A prospective open-label treatment trial of olanzapine monotherapy in children and adolescents with bipolar disorder.

OBJECTIVE: The goal of this study was to assess the effectiveness and tolerability of olanzapine in the treatment of acute mania in children and adolescents. METHODS: This was an 8-week, open-label, prospective study of olanzapine monotherapy (dose range 2.5-20 mg/day) involving 23 bipolar youths (manic, mixed, or hypomanic; 5-14 years old). Weekly assessments were made using the Young Mania Rating Scale (YMRS), Clinical Global Impressions Severity Scale (CGI-S), Brief Psychiatric Rating Scale, and Children's Depression Rating Scale. Adverse events were assessed through self-reports, vital sign and weight monitoring, laboratory analytes, and extrapyramidal symptom rating scales (Barnes Akathisia Scale, Simpson-Angus Scale, and Abnormal Involuntary Movement Scale). RESULTS: Twenty-two of the 23 youths (96%) completed the study. Olanzapine treatment was associated with significant improvement in mean YMRS score (-19.0 +/- 9.2, p < 0.001). Using predefined criteria for improvement of > or = 30% decline in the YMRS and a CGI-S Mania score of < or = 3 at endpoint, the overall response rate was 61%. Overall, olanzapine was well tolerated, and extrapyramidal symptom measures were not significantly different from baseline. Body weight increased significantly over the study (5.0 +/- 2.3 kg, p < 0.001). CONCLUSIONS: Open-label olanzapine treatment was efficacious and well tolerated in the treatment of acute mania in youths with bipolar disorder. Future placebo-controlled, double-blind studies are warranted.

Hypocoagulable state of human preovulatory ovarian follicular fluid: role of sulfated proteoglycan and tissue factor pathway inhibitor in the fluid.

Ovulation accompanied by tissue damage can cause an increase in the level of tissue factor (TF) in the follicular fluid, triggering the extrinsic coagulation pathway. However, follicular fluid must block fibrin formation and maintain fluidity until the release of the oocyte at ovulation. The combination of sulfated proteoglycan, antithrombin, and TF pathway inhibitor (TFPI) appears to play a critical role in the hypocoagulability of human follicular fluid. When compared with plasma, folicular fluid differs markedly in the levels of a number of important coagulation proteins. Principal among these are 15-fold, 13-fold, and 3.7-fold increases in free TFPI, thrombin-antithrombin complex, and TF, respectively. The excessively prolonged activated partial thromboplastin time (APTT) and prothrombin time (PT) of human ovarian follicular fluid appear to be primarily due to high concentrations of sulfated proteoglycans, which accelerate the inactivation of thrombin and the anti-Xa activity of TFPI. Thus, heparitinase treatment shortened the clotting times of follicular fluid and reduced the inhibition of thrombin by the proteoglycan fraction combined with a fraction containing antithrombin. The remaining prolongation of APTT and PT may be caused by high levels of free TFPI in follicular fluid, which were confirmed by Northern blotting analysis, demonstrating TFPI mRNA expression by granulosa cells.

Multifocal serous cystadenoma of the pancreas. A case report and review of the literature.

Serous cystadenoma of the pancreas is usually unifocal; multifocal tumors are rare. We report a case of multifocal serous cystadenoma of the pancreas in a 48-yr-old female complaining of general malaise. Serum tumor markers, such as CA 19-9, DUPAN-2, and Span-1, were elevated. Abdominal ultrasound (US) and computed tomography (CT) scans revealed two distinct cystic masses in the head and body of the pancreas, respectively. The patient underwent total pancreatectomy. The resected pancreas contained two discrete cystic masses in the head and body; no solid components were observed. Microscopically, the inner surfaces of the cysts were evenly lined by a single layer of low cuboidal or significantly attenuated epithelial cells containing clear cytoplasm and abundant glycogen without other morphological alterations. The histogenesis of serous cystadenoma is not clear; multicentric tumors may be helpful in understanding histogenesis.

[Clinical study of Mallory-Weiss syndrome in the aged patients over 75 year--mainly five cases induced by the endoscopic examination].

Cases of Mallory-Weiss syndrome aged over 75 year were analyzed with regard to their clinical features. In a 5-year period, there were 9 such cases, representing 19% of the total number of Mallory-Weiss syndrome cases. Four patients had a history of retching or vomiting, but in the other 5 patients, Mallory-Weiss tears occurred during endoscopic examination with slight vomiting reflex or even almost vomiting reflex. The latter cases had a spindle-shaped tear which was located on the lesser curvature at the cardia of the stomach. All patients were managed conservatively by observation without endoscopic hemostatic procedure, because the amount of bleeding was small. The 5 patients were thin and three of them had chronic atrophic gastritis. Mucosal weakness is an important etiologic factor in aged patients who develop Mallory-Weiss syndrome.

The new ceiling mount with "Space Pointer/Cygnus" system for the Leica Wild M690 operating microscope.

The new ceiling mount with the "Space Pointer/Cygnus" system for the Leica Wild M690 operating microscope (Leica AG, Heerbrugg, Switzerland) is reported. Two modes of action, "focus lock" and "point lock", are used with this system, in addition to counterbalanced free motion and electromagnetic brakes. The system also considerably improves space factors around the microscope.

Intraductal papillary neoplasms of the pancreas: diagnosis by endoscopic pancreatic biopsy.

Intraductal papillary neoplasms of the pancreas (IPN) are rare tumors, distinct from other pancreatic duct cell carcinomas both in terms of papillary polyp formation in the main pancreatic duct and their favorable prognosis. In the present study, endoscopic pancreatic biopsy (EPB) under fluoroscopic control was employed in three cases of IPN to obtain a tissue diagnosis prior to surgery. There were no complications and all biopsy specimens were adequate for histopathological evaluation. In our experience, EPB is a simple, safe and effective method, yielding sufficient material for preoperative tissue diagnosis of pancreatic tumors, especially in the case of IPN.

[Usefulness of selective endoscopic retrograde pancreatography (selective ERP) and endoscopic pancreatic biopsy (EPB) in the diagnosis of mucin-producing tumor of the pancreas].

Selective ERP and EPB were employed in the diagnosis of mucin-producing tumor (MPT) of the pancreas and their usefulness was evaluated. Thirty five cases of MPTs were subdivided into three subtypes, i.e., 1) main duct type, 2) branch duct type and 3) peripheral type (mucinous cystadenoma/cystadenocarcinoma). Selective ERP was proved to be useful in demonstrating precise and whole pancreatograms, especially in revealing multiple lesions, when compared with standard ERP. Selective ERP could demonstrate communication between cystic tumors of the peripheral type and the pancreatic duct in seven (88%) of eight cases of the peripheral type, which suggests high frequency of the communication in the peripheral type. For preoperative tissue diagnosis, EPB was shown to be a useful method to yield sufficient tissue materials for histopathological evaluation and may be used as an adjunction method to diagnose the intraductal extent of the tumorous lesion.

[Duodenal varices treated successfully by percutaneous transhepatic obliteration: report of a case].

A 73-year-old female with bleeding from duodenal varices treated by percutaneous transhepatic obliteration (PTO) was reported. She was admitted to our hospital because of tarry stool and general malaise. Gastroduodenoscopy revealed tortous elevations in the descending part of the duodenum, and observed intermittent bleeding. Percutaneous transhepatic portography (PTP) was carried out. PTP revealed duodenal varices supplied via the inferior pancreaticoduodenal vein and drained to the inferior vena cava, and continuously obliterated by gelfoam. Duodenal varices disappeared after obliteration and we observed no recurrence of varices for a year endoscopically. In general, it is accepted that the causes of the upper gastrointestinal bleeding secondary to portal hypertension are esophagogastric varices, hemorrhagic gastritis, gastro-duodenal ulcer, and so on. However, we must keep in mind the case with duodenal varices in which bleedings are of unknown origin. We also reviewed duodenal varices reported in Japanese literature from 1968 to 1989.

[Disturbance of inhibitory capacity of endothelial cell for platelet adhesion or aggregation following experimental subarachnoid hemorrhage].

Time sequential changes of the endothelial cells of feline basilar arteries after experimental subarachnoid hemorrhage (SAH) were studied morphologically and functionally under the scanning electron microscope (SEM). Experimental SAH was induced by the two-hemorrhage method, and the basilar artery was removed at 1 hour, or 2, 4, 7, or 14 days respectively after the 1st cisternal blood injection. At each stage, morphological changes of the luminal surface and endothelial cells of the basilar artery were observed by SEM. In another group, adenosin diphosphate (ADP) was infused through the right vertebral artery at the various stages mentioned above, for the purpose of activating platelets, and the basilar artery was then removed. The platelet adhesion or aggregation on the luminal surface was observed quantitatively also by SEM, for evaluating the inhibitory capacity of the endothelial cells upon platelet adhesion or aggregation after SAH. The fold formation of the arterial luminal surface and the ballooning of the endothelial cells were observed initially at 1 hour and 2 days respectively after the 1st cisternal blood injection. The latter findings became most remarkable during the 4 to 7 days after the said blood injection. They were accompanied by intercellular gap formation. None of these findings were seen, however, in the specimens taken 14 days after the said blood injection. In the group with pre-sacrificing ADP infusion, adhesion or aggregation of platelets on the arterial luminal surface was scarcely seen before the second day, but became remarkable 4 to 7 days after the 1st cisternal blood injection, and were reduced by the time 14 days had passed.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinico-statistical study on morphological risk factors of middle cerebral artery aneurysms.

Influences of various factors on postoperative outcome of 122 well-documented cases, out of a total of 151 cases of middle cerebral artery aneurysm, are discussed in this paper. The shape of the aneurysm, major axis, major axis/neck and major/minor axis ratio were correlated with the presence or absence of a bleb (p less than 0.0000001), and indicated a correlation not only between aneurysmal shape and the outcome (p less than 0.05) but also between preoperative seriousness and the outcome (p less than 0.05). The preoperative seriousness and the grade of subarachnoid haemorrhage indicated a close correlation between each of these two parameters and the outcome (p less than 0.000001 for each). Both the quantity and the colour of CSF outflow from the chiasmal cistern showed close correlation with vasospasm (p less than 0.01), onset of hydrocephalus (p less than 0.01) and the outcome (p less than 0.001). Moreover, vasospasm and hydrocephalus grade itself also showed close correlation with the outcome (p less than 0.001 and p less than 0.00001). All parameters: blood pressure grade, BPmax, BPmin, BP fluctuation showed correlations not only with preoperative seriousness (p less than 0.001) and the outcome (p less than 0.0001) but also with subarachnoid haemorrhage frequency, number of aneurysms, and major axis/neck ratio.

[Two cases of unresectable pancreatic cancer responding to combined chemotherapy with cisplatin, PSK and UFT].

Two patients who had unresectable pancreatic cancer were treated with a combined chemotherapy using Cisplatin, PSK and UFT. A remarkable decrease of tumor size was observed on CT. These two cases corresponded to partial response (PR) according to the response criteria proposed by Koyama-Saitoh. No significant side effects were observed during this therapy. From the results in these two cases, this combination chemotherapy was considered to be one of the most effective antineoplastic therapies available for pancreatic cancer.

Scanning electron microscopic determination of quantitative parameters of villi in the rat jejunum.

In rat jejunum, the number of epithelial cells per villus and the villus surface area were measured directly on the scanning electron micrograph. The villus height and the number of epithelial cells of the same villus were measured on the histological sections under a light microscope. Both the number of epithelial cells per villus and the villus surface area correlated well with the villus height and with the number of epithelial cells per villus sections. In the normal rat jejunum, the approximate values of the number of epithelial cells per villus surface and villus surface area may be estimated from the villus height or the number of epithelial cells per villus section.

Ultrastructural changes in pancreatic acinar cells of rats after administration of 4-hydroxyaminoquinoline-1-oxide.

Ultrastructural changes in the exocrine pancreas 24, 48, 72 and 168 hours after a single intravenous injection of 4-hydroxyaminoquinoline-1-oxide (4-HAQO), at a dose of 14 mg.per kg., were observed in male rats. At 24 hours after administration, multiple focal degenerative lesion-like large vacuoles in the acini, and a decrease in zymogen granules with dilation of the rough endoplasmic reticulum cisternae in the acinar cells were marked. At 48 hours, acinar cell degeneration and necrosis progressively increased. The nucleus, especially, appeared to be disorganized and lysosome-like bodies with various sizes were frequently observed. At 72 hours, acinar cell degeneration persisted in the acini, and the interstitial space with infiltration of inflammatory cells appeared edematous. In addition, ductular-like cells, which resembled intercalated duct cells, possessing a light cytoplasm with occasional mitoses were observed around the duct lumen. At 168 hours, the exocrine pancreas was occupied with proliferated ductular-like cells. Furthermore, acinar cells and acini regenerated to the normal pattern were sometimes found. Thus, the exocrine pancreas degenerated progressively up to 48 hours after administration of 4-HAQO, gradually came to be repaired by degrees from 72 hours and then partly appeared to be regenerated at 168 hours. It is suggested that the ductular-like cell might be the precursor of the acinar cell in the regenerating process after injection of 4-HAQO.

Annulate lamellae of the pancreatic exocrine cells in starved rats.

The ultrastructure of annulate lamellae in the pancreatic exocrine cells of rats starved for 3-42 days was studied. Annulate lamellae were rarely encountered in the pancreatic exocrine cells of control rats, but their incidence and size of stack was increased in those of starved rats depending on the duration of starvation, despite marked ultrastructural changes in these cells. Annulate lamellae were located in the para- or infranuclear cytoplasm of the cells and most of them were continuous with the relative normal rough endoplasmic reticulum. A close apposition in parallel was often found between the annulate lamellae and the outer nuclear envelope and occasionally pores in line with those of the nuclear membrane were observed in the lamellae of rough endoplasmic reticulum in 35- and 42-day-starved rats. An unequivocal continuity between the annulate lamellae and the nucleus and/or rough endoplasmic reticulum in pancreatic exocrine cells might be related to their origin and function.

Annulate lamellae of the jejunal absorptive cells in 21-day-starved rats.

The ultrastructure of annulate lamellae of the jejunal absorptive cells in control and 21 d starved rats was investigated. Annulate lamellae were only rarely encountered in the jejunal absorptive cells of control rats, and then frequently in small stacks continuous with the rough-surfaced endoplasmic reticulum. In contrast, there was a relatively frequent incidence of annulate lamellae in the jejunal absorptive cells of 21 d starved rats, and larger stacks of annulate lamellae were also observed in spite of marked ultrastructural changes of these cells. The annulate lamellae were also continuous with the rough-surfaced endoplasmic reticulum, which was degenerating. The degenerative process of the absorptive cells following starvation might be related to the origin and function of the annulate lamellae.

Ultrastructural localization of acid phosphatase activity in the jejunal absorptive cells of fasted rats.

Ultrastructural localization of acid phosphatase activity was investigated in the jejunal absorptive cells of 21 d fasted rats (about 500 g). The enzyme activity was localized on the membrane of microvilli, the lateral cell membrane, the Golgi complex, the lysosomes and the GERL of Novikoff (a part of the smooth surfaced endoplasmic reticulum located in close proximity to the Golgi saccules) of jejunal absorptive cells. Moreover, the lysosomes of various sizes and shapes with acid phosphatase activity was characteristically encountered in the infranuclear cytoplasm. The lysosomes appeared to be autolysosomes .

Ultrastructure of the absorptive cells in the small intestine of the rat during starvation.

The ultrastructure of the absorptive cells in the duodenum, jejunum and ileum after 7, 14 and 21 days of starvation was investigated using rats aged from 12 to 18 months weighing about 500 g. In the basal cytoplasm of the absorptive cells (in the duodenum and ileum of 21-day-starved rats and the jejunum of 14- and 21-day-starved rats), the following changes were found: atrophied mitochondrion-like bodies, small vesicles, a short and sparse rough-surfaced endoplasmic reticulum and a lack of density in a portion of the cytoplasm. Moreover, many autolysosomes of various sizes and shapes were encountered in the basal cytoplasm; occasionally these elements accumulated and appeared to fuse to one another. In contrast, in the apical cytoplasm of absorptive cells in the intestine of starved rats, the ultrastructure was similar to that of control rats. It was considered that the apical cytoplasm of the absorptive cells in the starved rat intestine might be preserved as long as possible during starvation in order to absorb nutrients when they become available again.