Choroidal and cutaneous metastasis from urothelial carcinoma of the bladder after radical cystectomy: a case report and literature review.

Bladder cancer is the second most common genitourinary malignancy and has variable metastatic potential; however, choroidal and cutaneous metastases are extremely rare. Generally, a patient with these uncommon metastases has a very poor prognosis. We present a bladder cancer patient with a visual disorder in the right eye and multiple nodules on head and lower abdomen that developed 17 months after a radical cystectomy. These symptoms were determined to be caused by choroidal and cutaneous metastasis of bladder cancer. Although two cycles of combination chemotherapy were performed, the patient died 5 months after diagnosis of multiple metastases.

[A case of renal malacoplakia that was difficult to distinguish from cystic renal cell carcinoma].

A 66 years old man visited our hospital with a chief complaint of right flank pain and abdominal palpable mass. Abdominal enhanced computed tomography scan showed a large cystic mass with infiltrating surrounding tissue in the right kidney. We diagnosed it infected cystic renal cell carcinoma because of high grade fever and acute inflammatory response. It was surgically unresectable tumor. Therefore, percutaneous puncture and drainage was performed under ultrasound guidance. In the culture of drainage fluid, Escherichia coli (E. coli) was isolated. Then, we confirmed reduction in the size of the tumor, right radical nephrectomy was performed. Because of tumor invasion to ascending colon, we performed the excision of right kidney together with ascending colon. Histological study confirmed target-shaped Michaelis-Gutmann body, and the definitive diagnosis was malacoplakia of the kidney. We reported a case of renal malacoplakia that was difficult to distinguish from cystic renal cell carcinoma. Our case is 12th case of renal malacoplakia in the Japanese literature.

[A case of neurosarcoidosis with recurrent episodes of neurological dysfunction and diffuse cortical lesions on magnetic resonance imaging].

We report a case of a 35-year-old man with histologically confirmed neurosarcoidosis who developed recurrent episodes of right-hemispheric dysfunction with diffuse cortical lesions of the right hemisphere on magnetic resonance imaging (MRI). A brain biopsy revealed granulomatous inflammatory cells in both the subarachnoid space and Virchow-Robin space, which might relate to the recurrent neurological dysfunction and MRI findings.

Incidence of dementia, Alzheimer disease, and vascular dementia in a Japanese population: Radiation Effects Research Foundation adult health study.

OBJECTIVE: To determine the age-, sex-, and subtype-specific incidence of dementia and to assess the effect of education level on the incidence in a Japanese population. METHODS: 2,286 dementia-free subjects, aged > or =60 years, were followed for 5.9 years through biennial two-phase examinations. RESULTS: 206 cases of dementia were newly diagnosed based on DSM IV. The incidence per 1,000 person-years was 12.0 for men and 16.6 for women. Based on NINCDS-ADRDA criteria, 80 cases of probable Alzheimer disease (AD) and 50 cases of possible AD were diagnosed. Based on NINDS-AIREN criteria, 36 cases of probable vascular dementia (VaD) and 40 cases of possible VaD were diagnosed. Age and education showed the most statistically significant effects for all dementia. Probable AD showed the most remarkable increase with age and decreased with increasing education level (p = 0.001). Probable VaD showed significant effects of sex (p = 0.033) and sex-age interaction (p = 0.048), but not education (p = 0.26). CONCLUSION: AD was the predominant type of dementia in this recent incidence study conducted in Japan, suggesting a reduction in VaD and an increase in AD. Age, sex, and education effects differed by dementia subtype.

Clinical features of malignant syndrome in Parkinson's disease and related neurological disorders.

INTRODUCTION: We elucidated the cause and clinical characteristics of malignant syndrome (MS) in patients with Parkinson's disease (PD), early-onset parkinsonism (EOP), and other neurological disorders. MATERIALS AND METHODS: Subjects were 260 patients with PD or EOP, and three patients with other neurological disorders associated with MS. We studied clinical symptoms before and after the onset of MS, and evaluated autonomic function particularly before the onset of MS. RESULTS: The overall incidence of MS accompanying PD and EOP in our department was eight of 260 patients (3.1%). The incidence of MS in EOP was significantly higher than that in PD. All patients with MS showed comparatively longer duration of illness and advanced stage of PD and EOP. Factors triggering MS included reduced dosage or discontinuation of anti-parkinsonian drugs, reduction of oral intake, dehydration, infectious disease, postoperative state, and treatment with major tranquilizers. Although patients demonstrated marked autonomic symptoms at the onset of MS, in many cases autonomic dysfunction developed before the onset of MS. Even EOP patients, who usually demonstrated milder autonomic dysfunction, showed abnormalities in the correlation between circadian rhythm of blood pressure and pulse rate, and/or abnormal gastric emptying test, suggesting that autonomic dysfunction plays an important role in the cause of MS. Cooling the body, fluid replacement, resumption or increasing the dosage of anti-parkinsonian drugs and administration of dantrolene sodium overcame MS in all cases. CONCLUSION: Autonomic dysfunction is related to the cause and clinical features of MS in PD, EOP and some other neurological disorders.

A collaborative study on the malignant syndrome in Parkinson's disease and related disorders.

We report the results of a collaborative study on malignant syndrome (MS) that developed in patients being treated with levodopa and other anti-parkinsonian drugs. We analyzed clinical features, laboratory findings, precipitating events, and risk factors for poor outcome. The study was conducted in five centers in Japan. Patients who developed MS between January 1991 and December 1997 were included. The enrollment criteria used were the same as those for neuroleptic MS proposed by Levenson et al. (1985).A total of 99 episodes were encountered in 93 patients (72 with Parkinson's disease and 21 with secondary parkinsonism); one patient had four recurrences of MS and three patients had two recurrences. High fever was the most frequent clinical manifestation of MS followed by worsening of parkinsonism, and then altered levels of consciousness. Serum creatine kinase was abnormally elevated in all the patients studied. Life-threatening complications were rhabdomyolysis, disseminated intravascular coagulation, and acute renal failure. The most frequent precipitating event was discontinuation or dose reduction of anti-parkinsonian drugs, particularly levodopa. No drug was the exception in the precipitation of MS. Intercurrent infection was the next most common precipitating event. MS developed without drug withdrawal or infection in some patients. In five patients, severe "wearing off" phenomenon was the only event preceding the onset of MS. Hot weather and dehydration appeared to be the cause in three patients. Among the total of 99 episodes, patients recovered to the pre-MS state following 68 episodes (68.7%); in the remaining 31.3%, patients failed to recover to their previous state. Older age, higher Hoehn and Yahr stage during the symptomatic phase of MS, higher akinesia score, and the absence of wearing off phenomenon prior to developing MS were associated with poor outcome. The most frequently used treatments of MS were intravenous fluid, levodopa, dantrolene sodium, and intragastric bromocriptine. Early introduction of treatment is important. Any elevation of body temperature during the course of anti-parkinsonian drug treatment should be considered as MS until proved otherwise.

Prevention and treatment of malignant syndrome in Parkinson's disease: a consensus statement of the malignant syndrome research group.

We report a consensus statement of the collaborative research group on the prevention and treatment of malignant syndrome (MS) in Parkinson's disease. The syndrome is quite similar to neuroleptic MS. Although sudden withdrawal of levodopa was the most frequent cause, many other precipitating events were found such as intercurrent infections, dehydration, hot weather, discontinuation of other anti-parkinsonian drugs, and "wearing off" phenomenon. Awareness of this syndrome is most important for its early detection and the prompt commencement of treatment. MS should be suspected whenever the body temperature rises above 38 degrees C without an apparent cause. Treatment consists of ample intravenous fluid, cooling the body, anti-parkinsonian drugs (particularly levodopa and bromocriptine), dantrolene sodium, and antibiotics if infection is present. Rhabdomyolysis, disseminated intravascular coagulation, and acute renal failure constitute serious complications.

Changes in serum macrophage-related factors in patients with chronic inflammatory demyelinating polyneuropathy caused by intravenous immunoglobulin therapy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a slowly progressive or recurrent neuropathy accompanied by infiltration of macrophages in the peripheral nerves. Macrophage colony-stimulating factor (M-CSF) and monocyte chemoattractant protein-1 (MCP-1) are a macrophage-related cytokine and chemokine, respectively. Although, intravenous immunoglobulin (IVIg) infusion therapy has been used for treating CIDP patients, not all CIDP patients have responded to IVIg infusion therapy. To determine the mechanisms of the action of IVIg, we examined serum M-CSF and MCP-1 levels during and after IVIg infusion therapy in 19 CIDP patients treated with IVIg (0.4 g/kg/day for 5 days). Ten of the 19 patients (52.6%) responded to IVIg therapy. Both M-CSF and MCP-1 concentrations in IVIg responders were significantly higher on day 1 postinfusion than those in nonresponders, but decreased to their pretreatment values on day 5 postinfusion. The results suggest that immunomodulation through M-CSF and MCP-1 is involved in the mechanisms underlying the effect of IVIg infusion therapy in CIDP patients.

[A sporadic case of late-onset familial amyloid polyneuropathy type I (transthyretin Met 30-associated familial amyloid polyneuropathy) inborn habitant of Ehime prefecture].

We reported a 62-year-old man of late-onset familial amyloid polyneuropathy type I(transthyretin Met 30-associated familial amyloid polyneuropathy) from Ehime Prefecture. There was no family history related to endemic Japanese foci (Nagano and Kumamoto foci). He demonstrated paraesthesia in the legs and mild autonomic symptoms at the age of 52. These symptoms gradually developed. Analysis of the transthyretin gene from his leucocytes demonstrated he had Met 30 transthyretin mutation. Therefore, he was diagnosed with late-onset familial amyloid polyneuropathy type I(FAP 1). In some families, asymptomatic carriers with the mutant transthyretin gene were diagnosed. In early stage, this patient's polyneuropathy and autonomic nervous system dysfunction were less serious than those of FAP 1 patients from endemic Japanese foci. These symptoms of this patient was slowly progressive. He hoped liver transplantation (brain death or living-related) treatment if possible. Now he became 68-year-old and bed-ridden.

Activation of Pyk2/RAFTK induces tyrosine phosphorylation of alpha-synuclein via Src-family kinases.

alpha-Synuclein (alpha S) is a neuronal protein that has been implicated in the pathogenesis of Parkinson's disease. The present report demonstrates that the protein tyrosine kinase Pyk2/RAFTK is involved in cell stress-induced tyrosine phosphorylation of alpha S. Hyperosmotic stress induced tyrosine phosphorylation of alpha S via Pyk2/RAFTK at tyrosine residue 125. Pyk2/RAFTK-mediated phosphorylation of alpha S was primarily achieved with Src-family kinases. In addition, osmotic stress-induced phosphorylation of alpha S was dependent on Pyk2/RAFTK activation. Accordingly, such results indicate that Pyk2/RAFTK lies upstream of Src-family kinases in the signaling cascade by which osmotic stress induces tyrosine phosphorylation of alpha S.

[A case of late onset mitochondrial neuromyopathy].

A 68-year-old woman was admitted with dysesthesia on both soles, hands and buttocks. She first noticed the dysesthesia in the left first toe two years before admission. One year before admission, serum creatine kinase and lactate dehydrogenase levels were elevated but she had no clinical symptoms suggesting myopathy. Nerve conduction study showed no apparent abnormalities, and an electromyogram showed mild myogenic change. Computed tomography of the muscle showed fatty degeneration of the trunk, major gluteus muscle, and biceps femoris muscle and atrophic change of the biceps femoris muscle. Muscle biopsy revealed a slight variation in fiber size, the presence of cytochrome c oxidase (CCO)-negative fibers by CCO staining, ragged-red fibers by Gomori trichrome staining, and mild denervation fiber by neuron specific enolase (NSE) staining. Analysis of her mitochondrial DNA (mtDNA) revealed a large deletion of mtDNA (approximately 8.5 Kb), and mitochondrial neuromyophy was diagnosed. The frequency of mtDNA deletion increases with aging. Although her mtDNA abnormality was compatible with chronic progressive external ophthalmoplegia (CPEO), we speculate that the aging process may be contributed to the mtDNA abnormality, which would be related to the late onset of her symptoms. As the phenotype of this mitochondrial disorder shows a wide variation and mtDNA abnormality is more frequent among elderly people, we should consider the possibility of mitochondrial disorders even in elderly people.

Morphine analgesia suppresses tumor growth and metastasis in a mouse model of cancer pain produced by orthotopic tumor inoculation.

The present study was conducted to clarify whether relief from cancer pain by morphine would suppress tumor growth and metastasis. When given orthotopic inoculation of B16-BL6 melanoma cells into the hind paw, C57BL/6 mice showed moderate and marked hyperalgesia on days 7-10 and from day 14 post-inoculation, respectively. The volume of inoculated hind paw was increased exponentially as a function of time from day 8 post-inoculation, a phenomena being due to melanoma growth. Lung metastasis was apparent after day 12 post-inoculation. On day 16 post-inoculation, the hyperalgesia was completely inhibited by subcutaneous injection of morphine hydrochloride (5 and 10 mg/kg). The tumor growth and lung metastasis were markedly inhibited by repeated administration of morphine (5 and 10 mg/kg daily for 6 days) and also by the neurectomy of sciatic nerve innervating the inoculated region. The results suggest that relief from cancer pain by morphine inhibits tumor growth and metastasis.

Effects of nicotine chewing gum on UPDRS score and P300 in early-onset parkinsonism.

It has been reported that nicotine shows some beneficial effects on Parkinson's disease. The purpose of the present study is to assess the therapeutic effects of nicotine chewing gum in patients with early-onset parkinsonism (EOP). The subjects were 8 patients with early-onset parkinsonism (male/female = 4/4, mean age; 51.3 years). Four out of 8 patients had a history of smoking (smokers). To estimate the effects of nicotine gum, the scores on the Unified Parkinson's Disease Rating Scale (UPDRS) and auditory event-related potentials (ERPs) were studied before and after taking nicotine gum in the EOP patients. In smokers, UPDRS scores improved by more than 10% and the P300 latency of auditory ERPs was shortened by more than 30 msec. In contrast, nicotine had no remarkable effects on UPDRS scores or auditory ERPs in non-smokers. We suggest that nicotine chewing gum may be a possible choice for the treatment of patients with EOP, especially when they are smokers.

[An elderly case of microscopic polyangiitis following bronchial asthma].

A 78-year-old woman who had bronchial asthma for 15 years developed dysesthesia, neuralgia, muscle weakness and atrophy in both feet and her left hand. Prednisolone (maximum dose 80 mg) was not effective, and she displayed gait disturbance. Laboratory findings showed leukocytosis (neutrophils dominant), renal dysfunction, elevation of CRP and positive P-ANCA. Biopsy revealed vasculitis, and reduced density of myelinated fibers. Although steroid pulse therapy improved neuralgia and renal dysfunction, severe disability of motor function and sensory disturbance still remained. Vasculitis syndrome following bronchial asthma indicated Churg-Strauss syndrome (CSS), while severe renal dysfunction and lack of eosinophilia were symptoms compatible with microscopic polyangiitis (MPA). The present case showed properties of both MPA and CSS.

Dinucleotide repeat polymorphisms in the neprilysin gene are not associated with sporadic Alzheimer's disease.

In the pathological process of Alzheimer's disease (AD), deposition of amyloid beta-peptide (A beta) in the brain parenchyma plays an important role. Neprilysin (NEP), a neutral endopeptidase, degrades A beta, and it is postulated that decreased NEP activity may contribute to the development of AD by promoting the accumulation of A beta. The human NEP gene possesses four dinucleotide repeat polymorphisms, and it is possible that these polymorphisms regulate the NEP expression levels and influence the pathological cascade of AD. Therefore, we investigated the association of these polymorphisms with AD. We performed genotyping of each polymorphism in 201 Japanese sporadic AD patients and 208 Japanese controls. There were no significant differences between the AD and control groups in allele frequencies of each polymorphism. We conclude that these polymorphisms in the NEP gene do not contribute to genetic risk factors for sporadic AD.