Clinical evaluation of cefixime in children

A new beta-lactamase-stable oral cephem antibiotic, cefixime (CFIX), was evaluated for safety, efficacy and pharmacokinetics in children. CFIX was effective in 19 of 20 cases (95%) with bacterial infections. The drug was especially effective against the cases of pneumonia due to beta-lactamase-producing H. influenzae or B. catarrhalis. Pharmacokinetic parameters of CFIX (3 mg/kg) with premeal administration were as follows: Kel 0.328 +/- 0.066 hr-1, T 1/2 2.14 +/- 0.36 hrs, AUC 10.9 +/- 8.7 micrograms X hr/ml, and Vd/F 1.64 +/- 1.42 L/kg. In most of the cases tested, the urinary excretion rate in 12 hours was 5 to 17%. A dose of 3 mg/kg twice daily seems to be adequate for a regular treatment.     

Pharmacokinetic and clinical studies with imipenem/cilastatin sodium in the pediatric field. Pediatric Study Group for Imipenem/Cilastatin Sodium

Pharmacokinetic and clinical studies of imipenem/cilastatin sodium (MK-0787/MK-0791), a new carbapenem antibiotic and a dehydropeptidase-I inhibitor, respectively, were carried out in a joint study in the pediatric field by a study group consisting of investigators at 16 institutions. The results were summarized below. Pharmacokinetic studies Peak plasma concentrations of MK-0787/MK-0791 were 27.7-190.0/28.3-216.4 micrograms/ml at doses of 10/10-50/50 mg/kg administered by a 30 or 60-minute drip infusion. The above findings proved that dose response was clearly observed. Over a period of 6 or 7 hours, the urinary excretion of MK-0787 and MK-0791 totaled 54.2-88.0% and 53.6-89.0% of the dose administered, respectively. Plasma half-lives of MK-0787 and MK-0791 in the beta-phase were 0.87-1.05 hours and 0.59-0.95 hour, respectively. The cerebrospinal fluid (CSF) levels of MK-0787 in patients with purulent meningitis were 2.0-14.4 micrograms/ml; however, the penetration rate of the drug into the CSF was relatively poor in patients with normal meninges. Clinical study Clinical efficacy was evaluated in 283 patients. In 112 patients the daily dosage ranged from 30/30 mg/kg to 59/59 mg/kg, and in 138 patients it ranged from 60/60 mg/kg to 99/99 mg/kg. The maximum dose administered was 222/222 mg/kg. The drug was administered either 3 or 4 times per day. The clinical efficacy rate was 92.5% among 187 patients with identified etiologic pathogens. The drug was effective in 3 out of 4 patients with purulent meningitis and in 7 out of 10 patients with septicemia. The clinical efficacy rate was 96.7% in 90 patients with respiratory tract infection (pneumonia, lung abscess, etc.), 96.5% in 57 patients with urinary tract infection, 90.9% in 11 patients with SSTI. The clinical efficacy rate in those with no identified etiologic pathogen was 97.0% among 101 patients. Bacteriologically, the eradication rate for S. aureus was 87.9% of 33 isolates. Comprehensively, the eradication rate for Gram-positive bacteria was 94.7% of 75 isolates. The eradication rate for P. aeruginosa was 87.5% of 8 isolates. Including these strains, the eradication rate for Gram-negative bacteria was 90.3% of 134 isolates. The MK-0787/MK-0791 exhibited an eradication rate of 91.9% among a total of 211 Gram-positive and Gram-negative bacteria including anaerobes.(ABSTRACT TRUNCATED AT 400 WORDS)     

Bacteriological, pharmacokinetic and clinical studies on clarithromycin in the pediatric field. Pediatric Study Group of Clarithromycin

Clarithromycin (TE-031, A-56268), a new macrolide antibiotic agent, was evaluated bacteriologically and clinically for its efficacy and safety in pediatrics by a study group organized with pediatricians from all over the country. A summary of the results of the evaluation is as follows. 1. Absorption and excretion Pharmacokinetics of TE-031 was examined by single oral administration of 10% granules and 50 mg tablets at doses of 1, 5, 10 and 15 mg/kg. There were no significant differences between 10% granules and 50 mg tablets, and between administrations before and after meal. Peaks and half-life periods of blood level of TE-031 given once at doses of 5, 10 and 15 mg/kg (10% granules) before meal were 1.58, 4.37 and 3.79 micrograms/ml, and 2.53, 3.17 and 2.20 hours, respectively, and the urinary excretion in 6 hours after the administration were about 20-30%. 2. Antibacterial effects TE-031 was proved to have excellent antibacterial effect, i.e., inhibiting growth over 80% of strains of Streptococcus pneumoniae and Streptococcus pyogenes at 0.10 micrograms/ml, Branhamella catarrhalis at 0.39 micrograms/ml, and Campylobacter jejuni at 0.78 micrograms/ml. Against Staphylococcus aureus, TE-031 showed very similar activity spectrum to EM, and EM resistant strains were also resistant to TE-031. 3. Clinical results A total of 764 cases was studied. Clinical effects of TE-031 were evaluated in 717 cases out of the 764, excluding drop-outs and cases which did not meet specified protocols. Clinically, efficacies of TE-031 were "excellent" in 265 cases and "good" in 161 cases out of 453 cases of Group A in which causal agents were identified, with an efficacy rate of 94.0%, and out of 264 cases of Group B in which pathogens were not detected, clinical effects of TE-031 were "excellent" in 115 cases and "good" in 124 cases, with an efficacy rate of 90.5%. In terms of clinical effects of TE-031 classified by diseases when Group A and B were combined, efficacy rates were 91.6% for upper respiratory tract infection (217/237), 90.0% for bacterial pneumonia (108/120), 97.4% for Mycoplasma pneumonia (111/114), 100% for Chlamydia pneumonia (4/4), 85.0% for pertussis (34/40), 100% for scarlet fever (16/16), 83.9% for skin and soft tissue infection (26/31), and 98.9% for Campylobacter enteritis (87/88).(ABSTRACT TRUNCATED AT 400 WORDS)     

Whole genome association study of rheumatoid arthritis using 27 039 microsatellites

A major goal of current human genome-wide studies is to identify the genetic basis of complex disorders. However, the availability of an unbiased, reliable, cost efficient and comprehensive methodology to analyze the entire genome for complex disease association is still largely lacking or problematic. Therefore, we have developed a practical and efficient strategy for whole genome association studies of complex diseases by charting the human genome at 100 kb intervals using a collection of 27,039 microsatellites and the DNA pooling method in three successive genomic screens of independent case-control populations. The final step in our methodology consists of fine mapping of the candidate susceptible DNA regions by single nucleotide polymorphisms (SNPs) analysis. This approach was validated upon application to rheumatoid arthritis, a destructive joint disease affecting up to 1% of the population. A total of 47 candidate regions were identified. The top seven loci, withstanding the most stringent statistical tests, were dissected down to individual genes and/or SNPs on four chromosomes, including the previously known 6p21.3-encoded Major Histocompatibility Complex gene, HLA-DRB1. Hence, microsatellite-based genome-wide association analysis complemented by end stage SNP typing provides a new tool for genetic dissection of multifactorial pathologies including common diseases.     

A comparative, well-controlled study of ceftizoxime suppository against ceftizoxime intravenous injection in infantile acute pneumonia

We have attempted to clinically define the therapeutic usefulness of ceftizoxime suppository (CZX-S) in children with bacterial pneumonia, in a randomized trial. Intravenous injection of ceftizoxime (CZX) was used as the control. The results are summarized below. Subjects were inpatients with bacterial pneumonia, ranging in age from 9 months to 7 years and 10 months. As a rule, the daily dose was either four 250 mg (in potency) suppositories given at 6-hour intervals or 60 mg/kg body weight intravenous CZX (control) given in 4 injections at 6-hour intervals over a period of 7 days. The number of children in the study was 67. These children were divided into 2 dosage groups (suppository, 35; injection, 32) with matching pretreatment background factors. The severity of the target disease in the majority of the children was "moderate". The rate of therapeutic effectiveness was 97.1% for the suppository and 93.8% for the injection, and did not differ significantly between the 2 groups. Rates of efficacy by severity, presence or absence of underlying diseases, daily dose and/or complications were high without exception, and did not differ significantly between the 2 groups. Eradication rates for causative microorganisms, as studied in 16 children of each group, were both 93.8%. The 2 most frequently isolated causative organisms were Haemophilus influenzae and Streptococcus pneumoniae. Side effects were examined for 36 children of each group. The frequency of side effects did not differ significantly between the suppository group (2 with diarrhea and 1 with abdominal pain) and the injection group (1 with urticaria), and 8.3% and 2.8%, respectively. The frequency of abnormal laboratory test findings differed significantly (P less than 0.01) with respect to eosinophilia which occurred in 7 (20.6%) of the injected subjects but was not encountered in the subjects treated with suppositories. Other abnormal laboratory findings included thrombocytosis in 3 (14.3%) of the injection group and increased GOT in 1 (3.2%) of the suppository group. The suppository formulation of CZX appears to be a highly useful substitute for the injectable form, and should find a special use in children whose treatment with injections experiences some difficulty.     

Modified load sharing rip-stop technique in patients with traumatic transtendinous rotator cuff tear: Surgical technique and clinical outcomes

BackgroundTranstendinous rotator cuff tear is likely to occur due to trauma in sports activities, with a frequency of <2% of total rotator cuff tears. These tears are difficult to treat because of limited tendon tissue in the proximal stump, and standard repair techniques are sometimes ineffective. Few studies have reported on the repair technique and clinical outcomes for transtendinous rotator cuff tear, and an appropriate repair technique has, therefore, not been established. The purpose of this study was to use our modified load sharing rip-stop technique to repair transtendinous rotator cuff tear and to clarify the clinical effectiveness of this technique.MethodsThis was a retrospective case series review of eight patients who underwent the modified load sharing rip-stop technique for repairing traumatic transtendinous rotator cuff tear between January 2013 and June 2017. The eight patients were followed up for at least 2 years (range: 24–41 months). Cuff integrity was evaluated using magnetic resonance imaging at 12 months after surgery using the Sugaya classification. We evaluated the pre- and postoperative ranges of motion, American Shoulder and Elbow Surgeons score, Constant Shoulder Score, and muscle strength at 90° abduction. Data were analyzed using the Mann–Whitney U test and Fisher's exact tests. P < .05 was considered to indicate statistical significance.ResultsSix patients were classified as Sugaya I and two as Sugaya II. ASES score (38.5–90.2, P = .0008), Constant shoulder score (36.5–79, P = .002), flexion (85°–158.1°, P = .002), abduction (85°–157.5°, P = .001), external rotation (38.8°–55°, P = .024), and muscle strength at 90° abduction (2.95–5.39 kg, P = .028) improved significantly. Six patients were able to return to their previous sports activity.ConclusionUsing our modified load sharing rip-stop technique for repair of transtendinous rotator cuff tear, patients obtained good clinical outcomes and could return to sports activities.     

Relationship between depression and risk of malnutrition among community-dwelling young-old and old-old elderly people

Objectives: This study explores the association between nutritional status and depression among healthy community-dwelling young-old (aged 65–74) and old-old elderly (aged 75 and older).

Method: A cross-sectional design was implemented. A total of 274 community-dwelling older individuals (142 young-old; 132 old-old) were assessed using the Geriatric Depression Scale (GDS), Mini-Nutritional Assessment Short-Form (MNA-SF) and Life-Space Assessment. Logistic regression analysis was used to determine if depression was independently associated with risk of malnutrition, stratified by age (young-old vs. old-old).

Results: In the logistic regression model for young-old, being at risk of malnutrition (MNA-SF (≦11) was strongly associated with depression (GDS (≧5;) (likelihood ratio ν?=?6.26; 95% confidence interval [CI]: 1.91–20.49). In contrast, in the old-old group, the model was not statistically significant.

Conclusion: Depression and nutritional status were strongly correlated in young-old but not in old-old community-dwelling elderly. This study reveals that not only the factors correlated with but also the symptoms of depression may vary among different age stratifications of the elderly.     

Persistent verbal and behavioral deficits after resection of the left supplementary motor area in epilepsy surgery

An 8-year-old boy underwent a resection for focal cortical dysplasia at the left supplementary motor area (SMA) for the treatment of intractable epilepsy. The manifestations of SMA syndrome, such as transient mutism and right hemiparesis, resolved within a few weeks. Verbal disfluency and impaired executive function, accompanied by impulsivity and distractibility, persisted for more than 12 months. The verbal and behavioral problems caused serious difficulties in the school life of the patient, until they became less evident at 18 months after surgery. Tractography performed 18 months after surgery revealed a defect in the subportion of fronto-parietal association fibers within the left superior longitudinal fascicles. Verbal influency can persist with unusually long duration after resection of SMA during childhood. Although not discernible on the routine neuroimaging, white matter damage beneath the SMA region could result in serious disabilities in executive function. These complications should be recognized for the prediction and assessment of deficits in children after surgical intervention involving this region.