In recent year, problems caused by the abuse of drugs hove been analyzed in many cases, especially women's pregnancy. The purchasing of drugs without prescription, the misunderstanding of symptoms of pregnancy(such os vomiting, headache) os other ilnnesses, taking medicine during the pregnancy because of a chronic disease has caused many unfortunate cases Apart from these cases, pregnant women may take several medicines such as anodyne, tranquilizers, hypnotics, and diuretics which also cause critical situations. According to Piper and his colleagues 1987 study, in overage, pregnant women in the United Slates intake 3.1 kinds of additional dregs other than prenatal vitamins and mineral supplements. In those cases, both pregnant women and physicians anticipate inborn deformity. Most drugs which have whole body effects get to the unborn child via the placenta, however, many of these drugs do not have adverse effects(Shepard 1986, 1989). In general, drugs present a stronger effect to unborn children than they do to pregnant women due to the baby's excretion and to the drug metabolism that occurs in the mother's body through the placenta. The effects of dregs on unborn children show different results. depending upon the type of drug, dosage, characteristics. gestational weeks, genetic characteristics of the mother an baby, and many other environmental factors.

Doctors who treat pregnant women ore usually cautious in writing their prescription for the drugs. The problem of which psychotropic medications ore sale during pregnancy seems to remain unsolved for many years. Although the rate of absorption is reduced due to a reduced rate of gastric emptying, the extent of absorption of drug is generally unchanged during pregnancy. Plasma volume and total body water increase during pregnancy. There is suggestion that drug metabolizing activity may be increased in pregnancy. Since the pregnancy increase the glomerular filtration rate significantly, drugs mainly eliminated by renal excretion will be cleared more quickly. Factors contributing to the potential teratogenecity of a drug include the type of compound, dose and duration of use, developmental stage of fetus at the time of exposure, and the effect of the drug on fetal pharmacokinetics. All major classes of psychotropic agents should be assumed to diffuse readily across the placenta to the fetus and to be present in some quantity in the breast milk. To decide when and how to start the drug treatment depends on an assessment of the risks related both with and without drug treatment of psychiatric disorders.

Many pregnant women have to receive psychotropic medication during pregnancy and lactation period, despite the proven and assumed risks to the fetus ar neonate. A brief summary of drug metabolism and pharmacodynamics is given. Principles and quidelines of using psychotropic agents during pregancy and lactation period are presented for psychotic disorders, bipolar affective disorders. depression and anxiety disorders, with due consideration for relative benefits and risks of choosing among psychotropic drugs and alternative treatments.

An association study with korean schizophrenic patients(N=75) and normal controls(N=87) was performed to find the relationship between D6S274 polymorphism and schizophrenia using polymerase chain reaction. Nine different alleles of a dinucleotide polymorphism on D6S273 locus were observed in both group. When we compared the frequencies of alleles between schizophrenics and normal controls, there was no significant difference between two groups. To increase homogeneity of schizophrenic group, we divided schizophrenic group by clinical phenotypes such as DSM-IV diagnostic subtype, family history, negative and positive symptoms(PANSS), soft neurologic signs(NES-K). Then we compared the frequencies of alleles among subgroups of clinical phenotypes. there was only significant difference between two subgroups on soft neurologic signs(p<0.05). Although our findings fail to provide on evidence of association between schizophrenia and D6S274 locus, follow-up investigation of this locus may be needed in homogeneous subtypes of schizophrenia and schizophrenic pedigrees.

Lowered immune function in the senile dementia patients may be related to the abnormal metabolism of amyloid precursor protein(APP). To investigate the passibility of an abnormal metabolism of APP in lymphocytes and the possible role of APP in the activation of lymphocytes in senile dementia patients, immunohistochemical study of rat spleen and fluorescence activated cell sorter analysis(FACS) of human lymphocytes with the specific antigen far each lymphocyte and double fluorescent marker with antibody to APP were performed. After stimulating lymphocyte with phytohemagglutinin(PHA), APP mRNA and protein were extracted and quantitfied and the influence of ${\beta}$-amyloid protein($A{\beta}$) specific antibody on lymphocyte division was investigated. In spleen, the majority of cells showing $A{\beta}$ immunoreactivity was found in the T-sell dependent zone. FACS indicated that around 90% $CD_4(+)$ T-cells and 60% of $CD_8(+)$ T-sell were immunoreactive to $A{\beta}$ specific antibody(mAb 4G8). Northern blot analysis shows that lymphocyte APP mRNA was gradually increased to reach a maximum at 3 days after activation with lectin mitogen PHA. However, the $A{\beta}$ immunoreactivity an cell surface remained constant during stimulation with PHA, indicating that the release of APP(secreted farm of APP) might be increased. A very large increase in soluble APP secretion was observed in T-lymphocyte upon activation, but only law levels in the resting stale. Immunoblot was carried out an the protein obtained from cell lysate after stimulating lymphocyte by applying PHA to the cultured lymphocyte, and the result was that $A{\beta}$ band of immature farm under 116 KDa marker decreased as the duration of culture was increased after PHA stimulation. The monoclonal $A{\beta}$ specific(4G8) and polyclonal APP antibodies did not inhibit the [$^3H$]-thymidine uptake of mitogen-treated lymphocytes significantly, suggesting that mitogenesis can not be inhibited by specific $A{\beta}$ and polyclonal APP antibody. These results suggest that APP is expressed in T-cell and might be closely associated with the function of T-cells.

To clarify the mechanism of action of electroconvulsive shack(ECS) in respect to molecular biology, and to detect the quantitative amount of change of c-fos gene expression after ECS in the rat's brain, the authors obtained brain specimens from the striatum, cerebral cortex, hippocampus, and cerebellum. Each brain was removed within 30min. after ECS(130V, 0.5sec) and ECS-sham. Then we performed RT-PCR. The results are 1) ECS was found to affect the expression of immediate early genes. 2) the cerebral cortex and hippocampus was more influenced by ECS thon in the cerebellum and striatum. From these results, we can suggest that ECS is related to the mechanism of cognition, mood, memory which is correlated to cerebral cortex and hippocampus.

This study was aimed to charily the change of NADPH-diaphorase(NADPH-d) and neuropeptide Y(NPY) associated with aging of the rots. To verily the effect of aging of NPY and NADPH-d-positive neurons in the brain stem, the neurons were stained by the immunohistochemical and histochemical method. In the aged group, the number of NADPH-d-positive neurons was significantly decreased in substantia nigra lateralis, supragenual nucleus, raphe magnus nucleus and raphe obscurus nucleus as compared with control group. The number of NADPH-d-positive neurons was not significantly decreased in superior colliculus, interpeduncular nucleus, central gray. dorsal raphe nucleus, retrorubral nucleus, pedunculopontine tegmental nucleus, laterodorsal tegmental nucleus, pontine reticular nucleus, prepositus hypoglossal nucleus and nucleus solitarius of the aged rats. The NADPH-d and NPY-positive neurons were found in the interpeduncular nucleus, central gray, substantia nigra lateralis, laterodorsal tegmental nucleus, nucleus solitarius, raphe magnus nucleus, raphe obscurus nucleus of the control and aged groups. The coexistence of NADPH-d and NPY in the some cell was not found in the brain stem of both groups.

알쯔즈하이머형 치매 환자의 뇌자기공명영상(腦磁氣共鳴影像)에 나타난 뇌위축(腦萎縮) 및 백질병변(白質病變)과 치매 발병연령(發病年齡)과의 상관관계(相關關係)를 밝히기 위해, NINCDS-ADRDA 진단기준(診斷基準)에 의한 조발성(早發性)(n=9) 및 만발성(慢發性)(n=18) 알쯔하이머형 치매군과 각각의 정상대조군(n=10 : n=11)에서 뇌위축(腦萎縮)은 대뇌피질위축(大腦皮質萎縮)과 뇌실확장(腦室擴張)의 체적(體積)을 계측(計測)하고 백질병변(白質病變)은 뇌실주변, 심부백질, 기저핵 및 천막하영역의 백질(白質) 신호(信號) 고강도(高剛度)의 반정량적(半定量的) 평가척도(評價尺度)로 측정하였다. 조발성(早發性) 환자군의 뇌위축(腦萎縮)은 대조군보다 유의하게 컸고(p<0.05) 백질병변(白質病變)에서는 모든 영역에서 차이가 없었으며, 만발성(慢發性) 환자군은 뇌위축(腦萎縮) 정도에서는 대조군과 차이가 없었으나 백질병변(白質病變)은 심부백질 및 시상에서 유의한 차이(p<0.05)를 보였고 나머지 모든 영역에서도 대조군보다 심한 경향을 보였다. 알쯔하이머형 치매가 (1) 뇌위축(腦萎縮)을 주로 보이고 백질병변(白質病變)은 심하지 않은 조기발병군(早期發病郡)과, (2) 백질병변(白質病變)이 두드러지고 뇌위축(腦萎縮)은 심하지 않은 만기발병군(晩期發病郡)으로 나누어질 가능성과 양군의 병태생리(病態生理)가 상이(相異)할 가능성이 시사되었다.

The present study investigated the associations between CT measures and obstetric complications and family history of major mental illnesses. We had the hypothesis of diosthesis-stress model in the etiology of schizophrenia. We had the following findings. 1) Family history of major mental illnesses is inversely related to obstetric complications. 2) Prefrontal sulcal widening and family history of schizophrenia. are inversely related. 3) In female but not in male patients those with family history of schizophrenia tended to have less prefrontal sulcal widening and ventricular brain ratio. These results suggest that more genetic factors contribute to structural brain abnormalities in female than in male patients.

서울대학교병원 신경정신과 외래를 방문한 강박 장애 환자 19명(남자 14명, 여자 5명)과 연령과 성별을 맞춘 정상 대조군 19명을 내상으로 뇌파를 측정하고, 스펙트럼 분석하여 절대력, 상대력, 양반구간 비대칭도 등의 지표를 비교하였다. 그 결과를 뇌 영상화 방법을 사용한 기존의 강박 장애의 이상 소견과 비교하고, 강박 장애 환자에서 특징적으로 나타나는 정량화 뇌파의 지표를 발견하고자 하였다. 결과를 요약하면 다음과 같다. 1) 절대력은 환자군의 Fp1-Fp2, T3-T4 부위에서 theta파의 절대력이 감소가 통계적으로 의미있게 관찰되었다. 2) 상대력은 환자군의 Fp1-Fp2, F3-F4 부위에서 delta파의 증가가 통계적으로 의미있게 관찰되었다. 3) 양반구간 비대칭도의 경우 환자군에서 alpha파와 beta파의 F7/T3-F8/T4의 전극에서 비대칭도가 유의미하게 증가되는 것이 관찰되었다. 이상에서 강박장애에서 나타나는 정량화 뇌파의 각 지표의 소견이 기존의 여러 뇌 영상화 방법을 이용한 강박 장애의 소견과 비슷한 결과를 보이고 있음올 알 수 있고, 이는 강박 장애의 발병 기전과 전두엽과 기저핵의 이상이 서로 관련이 있을 것이라는 가성을 뒷받침해주는 소견이다.

ALDH-I 활성군과 비활성군에서 음주후 정신운동성 수행 및 주관적 평가에 미치는 영향을 비교하였다. 사교적 음주에 상응하는 4종류의 알콜(0.25, 0.5, 0.75, 1.0g/kg)을 투여한 결과 비활성군이 활성군에 비해 보다 부정적인 평가를 하였다. 이는 특히 고용량의 알콜(0.75 및 1.0g/kg)을 투여시 분명하였다. 이러한 결과는 비활성군이 활성군에 비해 알콜에 대한 민감성이 주관적인 판단과 객관적인 수행에서 모두 더 높다는 사실을 반영한다.

흰쥐에 항정신병약물인 haloperidol을 장기간 투여한 뒤 줄무늬체와 후결절 조직에서의 DA $D_2$양 수용체의 변동에 대해 조사하였다. 약물투여군 4군에게 haloperidol을 각기 0.05, 0.15, 0.5, 1.5mg/kg/day이 되게끔 4주간 투여하였다. DA수용체의 변동은 [$^3H$]spiperone을 이용한 결합반응법을 통해 알아 보았다. 정상대조군에 비해 4주 동안 haloperidol을 투여받은 군 모두에서 줄무늬체에서의 DA 수용체의 최대 결합치가 증가한 것으로 나타났다. 기존의 연구에서 사용한 용량보다 대단히 낮은 0.05mg/kg/day을 투여받은 군 역시 유의한 증가를 보여 낮은 용량의 haloperidol이 DA계에 영향을 미치는 것을 알 수 있었다. 후결절조직의 최대결합치는 haloperidol투여군 모두에서 증가한 경향을 볼 수 있었으나 정상대조군에 비해 1.5mg/kg/day투여군에서 유의한 증가를 볼 수 있었다. 본 실혐의 결과로 미루어 낮은 용량의 haloperidol을 장기간 투여했을 때 뇌내 DA계에 수용체증식이 나타나며 항정신병 효과의 발현과도 관련성이 시사된다. 이러한 결과는 최근 거론되고 있는 항정신병약물의 저용량투여를 간접적으로 지지하는 것으로 생각되며 DA계의 연동을 알리는 다른 생물학적 지표와의 관련성을 살피면 흥미로운 결과를 얻을 것으로 기대된다.

본 연구는 알코올사용장애 환자의 혈소판막에 있는 serotonin수용체가 대조군과 비교했을 때 어떤 차이가 있는지 알아보기 위해 시행되었다. $_{125}I-LSD$를 radioligand로 사용하여 포화반응을 해 봄으로서 다음의 결과를 얻었다. 1) 환자군과 대조군간은 $B_{max}$에 있어서만 유의한 차이를 보였다(P<0.0017). 2) Type 1군과 type 2군 사이 역시 $B_{max}$에 있어서만 유의한 차이를 보였다(P<0.0396). 3) 알코올남용군과 알코올의존군 사이의 $B_{max}$와 $K_d$는 모두 유의한 차이가 없었다. 위 결과들은 알코올사용장애의 serotonin 결핍가설을 지지해주며 혈소판의 serotonin 수용체 수의 증가가 알코올사용장애의 trait marker가 될 수 있음을 시사해 준다.

Selective serotonin reuptake inhibitors(SSRIs), as haloperidol, ore metabolized in the cytochrome P450IID6. They can cause inhibition of metabolism of antipsychotics to elevate the serum level of antipsychotics and exacerbate the extrapyramidal symptoms when co-administered with antipsychotics. Among these SSRIs, there ore a few studies about paroxetine compared to fluoxetine or sertraline. In this study, we have intended to know the drug interaction of paroxetine and haloperidol when co-administered two drugs for the chronic schizophrenics by assessing the changes of positive, negative symptoms and extrapyramidal symptoms. for this purpose, we selected 29 subjects, the chronic schizophrenics with no physical problems. They were under maintenance therapy of haloperidol. They ore randomly assigned to placebo group(n=12) and drug group(n=17) by using double blind method. And then, placebo or paroxetine 20mg were administered to the subjects of each groups during 8 week period. We have assessed their psychopathology and extrapyramidal symptoms using Positive and Negative Syndrome Scale(PANSS), Hamilton Rating Scale lor Depression(HRSD), Simpson-Angus Scale at 0, 2, 4, 6, 8 weeks and serum haloperidol, reduced haloperidol levels at 0, 4, 8 weeks during the period. The results ore analysed by using repeated measure MANOVA. 27 subjects have completed the study during 8 weeks. among the subjects, 1) PANSS, HRSD ; no significant difference between groups. 2) Simpson-Angus Scale ; no significant change according to the time and no significant difference between the groups(no group and time effect). 3) Haloperidol and reduced haloperidol level ; no significant change. When co-administered paroxetine and haloperidol, there ore no significant changes of the psychopothology and no significant changes of the extrapyramidal symptoms. In this result, paroxetine seems to be not to affect the metabolism of haloperidol.

Objective : Several studies hove suggested that reduction of cholesterol concentration and low cholesterol level increases suicide, homicide, and depression. The authors sought to determine whether low cholesterol is associated with a history of suicidal attempts among major depression patients. Method : The subjects were 105 patients with major depression, diagnosed according to the DSM-III-R criteria, and 105 age, sex matched healthy controls. Blood was token following overnight fast and serum cholesterol concentration were measured by a enzymatic method Results : The serum cholesterol level was significantly lower in the patients with major depression than in healthy controls($180.4{\pm}43.4mg/dl$ vs $199.7{\pm}35.8mg/dl$). And the serum cholesterol level was significantly lower in major depression patients with suicidal attempt than in major depression patients without suicidal attempt($156.7{\pm}38.2mg/dl$ vs $ 187.8{\pm}42.5mg/dl$) Conclusion : It is hypothesized that low cholesterol level is associated with depression by modifying the serotonin metabolism and the production of interleukin-2, low cholesterol concentration should be further investigated as a potential biological marker of suicidal risk in major depression. Prospective study with serial cholesterol determinations should be done.

It has been known that clozapine is more selective mesolimbic dopamin $D_2$ receptor antagonist and related to 5-HT receptor. In this study, we wxamined the plasma homovanillic acid(HVA), serotonin(5-HT), and 5-hydroxyindoleacetic acid(5-HIM) levels in refractory schizophrenics during clozapine treatment. And we assessed the effects of clozapine on these plasma monoamine metabolites and their association with psychopathology and treatment response. Eight refractory schizophrenic patients(DSM-IV) have entered the study for 3 months during clozapine treatment. Patients were admitted to the inpatient sevice and withdrawn from all neuroleptics for 7-14 days but exceptionally occasional doses of lorazepam was given if needed for behavioral control. The dose of clozapine was titrated as tolerated to 800mg/day. The plasma HVA. 5-HIM and 5-HT levels were measured before treatment and following 2nd week, 4th week, 8th week, and 12th during treatment. Psychopathology was assessed with Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Synrome Scale(PANSS) before and during clozapine treatment. During clozapine treatment, no statistically significant changes were found in plasma HVA, 5-HIM, 5-HT levels, and HVA/5-HIM ratio between baseline and following 2nd week, 4th week, 8th week, 12th week. However, the change in plasma 5-HIAA/5-HT ratio from baseline to 4th week was statistically significant. Generally, changes of plasma HVA, 5-HIAA, 5-HT levels and HVA/5-HIAA ratio were not associated with psychopathology but 5-HIAA was associated with in positive symptoms and general psychopathology of PANSS. These results suggest that clozapine has been found to have relatively weak dopaminergic blokade and stronger serotonergic antagonism.

Object : The aim of this study was to examine an association between plasma 5-Hydroxyindoleacetic Acid(HIAA) level and the change of depressive symptom after fluoxetine trial in haloperidol-stabilized schizoprenic in-patients. Method : According to plasma 5-HIM level, 32 patients were classified to either group with high 5-HIAA level(N=11) or that with low 5-HIM(N=11). For each patient, fluoxetine(20mg/day) added to stable haloperidol dose for 6 weeks. The authors measured Hamilton Rating Scale for Depression (HRSD) at baseline, the 2nd week, the 4th week, the 6th week of treatment. Result : 1) Age, duration of illness, number of admission, duration of present admission, dosage of haloperidol between high 5-HIAA group and low 5-HIM group were significantly different. 2) As time went on, the association between the change of depressive symptom and plasma 5-HIAA concentration was not significant. 3) Of depressed group, as lime went an, depressive symptoms were improved significantly in high 5-HIAA group, but not in law 5-HIM group. Conclusion : We suggest that the association between plasma 5-HIAA level and the change of depressive symptoms after fluoxetine trial in haloperidol stabilized schizophrenic in-patients was not significant.

본 연구는 주정중독에 동반된 우울증 환자의 치료에서 적어도 행동학적 부작용의 관점에서는 PAR이 AMI보다 우수함을 증명하였다. 이러한 PAR의 행동학적 효과의 우수성은 환자의 삶의 질을 향상시키고 결국 치료결과를 높이는데 관여하리라고 생각된다.

전기경련요법을 시행받은 9명의 정동자애 환자들과 2명의 정신분분열형장애 환자들에서 각각 3분 간격으로 혈액을 채취하여 각 채취하여 AVF, ACTH, PRL, cortisol 등의 호르몬에 대해 기저농도 및 전기경련요법 후의 농도 변화를 측정함으로써 각 호르몬 분비 반응 사이의 시간적인, 그리고 양적인 관계를 비교분석하였다. 또한 경련 지속 시간과 각 호르몬 분비반응들 사이의 상관관계도 검토하였다. 상기 호르몬 모두에서 전기경련요법 대한 의미있는 분비반응이 관찰되었다. 즉, AVP는 1.2pg/ml에서 33.3pg/ml(P<0.001). PRL은 21.8ng/ml에서 102.2ng/ml(P<0.005)로 cortsol은 20.1ug/dl에서 31.1ug/dl(P<0.001)로 각각 중가 되었다. 뇌하수체에서 분비되는 AVP, ACTH, PRL 세가지 호르몬 모두는 전기경련 요법 후 3분내에 분비 반용이 시작되었지만, 최고 농도에 도달하는 시간은 각각 3분, 6분, 12~15분대로 분명히 구별되는 소견을 보였다. cortisol은 6분후부터 증가하기 시작하여 20~30분 사이에 최고 농도를 보였다. 경련 지속 시간과 분비 반응과는 의미있는 상관관계를 보이지 않았다. 이상의 연구결과를 토대로 저자들은 다음과 같은 결론에 도달하였다. 1) 전기경련 요법에 대한 뇌하수체 호르몬의 반응은 동시적이라기 보다는 순차식으로 일어나는 것이다. 2) AVP는 다른 어떤 호르몬 보다도 아주 빠르고 양적으로 많은 반응을 보였다. 3) AVP 반응 후에 뒤따르는 ACTH 반응은 대부분의 과거 연구들에서 보고된 것보다 빠르고 강력했다. 4) 이러한 결과들은 뇌하수체 호르몬이 전기 자극보다는 경련의 결과로 분비된다는 가설을 지지해 주는 소견이다. 5) 시상하부-뇌하수체-부신피질 축 호르몬들의 순차적 반웅 양상은 각 호르몬의 분비 반응에 되먹임 조절 기전이 관여할 수 있음을 추정케 한다.

환청을 보이는 정신분열증 환자 27명을 대상으로 환청의 특성(주체, 내용, 환청에 대한 이해, 환청의 심한 정도), 환청에 대한 인지행동반응의 내용 및 그 빈도, good/fair copers와 poor copers의 환청의 특성 및 인지행동반응의 비교, 세가지 변인에 따른 인지행동반응의 차이를 살펴봄으로서 다음과 같은 결과를 얻었다. 1) 환청의 주체는 모르는 사람, 내용은 박해적인 것, 감정반응은 부정적인 것과 혼합된 것, 그리고 환청에 대한 이해는 정신역동적인 것이 가장 많았다. 2) 환청에 대한 반응중 가장 많이 사용된 인지반응은 억압, 무시와 같은 건강한 반응이었으며 가장 많이 사용된 행동반응은 생리적 각성을 증가시키는 반응이었다. 3) Good/fair copers 의 특징은 poor copers에 비하여 환청의 정도가 경하고 또 환청에 대한 병식이 있는 사람들이 많다는 것이었으며 인지행동반응에 있어서도 무반응이나 몰두와 같은 건강치 못한 인지반응과 탐닉이나 증상적 행동과 같은 건강치 못한 행동반응은 훨씬 적게, 그리고 생리적 각성을 증가시키는 건강한 행동반응은 훨씬 많이 사용하고 있었다. 4) 세가지 변인 중에서 환청에 대한 병식유무가 인지행동반응의 차이를 결정 짖는 가장 중요한 요인임을 시사 받을 수 있었다. 상기 결과는 환청을 경험하는 정신분열증 환자들이 단순히 피해자로서 수동적으로 머물러 있는 것이 아니라 이질적이고 침투적인 현상을 나름대로 받아들이고 극복하기 위하여 다양한 대응방식을 보이게 되며 이와 같은 대응방식의 형태 및 그 빈도를 결정짖는 중요한 요인이 환청에 대한 이해일 수 있음을 시사해 주고 있다.

A case of rapid cycling mania secondary to gamma-knife radiosurgery for the treatment of refractory epilepsy was reported. A 21-year old woman who had a gamma-knife radiosurgical operation for the treatment of refractory seizure two years ago was admitted because of manic episodes. Although seizure was relieved, manic symptoms like decreased need for sleep, elated mood, unprovoked laughing, grandiose delusion and bizarre behaviors were developed 11 months after the operation. These symptoms recurred lour rimes for eight months. There were no past personal and family history of mood disorders. Laboratory examinations including electroencephalogram ana endocrinological study did not show any abnormal findings. The rapid cycling secondary manic was relieved by lithium. She was then discharged after 5 months. Mood change was not significant during follow-up while hypomania emerged by dose reduction. The secondary mania seemed to be caused or triggered by the right temporal lobe damage induced by gamma-knife radiosurgery.