As a strategy to prevent the progression of diabetes mellitus, it is important to screen out the subjects who will develop a pre-diabetic state (PDS) in the future. To find out the potential risk factors for PDS, we employed the values of fasting plasma glucose and hemoglobin A1c (HbA1c), which are routinely measured in our health checkup. We selected 3,879 individuals who had normal glucose regulation at both fasting plasma glucose < 6.1 mmol/l and HbA1c < 5.5% in 1997 and investigated whether they would develop PDS in the next 5 years. PDS is defined at fasting plasma glucose ≥ 6.1 mmol/l and HbA1c ≥ 5.5%. Among 3,879 individuals, 21 developed PDS and 2,128 maintained normal glucose regulation in 2001. The remaining 1,730 subjects fit one of the two criteria for PDS. The parameters measured in 1997, including fasting plasma glucose, HbA1c, triglyceride, alanine aminotransferase, γ-glutamyltranspeptidas, cholinesterase, uric acid, red blood cells, hemoglobin, percent body fat and diastolic blood pressure, were significantly higher in the individuals who developed PDS than in those who maintained normal glucose regulation. On the other hand, hematocrit was significantly lower in PDS than in normal glucose regulation. Logistic regression analysis identified alanine aminotransferase ≥ 40 U/l, triglyceride ≥ 1.69 mmol/l, low-density lipoprotein cholesterol ≥ 3.62 mmol/l and hematocrit < 38% as valuable factors for predicting the development of PDS. The present study demonstrates that the subjects with high risks for PDS could be identified from several clinical parameters and that they should be encouraged to improve their living habits not to develop diabetes mellitus.
Arterial blood gas (ABG) analysis has an important role in the clinical assessment of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, arterial puncture or insertion of an arterial catheter has many drawbacks. The aim of this study was to evaluate whether venous blood gas (VBG) values of pH, partial pressure of carbon dioxide (PCO2) and oxygen (PO2), bicarbonate (HCO3), and oxygen saturation (SO2) can reliably predict ABG levels in patients with AECOPD. One hundred and thirty-two patients with a prior diagnosis of COPD presenting with acute exacerbation according to AECOPD criteria were included in this prospective study. AECOPD is defined as a recent increase in cough, wheezing, the volume and purulence of sputum or shortness of breath necessitating a change in regular medication, including corticosteroids or antibiotics. ABG samples were taken immediately after venous sampling, and both were analyzed. Linear regression analysis was performed and equations were established for the estimation of arterial values. The Pearson correlation coefficients for pH, PCO2, HCO3, PO2, and SO2 were 0.934, 0.908, 0.927, 0.252, and 0.296, respectively. There was a significant correlation between ABG and VBG values of pH, PCO2, and HCO3 (p < 0.001). Linear regression equations for the estimation of pH, PCO2, and HCO3 were as follows: arterial pH = 1.004 × venous pH; arterial PCO2 = 0.873 × venous PCO2; and arterial HCO3 = 0.951 × venous HCO3. VBG analysis can reliably predict the ABG values of pH, PCO2 and HCO3 in patients with AECOPD.
The extracellular calcium-sensing receptor (CaSR) located in either luminal or basolateral cell membranes of various types of renal tubules including proximal tubules, Henle's loop and collecting ducts has been thought to play a fundamental role in electrolyte metabolism. To further identify the physiological roles of the CaSR, we examined the effects of Ca2+ and calcimimetics neomycin (Neo), gentamicin and gadolinium chloride (Gd3+) on the intracellular pH (pHi) of in vitro microperfused mouse medullary thick ascending limb (mTAL) cells of Henle's loop, by loading the cells with fluorescent pH indicator 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein and measuring the ratio of fluorescence emission at 530 nm after exciting the dye at 490 and 440 nm. In a steady-state condition in Hepes-buffered solution, the pHi in the mTALs was 7.29 ± 0.04 (n = 9). A concentration of 200 μmol/l Neo in the basolateral side decreased the pHi after 1 min by −0.13 ± 0.02 (n = 34, p < 0.0001). The other calcimimetics showed similar effects on pHi, whereas none of these calcimimetics in the lumen affected pHi. Na+ removal or the inhibition of Na+ and proton transport with amiloride, bumetanide, or bafilomycin did not eliminate the effect of Neo on pHi. On the other hand, Cl− removal clearly eliminated the Neo-induced pHi decrease (−0.06 ± 0.01 vs −0.00 ± 0.05 in Cl− removal, n = 4, p < 0.003). Thus, we have demonstrated for the first time that the CaSR is involved in the regulation of the pHi in the mTAL and requires Cl− to exert its effect.
The concentration of methylmercury (MeHg) in human hair is an excellent marker for its exposure, since a portion of MeHg is taken up from the blood circulation to the hair protein in a dose-dependent manner. However, a small portion of the mercury in human hair is found in the inorganic form, though the mechanism of its occurrence is not well established. Here, we examined the hair uptake of inorganic mercury in the rat. Male Wistar rats were exposed to MeHg (1 μg Hg/ml) or HgCl2 (20 μg Hg/ml) for 84 days through drinking water. The hair, grown from 49 to 84 days, was collected from the MeHg-exposed rats, and the hair samples showed 54.5 μg/g hair of the total mercury concentration, 6.1% of which was in the inorganic form. The inorganic mercury in the plasma (0.022 μg/ml), which would probably be formed from MeHg in rat tissues, accounted for as high as 29% of the total mercury (0.076 μg/ml). The hair uptake rate of inorganic mercury estimated from the hair/plasma ratio was about 1/6 lower than that of MeHg. On the other hand, the total hair mercury level in the HgCl2-exposed group at the same time point was 2.86 μg/g, with the inorganic portion being as high as 62%. These findings suggest that the inorganic mercury is also taken up by rat hair from the blood circulation, as is the MeHg, irrespective of the consequences of the biotransformation of MeHg or exposure to inorganic mercury itself. Accordingly, a selective quantification of inorganic mercury in human hair may be useful in detecting inorganic mercury exposure.
Neuromyelitis optica (NMO) is a devastating neurologic disease characterized by severe optic neuritis and transverse myelitis. Recently, its disease-specific serum autoantibody, NMO-IgG, was discovered with indirect immunofluorescence. However, the substrates of the immunofluorescence assay were not human but mouse brain tissues, which could influence the sensitivity and specificity of the antibody. The target antigen of NMO-IgG was recently identified as aquaporin-4 (AQP4) water channel protein, which is mainly expressed in brain and spinal cord. In the present study, we have established human cell lines that stably express human AQP4 and used these cells to detect and titrate anti-AQP4 antibody present in the sera of patients with NMO by immunofluorescence assay. The results were compared with those of the original NMO-IgG assay. We tested the sera from 10 patients with NMO, 10 with MS and five with other neurological disorders. Among the patients with NMO, six were NMO-IgG-positive. However, using the new anti-AQP4 antibody assay, we showed that eight patients with NMO including the six NMO-IgG-positives were positive for anti-AQP4 antibody. The staining pattern of AQP4-expressing cells treated with each serum of these eight NMO patients corresponded to that with a commercially available anti-AQP4 antibody. The antibody titer (maximum serum dilution for positive staining) ranged from 64× to 16,384×. The serum dilution titers were reproducible in blinded studies. In contrast, the patients with MS or other neurological disorders showed negative for anti-AQP4 antibody. Thus, the newly developed anti-AQP4 antibody assay appears to have a higher sensitivity for NMO than the original NMO-IgG assay and is expected to be useful for the diagnosis of NMO.
Mucosal toxicity is an incapacitating complication of intensive chemo-radiotherapy for children with malignant disorders, and is physically and psychologically distressful. It is therefore important to minimize mucosal toxicity in those patients. In this report, the effects of the combined prophylaxis of oral cooling (cryotherapy) and administration of propantheline, an anticholinergic drug, were studied in patients (aged 2-16 year) with acute leukemias or solid tumors, who underwent myeloablative chemo-radiotherapy and autologous peripheral blood stem cell rescue from 1993 to 1997. Patients were pretreated with the combined prophylaxis (n = 12) or single prophylaxis (n = 5), or left untreated (n = 7). The combined prophylaxis significantly reduced the severe mucositis (combined, 8.3%; single, 20.0%; and untreated, 42.9%) and severe diarrhea (combined, 16.7%; single, 60.0%; and untreated, 57.1%). Moreover, the combined prophylaxis tended to shorten the periods of febrile episodes defined as temperature > 38°C (combined, 3.8 days; single, 4.6 days; and untreated, 5.6 days). Therefore, the combination of propantheline and oral cryotherapy may be feasible and effective for reduction of mucosal toxicity in patients with malignancy who undergo high-dose chemotherapy.
All over the world, the increased awareness of the importance of early diagnosis of genetic diseases has given them priority in primary health care. However, more recent surveys indicate that genetics content is still lacking in nursing curricula. This survey aimed to measure the current status of primary care nurses' knowledge about genetics and genetic counseling, and the educational needs of nurses related to human genetics in the Denizli region of Turkey. This area in western Turkey has an 11.7% rate of consanguineous marriages; about 3.5% of the population are hemoglobinopathies carrier and 3.2% are thalassemia carriers. Data were collected on forms that aimed to obtain information about nurses' approaches to genetics and genetic counseling. A total of 86 of 106 nurses working in Denizli province returned the questionnaire (response rate of 81.1%). Phenylketonuria, at 61.5%, and Cooley's anemia, at 60.0%, were identified as the subjects these nurses were most knowledgeable about in terms of genetic disorders. A high percentage of nurses admitted they had insufficient knowledge about the genetic basis of diseases (96.4%), inheritance patterns (98.9%), ethical and legal issues (100.0%), genetic counseling (100.0%), gene testing (95.9%), and genetic engineering (97.9%). About 67% of nurses stated they would like to attend a training course on these subjects. As a result of this study a genetics course is planned for nurses so they can actively participate in the prevention and early diagnosis of genetic diseases.
The incidence of late-onset circulatory dysfunction (LCD) of premature infants, which is characterized by sudden hypotension and oliguria, has recently increased in Japan. This condition suddenly occurs after several days of age without obvious causes in preterm infants with stable respiration and circulation. Intravenous steroids frequently improve the hypotension. The main problem with LCD is the subsequent and frequent onset of periventricular leukomalacia (PVL), and neurological development appears to be worse in PVL patients with LCD than those without LCD. The aim of this study was to determine whether the severity of magnetic resonance imaging (MRI) findings and neurological outcomes differ between infants who developed PVL after LCD and those who developed PVL without LCD. We retrospectively studied preterm infants who were delivered at less than 33 weeks of gestation between the years 2000 and 2003. During the study period, 10 and 26 infants developed PVL with and without LCD, respectively. The incidence of severe or moderate MRI findings was significantly higher in PVL patients with LCD (100%) than those without LCD (50%; p < 0.05). The incidence of severe cerebral palsy was 88% in PVL infants with LCD and 43% in PVL infants without LCD (p < 0.05). Moreover, the incidence of visual disorders was significantly higher in PVL infants with LCD (63%) than those without LCD (9%; p < 0.01). In conclusion, neurological outcomes are worse in preterm infants who develop PVL with LCD than those without LCD, which is well correlated to the severity judged by MRI findings.
Bone mineral density (BMD) has been known to decline in middle-aged and elderly individuals, but when this decline begins and the rate at which it occurs remain unclear. We thus undertook this study to examine the association between BMD and age by their mean values in women visiting the Shimane Institute of Health Science for medical examination. We performed dual energy x-ray absorptiometry measurement of lumbar vertebrae in 1,167 women, and of the entire skeleton in 1,038 women. The ages of subjects ranged from 30 to 70 years. We found that the mean value of whole-body and lumbar BMD changed little in the age range of 30-51 years, and any change after 58 years was a gradual decrease, unlike the sharp decrease found between 52 and 57 years of age. The effects of endocrine kinetics may be reflected in women by the decrease of bone density relative to age. In conclusion, BMD declines more rapidly in women within the age range of 52-57 years than in those 58 years and over. This regression line is considered useful in predicting BMD of whole-body skeleton and lumbar vertebrae relative to age for the prevention of osteoporosis in women.
Controls for second hand smoke (SHS) and adolescent smoking have been still sociomedical concerns in Japan. Restaurant smoking restrictions are associated with community social norms affecting adolescent smoking behavior, and the status in areas around Junior high schools (JHSs) in the community could be a sign of community practices on regulating SHS for adolescents. To examine whether restaurant smoking restrictions are seen especially in areas around JHSs in Japan, a survey using the direct inspection of a total of 163 restaurants (64 restaurants within and 99 outside a 1-km radius from the nearest JHSs) was conducted in May 2003 in Yonago city, Japan. We assessed smoking restriction status in each restaurant and classified them into 2 groups according to the distance from the nearest JHSs. There were only 2 (3.1%) restaurants with 100% non-smoking and 11 (17.2%) with some partial restrictions among the restaurants within a 1-km radius of JHSs. There were 1 (1.0%) restaurant with 100% non-smoking, 3 (3.0%) with complete non-smoking sections and 17 (17.2%) with some partial restrictions among the restaurants outside a 1-km radius of JHSs. Among restaurants with some partial restrictions, restriction methods were considered insufficient. The smoking restriction status was not significantly different between the restaurant groups within and outside a 1-km radius of JHSs. These results suggest that the public awareness of and attitude toward adolescent smoking problems remains low in Japan. Further SHS control actions for adolescents are needed in Japan.
Chronic myelogenous leukemia (CML) is a hematological malignancy that is characterized by the chromosome anomaly, t(9;22)(q34;q11). By this chromosomal translocation, a novel activated tyrosine kinase, BCR-ABL chimeric protein, is generated, and the protein is causative of the disease. Recently, Imatinib mesylate targeting to a BCR-ABL chimeric protein has been developed, and shown to achieve complete remission at a high rate. Patients are currently required to receive a fixed dose, 400 mg daily; however, it is possible that some of patients can maintain their remission with reduced doses of imatinib. In this study, we determined levels of BCR-ABL transcript in CML patients by real-time quantitative polymerase chain reaction analysis, and explored the possibility of individualization of therapeutic doses of imatinib. Thirty-five CML patients, including 17 newly diagnosed patients, 16 patients pre-treated with interferon-alpha, and 2 relapsed patients after allogeneic transplantation, were treated with imatinib. Complete cytogenetic response was achieved in 31 (89%) patients. Major molecular response (MMR) was achieved in 21 (60%). Complete molecular response (CMR) was achieved in 7 (20%). Imatinib was discontinued in 2 patients, one patient with MMR due to noncompliance and other patient sustaining CMR, but both patients relapsed 7 and 13 months later, respectively. The doses of imatinib were reduced in 7 patients due to its side effects, but 4 out of the 7 patients have sustained MMR, and 2 of them have sustained CMR for more than 23 months. These results indicate that some patients are able to maintain MMR with low-dose imatinib.
Repeated deliveries might disturb the levator function and increase defecation disorders. In this prospective study, we determined the electric activity of the levator ani muscle (LAM) in nullipara, multipara, grand multipara, and great grand multipara (20 subjects for each group). Multiparity, grand multiparity, and great grand multiparity were defined as women having 2 - 5, 6 - 9, and 10 and over deliveries, respectively. The number of deliveries of multipara, grand multipara and great grand multipara were 4.05 ± 1.14 (2 - 5), 7.55 ± 1.23 (6 - 9) and 12.2 ± 2.16 (10 - 17), respectively. All women were asked whether they had experienced constipation, fecal or urinary incontinence, and/or pelvic pain. All women were also evaluated for pelvic organ prolapse. Electromyography (EMG) of the LAM at rest and on contraction was recorded. EMG is an electrical recording of muscle activity. Constipation, incontinence and pelvic organ prolapse were encountered in multipara, grandmultipara and great grand multipara women. The LAM EMG at rest and on contraction in the nullipara was accepted as control. Both the resting and contractile activities of the LAM were as follows: nullipara > multipara > grand multipara > great grand multipara. These findings indicate that levator dysfunction and defecation disorders are increased with repeated deliveries because of pudendal and/or levator ani nerve injury and traumatic injury to the LAM occurred with the mechanical stresses of vaginal deliveries.
Given that a medical practice exists for patients, it is worth determining the degree of patient satisfaction with regard to the medical practice's quality of care. Considering the importance of noticing patient satisfaction and its influence on clinical care, intense evaluation of a questionnaire's validity and reliability is essential. The purpose of this study was to establish a valid and reliable self-administered scale to measure patient satisfaction with fewer questions than previous scales applicable in medical settings in Japan. A qualitative method was used to develop and revise content-valid question items of the questionnaire. Factor analysis revealed five subscales among 12 items: “overall satisfaction”, “complete examination”, “patient centeredness”, “examination time”, and “whole person care”. A test of internal consistency was also assessed. The concurrent validity was assessed to evaluate the association between the score of the current questionnaire and that of the visual analogue scale or other questionnaire. Agreement between two sets of score, scores just after consultation and 30-50 min after that, was assessed to evaluate the test-retest reliability of each question item. The results revealed satisfactory validity, including the content and concurrent validity, internal consistency (Cronback alpha = 0.77-0.85), and the test-retest reliability of our questionnaire (Kappa score = 0.61-0.71). In conclusion, we have developed a short-form self-administered patient satisfaction questionnaire applicable in Japan, with acceptable validity and reliability. This questionnaire may contribute to conducting further studies related to patient subjective responses to encounters in Japanese medical settings, and evaluating and improving the clinical interview skills of medical students or trainees in medical education.