Pharmacological properties of various anesthetic protocols in 10-day-old neonatal rats.

In general, the anesthesia in neonates involves high risk. Although hypothermic anesthesia is recommended in rats up to the age of 7 days, neonatal anesthesia for later periods has not been standardized. The present study investigated the pharmacological properties of conventional anesthetic protocols in 10-day-old SD rats. The rats were anesthetized with four anesthetics: a combination of ketamine and xylazine (K/X); a combination of medetomidine, midazolam, and butorphanol (M/M/B); isoflurane; and sevoflurane. Anesthetic depth was scored by reflex response to noxious stimuli. Induction and recovery times were recorded. Vital signs and mortality rate were evaluated for safety assessment. All rats died after administration of K/X at a dose of 60/6 mg/kg, whereas K/X at 40/4 mg/kg resulted in insufficient anesthetic depth, indicating inappropriate for neonatal anesthesia. Although M/M/B at the adult rat dose (0.15/2/2.5 mg/kg) did not provide surgical anesthetic depth, the mouse dose (0.3/4/5 mg/kg) showed sufficient anesthetic depth with relatively stable vital signs. Isoflurane required a long induction period, and caused remarkable respiratory depression and hypothermia, resulted in a 25% mortality rate. In contrast, sevoflurane provided consistent surgical anesthetic depth with rapid induction. Although respiratory rate decrease was markedly observed, all rats survived. Among the anesthetic protocols investigated in the present study, sevoflurane and M/M/B at the mouse dose were recommended for the neonatal anesthesia. Compared with adult rats, the required dose of both anesthetics in neonates was higher, possibly associated with their lower anesthetic sensitivity.

Successful treatment of proton pump inhibitor induced sporadic fundic gland polyps with an argon plasma coagulator in a patient with polycythaemia vera.

INTRODUCTION: Proton pump inhibitor (PPI) use is associated with the development of fundic gland polyps (FGPs); discontinuing PPIs is associated with regression of FGPs. Here, we report a rare case of non-respondent FGPs after discontinuation of PPI that were successfully treated using an argon plasma coagulator (APC). PRESENTATION OF CASE: We present the case of a 68-year-old woman with a history of polycytheamia vera. She also had gastroesophageal reflux disease (GERD) and had been taking 10 mg of omeprazole daily for the past three years. Esophagogastroduedenoscopy (GF) revealed over 100 pedunculated polyps in the gastric body and fundus. Histological examination of the specimens showed dilated oxyntic glands with flattened parietal and mucous cells. Based on these findings and the clinical history, a diagnosis of FGPs was made. Omeprazole use was then discontinued. Repeat GF performed 6 months and 1 year later showed a significant increase in the number and size of the polyps. APC treatment was performed every 6 months for 3 years. Further GF showed a significant decrease in the number and size of the FGPs 4 years after discontinuing PPI. DISCUSSION: We conclude that PPI use is a strong risk factor for the development of FGPs and discontinuing PPI is associated with regression of FGPs, but not in patients with polycythaemia vera. However, the mechanism involved in the interaction between FGP and polycytheamia vera remains unknown. CONCLUSION: Non-respondent FGPs after discontinuation of PPI use may be successfully treated using APC.

Computed tomography-gastro-colonography for percutaneous endoscopic gastrostomy using a helical computed tomography.

BACKGROUND: Despite the widespread use of percutaneous endoscopic gastrostomy (PEG) tubes, their placement may be associated with a variety of complications, including gastrocolic fistula. METHODS: In total, 48 individuals underwent computed tomography-gastro-colonography (CT-GC)-guided PEG placement. Study end points included success of CT-GC, inability to thread the PEG tube, the eventual tube location, tube adjustments needed, adverse events, operating time, and PEG tube-related infection. RESULTS: A successful CT-GC was achieved in all 48 patients (100%), and we successfully used a standard PEG technique to place the gastrostomy tube in 44 patients (92%). In 4 patients (8%), the laparoscopic-assisted PEG technique was used because the transverse colon became interposed between the abdominal wall and the anterior wall of the stomach. The overall procedure-related minor complication rate was 8%. CONCLUSION: CT-GC is an optional method for the estimation of intra-abdominal, anatomical orientations that may minimize the risk of complications before PEG placement.

Pravastatin-induced rhabdomyolysis and purpura fulminans in a patient with chronic renal failure.

INTRODUCTION: Rhabdomyolysis associated with the use of pravastatin has been demonstrated to be a rare but potentially life-threatening adverse effect of statins. Here, we report a rare case of rhabdomyolysis and purpura fulminans in a patient who had used pravastatin and developed chronic renal failure (CRF) necessitating the initiation of dialysis. PRESENTATION OF CASE: We present the case of an 86-year-old man with chronic kidney disease (CKD) treated with dialysis who was admitted with back pain. He was prescribed and took pravastatin for almost 3 years to treat hyperlipidemia. He received hemodialysis therapy 7 times prior to presentation. Laboratory values included a serum creatine concentration of 6.6mg/dl and a creatinine phosphokinase (CPK) concentration of 2350IU/L. An abdominal computed tomography scan showed swollen muscles with reduced muscle density and air density in the multifidus muscle. Two days after admission, he had large, tender ecchymotic lesions and purpuric progressive skin necrosis over the back, abdomen, and upper and lower extremities. The patient died 6 days after the initial admission due to disseminated intravascular coagulation (DIC). Based on these findings and the clinical history, a diagnosis of pravastatin-induced rhabdomyolysis and purpura fulminans was made. DISCUSSION: The long-term use of statin therapy and the initiation of dialysis therapy due to ESRD, followed by a rapid onset of rhabdomyolysis within 6 days, is indicative of an elevated statin concentration. CONCLUSION: We report an extremely rare case of pravastatin-induced rhabdomyolysis and purpura fulminans with DIC in a patient with CRF.

Primary colon cancer with a high serum PIVKA-II level.

INTRODUCTION: Protein induced by vitamin K absence/antagonist-II (PIVKA-II) is an abnormal protein, and several reports have demonstrated the efficacy of PIVKA-II in the diagnosis of hepatocellular carcinoma (HCC). We report an extremely rare case of adenocarcinoma of the colon with a high serum PIVKA-II level. PRESENTATION OF CASE: A 95-year-old woman presented with right lower quadrant pain and appetite loss. An abdominal computed tomography scan and ultrasonography showed an ascending colon tumor and multiple metastatic tumors in the liver. The serum level of PIVKA-II was extremely high, 11,900ng/mL. Colonoscopic examination revealed a tumor accompanied by an ulcer in the ascending colon, which was highly suspicious for malignancy. Multiple biopsies showed well-differentiated adenocarcinoma of the colon, which was evaluated as colon cancer, stage IV. PIVKA-II-productive colon cancer was confirmed. Chemotherapy with TS-1 was administered. The patient died 3 months after initial admission. DISCUSSION: The expression of PIVKA-II was detected in non-cancer areas, with non-specific expression observed in plasma cells in our case. There might be some possibility that hepatoid differentiation exists in other regions of the colon tumor or in the liver tumor, parenchymal cells or lung metastases, which were composed of PIVKA-II-positive and AFP-negative cells. CONCLUSION: To the best of our knowledge, high serum levels of PIVKA-II resulting from colon adenocarcinoma have not been reported previously. We report this rare case together with a review of the literature.

Successful treatment of acute myeloid leukaemia in a patient with ataxia telangiectasia.

Ataxia telangiectasia (AT) is a rare autosomal recessive multisystem disorder characterised by cerebellar degeneration, immunodeficiency and cancer predisposition. Around 10% of AT patients develop lymphoid malignancies, but the development of myeloid leukaemia with AT (AT-AML) is extremely rare, and there have been no previous publications regarding suitable therapies. Here, we first describe a successful therapeutic experience in a patient with AT-AML (FAB-M1) who attained remission after induction therapy and maintained stable disease for a year. To minimise therapy-induced toxicity, low-dose induction was applied first, though this was obviously insufficient and the patient subsequently responded well to dose-intensified short-term chemotherapy. In this report, we suggest a curative therapeutic approach for AT-AML, though the issue of how best to manage patients with cancer complicated by immunodeficiency remains undecided.

[Successful treatment with sorafenib for primary refractory acute monoblastic leukemia with FLT3-ITD].

A 6-year-old boy was diagnosed with FLT3-ITD+acute monoblastic leukemia (AMoL). He showed resistance to 2 cycles of induction chemotherapy with etoposide, cytarabine, and mitoxantrone or idarubicin performed according to the Japan Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 protocol. His condition was also refractory to salvage FLAI-GO (fludarabine, cytarabine, idarubicin, and gemtuzumab ozogamicin) chemotherapy. Sequential administration of sorafenib at doses of up to 300 mg/day resulted in the first remission. He underwent bone marrow transplantation from his HLA 2-locus mismatched father. Recurrence was observed on post-transplantation day 71. A sustained partial response was observed after alternate-day readministration of sorafenib 150mg/day. In spite of a donor lymphocyte infusion, his blast cell count increased on day 245. Chemotherapy with an increased dose of sorafenib reduced the blast cell count. Although a second HLA-mismatched allogeneic peripheral blood stem cell transfusion was performed, the patient died of regimen-related toxicity. Herein, we report a pediatric case of primary refractory FLT3-ITD+ AMoL. Further prospective studies are necessary to validate the efficacy of sorafenib treatment.

Primary adenocarcinoma of the stomach in von Recklinghausen's disease with high serum levels of multiple tumor markers: a case report.

INTRODUCTION: Gastric tumors in patients affected by neurofibromatosis type 1 are usually carcinoids or stromal tumors, and rarely adenocarcinomas. CASE PRESENTATION: We report a case of an adenocarcinoma of the stomach in a 53-year-old Japanese man with neurofibromatosis type 1. An abdominal computed tomography scan and ultrasonography showed tumors in his liver. Gastric fibroscopy revealed a Borrmann type III tumor on his cardia that had spread to his esophagus and was highly suspicious for malignancy. Multiple biopsies showed an adenocarcinoma of the stomach, which was evaluated as gastric cancer, stage IV. Chemotherapy with TS-1 was performed. Our patient died four weeks after initial admission. Histological examination of a liver needle biopsy showed metastatic adenocarcinoma in his liver. CONCLUSION: To the best of our knowledge, high serum levels of α-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 72-4, resulting from gastric adenocarcinoma, have not been reported previously in a patient with neurofibromatosis type 1. We report this rare case along with a review of the literature.

Rhabdomyolysis associated with fenofibrate monotherapy in a patient with chronic myelogenous leukemia.

Rhabdomyolysis associated with fenofibrate monotherapy is extremely rare. Here, we report a rare case of rhabdomyolysis of the psoas muscle in an 82-year-old man with chronic myelogenous leukemia (CML). He was prescribed fenofibrate because of a hypertriglyceridemia. The patient reported generalized muscle pain and right abdominal pain while receiving fenofibrate monotherapy. An abdominal computed tomography scan and an abdominal ultrasound showed a large and low attenuation and high echogenicity, respectively, in the right middle abdominal area. Laboratory values included a serum creatine concentration of 4.1 mg/dl and a creatinine phosphokinase concentration of 5,882 IU/l. During laparotomy, a large hematoma and necrotic mass was identified in the right psoas muscle. Histological examination revealed that the resected specimens were of the psoas muscle with irregular fiber sizes, degenerating fibers surrounding the inflammatory reaction, and fiber necrosis that is typical for polymyositis. Based on these findings and the clinical history, a diagnosis of fenofibrate-induced rhabdomyolysis was made. To the best of our knowledge, no patient has ever been diagnosed with fulminant psoas rhabdomyolysis due to a fenofibrate monotherapy. This report details the rare case of rhabdomyolysis in a patient with CML associated with fenofibrate monotherapy and offers a review of the literature.

Gastric Cancer with a Very High Serum CA 19-9 Level.

Carbohydrate antigen 19-9 (CA 19-9) is a sensitive marker for pancreatic and hepatobiliary malignancies. The highest frequency of elevated serum CA 19-9 levels is found among patients with pancreatic cancer. CA 19-9 has recently been demonstrated to be a marker of digestive tract malignancies. We report the case of a patient with a gastric cancer and a very high serum CA 19-9 level. During laparotomy, a large mass was found in the antrum. A distal gastrectomy with D2 dissection of the lymph nodes was performed. Histological examination, including immunohistochemistry, revealed an adenocarcinoma of the stomach producing CA 19-9. To the best of our knowledge, no patient with an extremely high serum CA 19-9 level resulting from a gastric adenocarcinoma has been reported previously.

Histological protection by cilnidipine, a dual L/N-type Ca(2+) channel blocker, against neurotoxicity induced by ischemia-reperfusion in rat retina.

Although a blockade or lack of N-type Ca(2+) channels has been reported to suppress neuronal injury induced by ischemia-reperfusion in several animal models, information is still limited regarding the neuroprotective effects of a dual L/N-type Ca(2+) channel blocker, cilnidipine. We histologically examined the effects of cilnidipine on neuronal injury induced by ischemia-reperfusion, intravitreous N-methyl-D-aspartate (NMDA) (200nmol/eye) and intravitreous NOC12 (400nmol/eye), an nitric oxide donor, in the rat retina, and compared its effects with those of omega-conotoxin MV IIA, an N-type Ca(2+) channel blocker and amlodipine, an L-type Ca(2+) channel blocker. Morphometric evaluation at 7 days after ischemia-reperfusion showed that treatment with cilnidipine (100microg/kg, i.v. or 0.5pmol/eye, intravitreous injection) prior to ischemia dramatically reduced the retinal damage. Treatment with omega-conotoxin MV IIA before ischemia (0.1pmol/eye, intravitreous injection) significantly reduced the retinal damage. However, amlodipine (30-100microg/kg, i.v. or 0.1-1pmol/eye, intravitreous injection) did not show any protective effects. Treatment with cilnidipine (100microg/kg, i.v.) reduced the retinal damage induced by intravitreous NMDA, but not NOC12. These results suggest that cilnidipine reduces Ca(2+) influx via N-type Ca(2+) channels after NMDA receptors activation and then protects neurons against ischemia-reperfusion injury in the rat retina in vivo. Cilnidipine may be useful as a therapeutic drug against retinal diseases which cause neuronal cell death, such as glaucoma and central retinal vessel occlusion.

Genetic analysis of Shwachman-Diamond syndrome: phenotypic heterogeneity in patients carrying identical SBDS mutations.

Shwachman-Diamond syndrome (SDS) is a rare hereditary disorder characterized by pancreatic exocrine insufficiency, bone marrow dysfunction and skeletal changes. Recently, the cause of SDS was identified as mutations of Shwachman-Bodian-Diamond syndrome gene (SBDS) and most mutations are caused by gene conversion between SBDS and its highly homologous pseudogene. Clinical variations especially in skeletal and bone marrow abnormalities are well known in this syndrome. To study the relationship between SBDS mutation and its clinical features, we analyzed 9 Japanese patients including one sibling and detected the three different SBDS mutations in 7 patients: a mutation that disrupts the donor splice site of intron 2, deletes 8 bp of the exon 2 and produces premature termination (258+2 T > C), a dinucleotide change that replaces a lysine at 62 nd amino acid to a termination codon (183-184 TA > CT), and a 4-bp deletion that causes premature termination by frameshift (292-295 delAAAG). The 5 patients represent compound heterozygotes of the 258+2 T > C and 183-184 TA > CT mutations. One patient is a compound heterozygote of the 258+2 T > C and 292-295 delAAAG mutations, and in the remaining one case only a 258+2 T > C mutation could be detected. Thus, the 258+2 T > C and 183-184 TA > CT mutations are prevalent among Japanese patients. No mutations were found in two cases, despite the clinical features. Of the 7 patients with SBDS mutations, persistent hematologic abnormalities and skeletal changes were not observed in 3 and 2 patients, respectively. Notably, clinical variations are present even among the patients with the identical genotype: compound heterozygotes of the 258+2 T > C and 183-184 TA > CT mutations. Further study will be required to explain the clinical heterogeneity.

Successful unrelated donor bone marrow transplantation for Shwachman-Diamond syndrome with leukemia.

Shwachman-Diamond syndrome (SDS) is a rare congenital disorder featuring exocrine pancreatic insufficiency, growth retardation, and bone marrow dysfunction. Reports suggest that nearly 25% of all cases are complicated with leukemia. Although stem cell transplantation is the sole option for these patients, successful results are rarely obtained. Poor outcomes are often related to graft failure and cardiac and other organ toxicities. We describe in this report successful unrelated donor bone marrow transplantation for a patient with SDS who progressed to acute myelogenous leukemia. The patient received attenuated intensified chemotherapy because of his intolerance to ordinary chemotherapy and went into remission. Sustained unrelated donor bone marrow engraftment was accomplished after treatment with a reduced amount of cyclophosphamide and antithymocyte globulin with 12 Gy of total body irradiation as a conditioning regimen. To the best of our knowledge, this report is the first to describe unrelated donor bone marrow transplantation with complete engraftment for an SDS patient with myelogenous leukemia.

Haemophagocytic lymphohistiocytosis following measles vaccination.

UNLABELLED: A 19-month-old girl developed haemophagocytic lymphohistiocytosis following a measles vaccination. She developed persistent high fever 1 week after vaccination, and then showed pancytopenia, liver dysfunction and hepatosplenomegaly with marked haemophagocytosis. Based on the clinical and laboratory findings, she was diagnosed as having haemophagocytic lymphohistiocytosis probably due to measles vaccination. She did not respond fully to first-line immunosuppressive therapy and required immunochemotherapy with cytotoxic drugs. CONCLUSION: To the best of our knowledge, this is the first detailed report of haemophagocytic lymphohistiocyosis associated with measles vaccination documented in the English literature. Haemophagocytic lymphohistiocyosis should be kept in mind as one of the rare adverse effects of vaccination.

[Acute pancreatitis following hematopoietic stem cell transplantation: prevalence and cause of pancreatic amylasemia].

To clarify the frequency and cause of acute pancreatitis following hematopoietic stem cell transplantation (SCT), we examined retrospectively 57 patients who underwent hematopoietic SCT in our institute from 1984 to 2000. Twelve (21%) of the patients showed an elevated level of serum pancreatic amylase following SCT. However, only 3 patients were clinically diagnosed as having acute pancreatitis. Among these 12 patients, 11 had undergone allogeneic transplantation. Furthermore, patients who had undergone unrelated transplantation (7/16; 44%) tended to show a higher incidence of increased amylase than those who had undergone related transplantation (4/24; 17%). Six patients were at an advanced stage of acute GVHD (grade III or IV) and all showed an elevated level of serum amylase, whereas only four patients showed an elevated serum amylase level among 34 with mild acute GVHD (grade I or II) or without GVHD. Furthermore, five out of 12 patients who showed an increased amylase level were concurrently diagnosed as having viral infection such as cytomegalovirus, adenovirus, or varicella zoster virus. We conclude that pancreatitis following SCT occurs more often than realized, and is mostly subclinical. This is closely associated with severe acute GVHD, and possibly viral infection.

Association of the uteroglobin gene polymorphism with IgA nephropathy.

Immunoglobulin A (IgA) nephropathy results from the abnormal deposition of IgA in the renal mesangium. Genetic factors may be involved in the development and progression of IgA nephropathy. Uteroglobin (UG) is a steroid-inducible, cytokine-like, multifunctional protein with anti-inflammatory and immunomodulatory properties. The knockout or antisense mouse of the UG gene develops renal disease similar to IgA nephropathy. We analyzed the UG gene as a candidate for a predisposing factor in 61 Japanese patients with IgA nephropathy (23 children, 38 adults) and detected only the G38A mutation. The gene frequency of the G38A mutation in patients was 0.43, not significantly different from the frequency of 0.36 in healthy controls. However, the frequency of patients homozygous for G38A was twice that of controls, and a significant increase was seen in child patients. We measured serum UG levels in patients and healthy adults. A significant decrease in serum UG levels in homozygotes of G38A compared with homozygotes of G38 was detected only in adult women patients and controls. There is no information on where serum UG is produced or how UG may work in association with IgA nephropathy. However, it is possible that the effect of G38A may be apparent under such stimulation as sex steroids or infections, and homozygotes of the G38A mutation cannot produce sufficient UG in response to stimulation and may be predisposed to IgA nephropathy, especially in childhood.