Fibroblast growth factor 23 in chronic kidney disease: bridging the gap between bone mineral metabolism and left ventricular hypertrophy.

BACKGROUND: Left ventricular hypertrophy (LVH) is a major cardiovascular complication in chronic kidney disease (CKD) patients. For a successful management of LVH, the comprehensive understanding of the classical and the new emerging factors associated with LVH is of paramount importance. The aim of the present study was to evaluate the clinical correlates of bone mineral metabolism with the occurrence of LVH in nondialyzed CKD patients. METHODS: This cross-sectional study included 96 patients with stages 2-4 CKD. Demographic characteristics, clinical profiles, laboratory tests and transthoracic echocardiogram were performed. RESULTS: LVH was observed in 36% of the patients. Patients with LVH were older, had a higher prevalence of hypertension, and higher levels of intact parathormone, fibroblast growth factor 23 and C-reactive protein. Serum phosphorus, alkaline phosphatase and vitamin D were not associated with the presence of LVH. In the multiple logistic regression analyses only FGF23 remained as a variable independently associated with LVH. CONCLUSION: We confirmed the high prevalence of LVH in nondialyzed CKD patients and showed that FGF23, an early marker of phosphorus load, was an important factor associated with LVH in these patients. Monitoring of FGF23 could be important for the management of LVH in this population.

Cyclic sinus node dysfunction in a patient with hyperthyroidism.

In a 54-year-old woman with hyperthyroidism, episodic sinus node dysfunction (SND) recurred in a cyclic fashion. The SND occurred suddenly during normal sinus rhythm and progressed to marked sinus bradycardia; occasionally, sinus arrest developed with or without ventricular escape beats. A 1-mg dose of intravenous atropine sulfate suppressed the occurrence transiently. After a 200-mg dose of propylthiouracil and a 20-mg dose of prednisolone every six hours, the SND was completely abolished within 21 hours. It is probable that, together with a pathologic process induced by hyperthyroidism, the autonomic nervous system participated in our patient's episodic SND.

Hepatic eosinophilopoiesis from multipotent hemopoietic stem cells in Toxocara canis-infected mice.

Extramedullary hemopoiesis, recognized as hemopoietic foci, increased in the livers of Toxocara canis-infected mice. At the peak of the response (day-13 after infection), the majority of hepatic hemopoietic foci were of the eosinophil lineage. Hepatic nonparenchymal cells prepared from T. canis-infected mice on day 13 contained large numbers of hemopoietic stem cells, more than half of which were cycling. When W/Wv mice, which are genetically deficient in multipotent hemopoietic stem cells, were infected with T. canis, hepatic hemopoietic foci were rare throughout the course of infection. This impaired response of W/Wv mice was restored by bone marrow grafting from normal +/+ littermates. These results indicate that, in response to the increased demand, eosinophils are generated in the liver by the differentiation from multipotent stem cells, not only from the committed precursors.

Mg2+-activated adenosine triphosphatase from Crithidia fasciculata: purification and inhibition by suramin and efrapeptin.

The mitochondrial Mg2+-activated adenosine triphosphatase (ATPase; EC 3.6.1.4) from the insect flagellate Crithidia fasciculata ATCC 11745 has been extracted from the membrane by chloroform treatment and purified to electrophoretic homogeneity by a method involving ammonium sulphate fractionation, gel filtration on Sephadex G-200 and DEAE-cellulose chromatography. The molecular weight of the native enzyme, determined by gel filtration, was about 350 000. Five subunits were detected by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate, with molecular weights of 54 000, 45 000, 35 000, 20 000 and 10 000. The membrane-bound, but not the soluble (F1) ATPase was inhibited by oligomycin and leucinostatin. Both forms of the enzyme were strongly inhibited by the antibiotic efrapeptin and the trypanocidal drug suramin. The inhibition by efrapeptin was of the mixed type, with double-reciprocal plots intersecting below the abscissa, as in the case of the enzyme present in beef heart submitochondrial particles. Suramin, on the other hand, acted as a non-competitive inhibitor of the membrane-bound ATPase and as a strictly competitive inhibitor of the purified F1 ATPase.

Attenuation of epithelial injury in acute experimental colitis by immunomodulators.

Intestinal epithelial permeability can be modulated by the immune system and can be greatly increased by transepithelial migration of neutrophils. Since immunosuppressants have been reported to inhibit the ability of neutrophils to migrate, we assessed the effects of two immunosuppressants on epithelial permeability and granulocyte infiltration in a model of acute colitis. Epithelial permeability was measured at 3 and 6 h after induction of colitis in the rabbit by intracolonic administration of trinitrobenzene sulfonic acid. At these times, blood-to-lumen leakage of 51Cr-EDTA was elevated by approximately 8- and 18-fold, respectively, above levels observed in healthy controls. Pretreatment with either of the immunosuppressants (cyclosporin A and L-683,590) significantly reduced the changes in 51Cr-EDTA leakage observed at the latter time point. These drugs also significantly attenuated granulocyte infiltration of the colon after induction of colitis, as measured by tissue myeloperoxidase activity. Unlike the immunosuppressants, misoprostol, a prostaglandin analogue, attenuated the increases in colonic permeability but had no effect on granulocyte infiltration in this model. These results demonstrate that two structurally unrelated immunosuppressants are capable of markedly reducing neutrophil infiltration and the colonic permeability changes observed in an experimental model of acute colitis, although the mechanisms through which these effects are produced remain unclear.

Prevention and reversal of experimental colitis by a monoclonal antibody which inhibits leukocyte adherence.

The role of neutrophils in the pathogenesis of acute colitis was investigated using a rabbit model. Colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid in 30% ethanol. Myeloperoxidase activity was measured at various times after induction of colitis as an index of neutrophil infiltration, and this was confirmed by histology. The permeability of the colonic epithelium to [51Cr]EDTA was also measured at various times after induction of colitis. The most marked increase in neutrophil infiltration of the colon occurred during the period 3-6 h after induction of colitis. This was also the period in which the greatest increase in colonic permeability was observed. Pretreatment with a monoclonal antibody (IB-4) directed against the leukocyte adhesion molecule, CD18, markedly suppressed neutrophil infiltration into the colonic tissue after induction of colitis. This pretreatment also significantly reduced the extent of epithelial injury. Administration of IB-4 to rabbits 12 h after induction of colitis resulted in a rapid decline in tissue myeloperoxidase activity. When measured 12 h after IB-4 administration (3 mg/kg), colonic myeloperoxidase activity was reduced by about 80% compared to the control group treated with the vehicle. These results are consistent with the hypothesis that neutrophils contribute significantly to the epithelial dysfunction that characterizes colitis and suggest that antibodies directed against adhesion molecules may represent a novel approach to the treatment of intestinal inflammatory disorders.

Technetium-99m serum albumin measurement of gastrointestinal protein loss in a subtotal gastrectomy patient with giant hypertrophic gastritis.

Gastrointestinal protein loss was measured using Tc-99m labeled human serum albumin in a patient with giant hypertrophic gastritis. Gastric secretion was aspirated via a nasogastric tube and measured for radioactivity after intravenous injection of Tc-99m albumin. Assessment of radioactivity of the collected gastric secretion yielded a total radiocount of 98.7 kilocounts per minute within 6 hours, which is equivalent to 1.1% of the total dose. Therefore, at least 1.1% of the circulating albumin was excreted into the gastric cavity within 6 hours, and, since simultaneous abdominal imaging did not demonstrate obvious accumulation of tracer in the gastrointestinal tract, protein loss was thought to be due to giant gastric rugae of the resected stomach. It was concluded that Tc-99m albumin is a valuable means for detection of the site of protein loss in patients with protein-losing gastroenteropathy. This method has several advantages in the clinical setting; it is less time consuming, easy to perform, and provides quantitative and qualitative assessment of protein loss.

[Effect of antioxidants on radical-initiated peroxidation of retinal homogenate].

PURPOSE: To compare the effect of antioxidants on radical-initiated peroxidation of retinal homogenate. METHODS: Lipid peroxides in bovine retinal homogenate were induced by 5 mM FeNO3 (Fe), 25 mM 2, 2'-azobis(2,4'-dimethylvaleronitrile) (lipid-soluble, AMVN) or 50 mM 2,2'-azobis (2-amidinoprpane) dihydrochloride (water-soluble, AAPH) and the preventive effects of antioxidants were measured. Phosphatidylcholine hydroperoxide (PC-OOH) was analyzed with high performance liquid chromatography (HPLC) as the endpoint biomarker. RESULTS AND CONCLUSION: Troglitazone, an oral hypoglycemic agent, inhibited PC-OOH production by Fe and AMVN. Therefore, it may be effective for protecting against oxidative stress on the inner surface plasma membranes and subcellular organelle. Quercetin has radical scavenging effects on both sides of the membrane, because it prevents PC-OOH production by AMVN or AAPH. These results demonstrate the usefulness of an in vitro screening test that can accurately and rapidly determine the capacity of an antioxidant against lipid peroxidation or oxidative stress.

[Pharmacokinetic, bacteriological, and clinical studies on panipenem/betamipron in children].

Pharmacokinetic, bacteriological and clinical studies were performed on panipenem/betamipron (PAPM/BP) in children. The results are summarized as follow: 1. Twelve patients with various bacterial infectious diseases were treated with PAPM/BP. Each dose was 20 mg/20 mg/kg, administered 3 times daily, in 30-minute intravenous drip infusion. Treatments were continued for 5-22 days. Clinical efficacies of PAPM/BP in 12 patients with bacterial infections (1 with suspected sepsis, 5 with pneumonia, 1 with acute maxillary sinusitis, 2 with acute otitis media, 1 with cervical abscess and 2 with urinary tract infection complexed type) were evaluated as excellent in 7, good in 4 and fair in 1, with an efficacy rate of 91.7%. Seventeen causative organisms found in 10 patients (Haemophilus influenzae in 4, Branhamella catarrhalis in 3, Streptococcus pneumoniae in 2, Pseudomonas aeruginosa in 2, Staphylococcus aureus in 1, alpha-Streptococcus in 1, Corynebacterium sp. in 1, Peptostreptococcus micros in 1 and Klebsiella pneumoniae in 2) were eradicated except 2 strains (S. aureus and P. aeruginosa) from 1 patient (patient No. 2). No adverse reactions were observed in any of the 12 patients. 2. MICs of PAPM were examined against 22 clinical isolates (H. influenzae 5, B. catarrhalis 3, alpha-Streptococcus 3, S. pneumoniae 2, Corynebacterium sp. 2, S. aureus 1, P. aeruginosa 1, P. micros 1, Enterobacter cloacae 1, Escherichia coli 1, Group D Streptococcus 1 and Staphylococcus epidermidis 1) from children with bacterial infections. PAPM showed a good antibacterial activity comparable to the activity of cefoperazone (CPZ) against S. pneumoniae strains relatively tolerant to penicillins. However, the activity of PAPM against H. influenzae was somewhat weaker than that of CPZ. 3. Pharmacokinetic studies.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical evaluation of clarithromycin, a new macrolide antibiotic in children].

A new oral macrolide, clarithromycin (TE-031, A-56268), was evaluated for its safety, efficacy and pharmacokinetics in 33 children. TE-031 was effective in all cases of mycoplasmal pneumonia, pneumococcal pneumonia, streptococcal pharyngitis, pertussis and Campylobacter gastroenteritis. The pharmacokinetic availability of TE-031 granule and tablets was much better than the older macrolides; serum half-lives of TE-031 averaged 3.2 +/- 0.25 hours (for the granule preparation). No clinical adverse reaction was encountered, but cases of transient mild elevation of the serum GPT (2 cases) and eosinophilia (2 cases) were encountered. From these preliminary data, TE-031 seems to have a place in the treatment of pediatric infectious diseases.

[Pharmacokinetic, bacteriological and clinical studies on meropenem in children].

Pharmacokinetic, bacteriological and clinical studies on meropenem (MEPM) were performed in children. The results are summarized as follows: 1. A total of 16 patients was treated with MEPM. Each dose was 20 mg/kg, and administration was made 3 times daily using 30-minute intravenous drip infusion for 5-28 days. Clinical efficacies of MEPM in 16 patients with bacterial infections (1 with purulent meningitis, 1 with suspected subdural abscess, 2 with suspected sepsis, 4 with pneumonia, 1 with acute maxillar sinusitis, 2 with cervical abscess, 1 with acute gastroenteritis, 2 with skin soft tissue infection and 2 with urinary tract infection) were evaluated as excellent in 7 patients, good in 8 patients and fair in 1 patient with an efficacy rate of 93.8%. Fourteen causative organisms found in 11 patients (Streptococcus pneumoniae in 4, Branhamella catarrhalis in 3, Staphylococcus aureus in 3, Group B Streptococcus in 1, Escherichia coli in 3) were all eradicated. No adverse reactions were observed in any of the 16 patients. 2. MICs of MEPM against 6 clinically isolated bacteria (B. catarrhalis 2, S. pneumoniae 3 and S. aureus 1) from children with bacterial infections were examined. MEPM showed good antibacterial activities. 3. Pharmacokinetic studies: Peak plasma concentrations of MEPM averaged 43.07 micrograms/ml (37.20-46.30 micrograms/ml) at dose of 20 mg/kg administered by 30-minute drip infusion. In the first 8 hours after administration, the urinary excretion rates of MEPM averaged 39.9% of the administered dose.(ABSTRACT TRUNCATED AT 250 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)

[Intestinal duplication. Report of 2 cases]. / Duplicación intestinal. Informe de dos casos.

Intestinal duplications are rare and they result from embryological failures in the canalization of the gastrointestinal tract. This paper presents a case of ileal intestinal duplication and its differential diagnosis from Meckel's diverticulum. Besides, a case of rectal duplication in an asymptomatic elder patient is presented.

Gastric mucosal microcirculation measured by laser Doppler velocimetry in patients with gastric ulcer.

In order to evaluate the role of gastric mucosal blood flow in patients with gastric ulcer, we applied laser Doppler velocimetry to the human gastric mucosa to study the regional microcirculatory mechanism. We measured 5 spots each in 34 control stomachs, and in 47 patients with gastric ulcer at the angle and antrum of the stomach, 2 additional spots around the ulcer. During the healing process, mucosal blood flow around the gastric ulcer increased as compared to that of the active or scarring stages. Compared with that of surrounding mucosa, mucosal blood flow around the gastric ulcer increased significantly during healing stage. Mucosal blood flow at the ulcer margin in healing stage (H1 stage) was 52% more than in the active stage. The increase in mucosal blood flow in the ulcer margin during healing stages (H1 and H2 stage) was 45% in cases with initial ulcer and 22% in cases with recurrent ulcer. It was concluded that increased blood flow in the ulcer margin during healing stages promotes healing of the ulcer. Laser Doppler velocimetry is useful in measuring mucosal blood flow sequentially in various stages of gastric ulcer, and also provides effective evaluation of medical treatment.