Successful Treatment of Acute Chest Syndrome with Manual Exchange Transfusion in a Patient with Sickle Beta+-thalassemia.

Acute chest syndrome (ACS), characterized by fever, respiratory symptoms, and new pulmonary infiltration, is a serious complication of sickle cell disease (SCD). Regardless of the etiology, the conventional treatment options for ACS include empirical antibiotic therapy, the administration of analgesics, and red cell transfusion. The indications and methods of red cell transfusion are critical. We herein report the case of a 26-year-old African-American man with SCD who developed ACS and who was successfully treated with manual exchange transfusion. Despite increasing globalization, SCD remains extremely rare in Japan. Manual exchange transfusion can be performed easily anywhere and should be considered for treating SCD patients presenting with ACS.

Five Cases of Familial Mediterranean Fever in Japan: The Relationship with MEFV Mutations.

Familial Mediterranean fever (FMF) is the most common genetic autoinflammatory disease, but it has been considered a rare disease in Japan. We herein describe five patients with FMF who were diagnosed both clinically and genetically at a single Japanese institute. A genetic investigation of Mediterranean fever (MEFV) detected heterozygosity for the compound mutations L110P/E148Q (n=2) and L110P/148Q/P369S/R406Q (n=1), and heterozygosity for M694I (n=1) and S503C (n=1). Colchicine prevented febrile attacks and accompanying symptoms in four patients. One patient with an S503C mutation showed resistance. Physicians should be aware of the characteristic symptoms, as well as the more unusual symptoms such as headache, when diagnosing FMF.

Primary Signet Ring Cell Carcinoma of Rectum Diagnosed by Boring Biopsy in Combination with Endoscopic Mucosal Resection.

A 46-year-old man with severe back pain visited our hospital. Magnetic resonance imaging revealed extensive bone metastasis and rectal wall thickness. Colonoscopy revealed circumferential stenosis with edematous mucosa, suggesting colon cancer. However, histological findings of biopsy specimens revealed inflammatory cells but no malignant cells. The patient underwent endoscopic ultrasound, which demonstrated edematous wall thickness without destruction of the normal layer structure. After unsuccessful detection of neoplastic cells by boring biopsies, we performed endoscopic mucosal resection followed by boring biopsies that finally revealed signet ring cell carcinoma. Herein, we present a case and provide a review of the literature.

Key diagnostic features of fever of unknown origin: Medical history and physical findings.

Background: Fever of unknown origin (FUO) has many possible causes, so detailed history taking and physical examination are required. We identified key diagnostic features of medical history and physical findings for an efficient diagnosis of FUO. Methods: A total of 42 consecutive patients (mean age: 50.6±20.3 years) with classic FUO were retrospectively recruited from January 2010 to March 2012. Key diagnostic features were identified from among diagnostic criteria for underlying diseases, indicators for diagnostic tests, and more useful factors for differential diagnosis. Results: The mean number of abnormal findings per patient was 5.8 from taking the history and 2.0 from performing physical examination. In addition, the mean number of key diagnostic features identified was 0.7 (14.0%) from history taking and 0.6 (35.0%) from physical examination. The most relevant key diagnostic feature was arthritis, followed by cervical lymphadenopathy, dyspnea (with hypoxia), and ocular symptoms. Conclusion: The usefulness of certain features of medical history and physical findings for diagnosing FUO was determined. Focusing on arthritis, cervical lymphadenopathy, dyspnea with hypoxia, and ocular symptoms might improve diagnostic efficiency in patients with FUO.

General practice departments of university hospitals and certified training programs for general practitioners in Japan: A nationwide questionnaire survey.

Background: In the reform of specialist training by Japanese Medical Specialty Board, general practice is expected to be one of 19 core specialties. University departments of general practice can play a central role in training board-certified generalists, but whether they are actually preparing to do so is unknown. Method: We sent a questionnaire to 79 universities and requested to forward it to the general practice department. Fifty-six departments of general practice (37 public and 19 private universities) completed the questionnaire (response rate 71%). Results: Fifty-one (91.9%) universities planned to be the base institutes of certified programs. The annual seats per program ranged from 2 to 20 (median 5). In these 51 university-based programs, 33 (64.7%) departments provide the general practice II element. Twenty-eight (54.9%) require the program trainees to belong to the departments (do nyukyoku) and 11 (21.6%) recommend that they do so. Forty-seven (92.2%) programs had affiliated institutions in rural areas. Thirty-nine (76.5%) were willing to accept graduates of regional quota (chiikiwaku). Twenty-nine (56.9%) program directors took into account the obligatory service of regional quota when making the programs. Programs that accept regional quota graduates were more likely to be affiliated with rural institutions (P=.002) and conscious of the obligatory service in making the program than other programs (P<.001). Conclusion: Most of the university departments have their own training programs. Many of them are willing to accept nyukyoku doctors and regional quota graduates. Universities intend to play an important role in graduating generalists and supporting their careers.

Systemic Inflammatory Syndrome Associated with a Case of Jugular Paraganglioma.

Jugular paraganlioma is a benign, slow-growing tumor originating from the paraganglion cells and it is associated with catecholamine secretion. Paragangliomas can secrete Interleukin-6 (IL-6) and present as a systemic inflammatory syndrome; these characteristics have not been previously associated with jugular paragangliomas. A 63-year-old man with a jugular tumor in the skull base was referred to our hospital for an evaluation of pyrexia, back pain, and acute inflammation. His serum IL-6 level was elevated on admission and it decreased after radiotherapy. This is the first known case of a jugular paraganglioma exhibiting systemic inflammatory syndrome.

The Practice Guidelines for Primary Care of Acute Abdomen 2015.

BACKGROUND: Since acute abdomen requires accurate diagnosis and treatment within a particular time limit to prevent mortality, the Japanese Society for Abdominal Emergency Medicine in collaboration with four other medical societies launched the Practice Guidelines for Primary Care of Acute Abdomen that were the first English guidelines in the world for the management of acute abdomen. Here we provide the highlights of these guidelines [all clinical questions (CQs) and recommendations are shown in supplementary information]. METHODS: A systematic and comprehensive evaluation of the evidence for epidemiology, diagnosis, differential diagnosis, and primary treatment for acute abdomen was performed to develop the Practice Guidelines for Primary Care of Acute Abdomen 2015. Because many types of pathophysiological events underlie acute abdomen, these guidelines cover the primary care of adult patients with nontraumatic acute abdomen. RESULTS: A total of 108 questions based on 9 subject areas were used to compile 113 recommendations. The subject areas included definition, epidemiology, history taking, physical examination, laboratory test, imaging studies, differential diagnosis, initial treatment, and education. Japanese medical circumstances were considered for grading the recommendations to assure useful information. The two-step methods for the initial management of acute abdomen were proposed. Early use of transfusion and analgesia, particularly intravenous acetaminophen, were recommended. CONCLUSIONS: The Practice Guidelines for Primary Care of Acute Abdomen 2015 have been prepared as the first evidence-based guidelines for the management of acute abdomen. We hope that these guidelines contribute to clinical practice and improve the primary care and prognosis of patients with acute abdomen.

Practice Guidelines for Primary Care of Acute Abdomen 2015.

Since acute abdomen requires accurate diagnosis and treatment within a particular time limit to prevent mortality, the Japanese Society for Abdominal Emergency Medicine, in collaboration with four other medical societies, launched the Practice Guidelines for Primary Care of Acute Abdomen that were the first English guidelines in the world for the management of acute abdomen. Here we provide the highlights of these guidelines (all clinical questions and recommendations were shown in supplementary information). A systematic and comprehensive evaluation of the evidence for epidemiology, diagnosis, differential diagnosis, and primary treatment for acute abdomen was performed to develop the Practice Guidelines for Primary Care of Acute Abdomen 2015. Because many types of pathophysiological events underlie acute abdomen, these guidelines cover the primary care of adult patients with nontraumatic acute abdomen. A total of 108 questions based on nine subject areas were used to compile 113 recommendations. The subject areas included definition, epidemiology, history taking, physical examination, laboratory test, imaging studies, differential diagnosis, initial treatment, and education. Japanese medical circumstances were considered for grading the recommendations to assure useful information. The two-step methods for the initial management of acute abdomen were proposed. Early use of transfusion and analgesia, particularly intravenous acetaminophen, were recommended. The Practice Guidelines for Primary Care of Acute Abdomen 2015 have been prepared as the first evidence-based guidelines for the management of acute abdomen. We hope that these guidelines contribute to clinical practice and improve the primary care and prognosis of patients with acute abdomen.

Long-term administration of a Niemann-Pick C1-like 1 inhibitor, ezetimibe, does not worsen bile lithogenicity in dyslipidemic patients with hepatobiliary diseases.

BACKGROUND: Certain lipid-lowering drugs increase bile lithogenicity. Here we investigated whether long-term administration of ezetimibe, a new class of hypocholesterolemic agents designed to inhibit intestinal cholesterol absorption by inhibiting Niemann-Pick C1-like 1, alters bile lithogenicity in patients with hepatobiliary diseases. METHODS: Eleven dyslipidemic patients with gallstones and/or fatty liver diseases were treated with ezetimibe (10 mg/day) for 12 months. Bile samples were collected by nasal endoscopy before and after 3 and 12 months of treatment. Serum and bile lipids and serum metabolic parameters were analyzed. RESULTS: Serum levels of campesterol, total cholesterol, and low-density lipoprotein cholesterol were significantly decreased after 3 and 12 months of treatment. In contrast, serum lathosterol levels increased gradually. The lithogenic index of bile was unsaturated and unchanged in patients who were previously and concomitantly receiving ursodeoxycholic acid (UDCA). In patients who were not receiving UDCA, bile was initially supersaturated, but eventually was unsaturated. However, ezetimibe tended to elevate bile lithogenicity in cholecystectomy patients. CONCLUSIONS: Long-term treatment with ezetimibe improves lipid metabolism without significantly altering the bile lithogenicity. Therefore, inhibiting intestinal cholesterol absorption in dyslipidemic patients with hepatobiliary diseases is a safe therapeutic strategy without worsening biliary physiology.

Relationships between Causes of Fever of Unknown Origin and Inflammatory Markers: A Multicenter Collaborative Retrospective Study.

OBJECTIVE: Although inflammatory markers, such as the white blood cell (WBC) count, erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP) and procalcitonin, are widely used to differentiate causes of fever of unknown origin (FUO), little is known about the usefulness of this approach. We evaluated relationships between the causes of classical FUO and the levels of inflammatory markers. METHODS: A nationwide retrospective study including 17 hospitals affiliated with the Japanese Society of Hospital General Medicine was conducted. PATIENTS: This study included 121 patients ≥18 years old diagnosed with "classical FUO" (axillary temperature ≥38.0°C at least twice over a ≥3-week period without elucidation of the cause on three outpatient visits or during three days of hospitalization) between January and December 2011. RESULTS: The causative disease was infectious diseases in 28 patients (23.1%), non-infectious inflammatory disease (NIID) in 37 patients (30.6%), malignancy in 13 patients (10.7%), other in 15 patients (12.4%) and unknown in 28 patients (23.1%). The rate of malignancy was significantly higher for a WBC count of <4,000/µL than for a WBC count of 4,000-8,000/µL (p=0.015). Among the patients with a higher WBC count, the rate of FUO due to NIID tended to be higher and the number of unknown cases tended to be lower. All FUO patients with malignancy showed an ESR of >40 mm/h. A normal ESR appeared to constitute powerful evidence for excluding a diagnosis of malignancy. In contrast, the concentrations of both serum CRP and procalcitonin appeared to be unrelated to the causative disease. CONCLUSION: The present study identified inflammatory markers that should be considered in the differential diagnosis of classical FUO, providing useful information for future diagnosis.

Clinical evaluation of ezetimibe on bile lithogenicity in humans: Use of transnasal endoscopy for bile sampling.

AIM: Ezetimibe inhibits cholesterol absorption by blocking Niemann-Pick C1-like 1 proteins (NPC1L1) expressed in the small intestine. Because NPC1L1 is also expressed in human liver, ezetimibe conceivably alters biliary lipid compositions. Here, we performed a clinical trial investigating the effect of ezetimibe on biliary lipids using transnasal endoscopy for bile collection. METHODS: Eight patients with dyslipidemia enrolled in this study completed blood and bile sampling before and at 3 months after ezetimibe treatment (10 mg/day), and the samples are analyzed. RESULTS: Endoscopic bile sampling was performed safely and painlessly. Serum sterol-based biomarkers declared decreased cholesterol absorption and increased synthesis. On analysis of biliary lipids, four of the eight patients showed relative decrease of cholesterol and increase of bile acids with improved lithogenicity while the remainder exhibited the symmetrical changes. CONCLUSION: Our data suggests that biliary lithogenicity is not worsened by ezetimibe. The regulation of biliary cholesterol is presumably multifactorial such as body cholesterol pool size and biliary cholesterol reabsorption by NPC1L1 in the liver.

Diagnostic workup for fever of unknown origin: a multicenter collaborative retrospective study.

OBJECTIVE: Fever of unknown origin (FUO) can be caused by many diseases, and varies depending on region and time period. Research on FUO in Japan has been limited to single medical institution or region, and no nationwide study has been conducted. We identified diseases that should be considered and useful diagnostic testing in patients with FUO. DESIGN: A nationwide retrospective study. SETTING: 17 hospitals affiliated with the Japanese Society of Hospital General Medicine. PARTICIPANTS: This study included patients ≥18 years diagnosed with 'classical fever of unknown origin' (axillary temperature ≥38°C at least twice over a ≥3-week period without elucidation of a cause at three outpatient visits or during 3 days of hospitalisation) between January and December 2011. RESULTS: A total of 121 patients with FUO were enrolled. The median age was 59 years (range 19-94 years). Causative diseases were infectious disease in 28 patients (23.1%), non-infectious inflammatory disease in 37 (30.6%), malignancy in 13 (10.7%), other in 15 (12.4%) and unknown in 28 (23.1%). The median interval from fever onset to evaluation at each hospital was 28 days. The longest time required for diagnosis involved a case of familial Mediterranean fever. Tests performed included blood cultures in 86.8%, serum procalcitonin in 43.8% and positron emission tomography in 29.8% of patients. CONCLUSIONS: With the widespread use of CT, FUO due to deep-seated abscess or solid tumour is decreasing markedly. Owing to the influence of the ageing population, polymyalgia rheumatica was the most frequent cause (9 patients). Four patients had FUO associated with HIV/AIDS, an important cause of FUO in Japan. In a relatively small number of cases, cause remained unclear. This may have been due to bias inherent in a retrospective study. This study identified diseases that should be considered in the differential diagnosis of FUO.

Prevalence of chlamydia pneumoniae in Japanese rural districts; association of smoking and physical activity with Chlamydia pneumoniae seropositivity.

OBJECTIVE: We conducted a large-scale cross-sectional study to assess the prevalence of Chlamydia pneumoniae and clarify the association between seropositivity and risk factors, such as smoking status, physical activity and body mass index in Japanese rural districts. METHODS: A total of 1,063 men and 1,573 women aged 18-94 years participated in 1999. Serum index values (ID) of IgA and IgG antibodies to C. pneumoniae were measured by ELISA. Index values were categorized as "negative" (ID < 1.10), "positive" (ID > or = 1.10) and "high positive" (ID > or = 3.00). Logistic regression analysis was performed to estimate the crude and adjusted odds ratios for C. pneumoniae seropositivity. RESULTS: The overall prevalence of C. pneumoniae IgA seropositivity was 52.5%, and that of IgG was 55.2%. Each seropositivity significantly increased with age. The prevalence among men was significantly higher than in women in C. pneumoniae IgG "high positive" subjects. Compared with never-smokers, the adjusted odds ratio of current smokers was 2.00 (95% CI: 1.45-2.77) for C. pneumoniae IgA seropositivity. The adjusted odds ratio of the higher tertiles of physical activity for C. pneumoniae IgG seropositivity was 1.42 (1.12-1.80) compared with the lower tertiles. In "high positive" subjects, smoking was associated with both immune complexes. CONCLUSION: We confirmed a high prevalence of C. pneumoniae seropositivity among healthy Japanese adults. The results indicated that smoking and high physical activity were associated with C. pneumoniae infection.

Job characteristics and serum lipid profile in Japanese rural workers: the Jichi Medical School Cohort Study.

To observe the association between adverse psychosocial job characteristics, measured by the Karasek job demand-control questionnaire, and a lipid profile, cross-sectional analyses were performed for a Japanese rural working population. The study population comprised 3,333 male and 3,596 female actively employed workers, aged 65 years and under. Among men, higher psychological demands were associated with high total cholesterol levels, with an adjusted difference from the top to bottom tertiles of 3.3 mg/dl (F = 3.03; p = 0.048). High demands were also positively associated with the total/HDL cholesterol ratio (F = 3.94; p = 0.020). Neither job control nor job strain (the ratio of demands to control) was associated with any of the lipid levels in either gender. A psychologically demanding job may be associated with an unfavorable lipid profile, but the impact of job strain on atherogenic lipids is negligible.