Clinical and pharmacokinetic evaluation of imipenem/cilastatin sodium in children

Nineteen episodes of infection in 17 children (one had 3 episodes) were treated with imipenem/cilastatin sodium (MK-0787/MK-0791), and the clinical efficacy and side effects were evaluated. The ages of patients ranged from 1 month to 8 years 1 month and their body weights ranged from 3.9 to 25.2 kg. The MK-0787/MK-0791 was administered intravenously by a 30-60 minutes infusion, in doses ranging from 8-42 mg/8-42 mg/kg every 6 to 12 hours for 3 to 40.5 days. Among 18 episodes in 16 patients (one patient proved to have rubella meningoencephalitis and was excluded from evaluation of the clinical efficacy) with bacterial infections including sepsis, pneumonia, acute suppurative thyroiditis and urinary tract infections, the results were excellent in 10, good in 5, fair in 2, and poor in 1 episode. Some side effects were noted; among all 19 episodes in the 17 patients diarrhea was noted in 3, rash in 1, slightly elevated serum transaminases in 1 and thrombocytosis in 1 episode. Pharmacokinetic studies were done in 7 patients whose ages ranged from 3 years 2 months to 13 years 1 month. Plasma concentrations of MK-0787 in 2 children were 19.6 and 20.0 micrograms/ml at 15 minutes and 5.6 and 2.1 micrograms/ml at 2 hours after a 10 mg/10 mg/kg intravenous 30-minute drip infusion of MK-0787/MK-0791. Plasma half-lives of MK-0787 were 1.52 and 0.74 hour, and total urinary recoveries were 54.6 and 71.4% during 0-6 hours. After a 20 mg/20 mg/kg intravenous 30-minute drip infusion into 2 other children, plasma concentrations of MK-0787 were 46.8 and 44.0 micrograms/ml at 15 minutes and 7.8 and 7.4 micrograms/ml at 2 hours. Plasma half-lives were 0.82 and 0.83 hour, and total urinary recoveries were 110.2 and 80.5% during 0-6 hours. Plasma concentrations of MK-0787 were less than 0.2, 0.2 and 1.2 micrograms/ml just before the next doses in 3 patients given 11-20 mg/11-20 mg/kg of MK-0787/MK-0791 every 6-8 hours. The time course of the plasma levels and urinary excretion in these patients were similar to those noted in the previous 4 patients following a single dose. Plasma concentrations of MK-0787 in a girl were 0.3 micrograms/ml just before the next dose and 8.2 micrograms/ml at 2 hours after multiple doses of 14 mg/14 mg/kg every 6 hours for 3 days and then 28 mg/28 mg/kg every 6 hours for 35 days.(ABSTRACT TRUNCATED AT 400 WORDS)     

Vascular endothelial cell injury and platelet embolism in Duchenne muscular dystrophy at the preclinical stage

Blood vessels in muscle biopsy specimens from 4 Duchenne muscular dystrophy (DMD) patients (including 3 at the preclinical stage) were examined by electron microscopy and compared with those in non-diagnostic biopsy specimens from age-matched controls and cases of other childhood neuromuscular disorders. The most striking feature was the blister-like swelling of vascular endothelial cells in the biopsied muscle specimens from the 3 preclinical stage DMD patients, which was observed in 23-39% of the small blood vessels examined. Other noticeable features in the preclinical DMD patients were: (1) replication of the basement membrane, there being more than 3 layers in 30% of the capillaries; (2) many degenerating and regenerating capillaries; and (3) platelet adhesion and aggregation in small blood vessels including small arteries and veins. Morphometric analysis showed that the capillary and endothelial cell areas were much greater in the preclinical DMD patients than in the controls or the cases of the other neuromuscular disorders. These phenomena strongly suggest an as yet undetermined process in blood vessels in preclinical DMD.     

Kinetic simulation of signal transduction system in hippocampal long-term potentiation with dynamic modeling of protein phosphatase 2A.

We modeled and analyzed a signal transduction system of long-term potentiation (LTP) in hippocampal post-synapse. Bhalla and Iyengar [Science 283(1999) 381] have developed a hippocampal LTP model. In the conventional model, the concentration of protein phosphatase 2A (PP2A) was fixed. However, it was reported that dynamic inactivation of PP2A was essential for LTP [J. Neurochem. 74 (2000) 807]. We introduced a dynamic modeling of PP2A; inactivation (phosphorylation) of PP2A by calcium/calmodulin-dependent protein kinase II (CaMKII) in the presence of calcium/calmodulin, self-activation (autodephosphorylation) of PP2A, and inactivation (dephosphorylation) of CaMKII by PP2A. This model includes complex feedback loops; both CaMKII and PP2A are autoactivated, while they inactivate each other. Moreover, we proposed an analysis strategy for model validation by applying the results of sensitivity analysis. In our system, calcineurin (CaN) played an essential role, rather than the activation of protein kinase C (PKC) as documented in the conventional model. From results of the analysis of our model, we found the following robustness as characteristics of bistability in our model: (1). PP2A reactions against calcium ion (Ca(2+)) perturbation; (2). PP2A inactivation against PP2A increase; (3). protein phosphatase 1 (PP1) activation against PF2A increase; and (4). PP2A reactions against PP2A initial concentration. These properties facilitated LTP induction in our system. We showed that another mechanism could introduce bistable behavior by adding dynamic reactions of PP2A.     

Tuberculous meningitis with hydrocephalus Contribution of PCR assay of CSF before VP shunting

A 10-month-old infant with tuberculous (Tb) meningitis accompanying hydrocephalus was successfully treated with a VP shunt operation soon after a PCR assay of CSF was found to be negative for Mycobacterium tuberculosis. PCR assay of CSF is helpful for determination of the timing for VP shunting in Tb meningitis. Received: 15 March 1996 Revised: 9 January 1998     

Brain activation of patients with obsessive-compulsive disorder during neuropsychological and symptom provocation tasks before and after symptom improvement: a functional magnetic resonance imaging study.

BACKGROUND: Functional neuroimaging studies have implicated hyperactivity of the frontal cortex in obsessive-compulsive disorder (OCD); however, relationships between abnormal brain activity, clinical improvement, and neuropsychological function have not been clarified in OCD. To clarify the pathophysiology of this disorder, regional changes in brain function were examined during administration of cognitive and symptom provocation tasks in patients with OCD before and after treatment. METHODS: Ten outpatients with OCD participated in the study. Functional magnetic resonance imaging (fMRI) was performed before and after treatment. Stroop and symptom provocation tasks were administered during fMRI. Each patient was randomly allocated to receive either pharmacotherapy with fluvoxamine 200 mg/day (n = 4) or behavior therapy (n = 6) for 12 weeks. RESULTS: After 12-week treatment, mean (+/- SD) total score on the Yale-Brown Obsessive-Compulsive Scale decreased from 29.00 +/- 3.59 to 14.60 +/- 9.22, representing symptomatic improvement from moderate to mild. After symptom improvement, symptom provocation-related activation in the orbitofrontal, dorsolateral-prefrontal, and anterior cingulate cortices decreased. Conversely, Stroop task-related activation in the parietal cortex and cerebellum increased. CONCLUSIONS: After improvement of OCD with either fluvoxamine or behavioral therapy, hyperactivation of the frontal lobe related to a symptom-provocative state decreases, and posterior brain activity related to action-monitoring function increases.     

The effect of kanpou medicine on the growth and aggregation of calcium oxalate crystals in vitro]

The effects of the compositional drugs of kanpou medicine on the growth and aggregation of calcium oxalate crystals were investigated in vitro. In the seeded crystal system, the inhibitory activities were calculated from the change of the number (Ia), total volume (Ig) and fractional volume (I) of crystals determined by a Coulter Multisizer. Among the tested drugs (Takusha, Akyou, Chorei, Bukuryou, Kasseki, Kinsensou, Kagosou), only Takusha and Kagosou had strong inhibitory activities on the growth and aggregation at the concentration of 5 micrograms/ml and 10 micrograms/ml (Ia greater than 80%, Ig, I greater than 90%). No significant correlation was observed between inhibitory activities and alcian blue precipitable polyanions (ABPP) of each drug. Thus some naturally existing substances composing the kanpou medicine may help prevent the stone formation in clinical use.     

Rapidly progressive glomerulonephritis due to rifampicin therapy.

A 60-year-old man was treated with rifampicin, isoniazid, ethambutol and pyrazinamide for pulmonary tuberculosis. Acute renal failure developed 1 month after re-administration of rifampicin following 1 month's interruption of treatment. A renal biopsy showed crescentic lesions characteristic of rapidly progressive glomerulonephritis. This is, to our knowledge, the fourth case of rapidly progressive crescentic glomerulonephritis associated with rifampicin treatment, which responded to methylprednisolone pulse therapy followed by oral steroid therapy.     

K1 Antigen, Serotype and Antibiotic Susceptibility of Escherichia coli Isolated from Cerebrospinal Fluid, Blood and Other Specimens from Japanese Infants

K1 antigens, serotypes and antibiotic susceptibilities of Escherichia coli isolates from neonates and infants were investigated. The presence of K1 antigen was tested by the K1-specific phage method. The number of K1 positive strains was 27 (84%) of 32 isolates from cerebrospinal fluid, 11 (25%) of 44 from blood and 4 (22%) of 18 from other specimens. Fourteen (33%) of the K1 positive strains were serotyped as O16:H6, and 8, 7 and 5 were serotyped as O18ac:H7, O1:H7 and O7:H-, respectively. One of 5 of the K1 negative strains were distributed into 30 different combinations of O and H antigens. The ampicillin resistance rates were 19% in K1 positive strains and 45% in K1 negative ones. The incidence of chloramphenicol resistance was the same in K1 positive and negative strains (21%). Ampicillin resistance was not noted in O16: H6 strains, but the incidence of antibiotic resistance was high (65% to ampicillin and 53% to chloramphenicol) in the rough-type strains.     

Duodenal Carcinoid Tumor: Endosonographic Imaging and Endoscopic Resection

A 75-yr-old Japanese woman was shown by endoscopy to have a sessile polyp in the duodenal bulb. Endoscopic biopsy confirmed the diagnosis of carcinoid tumor. The endoscopic ultrasound probe showed a 6-mm hypo-echoic tumor that was confined to the suhmucosal layer; the underlying muscularis propria layer was intact. On the basis of these findings, endoscopic resection was chosen, and the tumor was completely resected by the strip biopsy technique with prior hypertonic saline and epincphrine injection; there were no complications.     

Campylobacter jejuni strains from patients with guillain-barré syndrome belong mostly to penner serogrpup 19 and contain β-N-acetylglucosamine residues

Campylobactor jejuni was isolacted from stool cultures from 14(30%) of 46 partients with Guillain-Barré syndrome and from 6(1.2%) of healthy persons, and the difference was highly significant (P<0.0001). In addition, serological evidence of recent. C. Jejuni infection. Ten of 12(83%) isolated from partients with Guillain-Barré syndrome belonged to Penner serogroup 19, which is a rare serogroup in sporadic patients with C. Jejuni enterties. In the lection typing stude, all serogroup 19 strains from patients with Guillain-Barré syndrome patients with Guillain-Barré syndrome were shown to contain terminal b?-N-acetylglucosamine residues on their cell surface, bur serogroup 19 strains from patients with enteritis were not.