Hyponatremia and hypokalemia as risk factors for falls.

BACKGROUND/OBJECTIVES: Fall accidents may reduce an individual's quality of life and ability to perform the activities of daily life, and may delay recovery from illness. Consequently, medical institutions need to take measures to prevent falls. There are various risk factors for falls, including advanced age, illness and medication effects. Although hyponatremia and hypokalemia have been reported to increase the rate of falls, how they affect falls is not fully understood. SUBJECTS/METHODS: We retrospectively examined 2948 patients, ⩾18 years old who had been hospitalized for ⩾3 days at Gifu (Japan) Municipal Hospital between May 2012 and April 2013 to determine the effects of hyponatremia and hypokalemia on the risk of falls. After the patients had been divided into fall and non-fall groups, their data were subjected to univariate and multiple regression analysis to identify significant differences. RESULTS: The univariate analysis results revealed significant differences between the groups in terms of age (⩾65 years); the presence of hyponatremia, hypokalemia, central nervous system disease, cardiovascular disease and/or peripheral nerve/muscular disease; intake of medications that increase the risk of falls; and increased sedative dosage. The multivariate analysis results revealed significant differences between the groups in terms of the presence of hyponatremia (odds ratio (OR), 1.751; 95% confidence interval (CI), 1.020-3.005), hypokalemia (OR, 2.209; 95% CI, 1.280-3.813), central nervous system disease (OR, 2.492; 95% CI, 1.629-3.814) and/or age ⩾65 years (OR, 2.180; 95% CI, 1.242-3.826). CONCLUSIONS: The results indicated that the presence of hyponatremia or hypokalemia increases the risk of falls.

Efficacy of recombinant human granulocyte colony-stimulating factor on neutropenia in patients with AIDS.

The efficacy of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on neutropenia was evaluated in 14 patients with AIDS and AIDS-related complex (ARC). In all patients, including 11 neutropenic patients, 100 or 200 micrograms/m2 of rhG-CSF significantly increased the neutrophil counts. The response was greater in patients with higher neutrophil counts before the treatment, and was also dose-dependent. Although the effect seemed to be less potent, the agent also increased the neutrophil counts even when zidovudine (azidothymidine, AZT) and other myelosuppressive antiviral agents were administered simultaneously. These observations indicate that rhG-CSF may be beneficial in preventing and treating some secondary infections, and will make it easier to continue therapy with antiviral agents in patients with AIDS or ARC.

Presence of multiple HIV type 1 subtypes among mothers and children in Japan.

We collected blood samples from 70 HIV-1-infected pregnant women and 76 babies born to HIV-1-infected women in Japan, from 1989 to 1999. To analyze the genetic diversity of HIV-1 among mothers and children, we sequenced the C2-V3 regions of HIV-1 gp120. Phylogenetic tree analysis of these regions revealed that multiple HIV-1 subtypes, A, B, D, E, and G, were circulating among mothers and children in Japan. Thus, the genetic heterogeneity of HIV-1 among mothers and children in Japan is steadily increasing, although the number of cases remains small. Perhaps the longest term survivor, an 11-year-old child with a vertical HIV-1 subtype G infection in Japan, is one of our subjects.

Immunohistochemical distribution of surfactant apoproteins in hypoplastic lungs of nonimmunologic hydrops fetalis.

Forty-three patients with nonimmunologic hydrops fetalis (NIHF), including 32 patients (74%) with hypoplastic lung, were immunohistochemically examined for the expression of surfactant apolipoproteins (SPs), using anti-gamma G immunoglobulins against human SP-A with a molecular weight (MW) of 35 K and SP-B with a MW of 5 K compared with that in 59 patients in a control group and 45 patients with hypoplastic lung induced by causes other than NIHF. In the control group, SP-A was expressed in the lungs from 23 gestational weeks and became more numerous and intense in alveolar type II cells after 31 gestational weeks, whereas SP-B began to be expressed from 20 gestational weeks, and almost all patients showed a diffuse positivity after 26 gestational weeks. In the NIHF group, SP-A expression was generally weak, even after 31 gestation weeks. Moreover, most of the patients showing a weak expression of SP-A were also associated with hypoplastic lung and had a clinical history of persistent intrauterine pleural effusion of more than 2 weeks. Conversely, the immunoreactivity of SP-B was well preserved in NIHF cases either with or without hypoplastic lung. These results suggest that in the NIHF lung, there is a possible delay in the functional maturation or development of SP-A synthesis by alveolar type II cells, and this retardation of the functional maturation in type II cells also participates in the postnatal respiratory insufficiency in NIHF.

Peculiar eosinophilic inclusions within astrocytes in a patient with malformed brain.

At autopsy, we observed eosinophilic inclusions within the astrocytic cytoplasm in areas of polymicrogyria and heterotopic gray matter in a 17-year-old female with severe mental retardation and physical handicaps who had died of respiratory failure. The inclusions stained with acid fuchsin, azocarmine, Holzer's stain and phosphotungstic acid hematoxylin (PTAH). They reacted with anti-S-100 protein antibody. The cytoplasm of the astrocytes containing the inclusions reacted with antibody to GFAP. The inclusions were amorphous masses that consisted of aggregated clusters of osmiophilic coarse granules about 30 nm in diameter. Some rough endoplasmic reticulum was observed on the inside and outside of the inclusions and in the cytoplasm of the astrocytes lacking such inclusions. We suggest that these inclusions resulted from an abnormality at or near the rough endoplasmic reticulum.

Bax-induced apoptosis not demonstrated in the congenital toxoplasmosis in mice.

A prominent neuropathological change observed in a murine model of congenital toxoplasmosis is cerebral cortical hypoplasia. In the early embryonic life of toxoplasmosis mice, the number of apoptotic cell observed in cerebral cortex is increased, indicating that increased number of apoptotic cells might relate to the pathogenetic mechanism of the cortical hypoplasia. Immunohistochemical expression of apoptosis-related factors, Bcl-2 and Bax has been studied in fetal murine brains infected with toxoplasma and in controls. Paraffin sections of the fetal brains on embryonic day (ED) 10, 12, 14, 16 and 18 were applied for the immunostains of Bcl-2 and Bax. Totally, 47 experimental animals (ED10: n=8, ED12: n=6, ED14: n=12, ED16: n=6, ED18: n=15) and 48 control animals (ED10: n=6, ED12: n=8, ED14: n=9, ED16: n=9, ED18: n=16) were examined. Bcl-2 positive cells were detected on ED10, whereas Bax positive cells appeared on ED14. No difference of Bcl-2 and Bax expression between toxoplasmosis and control groups was detected, suggesting that there is no clear relation between Bax-induced apoptosis and cortical dysplasia in congenital toxoplasmosis.

Pathomechanism of cerebral hypoplasia in experimental toxoplasmosis in murine fetuses.

In order to elucidate the pathological mechanism of cerebral hypoplasia in congenital toxoplasmosis, fetal toxoplasmosis was induced by intraperitoneal injection of Toxoplasma gondii into five pregnant mice on embryonal Day 5 (E5). The maternal and fetal brains were examined histologically and immunohistochemically; six fetuses were examined on E16 and 21 on E18. T. gondii organisms were immunohistochemically detected in the maternal brains, placentas and the ventricular zone of the fetal cerebrum. In none of the fetal brains was any gross deformity observed, except for cerebral hypoplasia. On E16 and E18, the cerebral cortices were seen to consist of immature laminations, and the cells had less cytoplasm and rounder hyperchromatic nuclei than those in the control mice. The cerebral walls and the cortical layers, except in the ventricular zone, were thinner than in the controls (P < 0.01 in each case). On E18, the proliferating cell nuclear antigen immunolabeling index was higher, and the cytoplasm of more cells in the cortical plate was immunoreactive with anti-beta-tubulin antibody compared with control mice. Using an in situ end-labeling technique, apoptotic cells were not observed in the cortices in mice of both groups. It is suggested that the cerebral hypoplasia following Toxoplasma infection is related to delayed maturation.

[Mild varicella observed in children vaccinated with varicella vaccine between 1984 and 1987].

We investigated varicella cases developed in children who received varicella vaccine in the period from October 1984 to March 1987. In this period 463 children were vaccinated and 334 of the vaccines were seronegative before injection. Seroconversion was observed in 276 seronegative vaccinees producing a seroconversion rate of 83.1%. Thirty-five children developed exanthem more than 4 weeks after the vaccination and were diagnosed as varicella. Among them one child was found to be antibody-positive in his preserum and five were seronegative in both their pre- and post-sera. Thus, among the children who were seroconverted by the vaccination only 30 had varicella (the attack rate = 10.9%). No varicella cases were reported, however, among 27 children who first became seropositive after revaccination. When these children were added to the seroconverted ones, the case rate amounted to 9.9% (30/303). The general symptoms of varicella observed in the vaccinated children were mild or extremely mild, so varicella vaccine is reasonably indicated to be efficient and useful although it could no completely protect the vaccinees from natural varicella.

[A case of perinatal transmission of human immunodeficiency virus--diagnosis of HIV infection by culture and PCR].

A child born from a mother with HIV infection was reported. We have followed the patient from 3 month old of age. Her HIV antibody disappeared at 7 month by EIA, and at 10 month by WR. But we confirmed her HIV infection by PCR and HIV culture, repeatedly at those times, PCR and HIV culture are thought to be necessary for sero-negative infants born from mothers positive for HIV antibody.

[Varicella in adulthood: clinical features, severity scores, source of infection and complications].

Varicella has been thought to be one of the representative infectious disease in childhood, but recently we are under the impression that adults contracting varicella are increasing in number. On the other hand, they say that varicella generally causes a serious illness in adult patients. So we investigated signs and symptoms of varicella, source of infection, occupations of adult patients, except those who were immunologically compromised, by means of medical records, to know the characteristics of varicella in adulthood. According to the varicella severity score proposed by Nagai et al., varicella in the hospitalized adult patient was found to be much severer than that in children. The most remarkable symptoms, were high fever and sore throat, and these were the main reason of hospitalization in most of our patients. Although severity scores were very high in admitted adult patients with varicella, their clinical courses were not serious, and most of them recovered with only supportive therapy. These patients rarely suffered from complications, like pneumonia. If adult patients with varicella hospitalized in the early stage and received supportive care, they could recover without any complications. In most cases of adult varicella the source of infection was unknown. In the case of married persons, however, many of them were infected through their child. When adults contract varicella, not only the patients themselves suffer from high fever and sore throat, but also they act as the source of infection, if they are medical care workers. Furthermore, in public, the contraction of varicella results a socioeconomic loss from suspension of business caused by the illness. Prophylaxis with varicella vaccine, therefore, should be considered, when there are people who have never contracted varicella, whether or not they are medical staff.

[Clinical study of PC-904 in pediatrics (author's transl)].

Clinical study of PC-904 was performed in 8 children with infectious diseases and the following results were obtained. 1) The patients treated with PC-904 were each one case of acute pharyngitis, lacunar tonsillitis, scarlet fever, phlegmone, acute bronchitis and lung abscess, and 2 cases of bronchopneumonia. 2) The administration methods were drip infusion, one-shot intravenous injection and the combined use of these administrations. The daily dosage varied from 30 to 49 mg/kg in 3 cases and from 50 to 70 mg/kg in 3 cases, and was 227 mg/kg in 1 case. 3) Clinical evaluation was examined in 7 cases and 57.1% of effectiveness was obtained. Out of 2 cases of pneumonia, one case with the causative organism of My. pneumoniae was excluded from the clinical evaluation. 4) No side effects were observed in all 8 cases treated with PC-904.

[Clinical study on norfloxacin in pediatrics].

Pediatric infections were treated with norfloxacin (NFLX), a pyridonecarboxylic acid antibiotic developed by Kyorin Co., Ltd., to investigate its clinical efficacy. 1. Thirteen patients were treated with NFLX. These patients included of 5 with Campylobacter enteritis, 4 with Salmonella enteritis, 3 with dysentery and 1 with acute enteritis. 2. Of 14 pathogens identified, complete eradications were observed with 13 strains and partial eradication was seen in 1 case. Thus, overall eradication rate was 92.9%. 3. These were no symptoms nor abnormal laboratory findings which indicated an occurrence of side effect due to the NFLX treatment.

[Clinical study of rokitamycin dry syrup in pediatrics].

A total of 22 patients with acute pediatric infections was treated with rokitamycin (TMS-19-Q, RKM) dry syrup, a new macrolide antibiotic developed by Toyo Jozo Co., Ltd., Ohhito, Japan, to investigate its clinical efficacy. 1. A girl of an age 4 years 2 months (weighing 16.5 kg) was administered orally 10 mg/kg of RKM, and a boy of an age 8 years 7 months (weighing 24.5 kg), 15 mg/kg, and blood concentrations of RKM in these subjects were measured to investigate its absorption and excretion. Blood concentrations of the drug reached a peak of 0.84 microgram/ml in an hour after the administration in the girl, 0.72 microgram/ml in 30 minutes in the boy, with T1/2 of 0.86 and 1.82 hours, respectively. Their 6-hour cumulative urinary recovery rates were 2.79 and 2.13%, respectively. 2. A total of 20 patients was treated with RKM dry syrup. These patients included 3 with acute pharyngitis, one with acute tonsillitis, 4 with hemolytic streptococcal infections, 7 with acute bronchitis, 2 with pneumonia, another 2 with pertussis, and one with Campylobacter enteritis. The treatment was effective in 18 of them with a clinical efficacy of 90.0%. 3. Bacteriological responses to RKM dry syrup were as follows: eradication of pathogens in 5, pathogens decreased in 3, and no changes were observed in 3 of 12 patients from whom pathogens had been isolated prior to the treatment, thus the eradication rate was 45.5% with the exception of 1 patient whose bacteriological response was unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

[Experimental and clinical studies of BRL 25000 (clavulanic acid-amoxicillin) granules in the field of pediatrics].

BRL 25000 granules, a formulation consisting of amoxicillin (AMPC) and clavulanic acid (CVA), was evaluated in the field of pediatrics. In a pharmacokinetic study, serum concentrations were determined in a patient after oral administration of BRL 25000 granules in the non-fasting state at a dose of 11.76 mg/kg. The serum levels of amoxicillin (AMPC) and clavulanic acid (CVA) 1 hour after administration were 7.76 micrograms/ml and 6.64 micrograms/ml, with biological half-lives of 0.86 hour and 0.88 hour respectively. The serum concentration profile at a dose of 31.58 mg/kg showed almost the same tendency as at 11.76 mg/kg, although the peak level and biological half-life of the serum concentrations were not obtained. These serum levels and their peak levels were considered reasonable compared with those obtained in adults at similar dose levels. In clinical studies, 34 patients were evaluated including 8 patients with acute pharyngitis or acute tonsillitis, 1 patient with acute bronchitis, 1 patient with bronchopneumonia, 23 patients with scarlet fever and 1 patient with pertussis. BRL 25000 granules were administered orally 3-4 times per day for 4-8 days to 2 patients at doses of 20 approximately less than 30 mg/kg/day, to 18 patients at doses of 30 approximately less than 40 mg/kg/day, to 11 patients at doses of 40 less than approximately 50 mg/kg/day, and to 3 patients at doses of 50-60 mg/kg/day. The clinical response was assessed excellent in 13 cases and good in 21 cases giving an overall clinical efficacy rate of 100% (34/34). The causative organisms were isolated in 17 cases and included 12 strains of Streptococcus group A, 2 S. pneumoniae, 3 H. influenzae and 1 H. parainfluenzae.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical study on imipenem/cilastatin sodium in the field of pediatrics].

Imipenem/cilastatin sodium (MK-0787/MK-0791) was administered to pediatric patients with infections, and the following results were obtained. Pharmacokinetic study Two children, 11 years of age (38 kg body weight) and 3 years of age (15.5 kg body weight), were administered by 30 minutes intravenous drip infusion a single dose of 500 mg/500 mg (13.2 mg/13.2 mg per kg) and 250 mg/250 mg (16.1 mg/16.1 mg per kg) of MK-0787/MK-0791, respectively. Serum concentrations of MK-0787 reached their peaks at the end of drip infusion at a value of 56.33 micrograms/ml and 55.98 micrograms/ml, respectively. Concentrations of the drug decreased as the time after the administration increased, and they reached 0.14 microgram/ml and 0.12 microgram/ml, respectively in the older and the younger children at 6 hours after the administration. Half-lives (T 1/2) of the drug in serum were calculated to be 1.21 hours and 1.04 hours, respectively. The concentration of the drug in cerebrospinal fluid for the 11 years old was 0.52 microgram/ml 2 hours after the drip infusion and the serum concentration at the time was 4.02 micrograms/ml. Peak serum concentrations of MK-0791 in the 2 children were 53.73 micrograms/ml and 22.99 micrograms/ml, respectively, at the end of drip infusion. After 1 hour, the serum concentration of the drug decreased to 10.54 micrograms/ml in 1 case and not detectable in the other case. Urinary recovery rates of MK-0787 in 6 hours after the drip infusion was 82.9% and 63.6% in the 2 children and those of MK-0791 were 57.9% and 74.6%. Clinical study Clinical studies on MK-0787/MK-0791 were carried out in 6 pediatric patients; 1 each with femoral cellulitis, sepsis suspected, salmonellosis, acute tonsillitis, bronchopneumonia and streptococcosis. Lengths of treatment were 2 2/3-4 days for 5 cases and 6 days for 1 case. The patients were treated by 30-60 minutes intravenous drip infusions twice a day for 1 case, and 3 times a day for 5 cases at daily doses of 54.5-66.7 mg/kg. The treatment was effective in all cases, with 3 cases judged excellent and 3 cases good. The safety of the drug was studied in 7 patients. No side effects nor clinically abnormal values were observed in any cases.

[A clinical evaluation of cefpodoxime proxetil in pediatrics].

Children with acute infections were treated with cefpodoxime proxetil (CPDX-PR, CS-807), a new oral cephalosporin. 1. A girl of 4 years old, weighing 17 kg, and another girl of 12 years old, weighing 33 kg, were administered orally each 3 mg/kg of CPDX-PR. Blood levels of CPDX reached peaks of 1.39 and 2.26 micrograms/ml at 4 hours-post-dose, and T1/2's were 2.09 and 2.63 hours, respectively. Cumulative urinary recovery rates for 8 hours were 57.3 and 80.9%, respectively. 2. A total of 30 patients was treated with CPDX-PR. These patients included 10 with acute tonsillitis, 6 with acute bronchitis, 5 with bronchopneumonia, 2 with scarlet fever and 2 with urinary tract infections, and one each with acute pneumonia, acute otitis media, acute otitis media plus sweat gland abscess, staphylococcal scalded skin syndrome and acute lymphadenitis. The treatment was effective in 27 cases out of 29 (except one with an unknown response) with a clinical efficacy rate of 93.1%. 3. Bacteriological responses to CPDX-PR were as follows; eradication of pathogen in 7, and unknown in 2 out of 9 cases from whom pathogens had been isolated prior to the treatment. 4. As a side effect, diarrhea was observed in 1 patient, but it was possible to continue the treatment. With regard to laboratory tests, a slight elevation of GOT and slight elevations of GOT and GPT were found in 1 case each.

[A clinical study on cefteram pivoxil in the field of pediatrics].

Cefteram pivoxil (CFTM-PI, T-2588), a new oral cephem antibiotic of ester type, was evaluated for its safety, efficacy and pharmacokinetics. 1. One child, 4 years of age (18 kg body weight), was administered orally 3 mg/kg after meal. The peak serum level of CFTM was 0.78 microgram/ml after 2 hours, and cumulative urinary excretion rate during the first 6 hours was 15.0%. 2. Clinical studies on CFTM-PI were carried out in 17 pediatric patients; 1 with acute pharyngitis, 2 with acute tonsillitis, 1 each with pertussis, acute bronchitis, 2 with broncho-pneumonia, 4 with scarlatina, 3 with acute otitis media, and 1 each with lymphadenitis, acrobystitis and urinary tract infection. Clinical responses were excellent in 9, good in 6, fair in 1, poor in 1, and the overall clinical efficacy rate was 88.2%. 3. Bacteriological efficacy was investigated with 10 strains of 5 species (Streptococcus pyogenes 4, Streptococcus pneumoniae 2, Haemophilus influenzae 2, Enterococcus and Bacteroides 1) isolated from 9 patients. All strains were eradicated. 4. As to adverse reactions, mild diarrhea was observed in 1 patient. But therapy had to be continued without procedure and the diarrhea disappeared after 6 days. No adverse hematological, renal or hepatic effects were noted.

[Clinical study of S-6437 in pediatrics (author's transl)].

Clinical study of sustained release cephalexin (granules, 200 mg/g, S-6437) was conducted in pediatric patients as follows: 1. For infants under 20 kg of body weight, 25 approximately 50 mg/kg/day of this preparation (or 50 approximately 100 mg/kg/day for severe diseases) were given in two divided doses, and for infants over 20 kg, 1 g (or 2 g for severe diseases) were administered at two divided doses. 2. Patients treated with this preparation were 27 cases with scarlet fever, 3 with acute pharyngitis, 2 with acute tonsillitis, 1 with acute laryngitis, 1 with acute cystitis and 1 with acute enteritis. 3. Out of the 35 patients, 11 showed "very good" response to this preparation, 18 "good", 3 "fair", 1 "poor", and 2 "unknown" indicating 87.9% of effectiveness. 4. Side effects of cheilitis in one patient and vomiting in 1 were observed, and other 2 patients had difficulty in taking this preparation. No other side effects were found.

[Clinical studies of cefsulodin in the pediatric field].

Pharmacokinetic and clinical evaluations of cefsulodin (CFS) were made and the following results were obtained. 1. Pharmacokinetic study Three hundred fifty grams of CFS (20 mg/kg) was administered by 30 minutes intravenous drip infusion to 7 years old child (17.5 kg in weight). Serum concentrations of CFS at the end of the infusion and 1,1.5,2.5,6.5 hours thereafter were 46.0,44.9,23.0,11.9 mcg/ml and 0.6 mcg/ml respectively. Urinary recovery rate until 6 hours from the start of infusion was 66.2%. 2. Clinical study CFS was administered to the case of bronchitis with cystic fibrosis of the pancreas and bronchiectasia (treatment was made 2 times), and each 1 case of pyelonephritis with renal calculus and measles pneumonia with infantile spasm. All infections were caused by P. aeruginosa and administration and dosage of CFS was 47 to 86 mg/kg/day, 2 to 4 times daily by intravenous injection or intravenous drip infusion for 5 to 11 days. Result was good in 3 infections (2 cases) and fair in 1 case, i.e. measles pneumonia. Effectiveness rate was 75.0%. Side effect as well as abnormal change of laboratory findings were not observed. Thus, CFS is considered to be the useful drug for the treatment of pediatric infection caused by P. aeruginosa.