High-power laser experiment on developing supercritical shock propagating in homogeneously magnetized plasma of ambient gas origin.

A developing supercritical collisionless shock propagating in a homogeneously magnetized plasma of ambient gas origin having higher uniformity than the previous experiments is formed by using high-power laser experiment. The ambient plasma is not contaminated by the plasma produced in the early time after the laser shot. While the observed developing shock does not have stationary downstream structure, it possesses some characteristics of a magnetized supercritical shock, which are supported by a one-dimensional full particle-in-cell simulation taking the effect of finite time of laser-target interaction into account.

From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal.

The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53. In addition, the current classification of neoplasms of the anterior pituitary does not accurately reflect the clinical spectrum of behavior. Invasion and regrowth of proliferative lesions and persistence of hormone hypersecretion cause significant morbidity and mortality. We propose a new terminology, pituitary neuroendocrine tumor (PitNET), which is consistent with that used for other neuroendocrine neoplasms and which recognizes the highly variable impact of these tumors on patients.

The long-term outcome of open-wedge osteotomy of the proximal tibia with hemicallotasis.

We report the long-term outcome of 33 patients (37 knees) who underwent proximal tibial open-wedge osteotomy with hemicallotasis (HCO) for medial osteoarthritis of the knee between 1995 and 2000. Among these, 29 patients with unilateral HCO were enrolled and 19 were available for review at a mean of 14.2 years (10 to 15.7) post-operatively. For these 19 patients, the mean Hospital for Special Surgery knee score was 60 (57 to 62) pre-operatively and 85 (82 to 87) at final follow-up (p < 0.001; paired t-test). The femorotibial angle and tibial inclination angle (IA) were measured at short-term follow-up, one to four years post-operatively, and showed no significant subsequent changes. The clinical scores and radiological measurements showed little change over time. One patient required conversion to total knee replacement during this time. These results suggest that the coronal angle achieved at operation is maintained at long-term follow up after HCO without alteration of the IA, providing a good long-term clinical outcome.

Granulomatous hypophysistis associated with rathke's cleft cyst: a case report.

OBJECTIVE: The value of surgical intervention in the management of hypophysitis remains controversial. PATENT: We describe a 57-year-old man presenting with general fatigue persisting for three months. Endocrine examination revealed hypopituitarism and diabetes insipidus. Magnetic resonance (MR) imaging showed a dumbbell-shaped pituitary mass lesion without a cystic component. We partially removed the lesion via a transsphenoidal approach. Histological examination yielded the diagnosis of granulomatous hypophysitis associated with Rathke's cleft cyst. No deterioration of pituitary function was observed postoperatively. Twenty months after the surgery, the lesion has spontaneously regressed on MR imaging, and he is doing well with continuing replacement therapy of hydrocortisone, levothyroxine and desmopressin acetate. CONCLUSION: The diagnosis of hypophysitis, apart from typical lymphocytic hypophysitis, is difficult even with a surgical biopsy. Because a small specimen may lead to a diagnosis of non-specific hypophysitis, partial removal of the lesion is less invasive and recommended for preservation of the pituitary function.

Delayed massive epistaxis following endonasal transsphenoidal surgery.

OBJECTIVE: To describe delayed massive epistaxis, a rare but serious complication after transsphenoidal surgery. PATIENTS: Two patients underwent microscopic transsphenoidal surgery through a right endonasal approach for nonfunctioning pituitary adenoma. Severe epistaxis suddenly developed on day 8 and on day 13, respectively, after uneventful surgery. In each patient, the epistaxis was due to arterial haemorrhage from the left posterior nasal cavity. Otolarygologists failed to detect the origin of bleeding which was refractory to conservative treatment. Emergency internal carotid or external carotid angiography, performed during tight packing of the posterior nasal cavity, did not show abnormal findings; nevertheless, each patient was treated successfully by endovascular embolisation of the external carotid artery without further complication. CONCLUSION: When severe delayed epistaxis follows transsphenoidal surgery and damage to the internal carotid artery has been ruled out, endovascular embolisation of the external carotid artery should be considered in patients refractory to conservative treatment.

Management of intracranial germ cell tumors presenting with rapid deterioration of consciousness.

OBJECTIVES: The value of surgical intervention in the management of intracranial germ cell tumors remains controversial. PATIENTS: We report three patients who presented with rapid deterioration of consciousness but resulted in complete remission of the tumor after emergency surgery for both diagnostic (biopsy) and therapeutic (for hydrocephalus) purposes followed by prompt initiation of radiochemotherapy. CONCLUSION: For management of these rapidly deteriorating patients, immediate histological verification and avoidance of delay in the induction of radiochemotherapy are essential. Thus, emergency surgery with a less invasive procedure is the first choice of treatment, i. e., endoscopic surgery for pineal region tumor and CT-guided biopsy for basal ganglia tumor.

Hypopituitarism and anemia: effect of replacement therapy with hydrocortisone and/or levothyroxine.

Although common, anemia associated with hypopituitarism has received little attention. We conducted a retrospective study to elucidate the effect of replacement therapy with hydrocortisone and/or levothyroxine on the decreased hemoglobin (Hb) level. A total of 68 patients who had been suffering from anterior pituitary deficiencies for more than 12 months were studied. The Hb level was significantly lower in patients with hypopituitarism (p=0.0012). Decreased Hb level (<12.0 g/dl) was observed in 22 patients (32.4%). It was related to hypocortisolism (regression weights=0.39), hypothyroidism (0.37), GHD (0.32) and hypogonadism in men (0.17). Among 68 patients, 30 patients had been receiving replacement therapy for at least 12 months. Hydrocortisone and levothyroxine increased the Hb level in 20 patients whose data were available before the replacement (p=0.0002). However, the Hb level was still lower in 30 patients receiving the replacement (p=0.0001). In 13 patients (8 men) with decreased Hb level (<12.0 g/dl) despite the replacement, GH and testosterone were deficient in 12 (92.3%) and 8 (100%) patients, respectively. In conclusion, replacement therapy with hydrocortisone and/or levothyroxine is effective in most patients but is not sufficient, at least in some patients, to improve the decreased Hb level. These results suggest that additional replacement therapy, i.e. with GH and/or androgen, is necessary to obtain further improvement.

Risk factors of cerebrospinal fluid rhinorrhea following transsphenoidal surgery.

OBJECTIVE: Cerebrospinal fluid (CSF) rhinorrhea is a potentially life-threatening complication following transsphenoidal surgery (TSS). METHODS: To elucidate the risk factors that may affect the incidence of postoperative CSF rhinorrhea, we retrospectively reviewed 200 consecutive cases of TSS performed by a single surgeon for 168 adenomas and 32 other sellar and parasellar lesions. RESULTS: Intra-operative CSF leakage was encountered in 38 cases (19.0%). Its incidence did not correlate to tumor size. Among 4 microadenoma cases with CSF leak, 3 were ACTH adenomas. In contrast, postoperative CSF rhinorrhea was observed in 5 cases (2.5%), all following TSS for adenomas. It was frequently noted in cases with prior TSS (3/40, 7.5%, p = 0.0235) and prior radiotherapy (2/7, 28.6%, p < 0.0001). Two cases who required surgical intervention had received TSS and radiotherapy previously. CONCLUSION: The risk of postoperative CSF rhinorrhea is significantly increased in cases with prior TSS or radiotherapy or both. In addition, these cases tended to show delayed CSF leaks and require sellar reconstruction for its treatment. When a CSF leak was encountered during TSS in these high-risk cases, thorough sellar reconstruction and long-term follow-up is necessary.

Gender-related differences in prolactin secretion in pituitary prolactinomas.

In pituitary prolactinomas, serum prolactin (PRL) levels usually parallel the tumor size. We conducted a retrospective study to determine differences in PRL production between men and women with prolactinomas. A total of 51 patients, 16 men and 35 women, was studied. We investigated clinical, endocrinological, radiological and histological findings, and estimated the tumor volume (TV) by high-resolution magnetic resonance imaging (MRI). Correlation between PRL level and TV was low in men (R=0.458), in contrast to women (R=0.953), c. Men with prolactinomas showed predominance of large tumors (P=0.0009) with high PRL levels (P=0.0009) and had greater tendencies for cyst formation (P=0.0047). Large prolactinomas tended to be accompanied by cyst(s) (P=0.0051) and hemorrhage ( P=0.0015), both of which were associated with reduced PRL secretion (P=0.0004 and P<0.0001, respectively). When the volume of the cysts and hemorrhage was subtracted from the total TV, correlation between PRL level and TV became greater (R=0.905) with no gender difference. Histological examination demonstrated a sparsely granulated type of lactotroph adenoma with occasional fibrosis, particularly in tumors with hemorrhage and cysts. Although a significant discrepancy between PRL level and TV may exist in prolactinomas when intratumoral hemorrhage and/or cysts are present, there is no essential difference in PRL secretion between the sexes.

Serum levels of advanced glycosylation end products in diabetic nephropathy.

BACKGROUND/AIMS: Advanced glycosylation end products (AGEs) are important pathogenetic factors underlying diabetic complications. Recently, a highly reliable new enzyme-linked immunosorbent assay for these metabolites has been established. We used the assay to correlate AGEs in serum with renal function categories and histopathology in patients with diabetic nephropathy. METHODS: Type 2 diabetic patients (n = 71) and healthy control subjects (n = 35) were studied. The diabetic subjects were divided into two groups: normal renal function and chronic renal failure not requiring dialysis. In renal biopsy specimens from 22 diabetic subjects with a normal renal function, the severity of glomerular lesions was assessed morphometrically in terms of the ratio of the area of periodic acid-Schiff stained mesangium to total glomerular area. RESULTS: The serum AGE concentrations were higher in both undialyzed diabetic groups, especially in those with renal failure, than in the controls. The serum AGE concentrations increased with the severity of glomerular lesions (morphometric ratio under 15%, 2.85 +/- 0.73 mU/ml; 15-24%, 4.01 +/- 0.71 mU/ml; 25% or more, 5.12 +/- 0.64 mU/ml). CONCLUSIONS: The serum AGE levels measured by the new enzyme-linked immunosorbent assay reflected the severity of glomerulopathy, and, therefore, it may be a clinically useful tool for assessing diabetic renal complications.

Identification of protein kinase Calpha as an essential, but not sufficient, cytosolic factor for Ca2+-induced alpha- and dense-core granule secretion in platelets.

Upon activation, platelets release many active substances. Here, we have analyzed the mechanism governing Ca(2+)-induced secretion of von Willebrand factor stored in alpha-granules and 5-hydroxytryptamine in dense-core granules in permeabilized human platelets. Both secretions were dependent on ATP and cytosol. An essential factor for both granule secretions was purified from rat brain cytosol and identified to be protein kinase Calpha (PKCalpha) by partial amino acid sequencing. Purified PKCalpha efficiently stimulated both secretions in the presence of cytosol, whereas PKCalpha alone did not support the secretion of either type of granules, suggesting that PKCalpha is not a sufficient factor. Finally, in human platelet cytosol fractionated by a gel filtration column, the stimulatory activity for dense-core granule secretion paralleled with the concentration of PKC, suggesting that PKC could also be such a stimulatory factor in platelet cytosol. Thus, we identified PKCalpha as an essential, but not sufficient, cytosolic factor for the Ca(2+)-induced secretions of both alpha- and dense-core granules in platelets.

Improvement of the quantitative method for glucose determination using hexokinase and glucose 6-phosphate dehydrogenase.

This paper has two aims. The first one is to point out the shortcomings of Food and Drug Administration's (FDA's) reference method for the measurement of glucose. We found that the quantity of enzyme used in the method recommended by the FDA was more than the exact quantity needed for accurate measurement. The use of exact quantity of enzyme is important to minimize the negative effects due to impurity and side reactions of enzymes. The second aim is to simulate the coupling enzyme reaction using computer. We have successfully established the exact quantity of enzyme needed in the assay through the computer simulation. The quantity of the enzyme was lesser than the that recommended by FDA, but the reaction ended at the same time as in the FDA method. In addition, optimum conditions and inhibitory effects of various reagents have also been successfully analyzed using computer. In conclusion, we suggest a reference method using computer simulation to determine the exact quantity of the coupling enzyme needed in the assay.

Histological changes in the hypofunctional pituitary gland following conventional radiotherapy for adenoma.

AIMS: Although delayed hypopituitarism is a common complication of conventional radiotherapy of sellar tumours, histological changes that may account for it have been rarely reported. To elucidate the changes, hypofunctional pituitary glands following irradiation were studied. METHODS AND RESULTS: Two pituitary glands obtained at autopsy from patients who had been irradiated for adenoma and exhibited hypopituitarism were examined. In both cases diffuse fibrosis was observed in the adenohypophysis, whereas the neurohypophysis remained unchanged. Immunohistochemistry showed that stellate-shaped S100 protein-positive cells were increased in number and distributed among the endocrine cells. Some irradiated endocrine cells showed dense granular immunoreactivity for mitochondrial protein, cytochrome oxidase and manganese-superoxide dismutase. In addition to faint reactivity with anti-cytokeratin 8, 18 antibody, many cells were densely positive with anti-cytokeratin 1, 5, 10, 14 antibody. CONCLUSIONS: These results indicate that radiation- induced fibrosis is associated with an increased number of folliculo-stellate cells and the presence of metabolic dysfunctional mitochondria resembling mitochondria in oncocytes. Squamous metaplasia in the irradiated endocrine cells was also noted. Various intracellular changes may participate in delayed pituitary hypofunction following radiotherapy.

Growth potential of female prolactinomas.

BACKGROUND: The indications for treatment in female patients with small prolactinomas and mild or no symptoms are controversial. The aim of this study was to investigate whether we can predict the growth potential of a given small prolactinoma. METHODS: The proliferation potential of 25 female prolactinomas and 5 prolactin-containing adenomas found incidentally at autopsy was determined immunohistochemically using the Ki-67 (MIB-1) antibody. The results were compared according to age, clinical and endocrine findings, and tumor volume. RESULTS: Small prolactinomas (<1.0 cm(3)) with mild hyperprolactinemia (<150 ng/mL) showed significantly low proliferation potential irrespective of age, resembling prolactin-containing adenomas found at autopsy. The patients tended to present with mild symptoms and rarely had estrogen deficiency. CONCLUSION: These findings indicate that female patients with a small prolactinoma, mild hyperprolactinemia, and no symptoms or those who do not desire fertility may have no specific reason for treatment, but can be followed by serum prolactin level and serial magnetic resonance imaging.

Differences in adaptation to growth of children between internal thoracic artery and saphenous vein coronary bypass grafts.

BACKGROUND: It is not known how the internal thoracic artery (ITA) and saphenous vein graft (SVG) adapts to somatic growth of pediatric patients who underwent coronary artery bypass grafting (CABG). METHODS: Twenty-two ITAs and 6 SVGs in 17 patients who underwent at least three postoperative catheterizations with biplanar cineangiography and followed for a minimum of 5 years were evaluated. We evaluated the length, diameter and curvature of the grafts by cineangiographies which were performed at 1 month, 1 year, 5 years and more than 5 years postoperatively. RESULTS: The length of the ITA (1-month: 117+/-31 mm, 1-year: 134+/-32 mm, 5-years: 146+/-28 mm, and >5-years: 155+/-34 mm, p=0.032) and diameter of the ITA (1.4+/-0.4 mm, 2.0+/-0.7 mm, 2.3+/-0.6 mm and 2.6+/-0.6 mm, p<0.0001) significantly increased over time, but neither the length nor diameter of the SVG length: 121+/-33 mm, 119+/-29 mm, 119+/-25 mm and 126+/-1 mm, p=0.9907; diameter: 4.1+/-1.0 mm, 3.9+/-0.7 mm, 4.0+/-0.8 mm and 3.3+/-0.4 mm, p=0.5784) increased. Although the ITA exhibited no change in curvature over time (1 month: 1.15+/-0.07, late: 1.15+/-0.07, p=0.8490), the curvature of the SVG significantly decreased over time (1 month: 1.42+/-0.19 and late: 1.25+/-0.16, p=0.0277). The percent segmental length of ITAs were changed little from early to late after CABG (1 month: proximal: 33.7+/-7.0%, middle: 33.3+/-7.9% and distal: 32.9+/-7.9%, vs late: 34.3+/-7.2%, 33.2+/-7.9% and 32.5+/-7.9%, p=0.937). CONCLUSIONS: ITAs grow in proportion to somatic growth, while SVGs course in a more linear fashion in adapting to patient growth.

Cerebral vasospasm following transsphenoidal removal of a pituitary adenoma.

We report a case of pituitary macroadenoma that developed symptomatic vasospasm 12 days after transsphenoidal removal, but showed an excellent recovery following active treatment identical to those for vasopasm following aneurysmal subarachonid haemorrhage. Subarachnoid haematoma in the basal cisterns secondary from postoperative intracapsular haemorrhage was the most probable cause of the vasopasm.

Effects of a novel hepatoprotective drug, ZNC-2381, on fas-induced hepatocellular caspase-3 activity and apoptosis in mice.

We examined the effects of ZNC-2381 (1-(4-aminophenyl)methyl-3-(3-nitrophenyl)-1,3-dihydroimidazo[4,5-b] pyridine-2-one), a new oral hepatoprotective agent, on hepatocellular caspase-3 activity and apoptosis induced by anti-mouse Fas antibody (anti-Fas ab) in mice. Oral ZNC-2381, administered at doses of 10, 30 and 100 mg/kg 1 h before inducing hepatic injury with anti-Fas ab, dose-dependently inhibited the increase in serum alanine aminotransferase (s-ALT) activity 8 h after injection of anti-Fas ab. Increases in DNA fragmentation (nucleosome assay) and caspase-3 activity in the liver 2 h after injection of anti-Fas ab were also inhibited by ZNC-2381 in a dose-dependent manner. As shown by histopathological examination, ZNC-2381 dose-dependently inhibited the appearance of TUNEL-positive apoptotic cells in the liver. Moreover, in studies in vitro, ZNC-2381 (1- 100 micromol/l) concentration-dependently inhibited increases in DNA fragmentation and caspase-3 activity caused by anti-Fas ab in isolated mouse hepatocytes. N- Acetyl-Asp-Glu-Val-Asp aldehyde (Ac-DEVD-cho), a caspase-3-specific inhibitor, inhibited hepatocellular apoptosis caused by anti-Fas ab both in vivo and in vitro, as well as the increase in s-ALT activity in vivo. These results demonstrate that orally administered ZNC-2381 inhibits hepatocellular apoptosis induced by anti-Fas ab and presents the progression of hepatic injury. We propose that the mechanism of action of ZNC-2381 may involve blockade of the signal transduction pathway (caspase-3) of apoptosis mediated by anti-Fas ab.

Mut-Test to detect substances suppressing spontaneous mutation due to oxidative damage.

Since it has been considered that suppression of spontaneous mutation in cells is related to suppression of spontaneous carcinogenesis, it is significant to detect substances which suppress spontaneous mutation in bacterial cells such as Escherichia coli and Salmonella typhimurium in the environment. However, since the frequency of spontaneous mutation in bacteria is usually very low, generally 10(-8)-10(-10),it is difficult to determine significant suppressive ability of such substances on spontaneous mutation. A new method, Mut-Test, was developed by us, applying Luria & Delbruck fluctuation test, to detect substances which suppress spontaneous mutation using E. coli mutT mutant in which spontaneous mutation frequency due to oxidative damage is enhanced to approximately 500-1000 times of the wild type strain. Suppressive abilities of two hydroxyl radical scavengers: D(-)-mannitol and thiourea, were examined and clear positive results were obtained, suggesting that the radical scavengers are suitable as the positive control for the test. Using Mut-Test, suppressive abilities of four vitamins: L-ascorbic acid, beta-carotene, folic acid and riboflavin; 10 polyphenols: caffeic acid, ellagic acid, (-)-epicatechin, (-)-epicatechin gallate, (-)-epigallocatechin, gallic acid, pyrocatechol, pyrogallol, quercetin and tannic acid which are recognized as antimutagens, were examined. Furthermore, the concentrations for 50% of suppressive abilities of five positive samples, L-ascorbic acid, folic acid, caffeic acid, pyrocatechol and pyrogallol were compared. Negative results were obtained in nine samples, riboflavin, tannic acid, etc. suggesting that their antimutagenic effect on cells may not be related to oxidative damage in cells.

[A case of high dose administration of propofol].

A 34 year-old-man was scheduled for clipping and bypass surgery of dissecting aneurysm of the right vertebral artery. He previously had an episode suggesting malignant hyperthermia susceptibility during anesthesia managed with suxamethonium and isoflurane. Before the present operation, oral dantrolene 200 mg was administered. Anesthesia was induced with 120 mg of propofol and maintained with 10-6 mg.kg-1.hr-1 of propofol and 60 micrograms.hr-1 of fentanyl for 24 hours. Total dose of propofol amounted to 9,900 mg. Because propofol is formulated as a 10% oil in water emulsion, its high dose administration could alter serum lipid concentrations. However postoperative triglyceride and cholesterol concentrations remained within normal ranges in our case.