First observation of 28O.

Subjecting a physical system to extreme conditions is one of the means often used to obtain a better understanding and deeper insight into its organization and structure. In the case of the atomic nucleus, one such approach is to investigate isotopes that have very different neutron-to-proton (N/Z) ratios than in stable nuclei. Light, neutron-rich isotopes exhibit the most asymmetric N/Z ratios and those lying beyond the limits of binding, which undergo spontaneous neutron emission and exist only as very short-lived resonances (about 10-21 s), provide the most stringent tests of modern nuclear-structure theories. Here we report on the first observation of 28O and 27O through their decay into 24O and four and three neutrons, respectively. The 28O nucleus is of particular interest as, with the Z = 8 and N = 20 magic numbers1,2, it is expected in the standard shell-model picture of nuclear structure to be one of a relatively small number of so-called 'doubly magic' nuclei. Both 27O and 28O were found to exist as narrow, low-lying resonances and their decay energies are compared here to the results of sophisticated theoretical modelling, including a large-scale shell-model calculation and a newly developed statistical approach. In both cases, the underlying nuclear interactions were derived from effective field theories of quantum chromodynamics. Finally, it is shown that the cross-section for the production of 28O from a 29F beam is consistent with it not exhibiting a closed N = 20 shell structure.

Observation of a correlated free four-neutron system.

A long-standing question in nuclear physics is whether chargeless nuclear systems can exist. To our knowledge, only neutron stars represent near-pure neutron systems, where neutrons are squeezed together by the gravitational force to very high densities. The experimental search for isolated multi-neutron systems has been an ongoing quest for several decades1, with a particular focus on the four-neutron system called the tetraneutron, resulting in only a few indications of its existence so far2-4, leaving the tetraneutron an elusive nuclear system for six decades. Here we report on the observation of a resonance-like structure near threshold in the four-neutron system that is consistent with a quasi-bound tetraneutron state existing for a very short time. The measured energy and width of this state provide a key benchmark for our understanding of the nuclear force. The use of an experimental approach based on a knockout reaction at large momentum transfer with a radioactive high-energy 8He beam was key.

Extending the Southern Shore of the Island of Inversion to

Detailed spectroscopy of the neutron-unbound nucleus ^{28}F has been performed for the first time following proton/neutron removal from ^{29}Ne/^{29}F beams at energies around 230 MeV/nucleon. The invariant-mass spectra were reconstructed for both the ^{27}F^{(*)}+n and ^{26}F^{(*)}+2n coincidences and revealed a series of well-defined resonances. A near-threshold state was observed in both reactions and is identified as the ^{28}F ground state, with S_{n}(^{28}F)=-199(6) keV, while analysis of the 2n decay channel allowed a considerably improved S_{n}(^{27}F)=1620(60) keV to be deduced. Comparison with shell-model predictions and eikonal-model reaction calculations have allowed spin-parity assignments to be proposed for some of the lower-lying levels of ^{28}F. Importantly, in the case of the ground state, the reconstructed ^{27}F+n momentum distribution following neutron removal from ^{29}F indicates that it arises mainly from the 1p_{3/2} neutron intruder configuration. This demonstrates that the island of inversion around N=20 includes ^{28}F, and most probably ^{29}F, and suggests that ^{28}O is not doubly magic.

Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial.

BACKGROUND: Soluble thrombomodulin is a promising therapeutic natural anticoagulant that is comparable to antithrombin, tissue factor pathway inhibitor and activated protein C. OBJECTIVES: We conducted a multicenter, double-blind, randomized, parallel-group trial to compare the efficacy and safety of recombinant human soluble thrombomodulin (ART-123) to those of low-dose heparin for the treatment of disseminated intravascular coagulation (DIC) associated with hematologic malignancy or infection. METHODS: DIC patients (n = 234) were assigned to receive ART-123 (0.06 mg kg(-1) for 30 min, once daily) or heparin sodium (8 U kg(-1) h(-1) for 24 h) for 6 days, using a double-dummy method. The primary efficacy endpoint was DIC resolution rate. The secondary endpoints included clinical course of bleeding symptoms and mortality rate at 28 days. RESULTS: DIC was resolved in 66.1% of the ART-123 group, as compared with 49.9% of the heparin group [difference 16.2%; 95% confidence interval (CI) 3.3-29.1]. Patients in the ART-123 group also showed more marked improvement in clinical course of bleeding symptoms (P = 0.0271). The incidence of bleeding-related adverse events up to 7 days after the start of infusion was lower in the ART-123 group than in the heparin group (43.1% vs. 56.5%, P = 0.0487). CONCLUSIONS: When compared with heparin therapy, ART-123 therapy more significantly improves DIC and alleviates bleeding symptoms in DIC patients.

Stimulation of primary motor cortex for intractable deafferentation pain.

To treat intractable deafferentation pains, we prefer stimulation of the primary motor cortex (M1). The methods of stimulation we utilize are electrical stimulation and repetitive transcranial magnetic stimulation (rTMS). In our department, we first attempt rTMS, and if this rTMS is effective, we recommend the patient to undergo procedures for motor cortex stimulation (MCS). A 90% intensity of resting motor threshold setting is used for rTMS treatment. In this study ten trains of 5 Hz rTMS for 10 seconds (50 seconds resting interval) were applied to the M1, S1, pre-motor and supplementary motor areas. Only M1 stimulation was effective for pain reduction in 10 of 20 patients (50%). Twenty-nine MCS procedures were performed by subdural implantation of electrodes, and in the case of hand or face pain, electrodes were implanted within the central sulcus (11 cases), because the main part of M1 is located in the central sulcus in humans. The success rate of MCS was around 63%, and seemed to be higher in cases of pain with spinal cord and peripheral origins, while it was lower in cases of post-stroke pain.

Differences between Mitiglinide/Voglibose Fixed-dose Combination and Glimepiride in Modifying Low-density Lipoprotein Heterogeneity in Japanese Type-2 Diabetic Patients: A Pilot Study.

PURPOSE: The purpose of this study was to compare the effects of mitiglinide/voglibose fixed-dose combination and glimepiride on low-density lipoprotein (LDL)-heterogeneity in type-2 diabetic patients with unstable glycemic control after treatment with dipeptidyl peptidase-4 (DPP-4) inhibitors. METHODS: This was an open-label pilot study in which type-2 diabetic patients were randomly assigned to the mitiglinide/voglibose (fixed-dose combination of mitiglinide 10 mg and voglibose 0.2 mg, n=14) or glimepiride (0.5 mg, n=16). RESULTS: In the glimepiride group, serum LDL cholesterol (LDL-C) and small-dense (sd) LDL levels decreased significantly (-8.5% and -9.0%), while sd-LDL/LDL-C and an indicator of LDL-particle size, LDL-C/apoB, did not change significantly. In the mitiglinide/voglibose group, serum LDL-C levels did not change, while sd-LDL levels and sd-LDL/LDL-C decreased significantly (-8.6% and -7.9%) and LDL-C/apoB increased significantly (5.8%). Fasting blood glucose levels tended to be reduced to a greater extent in the glimepiride group than in the mitiglinide/voglibose group (-13.9% vs. -8.4%, p=0.08), while the rate of reduction of HbA1c levels tended to be higher in the mitiglinide/voglibose group than in the glimepiride group (-6.9% vs. -3.4%, p=0.09), suggesting differences in fluctuating blood glucose levels between the 2 groups. CONCLUSION: There were differences in the effects of mitiglinide/voglibose fixed-dose combination and glimepiride in addition to DPP-4 inhibitors on LDL-metabolism, and this may be related to fluctuations in blood glucose levels after treatment with these agents.

Centripetal Propagation of Vasoconstriction at the Time of Headache Resolution in Patients with Reversible Cerebral Vasoconstriction Syndrome.

BACKGROUND AND PURPOSE: Reversible cerebral vasoconstriction syndrome is characterized by thunderclap headache and diffuse segmental vasoconstriction that resolves spontaneously within 3 months. Previous reports have proposed that vasoconstriction first involves small distal arteries and then progresses toward major vessels at the time of thunderclap headache remission. The purpose of this study was to confirm centripetal propagation of vasoconstriction on MRA at the time of thunderclap headache remission compared with MRA at the time of reversible cerebral vasoconstriction syndrome onset. MATERIALS AND METHODS: Of the 39 patients diagnosed with reversible cerebral vasoconstriction syndrome at our hospital during the study period, participants comprised the 16 patients who underwent MR imaging, including MRA, within 72 hours of reversible cerebral vasoconstriction syndrome onset (initial MRA) and within 48 hours of thunderclap headache remission. RESULTS: In 14 of the 16 patients (87.5%), centripetal propagation of vasoconstriction occurred from the initial MRA to remission of thunderclap headache, with typical segmental vasoconstriction of major vessels. These mainly involved the M1 portion of the MCA (10 cases), P1 portion of the posterior cerebral artery (10 cases), and A1 portion of the anterior cerebral artery (5 cases). CONCLUSIONS: This study found evidence of centripetal propagation of vasoconstriction on MRA obtained at the time of thunderclap headache remission, compared with MRA obtained at the time of reversible cerebral vasoconstriction syndrome onset. If clinicians remain unsure of the diagnosis during early-stage reversible cerebral vasoconstriction syndrome, this time point represents the best opportunity to diagnose reversible cerebral vasoconstriction syndrome with confidence.

Intracoronary morphology of culprit lesions after reperfusion in acute myocardial infarction: serial angioscopic observations.

OBJECTIVE: This study sought to elucidate the morphologic and pathologic characteristics of culprit lesions in patients with acute myocardial infarction. BACKGROUND: The pathogenic mechanisms of acute myocardial infarction have been discussed on the basis of postmortem histologic examinations. Disruption of lipid-rich plaques is thought to render them thrombogenic. However, the details of coronary morphology have not been elucidated in survivors of myocardial infarction. The quality of angioscopic images has been greatly improved, and clear visualization of the intracoronary milieu can now be obtained. METHODS: Eleven patients with acute myocardial infarction and angiographic demonstration of the culprit lesion were entered into the study. Angioscopic observations were made immediately after reperfusion and at 1-month follow-up. RESULTS: Angioscopic observations were successfully performed in 10 patients immediately after reperfusion and in 10 at 33 +/- 26 (mean +/- SD) days of follow-up. Immediately after reperfusion, red thrombus, white thrombus, yellow plaques and intimal flaps were recognized in 30% (95% confidence interval [CI] 25.7 to 35.7), 100%, 100% and 50% (95% CI 45.0 to 55.0) of patients, respectively. At follow-up, these were recognized in 10% (95% CI 6.6 to 16.4), 60% (95% CI 54.6 to 64.7), 100% and 40% (95% CI 35.3 to 45.4) of patients, respectively. CONCLUSIONS: The thrombus in acute myocardial infarction was always recognized over the yellow plaques. The thrombus formed directly over the plaque was mainly white. Red thrombus might be formed after the blood flow was obstructed by the white thrombus. At approximately 1 month, yellow plaques remained in all patients, and > 50% still had adherent white thrombus.

The healing process of infarct-related plaques. Insights from 18 months of serial angioscopic follow-up.

OBJECTIVES: To clarify the healing process of disrupted culprit plaques of acute myocardial infarction (MI), we serially observed the culprit plaques for 18 months after the onset of acute MI by angioscopy. BACKGROUND: Although it has been reported that disruption of the yellow plaque and subsequent thrombosis cause acute MI and that the thrombogenicity of the plaque lasts for a month, the healing process of the plaque after disruption has not been clarified. METHODS: Eighty-five patients with acute MI were prospectively and consecutively enrolled. Angioscopic studies were performed immediately and at 1, 6 and 18 months after successful reperfusion. The prevalence of yellow plaques and thrombus was examined. The color grade of the plaque was determined as 0 (white), 1 (light yellow), 2 (yellow) or 3 (bright yellow). RESULTS: Although yellow plaque was present at the culprit lesion in most patients throughout follow-up, its color grade was reduced from one to six months (1.9 +/- 0.6 vs. 1.1 +/- 0.7, p = 0.0003) after reperfusion, especially in the patients without hyperlipidemia (HL). The incidence of thrombus was 92.5% immediately after reperfusion, which was reduced significantly to 63.8%, 4.8% and 11.8% at 1, 6 and 18 months, respectively. The incidence of thrombus (77.8% vs. 45.0%, p = 0.03) at one month was higher in the patients with diabetes mellitus (DM). CONCLUSIONS: The healing process of yellow plaques at the culprit lesions of MI was detected by angioscopy as reductions of color grade and thrombogenicity at six months and partially at one month after the onset of acute MI. This healing process appears to deteriorate by complicating cases of DM or HL.

Attenuation of increased regional myocardial oxygen consumption during exercise as a major cause of warm-up phenomenon.

OBJECTIVES: The aim of this study was to test the hypothesis that the warm-up phenomenon is attributable to a reduction of increased myocardial oxygen consumption rather than to increased coronary blood flow during exercise. BACKGROUND: The underlying mechanism of the warm-up phenomenon is not elucidated. METHODS: Thirteen patients with effort angina were subjected to two consecutive supine ergometer exercise tests performed 15 min apart. All patients had severe proximal stenosis (> 90%) in the left anterior descending coronary artery. Great cardiac vein flow was measured before and during exercise. Both regional myocardial oxygen consumption and adenosine release were determined. RESULTS: Exercise was continued for significantly longer before angina onset in the second than in the first exercise test (507 +/- 44 vs. 410 +/- 42 s, p < 0.01). The extent of ST segment depression in lead V5 of the electrocardiogram (ECG) was larger at the time of angina onset in the first (1.7 +/- 0.2 mm) than in the second (1.1 +/- 0.2 mm, p < 0.01) exercise test. Neither systemic hemodynamic variables nor great cardiac vein flow differed between the first and second exercise tests. In contrast, regional myocardial oxygen consumption assessed at 3 min of exercise was significantly (p < 0.01) less in the second than in the first test (8.0 +/- 0.8 vs. 8.7 +/- 0.9 ml/min). Adenosine release during the second test was higher (p < 0.05) than in the first test (2.5 +/- 0.5 vs. 3.9 +/- 0.5 nmol/min at 3 min of the first and second tests, p < 0.01). CONCLUSIONS: These results indicate that the warm-up phenomenon is not attributable to increased coronary flow but to attenuation of increased regional myocardial oxygen consumption, which may be mediated by adenosine A1 receptor activation.

Extensive development of vulnerable plaques as a pan-coronary process in patients with myocardial infarction: an angioscopic study.

OBJECTIVES: To test our hypothesis that the development of vulnerable plaques is not limited to the culprit lesions, but is a pan-coronary process, we directly observed all three major coronary arteries by angioscopy and evaluated the prevalence of yellow plaques in patients with myocardial infarction (MI). BACKGROUND: Although pathologic studies have suggested that the disruption of atheromatous plaque plays a major role in the development of acute MI, the prevalence of yellow plaques in the whole coronary arteries of patients with MI has not been clarified. METHODS: Thirty-two patients undergoing follow-up catheterization one month after the onset of MI were prospectively and consecutively enrolled in this study. The prevalence of yellow plaques and thrombus in the major coronary arteries was successfully evaluated in 20 patients (58 coronary arteries, 21 culprit lesions) by coronary angioscopy. The diameter stenosis (DS) of the culprit lesions and the maximal diameter stenosis (maxDS) of nonculprit segments were angiographically measured for each coronary artery. RESULTS: The DS of the culprit lesions and maxDS were 27 +/- 17% and 19 +/- 13%, respectively. Yellow plaques and thrombus were detected in 19 (90%) and 17 (81%) of 21 culprit lesions, respectively. Yellow plaques were equally prevalent in the infarct-related and non-infarct-related coronary arteries (3.7 +/- 1.6 vs. 3.4 +/- 1.8 plaques/artery). However, thrombus was only detected in the nonculprit segments of one (2%) coronary artery. CONCLUSIONS: In patients with MI, all three major coronary arteries are widely diseased and have multiple yellow though nondisrupted plaques. Acute MI may represent the pan-coronary process of vulnerable plaque development.

Collateral channels that develop after an acute myocardial infarction prevent subsequent left ventricular dilation.

OBJECTIVES: We sought to evaluate the effect of collateral channels that develop late after a first anterior myocardial infarction on left ventricular dilation and function. BACKGROUND: Collateral channels in an infarct-related artery may develop long after occlusion of the artery. Well visualized collateral channels that appear immediately after a myocardial infarction reduce infarct size and preserve left ventricular function. However, the functional significance of collateral channels that develop late after myocardial infarction has not been evaluated in terms of left ventricular function. METHODS: We studied 21 patients with a first anterior myocardial infarction and an infarct-related artery that remained totally occluded after reperfusion therapy and did not reopen within 1 month of infarction. No collateral channels were observed during the acute period. Patients were classified into two groups according to the extend of collateral formation 1 month after infarction: group C, patients with well developed collateral channels (n = 11), and group NC, patients with absent or poorly developed collateral channels (n = 10). Infarct size was determined by peak creatine kinase activity and thallium-201 single-photon emission computed tomography. Global and regional left ventricular function and left ventricular volumes were assessed by left ventriculography. These measurements were identical in both groups 1 month after infarction. Left ventricular function was reevaluated after 2.12 +/- 0.79 years (mean +/- SD). RESULTS: There were no significant changes in global and regional left ventricular function between the two groups during the long-term follow-up period. However, the end-diastolic volume index of group NC increased from 71 +/- 14 to 85 +/- 19 ml/m2, whereas that of group C decreased from 64 +/- 18 to 59 +/- 12 ml/m2. This important change during the long-term follow-up period resulted in a significant difference (p = 0.0006) in the end-diastolic volume index between the groups 2 years after onset (p = 0.002), whereas 1 month after infarction the difference was not significant (p = 0.36). A similar pattern was observed for the end-systolic volume index (group C: 38 +/- 16 to 35 +/- 14 ml/m2; group NC: 45 +/- 12 to 58 +/- 18 ml/m2, p = 0.018). The power of the tests to detect the observed differences showing nonsignificant results ranged from 0.05 to 0.38, whereas the power of the tests indicating a significant difference in end-diastolic and end-systolic volume indexes was >0.88. CONCLUSIONS: Collateral channels that develop after a myocardial infarction do not reduce the infarct size or prevent left ventricular dilation within 1 month of infarction. In contrast, such collateral channels prevent subsequent ventricular dilation and the deterioration of left ventricular function over 2 years. However, our results may have been biased because of the small number of patients.

Different mechanisms of ischemic adaptation to repeated coronary occlusion in patients with and without recruitable collateral circulation.

OBJECTIVES: The aim of this study was to investigate the interaction between ischemic preconditioning (IP) and collateral recruitment (CR) during ischemic adaptation in patients. BACKGROUND: The mechanism of ischemic adaptation still remains controversial in humans. METHODS: The clinical, electrocardiographic, hemodynamic and echocardiographic responses to three 150-s occlusions of the left anterior descending coronary artery were assessed in relation to CR in 18 patients with effort angina undergoing elective percutaneous transluminal coronary angioplasty. RESULTS: During the first occlusion, recruitable collateral circulation (RCC) to the occluded myocardium was detected by myocardial contrast echocardiography in 6 patients (Group C) and was not seen in 12 (Group N). In Group N, all patients manifested signs of severe ischemia during each inflation. However, their symptoms and ST segment shift significantly decreased from the first to the third occlusions, suggesting the occurrence of IP. The elevation of mean pulmonary artery pressure and deterioration of anterior wall motion were comparable between the first and the third occlusions in Group N. In contrast, myocardial ischemia was significantly less marked during occlusion in Group C than in Group N, and no preconditioning effect was observed. The extent of RCC did not differ between the first and the third occlusions in each group. CONCLUSIONS: Both IP and CR may play independent roles in ischemic adaptation in humans. With RCC, myocardial ischemia was greatly reduced. Without RCC, preconditioning clinically and electrocardiographically lessened myocardial ischemia but failed to preserve left ventricular function.

Coronary endothelial dysfunction in the insulin-resistant state is linked to abnormal pteridine metabolism and vascular oxidative stress.

OBJECTIVES: We investigated whether abnormal pteridine metabolism is related to coronary endothelial dysfunction in insulin-resistant subjects. BACKGROUND: Depletion of tetrahydrobiopterin (BH(4)) and elevation of the 7,8-dihydrobiopterin (BH(2)) (activating and inactivating cofactors of nitric oxide synthase [NOS], respectively) contribute to impairment of NO-dependent vasodilation through reduction of NOS activity as well as increased superoxide anion generation in insulin-resistant rats. METHODS: Thirty-six consecutive nondiabetic, normotensive and nonobese subjects with angiographically normal coronary vessels were studied. Traditional coronary risk factors, plasma pteridine levels, activities of erythrocyte dihydropteridine reductase (DHPR), the recycling enzyme that converts BH(2) to BH(4) and lipid peroxide (LPO) levels were measured and coronary endothelial function was assessed with graded infusions of acetylcholine (ACh). RESULTS: When we divided patients into tertiles based on insulin sensitivity, we observed stepwise decreases in the maximal ACh-induced vasodilation and plasma BH(4)/7,8-BH(2) ratio, and increases in coronary LPO production as insulin sensitivity decreased. The ACh-induced vasodilation was positively correlated with insulin sensitivity, BH(4)/7,8-BH(2) ratio and DHPR activity. Furthermore, BH(4)/7,8-BH(2) was inversely correlated with DHPR activity and insulin sensitivity. In multiple stepwise regression analysis, BH(4)/BH(2) was independently related to ACh-induced vasodilation and accounted for 39% of the variance. However, no significant correlation existed between other traditional risk factors and BH(4)/7,8-BH(2). CONCLUSIONS: These results indicate that both abnormal pteridine metabolism and vascular oxidative stress are linked to coronary endothelial dysfunction in the insulin-resistant subjects.

Crescentic glomerulonephritis associated with renal cell carcinoma after cancer immunotherapy.

A 59 year-old woman showed rapidly progressive glomerulonephritis during immunotherapy for metastatic renal cell carcinoma. She received unilateral nephrectomy and cytotoxic T lymphocyte (CTL) therapy for the treatment of retroperitoneal lymph node metastasis of renal cell carcinoma. With CTL therapy, her retroperitoneal lymph node mass decreased in size. One year after the third round of CTL therapy, her serum creatinine was increased and massive proteinuria occurred. Her renal biopsy specimen revealed necrotizing and crescentic glomerulonephritis with immune complex deposition. Her retroperitoneal lymph node mass continued to decrease in size. Consequently, for the purpose of avoiding interfering with the CTL therapy, we performed double filtration plasmapheresis (DFPP) monotherapy for removal of immune complexes without using immunosuppressive drugs or prednisolone. After 24 sessions of DFPP, her serum IgG was reduced from 3,942 mg/dL to 2,400 mg/dL, and proteinuria (from 9.0 g/day to 0.9 g/day) and renal function (serum creatinine; from 5.6 mg/dL to 2.2 mg/dL) also improved. However, 3 months after the final DFPP, she expired due to perforation of the colon. The autopsy sample of the kidney showed that most of the glomeruli were obsolescent, but immunoglobulin depositions were reduced and necrotizing lesions were diminished. In the patients with RPGN associated with renal cell carcinoma, renal functional recovery has not been observed upon immunosuppressive treatment. Consequently, plasmapheresis is considered to be one of the effective and safe methods for patients with this association. We also discuss previous reports of RPGN associated with renal cell carcinoma, or RPGN after cancer immunotherapy.

Neuroradiologic Diagnosis of Minor Leak prior to Major SAH: Diagnosis by T1-FLAIR Mismatch.

BACKGROUND AND PURPOSE: In major SAH, the only method to diagnose a preceding minor leak is to ascertain the presence of a warning headache by interview; however, poor clinical condition and recall bias can cause inaccuracy. We devised a neuroradiologic method to diagnose previous minor leak in patients with SAH and attempted to determine whether warning (sentinel) headaches were associated with minor leaks before major SAH. MATERIALS AND METHODS: We retrospectively evaluated 127 patients who were admitted with SAH within 48 hours of ictus. Previous minor leak before major SAH was defined as T1WI-detected clearly bright hyperintense subarachnoid blood accompanied by SAH blood on FLAIR images that was distributed over a larger area than bright hyperintense subarachnoid blood on T1WI (T1-FLAIR mismatch). RESULTS: The incidence of warning headache before SAH was 11.0% (14 of 127 patients, determined by interview). The incidence of T1-FLAIR mismatch (neuroradiologic diagnosis of minor leak before major SAH) was 33.9% (43 of 127 patients). Of the 14 patients with warning headache, 13 had a minor leak diagnosed by T1-FLAIR mismatch at the time of admission. Variables identified by multivariate analysis as significantly associated with minor leak diagnosed by T1-FLAIR mismatch included 80 years of age or older, rebleeding after admission, intracerebral hemorrhage on CT, and mRS scores of 3-6. CONCLUSIONS: We conclude that warning headaches diagnosed by interview are not a product of recall bias but are the result of actual leaks from aneurysms.

A compound adrenal medullary tumor (pheochromocytoma and ganglioneuroma) and a cortical adenoma in the ipsilateral adrenal gland. A case report with enzyme histochemical and immunohistochemical studies.

Neoplasms of all the adrenal parenchymatous elements [i.e., a compound adrenal medullary tumor (MT) consisting of pheochromocytoma (Pheo) and ganglioneuroma (GN) and a cortical adenoma] were found in the right adrenal gland of a 53-year-old man. A mature GN element was predominant in the MT, and nodules of small polygonal Pheo cells were scattered in GN. No neuroblastomatous element or malignant Pheo was found. The cortical adenoma consisted of compact cells and clear cells; it showed 3 beta hydroxysteroid dehydrogenase, glucose-6-phosphate dehydrogenase, and succinate dehydrogenase activity. The nonneoplastic cortex was slightly atrophic and showed weaker activity of the enzymes, suggesting that the adenoma was cortisol-producing. The cortex surrounding the MT was invaded and replaced by either GN or Pheo. In some places, however, hypertrophic compact cells constituted the cortex and were in contact with ACTH-immunoreactive chromaffin cells. A few of the latter were also positive for other proopiomelanocortin (POMC)-derived peptides. Pheo cells in the other parts were negative for POMC-derived peptides.

Elevation of the plasma histamine concentration in the coronary circulation in patients with variant angina.

In the present study plasma histamine was found to be elevated in the great cardiac vein in 8 of 11 patients with variant angina but in none of 8 control patients. Although further investigation is required to determine the exact cause-and-effect relation between histamine release and provocation of spontaneous variant anginal attacks, the present study presents clinical evidence that histamine may well be related to episodes of variant angina as suggested in animal studies.