Effect of hyperbaric oxygen treatment on irradiated oral mucosa: microvessel density.

The aim of this study was to evaluate the effect of hyperbaric oxygen therapy (HBOT) on microvascular tissue and cell proliferation in the oral mucosa. Twenty patients, aged 51-78 years, were allocated randomly to a treatment or a control group. All had a history of radiotherapy (50-70 Gy) to the orofacial region 2-6 years previously. Tissue samples were taken from the irradiated buccal oral mucosa before HBOT and at 6 months after treatment. In the control group, tissue samples were taken on two occasions, 6 months apart. The samples were subjected to immunohistochemistry staining: double staining with CD31 and D2-40 for microvessels, or Ki-67 for the analysis of cell proliferation. Blood vessel density and area were significantly increased after HBOT (P=0.002-0.041). D2-40-positive lymphatic vessels were significantly increased in number and area in the sub-epithelial area (P=0.002 and P=0.019, respectively). No significant differences were observed in the control group. There were no significant differences in Ki-67-expressing epithelial cells between the two groups. It is concluded that the density and area of blood and lymphatic vessels in the irradiated mucosa are increased by HBOT 6 months after therapy. Epithelial cell proliferation is not affected by HBOT.

Predictors for PaO2 and hypoxemic respiratory failure in COPD-A three-year follow-up.

BACKGROUND: Knowledge about predictors for developing hypoxemia in the course of chronic obstructive pulmonary disease (COPD) progression is limited. The objective of the present study was to investigate predictors for overall PaO2, for a potential change in PaO2 over time, and for first occurrence of hypoxemia. METHODS: 419 patients aged 40-76 years with COPD GOLD stages II-IV underwent clinical and pulmonary function measurements, including repeated arterial blood gases over three years. Airway obstruction, lung hyperinflation, markers of systemic inflammation and cardiovascular health, exacerbation frequency, smoking habits, and body composition were tested as possible predictors of PaO2 and first episode of hypoxemia. RESULTS: In multivariate adjusted longitudinal analyses, forced expiratory volume in 1 second, total lung capacity and functional residual capacity (all in% predicted), resting heart rate and fat mass index were all associated with overall PaO2 (all P < 0.005). We found no change in PaO2 over time (ρ = 0.33), nor did we find evidence that any of the tested variables predicted change in PaO2 over time. In multivariate adjusted survival analyses, functional residual capacity and resting heart rate were predictors of episodic hypoxemia (both ρ < 0.005). CONCLUSIONS: This longitudinal study identified pulmonary, cardiac and metabolic risk factors for overall PaO2 and episodic hypoxemia, but detected no change in PaO2 over time.

Effect of hyperbaric oxygen treatment on oxygen tension and vascular capacity in irradiated skin and mucosa.

The aim of this study was to evaluate the effect of hyperbaric oxygen therapy (HBOT) on vascular function and tissue oxygenation in irradiated facial skin and gingival mucosa. Twenty-two patients, aged 51-90 years, were randomly allocated to a treatment or control group. All had a history of radiotherapy (50-70 Gy) to the orofacial region 2-20 years previously. Skin and mucosal perfusion were recorded with laser Doppler flowmetry (LDF). Tissue oxygenation was recorded by transcutaneous oximetry (TcPO(2)). Measurements were taken before HBOT and 3 and 6 months after a mean of 28 HBOT sessions (partial pressure of oxygen of 240 kPa for 90 min). For control subjects, measurements were taken on two occasions 6 months apart. After HBOT, blood flow in mucosa and skin after heat provocation increased significantly (P < 0.05). TcPO(2) increased significantly in the irradiated cheek (P < 0.05), but not at reference points outside the field of radiation. There were no differences between the 3- and 6-month follow-ups. In the control group, no significant changes in LDF or TcPO(2) were observed. It is concluded that oxygenation and vascular capacity in irradiated facial skin and gingival mucosa are increased by HBOT. The effects persist for at least 6 months.

Mortality among professional divers in Norway.

BACKGROUND: Diving operations are technically complex, and the underwater environment poses a high risk of fatal or near miss accidents. Furthermore, long-term effects of diving on bone, the central nervous system and the lung have been observed in divers who have not experienced any diving-related accidents. AIMS: To compare total and cause-specific mortality among Norwegian professional divers by class of diving certificate, relative to the general population. METHODS: Data on mortality were obtained for divers in the Norwegian Inshore Diving Registry, which comprises data on all divers with a certificate valid for professional diving after 1980. By August 2010, 5526 male divers born between 1950 and 1990 were identified, 3130 of whom were fully certified professional divers. The rest of the Norwegian male population born in the same period (1 604 147) served as referents. Data on mortality were obtained by linkage to the Cause of Death Registry. RESULTS: Mortality was 23 per 1000 in professional divers and 24 per 1000 in referents. The hazard ratio was 0.79 (confidence interval [CI] 0.63-0.997). Diving-related accidents and suicide were the most common causes of death among divers. Both were significantly more common among divers with the higher level diving certificates. CONCLUSIONS: Overall, mortality in professional divers was lower than that of the general population. However, professional divers had a higher risk of dying from work-related accident or suicide.

Exhaled nitric oxide concentration upon acute exposure to moderate altitude.

The purpose of this study was to assess immediate changes in the partial pressure of nitric oxide (NO) in exhaled gas (PE NO ) in healthy trained subjects who were acutely exposed to moderate altitude. One group of nine and another group of 20 healthy subjects were exposed to an ambient pressure of 728 hPa (546 mmHg) corresponding to an altitude of 2800 m for 5 and 90 min, respectively, in an altitude chamber. PE NO was measured offline by sampling exhaled gas in tight metal foil bags at 5, 30, 60, and 90 min. A correction for increased expiratory flow rate due to gas density effects at altitude was performed (PE NO corr). PE NO was significantly decreased by 13-16%, while the fraction of NO in exhaled gas (FE NO) was increased by 16-19% compared to sea level. There was no significant change in PE NO corr after exposure to altitude for 5, 30, 60, and 90 min. We conclude that there was no change in PENO upon arrival at altitude after correcting for gas density effects on expiratory flow rate. Corrections for altitude effects must be done before comparing measurements performed at different altitudes when using measurements of FENO to monitor athletes who have asthma during training at altitude.

Reproducibility of transcutaneous oximetry and laser Doppler flowmetry in facial skin and gingival tissue.

Laser Doppler flowmetry (LDF) and transcutaneous oximetry (TcPO(2)) are non-invasive techniques, widely used in the clinical setting, for assessing microvascular blood flow and tissue oxygen tension, e.g. recording vascular changes after radiotherapy and hyperbaric oxygen therapy. With standardized procedures and improved reproducibility, these methods might also be applicable in longitudinal studies. The aim of this study was to evaluate the reproducibility of facial skin and gingival LDF and facial skin TcPO(2). The subjects comprised ten healthy volunteers, 5 men, aged 31-68 years. Gingival perfusion was recorded with the LDF probe fixed to a custom made, tooth-supported acrylic splint. Skin perfusion was recorded on the cheek. TcPO(2) was recorded on the forehead and cheek and in the second intercostal space. The reproducibility of LDF measurements taken after vasodilation by heat provocation was greater than for basal flow in both facial skin and mandibular gingiva. Pronounced intraday variations were observed. Interweek reproducibility assessed by intraclass correlation coefficient ranged from 0.74 to 0.96 for LDF and from 0.44 to 0.75 for TcPO(2). The results confirm acceptable reproducibility of LDF and TcPO(2) in longitudinal studies in a vascular laboratory where subjects serve as their own controls. The use of thermoprobes is recommended. Repeat measurements should be taken at the same time of day.

Reduced nitric oxide concentration in exhaled gas after exposure to hyperbaric hyperoxia.

The objective of this study was to evaluate exhaled nitric oxide concentration (FENO) and exhaled breath condensate (EBC) pH and H2O2 as biochemical markers of pulmonary oxygen toxicity in association with hyperbaric oxygen (HBO2) therapy. FENO, EBC pH and H2O2 were measured during the course of a 4 week HBO, treatment period, and the responses to a single HBO2 exposure at the start and end of the treatment period were assessed. The HBO2 exposure was at a pressure of 240 kPa for 90 min 5 days a week for 4 weeks. Eight patients undergoing HBO2 therapy and eight control subjects participated in the study. There was a reduction in FENO immediately after HBO2 exposure of 33.1 (SD = 7.8) % on Day 1 and 40.7 (SD = 8.9) % on Day 25. EBC pH was reduced after the first exposure only. Baseline F(E)NO and EBC pH and H2O2 measured before the HBO2 exposures did not change throughout the HBO2 treatment period. A single HBO2 exposure induces a significant transient decrease in FENO. Repeated exposures do not appear to induce inflammatory processes in the lung associated with an increase in FENO.

No changes in lung function after a saturation dive to 2.5 MPa with intermittent reduction in Po2 during decompression.

Decompression stress and exposure to hyperoxia may cause a reduction in transfer factor of the lung for carbon monoxide and in maximal aerobic capacity after deep saturation dives. In this study lung function and exercise capacity were assessed before and after a helium-oxygen saturation dive to a pressure of 2.5 MPa where the decompression rate was reduced compared with previous deep dives, and the hyperoxic exposure was reduced by administering oxygen intermittently at pressures of 50 and 30 kPa during decompression. Eight experienced divers of median age 41 years (range 29-48) participated in the dive. The incidence of venous gas microemboli was low compared with previous deep dives. Except for one subject having treatment for decompression sickness, no changes in lung function or angiotensin converting enzyme, a marker of pulmonary endothelial cell damage, were demonstrated. The modified diving procedures with respect to decompression rate and hyperoxic exposure may have contributed to the lack of changes in lung function in this dive compared with previous deep saturation dives.

Post-exercise reduction in diffusing capacity of the lung after moderate intensity running and swimming.

A reduction in transfer factor of the lung for carbon monoxide (Tl(co)) is a consistent finding after saturation dives and is reported after some open sea air dives. Several diving associated factors may contribute to this reduction in Tl(co) including hyperoxia, venous gas microembolism, increased breathing resistance and immersion. Exercise, which inevitably is associated with open sea diving, may itself cause a reduction in Tl(co) up to at least 12 hours post-exercise. Six trained swimmers and six trained runners who had never dived performed 30 min moderate intensity swimming and running on different days and in random order at approximately 75% of their maximal heart rate. Lung function including a flow-volume loop and Tl(co) was measured 30 min before and 60-90 min after exercise. There were no significant changes in dynamic lung volumes or maximal expiratory flow rates, but there was a reduction in Tl(co) of 4.5 (SD = 4.8) and 4.7 (SD = 4.6) % after swimming and running respectively (p < 0.01). There was no difference in this response between runners and swimmers, and the response was not associated with lung size. Even moderate exercise preceding measurements of Tl(co) should generally be accounted for, and this effect may contribute significantly to lung function changes immediately after open sea dives.

Electroencephalography and magnetic resonance imaging in neurological decompression sickness.

The purpose of this study was to evaluate the use of electroencephalography (EEG) and magnetic resonance imaging (MRI) in the clinical evaluation of acute decompression sickness (DCS) in the central nervous system (CNS). Twenty-one patients treated because of acute DCS in the CNS during 1999-2001 were included, 15 patients with clinical cerebral DCS and five with clinical spinal cord DCS. Seven patients had abnormalities in their EEG, five with cerebral DCS and two with spinal cord DCS. MRI showed high intensity lesions in the spinal cord in four patients with clinical spinal cord DCS and in one with clinical cerebral DCS. Cerebral lesions were not identified by MRI in any patient. In conclusion, EEG showed unspecific abnormalities in only one third of the cases. Conventional MRI with a 1.5 T scanner may be of help in the diagnosis of DCS in the spinal cord, but not in the brain. EEG and MRI have low sensitivity in the diagnosis of acute DCS in the CNS. Recompression treatment of DCS should still be guided by clinical neurological examination and assessment of symptoms.

Venous gas embolism in chamber attendants after hyperbaric exposure.

An initial occupational survey (OS) was initiated to investigate the prevalence of venous gas embolism (VGE) in chamber attendants assisting hyperbaric oxygen (HBO2) treatments. Nine female subjects were exposed for three consecutive days to the routine hospital procedure of compressed air exposure to 240 kPa for approximately 115 min with 12 min of terminal oxygen (O2) breathing. VGE was monitored with ultrasound Doppler in 15 min intervals for 2h after the first and third exposure. A follow-up experimental study was completed to investigate whether changed breathing gases and decompression would affect the high incidence of VGE observed in the OS. Ten female subjects were randomly exposed to the routine or revised profile (12 and 24 min of terminal O2 breathing respectively), and a Nitrox profile (breathing gas 40.5% O2 in Nitrogen during 90 min of the isobaric phase). VGE was monitored with transthoracic ultrasound scanner and Doppler. In the OS precordial VGE grade III (Doppler) was observed in five subjects, but median resting precordial VGE was Grade 0 both days and VGE score at all sites were equal Days 1 and 3. In the experimental study, median resting precordial VGE was Grade 0 (Doppler) and Grade 1 (Scanner). VGE Grade III (Doppler) was observed in all series, but VGE scores were not significantly different between the series. We conclude that chamber attendants assisting HBO2 treatment at 240 kPa for approximately 115 min are exposed to a significant decompression stress using the profiles tested in the present study.

Lung function over six years among professional divers.

AIMS: To analyse longitudinal changes in pulmonary function in professional divers and their relation with cumulative diving exposure. METHODS: The study included 87 men at the start of their education as professional divers. At follow up one, three, and six years later, 83, 81, and 77 divers were reexamined. The median number of compressed air dives in the 77 divers over the follow up period was 196 (range 37-2000). A group of non-smoking policemen (n = 64) were subjected to follow up examinations in parallel with the divers. Assessment of lung function included dynamic lung volumes, maximal expiratory flow rates, and transfer factor for carbon monoxide (Tl(CO)). The individual rates of change of the lung function variables were calculated by fitting linear regression lines to the data, expressed as percent change per year. RESULTS: The annual reductions in forced vital capacity (FVC) and forced expired volume in one second (FEV(1)) were 0.91 (SD 1.22) and 0.84 (SD 1.28) per cent per year in divers, which were significantly higher than the reductions in the policemen of 0.24 (SD 1.04) and 0.16 (SD 1.07) per cent per year (p < 0.001). The annual reduction in the maximal expiratory flow rates at 25% and 75% of FVC expired (FEF(25%) and FEF(75%)) were related to the log(10) transformed cumulative number of dives in a multiple regression analysis (p < 0.05). The annual reductions in Tl(CO) were 1.33 (SD 1.85) and 0.43 (SD 1.53) per cent per year in divers and policemen (p < 0.05). CONCLUSIONS: FVC, FEV(1), maximal expiratory flow rates, and Tl(CO) were significantly reduced in divers over the follow up period when compared with policemen. The contrasts within and between groups suggest that diving has contributed to the reduction in lung function.

Effects of normobaric hyperoxia on water content in different organs in rats.

Pulmonary oxygen toxicity is a dose-dependent effect on alveolar epithelial and endothelial cells resulting in pulmonary oedema. Any concomitant effects on systemic capillary endothelium would be expected to result in capillary leakage and an increase in the tissues' water content. Total tissue water (TTW) in different organs was therefore studied in freely moving rats exposed to 100% O2 at normobaric pressure for 24 or 48 h, and compared to air-breathing control rats. The TTW for the following tissues was measured: Trachea, left bronchus, left lung, left and right ventricle, left kidney, skin (left paw-hindlimb), skin (back of the rat), left brain, left eye and thigh muscle left side. There was a significant increase in TTW of the lung accompanied by pleural effusion after 48 h of oxygen exposure as expected in all exposed animals. There was a small increase in TTW of the paw only, and a small decrease or no change in other tissues after 24 and 48 h of exposure. We conclude that there is no evidence of systemic capillary dysfunction as measured by tissue water content after exposure to hyperoxia in a dosage causing pulmonary oedema.

Increased lung compliance in response to a moderate hyperoxic exposure.

With deep saturation diving a reduction in vital capacity caused by oxygen toxicity may be opposed by a training effect of respiratory muscles due to increased gas density and work of breathing. We measured lung and chest wall mechanics before and after a 28-day saturation dive to a pressure of 0.25 MPa with the same profile of oxygen exposure as in a deep dive to a pressure of 3.7 MPa; 40 kPa during the isopression phase and 50 kPa during the decompression phase. Eight males aged 22-28 yr served as subjects. The measurements included dynamic lung volumes, static lung compliance, lung recoil pressure, and maximal respiratory pressures. Only one subject had decreased lung compliance and increased recoil pressure after the dive. The others had an increase in compliance and decrease in recoil pressure. There was a significant increase in inspiratory lung compliance (P = 0.041) and a trend for a decrease in lung recoil pressure (P = 0.061). We found no change in forced vital capacity, but decreases in forced expired volume in 1 s (P = 0.049) and forced midexpiratory flow rate (P = 0.009) were noted. There were no changes in maximal respiratory pressures. These findings are opposite to the classical findings associated with pulmonary oxygen toxicity. The results may reflect an increase in surfactant production and turnover as an early adaptive response to hyperoxic stress.

Lipid rafts exist as stable cholesterol-independent microdomains in the brush border membrane of enterocytes.

Glycosphingolipid/cholesterol-rich membranes ("rafts")can be isolated from many types of cells, but their existence as stable microdomains in the cell membrane has been elusive. Addressing this problem, we studied the distribution of galectin-4, a raft marker, and lactase, a protein excluded from rafts, on microvillar vesicles from the enterocyte brush border membrane. Magnetic beads coated with either anti-galectin-4 or anti-lactase antibodies were used for immunoisolation of vesicles followed by double immunogold labeling of the two proteins. A morphometric analysis revealed subpopulations of raft-rich and raft-poor vesicles by the following criteria: 1) the lactase/galectin-4 labeling ratio/vesicle captured by the anti-lactase beads was significantly higher (p < or = 0.01) than that of vesicles captured by anti-galectin-4 beads, 2) subpopulations of vesicles labeled by only one of the two antibodies were preferentially captured by beads coated with the respective antibody (p < or = 0.01), 3) the average diameter of "galectin-4 positive only" vesicles was smaller than that of vesicles labeled for lactase. Surprisingly, pretreatment with methyl-beta-cyclodextrin, which removed >70% of microvillar cholesterol, did not affect the microdomain localization of galectin-4. We conclude that stable, cholesterol-independent raft microdomains exist in the enterocyte brush border.

Caveolae/lipid rafts in fibroblast-like synoviocytes: ectopeptidase-rich membrane microdomains.

Membrane peptidases play important roles in cell activation, proliferation and communication. Human fibroblast-like synoviocytes express considerable amounts of aminopeptidase N/CD13, dipeptidyl peptidase IV/CD26, and neprilysin/CD10, transmembrane proteins previously proposed to be involved in the regulation of intra-articular levels of neuropeptides and chemotactic mediators as well as in adhesion and cell-cell interactions. Here, we report these peptidases in synoviocytes to be localized predominantly in glycolipid- and cholesterol-rich membrane microdomains known as 'rafts'. At the ultrastructural level, aminopeptidase N/CD13 and dipeptidyl peptidase IV/CD26 were found in caveolae, in particular in intracellular yet surface-connected vesicle-like structures and 'rosettes' made up of several caveolae. In addition, clusters of peptidases were seen at the cell surface in flat patches ranging in size from about 60 to 160 nm. Cholesterol depletion of synoviocytes by methyl-beta-cyclodextrin disrupted >90% of the caveolae and reduced the raft localization of aminopeptidase N/CD13 without affecting Ala-p-nitroanilide-cleaving activity of confluent cell cultures. In co-culture experiments with T-lymphocytes, cholesterol depletion of synoviocytes greatly reduced their capability to induce an early lymphocytic expression of aminopeptidase N/CD13. We propose caveolae/rafts to be peptidase-rich 'hot-spot' regions of the synoviocyte plasma membrane required for functional cell-cell interactions with lymphocytes. The peptidases may act in concert with other types of proteins such as receptors and signal transducers localized in these specialized membrane domains.

Exposure to hyperoxia in diving and hyperbaric medicine--effects on blood cell counts and serum ferritin.

A reduction in hemoglobin concentration has been consistently reported after deep saturation dives, whereas reductions in thrombocyte counts and changes in biochemical parameters specific for liver function have been reported after some dives. In this study the contribution of exposure to hyperoxia to these changes were studied. Hemoglobin concentration, blood cell counts, serum ferritin, and biochemical parameters specific for liver damage were measured before and after a shallow 28-day saturation dive to a pressure of 250 kPa with the same hyperoxic exposure (40-50 kPa) as in a deep saturation dive in eight male divers. The same parameters were measured before, during, and after a standard 21-day hyperbaric oxygen (HBO2) treatment series in a selected group of 16 patients (8 male). There were significant reductions in hemoglobin concentrations of 3.8 +/- 4.7% (P = 0.023) and 10.2 +/- 5.3% (P = 0.003) after the HBO2 treatment series and dive, respectively, accompanied with reductions in red cell counts, reticulocyte counts, and hematocrit. There was an increase in ferritin concentrations of 29 +/- 21% (P = 0.002) and 107 +/- 43% (P < 0.001). In contrast to some deep dives, there were no changes in thrombocyte counts or biochemical parameters specific for liver damage. Exposure to hyperoxia contributes significantly to reduced hemoglobin and increased ferritin concentrations after saturation dives. The changes may reflect a shift of iron from synthesis of hemoglobin in the bone marrow to storage in macrophages caused by a downregulation of hemoglobin synthesis, or an increased oxidative stress. The changes are too small to be of clinical significance with respect to diving and HBO2 treatment.

[Hyperbaric oxygen treatment for radiation reactions]. / Hyperbar oksygenbehandling ved strålereaksjoner.

BACKGROUND: A national hyperbaric centre was established in 1994 at Haukeland Hospital with responsibility for all hyperbaric oxygen (HBO) treatment in Norway. In hypoxic tissues with symptomatic radiation reactions, hyperbaric oxygen induces the formation of collagen and angiogenesis resulting in permanently improved local microcirculation. MATERIAL AND METHODS: 234 patients received elective HBO treatment at Haukeland Hospital in 1997 with a total of 4,048 treatments. All 47 patients treated for radiation reactions in the pelvic area in 1997 received a questionnaire 3-15 months after HBO therapy; 81% responded. RESULTS: Rectal bleeding and haematuria were reported as much improved in 61% and 55% respectively, while bladder incontinence was much improved in 46%. INTERPRETATION: This treatment modality may be an alternative in symptomatic radiation reactions of the urinary bladder and the bowel when conventional treatment has given unsatisfactory results.

Lung function over the first 3 years of a professional diving career.

OBJECTIVES: To characterise diving exposure and pulmonary function in professional divers at the start of their formal education and during the first 3 years of their professional career. METHODS: The study included 87 men at the start of their education as professional divers. At follow up 1 and 3 years after the school 83 and 81 divers respectively were re-examined. Assessment of lung function included dynamic lung volumes and flows and transfer factor for carbon monoxide (Tl(CO)). RESULTS: 69 Divers had preschool SCUBA diving experience and had a median number of 70 dives (range 2-3000) to a median maximal depth of 40 (range 10-73) metres. During the 15 week introductory diving course, they had 44 dives (range 38-50) in the depth range 10-50 metres. The median number of dives over the follow up period was 95 (range 0-722) to a maximal median depth of 38 (range 0-98) metres. At the start of the diving course there were no differences in forced vital capacity (FVC), forced expired volume in 1 second (FEV(1)), and in Tl(CO) between the 69 pre-exposed divers and the 18 never exposed divers. The FVC was significantly larger than predicted in both groups. At follow up at 3 years there was a significant reduction in mean (SD) FEV(1) of 1.8% (6.5), in forced mid-expiratory flow rate (FEF(25-75%)) of 6.5% (11.7) and in forced expiratory flow at 75% of FVC expired (FEF(75%)) of 10.4% (16. 8). There was no change in FVC. The Tl(CO) was significantly decreased by 4.6% (8.8). No significant effects were found of cumulative diving exposure, including the number of dives, on the relative changes of any of the lung function variables. CONCLUSIONS: The results indicate that divers initially belong to a selected group with large FVC. Exposure to diving may contribute to changes in pulmonary function, mostly affecting small airways conductance.