A case of immediate allergy to anisakis following saury intake]

We report here a 76-year-old male that presented with an immediate allergy to Anisakis following saury intake. Three and a half hours after eating pressed saury sushi, whole-body pomphus appeared including itching, facial dropsical swelling, and dyspnea. Diagnostic tests revealed specific IgE antibodies against anisakis simplex and a skin prick test was positive using an extraction of anisakis simplex. The results of skin prick tests using the body and internal organs of a saury were negative. Based on these results, we diagnosed the case as immediate allergy to Anisakis. Anisakis is parasitic to a diverse array of fish, and it seems rare that eating saury will induce an allergic response because the reported parasitic rate of Anisakis on saury is only 5%. In addition, as tropomyosin is currently considered to be the primary cause of allergies to Anisakis, renewed attention should be paid to other foods for which tropomyosin is also assumed to be a common antigen.     

Frequent premature ventricular contractions induced by itraconazole.

Itraconazole is widely used to treat onychomycosis because of its significant therapeutic effects. An otherwise healthy 30-year-old man treated with itraconazole developed frequent premature ventricular contractions (PVC). He presented with a dry cough and palpitation. The results of 12-lead electrocardiography (ECG) were essentially normal, but Holter ECG revealed 17,484 (18%) uniform PVC, including 4 short runs among 96,930 beats/day. Another Holter ECG after withdrawing itraconazole revealed 1,032 premature atrial contractions but no PVC. The corrected QT interval was 0.39 s without itraconazole, 0.41 s with itraconazole, and 0.43 s when multiple PVC were documented. Itraconazole inhibits the fungal cytochrome P450 that is involved in fungal cell membrane formation, interrupts human cytochrome P450A4 in the liver and causes adverse interactions with various drugs such as antiarrythmics, but its cardiac side-effects are obscure. Both patients and physicians should be aware that itraconazole can cause PVC as a side-effect.     

Surface epithelial cell damage induced by restraint and water-immersion stress in rats effects of 16,16-dimethyl prostaglandin E2 on stress-induced gastric lesions

The time-course of gastric mucosal surface epithelial cell damage and macroscopically visible lesions in response to restraint and water-immersion stress (22 degrees C) in rats was examined, and the effects on it of 16,16-dimethyl prostaglandin E2 (dmPGE2) were compared with those of papaverine, timoprazole and atropine. The stress produced surface epithelial cell damage prior to visible lesion, the former increasing in severity with time and reaching a plateau 60 min later, by which time exfoliation of surface epithelial cells was observable along the mucosal folds. In contrast, macroscopically visible lesions appeared 2 hr after stress, and severity continued to increase with time. Pretreatment injections (s.c.) of dmPGE2 (3, 30 micrograms/kg), papaverine (100 mg/kg) and atropine (1 mg/kg) protected the surface cells against stress (1 hr)-induced damage, and inhibited visible lesion formation after 4 hr stress. Timoprazole (30 mg/kg, s.c.) did not protect the surface cells, but did markedly inhibit visible lesion formation. dmPGE2, papaverine and atropine, but not timoprazole, inhibited stress-induced increases in gastric contractions. dmPGE2, timoprazole and atropine, but not papaverine, inhibited acid secretion in stress-conditions. These results indicated that stress induced damage to the gastric mucosa within 1 hr due to increased gastric contractions, and the surface epithelial cell damage developed into macroscopically visible lesions in the presence of acid, and that dmPGE2 protected the surface epithelium against stress-induced damage probably by inhibiting gastric contractions.     

A case of heparin-induced thrombocytopenia that worsened preexisting cerebral infarction]

A 75-year-old man was admitted to our hospital with dysesthesia of the right lip, dysphagia and gait disturbance. He presented with right Wallenberg syndrome and brain MR image showed a fresh infarction in the right lateral medulla. Therapy with heparin and ozagrel sodium was started. For a time his symptom improved a little, but after 8 days he developed re-infarction, thrombocytopenia and DIC, while being treated with heparin for cerebral infarction. Heparin was discontinued, and these symptoms improved quickly. The clinical course and the positive anti-platelet factor 4-heparin complex antibody suggested that these symptoms were caused by heparin-induced thrombocytopenia (HIT). HIT should be included as a differential diagnosis for progression of ischemic stroke under heparin therapy.     

Congenital pseudarthrosis of the tibia: analysis of the histology and the <Emphasis Type="Italic">NF1</Emphasis> gene

Background Congenital pseudarthrosis of the tibia (CPT) is frequently, but not always, associated with neurofibromatosis type 1 (NF1). Double inactivation of the NF1 gene has been reported to be the pathogenesis of CPT in NF1 cases. Methods We analyzed the loss of heterozygosity (LOH) of the NF1 gene in cases of CPT with NF1 to examine whether double inactivation was seen in the case. In addition to morphological analysis, immunoexpression of differentiation markers was examined. Results and discussion The tibia tapered with the zone phenomenon from mature to immature bone with osteoblastic rimming, resembling osteofibrous dysplasia. Osteosclerotic bowed bone with a small number of osteoclasts suggested dysfunction of bone remodeling. Fibrous tissue at the site of pseudarthrosis was associated with the periosteum and demonstrated myofibroblastic differentiation accompanied by massive cartilage formation, suggesting some misdirection during the differentiation of periosteum to myofibroblasts or chondrocytes. LOH of the NF1 gene locus was not seen in fibrous tissue. This result suggests that CPT is not accompanied by double inactivation in every NF1 case.     

Two Cases of Peritoneal Serous Papillary Adenocarcinoma

Two cases of peritoneal papillary carcinoma are reported. The patient in the first case was a 71-year-old woman with symptoms of obstructive ileus. Laparotomy revealed a tumor in the omentum involving the transverse colon, and several small tumors in the peritoneum and pelvic wall. However, no primary site of the tumor was seen in the ovary, pancreas, or gastrointestinal tract. The patient in the second case was a 44-year-old woman with carcinomatous peritonitis. Postmortem examination revealed multiple tumors in the peritoneum, omentum, and pelvic wall. Tumors were also found in the cortex with mild invasion of the underlying parenchyma of the bilateral ovaries, although these lesions were thought to be metastatic. The histologic features of the tumor in both cases were those of tubulopapillary adenocarcinoma containing scattered psammoma bodies. The cells were positive with the PAS D technique, but negative with alcian blue staining. In both cases, the serum levels of CA-125 were considerably elevated, and the tumor cells showed positivity for CA-125, S 100 protein, cytokeratin and EMA by im-munohistochemistry. The present cases were most likely peritoneal serous papillary adenocarcinoma derived from extraovarian peritoneal mesothelium with miillerian potential, being different from the usual type of diffuse malignant mesothelioma. Acta Pathol Jpn 41: 642-646, 1991.     

SF-1/Ad4BP transforms primary long-term cultured bone marrow cells into ACTH-responsive steroidogenic cells

Bone marrow stem cells develop into haematopoietic and mesenchymal lineages, but have not been known to participate in steroidogenic cell production. Steroidogenic factor 1 (SF-1), also designated adrenal 4 binding protein (Ad4BP), is an essential orphan nuclear receptor for steroidogenesis as well as for adrenal and gonadal gland development. In the present study, we revealed that the adenovirus-mediated forced expression of SF-1 can transform cultured primary long-term cultured bone marrow cells into steroidogenic cells, showing the de novo synthesis of multiple steroid hormones in response to adrenocorticotropic hormone (ACTH). This finding may provide an initial step in innovative autograft cell transfer therapy for steroid hormone deficiencies.     

Mechanisms of inactivation of the p16INK4a gene in leiomyosarcoma of soft tissue: decreased p16 expression correlates with promoter methylation and poor prognosis

The p16INK4a tumour suppressor gene, encoding p16 protein, plays a crucial role in regulation of the G1 cell-cycle phase. To investigate the potential role of p16 in soft tissue leiomyosarcoma (LMS), an immunohistochemical analysis was performed of 77 LMSs for p16 expression. Decreased expression of the p16 protein was identified in 25 of 77 LMSs (32%). Decreased expression of p16 correlated significantly with large tumour size (p=0.0038). In a univariate analysis, large tumour size and decreased expression of p16 were statistically significant adverse prognostic factors (p=0.025 and p=0.0021, respectively). In a multivariate analysis including conventional clinicopathological parameters, decreased expression of p16 protein was revealed as the only independent unfavourable prognostic factor (p=0.012). To elucidate the mechanisms of inactivation of the p16INK4a gene, 49 LMSs for which genomic DNA was available were examined; analysis for homozygous deletion, mutation, and promoter hypermethylation was conducted using differential PCR, PCR-SSCP, and methylation-specific PCR, respectively. Promoter hypermethylation was detected in 11 of 49 LMS cases (22%); homozygous deletion was detected in 3 of 49 cases (6%); and mutation was not recognized in any of the cases studied. Eight of 15 cases (53%) with decreased expression of p16 protein revealed methylation of the p16INK4a gene promoter. Promoter hypermethylation correlated closely with decreased expression and poor prognosis (p=0.0014 and p=0.0088, respectively). These results suggest that decreased expression of p16 protein can be considered as an independent reliable prognostic parameter in patients with soft tissue LMS. Furthermore, promoter methylation was more frequent than either homozygous deletion or mutation in this tumour, and promoter methylation was also shown to have a strong association with inactivation of the p16INK4a gene.     

Low-grade fibrosarcoma of the proximal humerus

We present the clinical, radiographical and pathological features of low-grade fibrosarcoma of the left proximal humerus in a 23-year-old man in whom it was necessary to distinguish the tumor from desmoplastic fibroma, malignant fibrous histiocytoma and intramedullary well-differentiated osteosarcoma. The patient presented with a 10-day history of pain in his left upper arm sustained when trying to break his fall with his left hand when slipping in the street. Plain radiography revealed an expanding multilobular osteolytic lesion from the proximal metaphysis to the diaphysis of his left humerus, accompanied by a pathological fracture at the distal portion of the lesion. Open biopsy of the lesion was performed twice; however, a conclusive diagnosis could not be obtained. The patient underwent wide excision and prosthetic replacement of the left proximal humerus. Histologically, the resected tumor was composed of both cellular areas and hypocellular areas. Cellular areas revealed a proliferation of bundles of uniform fibroblastic spindle-shaped cells with minimal cellular atypia, mixed with abundant intercellular collagenization. Mitotic figures were occasionally seen. Hypocellular areas showed myxoid features with loose bundles of collagen fibers. The patient demonstrates no evidence of disease 42 months after surgery. It is important to detect the scant atypical cells for the differential diagnosis of low-grade fibrosarcoma and desmoplastic fibroma of bone.