Small extra-adrenal pheochromocytoma causing severe hypertension in an elderly patient.

We report the case of a 67-year-old woman with severe hypertension caused by an extra-adrenal pheochromocytoma. The tumor was detected by 131I metaiodobenzylguanidine scintigraphy and it was found to be small (2 cm ?) by enhanced CT. After the extirpation of the tumor, the blood pressure of the patient immediately normalized. It should be taken into account that a small extra-adrenal pheochromocytoma can be one of the causes of secondary hypertension in elderly patients. Since small extra-adrenal pheochromocytomas are difficult to detect, it is also important to perform suitable examinations to establish the diagnosis. Furthermore, we emphasize the importance of an accurate diagnosis in elderly patients with pheochromocytoma, for they often have less symptomatology and more severe cardiovascular complications due to refractory hypertension than younger patients.     

Internalization of Mycobacterium bovis Bacillus Calmette-Guérin into Osteoblast-Like MC3T3-E1 Cells and Bone Resorptive Responses of the Cells against the Infection

Mycobacterium bovis BCG (BCG) is a live vaccine used worldwide against tuberculosis. However, it has unfavourable side effects such as osteitis or osteomyelitis, and these sometimes lead to vertebral caries in some patients as a result of bone resorption. Osteoblasts might play a role in the bone resorption caused by BCG infection, because they are central cells in bone metabolism. Cultured osteoblast-like cell lines (MC3T3-E1) derived from C57BL mice susceptible to BCG infection cells were infected with BCG at several doses. Interestingly, internalization of BCG-enveloped phagosome-like membrane in osteoblast-like cells were observed by transmission electron microscopy (TEM). Owing to infection, the proliferation and alkaline phosphatase activity of the osteoblast-like cells were reduced in a dose-dependent manner. On the other hand, interleukin (IL)-6 production was considerably enhanced by infection. These results suggest that BCG infects osteoblasts, suppressing their proliferation and differentiation and inducing bone resorption, which may be related to osteitis/osteomyelitis and bone caries caused by BCG infection.     

Intravenous ulinastatin therapy for Stevens-Johnson syndrome and toxic epidermal necrolysis in pediatric patients. Three case reports

BACKGROUND: More effective therapy is needed for the treatment of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The clinical efficacy of intravenous ulinastatin therapy was investigated in 3 Japanese pediatric patients with SJS or TEN. METHODS: Ulinastatin was given to 1 pediatric SJS patient and 2 pediatric TEN patients within 7 days (patient 1; SJS), 6 days (patient 2; TEN), or 4 days (patient 3; TEN) after the onset of the skin rash. Ulinastatin was administered intravenously at a dose of 7,500 U/kg/day (maximum dose: 300,000 U/day). No corticosteroids were given. After the skin lesions resolved, the ulinastatin dose was reduced to between 2,500 and 5,000 U/kg/day as maintenance therapy and then the drug was withdrawn. RESULTS: Erythema, fatigue, and fever improved within 12-36 h of starting the ulinastatin infusion, and the skin lesions resolved completely after 4-7 days of ulinastatin therapy. None of the patients had cutaneous or ocular sequelae. No patient developed secondary infection or relapse and ulinastatin therapy caused no side effects. CONCLUSION: Ulinastatin dramatically reduced the febrile period with no adverse effects and was very safe in this study. Ulinastatin appears to be a useful and effective therapy for controlling SJS and TEN without sequelae.     

Lowered effectiveness of immunotherapy for cypress pollinosis by using Japanese cedar pollen extract]

BACKGROUND: Japanese cedar and cypress pollen share a common antigen. The cedar pollen season is followed by the cypress pollen season. However, both the clinical significance and involvement of cypress pollinosis in the treatment of the cedar pollinosis have not yet been clarified. METHODS: The clinical efficacy of sublingual immunotherapy with cedar pollen extract for cedar pollinosis was evaluated during the cypress pollen dispersal season in Japan. In addition, the change in cypress pollen specific IgE antibodies of the patients with cedar pollinosis was examined before and after the pollen season. RESULTS: Sublingual immunotherapy with cedar pollen extract did not improve the clinical symptoms of the cedar pollinosis patients combined with cypress pollinosis in the cypress pollen season. The cypress pollen specific IgE antibodies were found to demonstrate significant seasonal changes. CONCLUSION: The presence of cypress pollinosis should therefore be taken into consideration when planning the optimal treatment for cedar pollinosis. Sublingual immunotherapy with cedar pollen extract may not be effective for cypress pollinosis.     

Exacerbation of rheumatoid arthritis following Helicobacter pylori eradication: disruption of established oral tolerance against heat shock protein?

A 62-year-old Japanese woman with RA received an eradication therapy against Helicobacter pylori in November 1999. Eight weeks later, successful eradication was confirmed by negative results for rapid urease test, pathologic findings, and a fall in anti-H. pylori IgG antibody titer. During the course, parameters for RA activity were exacerbated: C-reactive protein 1.1-4.2 mg/dL, rheumatoid arthritis precipitation antigen 2560-5120 dils., erythrocyte sedimentation rate 52-123 mm/h, and complements CH50 50 to over 60 U/mL. Lansbury index increased from 70% to 105%. Two more weeks later, the patient noticed right shoulder pain. She also complained of bilateral gonalgia two months later, and physical examination revealed increased fluid in the knee joints. Prednisolone was required to control the disease activity. The results of this case suggested that RA patients might experience a deleterious effect on the disease activity following H. pylori eradication possibly through disruption of the established oral tolerance against stress protein such as mycobacterial heat shock protein 65.     

Porphyromonas gingivalis Fimbriae Use β2 Integrin (CD11/CD18) on Mouse Peritoneal Macrophages as a Cellular Receptor, and the CD18 β Chain Plays a Functional Role in Fimbrial Signaling

In this study, we demonstrate that Porphyromonas gingivalis fimbriae use molecules of β₂ integrin (CD11/CD18) on mouse peritoneal macrophages as cellular receptors and also show that the β chain (CD18) may play a functional role in signalling for the fimbria-induced expression of interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) genes in the cells. Using a binding assay with ¹²⁵I-labeled fimbriae, we observed that fimbrial binding to the macrophages was inhibited by treatment with CD11a, CD11b, CD11c, or CD18 antibody but not by that with CD29 antibody. Western blot assays showed that the fimbriae bound to molecules of β₂ integrin (CD11/CD18) on the macrophages. Furthermore, Northern blot analyses showed that the fimbria-induced expression of IL-1β and TNF-α genes in the cells was inhibited strongly by CD18 antibody treatment and slightly by CD11a, CD11b, or CD11c antibody treatment. Interestingly, intracellular adhesion molecule 1 (ICAM-1), a ligand of CD11/CD18, inhibited fimbrial binding to the cells in a dose-dependent manner. In addition, ICAM-1 clearly inhibited the fimbria-induced expression of IL-1β and TNF-α genes in the cells. However, such inhibitory action was not observed with laminin treatment. These results suggest the importance of β₂ integrin (CD11/CD18) as a cellular receptor of P. gingivalis fimbriae in the initiation stage of the pathogenic mechanism of the organism in periodontal disease.     

Transforming growth factor-beta inhibits lipopolysaccharide-stimulated expression of inflammatory cytokines in mouse macrophages through downregulation of activation protein 1 and CD14 receptor expression

The septic shock that occurs in gram-negative infections is caused by a cascade of inflammatory cytokines. Several studies showed that transforming growth factor-beta1 (TGF-beta1) inhibits this septic shock through suppression of expression of the lipopolysaccharide (LPS)-induced inflammatory cytokines. In this study, we investigated whether TGF-beta1 inhibition of LPS-induced expression of inflammatory cytokines in the septic shock results from downregulation of LPS-stimulated expression of CD14, an LPS receptor. TGF-beta1 markedly inhibited LPS stimulation of CD14 mRNA and protein levels in mouse macrophages. LPS-stimulated expression of CD14 was dramatically inhibited by addition of antisense, but not sense, c-fos and c-jun oligonucleotides. Since TGF-beta1 pretreatment inhibited LPS-stimulated expression of c-fos and c-jun genes and also the binding of nuclear proteins to the consensus sequence of the binding site for activation protein 1 (AP-1), a heterodimer of c-Fos and c-Jun, in the cells, TGF-beta1 inhibition of CD14 expression may be a consequence of downregulation of AP-1. LPS-stimulated expression of interleukin-1beta and tumor necrosis factor alpha genes in the cells was inhibited by addition of CD14 antisense oligonucleotide. Also, TGF-beta1 inhibited the LPS-stimulated production of both inflammatory cytokines by the macrophages. In addition, TGF-beta1 inhibited expression of the two cytokines in several organs of mice receiving LPS. Thus, our results suggest that TGF-beta1 inhibition of LPS-stimulated inflammatory responses resulted from downregulation of CD14 and also may be a possible mechanism of TGF-beta1 inhibition of LPS-induced septic shock.     

A case of "interval" form of acute carbon monoxide poisoning--brain MRI and therapeutic effect of hyperbaric oxygenation

A 43-year-old female who had suffered from paranoid reaction attempted suicide with city gas. She was admitted to an emergency hospital in a comatose state, regained consciousness the next day and was discharged 12 days after. However, on the 21st day after the poisoning, behavioral anomalies and staggering appeared. She was readmitted into another emergency hospital with the diagnosis of an "interval" form of acute carbon monoxide poisoning. She was performed hyperbaric oxygen therapy 42 times until the 53rd day after the accident. Nevertheless, her symptoms did not improve and remained in a state like an apallic syndrome. With little promise of improvement, she was moved to our hospital, and hyperbaric oxygen therapy further continued for 40 times which resulted in a remarkable recovery. Repeat EEGs were performed. On the 32nd day, EEG showed an abnormality consisting of generalized delta waves. On the 56th day, the abnormal EEG improved slightly with more alpha activity. EEG was normalized 126 days after. The X-ray CT scan on the 32nd day revealed low densities in the bilateral globus pallidus and the deep white matters adjacent to the frontal horns of the lateral ventricle and in the semioval centers. On the 57th day, these low density areas were depicted more clearly by the X-ray CT scan, which became less marked on the 73rd day. MRI was performed 3 times.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fatal chronic active Epstein-Barr virus infection mimicking autoimmune hepatitis

We report a 22-year-old female who presented with pyrexia, pancytopenia and liver dysfunction. The patient showed mild liver dysfunction with low-grade fever and mild hepatosplenomegaly 6 years previously, and autoimmune hepatitis (AIH) was diagnosed based on the examination of the laboratory data and liver biopsy. On admission, both markers of Epstein-Barr virus (EBV) and in-situ hybridisation from a liver biopsy specimen indicated chronic active EBV infection (CAEBV). The patient was administered an immunosuppressive agent and antiviral drug added to steroid therapy, but ultimately died from liver failure and virus-associated haemophagocytosis 10 months after the definite diagnosis. Retrospective examination of the serum at the diagnosis of AIH revealed extremely high titres of antibody to EBV, and EBV-DNA was also detectable by polymerase chain reaction. These results suggest the possibility that the patient may already have suffered from CAEBV at the initial diagnosis. We presume that hepatic involvement of CAEBV should be considered as differential diagnosis in cases showing liver dysfunction with clinical and biochemical features observed in AIH.