Appropriate Needle Length Determined by Ultrasonic Echography for Intramuscular Injection in Japanese Elderly over 50 Years.

Adjuvanted vaccines are administered through intramuscular injection. To perform appropriate injection using an appropriate needle in different age groups or different daily living activities, we investigated the depth from the skin surface to muscle fascia and bone in the deltoid muscle area in 156 elderly aged ≥ 50 years by ultrasonic echography. Subjects consisted of 50 healthy elderly aged 50−64 years, 50 subjects aged 65−74 years, and 56 subjects aged ≥ 75 years (20 outpatients, 18 who needed nursing care, and 18 bedridden in a nursing home). The mean depth ± 1.0 SD from the skin surface to muscle fascia was 7.52 ± 2.13 mm for subjects aged ≥ 75 years, being shorter than 9.16 ± 3.02 mm in those aged 50−64years (p < 0.01). The depth from the skin surface to bone was 22.54 ± 3.85 mm for subjects aged ≥ 75 years and 25.41 ± 4.24 mm for those aged 65−74 years, significantly shorter than those aged 50−64 years (p < 0.01), depending on the reduced muscle volume. The subcutaneous volume length was greater in females (8.29 ± 2.63 mm) than in males (5.62 ± 2.80 mm) aged 50−64 years (p < 0.01). A similar result was obtained in those aged 65−74 years, but there was no difference in the muscle volume length. Our study found that a five-eighths of an inch (16 mm) needle was an appropriate length for average-sized elderly aged ≥ 50 years, but it should be longer for those with large body sizes.

Impact of Long-Term Low Dose Antibiotic Prophylaxis on Gut Microbiota in Children.

PURPOSE: We evaluated the effect of long-term low dose antibiotic prophylaxis on children's gut microbiota. MATERIALS AND METHODS: We conducted 16S ribosomal RNA gene sequencing using stool samples from 35 patients younger than 3 years old (median age 5.2 months; male-to-female ratio 17:18) who underwent antibiotic treatment during the acute phase of febrile urinary tract infection. Samples were collected at 5 time points, ie before, during and at 1 to 2, 3 to 4, and 5 to 6 months after febrile urinary tract infection onset and antibiotic treatment. Continuous antibiotic prophylaxis using trimethoprim-sulfamethoxazole was initiated in 23 patients with grade III or higher vesicoureteral reflux and was not administered in 12 patients without reflux. RESULTS: Within 2 weeks after initiation of treatment for febrile urinary tract infection almost all enteric bacteria belonged to the order Lactobacillales, and gut microbiota diversity decreased compared to the pretreatment level (average Shannon index 2.9 before treatment, 1.4 during treatment). The diversity recovered within 1 to 2 months after febrile urinary tract infection onset in both groups. Diversity was maintained during the study period in both groups (p=0.43). A smaller proportion of gut microbiota component belonged to the order Enterobacteriales (p=0.002) in the antibiotic prophylaxis group. CONCLUSIONS: Our results revealed that patients receiving continuous antibiotic prophylaxis had normal gut microbiota diversity, indicating that the effect of trimethoprim-sulfamethoxazole on gut microbiota was insignificant. Furthermore, prophylaxis with trimethoprim-sulfamethoxazole might selectively suppress the growth of bacteria belonging to the order Enterobacteriales, such as Escherichia coli and Klebsiella species, which are the main causative bacteria of febrile urinary tract infections.

Optimal bacterial colony counts for the diagnosis of upper urinary tract infections in infants.

BACKGROUND: There are no consensus criteria for diagnosing upper urinary tract infections (UTI). Therefore, we conducted a study to assess whether bacterial colony counts of ≥ 103 CFU/ml are optimal for diagnosing upper UTIs among infants. METHODS: This retrospective observational study included 673 patients (<4 months of age) with urine samples obtained by catheterization for bacterial cultures. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were obtained when cutoff values of 103, 104, and 105 CFU/ml were used for diagnosing upper UTIs. Upper UTI patients were divided based on cutoff values: Group A (103 CFU/ml), Group B (104 CFU/ml), and Group C (≥ 105 CFU/ml). RESULTS: Of the 197 positive (≥ 103 CFU/ml) patients, 92 were diagnosed with an upper UTI. These patients were divided into Group A (n = 23), Group B (n = 16), and Group C (n = 53). No significant differences were detected in terms of clinical findings, including the incidence of vesicoureteral reflex. When cutoff values of 103, 104, and 105 CFU/ml were used for diagnosing upper UTIs, the sensitivity/specificity percentages were 100/81.3, 75.0/95.9, and 57.6/97.5, and the PPVs/NPVs were 46.7/100, 75.0/95.9, and 79.1/93.4. CONCLUSION: Using ≥ 105 CFU/ml as a diagnostic threshold leads to approximately 40% of positive cases being missed. In contrast when ≥ 103 CFU/ml is used, all upper UTIs were identified. Therefore, bacterial colony counts of ≥ 103 CFU/ml should be considered the cutoff value for the diagnosis of upper UTIs in infants (< 4 months of age).

Japanese Male Siblings with 2-Methyl-3-Hydroxybutyryl-CoA Dehydrogenase Deficiency (HSD10 Disease) Without Neurological Regression.

2-Methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency (HSD10 disease) is a rare X-linked disorder caused by a mutation in the HSD17B10 gene. Fewer than 30 patients with this disorder have been reported worldwide. The classical infantile form of HSD10 disease is characterized by a progressive neurodegenerative course with retinopathy and cardiomyopathy, although HSD10 disease has broad clinical heterogeneity. However, several male patients have not shown neurological regression. Here, we describe two Japanese siblings with HSD10 disease without neurological regression. A 4-year-old boy presented with unconsciousness due to severe hypoglycemia. Laboratory testing on admission showed mild metabolic acidosis and mild hyperammonemia. Urinary organic acid analysis in the acute phase showed elevated excretion of 2-methyl-3-hydroxybutyric acid, tiglylglycine, and ketones. However, 2-methylacetoacetate was not elevated. HSD10 disease was suspected based on urinary organic acid data. The patient had a novel hemizygous c.470C>T (p.A157V) mutation in the HSD17B10 gene. His mother was a heterozygous carrier of this mutation. The patient's older brother also had the c.470C>T (p.A157V) mutation. Neurological development was normal at the time of evaluation. The pilot newborn screening results using tandem mass spectrometry of the proband were reevaluated retrospectively and showed a high C5:1 carnitine level of 0.070 nmol/mL (upper cutoff limit, 0.05 nmol/mL) and a normal C5-OH carnitine level of 0.290 nmol/mL (upper cutoff limit, 1.0 nmol/mL). His affected brother and another patient with the atypical form of HSD10 disease having p.A154T also showed elevated C5:1 but not C5-OH in serum acylcarnitine analysis. Thus, these data suggested that some patients with this disorder may be identified using newborn screening.

Voiding cystourethrography is mandatory in infants with febrile urinary tract infection.

Vesicoureteral reflux (VUR) is common condition in infants with febrile urinary tract infections (UTIs). Both VUR and febrile UTIs are risk factors for renal scars, characterized by glomerular hypertrophy with global or segmental sclerosis as cardinal features in pathology. Because renal scars may cause hypertension or chronic kidney diseases in later life, voiding cystourethrography (VCUG) has been mandatory for infants following their first febrile UTIs to identify VUR. However, increasing evidence suggests that the presence of VUR may not represent a direct risk factor for renal scars, which has led to an increase in the use of a stratified approach, in which VCUG is not performed for all patients. This study was conducted to verify whether the stratified approach is justified to identify infants at risk for renal scarring. The medical records of 306 infants with first febrile UTIs (median age, 4 months; 0-72 months) were reviewed. VUR was detected in 40.4% (67/166) of patients by the non-stratified approach, in which VCUG was performed in all patients. In contrast, VUR was identified in only 27.1% (38/140) of patients by the stratified approach, in which VCUG was performed only in the patients with high risk of developing renal scars. This difference in the discovery rate was significant (p = 0.02). Renal bladder ultrasonography had the sensitivities of as low as 45.7% and 52.9% in detecting VUR and in predicting renal scarring assessed by renal scintigraphy, respectively. In conclusion, VCUG should be performed in all infants after their first febrile UTIs.

Significance of twinkling artifact on ultrasound in the diagnosis of cystine urolithiasis.

Twinkling artifact (TA) refers to the finding characterized by both a high-echoic mass upon B-mode ultrasound (US) and turbulence-like signals over the entire mass without significant blood flow on color Doppler US. TA is a characteristic sign of urolithiasis, and there has been no previous report on this finding in the digestive tract. The authors recently encountered a 2-year 9-month-old boy with cystinuria presenting with an opacified abdominal mass. Although he was originally diagnosed as having calcified stool mass, the finding of TA upon US led to the correct diagnosis of huge urolith (4.2 cm in diameter) in the urinary bladder. Laparotomic stone removal was successfully conducted and the calculus was confirmed to be composed of cystine. The finding of TA upon US facilitates identification of the structure and location of the intra-abdominal mass.

Steroid pulse therapy for children with intravenous immunoglobulin therapy-resistant Kawasaki disease: a prospective study.

Patients with Kawasaki disease (KD) who did not respond to the initial IVIG are known to have higher risk for developing coronary arterial lesions (CALs). Our aim is to clarify whether patients with initial IVIG resistant KD may benefit from methylprednisolone pulse therapy (MPT) in comparison with re- treatment of IVIG (2nd IVIG). A total of 237 patients (median age: 2 years 2 months; range 1 months-10 years) with KD were initially treated with IVIG (2 g/kg). Among them, 41 patients (22 %) were assessed as IVIG resistance: these patients were allocated to either group A receiving MPT (n = 14) or group B receiving the 2nd IVIG (n = 27). Patients with resistant to the additional therapy (MPT or 2nd IVIG) were received second IVIG (group A) or MPT (group B). Changes in leukocyte count, C-reactive protein and albumin before and after an additional therapy were significantly greater in group A than those in group B. However, the prevalence of CALs did not differ between the groups (36 % in group A and 26 % in group B, p > 0.05). There was no significant difference in the medical cost between the groups (median cost: 92,032 JPY in group A and 97,331 JPY in group B). MPT does not reduce the risk of development to CAL and does not seem to be beneficial as single agent therapy for IVIG resistant KD.

Urinary sludge caused by ceftriaxone in a young boy.

It is known that ceftriaxone administration is associated with biliary pseudolithiasis, although the development of urolithiasis has been rarely reported. We encountered a young male with bacterial meningitis complicated by urinary precipitates composed of ceftriaxone-calcium salt which is confirmed by high-performance liquid chromatography. This patient suggested that ceftriaxone significantly increased urinary excretion of calcium, which may be linked to ceftriaxone-related urolithiasis or sludge. It is therefore worthwhile to monitor the levels of urinary calcium to creatinine ratio in patients on ceftriaxone, as they may be at greater risk for developing large stones and renal damage.

Increased urinary calcium excretion caused by ceftriaxone: possible association with urolithiasis.

The administration of ceftriaxone is known to be associated with biliary pseudolithiasis, although the development of urolithiasis has only rarely been reported. We treated a young male with bacterial meningitis complicated by urinary precipitates composed of ceftriaxone-calcium salt, which prompted us to study whether ceftriaxone administration predisposes children to the formation of urinary precipitates. The case-control study reported here included 83 children with bacterial pneumonia aged from 3 months to 8.9 years. The children were divided into one group of 43 children who received ceftriaxone (group A) and a second group of 40 children who received amoxicillin (group B). Paired samples of serum and urine before and after treatment were obtained from the patients in each group. There were no significant differences in demographic characteristics and blood biochemistry between the groups. However, the mean urinary calcium to creatinine ratio (uCa/Cr; mg/mg) was significantly higher in group A patients than in group B patients after treatment (0.19 vs. 0.09, respectively; p < 0.001), and analysis of the paired urine samples revealed that the uCa/Cr significantly increased after treatment only in group A patients(p < 0.001). There was a weak but non-significant relationship between the dose of ceftriaxone and the uCa/Cr in group A (p = 0.10, r = 0.24). Our results are the first to demonstrate that ceftriaxone has the potential to significantly increase urinary excretion of calcium, which may be linked to ceftriaxone-related urolithiasis or sludge. We therefore suggest that it is worthwhile monitoring the uCa/Cr levels in patients on ceftriaxone as they may be at greater risk for developing large stones and renal damage.

Two types of orthostatic dysregulation assessed by diameter of inferior vena cava.

AIMS: Orthostatic dysregulation (OD) is common in adolescents. This study was conducted to evaluate the usefulness of the measurement of the diameter of the inferior vena cava (IVC) for objective assessment of patients with OD. METHODS: Twenty children with OD (median 14 years, range 9-15 years) and 23 age-matched healthy children (median 12 years, range 10-15 years) were enrolled. A diameter of IVC was measured by an abdominal echogram before and after a head-up tilt table testing (HUT). Changes in IVC was assessed by an arbitrary parameter, collapse index (CI) as the following equation: [(maximal IVC diameter in the supine position - maximal IVC diameter in the standing position)/(maximal IVC diameter in the supine position)]× 100. CI was evaluated 4 weeks after treatment with an adrenergic agent. RESULTS: Children with OD demonstrated either higher CI or lower CI compared to that in control children: CI was more than 50 (range 50-71) in 12 patients with OD while that was equal to or less than 0 (range -225 to 0) in eight out of 20 patients. In contrast, CI was between 0 and 50 (range 1-26) in 23 healthy children. Pharmacological treatment induced the normalization in the CI in both higher and lower CI group. CONCLUSION: OD can be classified into two subtypes: by HUT, one is characterized by an increase of IVC diameter while another is characterized by its decrease. Measurement of IVC diameter by HUT is useful to understand the pathophysiology and to assess the efficacy of treatment.

Immunoglobulin preparations affect hyponatremia in Kawasaki disease.

Hyponatremia frequently occurs in Kawasaki disease (KD). The aim of this study was to investigate the effect of Na content of the intravenous immunoglobulin (IVIG) preparation on serum Na levels in KD. Seventy-eight subjects, of whom 27 had hyponatremia, were split up into two groups: group A receiving IVIG preparations containing high Na (0.9%) and group B receiving IVIG preparations containing trace Na. While the data before IVIG therapy revealed no significant differences in the median serum Na between the groups, an administration of IVIG preparations increased the serum levels of Na in group A (P < 0.01) but not in group B (P > 0.05). Furthermore, the median serum Na level was significantly higher in group A than that in group B (139.0 vs 137.0 mEq/L, respectively, P < 0.01). No significant difference was found in the prevalence of coronary artery lesions between the groups. In conclusion, we should keep it in mind that the IVIG products without Na have an adverse affect on hyponatremia in KD though their efficacy seems to be equivalent to those containing high Na.

Detection of adenovirus DNA in throat swabs and blood by SYBR green real-time PCR assay in patients with adenovirus-associated tonsillitis.

The adenovirus DNA load ranged from 10(5) to 10(10) copy/mL and from 10(4) to 10(7) copy/mL in throat swabs and blood from patients with adenovirus-associated exudative tonsillitis, respectively. The copy number of adenovirus DNA in blood was positively correlated with the duration of the fever.

Polymorphism of Fc gamma RIIa may affect the efficacy of gamma-globulin therapy in Kawasaki disease.

We evaluated whether there is a possible relationship between the effectiveness of gamma-globulin treatment for patients with Kawasaki disease (KD) and the polymorphism of Fcgamma RIIa, IIIb, and IIIa. Genomic DNA was extracted from whole blood collected from 56 patients with KD who received gamma-globulin treatment. The genotypes for Fcgamma RIIIb-NA(1, 2), Fcgamma RIIa-H/R131, and FcgammaRIIIa-F/V158 were determined to investigate the association between these polymorphisms and the development of coronary lesions (CALs). Twenty-three percent of patients with the HH allele for the Fcgamma RIIa polymorphism progressed to CALs, compared with 60% with the HR and RR alleles. HR and RR alleles may be a predictor of the progression of CALs in KD before the initiation of gamma-globulin therapy.

Detection of adenovirus DNA in clinical samples by SYBR Green real-time polymerase chain reaction assay.

BACKGROUND: Adenoviruses are associated with a variety of diseases including upper respiratory tract infections, acute conjunctivitis, cystitis and gastroenteritis. Adenoviruses can also cause fatal disseminated infections in patients undergoing stem cell transplantation. Measurement of adenovirus load in clinical samples from localized adenovirus infections or disseminated adenovirus infections may provide important information for analyzing the pathogenesis of various adenovirus infections. The purpose of the present study was to develop and optimize a highly sensitive real-time polymerase chain reaction (PCR) assay to detect a wide range of adenoviruses and to detect adenovirus DNA in clinical samples from immunocompetent children. METHODS: Clinical samples of throat swabs and blood were collected from 111 patients suspected of having adenovirus infection. The copy number of adenovirus DNA was measured by real-time PCR assay. RESULTS: SYBR Green real-time PCR assay is able to detect 10-10(6) copies of standard adenovirus DNA per run. Adenovirus DNA was detected in all culture-positive samples serotyped as 1, 2, 3, 4, 5, 6, 8 and 11. Viral loads on throat swabs from immunocompetent children with adenovirus infection ranged from 10(5) to 10(11) copies/mL. Adenovirus DNA was detected in 60% of blood samples and copy number ranged from 10(3) to 10(5) copies/mL. CONCLUSION: SYBR Green real-time PCR is a useful quantitative tool for analysis of adenovirus DNA. The present results for immunocompetent children with adenovirus infections provided basic data for comparison with data obtained from immunocompromised patients.

Measurement of inferior vena cava diameter for evaluation of venous return in subjects on day 10 of a bed-rest experiment.

We evaluated the usefulness of measurements of the inferior vena cava (IVC) diameters on abdominal echograms as an indicator of changes of venous return in subjects with orthostatic intolerance (OI) induced by simulated microgravity. We performed a standing test and recorded the IVC diameters on abdominal echograms in 12 subjects placed on a 20-day 6 degrees head-down-tilt bed-rest experiment. We found that different patterns of changes in IVC diameter occurred in the standing test on day 10 of the experiment; in five subjects with a marginal decrease in pulse pressure, IVC diameters in the upright position were markedly decreased compared with those in the supine position. In five subjects with feelings of discomfort, the IVC diameters in the upright position distended or did not decrease from those in the supine position. These results suggested that the changes in IVC diameter on the standing test indicated the presence of various types of hemodynamic responses of OI caused by simulated microgravity. In this study, we also evaluated changes in body-water compartments by conducting multifrequency bioelectrical impedance analysis. Longitudinal data analysis showed that the total body-water-to-fat-free mass and extracellular fluid-to-fat-free mass ratios decreased during the experimental period and recovered thereafter, and that the ratio of intracellular fluid to fat-free mass decreased during the experiment. No significant difference in changes in body-water compartments was seen among subjects with different patterns of changes in IVC diameters. Measurement of IVC diameter was useful to estimate hemodynamic changes in subjects with OI.

[Clinical efficacy and bacteriological studies of clarithromycin and cefdinir against group A beta-hemolytic streptococcal tonsillopharyngitis].

The clinical efficacy and safety of clarithromycin (CAM) and cefdinir (CFDN) were evaluated in 65 pediatric outpatients with group A beta-hemolytic streptococcal tonsillopharyngitis. Treatment was "effective" or better in 26 (78.8%) children receiving CAM and in 27 (87.1%) receiving CFDN based on antigen clearance and the "Criteria for Evaluation in Clinical Trials of Antibacterial Agents in Children" proposed by Japan Society of Chemotherapy (p = NS). The causative organisms were eradicated in 94.7% and 93.8% of subjects in the CAM and CFDN groups, respectively (p = NS). Adverse drug reactions were limited to moderate diarrhea in one patient in each group, and subsided during treatment. Causative organisms exhibited good susceptibility to CAM and CFDN. These results suggest excellent efficacy, safety and usefulness of CAM and CFDN in the treatment of group A beta-hemolytic streptococcal tonsillopharyngitsis in children.

Serial changes of plasma nitrate in the acute phase of Kawasaki disease.

BACKGROUND: Endogenous nitric oxide (NO) production increases with clinical conditions associated with immune stimulation. In Kawasaki disease (KD), various cytokines play a role in inflammatory reactions in the cardiovascular system. The authors hypothesized that elevated concentrations of nitrate was related to the severity of vasculitis. The aim of the present study was to evaluate serial changes of plasma nitrate concentrations in the acute phase of KD and to consider how NO is related to the inflammatory process of KD and to the coronary artery lesion (CAL). METHODS: Thirty patients with KD and 20 age-matched healthy controls were enrolled in the present study. Blood samples were obtained weekly for the first and second months. The patients were divided into two groups: one with CAL (n = 11) and another without CAL (n = 19). Plasma nitrate was measured by high-performance liquid chromatography. RESULTS: In both groups, plasma nitrate increased remarkably from the first week to the third week. Peak concentrations of nitrate (mean +/- SD, micro mol/L) in each group were as follows: 56.9 +/- 23.8 in the CAL(+) group and 68.2 +/- 33.8 in the CAL(-) group. Plasma nitrate decreased from the third week to the second month but was still elevated in both groups in comparison with the age-matched healthy controls. There was no correlation between plasma nitrates and white blood cell count or C-reactive protein, respectively (r = 0.013, 0.075). CONCLUSIONS: The results suggest that NO production may not be related to the severity of vascular inflammation and that elevated nitrate during the first month of illness may not be associated with a higher risk of CAL.