Comprehensive validation of early diagnostic algorithms for myocardial infarction in the emergency department.

OBJECTIVE: To comprehensively evaluate diagnostic algorithms for myocardial infarction using a high-sensitivity cardiac troponin I (hs-cTnI) assay. PATIENTS AND METHODS: We prospectively enrolled patients with suspected myocardial infarction without ST-segment elevation from nine emergency departments in Japan. The diagnostic algorithms evaluated: (i) based on hs-cTnI alone, such as the European Society of Cardiology (ESC) 0/1-h or 0/2-h and High-STEACS pathways; or (ii) used medical history and physical findings, such as the ADAPT, EDACS, HEART, and GRACE pathways. We evaluated the negative predictive value (NPV), sensitivity as safety measures, and proportion of patients classified as low or high-risk as an efficiency measure for a primary outcome of type 1 myocardial infarction or cardiac death within 30 days. RESULTS: We included 437 patients, and the hs-cTnI was collected at 0 and 1 hours in 407 patients and at 0 and 2 hours in 394. The primary outcome occurred in 8.1% (33/407) and 6.9% (27/394) of patients, respectively. All the algorithms classified low-risk patients without missing those with the primary outcome, except for the GRACE pathway. The hs-cTnI-based algorithms classified more patients as low-risk: the ESC 0/1-h 45.7%; the ESC 0/2-h 50.5%; the High-STEACS pathway 68.5%, than those using history and physical findings (15-30%). The High-STEACS pathway ruled out more patients (20.5%) by hs-cTnI measurement at 0 hours than the ESC 0/1-h and 0/2-h algorithms (7.4%). CONCLUSIONS: The hs-cTnI algorithms, especially the High-STEACS pathway, had excellent safety performance for the early diagnosis of myocardial infarction and offered the greatest improvement in efficiency.

Factors predictive of the presence of a CSF1R mutation in patients with leukoencephalopathy.

BACKGROUND AND PURPOSE: The purpose was to identify statistically factors that correlate with the presence of a colony-stimulating factor 1 receptor (CSF1R) mutation and to reevaluate the accuracy of the current diagnostic criteria for CSF1R-related leukoencephalopathy. METHODS: CSF1R testing was conducted on 145 consecutive leukoencephalopathy cases who were clinically suspected of having adult-onset leukoencephalopathy with axonal spheroids and pigmented glia. From these, 135 cases whose detailed clinical information was available were enrolled. Forward logistic stepwise regression was performed to generate a probability model to predict a positive CSF1R mutation result. The current diagnostic criteria were also applied to our cohort and their sensitivity and specificity were calculated. RESULTS: Twenty-eight CSF1R-mutation-positive cases and 107 CSF1R-mutation-negative cases were identified. Our probability model suggested that factors raising the probability of a CSF1R-mutation-positive result were younger onset, parkinsonism, thinning of the corpus callosum and diffusion-restricted lesions. It also showed that involuntary movements and brainstem or cerebellar atrophy were negative predictors of a CSF1R-mutation-positive result. In our cohort, the sensitivity and specificity for 'probable' or 'possible' CSF1R-related leukoencephalopathy were 81% and 14%, respectively. CONCLUSIONS: Clinical and brain imaging features predictive of the presence of a CSF1R mutation are proposed. Consideration of these factors will help prioritize patients for CSF1R testing.

Modulated function of multidrug resistance-associated proteins in cisplatin-induced acute renal failure rats.

The effect of cisplatin-induced acute renal failure (ARF) on the function and expression of multidrug resistanceassociated proteins (MRPs) was evaluated in rats. Rats received an intraperitoneal injection of cisplatin (9 mg/kg), and the induction of ARF state with high plasma concentrations of indoxyl sulfate and creatinine was observed 72 h after cisplatin treatment. The function of MRPs in the liver, kidney and brain was evaluated by measuring the tissue accumulation and biliary excretion of 2,4-dintrophenyl-S-glutathione (DNP-SG), a substrate for MRPs, after administration of 1-chloro-2,4-dintrobenzene (CDNB), a precursor of DNP-SG, in rats. The levels of MRP1-4 expression were evaluated by Western blot analysis. Effect of ARF plasma components on MRP function was also examined by using calcein acetoxymethyl ester (calcein-AM) in HepG2 cells. In ARF rats (72 h after cisplatin treatment), the accumulation of DNP-SG in the liver, kidney and brain was significantly higher than those in control and cisplatin-treated rats (1 h after treatment). In ARF rats, intrinsic biliary excretion clearance of DNP-SG, estimated by dividing the biliary excretion rate of DNP-SG with the liver concentration, was also significantly reduced, though the expression levels of MRP1-4 in the liver remained unchanged. ARF rat plasma (5%) significantly increased the accumulation of calcein, a MRP substrate, in HepG2 cells after application of calcein-AM. In conclusion, MRP function was found to be suppressed not only in the kidney but also in the liver and brain in cisplatin-induced ARF rats, possibly due to the accumulation of some MRP substrates/inhibitors in plasma.

Environmental radioactivity of water samples collected in Higashi-Hiroshima campus, Hiroshima University, Japan.

The relation between concentration of elements and microbial activity in the water samples of Higashi-Hiroshima Campus, Hiroshima University was investigated. Energy dispersive X-ray spectroscopy revealed that microbial mat contains iron, aluminium, silicon and phosphorus. Model experiment revealed that the potassium was adsorbed by living microorganism in the microbial mats, while it was not adsorbed by dead microbial mat. Iron was adsorbed by both living and dead microbial mats. The present results explain the increase in the total ß-radioactivity of water sample in summer and the decrease in winter.

Molecular and clinical characterization of plasmid-mediated AmpC ß-lactamase-producing Escherichia coli bacteraemia: a comparison with extended-spectrum ß-lactamase-producing and non-resistant E. coli bacteraemia.

Plasmid-mediated AmpC ß-lactamase-producing Escherichia coli (AmpC-E) bacteraemia was characterized by comparison with bacteraemia caused by extended-spectrum ß-lactamase (ESBL)-producing E. coli (ESBL-E) and non-resistant E. coli (NR-E) in the era of the worldwide spread of the CTX-M-15-producing O25b-ST131-B2 clone. Of 706 bloodstream E. coli isolates collected between 2005 and 2010 in three Japanese university hospitals, 111 ESBL screening-positive isolates were analysed for AmpC and ESBL genes by PCR. A case-control study was performed in which the cases consisted of all of the patients with AmpC-E bacteraemia. Phylogenetic groups, sequence types and O25b serotype were determined. Twenty-seven AmpC-E isolates (26 of which were of the CMY-2 type) were identified, and 54 ESBL-E and 54 NR-E isolates were selected for the controls. Nineteen AmpC-E isolates were also positive for ESBL. CTX-M-14 was the most prevalent ESBL type among both the AmpC-E and ESBL-E isolates. The O25b-ST131-B2 clone was the most prevalent among the ESBL-E isolates (26%) and the second most prevalent among the NR-E isolates (13%), but only one O25b-ST131-B2 clone was found among the AmpC-E isolates. Twenty-three different sequence types were identified among the AmpC-E isolates. When compared with bacteraemia with ESBL-E, previous isolation of multidrug-resistant bacteria and intravascular catheterization were independently associated with a lower risk for AmpC-E. When compared with NR-E bacteraemia, prior use of antibiotics was the only significant risk factor for AmpC-E. Unlike the spread of the O25b-ST131-B2 clone between ESBL-E and NR-E, the AmpC-E isolates were not dominated by any specific clone.

Regional dissemination of Acinetobacter species harbouring metallo-ß-lactamase genes in Japan.

Metallo-ß-lactamase (MBL) producers have been reported among the various Acinetobacter species worldwide. In this study, the epidemiology and molecular characteristics of carbapenemase-encoding genes and mobile elements were studied to analyse the regional dissemination of MBL genes in Acinetobacter species. From January 2001 to December 2006, 48 Acinetobacter isolates harbouring MBL genes identified from five hospitals in Kyoto and Shiga Prefecture, Japan were collected and analysed. The partial rpoB gene or the 16S-23S ribosomal RNA intergenic spacer region was sequenced to obtain a species-level identification. Molecular typing using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) was performed. Twenty-five Acinetobacter pittii isolates were divided into eight PFGE types and five sequence types (STs) using MLST. Nine Acinetobacter bereziniae isolates belonged to five PFGE types. Five Acinetobacter nosocomialis isolates were divided into two PFGE types and two STs. Three unclassified Acinetobacter species isolates were divided into two PFGE types. Eighteen of the 25 A. pittii isolates belonged to ST119 and were identified from four hospitals. The bla(IMP-19) gene was detected in 41 of 48 isolates, including all of the A. pittii ST119 isolates. The bla(IMP-1) and bla(IMP-11) genes were detected in four and three isolates, respectively. The MBL genes were all embedded within a class 1 integron as a gene cassette array: bla(IMP-19) -aac(6')-31-bla(OXA-21) -aadA1, catB8-like/aacA4-bla(IMP-1) and bla(IMP-11). This study is the first report demonstrating the regional dissemination of MBL-producing Acinetobacter species. A. pittii ST119 harbouring blaIMP-19 was widely spread throughout the Kyoto-Shiga region.

Cefotaxime for the detection of extended-spectrum ß-lactamase or plasmid-mediated AmpC ß-lactamase and clinical characteristics of cefotaxime-non-susceptible Escherichia coli and Klebsiella pneumoniae bacteraemia.

We investigated the performance of cefotaxime for the detection of extended-spectrum ß-lactamase (ESBL) or plasmid-mediated AmpC ß-lactamase (pAmpC) and the clinical characteristics of cefotaxime-non-susceptible Escherichia coli or Klebsiella pneumoniae (CTXNS-EK) bacteraemia. All of the consecutive bloodstream isolates between 2005 and 2010 in a Japanese university hospital were characterised using polymerase chain reaction (PCR). Risk factors and outcomes of CTXNS-EK were analysed by multivariate logistic regression analysis. We identified 58 CTXNS-EK (15.6%) from 249 E. coli and 122 K. pneumoniae. Cefotaxime with a minimum inhibitory concentration (MIC) of >1 µg/mL had a sensitivity of 98.3% and a specificity of 99.7% for the detection of ESBL or pAmpC. CTXNS-EK had increased from 4.5% in 2005 to 23% in 2009. Risk factors for CTXNS-EK were previous isolation of multidrug-resistant bacteria, use of oxyimino-cephalosporins or fluoroquinolones, and high Sequential Organ Failure Assessment (SOFA) score. Patients with CTXNS-EK bacteraemia less frequently received appropriate empirical therapy than patients with cefotaxime-susceptible EK bacteraemia (81% vs. 97%, p<0.001) and died within 30 days (21% vs. 5%, p=0.001). Using the current breakpoints of the Clinical and Laboratory Standards Institute (CLSI) or the European Committee on Antimicrobial Susceptibility Testing (EUCAST), cefotaxime alone can identify ESBL or pAmpC producers. CTXNS-EK is an important and increasingly prevalent bacteraemia pathogen.

Regional spread and control of vancomycin-resistant Enterococcus faecium and Enterococcus faecalis in Kyoto, Japan.

The purpose of this investigation was to control the post-outbreak prevalence of vancomycin-resistant enterococci (VRE) in the affected Kyoto region. The study period was from 2005 to 2010. Faecal samples were subjected to VRE screening, and vancomycin resistance genes were detected by polymerase chain reaction (PCR). The genotype was determined by pulsed-field gel electrophoresis (PFGE) of genomic DNA digested with SmaI and by multilocus sequence typing (MLST). A VRE control programme was established in 2006, consisting of a laboratory-based faecal VRE screening system, annual surveillance of hospital inpatients and the promotion of adequate infection control measures. vanA-Enterococcus faecium, vanB-E. faecium and vanB-E. faecalis were detected at 35, 12 and 5 hospitals, respectively. Genotype analysis revealed that all of the vancomycin-resistant E. faecium isolates obtained since 2005 belonged to ST78, and that clonally related vanB-E. faecalis of ST64 had spread to three hospitals. The rate of faecal VRE carriage among the patients enrolled in the annual surveillance increased until 2007, when it reached 24 (1.2%) of the 2,035 enrolled patients. The rate began to decrease in 2008 and, by 2010, reached a low of 4 (0.17%) of the 2,408 enrolled patients. While VRE did spread within the Kyoto region, the VRE control programme succeeded in controlling the overall VRE spread.

Quantitative real-time PCR and the (1→3)-ß-D-glucan assay for differentiation between Pneumocystis jirovecii pneumonia and colonization.

We evaluated whether quantitative PCR (qPCR) and (1 → 3)-ß-d-glucan assays could be used to differentiate Pneumocystis pneumonia (PCP) from Pneumocystis jirovecii colonization in immunocompromised patients with pulmonary infiltrates. A total of 40 bronchoalveolar lavage samples and 107 induced sputum samples from 147 patients who were suspected of having PCP were obtained for PCR detection of P. jirovecii. Diagnoses of definite PCP, probable PCP, pneumonia with P. jirovecii colonization (colonization) and pneumonia without colonization (non-colonization) were made in 11, 42, 15 and 60 patients, respectively. A PCP diagnosis was undetermined in 19 patients. The copy numbers, determined using qPCR, were significantly higher in definite PCP and probable PCP patients than in colonized patients. The area under the receiver-operating characteristic curve (AUC), sensitivity and specificity for discriminating definite PCP from colonization were 0.96, 100.0% and 80.0%, respectively, at a cut-off value of 1300 copies/mL. The values for discriminating probable PCP from colonization were 0.71, 66.7% and 73.3%, respectively, at a cut-off value of 340 copies/mL. ß-d-glucan levels were significantly higher in patients with both definite PCP and probable PCP than in colonized patients. The AUC, sensitivity and specificity for discriminating definite PCP were 0.91, 100.0% and 80.0%, respectively, at a cut-off value of 15.6 pg/mL. The values for discriminating probable PCP were 0.78, 76.2% and 73.3%, respectively, at a cut-off value of 6.0 pg/mL. Both qPCR and the ß-d-glucan assay displayed high accuracy for discriminating colonization from definite PCP and displayed moderate accuracy for discriminating colonization from probable PCP.

Control of an outbreak of carbapenem-resistant Pseudomonas aeruginosa in a haemato-oncology unit.

An outbreak of a multidrug-resistant Pseudomonas aeruginosa producing metallo-ß-lactamase (MBLPA) in a haemato-oncology unit was controlled using multidisciplinary interventions. The present study assesses the effects of these interventions by active surveillance of the incidence of MBLPA infection at the 1,240-bed tertiary care Kyoto University Hospital in Kyoto, Japan. Infection control strategies in 2004 included strengthening contact precautions, analysis of risk factors for MBLPA infection and cessation of urine collection. However, new MBLPA infections were identified in 2006, which prompted enhanced environmental cleaning, routine active surveillance, and restricting carbapenem usage. Between 2004 and 2010, 17 patients in the unit became infected with indistinguishable MBLPA strains. The final five infected patients were found by routine active surveillance, but horizontal transmission was undetectable. The MBLPA outbreak in the haemato-oncology unit was finally contained in 2008.

Pre-emptive contact precautions for intubated patients reduced healthcare-associated meticillin-resistant Staphylococcus aureus transmission and infection in an intensive care unit.

Healthcare-associated infection by meticillin-resistant Staphylococcus aureus (MRSA) is still a great concern in an intensive care unit (ICU). Our surveillance data in the ICU revealed that intubated patients were at eight times higher risk of acquiring MRSA than non-intubated patients, so we hypothesised that pre-emptive contact precautions for all intubated patients would prevent healthcare-associated infection by MRSA in the ICU. Patients staying in our ICU for >2 days were included in this study. The study period was divided into two periods. During 2004 (1st period), contact precautions were performed only for patients with MRSA. During 2005-2007 (2nd period), contact precautions were applied to all intubated patients regardless of MRSA infection status. Patients were defined as MRSA-positive on admission when MRSA was detected by surveillance or clinical culture on enrolment. Other MRSA-positive results were defined as healthcare-associated MRSA (HA-MRSA) transmission. HA-MRSA infection was diagnosed according to the National Nosocomial Infections Surveillance Manual. The 1st period comprised 415 patients, and the 2nd period comprised 1280 patients. In intubated patients, HA-MRSA infection rate decreased significantly in the 2nd period (1st period 12.2%, 2nd period 5.6%; P=0.015). HA-MRSA infection of all patients decreased from 3.6 to 2.3 incidents per 1000 patient-days (P<0.05), despite a significant increase in the rate of patients MRSA positive on admission in the 2nd period (1st period 2.9%; 2nd period 6.1%). Pre-emptive contact precautions for intubated patients would be helpful in reducing HA-MRSA infection in ICU.

Gastrointestinal dysmotility is associated with altered gut flora and septic mortality in patients with severe systemic inflammatory response syndrome: a preliminary study.

BACKGROUND: The gut is an important target organ for injury after severe insult, and resolution of feeding intolerance is crucial for critically ill patients. We investigated gut flora and motility to evaluate the impact of gastrointestinal dysmotility on septic complications in patients with severe systemic inflammatory response syndrome (SIRS). METHODS: Sixty-three ICU patients with severe SIRS were divided into two groups depending on their intestinal condition. Patients with feeding intolerance comprised patients who had feeding intolerance, defined as ≥ 300 mL reflux from nasal gastric feeding tube in 24 h, and patients without feeding intolerance comprised patients with no feeding intolerance. We compared fecal microflora, incidences of bacteremia, and mortality between these groups. KEY RESULTS: Analysis of feces showed that patients with feeding intolerance had significantly lower numbers of total obligate anaerobes including Bacteroidaceae and Bifidobacterium, higher numbers of Staphylococcus, lower concentrations of acetic acid and propionic acid, and higher concentrations of succinic acid and lactic acid than those in patients without feeding intolerance (P ≤ 0.05). Patients with feeding intolerance had higher incidences of bacteremia (86%vs 18%) and mortality (64%vs 20%) than did patients without feeding intolerance (P ≤ 0.05). CONCLUSIONS & INFERENCES: Gut flora and organic acids were significantly altered in patients with severe SIRS complicated by gastrointestinal dysmotility, which was associated with higher septic mortality in SIRS patients.

Regional spread of vanA- or vanB-positive Enterococcus gallinarum in hospitals and long-term care facilities in Kyoto prefecture, Japan.

Following an outbreak of vanA-positive Enterococcus faecium in 2005 in Kyoto prefecture, regional surveillance of vancomycin-resistant enterococci (VRE) was initiated. This revealed vanA- or vanB-positive Enterococcus gallinarum in multiple facilities. Eighty-eight vanA-positive E. gallinarum faecal carriers from 12 facilities and ten vanB-positive E. gallinarum faecal carriers from eight facilities were found. Pulsed-field gel electrophoresis profiles of the first isolate from each facility showed that 11 of the 12 vanA isolates and three of the eight vanB-positive E. gallinarum isolates belonged to a single clone. This study confirms the clonal spread of vanA- or vanB-positive E. gallinarum in a region and underlines the importance of surveillance of VRE for the presence of vancomycin resistance determinants.

Close cooperation between infectious disease physicians and attending physicians can result in better management and outcome for patients with Staphylococcus aureus bacteraemia.

Staphylococcus aureus bacteraemia (SAB) is a serious infection that demands prompt clinical attention for good outcome. To assess the impact of intervention by infectious diseases physicians (IDPs) in cases with SAB, a retrospective cohort study of patients with SAB was performed in a 1240-bed, university hospital in Japan, with the aim of comparing the management and outcome of patients during the initial and the latter half of the intervention period,. Three hundred and forty-six patients with SAB during the 7-year period, from 2002 to 2008, were included, and 194 patients in the initial half of the period (from 2002 to 2005) were compared with 152 patients in the later period (from 2006 to 2008). There was no significant difference between the two groups with respect to patient's clinical background, although more patients in the later period were receiving immunosuppressive treatment. The proportion of methicillin resistant S. aureus was lower during the later period (56.2% vs. 43.3%; p 0.02). Echocardiography was used more frequently (37.1% vs. 64.5%; p < 0.001). Infective endocarditis and metastatic infections were diagnosed more frequently (10.8% vs. 20.4%; p 0.01). Follow-up blood cultures were obtained more regularly (52.1% vs. 73.7%; p <0.001) and therapy was more frequently administered for at least 14 days (47.4% vs. 82.2%; p <0.001). The 30-day mortality improved during the intervention period (25.8% vs. 16.4%; p 0.04). The total number of blood cultures received by the laboratory increased annually and the total number of consultations increased by approximately 1.6-fold compared to 2002. Proactive intervention by IDPs raised awareness of optimal management of bacteraemia and improved the adherence to the standards of care, which subsequently resulted in an improvement in the outcome.

High prevalence of mutators among Enterobacter cloacae nosocomial isolates and their association with antimicrobial resistance and repetitive detection.

We determined the mutation frequencies of 59 nosocomial isolates of Enterobacter cloacae, and investigated their association with antimicrobial susceptibility, genotype, and history of exposure to antimicrobials. The frequencies of mutations leading to rifampicin resistance ranged from 5.8 × 10(-9) to 8.0 × 10(-6) (median, 5.0 × 10(-8)). Seven of the 59 (12%) isolates were graded as strong mutators exhibiting a more than 50-fold increase in the mutation frequency relative to that of E. cloacae ATCC 13047, and 30 (52%) were graded as weak mutators exhibiting a more than five-fold and not more than 50-fold increase in the mutation frequency. The isolates with higher grade of mutation frequency were resistant to significantly more antimicrobials (medians of two, one and zero agents for strong mutators, weak mutators and non-mutators, respectively; p 0.0078). The 59 isolates were classified into 36 genotypes, and all of the seven strong mutators had distinct genotypes. Mutation frequencies varied more than 10(2)-fold within a clone. In patient-based, univariate analysis, intensive-care unit admission, dense antimicrobial exposure (glycopeptide or multiple classes) and repetitive detection of this species were significantly more common among all of the four patients from whom strong mutators were obtained. Strong mutators are highly prevalent in surgical isolates of E. cloacae. Higher mutation frequency was associated with antimicrobial resistance and repetitive detection, and may contribute to the adaptability of this species.

Autosomal recessive ataxia with peripheral neuropathy and elevated AFP: novel mutations in SETX.

Mutations in the Senataxin gene (SETX) are associated with autosomal recessive ataxia-ocular apraxia 2 (AOA2) and autosomal dominant juvenile ALS (ALS4). Here, the authors describe novel homozygous missense mutations in SETX, M274I, and R1294C, found in two siblings with ataxia, peripheral neuropathy, and increased serum alpha-fetoprotein level and three other siblings with heterozygous missense mutations who were neurologically asymptomatic. The results demonstrate that the double missense mutations are responsible for AOA2 but not for ALS4.

Phenylalanine ammonia-lyase modified with polyethylene glycol: potential therapeutic agent for phenylketonuria.

Phenylketonuria (PKU) is an autosomal recessive genetic disease caused by the defects in the phenylalanine hydroxylase (PAH) gene. Individuals homozygous for defective PAH alleles show elevated levels of systemic phenylalanine and should be under strict dietary control to reduce the risk of neuronal damage associated with high levels of plasma phenylalanine. Researchers predict that plant phenylalanine ammonia-lyase (PAL), which converts phenylalanine to nontoxic t-cinnamic acid, will be an effective therapeutic enzyme for the treatment of PKU. The problems of this potential enzyme therapy have been the low stability in the circulation and the antigenicity of the plant enzyme. Recombinant PAL originated from parsley (Petroselinum crispum) chemically conjugated with activated PEG2 [2,4-bis(O-methoxypolyethyleneglycol)-6-chloro-s-triazine] showed greatly enhanced stability in the circulation and was effective in reducing the plasma concentration of phenylalanine in the circulation of mice. PEG-PAL conjugate will be an effective therapeutic enzyme for the treatment of PKU.

Homozygosity and linkage disequilibrium mapping of autosomal recessive distal myopathy (Nonaka distal myopathy).

Autosomal recessive distal myopathy or Nonaka distal myopathy (NM) is characterized by its unique distribution of muscular weakness and wasting. The patients present with spared quadriceps muscles even in a late stage of the disease. The hamstring and tibialis anterior muscles are affected severely in early adulthood. We have localized the NM gene to the region between markers D9S319 and D9S276 on chromosome 9 by linkage analysis. To further refine the localization of the NM gene, we conducted homozygosity and linkage disequilibrium analysis for 14 patients from 11 NM families using 18 polymorphic markers. All of the patients from consanguineous NM families were found to be homozygous for six markers located within the region between markers D9S2178 and D9S1859. We also provided evidence for significant allelic associations between the NM region and five marker loci. Examination of the haplotype analysis identified a predominant ancestral haplotype comprising the associated alleles 199-160-154-109 (marker order: D9S2179-D9S2180-D9S2181-D9S1804), present in 60% of NM chromosomes and in 0% of parent chromosomes. On the basis of the data obtained in this study, the majority of NM chromosomes were derived from a single ancestral founder, and the NM gene is probably located within the 1.5-Mb region between markers D9S2178 and D9S1791.

[Significance of retardation of abnormal uptake of iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid myocardial scintigraphy in patients with vasospastic angina].

OBJECTIVES: This study investigated retardation of abnormal uptake of iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid(BMIPP) scintigraphy in patients with vasospastic angina. METHODS: Twenty-three patients with vasospastic angina showed abnormal uptake of BMIPP before medical treatment and had coronary vasospasm induced by acetylcholine. The patients were divided into two groups according to uptake of BMIPP after medical treatment: retardation of abnormal uptake of BMIPP(Group R, n = 4) and normal uptake of BMIPP(Group N, n = 19). Frequency of chest pain, medical treatment and autonomic nervous activity were compared between the two groups. Furthermore, the frequency of chest pain and uptake of BMIPP in group R were obtained after intensive medical treatment. Autonomic nervous activity was evaluated by heart rate variability on Holter electrocardiography. Heart rate variability contained high-frequency elements(HF; 0.15-0.4 Hz) and low-frequency elements(LF; 0.04-0.15 Hz). LF/HF was estimated for sympathetic nervous activity and HF was estimated for parasympathetic nervous activity. Daytime and nighttime autonomic nervous activity were compared between the two groups. RESULTS: The frequency of chest pain was higher in Group R than in Group N(p < 0.05). Medical treatment was not different between the two groups. Circadian variation of sympathetic and parasympathetic nervous activity were absent in Group R. During the nighttime, Group R showed higher sympathetic nervous activity(p < 0.05) and lower parasympathetic nervous activity(p < 0.01) than Group N. The frequency of chest pain was significantly lower after intensive medical treatment(p < 0.05), and uptake of BMIPP returned to normal in Group R. We suspected that the disorder in autonomic nervous activity was more severe in Group R, and thus induced coronary vasospasm. CONCLUSIONS: Retardation of abnormal uptake of BMIPP in patients with vasospastic angina indicates poor control of coronary vasospasm. Uptake of BMIPP is useful in the evaluation of coronary vasospasm control in such patients.