• The Korean Journal of Gastroenterology
• /
• v.72 no.6
• /
• pp.325-328
• /
• 2018

위마비증(gastroparesis)이나 만성 구역 구토 증후군(chronic unexplained nausea and vomiting)으로 인한 구역과 구토에 대한 치료는 일반적으로 사용하는 위장관 촉진제에 만족스럽지 못한 경우가 많고, 여러 부작용으로 인하여 장기적으로 사용하기 어려워 보다 효과적인 치료 방법이 필요하다. 최근 미국에서 발표된 본 연구는 위마비증이나 연관 증후군 환자에서 구역과 구토 증상을 줄이기 위한 aprepitant(neurokinin-1 receptor antagonist) 치료의 효과를 분석한 것으로, 향후 일반적인 치료에 불응성 위마비증 환자에서 새로운 약제 사용을 시도해볼 수 있어 소개하고자 한다. 본 Aprepitant for the Relief of Nausea (APRON) 연구는 기질적 질환을 배제하기 위하여 최근 2년 이내 위내시경이 정상이며, 적어도 6개월 이상 조기 포만감(early satiety), 식후 만복감(postprandial fullness), 팽만감(bloating) 그리고 명치부 통증(epigastric pain)을 유발하는 증상과 함께 만성적인 구역이 있는 18세 이상의 성인 중 4시간의 위배출 검사를 시행받은 환자를 대상으로 하였다. 객관적인 지표로 0점에서 45점까지 보이는 9-증상 Gastroparesis Cardinal Symptom Index(GCSI)가 2주 이상 총 21점 이상이며, 0-100 mm의 visual analog scale (VAS)의 7일간의 구역 증상 평균 25 mm 이상인 환자를 대상으로 하였다. 일주일에 3일 이상 narcotics를 사용하였거나 와파린이나 pimozide, terfenadien, astemizole, cisapride를 복용하였던 환자, 2배 이상으로 간 효소 수치상승을 보이거나 Child-Pugh score 10점 이상, aprepitant에 알레르기를 보이는 환자는 제외되었다. 그렇지만 metoclopramide나 erythromycin을 안정적으로 사용 중인 환자는 제외되지 않았다. 위배출 검사는 2시간에서 60% 이상 남아 있거나 4시간에서 10% 이상 남아 있는 경우에 지연된 것으로 정의되었으며, 지연된 위배출 검사 결과 자체는 환자의 등록 기준에 포함되진 않았다. 등록 기준에 포함된 환자는 1:1로 무작위 배정되어 하루 한 번 125 mg의 aprepitant 복용군과 위약군으로 나누어져 연구가 진행되었으며, 약제 복용 4주간 2주 간격으로, 그리고 복용 후 2주 뒤까지 구역 증상의 호전 정도와 약제 안전성을 확인하였다. 이러한 효과를 판정하기 위하여 환자가 방문하는 동안 GCSI를 포함한 Patient Assessment of Upper GI Symptoms (PAGI-SYM), Gastrointestinal Symptom Rating Scale, daily VAS, daily diary version of the GCSI 그리고 정신 측정 도구와 삶의 질 도구인 Patient health Questionnaire 15와 Short Form 36 version이 측정되었다. 구역에 대한 aprepitant와 위약의 치료 효과의 일차적 판정은 이전 항암 요법에 대한 aprepitant 연구와 같이 28일 평균 VAS 25 mm 미만이거나 치료 전 7일간의 VAS와 비교하여 28일 치료 기간 동안 25 mm 이상 감소한 경우로 정의하였고, 이차 결과는 구역의 매일 시간, 치료 중 구역이 없는 날짜의 퍼센트, PAGI-SYM score의 개선 등으로 확인하였다. 2013년 4월부터 2015년 7월까지 총 126명의 환자가 등록되어 aprepitant군 63명, 위약군 63명으로 무작위 배정되었다. 전체의 57%인 72명에서 위배출 지연이 보였으며, 나머지 43%에서는 정상 또는 빠른 위배출 소견을 보여 만성적으로 설명할 수 없는 구역과 구토에 포함된 환자군으로 확인되었다. 또한 29%에서 당뇨를 가지고 있었으며, 8%에서 수면제를 사용하고 있었다. 최종적으로 aprepitant군은 59명, 위약군은 63명이 연구를 끝까지 종료하였다. 일차 결과에서 aprepitant 군 46%, 위약군 40%의 구역 호전을 보여 두 치료군 간에 통계적으로 의미 있는 차이는 보이지 않았다(상대 위험도 1.2, 95% CI: 0.8-1.7; p=0.43). 그러나 일차 분석의 두 가지 척도(28일 평균 VAS 25 mm 미만과 기저 VAS보다 평균 28일 VAS의 25 mm 이상 감소)를 모두 함께 고려한 민감도 분석에서는 aprepitant군이 37% (22/59)로 위약군의 17%(11/63)에 비하여 통계적으로 의미 있는 구역의 호전을 보였다(상대 위험도 2.1, 95% CI: 1.1-4.1; p=0.01). 또한 이차 분석을 살펴보면 aprepitant군에서 PAGI-SYM 중증도 지수로 확인하였을 때, 구역(1.8 vs. 1.0; p=0.005)과 구토(1.6 vs. 0.5; p=0.001)의 중증도 및 매일 구역 시간의 감소를 보였고, 28일 동안 구역이 없는 날짜의 퍼센트 증가 소견을 보였다. 다른 이차 결과 분석에서 aprepitant군이 PAGI-SYM 중증도 지수의 GCSI 종합 점수(1.3 vs. 0.7; p=0.001), 상당한 증상호전, 구역 구토의 세부 점수, 팽만감 세부 점수 그리고 위식도 역류 증상 점수에서 호전을 보였고, 매일 일기로 표현한 daily diary version of the GCSI에 상복부 통증 중증도, 전체 증상 그리고 Gastrointestinal Symptom Rating Scale의 종합 점수에서 호전을 보였다. 연구 중 발생한 부작용은 주로 경증과 중등도 정도의 부작용이 주로 발생하였지만, aprepitant군(35% vs. 17% 위약군, p=0.04)에서 더 많이 발생하였다. 결론적으로 위마비증 또는 위마비증 유사 증후군으로 인한 만성 구역 및 구토 환자의 무작위 시험에서 aprepitant는 VAS 점수를 통한 주요 결과를 분석하였을 때는 구역의 중증도를 호전시키지 못하였지만 다른 이차적 결과에 대해서는 위약군에 대하여 호전 소견을 보였다. 따라서 aprepitant에 효과적인 반응을 보이는 위마비증 환자를 감별하는 추가 임상시험이 필요할 것으로 판단된다.

• Journal of Korean Society of Forest Science
• /
• v.21 no.1
• /
• pp.1-34
• /
• 1974

The author intended to investigate external and internal changes in the cone structure, changes in water content, sugar, fat and protein during the period of seed maturation which bears a proper germinability. The experimental results can be summarized as in the following. 1. Male flowers 1) Pollen-mother cells occur as a mass from late in April to early in May, and form pollen tetrads through meiosis early and middle of May. Pollen with simple nucleus reach maturity late in May. 2) Stamen number of a male flower is almost same as the scale number of cone and is 69-102 stamens. One stamen includes 5800-7300 pollen. 3) The shape is round and elliptical, both of a pollen has air-sac with $80-91{\mu}$ in length, and has cuticlar exine and cellulose intine. 4) Pollen germinate in 68 hours at $25^{\circ}C$ with distilled water of pH 6.0, 2% sugar and 0.8% agar. 2. Female flowers 1) Ovuliferous scales grow rapidly in late April, and differentiation of ovules begins early in May. Embryo-sac-mother cells produce pollen tetrads through meiosis in the middle of May, and flower in late May. 2) The pollinated female flowers show repeated divisions of embryo-sac nucleus, and a great number of free nuclei form a mass for overwintering. Morphogenesis of isolation in the mass structure takes place from the middle of March, and that forms albuminous bodies of aivealus in early May. 3. Formation of pollinators and embryos. 1) Archegonia produce archegonial initial cells in the middle and late April, and pollinators are produced in the late April and late in early May. 2) After pollination, Oespore nuclei are seen to divide in the late May forming a layer of suspensor from the diaphragm in early June and in the middle of June. Thus this happens to show 4 pro-embryos. The organ of embryos begins to differentiate 1 pro-embryo and reachs perfect maturation in late August. 4. The growth of cones 1) In the year of flowering, strobiles grow during the period from the middle of June to the middle of July, and do not grow after the middle of August. Strobiles grow 1.6 times more in length 3.3 times short in diameter and about 22 times more weight than those of female flower in the year of flowering. 2) The cones at the adult stage grow 7 times longer in diameter, 12-15 times shorter diameter than those of strobiles after flowering. 3) Cone has 96-133 scales with the ratio of scale to be 69-80% and the length of cone is 11-13cm. Diameter is 5-8cm with 160-190g weight, and the seed number of it is 90-150 having empty seed ratio of 8-15%. 5. Formation of seed-coats 1) The layers of outer seed-coat become most for the width of $703{\mu}$ in the middle of July. At the adult stage of seed, it becomes $550-580{\mu}$ in size by decreasing moisture content. Then a horny and the cortical tissue of outer coats become differentiated. 2) The outer seed-coat of mature seeds forms epidermal cells of 3-4 layers and the stone cells of 16-21 layers. The interior part of it becomes parenchyma layer of 1 or 2 rows. 3) Inner seed-coat is formed 2 months earlier than the outer seed-coat in the middle of May, having the most width of inner seed-coat $667{\mu}$. At the adult stage it loses to $80-90{\mu}$. 6. Change in moisture content After pollination moisture content becomes gradually increased at the top in the early June and becomes markedly decreased in the middle of August. At the adult stage it shows 43~48% in cone, 23~25% in the outer seed-coat, 32~37% in the inner seed-coat, 23~26% in the inner seed-coat and endosperm and embryo, 21~24% in the embryo and endosperm, 36~40% in the embryos. 7. The content compositions of seed 1) Fat contents become gradually increased after the early May, at the adult stage it occupies 65~85% more fat than walnut and palm. Embryo includes 78.8% fat, and 57.0% fat in endosperm. 2) Sugar content after pollination becomes greatly increased as in the case of reducing sugar, while non-reducing sugar becomes increased in the early June. 3) Crude protein content becomes gradually increased after the early May, and at the adult stage it becomes 48.8%. Endosperm is made up with more protein than embryo. 8. The test of germination The collected optimum period of Pinus koraiensis seeds at an adequate maturity was collected in the early September, and used for the germination test of reduction-method and embryo culture. Seeds were taken at the interval of 7 days from the middle of July to the middle of September for the germination test at germination apparatus.

• Journal of Korean Society of Forest Science
• /
• v.52 no.1
• /
• pp.58-71
• /
• 1981

Thecodiplosis japonesis is sweeping the Pinus densiflora forests from south-west to north-east direction, destroying almost all the aged large trees as well as even the young ones. The front line of infestation is moving slowly but ceaselessly norhwards as a long bottle front. Estimation is that more than 40 percent of the area of P. densiflora forest has been damaged already, however some individuals could escapes from the damage and contribute to restore the site to the previous vegetation composition. When the stands were attacked by this insect, the drastic openings of the upper story of tree canopy formed by exclusively P. densiflora are usually resulted and some environmental factors such as light, temperature, litter accumulation, soil moisture and offers were naturally modified. With these changes after insect invasion, as the time passes, phytosociologic changes of the vegetation are gradually proceeding. If we select the forest according to four categories concerning the history of the insect outbreak, namely, non-attacked (healthy forest), recently damaged (the outbreak occured about 1-2 years ago), severely damaged (occured 5-6 years ago), damage prolonged (occured 10 years ago) and restored (occured about 20 years ago), any directional changes of vegetation composition could be traced these in line with four progressive stages. To elucidate these changes, three survey districts; (1) "Gongju" where the damage was severe and it was outbroken in 1977, (2) "Buyeo" where damage prolonged and (3) "Gochang" as restored, were set, (See Tab. 1). All these were located in the south temperate forest zone which was delimited mainly due to the temporature factor and generally accepted without any opposition at present. In view of temperature, the amount and distribution of precipitation and various soil factor, the overall homogeneity of environmental conditions between survey districts might be accepted. However this did not mean that small changes of edaphic and topographic conditions and microclimates can induce any alteration of vegetation patterns. Again four survey plots were set in each district and inter plot distance was 3 to 4 km. And again four subplots were set within a survey plot. The size of a subplot was $10m{\times}10m$ for woody vegetation and $5m{\times}5m$ for ground cover vegetation which was less than 2 m high. The nested quadrat method was adopted. In sampling survey plots, the followings were taken into account: (1) Natural growth having more than 80 percent of crown density of upper canopy and more than 5 hectares of area. (2) Was not affected by both natural and artificial disturbances such as fire and thinning operation for the past three decades. (3) Lower than 500 m of altitude (4) Less than 20 degrees of slope, and (5) Northerly sited aspect. An intensive vegetation survey was undertaken during the summer of 1980. The vegetation was devided into 3 categories for sampling; the upper layer (dominated mainly by the pine trees), the middle layer composed by oak species and other broad-leaved trees as well as the pine, and the ground layer or the lower layer (shrubby form of woody plants). In this study our survey was concentrated on woody species only. For the vegetation analysis, calculated were values of intensity, frequency, covers, relative importance, species diversity, dominance and similarity and dissimilasity index when importance values were calculated, different relative weights as score were arbitrarily given to each layer, i.e., 3 points for the upper layer, 2 for the middle layer and 1 for the ground layer. Then the formula becomes as follows; $$R.I.V.=\frac{3(IV\;upper\;L.)+2(IV.\;middle\;L.)+1(IV.\;ground\;L.)}{6}$$ The values of Similarity Index were calculated on the basis of the Relative Importance Value of trees (sum of relative density, frequency and cover). The formula used is; $$S.I.=\frac{2C}{S_1+S_2}{\times}100=\frac{2C}{100+100}{\times}100=C(%)$$ Where: C = The sum of the lower of the two quantitative values for species shared by the two communities. $S_1$ = The sum of all values for the first community. $S_2$ = The sum of all values for the second community. In Tab. 3, the species composition of each plot by layer and by district is presented. Without exception, the species formed the upper layer of stands was Pinus densiflora. As seen from the table, the relative cover (%), density (number of tree per $500m^2$), the range of height and diameter at brest height and cone bearing tendency were given. For the middle layer, Quercus spp. (Q. aliena, serrata, mongolica, accutissina and variabilis) and Pinus densiflora were dominating ones. Genus Rhodedendron and Lespedeza were abundant in ground vegetation, but some oaks were involved also. (1) Gongju district The total of woody species appeared in this district was 26 and relative importance value of Pinus densiflora for the upper layer was 79.1%, but in the middle layer, the R.I.V. for Quercus acctissima, Pinus densiflora, and Quercus aliena, were 22.8%, 18.7% and 10.0%, respectively, and in ground vegetation Q. mongolica 17.0%, Q. serrata 16.8% Corylus heterophylla 11.8%, and Q. dentata 11.3% in order. (2) Buyeo district. The number of species enumerated in this district was 36 and the R.I.V. of Pinus densiflora for the uppper layer was 100%. In the middle layer, the R.I.V. of Q. variabilis and Q. serrata were 8.6% and 8.5% respectively. In the ground vegetative 24 species were counted which had no more than 5% of R.I.V. The mean R.I.V. of P.densiflora ( totaling three layers ) and averaging four plots was 57.7% in contrast to 46.9% for Gongju district. (3) Gochang-district The total number of woody species was 23 and the mean R.I.V. of Pinus densiflora was 66.0% showing greater value than those for two former districts. The next high value was 6.5% for Q. serrata. As the time passes since insect outbreak, the mean R.I.V. of P. densiflora increased as the following order, 46.9%, 57.7% and 66%. This implies that P. densiflora was getting back to its original dominat state again. The pooled importance of Genus Quercus was decreasing with the increase of that for Pinus densiflora. This trend was contradict to the facts which were surveyed at Kyonggi-do area (the central temperate forest zone) reported previously (Yim et al, 1980). Among Genus Quercus, Quercus acutissina, warm-loving species, was more abundant in the southern temperature zone to which the present research is concerned than the central temperate zone. But vice-versa was true with Q. mongolica, a cold-loving one. The species which are not common between the present survey and the previous report are Corpinus cordata, Beltala davurica, Wisturia floribunda, Weigela subsessilis, Gleditsia japonica var. koraiensis, Acer pseudosieboldianum, Euonymus japonica var. macrophylla, Ribes mandshuricum, Pyrus calleryana var. faruiei, Tilia amurensis and Pyrus pyrifolia. In Figure 4 and Table 5, Maximum species diversity (maximum H'), Species diversity (H') and Eveness (J') were presented. The Similarity indices between districts were shown in Tab. 5. Seeing Fig. 6, showing two-dimensional ordination of polts on the basis of X and Y coordinates, Ai plots aggregate at the left site, Bi plots at lower site, and Ci plots at upper-right site. The increasing and decreasing patterns as to Relative Density and Relative Importance Value by genus or species were given in Fig. 7. Some of the patterns presented here are not consistent with the previously reported ones (Yim, et al, 1980). The present authors would like to attribute this fact that two distinct types of the insect attack, one is the short war type occuring in the south temperate forest zone, which means that insect attack went for a few years only, the other one is a long-drawn was type observed at the temperate forest zone in which the insect damage went on continuously for several years. These different behaviours of infestation might have resulted the different ways of vegetational change. Analysing the similarity indices between districts, the very convincing results come out that the value of dissimilarity index between A and B was 30%, 27% between B and C and 35% between A and C (Table 6). The range of similarity index was obtained from the calculation of every possible combinations of plots between two districts. Longer time isolation between communities has brought the higher value of dissimilarity index. The main components of ground vegetation, 10 to 20 years after insect outbreak, become to be consisted of mainly Genus Lespedeza and Rhododendron. Genus Quercus which relate to the top dorminant state for a while after insect attack was giving its place to Pinus densiflora. It was implied that, provided that the soil fertility, soil moisture and soil depth were good enough, Genus Quercuss had never been so easily taken ever by the resistant speeies like Pinus densiflora which forms the edaphic climax at vast areas of forest land. Usually they refer Quercus to the representative component of the undisturbed natural forest in the central part of this country.