Possible involvement of reusable towels in the high rate of Bacillus species-positive blood cultures in Japanese hospitals.

BACKGROUND: A number of outbreaks caused by Bacillus species have been reported to date. Outbreaks reported in the last decade have predominantly arisen in Japanese hospitals. AIM: To elucidate factors contributing to these real or pseudo outbreaks by Bacillus species, and to evaluate the rate of Bacillus species-positive blood culture samples in Japan. METHODS: A systematic review of the literature was performed. Reports including data on outbreaks caused by Bacillus species were searched for in PubMed, Google Scholar and Evidence-based Medicine BMJ from inception through 10 Aug 2014. Japanese nationwide data on bacteriological tests were collected from Japan Nosocomial Infections Surveillance. Regional bacteriological data for Akita prefecture were collected using the Akita Regional Network for Infection Monitoring/Control System. FINDINGS: Contamination of reusable towels was suspected as a cause for the high rate of Bacillus-positive blood cultures in Japan. The rate of Bacillus species in blood cultures was much higher in Japan than in reports from other countries. CONCLUSIONS: The high contamination rate of blood culture samples by Bacillus species in Japan is a matter of concern for infection control and medical treatment. Bacteriological investigation of reusable towels should be considered in hospitals with a high frequency of Bacillus-positive blood cultures.

[Role of university hospitals in regional infection control network].

Activities and the understanding of infection control in healthcare facilities have improved in the past decade since a certification system for medical personnel, such as infection control nurse and infection control doctor, were introduced in Japan. These specialists are distributed among tertiary general hospitals, while many small and mid-scale hospitals have no infection control specialists. In 2012, the Japanese Ministry of Health, Labour and Welfare launched a new strategy for further improvement of infection control by supporting a regional network of infection control activities. Through the infection control network, small or mid-scaled hospitals can utilize infection control specialists in tertiary general hospitals, enter educational programs on infection control and consult in cases of nosocomial infection outbreaks. As part of the regional infection control network, we established an information network system, named ReNICS, to share the bacteriological test results of the hospitals in Akita prefecture. ReNICS offers epidemiological data on bacteria identified in the region. We can identify the spread of multi-drug resistant bacteria and can roughly estimate the quality of infection control activities in each facility. As a similar information network is being prepared in Hirosaki University Hospital Infection Control Center in Aomori, a prefecture neighboring Akita, we discussed the roles of university hospitals for a regional infection control network.

[Problems in career planning for novice medical technologists in Japanese national hospitals].

Skills and knowledge regarding many different types of test are required for medical technologists (MTs) to provide accurate information to help doctors and other medical specialists. In order to become an efficient MT, specialized training programs are required. Certification in specialized areas of clinical laboratory sciences or a doctoral degree in medical sciences may help MTs to realize career advancement, a higher earning potential, and expand the options in their career. However, most young MTs in national university hospitals are employed as part-time workers on a three-year contract, which is too short to obtain certifications or a doctoral degree. We have to leave the hospital without expanding our future. We need to take control of our own development in order to enhance our employability within the period. As teaching and training hospitals, national university hospitals in Japan are facing a difficult dilemma in nurturing MTs. I hope, as a novice medical technologist, that at least university hospitals in Japan create an appropriate workplace environment for novice MTs.

[Current realities and problems in the clinical laboratory as a medical care support department at the Hirosaki University Hospital].

Public awareness, the social situation, and the needs of hospital administrators and others arbitrarily affect the significance and role of clinical laboratories at a given time. To manage clinical laboratories in a way that best uses the knowledge, skills, and judgment of the group that specializes in laboratory tests, a future perspective and essential philosophy to make use of their special characteristics seems essential. That philosophy is to contribute to high quality medical care through laboratory test performance, extend the healthy lifespan of people in the community and the nation, support re-integration of patients into society, and contribute to the well-being of society. To realize this philosophy it is essential to demonstrate the importance of the existence of clinical laboratory technicians and physicians. Without this, it may be impossible to discuss what clinical laboratories should be and adopt a future perspective for them. We herein discuss the ideal and current realities of the clinical laboratory as a medical care support department in the Hirosaki University School of Medicine Hospital, and we report issues and problems related to overcoming the gap between the two realities.

[Mutational analysis of a thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene in a Japanese population--the Iwaki Health Promotion Project].

Mutations in the thiazide-sensitive Na-Cl cotransporter (SLC12A3) are considered to cause Gitelman's syndrome (GS), an autosomal recessive inherited renal tubular disorder. In the present study, to assess the prevalence of 3 SLC12A3 missense mutations(T180K, L849H, and R919C), involving community-based subjects with hypokalemia, mutation analysis was performed in 1567 subjects in Aomori Prefecture, a northern part of Japan. All subjects were participants in the Iwaki Health Promotion Project. Genotypes of the SLC12A3 mutations were determined by the TaqMan PCR method. Among these 1567 subjects, we detected missense mutations of T180K, L849H, and R919C in 40, 49, and 57 subjects, respectively. One subject had a homozygous (L849H) and heterozygous (R919C) mutation. Two subjects had homozygous mutations (R919C). Five subjects had compound heterozygous mutations: 2 subjects with T180K and R919C, one subject with T180K and R919C, and 2 subjects with L849H and R919C. One hundred and thirty-two subjects had a heterozygous mutation, and 1427 subjects had no mutations. The overall frequency of GS mutations was 8.9%. The mutant allele frequency of T180K, L849H, and R919C was 1.3, 1.6, and 1.9%, respectively. The GS mutant allele frequency of the 1,567 Japanese was more than 4.8%. The present study revealed that the allele frequency of these GS mutations was 4.8% in a Japanese population. In addition, these findings suggest that the allele frequency of GS mutations may be higher than expected, although GS is considered to be a rare disorder.

A case of multiple endocrine neoplasia type II accompanied by thyroid medullary carcinoma and pheochromocytomas expressing corticotropin-releasing factor and urocortins.

A 38-year-old woman with RET gene mutation presented with tumors in her thyroid and bilateral adrenal glands. I-metaiodobenzylguanidine scintigraphy revealed accumulation of the radioisotope in both adrenal glands. Both plasma adrenaline and noradrenaline levels were elevated. The circadian rhythms for plasma adrenocorticotropic hormone (ACTH) and cortisol levels were disturbed. Plasma ACTH and cortisol levels failed to be suppressed by an overnight dexamethasone test, suggesting autonomic secretion of ACTH and cortisol, although the patient had no typical Cushingoid features, hypertension, or impaired glucose tolerance. Pathological examination showed that these tumors were pheochromocytoma and thyroid medullary carcinoma, respectively, both of which highly expressed corticotropin-releasing factor, urocortin1, and urocortin3. Together with the endocrinological and pathological observations, the patient was diagnosed as multiple endocrine neoplasia type II with corticotropin-releasing factor- and urocortin-producing tumors that stimulated ACTH and glucocorticoid secretion.

Lack of association between Y chromosome Alu insertion polymorphism and hypertension.

There is an inherited paternal predisposition to hypertension. Y chromosome alphoid satellite variation was recently reported to be linked to diastolic blood pressure. To determine whether there is also a Y chromosome marker linked to hypertension, we investigated the prevalence of the Y chromosome Alu insertion polymorphism (YAP) at DYS287 and its association with hypertension in the Aomori population in the northern area of Honshu Island, Japan. YAP was present in 98 of 285 male residents and absent in the rest. The YAP prevalence in the present study would appear to suggest that the present study population represents the general male population in central Japan. Within the study population, there were 110 hypertensive subjects and 104 normotensive subjects. YAP frequency in the hypertensive subjects was not different from that in the normotensive subjects. These results suggest that the YAP is not likely to be a genetic-susceptibility factor for hypertension in the Aomori population.

Depressive state and paresthesia dramatically improved by intravenous MgSO4 in Gitelman's syndrome.

A 69-year-old woman was referred to our department for evaluation of hypokalemia, which had been treated by oral potassium for more than ten years. She complained of headache, knee joint pain, sleeplessness and paresthesia in extremities and, most prominently, depression. Laboratory data suggested Gitelman's syndrome, which is caused by mutations in the gene encoding the thiazide-sensitive Na-Cl cotransporter. Direct sequencing of the gene in this patient revealed homozygous mutation R964Q in exon 25. Intravenous supplement of MgSO4 dramatically improved both the depression and the paresthesia, suggesting that hypomagnesemia played a role in the clinical manifestations.

[Development of flow cytometric method to detect antisense oligonucleotides delivery into human platelets: the significance in thrombocytopenia].

Antisense oligonucleotides act to hybridize with RNA in a sequence-related manner and to modulate the selective translation in living cells. Antisense oligonucleotides are expected to be potential therapeutic agents toward desired molecular targets. However, little efforts have been made to realize the use of antisense oligonucleotides as powerful laboratory markers for detecting selective transcriptional levels. We describe here that FITC-labeled antisense for 18S ribosomal RNA were delivered into human platelets which were countable with flow cytometry. In healthy volunteers, the FITC positive platelets were 2% of PECD42b positive platelets. The rate was not affected by reaction time of 20 to 360 min and by reaction temperature at 4, 37 degrees C, or room temperature. The FITC positive rate was unchanged in final concentrations of both 10(-6) and 10(-5) M of FITC-labeled antisense. However, the rate was three times higher in patients with thrombocytopenia. There was a significant negative relationship between platelet count and FITC positive rate. FITC-labeled antisense for c-Mpl mRNA were more sensitive than that for 18S ribosomal RNA. These results suggest that fluorescence-labeled antisense oligonucleotides might be potential laboratory tool to reveal the distribution of RNA containing cells in the population.

[Implication of single nucleotide polymorphisms in association study: mitochondrial variations as another genetic markers for hypertension].

Although multiple nuclear gene polymorphisms have been identified as potential risk factors for hypertension, the linkage between extranuclear DNA variations and hypertension has been uncertain. We investigated whether mitochondrial DNA(mtDNA) polymorphisms are implicated in Japanese hypertension. We used direct sequencing methods to search for single nucleotide polymorphisms(SNPs) in a hypervariable segment of the mitochondrial control region in each blood sample from 20 hypertensives and 20 normotensives. Then, we determined the distribution of two SNPs, T16223C and C16362T, in 183 hypertensives and 193 healthy subjects in the Aomori population in the northern area of Honshu island of Japan. The relationship between the gene polymorphism and hypertension was evaluated using chi-square test. Seventy SNPs were found there and the number of SNPs in each individual was significantly greater(p = 0.0111) in hypertensives than in normotensives. The C16223 genotype was more frequent in hypertensives than in normotensives(p = 0.0018). There was no significant difference in C16362T variant frequency between the groups. From these results, we conclude that mtDNA SNPs were enriched in Japanese hypertension and that the mtDNA C16223 genotype may be one of the genetic susceptibility factors for hypertension.

Eplerenone improved hypokalemia in a patient with Gitelman's syndrome.

A 47-year-old woman presented with hypokalemia (2.4 mmol/L). She also had hypomagnesemia, hypocalciuria, and hyperreninemic hyperaldosteronism. Sequence analysis revealed a compound heterozygous mutation, R655C and R955Q, in the SLC12A3 gene. These findings were compatible with Gitelman's syndrome (GS). Eplerenone, a selective aldosterone blocker, in combination with oral potassium chloride improved serum potassium level (3.6 mmol/L) with no apparent adverse effect. Although eplerenone has an advantage over spironolactone for its selective affinity for the aldosterone receptor, the efficacy and safety of eplerenone for GS is little understood. Our observation suggests that eplerenone is a useful treatment option for GS.

Study of V1a vasopressin receptor gene single nucleotide polymorphisms in platelet vasopressin responsiveness.

There is a significant heterogeneity among individuals in terms of platelet aggregation response to arginine vasopressin (AVP). The aim of this study was to evaluate whether four single nucleotide polymorphisms (SNPs) in the promoter region of vasopressin V1a receptor gene (V1aR) could be used as genetic markers for divergent platelet aggregation response to AVP. Seventeen of 33 subjects showed more than 60% of maximum platelet aggregation and were classified as responders. Sixteen were classified as nonresponders because they had less than 30% aggregation. In a preliminary study, V1aR gene sequences were determined in two responders and two nonresponders. We found four SNPs in the promoter region of the V1aR gene: -6951G/A, -4112A/T, -3860T/C, and -242C/T. In all 33 subjects the genotypes of four SNPs were determined using either polymerase chain reaction (PCR) with allele-specific primers or PCR followed by restriction-fragment length polymorphism (RFLP). There were no differences in the AVP-induced aggregation between the subjects with and without variant alleles of each four SNPs. The genotype frequencies of four SNPs of V1aR were almost identical between AVP responders and nonresponders. These results suggest that the four SNPs in the promoter region of the V1aR gene may not be useful as genetic markers for platelet aggregation heterogeneity.