Search

Objective: To determine the associations of pancreatobiliary maljunction (PBM) in the West., Background: PBM (anomalous union of common bile duct and pancreatic duct) is mostly regarded as an Asian-only disorder, with 200X risk of gallbladder cancer (GBc), attributed to reflux of pancreatic enzymes. Methods: Radiologic images of 840 patients in the US who underwent pancreatobiliary resections were reviewed for PBM and contrasted with 171 GBC cases from Japan., Results: Eight % of the US GBCs (24/300) had PBM (similar to Japan; 15/ 171, 8.8%), in addition to 1/42 bile duct carcinomas and 5/33 choledochal cysts. None of the 30 PBM cases from the US had been diagnosed as PBM in the original work-up. PBM was not found in other pancreatobiliary disorders. Clinicopathologic features of the 39 PBM-associated GBCs (US:24, Japan:15) were similar; however, comparison with non-PBM GBCs revealed that they occurred predominantly in females (F/M = 3); at younger (<50-year-old) age (21% vs 6.5% in non-PBM GBCs; P = 0.01); were uncommonly associated with gallstones (14% vs 58%; P < 0.001); had higher rate of tumor-infiltrating lymphocytes (69% vs 44%; P = 0.04); arose more often through adenoma-carcinoma sequence (31% vs 12%; P = 0.02); and had a higher proportion of nonconventional carcinomas (21% vs 7%; P = 0.03). Conclusions: PBM accounts for 8% of GBCs also in the West but is typically undiagnosed. PBM-GBCs tend to manifest in younger age and often through adenoma-carcinoma sequence, leading to unusual carcinoma types. If PBM is encountered, cholecystectomy and surveillance of bile ducts is warranted. PBM-associated GBCs offer an invaluable model for variant anatomy-induced chemical (reflux-related) carcinogenesis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aim: Opioid-induced constipation (OIC) is a frequent adverse event (AE) that impairs patients' quality of life (QOL). Peripherally acting μ-opioid receptor antagonists (PAMORAs) have been recognized as a treatment option for OIC, but the effect consistent across the studies has not been evaluated., Methods: We conducted a quantitative meta-analysis to explore the efficacy of PAMORA for OIC (registered with PROSPERO: CRD42018085298). We systematically searched randomized controlled trials (RCTs) in Medline, Embase, and Central databases. Change from baseline in spontaneous bowel movements, pooled proportion of responders, QOL, and AEs were calculated and compared with results in placebo cases., Results: We included 31 RCTs with 7849 patients. A meta-analysis revealed that patients under PAMORA therapy had considerably improved spontaneous bowel movement from baseline compared with those given placebo (20 RCTs; mean difference, 1.43; 95% confidence interval [CI], 1.18-1.68; n = 5622) and more responded (21 RCTs; risk ratio [RR], 1.81; 95% CI, 1.55-2.12; n = 4821). Moreover, QOL of patients receiving PAMORA was significantly better (8 RCTs; mean difference, -0.22; 95% CI, -0.28 to -0.17; n = 2884). AEs were increased significantly in the PAMORA group (26 RCTs; RR, 1.10; 95% CI, 1.06-1.15; n = 7715), especially in gastrointestinal disorders, whereas serious AEs were not significant (17 RCTs; RR, 1.04; 95% CI, 0.85-1.28; n = 5890)., Conclusion: Peripherally acting μ-opioid receptor antagonist has been shown to be effective and durable for patients with OIC and is the only drug with confirmed evidence in meta-analysis. The possibility of publication bias was the limitation of this study., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Pancreaticobiliary maljunction (PBM) is the anomalous union of the main pancreatic duct and common bile duct outside the Oddi-sphincter, allowing the reflux of pancreatic juice to the gallbladder. There is only limited awareness and understanding of the pathologic correlates of this condition, mostly from Japan; this entity is largely unrecognized in the West. In this study, 76 gallbladders from patients with PBM (64 from Japan; 12 from the United States) were analyzed and contrasted with 66 from non-PBM patients. These were predominantly females (54 vs. 22), mean age, 53 (range: 14 to 81). Cholelithiasis was uncommon (16% vs. 80% in non-PBM, P<0.01) whereas cholesterolosis was more common (49% vs. 29%, P=0.02) suggesting an altered chemical milieu. There was a distinctive diffuse mucosal hyperplasia (82% vs. 42%, P<0.01) with markedly elongated folds (mean: 1.1 vs. 0.7 mm, P<0.01) composed of compact villoglandular proliferation, often showing broad-based pushing into muscle, accompanied by prominent and more complex Rokitansky-Aschoff sinus formation (2.0 vs. 1.0/cm, P<0.01) at the base. At the tips, this villiform hyperplasia displayed frequent horizontal bridging of the folds (68% vs. 47%, P=0.01), bulbous dilatation (52% vs. 21%, P<0.01) as well as deposition of a peculiar amyloid-like hyaline material (56% vs. 15%, P<0.01). Despite paucity of inflammation and gallstones, findings attributed to mucosal injury were common including: pyloric gland metaplasia (70% vs. 48%, P=0.01) and intestinal metaplasia (24% vs. 6%, P<0.01). Invasive gallbladder carcinoma was present in 22 (29%) of the cases with 6 of these (27%) arising in association with intracholecystic papillary tubular neoplasm. Five cases had bile duct carcinoma at the time of cholecystectomy and 1 developed it 4 years after. In conclusion, gallbladders with patients with PBM display a distinctive pattern of mucosal hyperplasia with distinguishing features, which in constellation render it a microscopically diagnosable specific entity. We propose to refer to this entity as "reflux-associated cholecystopathy." Recognition of the pathologic characteristics of this entity is important so that investigation for, as well as treatment and prevention of, PBM-associated complications (biliary tract cancers and pancreatitis) can be instituted. This group also offers a distinct model of carcinogenesis (chemical rather than inflammatory) in the gallbladder for cancer researchers to scrutinize.

Benign nodular goiter is a common disease. Although large goiters with obstructive symptoms including shortness of breath and dyspnea are a clear indication for surgery, acute upper airway obstruction, particularly in benign cervical goiter cases, is rare. We herein report the case of 46-year-old female with acute upper airway obstruction due to benign nodular goiter. The patient had a large and elastic goiter which was more pronounced on the left side of her neck, and surgery was scheduled for within a few months. Three months after the initial presentation, while still waiting for surgery, the patient was brought to the emergency room due to loss of consciousness and breathing difficulty and was immediately intubated. A computed tomography (CT) scan revealed that the trachea was markedly compressed by a nodular lesion in the left lobe, and bilateral pneumonia was also evident. Total thyroidectomy was immediately performed via the supraclavicular approach. The patient had an uneventful postoperative course and recovered well. The resected specimen included a well-encapsulated solid and cystic mass. Histopathological examination mainly revealed adenomatous goiter. The present case suggests that benign asymptomatic nodular goiter mostly located in the neck may cause acute airway obstruction, even if the nodules are not large. Early surgery should be performed when tracheal deviation and stenosis due to a large goiter is prominent by CT scan.

We report a case of a patient with seminal vesicle-rectal fistula, an extremely rare complication of low anterior resection of the rectum. A 53-year-old man with rectal adenocarcinoma underwent low anterior resection in our hospital. The patient experienced diarrhea, pneumaturia, and low-grade fever on postoperative day 13. A computed tomography scan showed emphysema in the right seminal vesicle. We concluded that anastomotic leakage induced a seminal vesicle-rectal fistula. The patient underwent conservative therapy with total parenteral nutrition and oral intake of metronidazole. Diarrhea and pneumaturia rapidly improved after metronidazole administration and the patient was successfully cured without invasive therapy such as colostomy or surgical drainage. A seminal vesicle-rectal fistula is a rare complication of low anterior resection, and therapeutic strategies for this condition remain elusive. Our report provides valuable information on the successful conservative treatment of a secondary seminal vesicle-rectal fistula that developed after low anterior resection of the rectum in a patient.

Hypercalcemia with concomitant elevation of serum parathyroid hormone (PTH) and PTH-related protein (PTHrP) levels was found in a patient with advanced gastric carcinoma and multiple liver metastases. The most common features are hypercalcemia associated with hypersecretion of PTHrP and physiological suppression of PTH secretion in the syndrome of humoral hypercalcemia of malignancy (HHM). Although we initially made a diagnosis of primary hyperparathyroidism concomitant with HHM due to gastric cancer, diagnostic imaging studies, such as echography, CT, sestamibi scintigraphy, and autopsy findings, did not reveal evidence of any parathyroid tumors or ectopic parathyroid glands in the mediastinum. Both primary and metastatic tumor cells showed positive staining with PTH-specific antibody as well as PTHrP-specific antibody on immunohistochemical examination. PTH concentration in the cytosolic fraction of the metastatic tumor was elevated compared to that from a control patient with no calcium metabolic disorders in vitro. These findings indicated that PTH secreted ectopically by gastric cancer cells, not by parathyroid glands, caused hypercalcemia in this patient. To our knowledge, this is the first case report of PTH-secreting gastric carcinoma cells. We report the case and a review of the previous reported PTH-secreting non-parathyroid tumors along with the mechanisms of secretion.

Background: Hepatic steatosis may develop after pancreatic resection, but its clinicopathological features remain unclear. We explored the clinical characteristics of newly appearing nonalcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD), designated as de novo NAFLD after PD., Methods: Of 83 patients who underwent PD between 2001 and 2006, the patients with regular alcohol consumption after PD (n = 3), those who were unavailable for regular abdominal computed tomography follow-up (n = 12), and those who died within 6 months of PD (n = 8) were excluded from the study. In the remaining 60 patients, the prevalence and clinical features of de novo NAFLD after PD were examined., Results: NAFLD developed after PD in 14 (23%) patients in our cohort. Liver biopsy was performed in 8 patients and all showed typical steatohepatitis. Compared with the patients who had conventional nonalcoholic steatohepatitis (NASH), patients with post-PD de novo NASH demonstrated significant decreases in body mass index and lower levels of serum albumin, cholesterol, apolipoprotein B, and homeostasis model assessment for insulin resistance. Multivariate logistic regression analysis revealed that pancreatic head cancer was associated with an increased risk of developing NAFLD after PD (odds ratio 12.0, 95% confidence interval 2.0-71.4, P = 0.006). Increased dosage of oral pancreatic enzymes significantly ameliorated the steatosis, as well as leading to the recovery of body weight loss and resolution of the biochemical abnormalities., Conclusions: De novo NAFLD/NASH after PD is characterized by non-obesity and lack of hyperlipidemia and insulin resistance and is associated with pancreatic exocrine insufficiency. In such patients, intensifying pancreatic enzyme supplementation may be useful.

We report herein a rare case of gastrointestinal stromal tumor (GIST) type, arising from the greater omentum. A 65-year-old man who had a large abdominal tumor was referred to our hospital. Ultrasonography (US) and computed tomography (CT) scans showed a mass occupying almost the entire abdomen anterior to the bowel loops. Abdominal angiography showed that the main feeding artery of the tumor was the right gastroepiploic artery. The preoperative diagnosis was suspected gastric leiomyosarcoma. Laparotomy revealed a large mass arising from the greater omentum, and the tumor seemed to be completely excised. Histopathological and immunohistochemical studies indicated the tumor had the same characteristics as GIST. Twelve months after the operation, the tumor recurred in the peritoneal cavity at the site of the stomach, and was associated with multiple liver metastases. The patient died of hypovolemic shock. Necropsy revealed that rupture of one of the metastatic liver tumors had resulted in a massive intraperitoneal hemorrhage.

Evolution of the vertebrate jaw has been reviewed and discussed based on the developmental pattern of the Japanese marine lamprey, Lampetra japonica. Though it never forms a jointed jaw apparatus, the L. japonica embryo exhibits the typical embryonic structure as well as the conserved regulatory gene expression patterns of vertebrates. The lamprey therefore shares the phylotype of vertebrates, the conserved embryonic pattern that appears at pharyngula stage, rather than representing an intermediate evolutionary state. Both gnathostomes and lampreys exhibit a tripartite configuration of the rostral-most crest-derived ectomesenchyme, each part occupying an anatomically equivalent site. Differentiated oral structure becomes apparent in post-pharyngula development. Due to the solid nasohypophyseal plate, the post-optic ectomesenchyme of the lamprey fails to grow rostromedially to form the medial nasal septum as in gnathostomes, but forms the upper lip instead. The gnathostome jaw may thus have arisen through a process of ontogenetic repatterning, in which a heterotopic shift of mesenchyme-epithelial relationships would have been involved. Further identification of shifts in tissue interaction and expression of regulatory genes are necessary to describe the evolution of the jaw fully from the standpoint of evolutionary developmental biology.

Due to the peculiar morphology of its preotic head, lampreys have long been treated as an intermediate animal which links amphioxus and gnathostomes. To reevaluate the segmental theory of classical comparative embryology, mesodermal development was observed in embryos of a lamprey, Lampetra japonica, by scanning electron microscopy and immunohistochemistry. Signs of segmentation are visible in future postotic somites at an early neurula stage, whereas the rostral mesoderm is unsegmented and rostromedially confluent with the prechordal plate. The premandibular and mandibular mesoderm develop from the prechordal plate in a caudal to rostral direction and can be called the preaxial mesoderm as opposed to the caudally developing gastral mesoderm. With the exception of the premandibular mesoderm, the head mesodermal sheet is secondarily regionalized by the otocyst and pharyngeal pouches into the mandibular mesoderm, hyoid mesoderm, and somite 0. The head mesodermal components never develop into cephalic myotomes, but the latter develop only from postotic somites. These results show that the lamprey embryo shows a typical vertebrate phylotype and that the basic mesodermal configuration of vertebrates already existed prior to the split of agnatha-gnathostomata; lamprey does not represent an intermediate state between amphioxus and gnathostomes. Unlike interpretations of theories of head segmentation that the mesodermal segments are primarily equivalent along the axis, there is no evidence in vertebrate embryos for the presence of preotic myotomes. We conclude that mesomere-based theories of head metamerism are inappropriate and that the formulated vertebrate head should possess the distinction between primarily unsegmented head mesoderm which includes preaxial components at least in part and somites in the trunk which are shared in all the known vertebrate embryos as the vertebrate phylotype., (Copyright 1999 Academic Press.)

Neural crest cells contribute extensively to vertebrate head morphogenesis and their origin is an important question to address in understanding the evolution of the craniate head. The distribution pattern of cephalic crest cells was examined in embryos of one of the living agnathan vertebrates, Lampetra japonica. The initial appearance of putative crest cells was observed on the dorsal aspect of the neural rod at stage 20.5 and ventral expansion of these cells was first seen at the level of rostral somites. As in gnathostomes, cephalic crest cells migrate beneath the surface ectoderm and form three major cell populations, each being separated at the levels of rhombomeres (r) 3 and r5. The neural crest seems initially to be produced at all neuraxial levels except for the rostral-most area, and cephalic crest cells are secondarily excluded from levels r3 and r5. Such a pattern of crest cell distribution prefigures the morphology of the cranial nerve anlage. The second or middle crest cell population passes medial to the otocyst, implying that the otocyst does not serve as a barrier to separate the crest cell populations. The three cephalic crest cell populations fill the pharyngeal arch ventrally, covering the pharyngeal mesoderm laterally with the rostral-most population covering the premandibular region and mandibular arch. The third cell population is equivalent to the circumpharyngeal crest cells in the chick, and its influx into the pharyngeal region precedes the formation of postotic pharyngeal arches. Focal injection of DiI revealed the existence of an anteroposterior organization in the neural crest at the neurular stage, destined for each pharyngeal region. The crest cells derived from the posterior midbrain that express the LjOtxA gene, the Otx2 cognate, were shown to migrate into the mandibular arch, a pattern which is identical to gnathostome embryos. It was concluded that the head region of the lamprey embryo shares a common set of morphological characters with gnathostome embryos and that the morphological deviation of the mandibular arch between the gnathostomes and the lamprey is not based on the early embryonic patterning., (Copyright 1999 Academic Press.)

Early embryonic development of the nervous system of a lamprey, Lampetra japonica, was studied by using immunohistochemical techniques and by scanning electron microscopy. The earliest appearance of axons was detected at Tahara's stage 21-, when dorsolateral and ventral longitudinal fasciculi were present in the hindbrain and spinal cord regions. The branchiomeric nerve roots began to appear at stage 22; the fibers were joined to the dorsolateral fasciculus proximally and also extended distally into each pharyngeal arch. The anterior neural tube was divided into several neuromeres: the mid-hindbrain sulcus became apparent first, then the portion rostral to this sulcus was subdivided into two portions by the syn-parencephalic boundary. In the hindbrain around stage 23, rhombomeres developed transiently, of which, rhombomere 4 was the most distinctive. Putative crest cells forming the octavofacial nerve root anlage were selectively adhering to rhombomere 4, whereas no crest cells were found on rhombomere 3. The assignment of the crest-derived nerve anlage to rhombomeres is conserved between gnathostomes and L. japonica. The neuromerical scheme of the neural tube of L. japonica is also mostly in accordance with that in gnathostomes, sharing the basic developmental patterning of axon bundles at early developmental stages. The most distinct difference between these two groups is the topographical relationships between the hindbrain neuraxis and pharyngeal arches, as well as the otic placode.

Background: Hepatic invasion is an important factor in the selection of an operative procedure for patients with carcinoma of the gallbladder. Imaging modalities to detect the hepatic invasion were evaluated for accuracy, and postoperative patient outcome was analyzed., Study Design: Thirty-six patients who were treated for carcinoma of the gallbladder at our institution between 1984 and 1993 were studied. The imaging results of ultrasonography (US), computed tomography, and angiography were compared with histologic findings regarding intrahepatic invasion of the carcinoma., Results: Histologic examination of the operative specimens removed from 21 patients revealed that the detection of hepatic invasion with preoperative US was superior to that with the other two modalities. The preoperative US showed a diagnostic value that was almost the same as that of the intraoperative US. The postoperative patient outcome was not satisfactory, although extended radical operation was performed using image guidance in the 21 patients. The patients died as a result of nodal recurrence rather than hepatic recurrence., Conclusions: Preoperative US should be performed initially for detecting hepatic invasion from carcinoma of the gallbladder and can be substituted for intraoperative US. Considering the operative treatment for patients with carcinoma of the gallbladder, lymph node dissection is as important as the extent of hepatectomy.

This paper presents a case with lung metastases from breast cancer. Complete response was obtained by combined chemoendocrine therapy with 5'-DFUR and MPA. The patient was a 62-year-old female. She underwent a standard radical mastectomy in April, 1988. The primary legion was ER (-) and PgR (-). Postoperative treatments using CMF and CAF were eventually discontinued owing to profound damage to the bone marrow. An adjuvant chemotherapy with UFT has been employed since. Two years and 7 months later, hemosputum and coughing appeared, and metastases to the lung were revealed. Combined chemoendocrine therapy with 5'-DFUR and MPA was undertaken. A significant decrease in tumor size was observed 3 months after the chemoendocrine therapy was begun, and complete response was obtained at the 8th month. The state has been maintained for one year and 9 months. The use of combined chemoendocrine therapy with 5'-DFUR and MPA in patients for whom intensive chemotherapy is not possible due to damage to bone marrow function is considered effective for its antitumor effects or maintaining patients' quality of life.

A case of a gas-forming liver abscess developing after transcatheter arterial embolization for recurrent hepatocellular carcinoma (HCC) in a 65-year-old man is presented herein. He was admitted to hospital with fever and jaundice, following which ultrasonography (US) and computed tomography revealed a gas-containing abscess in the posterior segment of the hepatic lobe with multiple HCC. Percutaneous transhepatic drainage was performed using US. Antibiotics which were sensitive to the Escherichia coli bacteria detected in the abscess were administered both intravenously and through the drainage tube into the abscess. Four months later, the abscess had diminished and the patient was discharged after receiving percutaneous ultrasonographically guided ethanol injection therapy for the recurrent HCC.

Nine patients with liver metastases from gastric cancer were treated in our department since 1986. Hepatectomy was performed in 3 cases and hepatic arterial infusion chemotherapy was performed in 6 cases. In 3 patients in whom hepatectomy was performed, the extent of liver metastases showed 2 H1 and 1 H2. One has survived for 20 months, but the other 2 died after 5 and 7 months, respectively. In 6 patients in whom hepatic arterial infusion chemotherapy was performed, the extent of liver metastases was H3. These patients were treated with 5-FU.EPIR.MMC (3 cases), CDDP.MMC (1 case), MMC only (1 case) and 5-FU.ADM.MMC.CDDP (1 case). This treatment revealed a 50% response rate (CR 1, PR 2). The patient with CR has survived for 6 years and 2 patients with PR died after 8 and 12 months. The patient with CR showed high AFP level (55, 480 ng/ml), and 2 patients with PR showed high AFP level (24, 327 ng/ml) or high CEA level (3,903 ng/ml). The prognosis of hepatectomy for liver metastases from gastric cancer was not so good. Hepatic arterial infusion chemotherapy seemed to be a useful treatment for liver metastases from gastric cancer.

The antitumor activity and immunological effects of the local administration of 5FU were investigated by determining the tissue concentration of 5FU, histological appearance of the primary tumor, and lymphocyte subsets of the regional lymph nodes in 23 rectal cancer patients. Twelve patients were treated with 5FU suppositories preoperatively, being the 5FU group, while 11 patients were given no preoperative treatment, being the control group. The 5FU concentrations in the primary tumors were higher than those in the regional lymph nodes and appeared to remain high for an extended period. No histological changes peculiar to the 5FU group were observed in the primary tumors. An analysis of the lymphocyte subsets in the pararectal nodes revealed that Leu2a+15- cells, or cytotoxic T lymphocytes, were significantly decreased in numbers in the 5FU group compared to the control group. These results suggest that the local use of 5FU may not only exert an antitumor effect against rectal cancer, but can also cause the suppression of antitumor immunity in the regional lymph nodes.

To clarify the discrepancy in hepatitis B surface antigen (HBsAg) subtypes present in the serum and liver, as well as among hepatocytes, liver specimens which were resected from 37 HBsAg-positive patients with hepatocellular carcinoma (HCC) were examined. We evaluated HBsAg and the subtypic determinants of HBsAg and hepatitis B core antigen (HBcAg) using the peroxidase-antiperoxidase (PAP) staining method. Hepatitis B antigens were more frequently detected in small tumors (HBsAg in 67%. HBcAg in 40%) than in large ones (HBsAg in 36%, HBcAg in 14%). The prevalence of each subtypic determinant in the HBsAg positive non-tumorous vs. tumorous areas was 100% vs. 67% in a, 100% vs. 57% in d, 100% vs. not tested in y, 100% vs. 53% in r and 25% vs. 0% in w (a, d, y, r and w represent subtypic determinants). There was virtually no difference in a set of subtypic determinants between the serum and liver. However, there were some variations in a set of subtypic determinants among the hepatocytes. On the other hand, liver tissue of compound subtype adyr in serum contained both cells with a,d,r and with a,y,r as well as a few cells with a,d,y,r. These findings suggest that HBV genomes in hepatocytes of type B chronic liver disease may differ genetically among cells even in the same liver tissue.

Hepatectomy has been a treatment of choice for hepatocellular carcinoma and metastatic liver carcinoma. Recurrence in residual liver after hepatectomy is clinically a serious problem. Since 1987, postoperative hepatic arterial infusion chemotherapy using subcutaneously implanted reservoir has been undertaken to improve the prognosis after hepatectomy in hepatocellular carcinoma and liver metastasis of colorectal carcinoma. The indications for reservoir implantation were determined for high-risk cases in hepatocellular carcinoma and all cases in liver metastasis. The tip of a catheter was placed at the root of the common hepatic artery via gastroduodenal artery. Lipiodol-ADM was injected for hepatocellular carcinoma every 2 months and MMC-5-FU was injected for liver metastasis of colorectal carcinoma every one or two weeks. Complications of this procedure in every 2 cases of reservoir infection proved to be catheter obstruction and hepatic artery obstruction. In the process of this treatment, we observed 3 recurrences in residual liver of hepatocellular carcinoma and one case of peritoneal dissemination and 3 recurrences in residual liver of liver metastasis of colorectal carcinoma. All are still alive.

The bilateral hemispheric ischemia in rats was induced by the occlusion of bilateral common carotid arteries after permanent electrocauterization of bilateral vertebral arteries at the level of the second cervical vertebra. In ischemic rats, (a) electroencephalograms became flat immediately after occlusion of carotid arteries, and (b) mortalities reached maximum levels at day 3 after recirculation. These results suggested that a constant level of cerebral ischemia was produced in this rat model. Pentobarbital markedly inhibited the mortality in these ischemic rats, whereas cyproheptadine did not.