Objective The clinical picture of primary hyperparathyroidism (PHPT) has changed during the past 50 years. It is currently unknown whether or not PHPT is associated with an increased risk of cholelithiasis.
Patients To determine the frequency of cholelithiasis in PHPT we analyzed 645 consecutive patients seen at Prague University Hospital from 1992 through 2002 and compared them with a of normocalcaemic control group.
Methods We investigated 645 patients with proven PHPT (518 female and 127 males aged 20-80 years) during a period of 10 years. To determine the frequency of cholelithiasis in normal population we analyzed 2,015 patients receiving periodic health examination at an outpatient ward from January 1998 to December 1998 (1505 females and 510 males aged 24-85 years). A detailed history, physical examination, biochemical measurements and abdominal ultrasonography were done.
Results Cholelithiasis was proven in 157 of 518 women (30.3%) and in 11 of 127 men (8.66%) with PHPT. Their mean age was 59.67±12 years in women and 56.0±10 years in men. In the control group 260 of 1505 women (17.27%) and 54 of the 510 men (10.58%) had cholelithiasis. The mean age was 64.55±13.8 years in women and 61.2±12.4 in men. Only in the case of women, the difference was highly statistically significant (p<0.001). There were no significant differences between the mean values for the serum calcium level, bone alkaline phosphatase, total cholesterol, urinary hydroxyproline and body mass index in hyperparathyroid patients with and without cholelithiasis. However the hyperparathyroid women with cholelithiasis had an increased concentration of parathyroid hormone (236.1±56 pg/ml) compared with hyperparathyroid women without cholelithiasis (179.0±45 pg/ml), p<0.01.
Conclusion The mechanism of PTH associated gallstone formation may involve inhibition of gallblader emptying, hepatic bile secretion and sphincter Oddi motility as well as modification of bile composition. While it might be difficult to prove it seems likely that the association of cholelithiasis with primary hyperparathyroidism in women with a high concentration of parathyroid hormone is more than merely coincidental and from our study it is obvious that a significant association exists.

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Objective To estimate the prevalence and risk of ischemic stroke associated with metabolic syndrome.
Methods and Patients In 197 stroke patients (80 cases of atherothrombotic infarction, 97 lacunar infarction, 16 cardioembolic infarction, 4 others) and 356 age- and sex-matched control subjects aged 65 years and older in Seiyo Municipal Nomura Hospital, we investigated the association between metabolic syndrome and risk factor-dependent augmentation of ischemic stroke in subjects with several risk factors for atherosclerosis. The diagnosis of cerebral infarction in each patient was confirmed by CT findings of the brain and metabolic syndrome was defined as at least 3 of the 5 following conditions: visceral obesity, hypertension (HT), hypertriglyceridemia, low HDL-cholesterol and diabetes mellitus (DM).
Results After adjustment for sex, age, and smoking, metabolic syndrome was significantly related to atherothrombotic infarction (odds ratio, 3.08; 95% confidence interval, 1.69-5.61). Of the individual components, visceral obesity, HT and DM were independent risk factors for atherothrombotic infarction. Increased risk for atherothrombotic infarction was also associated with increases in the 5 component conditions of the metabolic syndrome.
Conclusion The clustering of cardiovascular risk factors called metabolic syndrome increases the risk of cardiovascular morbidity, and its identification may thus be important in risk assessment and treatment of patients.

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Objective The serotonin (5-HT) 2A and 2C receptor subtype plays an important role in the maintenance of upper airway stability and normal breathing in obesity. Polymorphisms in the 5-HT 2A receptor gene (HTR2A) and 5-HT 2C receptor gene (HTR2C) are associated with various diseases. The aim of this study was to investigate whether or not the HTR2A/C genotypes are associated with obstructive sleep apnea (OSA).
Methods The PCR-restriction fragment length polymorphism method was used to determine genotypes of the HTR2A/C gene. The genotype distributions and allele frequencies were statistically analyzed.
Subjects We studied 177 consecutive male patients with excessive daytime somnolence and an apnea plus hypopnea number [apnea-hypopnea index (AHI)] of greater than five per hour of sleep established by full polysomnography. One hundred Japanese men in whom OSA was clinically excluded were randomly selected as a control group.
Results Genotypes and allele frequencies of 102T/C polymorphism of the HTR2A and 796G/C polymorphism of the HTR2C did not differ between controls and patients with OSA. HTR2C polymorphism was considered inappropriate for association studies because of low frequency of the mutant allele. Multiple regression analysis showed that age and body mass index (BMI) were significantly associated with OSA, but HTR2A polymorphisms were not. HTR2A polymorphisms had no significant relationship with AHI or BMI, although further study with more samples will be needed for powerful statistical analyses.
Conclusions These results indicate that age and BMI, not these polymorphisms, are associated with OSA in this population.

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We evaluated the clinical courses of 216 patients with multiple sclerosis (MS) diagnosed according to the recommended diagnostic criteria of McDonald et al (10). Sixty-five patients clinically displaying selective involvement of the optic nerves and spinal cord were classified as opticospinal MS (OS-MS), while the other 151 showing disseminated involvement of the central nervous system were classified as conventional MS (C-MS). The disease duration did not differ significantly between the two subtypes (11.2 years vs. 11.5 years). In addition to a higher age of onset, female preponderance and higher Kurtzke’s expanded disability status scale (EDSS) scores, the OS-MS patients showed a markedly lower frequency of secondary progressive MS than the C-MS patients (4.6% vs. 29.1%, p=0.0001). The EDSS scores of the C-MS patients were significantly correlated with the disease duration, while those of the OS-MS patients were not. Among the C-MS patients, the frequency of secondary progressive MS was significantly more common in patients with a disease duration of more than 10 years than in those with a shorter duration. These results suggest that the irreversible disability in OS-MS is determined by relapses, rather than by chronic progression, whereas C-MS has a similar clinical course to MS in Westerners.

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Objective To investigate the efficacy and the rate of adverse events of chronic low-dose levodopa-carbidopa therapy in Japanese patients with Parkinson’s disease (PD).
Patients and Methods A total of 92 Japanese PD patients treated with low doses of levodopa from the outset were studied. Both disease-specific motor disabilities and quality of life (QOL) in the patients were evaluated using the Unified Parkinson’s Disease Rating Scale (UPDRS) and the Parkinson’s Disease 39 Quality of Life Questionnaire (PDQ39), respectively.
Results In the overall patient group, the mean duration of treatment, the mean daily dose of levodopa, the disability scores and the motor scores of UPDRS were 6.2 years, 186.4 mg, 8.0 and 19.2, respectively. The rates of motor fluctuations, dyskinesias and hallucinations were 8.7%, 6.5% and 14.1%, respectively. The mean summary index of PDQ39 scores was 23.1. Patients with motor fluctuations showed a significantly earlier disease onset. Dose of levodopa, age at onset, and treatment duration were not associated with the occurrence of dyskinesias. Patients with hallucination had higher doses of levodopa and dopamine agonist.
Conclusions Our results demonstrate that chronic administration of a low-dose levodopa preparation can provide satisfactory benefit with a low incidence of motor complications, and can result in good QOL in Japanese patients with PD. The concomitant use of a small amount of dopamine agonist and amantadine from the outset has partly contributed to a reduced dose of levodopa and the lesser occurrence of motor complications.

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We report four cases of peritoneal serous papillary adenocarcinoma (PSPC), a rare disease; all patients had ascites and high levels of serum CA125. Clinical and radiological examinations could not differentiate the disease from peritoneal metastatic tumors and mesothelioma, and histopathological analysis including immunochemistry on the specimen obtained at laparotomy or laparoscopy was necessary for the diagnosis. One patient lived for 58 months with cytoreductive surgery and chemotherapy, and another is still living after 20 months by chemotherapy alone. In patients with peritoneal tumors of unknown origin and a high level of serum CA125, taking PSPC into consideration in the differential diagnosis, histopathological examination should be performed.

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A 57-year-old woman was admitted due to a hemorrhage from esophageal varices. Laboratory tests showed liver dysfunction, elevated immunoglobulin G levels and positivity for anti-nuclear antibodies. Serum hepatitis B virus and hepatitis C virus markers were negative. The liver biopsy specimen was compatible with autoimmune hepatitis, and low-dose prednisolone was started. During the follow-up, her serum alanine aminotransferase levels continued to fluctuate between 40 and 60 IU/l. Nine years later, hepatocellular carcinoma 20 mm in diameter was detected. This case suggests that hepatocellular carcinoma develops even if serum alanine aminotransferase levels are maintained at less than twice the upper normal limit.

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We report a case of intestinal obstruction due to intramural hematoma of the duodenum following therapeutic endoscopy for a bleeding duodenal ulcer in a patient with liver cirrhosis. A 44-year-old man was admitted to our hospital with severe epigastralgia, nausea and tarry stool. Two years previously he had undergone endoscopic sclerotherapy for esophageal varices caused by alcoholic liver cirrhosis. Endoscopy revealed an open ulcer with a bleeding vessel in the duodenal bulb, and sclerotherapy was performed by clipping the vessel and injecting 20 ml of 0.2% epinephrine. His platelet count was 3.5×10⁴/μl. Twelve hours later, he again developed epigastralgia and hypotension. Emergency computed tomography and ultrasonography revealed an intramural hematoma, 15×18 cm in diameter, at the dorsal and lateral duodenum. Endoscopy and upper gastrointestinal series revealed severe stenosis of the duodenal lumen caused by intramural hematoma. He received parenteral feeding for 22 days and within 8 weeks the hematoma was gradually absorbed using conservative management. Intramural duodenal hematoma may be diagnosed as a complication of the endoscopic procedure in a patient with a bleeding tendency, such as liver cirrhosis.

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We report a 57-year-old woman with a primary hepatic carcinoid tumor who had been suffering from symptoms due to carcinoid syndrome and carcinoid heart disease for more than 9 years. Long-term injection of octreotide acetate was fairly effective to relieve the symptoms due to carcinoid syndrome, but its tumor contraction effect was not confirmed. The massive ascites in the follow-up period appeared to be diminished to a certain extent by timely chemotherapy including cisplatin. The patient died of multi-organ failure about 9 years after the onset of disease. Autopsy confirmed a primary hepatic carcinoid tumor with limited distant metastases.

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A 28-year-old man developed severe infundibular pulmonary stenosis (PS), coronary artery stenosis with sustained ventricular tachycardia (VT) 24 years after mediastinal irradiation (total amount of 40 Gray) for non-Hodgkin’s lymphoma. Repair of right ventricular outflow tract and coronary artery bypass graft procedure were performed. Infundibular PS was successfully relieved after operation and VT was also controlled by medication. Mediastinal irradiation often causes various cardiac complications after a latent period. Therefore, continuous careful observation is mandatory in patients with the history of mediastinal irradiation.

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A 31-year-old Chinese woman suffering from excessive thirst and appetite loss consulted our hospital. Laboratory examination revealed a high blood glucose level and evidence of diabetic ketoacidosis, however, the serum HbA1c was normal. The 24-hour urinary excretion of C-reactive protein and the glucagon stimulation test indicated the loss of endogenous insulin secretion. The patient satisfied the criteria for the diagnosis of fulminant type 1 diabetes mellitus. However, she tested positive for serum anti-IA2 antibody even though the titer was low. We considered it worthwhile reporting this case, because very few cases of fulminant type 1 diabetes mellitus among Chinese people have been published.

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A 53-year-old man with nephrotic syndrome and severe renal failure was diagnosed with light- and heavy-chain deposition disease (LHCDD) by renal biopsy. The patient had no monoclonal protein and mild marrow plasmacytosis (6%), but marrow plasma cells expressed CD19^-CD56⁺ and predominant monoclonal kappa-chain, indicating plasma cell dyscrasia. Conventional chemotherapy was ineffective and did not improve renal failure. High dose chemotherapy/peripheral blood stem cell transplantation (HDC/PBSCT) was introduced even after hemodialysis to eliminate aberrant clone and normalization of bone marrow cell surface markers. Immunophenotypic analysis of marrow cells facilitates clinical decision making regarding the use of HDC/PBSCT for LHCDD patients without monoclonal protein.

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A 44-year-old woman on maintenance hemodialysis was admitted to our hospital because of severe abdominal pain. The patient had been medicated with lisinopril and valsartan for hypertension for one month prior to admission. An abdominal computerized scan (CT) showed a dilated and thickened loop of the small bowel with massive ascites and a small nodule in the jejunum. The patient’s abdominal pain was thought to be due to isolated visceral angioneurotic edema induced by lisinopril and/or valsartan, and medication of these two drugs was therefore stopped. Her symptoms resolved and an abdominal CT demonstrated almost complete resolution of ascites and of small bowel edema except for a small nodule in the jejunum. A laparoscopic operation was performed to excise the small nodule of the jejunum, and a histological diagnosis of accessory pancreas of the jejunum was made. This is the first report of isolated visceral angioneurotic edema induced by lisinopril and/or valsartan in a patient on maintenance hemodialysis and, moreover, with the association of accessory pancreas of the jejunum.

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We describe a 55-year-old man with advanced adenocarcinoma of the lung who received gefitinib (‘IRESSA’). After gefitinib administration for 7 months, computed tomography scan of the chest demonstrated diffuse ground glass opacity and he was suspected to have developed gefitinib-induced interstitial lung disease (ILD). However, transbronchial lung biopsy (TBLB) revealed tumor cells in the middle-size lung vessels. Afterwards, multiple infarctions of the brain, spleen and left kidney were detected. Then, he was considered to have developed systemic tumor emboli, a rare complication. The clinical presentation of this patient was difficult to discriminate from that of ILD, and TBLB was useful in the differential diagnosis.

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A scaffold constructor lost consciousness at work, leading to emergency admission to our hospital. He had noted gradual worsening of exertional dyspnea over the previous 1 month. Chest radiography showed localized oligemia and enlarged hilar vessels. Pulmonary perfusion scintigraphy confirmed the existence of multiple perfusion defects, so a diagnosis of pulmonary thromboembolism was made. Upper and lower limb venography disclosed interruption of the right subclavian vein (so-called Paget-Schroetter syndrome). However, there was no difference in appearance between the right and left upper extremities. Five years after starting anticoagulant therapy, his symptoms have resolved, but serial perfusion scintigraphy and upper extremity venography revealed the persistence of abnormalities. In patients with pulmonary thromboembolism, lifestyle factors (especially heavy manual labor) should be considered and the possibility of subclavian vein thrombosis should be kept in mind.

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A 32-year-old woman was transported to our hospital by ambulance because of loss of consciousness and breathing induced by drug intoxication. After general status was recovered, her arterial blood gas analysis under breathing room air revealed hypercapnia and hypoxemia which were caused by hypoventilation. After exclusion of apparent pulmonary, neuromuscular and central nerve diseases, she was diagnosed with primary alveolar hypoventilation syndrome. She had the complication of antiphospholipid syndrome (APS), suggesting the possibility of small lesions of the brainstem due to APS, which were too small to be detected on CT or MRI; these small lesions could cause injuries to the respiratory center.

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Ferroportin disease, autosomal-dominant reticuloendothelial iron overload, may be more prevalent than hemochromatosis in Japan. Hyperferritinemia of 822 ng/ml with 24.8% transferrin saturation of iron was incidentally noted in a 43-year-old man. His iron overload was selective in Kupffer cells of the liver. Subsequently, his father was found to have asymptomatic hyperferritinemia of 2,283 ng/ml with 62.1% saturation. These affected subjects were heterozygous for 1467A>C (R489S) in SLC40A1, and without other mutations of the hemochromatosis genes. Here, we report a Japanese family with ferroportin disease, characterized by hyperferritinemia with relatively low transferrin saturations of iron.

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A 25-year-old Japanese man was diagnosed with steroid-resistant Adult Still’s Disease (ASD) in August 2000. No evidence of chronic myelogenous leukemia (CML) had been found during admissions in 2000 and 2001. In August 2002, he was diagnosed with CML with a peripheral white blood count of 69,940/μl and positivity for Philadelphia chromosome and BCR/ABL fusion gene on bone marrow aspiration. No case of CML was reported to develop from ASD. Because a diagnosis of ASD is based on the exclusion of other diseases, we must be cognizant of the possibility of the development of concurrent diseases.

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A 54-year-old Japanese woman with a 6-year history of systemic lupus erythematosus (SLE) was admitted to our hospital suffering from acute blindness in her right eye. Her condition recovered after steroid pulse therapy, however, 18 months later she suffered from nuchal pain for 2 weeks after which right hemiparesis with urinary incontinence developed. A spinal magnetic resonance imaging (MRI) revealed cord swelling from C2 to C7. She was diagnosed with neuromyelitis optica (NMO) and intravenous steroid administrations were immediately commenced. Her condition promptly improved. This case was unique because the steroid treatment was quite effective for this case of myelitis, which had passed the acute phase. We supposed that, because most of the lesion was not necrotic or demyelinated, but rather showed edematous change caused by vasculitis based on autoimmune pathogenesis, the symptoms progressed rather gradually and improved promptly in response to glucocorticoid treatment.

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We report a case of hypertensive brainstem encephalopathy (HBE) with unusual magnetic resonance imaging (MRI) findings. A 67-year-old woman presented with high blood pressure and stupor as the only symptoms. MRI revealed lesions localized in the area from the upper medulla oblongata to the lower pons with high fluid-attenuated inversion recovery (FLAIR) and T2-weighted signal intensity, but these were not seen in the whole brainstem and there were no accompanying occipital lobe changes. To our knowledge, no similar case has been reported. The lesions and symptoms dramatically improved after normalization of blood pressure. Severe hypertension that exceeded the range of autoregulation may have resulted in segmental vasodilatation and the increased vascular permeability may have lead to vasogenic edema in the localized areas of the brainstem.

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We report a 75-year-old man who developed herpes simplex encephalitis (HSE), presenting with bilateral hippocampal lesions on magnetic resonance imaging, and this case was simultaneously complicated by small cell lung carcinoma. We identified a new anti-neuronal antibody in the cerebrospinal fluid of this patient. Our findings suggest that HSE and paraneoplastic limbic encephalitis (PLE) can overlap, and we discuss the relationships of HSE, PLE, and related disorders.

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We report a patient with polymyalgia rheumatica (PMR) who showed a relapse soon after tapering of oral prednisolone. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were quickly normalized after the re-increase in oral prednisolone, and muscle pain and stiffness gradually improved in parallel with a decrease in serum amyloid A (SAA). Flow cytometry simultaneously demonstrated an increase in CD8⁺CD25⁺ cells and a decrease in CD4⁺CD25⁺ cells and CD4⁺CD45RA⁺ cells. When clinical symptoms remain with negative results for CRP and ESR even after the start of corticosteroid treatment, SAA might be a potent therapeutic marker for disease activity in PMR.

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A 72-year-old Japanese man displayed asymptomatic eosinophilia for 4 months. Computed tomography showed multiple space-occupying lesions in the liver. Zoonotic liver flukes were suspected based on occupational exposure to cattle, serological and radiological findings. Immunological examination was helpful in diagnosing the disease and laparoscopy was crucial in confirming Fasciola hepatica and excluding the possibility of malignant hepatic tumors. Human fascioliasis was finally diagnosed and praziquantel administered. Blood eosinophilia resolved within 4 months and liver tumors almost disappeared within 12 months. From our experience, laparoscopy with liver biopsy is very important for diagnosing human fascioliasis, particularly for asymptomatic fascioliasis.

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