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Studies on Ancylostomiasis I. An Experimental Study on Hookworm Infection and Anemia (구충증(鉤蟲症)에 관(關)한 연구(硏究) 제1편(第1篇) 구충(鉤蟲)의 감염(感染) 및 구충성빈혈(鉤蟲性貧血)에 관(關)한 고찰(考奈))

  • Lee, Mun-Ho;Kim, Dong-Jip;Lee, Jang-Kyu;Seo, Byong-Sul;Lee, Soon-Hyung
    • The Korean Journal of Nuclear Medicine
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    • v.1 no.1
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    • pp.55-66
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    • 1967
  • In view of its prevalence in the Far East area, a more detailed knowledge on the hookworm infection is one of the very important medical problems. The present study was aimed to; determine the infectivity of the artificially hatched ancylostoma duodenale larvae in man after its oral administration, evaluate the clinical symptomatology of such infection, determine the date of first appearance of the ova in the stool, calculate the blood loss per worm per day, assess the relation-ships between the ova count, infectivity(worm load), blood loss and severity of anemia. An erythrokinetic study was also done to analyse the characteristics of hookworm anemia by means of $^{59}Fe\;and\;^{51}Cr$. Materials and Methods Ten healthy male volunteers(doctors, medical students and laboratory technicians) with the ages ranging from 21 to 40 years were selected as the experimental materials. They had no history of hookworm infection for preceding several years, and care was taken not to be exposed to reinfection. A baseline study including a through physical examinations and laboratory investigations such as complete blood counts, stool examination and estimation of the serum iron levels was done, and a vermifuge, bephenium hydroxynaphoate, was given 10 days prior to the main experiment. The ancylostoma duodenale filariform larvae were obtained in the following manner; The pure ancylostoma duodenale ova were obtained from the hookworm anemia patients and a modified filter paper method was adopted to harvest larger number of infective larvae, which were washed several times with saline. The actively moving mature larvae were put into the gelatine capsules, 150 in each, and were given to the volunteers in the fasting state with 300ml. of water. The volunteers were previously treated with intramuscular injection of 15mg. of chlorpromazine in order to prevent the eventual nausea and vomiting after the larvae intake. The clinical symptoms and signs mainly of the respiratory and gastrointestinal tracts, appearance of the ova and occult blood in the stool etc. were checked every day for the first 20 days and then twice weekly until the end of the experiment, which usually lasted for about 3 months. Roentgenological survey of the lungs was also done. The hematological changes such as the red blood cell, white blood cell and eosinophil cell counts, hemoglobin content and serum iron levels were studied. The appearance of the ova in the stool was examined by the formalin ether method and the ova were counted in triplicate on two successive days using the Stoll's dilution method. The ferrokinetic data were calculated by the modified Huff's method and the apparent half survival time of the red blood cells by the modified Gray's method. The isotopes were simultaneously tagged and injected intravenously, and then the stool and blood samples were collected as was described by Roche et al., namely, three separate 4-day stool samples with the blood sample drawing before each 4-day stool collection. The radio-activities of the stools ashfied and the blood were separately measured by the pulse-height analyser. The daily blood loss was calculated with the following formula; daily blood loss in $ml.=\frac{cpm/g\;stool{\times}weight\;in\;g\;of\;4-day\;stool}{cpm/ml\;blood{\times}4}$ The average of these three 4-day periods was given as the daily blood loss in each patient. The blood loss per day per worm was calculated by simply dividing the daily blood loss by the number of the hookworm recovered after the vermifuge given twice a week at the termination of the experiment. The iron loss in mg. through the gastrointestinal tract was estimated with the daily iron loss in $mg=\frac{g\;Hgb/100ml{\times}ml\;daily\;blood\;loss{\times}3.40}{100}$ 3.40=mg of iron per g Hgb following formula; Results 1. The respiratory symptoms such as cough and sputum were noted in almost all cases within a week after the infection, which lasted about 2 weeks. The roentgenological findings of the chest were essentially normal. A moderate degree of febril reaction appeared within 2 weeks with a duration of 3 or 4 days. 2. The gastrointestinal symptoms such as nausea, epigastric fullness, abdominal pain and loose bowel appeared in all cases immediately after the larvae intake. 3. The reduction of the red blood cell count was not remarkable, however, the hemoglobin content and especially the serum iron level showed the steady decreases until the end of the experiment. 4. The white blood cells and eosinophil cells, on the contrary, showed increases in parallel and reached peaks in 20 to 30 days after the infection. A small secondary rise was noted in 2 months. 5. The ova first appeared in the stool in 40. 1 days after the infection, ranging from 29 to 51 days, during which the occult blood reaction of the stool became also positive in almost cases. 6. The number of ova recovered per day was 164, 320 on the average, ranging from 89,500 to 253,800. The number of the worm evacuated by vermifuge was in rough correlation with the number of ova recovered. 7. The infectivity of ancylostoma duodenale was 14% on the average, ranging from 7.3 to 20.0%, which is relatively lower than those reported by other workers. 8. The mean fecal blood loss was 5.78ml. per day, with a range of from 2.6 to 11.7ml., and the mean blood loss per worm per day was 0.30ml., with a range of from 0.13 to 0.73ml., which is in rough coincidence with those reported by other authors. There appeared to exist, however, no correlation between the blood loss and the number of ova recovered. 9. The mean fecal iron loss was 2.02mg. per day, with a range of from 1.20 to 3.89mg., which is less than those appeared in the literature. 10. The mean plasma iron disappearance rate was 0.80hr., with a range of from 0.62 to 0.95hr., namely, a slight accerelation. 11. The hookworm anemia appeared to be iron deficiency in origin caused by continuous intestinal blood loss.

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The Patterns of Change in Arterial Oxygen Saturation and Heart Rate and Their Related Factors during Voluntary Breath holding and Rebreathing (자발적 호흡정지 및 재개시 동맥혈 산소포화도와 심박수의 변동양상과 이에 영향을 미치는 인자)

  • Lim, Chae-Man;Kim, Woo-Sung;Choi, Kang-Hyun;Koh, Youn-Suck;Kim, Dong-Soon;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.4
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    • pp.379-388
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    • 1994
  • Background : In sleep apnea syndrome, arterial oxygen saturation($SaO_2$) decreases at a variable rate and to a variable degree for a given apneic period from patient to patient, and various kinds of cardiac arrythmia are known to occur. Factors supposed to affect arterial oxygen desaturation during apnea are duration of apnea, lung voulume at which apnea occurs, and oxygen consumption rate of the subject. The lung serves as preferential oxygen source during apnea, and there have been many reports related with the influence of lung volume on $SaO_2$ during apnea, but there are few, if any, studies about the influence of oxygen consumption rate of an individual on $SaO_2$ during breath holding or about the profile of arterial oxygen resaturation after breathing resumed. Methods : To investigate the changes of $SaO_2$ and heart rate(HR) during breath holding(BH) and rebreathing(RB) and to evaluate the physiologic factors responsible for the changes, lung volume measurements, and arterial blood gas analyses were performed in 17 healthy subjects. Nasal airflow by thermistor, $SaO_2$ by pulse oxymeter and ECG tracing were recorded on Polygraph(TA 4000, Gould, U.S.A.) during voluntary BH & RB at total lung capacity(TLC), at functional residual capacity(FRC) and at residual volume(RV), respectively, for the study subjects. Each subject's basal metabolic rate(BMR) was assumed on Harris-Benedict equation. Results: The time needed for $SaO_2$ to drop 2% from the basal level during breath holding(T2%) were $70.1{\pm}14.2$ sec(mean${\pm}$standard deviation) at TLC, $44.0{\pm}11.6$ sec at FRC, and $33.2{\pm}11.1$ sec at RV(TLC vs. FRC, p<0.05; FRC vs. RV, p<0.05). On rebreathing after $SaO_2$ decreased 2%, further decrement in $SaO_2$ was observed and it was significantly greater at RV($4.3{\pm}2.1%$) than at TLC($1.4{\pm}1.0%$)(p<0.05) or at FRC($1.9{\pm}1.4%$)(p<0.05). The time required for $SaO_2$ to return to the basal level after RB(Tr) at TLC was not significantly different from those at FRC or at RV. T2% had no significant correlation either with lung volumes or with BMR respectively. On the other hand, T2% had significant correlation with TLC/BMR(r=0.693, p<0.01) and FRC/BMR (r=0.615, p<0.025) but not with RV/BMR(r=0.227, p>0.05). The differences between maximal and minimal HR(${\Delta}HR$) during the BH-RB manuever were $27.5{\pm}9.2/min$ at TLC, $26.4{\pm}14.0/min$ at RV, and $19.1{\pm}6.0/min$ at FRC which was significantly smaller than those at TLC(p<0.05) or at RV(p<0.05). The mean difference of 5 p-p intervals before and after RB were $0.8{\pm}0.10$ sec and $0.72{\pm}0.09$ sec at TLC(p<0.001), $0.82{\pm}0.11$ sec and $0.73{\pm}0.09$ sec at FRC(p<0.025), and $0.77{\pm}0.09$ sec and $0.72{\pm}0.09$ sec at RV(p<0.05). Conclusion Healthy subjects showed arterial desaturation of various rates and extent during breath holding at different lung volumes. When breath held at lung volume greater than FRC, the rate of arterial desaturation significantly correlated with lung volume/basal metabolic rate, but when breath held at RV, the rate of arterial desaturation did not correlate linearly with RV/BMR. Sinus arrythmias occurred during breath holding and rebreathing manuever irrespective of the size of the lung volume at which breath holding started, and the amount of change was smallest when breath held at FRC and the change in vagal tone induced by alteration in respiratory movement might be the major responsible factor for the sinus arrythmia.

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Study on Medical Records In ${\ulcorner}$the Historical Records of the Three Kingdoms${\lrcorner}$ ("삼국사기(三國史記)"에 기록된 의약내용(醫藥內容) 분석)

  • Shin, Soon-Shik;Choi, Hwan-Soo
    • Journal of The Association for Neo Medicine
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    • v.2 no.1
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    • pp.35-54
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    • 1997
  • We tried to observe the features of ancient medical practice by analysing the records related to medicine in the book, ${\ulcorner}$the Historical Records of the Three Kingdom${\lrcorner}$ of which content includes the features of medicine in mythology, plague, delivery of twins, drugs, medical system, shamanism, constitutional medicine, psychiatry, forensic medicine, deformity, a spa, medical phrase, health and welfare work, religion, death. physiological anatomy, Taoist medicine, acupuncture, the occult af of transformation and etc. Our initial concern was about where to draw line as of medical field and we defined medicine in more broad meaning. The book ${\ulcorner}$the Historical Records of the Three Kingdoms${\lrcorner}$ describes the world of mythology by way of medicine which is not clearly a conventional one. There appears records of birth of multiple offsprings 7 times in which cases are of triplets or more. Delivering multiple offsprings were rare phenomenon though such fertility was highly admired. This shows one aspect of ancient country having more population meant more power of the nation. Of those medical records conveyed in that book includes stories of childbirth such as giving birth to a son after praying, giving birth to Kim Yoo-shin after 20 months after mother's dream of conception, and a song longing for getting a laudable child. Plagues were prevalent throughout winter to spring season and one can observe various symptoms of plagues in the record. Of these epidemic diseases, cold type might have been more common than the heat one. Appearance of epidemic diseases frequently coincided with that of natural disasters that this suggests a linkage between plague and underlying doctrine on five elements' motion and six kinds of natural factors. There exists only a few names of diseases such as epidemic disease, wind disease, and syndrome characterized by dyspnea. Otherwise there appeared only afflictions that were not specified therefore it remains cluless to keep track of certain diseases of prevalence. Since this ${\ulcorner}$Historical Records of the Three Kingdoms'${\lrcorner}$ wasn't any sort of medical book, words and terms used were not technical kind and most were the ones used generally among lay people. Therefore any mechanisms of the diseases were hardly mentioned. Some of medicinal substances such as Calculus Bovis, Radix Ginseng, Gaboderma Luciderm, magnetitum were also in use in those days. 53 kinds of dietary supplies appears in the records and some of these might have been used as medicinal purpose. Records concerning dicipline of one's body includes activities such as hunting, archery, horseback riding etc. In Shilla dynasty there were positions such as professor of medicine, Naekongbong(內供奉), Kongbong's doctor(供奉醫師), Kongbong's diviner(供奉卜師). As an educational facility, medical school was built at the first year of King Hyoso's reign and it's curricula included various subjects as ${\ulcorner}$Shin Nong's Herbal classic${\lrcorner}$, ${\ulcorner}$Kabeul classic of acupuncture and moxbustion${\lrcorner}$, ${\ulcorner}$The Plain Questions of the Yellow Emperor's Classic of Internal Medicine${\lrcorner}$, ${\ulcorner}$Classic of Acupuncturer${\lrcorner}$, ${\ulcorner}$The Pulse Classic${\lrcorner}$, ${\ulcorner}$Classic of Channels and Acupuncture Points${\lrcorner}$ and ${\ulcorner}$Difficult Classic${\lrcorner}$. There were 2 medical professors who were in charge of education. To establish pharmacopoeia, 2 Shaji(舍知), 6 Sha(史), 2 Jongshaji(從舍知) were appointed. In Baekje dynasty, Department of Herb was maintained. Doing praying for the sake of health, doing phrenology also can be extended to medical arena. Those who survived over 100 years of age appear 3 times in the record, while 98 appears once. The earliest psychiatrist Nokjin differentiated symptoms to apply either therapies using acupuncture and drug or psychotherapy. There appears a case of rape, a case of burying alive with the dead, 8 cases of suicide that can characterize a prototype of forensic medicine. Deformity-related records include phrases as follow: 'there seems protrudent bone behind the head', 'a body which has two heads, two trunks, four arms.', 'a body equipped with two heads' In those times spa can be said to be used as a place for he리ing, convalescence, and relaxation seeing the records describing a person pretended illness and went to spa to enjoy with his friends. Priest doctors and millitary surgeons were in charge of the medical sevice in the period of the Three Kingdoms by the record written by Mookhoja(墨胡子) and Hoonkyeom(訓謙). Poor diet and regimen makes people more vulnerable to diseases. So there existed charity services for those poor people who couldn't live with one's own capacity such as single parents, orphans, the aged people no one to take care and those who are ill. The cause of affliction was frequently coined with human relation. There appeared the phenomenon of releasing prisoners and allowing people to become priests at the time of king's suffering. Besides, as a healing procedure, sutra-chanting was peformed. There appears 10 cases of death related records which varies from death by drowning, or by freezing, death from animals, death from war, death from wightloss and killing oneself at the moment of spouse's death and etc. There also exist certain records which suggest the knowledge of physiology and anatomy in those times. Since the taoist books such as ${\ulcorner}$Book of the Way and Its Power(老子道德經)${\lrcorner}$ were introduced in the period of Three Kingdoms, it can be considered that medicine was also influenced by taoism. Records of higher level of acupuncture, records which links the medicine and occult art of transformation existed. Although limited, we could figure out the medical state of ancient society.

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The Predictable Factors for the Mortality of Fatal Asthma with Acute Respiratory Failure (호흡부전을 동반한 중증천식환자의 사망 예측 인자)

  • Park, Joo-Hun;Moon, Hee-Bom;Na, Joo-Ock;Song, Hun-Ho;Lim, Chae-Man;Lee, Moo-Song;Shim, Tae-Sun;Lee,, Sang-Do;Kim, Woo-Sung;Kim, Dong-Soon;Kim, Won-Dong;Koh, Youn-Suck
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.3
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    • pp.356-364
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    • 1999
  • Backgrounds: Previous reports have revealed a high morbidity and mortality in fatal asthma patients, especially those treated in the medical intensive care unit(MICU). But it has not been well known about the predictable factors for the mortality of fatal asthma(F A) with acute respiratory failure. In order to define the predictable factors for the mortality of FA at the admission to MICU, we analyzed the relationship between the clinical parameters and the prognosis of FA patients. Methods: A retrospective analysis of all medical records of 59 patients who had admitted for FA to MICU at a tertiary care MICU from January 1992 to March 1997 was performed. Results: Over all mortality rate was 32.2% and 43 patients were mechanically ventilated. In uni-variate analysis, the death group had significantly older age ($66.2{\pm}10.5$ vs. $51.0{\pm}18.8$ year), lower FVC($59.2{\pm}21.1$ vs. $77.6{\pm}23.3%$) and lower $FEV_1$($41.4{\pm}18.8$ vs. $61.l{\pm}23.30%$), and longer total ventilation time ($255.0{\pm}236.3$ vs. $98.1{\pm}120.4$ hour) (p<0.05) compared with the survival group (PFT: best value of recent 1 year). At MICU admission, there were no significant differences in vital signs, $PaCO_2$, $PaO_2/FiO_2$, and $AaDO_2$, in both groups. However, on the second day of MICU, the death group had significantly more rapid pulse rate ($121.6{\pm}22.3$ vs. $105.2{\pm}19.4$ rate/min), elevated $PaCO_2$ ($50.1{\pm}16.5$ vs. $41.8{\pm}12.2 mm Hg$), lower $PaO_2/FiO_2$, ($160.8{\pm}59.8$ vs. $256.6{\pm}78.3 mm Hg$), higher $AaDO_2$ ($181.5{\pm}79.7$ vs. $98.6{\pm}47.9 mm Hg$), and higher APACHE III score ($57.6{\pm}21.1$ vs. $20.3{\pm}13.2$) than survival group (p<0.05). The death group had more frequently associated with pneumonia and anoxic brain damage at admission, and had more frequently developed sepsis during disease progression than the survival group (p<0.05). Multi-variate analysis using APACHE III score and $PaO_2/FiO_2$, ratio on first and second day, age, sex, and pneumonia combined at admission revealed that APACHE III score (40) and $PaO_2/FiO_2$ ratio (<200) on second day were regarded as predictive factors for the mortality of fatal asthma (p<0.05). Conclusions: APACHE III score ($\geq$40) and $PaO_2/FiO_2$ ratio (<200) on the second day of MICU, which might reflect the response of treatment, rather than initially presented clinical parameters would be more important predictable factors of mortality in patients with FA.

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The Respiratory and Hemodynamic Effects of Prone Position According to the Level of PEEP in a Dog Acute Lung Injury Model (잡종견 급성폐손상 모델에서 Prone position 시행시 PEEP 수준에 따른 호흡 및 혈류역학적 효과)

  • Lim, Chae-Man;Chin, Jae-Yong;Koh, Youn-Suck;Shim, Tae-Sun;Lee, Sang-Do;Kim, Woo-Sung;Kim, Dong-Soon;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.1
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    • pp.140-152
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    • 1998
  • Background: Prone position improves oxygenation in patients with ARDS probably by reducing shunt Reduction of shunt in prone position is thought to be effected by lowering of the critical opening pressure (COP) of the dorsal lung because the pleural pressure becomes less positive in prone position compared to supine position. It can then be assumed that prone position would bring about greater improvement in oxygenation when PEEP applied in supine position is just beneath COP than when PEEP is above COP. Hemodynamically, prone position is expected to attenuate the lifting of cardiac fossa induced by PEEP. Based on these backgrounds, we investigated whether the effect of prone position on oxygenation differs in magnitude according to the level of PEEP applied in supine position, and whether impaired cardiac output in supine position by PEEP can be restored in prone position. Methods: In seven mongrel dogs, $PaO_2/F_1O_2$(P/F) was measured in supine position and at prone position 30 min. Cardiac output (CO), stroke volume (SV), pulse rate (PR), and pulmonary artery occlusion pressure (PAOP) were measured in supine position, at prone position 5 min, and at prone position 30 min. After ARDS was established with warmed saline lavage(P/F ratio $134{\pm}72$ mm Hg), inflection point was measured by constant flow method($6.6{\pm}1.4cm$ $H_2O$), and the above variables were measured in supine and prone positions under the application of Low PEEP($5.0{\pm}1.2cm$ $H_2O$), and Optimal PEEP($9.0{\pm}1.2cm$ $H_2O$)(2 cm $H_2O$ below and above the inflection point, respectively) consecutively. Results : P/F ratio in supine position was $195{\pm}112$ mm Hg at Low PEEP and $466{\pm}63$ mm Hg at Optimal PEEP(p=0.003). Net increase of P/F ratio at prone position 30 min, however, was far greater at Low PEEP($205{\pm}90$ mm Hg) than at Optimal PEEP($33{\pm}33$ mm Hg)(p=0.009). Compared to CO in supine position at Optimal PEEP($2.4{\pm}0.5$ L/min), CO in prone improved to $3.4{\pm}0.6$ L/min at prone position 5 min (p=0.0180) and $3.6{\pm}0.7$ L/min at prone position 30 min (p=0.0180). Improvement in CO was attributable to the increase in SV: $14{\pm}2$ ml in supine position, $20{\pm}2$ ml at prone position 5 min (p=0.0180), and $21{\pm}2$ ml at prone position 30 min (p=0.0180), but not to change in PR or PAOP. When the dogs were turned to supine position again, MAP ($92{\pm}23$ mm Hg, p=0.009), CO ($2.4{\pm}0.5$ L/min, p=0.0277) and SV ($14{\pm}1$ ml, p=0.0277) were all decreased compared to prone position 30 min. Conclusion: Prone position in a dog with saline-lavaged acute lung injury appeared to augment the effect of relatively low PEEP on oxygenation, and also attenuate the adverse hemodynamic effect of relatively high PEEP. These findings suggest that a PEEP lower than Optimal PEEP can be adopted in prone position to achieve the goal of alveolar recruitment in ARDS avoiding the hemodynamic complications of a higher PEEP at the same time.

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Effects of Percutaneous Balloon Mitral Valvuloplasty on Static Lung Function and Exercise Performance (승모판협착증 환자에서 경피적 풍선확장판막성형술의 폐기능 및 운동부하 검사에 대한 효과)

  • Kim, Yong-Tae;Kim, Woo-Sung;Lim, Chae-Man;Chin, Jae-Yong;Koh, Youn-Suck;Kim, Jae-Joong;Park, Seong-Wook;Park, Seung-Jung;Lee, Jong-Koo;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.1
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    • pp.1-10
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    • 1994
  • Background: Patients with mitral stenosis(MS) have been demonstrated to have a variable degree of pulmonary dysfunction and exercise impairment. The hemodynamic changes of MS can be reversed after percutaneous mitral balloon valvuloplasty(PMV), but the extent and time course of the imporvement in pulmonary function and exercise capacity are not defined. Methods: In order to investigate the early(3 weeks or less)and late(3 months or more) effects of PMV on pulmonary function and determine if the pulmonary dysfunction is reversible even in patients with moderate to severe pulmonary hypertension, we performed the spirometry, measurements of diffusing capacity and lung volumes, and incremental exercise tests in patients with MS before and after PMV. Results: In 46 patients with MS(age: $40{\pm}12$years, male to female ratio: 1:2, mitral valve area: $0.8{\pm}0.2cm^2$) there was a significant increase in FVC(P<0.0025), $FEV_1$(P<0.001), $FEF_{25-75%}$(P<0.001, $FEF_{50%}$(P<0.001), PEF(P<0.0005), MVV(P<0.005), $\dot{V}O_2$max (P<0.0001), and AT(P<0.0001) after average 10 days of PMV. Also there was a significant decrease in DLco(P<0.0001) and DL/VA(P<0.0001). At later($5{\pm}2$months) follow-up in 11 patients, there was no further improvement in any parameters of pulmonary function and exercise test. Twenty nine patients with sinus rhythm were divided into 16 patients with pulmonary arterial pressure(PAP) more than 35mmHg and/or tricuspid regurgitation grade n or more(group A) and 13 patients with PAP less than 35mmHg(group B). Group A Patients had significantly lower FVC(P<0.001), $FEV_1$(P<0.001), DLco(P<0.05), $\dot{V}O_2$ max(P<0.025) and mitral valve area(P<0.025) than group B patients. Group A patients after PMV, showed significant increase in FVC(P<0.001), maximum $O_2$ pulse(P<0.00001) and $\dot{V}O_2$ max(P<0.00025). Both group showed an increase in AT(P<0.0001, P<0.005), but group A showed greater decrease in $\dot{V}E/\dot{V}O_2$ and $\dot{V}E/\dot{V}CO_2$ both at AT(P<0.001, P<0.001) and $\dot{V}O_2$ max(P<0.0001, P<0.0001) after PMV compared with group B. Conclusion: These data suggest that patients with MS can show increased pulmonary function and exercise performance within 1 month after PMV. Patients with moderate to severe pulmonary hypertension had a significant increase in exercise performance compared with those with mild to no pulmonary hypertension and it is thought to be related to a significat decrease of ventilation for a given oxygen consumption at maximum exercise.

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