The conceptual framework of statistical tests and statistical inferences are discussed, and the epidemiological background of statistics is briefly reviewed. This study is one of a series in which we survey the basics of statistics and practical methods used in medical statistics. Arguments related to actual statistical analysis procedures will be made in subsequent papers.

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Functional dyspepsia is a highly prevalent and heterogeneous disorder. Functional dyspepsia involves many pathogenic factors, such as gastric motility disorders, visceral hypersensitivity, psychological factors, Helicobacter pylori infection, and excessive gastric acid secretion. The present article provides an overview of pathogenetic factors and pathophysiologic mechanisms.

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Corticotropin-releasing factor (CRF) in the medial prefrontal cortex (mPFC) is suggested to play an important role in mediating fear, anxiety, and depression. The results of the studies of the actions of CRF in the mPFC regarding anxiety-related behavior, however, seem contradictory. In one study, microinjection of CRF into the mPFC produced an increase in anxiety-related behavior on the elevated plus maze, whereas in another study CRF produced an anxiolytic-like effect. To test whether the different doses of CRF used in these experiments are responsible for the differing results, we examined the dose-dependent effects of CRF (0.015, 0.05, 0.15, 0.5, and 1.0 μg/0.5 μL/site) microinjected into the bilateral mPFC of male Wistar rats on anxiety-related behavior in the elevated plus maze. We found that microinjection of 0.05 μg CRF significantly decreased the number of open-arm entries, whereas 1.0 μg CRF significantly increased the time spent on the open arms. The results indicate that CRF has effects opposing anxiety-related behavior in the elevated plus maze: anxiety-related behavior at a lower dose and an anxiolytic-like effect at a higher dose.

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Dialysis-related complications have become a major concern as the number of patients receiving long-term maintenance dialysis increases. One cause of complications is contamination of the dialysis fluid. When dialysis fluid contaminated by bacteria or endotoxin (ET) or both has been used for a long time, cytokine production in vivo is enhanced and can lead to such complications as dialysis amyloidosis. The rate of dialysis-related complications might be reduced with a hemopurification method that uses a large amount of dialysis fluid as a substitution fluid (on-line hemodiafiltration) or an efficient dialyzer with enhanced internal filtration in which the dialysis fluid returns to the body as a replacement fluid; however, at the same time, there is an increased risk of ET entering the body because the dialysis fluid might be contaminated. Therefore, the dialysis fluid must be made aseptic, and the dialysis fluid line must be properly managed to prevent contamination of the dialysis fluid. A half-opened line is at great risk of contamination by living microbes, which can grow in dead spaces and where the flow of dialysis fluid is interrupted. The management of couplers is an important measure for maintaining cleanliness at the end of the dialysis fluid flow. We attempted to separate and regularly clean the main body of the coupler with ultrasonic equipment as a method of managing the conventional coupler. Using improved types of coupler, the water quality of the postcoupler flow was maintained at a level as high as that of the precoupler flow for the duration of the evaluation period without separate cleansing being done. Although separate once-a-week cleansing of the conventional coupler was able to keep ET values less than the detection limit, viable cell counts were unstable. On the other hand, twice-a-week ultrasonic cleansing eliminated almost all viable cells. No definite difference in ET values or viable cell counts was found between the cleansing groups, and ultrasonic cleansing was able, by itself, to provide a sufficient cleansing effect. We conclude that ultrasonic cleansing of conventional couplers is a useful method for maintaining the water quality of the postcoupler flow because the cleansing of the coupler twice or more a week is sufficient to keep the water quality of the postcoupler flow as high as that of the precoupler flow.

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To assist physicians, especially young physicians, in identifying tuberculosis (TB) infection before the terminal stage, we analyzed 7 cases of numerous tuberculous granulomas in multiple organs and compared clinical and autopsy findings between cases. Patients ranged in age from 41 to 86 years at the time of death. The main chief complaint was fever of unknown origin (3 of 7 cases [43%]). The main underlying conditions were liver cirrhosis (2 of 7 cases [29%]) and chronic renal failure (2 of 7 cases [29%]). Two patients (29%) had been given methylprednisolone pulse therapy for various lung disorders. Active TB was not diagnosed before autopsy in 4 of 7 (57%) patients. Calcified lesions indicative of old TB were present in 4 of 7 (57%) patients. Thus, miliary tuberculosis may represent a re-emergence of latent TB infection in these cases. Various histologic features of nonreactive exudative inflammation were seen, along with granulomas containing Langhans giant cells with or without caseous necrosis in hypervascular organs, such as the lung, liver, and bone marrow. Physicians should be mindful of the possibility of miliary TB when older patients with hepatorenal disease and a history of TB infection have undergone immunosuppressive treatment. Active tuberculous infection can depend on the presence of an underlying disease and immunocompromise.

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We describe a patient with intracystic hemorrhage from one of multiple hepatic cysts. A 66-year-old woman was admitted to Nippon Medical School Hospital because of pain in the right upper quadrant of the abdomen. The medical history included multiple hepatic cysts and angina pectoris, which had been treated with aspirin. Three weeks before presentation, pain occurred in the right upper quadrant of the abdomen but resolved spontaneously. Ultrasonography revealed multiple hepatic cysts. One of the cysts in segment 8 had a hypoechoic structure and contained fluid. Computed tomography showed an area of homogenous density (diameter, 6 cm) which was slightly greater than that of the other hepatic cysts in segment 8. There was calcification of the cyst wall. On magnetic resonance imaging, this cyst showed heterogeneous hyperintensity on T1- and T2- weighted sequences which was greater than that of the other hepatic cysts. Intracystic hemorrhage of one of the multiple hepatic cysts was diagnosed. The pain gradually resolved without drainage, embolization, or operation, and the patient was discharged. After discharge, the upper abdominal pain did not recur. On magnetic resonance imaging 14 months later, the cyst showed heterogeneous hyperintensity on T1- and T2- weighted sequences which was less than that on the previous scan.

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Hepatic angiomyolipoma is a rare hepatic mesenchymal tumor. We report a case of hepatic angiomyolipoma that was successfully resected along with a giant hemangioma. A 53-year-old Japanese woman was admitted to our hospital for further evaluation of a liver tumor in segment 4. The tumor was detected on positron emission tomography during a health check-up. Abdominal ultrasonography revealed a well-defined mass of mixed echogenicity, 1.5 cm in diameter, in segment 4, and a giant hemangioma of mixed echogenicity, 7 cm in diameter, in segment 7. On enhanced computed tomography, the tumor in segment 4 showed hyperattenuation in the early phase and hypoattenuation in the delayed phase. On magnetic resonance imaging, the tumor in segment 4 showed hypointensity on T1-weighted images, hyperintensity on T2-weighted images, and hyperintensity on diffusion-weighted images. On angiography, the tumor in segment 4 appeared as a circumscribed hypervascular mass in the early phase and a slightly hypovascular mass in the delayed phase. The imaging findings suggested a primary hepatocellular carcinoma. The patient consented to resection of the tumor in segment 4 along with the giant hemangioma in segment 7. These tumors were resected with tumor-free surgical margins by partial resection of segments 4 and 7 of the liver. The cut surface of the resected specimen of segment 4 showed a yellowish tumor consisting of mature adipose tissue. The histopathological diagnoses of the resected specimens were angiomyolipoma in segment 4 and cavernous hemangioma in segment 7. The tumor in segment 4 consisted of mature lipocytes with angiomatous and small lymphocytic components, but no mitotic figures. The tumor showed immunoreactivity to smooth muscle antigen and homatropine methylbromide 45 and no immunoreactivity to AE/E3. The postoperative course was uneventful, and the patient remains well 1 year after the operation.

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C1q deficiency is a rare complement deficiency in the early part of the complement cascade. Patients with C1q deficiency have severe recurring life-threatening infections and systemic lupus erythematosus (SLE)-like symptoms. We report on a boy with recurrent life-threatening infections and SLE-like recurrent skin conditions before 2 years of age. Immunological studies revealed an undetectable level of C1q. No abnormality was observed in the urine, but renal biopsy showed segmental granulonephritis. However, the changes observed were atypical for SLE nephritis. This case of C1q deficiency was unusual because the SLE-like symptoms appeared earlier than that normally seen in complement deficiency. Therefore, this case provides insights into the development of autoimmune disease, particularly in the early phase of component deficiency, and in managing renal disease that may develop in the future.

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A 27-year-old nulligravida woman without a history of dermatosis was hospitalized for threatened preterm labor at 29 weeks' gestation; therefore, continuous infusion of ritodrine hydrochloride was started. At 31 weeks' gestation, erythematous plaques appeared and spread over the body surface; therefore, a topical steroid preparation was applied. At 32 weeks' gestation, the eruptions developed into irregular annular areas of erythema with multiple pustules accompanied by severe itching, and oral prednisolone treatment was started. Bacterial cultures of the pustules were negative, and a crural cutaneous biopsy revealed Kogoj's spongiform pustules. Based on the clinicopathological findings, the most likely diagnosis was impetigo herpetiformis, which causes cutaneous symptoms closely resembling pustular psoriasis in pregnant females without a history of psoriasis. To rule out ritodrine-induced pustular eruptions, the ritodrine infusion was stopped and treatment with an MgSO₄ preparation was started at 33 weeks' 3 days' gestation; however, the uterine contractions could not be suppressed. Because of the patient's highly edematous, severely painful feet, a cesarean section was performed the same day. Within several days of delivery, the eruptions began to resolve, and no recurrence was observed after treatment with oral prednisolone was stopped 31 days after delivery. On the basis of a positive patch test for ritodrine, we diagnosed pustular drug eruptions caused by ritodrine hydrochloride. Although ritodrine-induced pathognomonic cutaneous eruptions are rare, we would like to emphasize that ritodrine can cause drug-induced pustular eruptions distinctly resembling life-threatening impetigo herpetiformis.

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Delivery before arrival at a hospital did not cause major perinatal complications; however, it may reflect a serious problem of perinatal medicine in eastern Tokyo, Japan.

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