A case of endobronchial mucosa-associated lymphoid tissue (MALT) lymphoma successfully treated with radiotherapy and a review of the literature.

A 60-year-old man was noted to have an elevated lesion in the right mainstem bronchus on chest computed tomography (CT) during his annual medical checkup 3 years previously. The lesion had gradually increased in size. FDG-PET showed no accumulation. Bronchoscopy revealed 5 nodular smooth surface protrusions on the ventral surface of the right mainstem bronchus, with the largest lesion that measured 5 mm in diameter. Biopsy showed diffuse infiltration of small lymphocytes, positive for CD20 and subsequently diagnosed with mucosa-associated lymphoid tissue (MALT) lymphoma. The lesions disappeared on chest CT after radiotherapy, and no recurrence has been observed after 5 years. We reviewed 48 cases of endobronchial MALT lymphoma in the literature and provided a comprehensive review of the literature to date including our case.

Silent Hypoxemia in COVID-19 Pneumonia.

In patients suffering from Coronavirus Disease 2019 (COVID-19), dyspnoea is less likely to occur despite hypoxemia. Even if the patient develops severe hypoxemia, it cannot be detected from subjective symptoms. In other words, it becomes more serious without the person or the surroundings noticing it. Initially less talked about, hypoxemia without dyspnoea (silent hypoxemia or happy hypoxia: hypoxemia that does not coincide with dyspnoea) is now experienced in many institutions. Dyspnoea is defined as "the unpleasant sensation that accompanies breathing." Dyspnoea occurs when afferent information is transmitted to the sensory area. Receptors involved in the development of dyspnoea include central and peripheral chemoreceptors, chest wall receptors, lung receptors, upper respiratory tract receptors and corollary discharge receptors. In the present study, we considered mechanisms mediating the silent hypoxemia through three cases experienced at our hospital as a dedicated coronavirus treatment hospital. We have treated about 600 people infected with COVID-19, of which about 10% were severe cases. In the present study, the patients' condition was retrospectively extracted and analysed. We investigated three typical cases of COVID-19 pneumonia admitted to our hospital (men and women between the ages of 58 and 86 with hypoxemia and tachypnoea). Silent hypoxemia is not entirely without dyspnoea, but hypoxemia does not cause dyspnoea commensurate with its severity. The virus may have specific effects on the respiratory control system. In our cases, respiratory rate significantly increased with hypoxemia, and hyperventilation occurred. Therefore, information about hypoxemia is transmitted from the carotid body. Since hyperventilation occurs, it is suggested that information is transmitted to effectors such as respiratory muscles. The fact that these patients did not feel the unpleasant sensation indicates that information is not accurately transmitted to the sensory area of the cerebral cortex. These cases suggest that there may be a problem somewhere in the path from the respiratory centre to the sensory area.

Hypobaric hypoxia is not a direct dyspnogenic factor in healthy individuals at rest.

Dyspnea consists of various uncomfortable respiratory sensations. It is believed that hypoxia causes dyspnea, but whether hypoxia is a direct dyspnogenic factor remains uncertain. We investigated whether hypoxia has a direct dyspnogenic effect. We evaluated changes in vital signs, arterial blood gases, SaO2, CaO2, Borg scale, and Mini-Mental State Examination in seven mountain climbers by using a hypobaric hypoxic chamber in which the barometric pressure was lowered to the simulated altitude of 4500 m. PaO2 and CaO2 both decreased significantly as the simulated altitude increased. On the other hand, Borg scale score which reflects dyspnea showed no significant difference. At the simulated altitude of 4500 m, Borg scale score was 1.5 ± 1.2 (mean ± SD), despite the presence of absolute hypoxia (PaO2, 46.8 ± 8.3T; CaO2, 16.4 ± 0.6 mL/dL). These results suggest that hypoxia is not a direct dyspnogenic factor in healthy individuals capable of breathing without restriction at rest.

Significant relationship between platelet activation and apnea-hypopnea index in patients with obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for arterial thrombosis, which is associated with high cardiovascular morbidity and mortality. To investigate the possible involvement of activated platelets, we evaluated the relationship between severity of OSAS and appearance of platelet aggregates (a marker of activated platelets) in 35 OSAS patients. Platelet aggregates were quantitatively determined by means of flow cytometry. There was a significant correlation between platelet aggregates and apnea-hypopnea index in the severe (AHI≥30 events/hour) group (r=0.756, p<0.001), but not in the mild-moderate (5≤AHI<30 events/hour) group (r=-0.032, p=0.905). The results indicate that the appearance of platelet aggregates increases with an increase in the severity of OSAS.

Polycythemia and changes in erythropoietin concentration in rats exposed to intermittent hypoxia.

It is not clear whether blood hemoglobin concentration ([Hb]) increases with an increase in the exposure period of intermittent hypoxia (IHx) and reaches a constant level. Furthermore, it is not known whether plasma erythropoietin concentration ([EPO]) also increases with an increase in the exposure period. Using a rat model, first, we evaluated changes in [EPO] every hour after single exposure of 10% O(2) for 120 min in order to determine a peak level of [EPO]. Second, we evaluated the effect of IHx of 10% O(2), 120 min/day for 0 (control), 1, 2, 3, 4, 6 and 8 weeks on [Hb], arterial blood pressure (BP), heart rate (HR), arterial blood gases (ABGs) and [EPO]. [EPO] increased after cessation of the single hypoxic exposure, reached a peak at 1 h, and decreased gradually to the control levels within 18 h. IHx of 10% O(2), 120 min/day, produced a time-dependent increase in [Hb], and [Hb] reached a constant level after the exposure for 6 weeks. BP increased after the exposure for 4 weeks and remained elevated. There was no significant difference in HR and ABGs. [EPO] increased significantly and remained elevated at the same level for 1-3 weeks, however, the peak level of [EPO] declined markedly after [Hb] reached a constant level.

A case of HAPE on K2 and literature review.

HAPE (High Altitude Pulmonary Edema) is a serious and fatal disease in mountains. Early diagnosis and immediate descent are important for successful treatment. One of the authors (GS), who was healthy and a well trained climber, participated in the expedition to K2 (8611 m) in 2006 and developed HAPE. Under the severe environmental condition, it was difficult to evaluate his condition in its early stage. The earliest symptoms were nonspecific for HAPE as reported in many papers. Neither had he suffered from HAPE on the previous expeditions. These facts probably delayed the diagnosis in spite of its typical onset. This is a rare case report by a medical doctor who suffered from HAPE. The present case may remind the climbers of the difficulties in diagnosing HAPE on a mountain.

[Effects of chronic repetitive hypercapnic hypoxia on systemic and pulmonary hemodynamics in a rat model].

We determined the effects of chronic repetitive hypoxia and hypercapnic hypoxia on systemic and pulmonary hemodynamics using an animal model simulating sleep apnea syndrome (SAS). Fifty-six rats were divided into the hypoxia (Pao2 44-46Torr) and the hypercapnic hypoxia (Pao2 44-46Torr, Paco2 48-49Torr) group. The hypoxic gas or the hypercapnic hypoxic gas was flushed into the chamber for 1 min, then air was flushed allowing return of gas fractions to ambient levels for 3 min. Each cycle was repeated 6h/day for 5 weeks. In the hypoxia group, there was no significant difference in baseline blood pressure (BP) and heart rate (HR) between controls and the exposure group. Only HR increased transiently during hypoxia in both controls and the exposure group. RV/(LV + S) did not change after 5 weeks of exposure. In the hypercapnic hypoxia group, there was no significant difference in baseline BP and HR between controls and the exposure group. However, acute BP elevation and transient bradycardia were induced during hypercapnic hypoxia, and the magnitude of the changes increased with an increase in the exposure period. RV/(LV + S) increased after 5 weeks of exposure. Phentolamine attenuated acute BP elevation and atropine abolished bradycardia, suggesting an increased sympathetic and parasympathetic tone. The results suggest that hypercapnia associated with hypoxia plays an important role in developing cardiovascular changes in SAS.

The threshold of the intermittent hypoxic exposure period to elicit polycythemia in rats.

It is not yet clear whether there is an intermittent hypoxia (IHx) threshold to elicit polycythemia and blood pressure elevation, and whether blood hemoglobin concentration ([Hb]) increases with an increase in the hypoxic exposure period. We have previously shown that repetitive exposure to 10% O2 for 60 min/day for up to 5 weeks does not produce polycythemia. In the present study, we evaluated the effect of IHx of 10% O2, 120 min/day for 1, 2, 3 and 4 weeks on [Hb], arterial blood pressure, heart rate and arterial blood gases in the rat. IHx of 10% O2, 120 min/day induced polycythemia at 1 week and produced a time-dependent increase in [Hb] from 0 week to 4 weeks. Arterial blood pressure significantly increased during IHx exposure for 4 weeks probably due to a combination of an increased sympathetic activity as well as increased blood viscosity. The IHx threshold for polycythemia might exist between 60 min/day and 120 min/day in this level of hypoxia.

Exposure to hypoxia results in uneven pulmonary blood flow distribution prior to pulmonary edema.

The effects of hypoxia on pulmonary arterial pressure (PAP) and on development of pulmonary edema, ascertained by changes in lung water and pulmonary vascular permeability were studied in rats using bronchoalveolar lavage (BAL). Rats were exposed to hypobaric hypoxia (P(B) = 290 Torr) for 24 h followed by 4 h of normobaric hypoxia (F(IO)2 0.07) (Hx). Controls were rats maintained in a normoxia (Nx). Mean PAP was 28.3 +/- 0.8 mmHg in Hx, and 18.8 +/- 1.7 mmHg in Nx (mean +/- SD). The wet-to-dry lung weight ratio was significantly higher in Hx. The ratio of fluorescence activity between BAL fluid and plasma 4 h after i.v. injection of FITC-albumin was higher in Hx, suggesting an increased pulmonary microvascular permeability in Hx. In a separate study, pulmonary blood flow distribution, measured after 10 min of hypoxia (F(IO)2 0.07) using non-radioactive microspheres, was significantly more heterogeneous than Nx, suggesting a non-homogeneous hypoxic pulmonary vasoconstriction. The combined data of both studies suggest that hypoxia induces heterogeneous pulmonary blood flow distribution which is followed by increased vascular permeability and the development of pulmonary edema.

[A national survey of results of lung volume reduction surgery (LVRS) for pulmonary emphysema in Japan].

We made a national questionnaire survey of conditions and results of lung volume reduction surgery (LVRS) performed for pulmonary emphysema in 273 hospitals. The survey covered: number of hospitals, number of patients, indications, operative procedures, improvement of FEV1% and dyspnea score, mortality, cause of death, 5-year survival rate, characteristics of patients who died, and current conditions of LVRS. The response rate was 63%. A total of 619 patients at 41 hospitals underwent LVRS. The most common types of surgical procedure were bilateral LVRS through median sternotomy and unilateral LVRS with video-assisted thoracoscopic surgery (VATS), followed by bilateral LVRS with VATS. Postoperative improvement in FEV1% averaged 39%. Dyspnea improved in 80% of patients. Mortality rate was 1.9% (8 of 432 cases). Postoperative infectious diseases, namely pneumonia and sepsis, were common causes of death. The 5-year survival was 65 +/- 8%. The causes of death over 5 years were respiratory failure in 60%, malignant neoplasms in 17%, cardiovascular accidents in 13% and others in 10%. The number of operations and hospitals decreased in 2002, compared to 2001.

[Pulmonary hypertension and cor pulmonale in COPD].

The prevalence and natural history of cor pulmonale in COPD are not yet clear. Factors that are known to contribute to the development of pulmonary hypertension in COPD include hypoxic pulmonary vasoconstriction(HPV), remodeling of pulmonary arteries, destruction of the pulmonary capillary bed and polycythemia. In addition, impaired mechanisms of endothelium-dependent vasodilation such as reduced NO synthesis or release, and abnormal secretion of vasoconstrictor peptides play an important role in the development of pulmonary hypertension. These factors can lead to right ventricular hypertrophy and right heart failure. Pulmonary hypertension develops late in the course of COPD (stage III) usually after the development of severe hypoxemia and is associated with a poor prognosis of the disease.

[Clinical aspect of diffuse alveolar hemorrhage syndrome].

Thirteen cases of diffuse alveolar hemorrhage (DAH) were encountered in our Hospital between January 1996 and October 2001. Eight patients were men and five were women, their mean age being 59.5 +/- 19.2 years (range, 18-88 years). Three patients had systemic lupus erythematosus (SLE), three (23%) had polyarteritis nodosa (including microscopic PN), one (7.7%) had allergic granulomatous angitis, one (7.7%) had Goodpasture syndrome, one (7.7%) had MPO-ANCA-associated vasculitis, one (7.7%) had Behçet's disease, one (7.7%) had chronic heart failure caused by mitral stenosis, one (7.7%) had chronic renal failure (etiology unknown), and the last had no particular disorder. Nine episodes (69%) had occurred as complications of primary diseases, four (31%) as the first symptoms of underlying diseases. Prognosis was poor in the former cases but in the latter, the prognosis was relatively favorable.

Regional vulnerability to chronic hypoxia and chronic hypoperfusion in the rat brain.

The purpose of this study was to compare the pathological findings of injury induced by chronic hypoperfusion and by chronic hypoxia in rat brain. Adult male Wistar rats were divided into three groups: chronic hypoperfusion (n=5), chronic hypoxia (n=5), and normal control groups (n=5). Hypoperfusion was induced by ligation of the bilateral carotid arteries under 2.5% halothane anesthesia. Chronic hypoxia was induced by keeping the animals in a chamber with an atmosphere of 10% O(2) in N(2) for 3 weeks. Twelve weeks later (chronic hypoperfusion group) and 3 weeks later (chronic hypoxia group), the animals were sacrificed and perfused through the femoral artery with a fixative containing 4% paraformaldehyde. Hematoxylin and eosin staining was done in all sections in the three groups, and the number of normal-appearing cells was counted. Normal-appearing cells in CA3 were significantly decreased in the chronic hypoperfusion group compared with those in the chronic hypoxia group, although neurons in CA1, CA2 and CA4 in both groups were equally damaged. We concluded that the CA3 hippocampus shows different vulnerabilities to chronic hypoperfusion and chronic hypoxia, possibly owing to a difference in the kinds of glutaminergic receptors.

[Evaluation of cardiopulmonary function in Japanese Himalayan climbers to the Himalayas underin a hypobaric hypoxic chamber].

The Tokai University and Tibet University Scientific Friendship Expedition 2001 succeeded in reaching the summit of Kula Kangri (7,538 m) in the Himalrayas without supplementary O2 in May, 2001. Before this expedition, the cardiopulmonary function of all members was evaluated using a hypobaric hypoxic chamber in which the barometric pressure was gradually lowered to a simulated altitude of 6000 m. Whenever a member's PaO2 was lower than 40 torr during the experiment, supplementary O2 was given. The results were divided into two groups, Group A and Group B, according to whether supplementary O2 was used. Group A subjects did not need O2 even at an altitude of 6,000 m, whereas Group B subjects did when they reached an altitude of 5,000 m. Seven the eight Group A members had climbed mountains over 4,000 m several times, whereas twelve out of the thirteen members of Group B had no mountaineering experience. The mean PaO2 and PaCO2 of Group A at 6000 m were 41.9 torr and 31.9 torr, respectively, while those of Group B at 5000 m were 35.8 torr and 35.9 torr. There was a significant difference in the degree of hyperventilation between Group A and Group B. No difference was observed between the two groups in systolic and diastolic arterial blood pressure, but the heart rate in Group B increased significantly under hypoxia. These results suggest that the experience of climbing mountains over 4000 m may lead to significant differences in cardiopulmonary function under hypoxia.