Devices for home blood pressure (BP) measurement are produced worldwide at a rate of more than 10 million a year and 30 million such devices have already been distributed in Japan. The clinical significance of home BP measurement is obvious; patients can recognize the effects of antihypertensive treatment. Home BP measurements encourage medication compliance, follow-up clinic visits, and active participation in the medical treatment, thus resulting in improved management of hypertension. Home BP measurements more accurately reflect damage to target organs and the prognosis of cardiovascular diseases. The purpose of home BP measurements is to obtain information on the patient's inherent BP pattern using longterm, repetitive measurement under controlled conditions. Since home BP is measured under controlled condition, values are reproducible, and thus, useful in the diagnosis and treatment of hypertension. Blood pressures measured under standardized condition are indispensable when comparing data among individuals, among groups and among institutes. Working Group of Japanese Society of Hypertension (JSH) established JSH Guidelines for Self-Monitoring of Blood Pressure at Home in 2003. Standardization of the measurement procedure may elevate the position of home BP measurements for the purpose of diagnosing and treating hypertension. As a result, home BP measurements may improve the accuracy of screening for hypertension and assessment of BP control during treatment and encourage drug compliance. Home BP measurements, under such controlled conditions, should have a beneficial effect on the economics of diagnosing and treating hypertension.

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  Objective  The optimal approach to relatively recent onset type 2 diabetes patients is still unknown. We speculated that the use of short-acting insulin analogs might be of particular benefit in this context.
  Patients and Methods  To explore this possibility, we compared the effect on β- and α-cell function of transient intensive insulin therapy using lispro versus human regular insulin in a total of 21 type 2 diabetic patients who were randomly assigned to 14-days intensive insulin therapy consisting of bedtime NPH insulin plus three injections of mealtime lispro (n=11) or regular insulin (n=10). The dosages of both types of insulin were adjusted to attain preprandial glucose levels of <6.1 mmol/l within 1 week with similar rates of glucose decline. An oral glucose tolerance test (OGTT) was performed at day 0 (baseline), 7, and 14; plasma glucose, serum insulin, and plasma glucagon responses over 0-120 minutes were measured, and calculated as the area under the curve (AUC).
  Results  Lispro led to a significant reduction in glucose-AUC and also an increase in insulin-AUC versus regular insulin on day 7. Glucagon secretion following OGTT was well suppressed with lispro on day 14 compared to regular insulin.
  Conclusion  Two-week intensive insulin therapy with lispro appeared to be more effective than that with regular insulin in type 2 diabetes in attaining both more rapid β-cell rest and greater suppression of glucagon. These changes may provide significant long-term benefits.

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  Objectives  Measurement of blood glucose is essential for better control of diabetes mellitus. The pain associated with repeated blood sampling is a significant problem, and a less painful technique would be advantageous. This study was conducted to establish a less painful method of blood sampling for monitoring of blood glucose concentrations.
  Methods  Fourteen healthy doctors and nurses at the age of 22 to 32 years were enrolled into this study. The earlobe was divided into 20 areas. Each area was punctured with a fine needle and the pain was assessed by the visual analog scale (VAS). Then, localized cooling or warming was applied before puncture and the pain was assessed by the VAS.
  Results  The VAS tended to be lower toward the lower part of the earlobe. The VAS in the uppermost area was 53.1±19.1 mm and 28.9±16.8 mm in the lowest part of the earlobe. The VAS was higher in the uppermost area than in the lowest area in six of the seven volunteers (p=0.028). We did not find significant differences in the VAS and blood glucose levels between the control sampling and the warming, or cooling sampling. The localized warming shortens the time to obtain blood by 4.4 seconds (p=0.0426).
  Conclusion  The area of the ear, but not localized cooling or warming, significantly affects the pain in sampling blood from the earlobe. Blood sampling for glucose tests are recommended to be obtained at the lower pole of the earlobe.

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  Objective  The accumulation of dioxins, characterized by its lipophilicity and persistency in human tissue, is a great concern since many of these compounds elicit adverse health effects and developmental toxicity. Although the half-life of dioxins in the human body have been described to be as long as 3-25 years, there are very few drugs or methods that can exclude them from the human body. Thus, it is necessary to establish a new method to reduce them and prevent adverse health effects. Here, a pilot study to reduce the dioxins accumulated in the human body using the cholesterol-lowering drug, colestimide, is reported.
  Patients and Methods  Eight male and two female subjects were investigated. All of them were treated with colestimide for six months, and the dioxin level of the blood samples was assessed before and after the treatment. The dioxins in the blood samples were measured by gas-chromatography/mass spectrometry.
  Results  Nine out of the ten subjects completed the treatment, and their blood samples were analyzed. The mean dioxin level in the blood samples before the treatment was 44.0±8.22 pg-TEQ/g-fat. Six months later, the mean dioxin level was lowered about 20% on average to 34.7±5.49 pg-TEQ/g-fat.
  Conclusion  Previous studies have reported that the blood dioxin level increases with age. In this study, the results suggest that colestimide can decrease the blood dioxin level of humans. A randomized placebo-controlled clinical study including large numbers of subjects are needed to confirm the present result.

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  Objective  We assessed the potential for estimating the effects of antiviral therapy on the clearance of intrathecal herpes simplex virus (HSV) antigens as evaluated by the chemiluminescence assay (CL) and on that of intrathecal HSV-DNA as evaluated by the nested polymerase chain reaction (PCR) in serial patients with herpes simplex virus encephalitis (HSVE).
  Methods  The materials comprised serial cerebrospinal fluid (CSF) samples from 18 patients with HSVE. All patients were diagnosed as having HSVE retrospectively based on the detection of intrathecal HSV antigens by the CL, that of HSV-DNA by the nested PCR, and also serological confirmation of intrathecal antibody production. The relationships between the days of aciclovir therapy and serial HSV viral loads as evaluated by the CL and nested PCR in the serial CSFs were assessed.
  Results  The serial intrathecal viral loads evaluated by the CL and nested PCR declined after the commencement of aciclovir administration in all patients. The serial alterations of the intrathecal viral load evaluated by the CL in each patient were similar to those of the intrathecal viral load evaluated by the nested PCR. The initial and maximum viral loads evaluated by the CL and nested PCR showed a wide distribution in the CSF samples taken from the patients with poor and good outcomes. Differences in the means of the viral loads in the CSF samples taken from the patients between a poor outcome and a good outcome were not evident. A transient increase of viral load as evaluated by these two methods was noted in the same 4 patients. The viral loads in these 4 patients also declined in the subsequent CSF samples. The outcome of these 4 patients was good in one patient and poor in the others.
  Conclusion  Evaluation of intrathecal viral antigens by the CL has a potential for estimating the effects of antiviral therapy, as does evaluation of the intrathecal HSV-DNA by the nested PCR. The intrathecal viral loads evaluated by CL and nested PCR were not a predictor of outcome in HSVE.

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A 34-year-old woman with liver insufficiency due to glycogen storage disease III underwent a living spousal liver transplantation. Soon after the successful operation, moderate hypercalcemia along with hyperbilirubinemia emerged without clarified reasons. The hypercalcemia persisted for over a month despite calcitonin treatment and the serum calcium level surged to 13.2mg/dl with albumin correction. Renal dysfunction was indicated by an acute increase in serum creatinine (∼0.8 to ∼2.8mg/ml), which was assumed to be hypercalcemia-induced and was effectively treated with bisphosphonate, pamidronate (30 mg, i.v.). Recent topics related to transplantation-associated hypercalcemia are discussed.

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In most cases of hepatitis E in Japan, patients acquire the viral infection abroad in countries where hepatitis E is endemic. However, in Nagano Prefecture, Japan, we encountered a patient with hepatitis E who had never been abroad. The diagnosis was made on finding hepatitis E viral RNA and antibodies against the virus in the serum. Prompt normalization of liver function test occurred without medication. The nucleotide sequence of the virus isolated from this patient was closely related to the sequence of previously isolated viruses of genotype III. The source of infection could not be identified.

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A 71-year-old man who had a history of open chest surgery was admitted due to anasarca and bilateral pleural effusions. Although imaging modalities could not demonstrate any pericardial abnormalities, right-sided cardiac catheterization revealed ‘dip and plateau’ in diastolic pressure waveform. He was admitted frequently because of the episodic right-sided congestive heart failure and hypoproteinemia due to protein-losing enteropathy. The peripheral lymphocyte count and serum gamma-globulin concentration were gradually decreased, and finally showed lymphocytopenia and hypoglobulinemia. On the last admission, the patient showed extensive cellulitis on both legs, and he developed septicemia, and finally died due to septic shock. Post-mortem examination showed that both visceral and parietal layers of the pericardium adhered tightly with mediastinal fibrosis. This case report suggested that constrictive pericarditis should be considered even if there is a lack of typical abnormal pericardial imaging findings when patients have a history of open chest surgery and recurrent rightsided congestive heart failure. In addition, we should be aware of a serious outcome due to immune compromised conditions such as lymphocytopenia and dysglobulinemia in this disorder.

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A 24-year-old woman was admitted to our department for further examination of hypercalcemia, a high level of intact parathyroid hormone (PTH) and a right parathyroid tumor. She complained of bone pain throughout her body and was unable to walk due to systemic cystic osteofibrosis, including a brown tumor of the left lower extremities. Neck ultrasonography (US) and magnetic resonance imaging (MRI) revealed a tumor 2 cm in diameter in the upper side of the right thyroid lobe. ^99mTc sestamibi (^99mTc-MIBI) imaging and F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) were performed to diagnose primary hyperparathyroidism and examination of other parathyroid glands. However, neither imaging modality detected the parathyroid tumor. To confirm the diagnosis, we performed selective venous sampling around the parathyroid and the patient was diagnosed with primary hyperparathyroidism due to a right parathyroid tumor. Resection of the right parathyroid tumor was performed and the pathological diagnosis was parathyroid adenoma. To date, both ^99mTc-MIBI and FDG-PET are useful to localize parathyroid tumors. In this case, however, neither modality detected the tumor. Although recent studies state that expression of P-glycoprotein (P-gp) in parathyroid tumors plays an important role in the false-negative results of both ^99mTc-MIBI scans and FDG-PET, immunohistological study detected no P-gp expression in the parathyroid tumor in the current case.

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We report an 80-year-old man who presented with non-islet cell tumor hypoglycemia (NICTH) in association with hepatic recurrence of gastric cancer. His serum potassium was reduced from 3.9 to 3.1 mmol/l 5 weeks after gastrectomy, and he subsequently developed hypoglycemic coma. He was diagnosed as having NICTH because of the presence of serum big IGF-II and positive staining for IGF-II in gastric cancer cells obtained at surgery. A computed tomography showed multiple liver metastases. His hypoglycemia was refractory to steroid therapy. This case suggested that NICTH could develop in association with hepatic metastases of gastric cancer. Unexpected hypokalemia may be a manifestation of occult NICTH.

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We report a case of tracheo-bronchitis in Crohn's disease. A 23-year-old Japanese woman who had been diagnosed with Crohn's disease three years previously was hospitalized. She had been suffering from dry cough for one month. Computed tomography of the chest revealed marked thickening of the tracheal wall. Bronchoscopy showed erythematous and edematous mucosa with diffuse whitish granular lesions in the trachea and bronchi. The bronchial biopsy specimens showed non-specific inflammatory infiltrates consisting of lymphocytes and plasma cells, and hyperplasia of bronchial glands. Inhaled corticotherapy, fluticasone propionate 800 μg/day, was effective for both the inflammatory mucosa and thickened tracheal wall.

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A 67-year-old man was admitted due to fever and exertional dyspnea. He used to raise budgerigars and hill mynahs from 1980 to 1988. He was diagnosed as having chronic bird fancier's lung (BFL) based on a positive peripheral lymphocyte proliferation to pigeon serum in 1994. His disease was stable until 2000. Three months before admission he became a daily user of a feather duvet. A chest CT showed newly-developed peribronchial ground-glass opacities and preexisting honeycombing. Inhalation provocation test was positive. Administration of steroids improved his condition. He has been well after refraining from the use of the feather duvet.

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Amyopathic dermatomyositis (ADM) is a clinical subtype of dermatomyositis, characterized by the lack of motor weakness and the presence of normal muscle enzyme levels. ADM is sometimes accompanied by interstitial pneumonia that shows a rapid progressive course associated with a poor prognosis. We report a 49-year-old patient who presented with nonspecific interstitial pneumonia (NSIP) associated with ADM. The patient failed to respond to prednisolone and immunosuppressive therapy and died. Although idiopathic NSIP is known to have a better prognosis, NSIP in ADM could be a fatal disease. Therefore, we should appropriately treat interstitial pneumonia in ADM even if it is NSIP.

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A 57-year-old woman presented with bloody sputum and high grade fever. She had been treated for Mycobacterium avium-intracellulare complex (MAC). High grade fever slightly decreased and bloody sputum disappeared after two weeks, but low grade fever persisted. After 3 days of recurrence of bloody sputum, she suddenly complained of palpable pururitic lesions on the bilateral lower extremities with bilateral gonalgia. Although there are some reports of direct skin lesions due to MAC, there are no reports of hypersensitivity vasculitis, Henoch-Schönlein purpura, in MAC. It is necessary to consider MAC infection as a potential cause of Henoch-Schönlein purpura.

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In the past two decades, low-dose methotrexate (MTX) has been widely used in the treatment of rheumatoid arthritis (RA). As adverse effects, various types of pulmonary toxicity have been reported with this therapy. We report a case of MTX-induced noncardiogenic pulmonary edema in a 35-year-old woman. MTX used in high dose for anti-cancer therapy is known to cause noncardiogenic pulmonary edema. However, there are no previous reports of noncardiogenic pulmonary edema caused by low-dose MTX therapy. This report suggests that patients receiving oral weekly, low-dose MTX may be at risk for the development of noncardiogenic pulmonary edema.

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The radiological manifestations of pulmonary nocardiosis are very diverse, and include non-segmental consolidation and pulmonary nodule(s). Cavitary nodules most commonly appear in AIDS patients, and are uncommon in non-AIDS patients. We report a case of pulmonary nocardiosis with bilateral multiple cavitary nodules in a HIV-negative 60-year-old man with nephrotic syndrome who was receiving corticosteroid treatment. It is suggested that pulmonary nocardiosis should be considered in the differential diagnosis of multiple cavitary nodules on chest radiographs, even in non-AIDS immunocompromised patients.

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A 56-year-old man with a past history of surgical resection of a primary pulmonary adenocarcinoma in the right upper lobe was admitted to our hospital because of a rapidly increasing solitary nodule (50×30 mm) in the right S⁵ followed on the chest computed tomography (CT) for three months. Although we suspected recurrence of the pulmonary adenocarcinoma and performed a CT-guided lung biopsy, we could not make a definite diagnosis. Therefore, to rule out recurrence of the primary pulmonary adenocarcinoma completely, a partial surgical resection of the right middle lobe was performed and a caseating epitheloid granuloma with acid-fast bacilli was found. As the causative pathogen, Mycobacterium avium complex (MAC) disease should be considered in the differential diagnosis of a rapidly increasing solitary nodule through this peculiar case of pulmonary MAC disease.

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A 46-year-old man with myeloproliferative disorder received a stem cell transplant from an HLA-identical unrelated donor. Eight months status post transplantation, during the course of tacrolimus therapy, the patient developed severe epigastric pain and fever. FGS findings showed eruptions with blisters in the esophagus and ulcers in the stomach. Biopsy specimens revealed acidophilic inclusion bodies in the nuclei. Varicella zoster virus (VZV) DNA copies were detected in the serum. No skin lesions were observed prior to hospital admission. The diagnosis of visceral VZV infection was made and the gastric and esophageal lesions were successfully healed with acyclovir (ACV). Severe abdominal pain is one of the most important signs of VZV infection for recipients of stem cell transplantation.

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We report a 70-year-old man who presented symptoms resembling those of meningoencephalitis and who was subsequently diagnosed as having a crowned dens syndrome. The patient exhibited severe neck pains, head-ache, high fever and a pain in his knee joints together with symptoms of the central nervous system. The patient's cerebrospinal fluid was almost clear and showed no sign of viral infection. An analysis of the synovial fluid in the right knee joint revealed typical calcium pyrophosphate dehydrate crystal deposition and a diagnosis of pseudogout was therefore made. A tomographic examination of the neck showed periodontoid calcification. The patient was first treated with non-steroidal anti-inflammatory drug, but its effect was only minimal. On the other hand, the administration of corticosteroid resulted in a dramatic improvement in his condition.

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Hyperhomocysteinemia is thought to cause ischemic strokes. We report two middle-aged widowers with frequent recurrences of small-artery strokes, two capsular infarcts and a thalamic hemorrhage in one patient, and two thalamic and pontine infarcts in the other. Blood tests following the final stroke showed hyperhomocysteinemia and methylenetetrahydrofolate reductase C677T gene mutation, with low concentration of vitamin B6. Multivitamin supplementation normalized plasma homocysteine levels in both patients. Hyperhomocysteinemia is treatable; therefore, serum homocysteine should be measured as a potential risk factor for stroke recurrence in relatively young patients with recurrent small-artery infarctions or hemorrhage, especially those with insufficient lifestyle factors.

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We report a 60-year-old woman with neurosarcoidosis. She was referred to our hospital for examination of the cause of pain in left Th4-6 dermatome. Chest X-ray and computed tomography (CT) revealed bilateral hilar and mediastinal lymphadenopathy, and her serum angiotensin converting enzyme (ACE) level was elevated. Histological finding of mediastinal lymph nodes consisted with sarcoidosis. Therefore, her pain was thought to be spinal root pain caused by neurosarcoidosis. With the administration of prednisolone, her symptom and bilateral hilar lymphadenopathy disappeared, and serum ACE level became normal. It is important to pay attention to neurosarcoidosis when patients show unknown spinal root symptom, although it is rare.

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A 39-year-old woman with mixed connective tissue disease suddenly developed repeated watery diarrhea two years after the onset of the disease. A colonic biopsy specimen revealed amyloid A protein deposition and the diagnosis of secondary amyloidosis was established. The amyloid deposition disappeared after the 8-month course of the treatment with prednisolone and azathioprine. Molecular genetic analysis showed the presence of the γ-allele in her serum amyloid A protein 1 gene. This might be associated with the early onset and progression of secondary amyloidosis in our case, just like cases reported in rheumatoid arthritis.

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