endometrioid endometrial cancer.

BACKGROUND: Genomic stability is one of the crucial prognostic factors for patients with endometrioid endometrial cancer (EEC). The impact of genomic stability on the tumour tissue proteome of EEC is not yet well established. METHODS: Tissue lysates of EEC, squamous cervical cancer (SCC), normal endometrium and squamous cervical epithelium were subjected to two-dimensional (2D) gel electrophoresis and identification of proteins by MALDI TOF MS. Expression of selected proteins was analysed in independent samples by immunohistochemistry. RESULTS: Diploid and aneuploid genomically unstable EEC displayed similar patterns of protein expression. This was in contrast to diploid stable EEC, which displayed a protein expression profile similar to normal endometrium. Approximately 10% of the differentially expressed proteins in EEC were specific for this type of cancer with differential expression of other proteins observed in other types of malignancy (e.g., SCC). Selected proteins differentially expressed in 2D gels of EEC were further analysed in an EEC precursor lesion, that is, atypical hyperplasia of endometrium, and showed increased expression of CLIC1, EIF4A1 and PRDX6 and decreased expression of ENO1, ANXA4, EMD and Ku70. CONCLUSION: Protein expression in diploid and aneuploid genomically unstable EEC is different from the expression profile of proteins in diploid genomically stable EEC. We showed that changes in expression of proteins typical for EEC could already be detected in precursor lesions, that is, atypical hyperplasia of endometrium, highlighting their clinical potential for improving early diagnostics of EEC.

Is the rate of whole-body nitrogen elimination influenced by exercise?

BACKGROUND: Because it has earlier been shown that exercise 24 or two hours pre-dive may suppress the appearance of venous gas bubbles (VGB) in connection with the dive, we studied whether exercise before or during N2 elimination would influence the rate of the latter. Nitrogen elimination was recorded in eight volunteers breathing a normoxic O2+argon mixture for two hours. The N2 washout was preceded two (Condition A) or 24 hours (Condition B) earlier, by one hour of exercise at 85% VO2max (two hours of exercise interspersed with two hours of rest). In separate experiments, exercise at -40% of VO2max was performed throughout the two-hour washout (Condition C), and control experiments (Condition D) with denitrogenation without exercise were also performed. RESULTS: There were no significant differences among conditions for the total N2 eliminated (904 +/- 196 mL). The half-times of N2 washout for A (35.2 +/- 10.8 minutes) and B (31.9 +/- 8.6 minutes) did not differ from control washouts. The rate of washout in C increased 14% compared to D (half-time: 30.4 +/- 7.6 vs. 34.5 +/- 7.8 minutes, p = 0.002), and correlated with cardiac output. CONCLUSION: Exercise 24 or two hours pre-N2 washout did not affect it, suggesting that the decreased VGB scores noted by others in dives preceded by conditions similar to A and B are not due to changes in nitrogen exchange but rather to factors related to bubble formation and/or appearance. That N2 elimination is enhanced by concomitant exercise makes physiological sense but does not necessarily explain the observation by others of a reduced risk of decompression sickness with exercise before diving.

Energy cost of breathing at depth: effect of respiratory muscle training.

INTRODUCTION: Respiratory muscle training against resistance (RRMT) increases respiratory muscle strength and endurance as well as underwater swimming endurance. We hypothesized that the latter is a result of RRMT reducing the high energy cost of breathing at depth. METHODS: Eight subjects breathed air in a hyperbaric chamber at 55 fsw, both before and after RRMT. They rested for 10 minutes, cycled on an ergometer for 10 minutes (100 W), rested for 10 minutes, and then, while still at rest, they voluntarily mimicked the breathing pattern recorded during the exercise (isocapnic simulated exercise ventilation, ISEV). RESULTS: Post-RRMT values of V(E) at rest, exercise and ISEV were not different from those recorded pre-RRMT. Pre-RRMT minute-ventilation (V(E)) during ISEV was not different from the exercise ventilation (49.98 +/- 10.41 vs. 47.74 +/- 8.44 L/minute). The end-tidal PCO2 during ISEV and exercise were not different (44.26 +/- 2.54 vs. 44.49 +/- 4.49 mmHg) or affected by RRMT. Oxygen uptake (VO2) was 0.32 +/- 0.08 L/ minute at rest, 1.78 +/- 0.15 during exercise pre-RRMT, and not different post-RRMT. During ISEV, VO2 decreased significantly from pre-RRMT to post-RRMT (0.46 +/- 0.06 vs. 0.36 +/- 0.11 L/minute). Post-RRMT delta VO2/delta V(E) was significantly lower during ISEV than pre-RRMT (0.0094 +/- 0.0021 L/L vs. 0.0074 +/- 0.0023 L/L). CONCLUSION: RRMT significantly reduced the energy cost of ventilation, measured as delta VO2/delta V(E) during ISEV, at a depth of 55 fsw. Whether this change was due to reduced work of breathing and/or increased efficiency of the respiratory muscles remains to be determined.

Practising in a post-truth world: Pandemic ethics can inform patient autonomy and clinical communication.

The COVID-19 pandemic posed an unprecedented challenge to modern bioethical frameworks in the clinical setting. Now, as the pandemic stabilises and we learn to 'live with COVID', the medical community has a duty to evaluate its response to the challenge, and reassess our ethical reasoning, considering how we practise in the future. This article considers a number of clinical and bioethical challenges encountered by the author team and colleagues during the most severe waves of the pandemic. We argue that the changed clinical context may require reframing our ethical thought in such a manner as to adequately accommodate all parties in the clinical interaction. We argue that clinicians have become relatively disempowered by the 'infodemic', and do not necessarily have adequate skills or training to assess the scientific literature being published at an unprecedented rate. Conversely, we acknowledge that patients and families are more empowered by the infodemic, and bring this empowerment to bear on the clinical consultation. Sometimes these interactions can be unpleasant and threatening, and involve inviting clinicians to practise against best evidence or even illegally. Generally, these requests are framed within 'patient autonomy' (which some patients or families perceive to be unlimited), and several factors may prevent clinicians from adequately navigating these requests. In this article, we conclude that embracing a framework of shared decision-making (SDM), which openly acknowledges clinical expertise and in which patient and family autonomy is carefully balanced against other bioethics principles, could serve us well going forward. One such principle is the recognition of clinician expertise as holding weight in the clinical encounter, when framed in terms of non-maleficence and beneficence. Such a framework incorporates much of our learning and experience from advising and treating patients during the pandemic.

Primary small intestinal neuroendocrine tumors are highly prevalent and often multiple before metastatic disease develops.

BACKGROUND: Small intestinal neuroendocrine tumors are the most common of small bowel malignancies with a clinical incidence of about 1 per 100,000 persons per year. There has been a threefold increase in the incidence of small intestinal neuroendocrine tumor during later decades, but there are no studies that clarify whether this is due to a true higher incidence or if the rise is a mere product of, for instance, improved diagnostic modalities. The aim of this study was to investigate the incidence of clinical as well as subclinical small intestinal neuroendocrine tumors found at autopsy as well as describing the frequency of concomitant malignancies in patients with small intestinal neuroendocrine tumor. MATERIALS AND METHODS: An autopsy registry from the Malmö county population from 1970 to 1982 with an 87% autopsy rate was used. The clinical autopsy reports for patients coded for the existence of "carcinoid tumor" were scrutinized for the presence of small intestinal neuroendocrine tumor, metastatic disease, and concomitant malignancies. Details of patients with clinically diagnosed small intestinal neuroendocrine tumor during this time period were gathered from the Swedish Cancer Registry. RESULTS: The mean annual incidence of small intestinal neuroendocrine tumor during this period was 5.33 per 100,000 individuals, and the mean annual prevalence was 581 per 100,000. The cause of death in the majority of cases was not due to small intestinal neuroendocrine tumor. In total, 48% of the people with small intestinal neuroendocrine tumor had at least one other malignancy, most commonly colorectal cancer. CONCLUSION: Most small intestinal neuroendocrine tumors are subclinical, and persons living with them will often die due to other causes. There was a high rate of multiple primary tumors (40%), suggesting that multiple tumors seem to arise before the advent of metastatic disease. Moreover, a comparably high rate of associated colorectal carcinoma was found.

The underwater environment: cardiopulmonary, thermal, and energetic demands.

Water covers over 75% of the earth, has a wide variety of depths and temperatures, and holds a great deal of the earth's resources. The challenges of the underwater environment are underappreciated and more short term compared with those of space travel. Immersion in water alters the cardio-endocrine-renal axis as there is an immediate translocation of blood to the heart and a slower autotransfusion of fluid from the cells to the vascular compartment. Both of these changes result in an increase in stroke volume and cardiac output. The stretch of the atrium and transient increase in blood pressure cause both endocrine and autonomic changes, which in the short term return plasma volume to control levels and decrease total peripheral resistance and thus regulate blood pressure. The reduced sympathetic nerve activity has effects on arteriolar resistance, resulting in hyperperfusion of some tissues, which for specific tissues is time dependent. The increased central blood volume results in increased pulmonary artery pressure and a decline in vital capacity. The effect of increased hydrostatic pressure due to the depth of submersion does not affect stroke volume; however, a bradycardia results in decreased cardiac output, which is further reduced during breath holding. Hydrostatic compression, however, leads to elastic loading of the chest wall and negative pressure breathing. The depth-dependent increased work of breathing leads to augmented respiratory muscle blood flow. The blood flow is increased to all lung zones with some improvement in the ventilation-perfusion relationship. The cardiac-renal responses are time dependent; however, the increased stroke volume and cardiac output are, during head-out immersion, sustained for at least hours. Changes in water temperature do not affect resting cardiac output; however, maximal cardiac output is reduced, as is peripheral blood flow, which results in reduced maximal exercise performance. In the cold, maximal cardiac output is reduced and skin and muscle are vasoconstricted, resulting in a further reduction in exercise capacity.

Titrating Pt Surface with CO Molecules.

Identification and quantification of the surface sites on Pt nanoparticles are essential for developing more active electrocatalysts for many practical devices such as fuel cells and electrochemical fuel generators. In this work, we studied CO adsorption from dissolved CO in an H2SO4 electrolyte solution on a polycrystalline Pt film electrode held at a constant potential in the underpotential hydrogen deposition region using in situ attenuated total reflectance-surface-enhanced IR absorption spectroscopy (ATR-SEIRAS). Slowing down the adsorption rate by limiting the CO addition rate to the solution allows the individual CO molecules arriving at the Pt surface to rearrange, move to, and occupy their most energetically favorable sites. By using ATR-SEIRAS spectroscopy to follow the stepwise CO adsorption process, one can identify and quantify the Pt surface sites along with uncovering the CO adsorption energetic sequence. This method of slow CO adsorption on the Pt surface is analogous to the chemical titrations used for quantitative chemical analyses.

Patient blood management: A solution for South Africa.

For more than 70 years the default therapy for anaemia and blood loss was mostly transfusion. Accumulating evidence demonstrates a significant dose-dependent relationship between transfusion and adverse outcomes. This and other transfusion-related challenges led the way to a new paradigm. Patient blood management (PBM) is the application of evidence-based practices to optimise patient outcomes by managing and preserving the patient's own blood. 'Real-world' studies have shown that PBM improves patient outcomes and saves money. The prevalence of anaemia in adult South Africans is 31% in females and 17% in males. Improving the management of anaemia will firstly improve public health, secondly relieve the pressure on the blood supply, and thirdly improve the productivity of the nation's workforce. While high-income countries are increasingly implementing PBM, many middle- and low-income countries are still trying to upscale their transfusion services. The implementation of PBM will improve South Africa's health status while saving costs.

Respiratory muscle training improves swimming endurance at depth.

Respiratory muscle training (RMT) has been shown to improve divers swimming endurance at 4 feet of depth; however, its effectiveness at greater depths, where gas density and the work of breathing are substantially elevated has not been studied. The purpose of this study was to examine the effects of resistance respiratory muscle training (RRMT) on respiratory function and swimming endurance at 55 feet of depth (270.5 kPa). Nine male subjects (25.9 +/- 6.8 years) performed RRMT for 30 min/day, 5 d/ wk, for 4 wks. Pre- and Post RRMT, subjects swam against a pre-determined load (70% VO2 max) until exhausted. As indices of respiratory muscle strength, maximal inspiratory and expiratory pressures were measured before and immediately following the swims pre- and post-RRMT. These measurements showed that ventilation was significantly lower during the swims and, at comparable swim duration, that the respiratory muscles were considerably less fatigued following RRMT. The reduced ventilation was due to a lower breathing frequency following RRMT. The ventilatory changes following RRMT coincided with significantly increased swimming time to exhaustion (approximately 60%, 31.3 +/- 11.6 vs. 49.9 +/- 16.0 min, pre- vs. post-RRMT, p < 0.05). These results suggest respiratory muscle fatigue limits swimming endurance at depth as well as at the surface and RRMT improves performance.

Prognostic factors for death after surgery for small intestinal neuroendocrine tumours.

BACKGROUND: Neuroendocrine tumours of the small intestine (SI-NETs) are rare gastrointestinal neoplasms with an annual incidence of about one per 100 000. Patients with apparently similar tumours have variable outcomes. The aim of this study was to identify postoperative prognostic factors identifiable after initial surgery. METHODS: This was a nested case-control study of patients with SI-NETs who were treated between 1961 and 2001. Data were retrieved from the Swedish Cancer Registry. Patients who died from the SI-NET and corresponding controls (who outlived cases by at least 1 month), matched by age at diagnosis and calendar period, were included. Sex, postoperative symptoms, postoperative 5-hydroxyindoleacetic acid (5-HIAA) values, European Neuroendocrine Tumor Society (ENETS) stage, insufficiency of the tricuspid valve, radical secondary surgery and secondary malignancy were studied as potential prognostic factors. RESULTS: In total, 1122 patients were included (561 cases, 561 controls). Postoperative factors of prognostic importance included hormone-related symptoms, stage IV disease, raised levels of 5-HIAA, insufficiency of the tricuspid valve, secondary surgery not being macroscopically radical and a second malignancy. CONCLUSION: Stage and symptomatic disease are important prognostic factors in SI-NET.

The effect of body position on inspiratory airflow in divers.

UNLABELLED: The purpose of this study was to examine the possibility that body position influences inspiratory airflow of submerged subjects. Our previous studies have suggested that for a given (negative) inspired gas pressure, exercising divers experience more dyspnea in the prone than in the upright position. METHODS: Six subjects performed maximal inspiratory efforts recorded as esophageal pressure (balloon catheter); simultaneously inspiratory flow and lung volumes were recorded. To standardize static lung load, the subjects' chest pressure centroids (representing the average water pressure on the chest) were held at a constant depth (0.33m) throughout the experiments. RESULTS: Recordings of peak inspiratory flow (PIF) showed a decrease of 25.56 +/- 4.14% (mean +/- SD, P = 0.01) from the submerged upright position mean flow of 6.19 +/- 1.48 (l/s) to the submerged prone mean flow of 4.37 +/- 0.69 (l/s). Nadiral esophageal pressure exhibited no significant differences: 5.40 +/- 4.32% (mean +/- SD, P = 0.512), from the upright mean pressure of (-) 51.70 +/- 24.09 (cm H2O) to the prone mean pressure of (-) 48.53 +/- 25.86 (cm H2O). CONCLUSIONS: The significant decrease in PIF when changing from the upright to the prone position, suggests a difference in the patency of the extra-thoracic airways. The higher water pressure exerted on the neck in the prone position may explain this difference. The similarity of pleural pressures in the two positions indicates that the differences in PIF were not due to differences in inspiratory effort.

Resistive respiratory muscle training improves and maintains endurance swimming performance in divers.

Respiratory work is increased during exercise under water and may lead to respiratory muscle fatigue, which in turn can compromise swimming endurance. Previous studies have shown that respiratory muscle training, conducted five days per week for four weeks, improved both respiratory and fin swimming endurance. This training (RRMT-5) consisted of intermittent vital capacity breaths (twice/minute) against spring loaded breathing valves imposing static and resistive loads generating average inspiratory pressures of approximately 40 cmH2O and expiratory pressures of approximately 47 cmH2O. The purpose of the present study (n = 20) was to determine if RRMT 3 days per week (RRMT-3) would give similar improvements, and if continuing RRMT 2 days per week (RRMT-M) would maintain the benefits of RRMT-3 in fit SCUBA divers. Pulmonary function, maximal inspiratory (P(insp)) and expiratory pressures (P(exp)), respiratory endurance (RET), and surface and underwater (4 fsw) fin swimming endurance were determined prior to and after RRMT, and monthly for 3 months. Pulmonary function did not significantly improve after either RRMT-3 or RMMT-5; while P(insp) (20 and 15%) and P(exp) (25 and 11%), RET (73 and 217%), surface (50 and 33%) and underwater (88 and 66%) swim times improved. VO2, VE and breathing frequency decreased during the underwater endurance swims after both RRMT-3 and RRMT-5. During RRMT-M P(insp) and P(exp) and RET and swimming times were maintained at post RRMT-3 levels. RRMT 3 or 5 days per week can be recommended to divers to improve both respiratory and fin swimming endurance, effects which can be maintained with RRMT twice weekly.

Alveolar gas composition before and after maximal breath-holds in competitive divers.

The urge to breathe, as stimulated by hypercapnia, is generally considered to cause a breath-hold diver to end the breath-hold, and pre-breath hold hyperventilation has been suggested to cause hypoxic loss of consciousness (LOC) due to the reduced urge to breathe. Competitors hyperventilate before "Static Apnea", yet only 10% surface with symptoms of hypoxia such as loss of motor control (LMC) or LOC. We hypothesized that the extensive hyperventilation would prevent hypercapnia even during prolonged breath-holding and we also recorded breaking-point end-tidal PO2 in humans. Nine breath-hold divers performed breath-holds of maximal duration according to their chosen "Static Apnea" procedure. They floated face down in a swimming pool (28 degrees C). The only non-standard procedure was that they exhaled into a sampling tube for end-expiratory air, before starting the breath-hold and before resuming breathing. Breath-hold duration was 284 +/- 25 (SD) seconds. End-tidal PCO2 was 18.9 +/- 2.0 mmHg before apnea and 38.3 +/- 4.7 mmHg at apnea termination. End-tidal PO2 was 131.7 +/- 2.7 mmHg before apnea and 26.9 +/- 7.5 mmHg at apnea termination. Two of the subjects showed LMC after exhaling into the sampling tube; their end-tidal PAO2 values were 19.6 and 21.0 mmHg, respectively. End-tidal CO2 was normocapnic or hypocapnic at the termination of breath-holds. These data suggest that the athletes rely primarily on the hypoxic stimuli, probably in interaction with CO2 stimuli to determine when to end breath-holds. The severity of hypoxia close to LOC was similar to that reported for acute hypobaric hypoxia in humans.

Negative pressure oxygen breathing and head-down tilt increase nitrogen elimination.

Negative pressure breathing (NPB) increases the rate of nitrogen elimination, which is thought to be due to an increase in cardiac output due to augmented venous return to the heart. Hyperoxia, however, decreases the rate of nitrogen elimination. The effect of hyperoxia on the increase in nitrogen elimination during NPB is not known. We hypothesized that NPB as and head down tilt (HDT), which is also thought to increase cardiac output, would counteract the detrimental effects of hyperoxia on nitrogen elimination. Nitrogen elimination was measured in 12 subjects while they lay supine breathing 100% O2 supplied at atmospheric pressure (control), -10 cm H2O (NPOB(-10)), and -15 cm H2O (NPOB(-15)). Nitrogen elimination was also measured in the subjects while they breathed 100% O2 supplied at atmospheric pressure in the supine position with a 6 degrees HDT. Over a two-hour washout period, NPOB significantly increased nitrogen elimination by more than 14%, although there was no significant difference between NPOB(-10) and NPOB(-15). HDT also significantly increased nitrogen elimination by almost 8%. Neither NPOB nor HDT significantly affected cardiac output but calf blood flow was significantly lower during NOPB(-15). Combining NPB or HDT with 100% oxygen breathing appear to be useful means of increasing nitrogen elimination and should be considered in situations where this effect may be beneficial, such as with oxygen prebreathing prior to decompression.

Effects of respiratory muscle training on respiratory CO2 sensitivity in SCUBA divers.

Typically, ventilation is tightly matched to CO2 production. However, in some cases CO2 is retained (SCUBA diving). One factor behind hypoventilation in divers may be low respiratory CO2 sensitivity. If this is due to inadequate respiratory muscle performance it might be remedied by respiratory muscle training (RMT). We retrospectively investigated respiratory CO2 sensitivity prior to and after RMT in several groups of SCUBA divers. CO2 sensitivity (slope of expired ventilation as a function of inspired PCO2) was measured with a rebreathing technique in 35 subjects with diving experience. RMT consisted of either isocapnic hyperventilation or intermittent vital capacity breaths (twice/minute) against spring loaded breathing valves imposing static and resistive loads generating average inspiratory pressures of approximately 40 cmH2O and expiratory pressures of approximately 47 cmH2O; RMT was performed 30 min/day, 3 or 5 days/week for 4 weeks. Based on pre-RMT CO2 sensitivity the subjects were divided into three groups: low sensitivity: < 2 l/min/mmHg PCO2, normal: 2-4 l/min/mmHg, and high sensitivity: > 4 l/min/mmHg of inspired PCO2. The normal group had a Pre-RMT CO2 sensitivity of 2.88 +/- 0.60 and a post RMT sensitivity of 2.51 +/- 0.88 l/min/mmHg (Mean +/- SD, n = 19, p = n.s). Response in low sensitivity subjects increased from 1.41 +/- 0.32 to 2.27 +/- 0.53 (n = 10, p = 0.002,) while in the high sensitivity group it decreased from 5.41 +/- 1.25 to 2.90 +/- 0.32 l/min/mmHg (n = 6, p = 0.003). These preliminary findings showed that 46% of the subjects had abnormal sensitivity, and suggest that RMT may normalize it in hypo- and hyper-ventilating divers. If the present results are verified, RMT may be an effective means of enhancing safety in CO2 retaining divers.

Increased intramural expression of plasminogen activator inhibitor type 1 after balloon injury: a potential progenitor of restenosis.

OBJECTIVES: This study was performed to determine whether altered gene expression of plasminogen activator inhibitor type 1 (PAI-1) occurs within the arterial wall after experimentally induced balloon injury. BACKGROUND: PAI-1, known to inhibit fibrinolysis in the circulation and to be present within atherosclerotic vessels, may influence proteolysis in the arterial wall and neointimal formation after angioplasty. METHODS: In rabbit carotid arteries subjected to balloon injury, both PAI-1 gene and protein expression were assayed sequentially with the use of Northern blotting, in situ hybridization and immunohistochemical studies. RESULTS: In uninjured, normal vessels PAI-1 messenger ribonucleic acid (mRNA) was not detectable by Northern blotting or in situ hybridization. However, injury was followed within 3 h by increases in PAI-1 mRNA (3.2 kb) of 5.9-fold compared with that in contralateral control carotid arteries (Northern blots). PAI-1 mRNA was detectable by in situ hybridization early after injury first in adventitia; after 24 h it was particularly prominent in the media. From 1 to 4 weeks after injury it was consistently detectable and was localized in neointimal vascular smooth muscle and endothelial cells at a time when neointimal thickening was marked. Cells of both types exhibited PAI-1 protein detected immunohistochemically. In vessels maintained in organ culture after balloon injury in vivo, sustained increases in PAI-1 activity appeared in conditioned media as well. CONCLUSIONS: Our results indicate that balloon injury simulating angioplasty in patients induces intramural expression of PAI-1 in vascular smooth muscle and endothelial cells. The decreased cell surface fibrinolytic activity likely to result from the increased PAI-1 expression may initiate or exacerbate mural thrombosis. Accordingly, excessive stimulation with clot-associated mitogens may stimulate vascular smooth muscle cell proliferation, which, coupled with increased accumulation of extracellular matrix attributable to decreased plasmin-mediated degradation, may contribute to restenosis.

Tissue nitrogen elimination in oxygen-breathing pigs is enhanced by fluorocarbon-derived intravascular micro-bubbles.

UNLABELLED: The present study tested the hypothesis that intravascular micro bubbles generated by i.v. infusion of a 2 % dodecafluoropentane (DDFP) emulsion will enhance tissue denitrogenation during oxygen breathing. Eleven spontaneously breathing pentobarbital anesthetized pigs were studied. Six pigs were treated with 0.08 ml/kg of DDFP-emulsion infused over 30 min and five (control) pigs received a matching dose of emulsion vehicle. Circulatory parameters were recorded. The pigs were connected via a tracheal tube to a closed circuit oxygen-primed breathing loop allowing volume measurements and nitrogen analysis by gas chromatography every 7 min. The nitrogen washout was recorded for up to four hrs in each group. The cumulative nitrogen yield during oxygen breathing was considerably larger in treated animals than in controls. Thus, the amount of nitrogen eliminated in the controls in 120 min was achieved already after 65 min in animals treated with the DDFP-emulsion. Blood pressure and cardiac output remained stable and were not different between the two groups during the four hrs of nitrogen washout. The central venous oxygen tension was significantly higher in the treated animals during oxygen breathing than in the controls. This difference was, in all probability due to enhanced oxygen transport by the micro-bubbles. CONCLUSION: Intravascular micro-bubbles generated by i.v. infusion of a small dose of 2 % DDFP-emulsion very effectively enhanced denitrogenation by oxygen breathing and deserve study as a means to improve prevention and treatment of decompression sickness.

Stimulation of migration of human aortic smooth muscle cells by vitronectin: implications for atherosclerosis.

OBJECTIVE: Migration of smooth muscle cells into the neointima has been implicated in atherogenesis. Vitronectin, a serum factor that promotes cell spreading and attachment, accumulates in atherosclerotic human tissues. The aim of this study was to determine the role of vitronectin and its receptor (integrin alpha V beta 3) in migration of smooth muscle cells. METHODS: Human aortic smooth muscle cell migration was studied in modified Boyden chambers. Expression of vitronectin receptor was determined by northern blotting of receptor mRNA and immunoprecipitation of receptor protein. RESULTS: Vitronectin dose dependently increased smooth muscle cell migration by an amount comparable to that induced by platelet derived growth factor, (PDGF)-BB. Antiserum to alpha V beta 3 diminished vitronectin driven migration. Northern blot analysis showed low constitutive expression of alpha V and beta 3 mRNA by smooth muscle cell and rapid induction with transforming growth factor beta (TGF-beta) and thrombin. Immunoprecipitation confirmed increased synthesis of the alpha V beta 3 vitronectin receptor complex by TGF-beta or thrombin. Smooth muscle cells pretreated with TGF-beta or thrombin showed increased vitronectin driven migration. cAMP suppressed induction of migration, but inhibition of protein kinase C increased it. CONCLUSIONS: These results show that vitronectin-induced human aortic smooth muscle cell migration is mediated by alpha V beta 3 vitronectin receptor and expression of the receptor is induced by TGF-beta and thrombin, which in turn induce vitronectin driven, vitronectin receptor modulated smooth muscle cell migration.