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.     

Myasthenia gravis and steroid therapy]

In the past 20 years, we experienced 242 myasthenic patients in our hospital. Fifty five cases were administered high doses of adrenocorticosteroid hormone for a long time. Among them, we analysed 39 cases with complete clinical records from admission to the present. We analysed 5 additional cases in whom responses to the therapy somewhat unique in that four cases have not shown any improvement until the drug was reduced to certain dosages, and in the 5th case change of method from alternate-day to every day brought good recovery of the symptoms. As a result, adrenocorticosteroid hormone was effective for 100% of the patients in this series. However, complete remission appeared in the above mentioned 10 patients (26%), after 2-3 years' continuous administration. Prognosis was far better in those who showed shorter durations between the onset of the disease and thymectomy or thymectomy than in those of longer one. In these cases, the maximum daily doses were 60-100 mg in alternate-day administration, and the total amount of prednisolone was 9-15 g in individual cases. Through data of these cases, it is recommended that the maximum dosage is to be continued for as long as 2 to 19 weeks with average 7 weeks.     

Myasthenia gravis developing after discovery of thymoma

We report 4 cases of myasthenia gravis in which myasthenic symptoms developed after a thymoma was known to be present. They include 3 invasive thymomas and one thymoma. In 3 of them, myasthenic symptoms developed 2–7 months after removal of the thymoma; in 1 case, myasthenic symptoms developed 11 years after the thymoma was known to be present. We also discuss here the possible pathogenetic mechanism of post-thymomectomic myasthenia gravis, and propose that it is due to the natural course of the disease.     

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.     

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.