Preliminary development and evaluation of the support system for care of mechanically ventilated patients.

BACKGROUND: We wanted to demonstrate the feasibility of a novel computer-assisted ventilator alarm system, the support system for care of mechanically ventilated patients (SCMVP), to detect gas leaks and provide graphical information on the site of the leak in a manikin model. METHODS: We tested six leakage scenarios. Four scenarios were applied to both the respiratory circuits with the SCMVP and without the SCMVP (conventional system), and two scenarios were each specific to one of the systems. Fifteen registered nurses were asked to manage three scenarios each (two mutual and one system-specific scenario). Time to identify the site of the leak was measured and compared between the two systems. RESULTS: The SCMVP showed significantly shorter time for troubleshooting in one of the four mutual scenarios and shorter accumulated time for troubleshooting in the four mutual scenarios [18.0 (range, 14.5-19.5) and 48.5 (9.0-180.0) s, respectively] compared with the conventional system [76.0 (47.0-133.8) and 82.5 (16.0-180.0) s, respectively]. In the mutual scenarios, SCMVP resulted in significantly more frequent incidences of successful troubleshooting within 30 s and less frequent incidences of troubleshooting requiring >180 s [43.3% (13/30) and 6.7% (2/30), respectively] compared with the conventional system [13.3% (4/30) and 30% (9/30), respectively]. CONCLUSIONS: The SCMVP can facilitate rapid and successful recognition of the site of leak in a respiratory circuit in a simulation environment.

Characterization of the cell surface protein gene of Corynebacterium ammoniagenes.

Three dominant cell surface proteins of Corynebacterium ammoniagenes ATCC 6872 were identified in the cell wall fraction. The cspA gene, which encodes one of the major cell surface proteins, was cloned using the N-terminal amino acid sequence of the protein. Then the cloned chromosomal fragment containing the cspA gene was sequenced and was shown to encode a mature polypeptide of 333 amino acids with a molecular mass of 36654 Da. The amino acid sequence of the cspA gene showed similarity to the amino acid sequence of C. glutamicum CspA, one of the two major secreted proteins of C. glutamicum, although C. ammoniagenes CspA and C. glutamicum CspA differed in size. Northern blot analysis and primer extension analysis respectively revealed a 1.1 kb transcript and a promoter sequence resembling that of the C. ammoniagenes fatty acid synthase B (fasB) gene.

Characterization of guanosine kinase from Brevibacterium acetylicum ATCC 953.

Guanosine kinase (GKase) activity was identified in a cell-free extract of Brevibacterium acetylicum ATCC 953. We have purified the enzyme 4000-fold from the cell-free extract to apparent homogeneity. Molecular weight of 71,300 and 36,300 determined by gel filtration and sodium dodecyl sulfate gel electrophoresis, respectively, revealed that the enzyme is a dimer molecule. Maximum activity of the GKase was attained when the magnesium/ATP concentration ratio was close to 1. The GKase activity was dependent on the presence of a divalent cation. The Km values for guanosine, inosine, and 2'-deoxyguanosine as phosphate acceptors were determined to be 0.022, 0.87, and 2.83 mM, respectively. In addition to ATP and dATP, GTP and dGTP were shown to be effective phosphate donors for the GKase. The optimal pH seemed to be around pH 8.3, although relatively high activity was observed in the alkaline pH range of 7.5-9.8. The addition of 0.1 mM pyrimidine nucleotides, especially CMP and CTP, activated the GKase activity. On the other hand, the addition of 1 mM AMP, ADP, and GMP inhibited the GKase activity. It is thus likely that the GKase activity might be regulated in vivo by nucleotide concentrations and may control the nucleoside monophosphate level by efficiently recycling guanosine.

Molecular characterization of guanosine kinase gene from a facultative alkalophile, Exiguobacterium aurantiacum ATCC 35652.

Guanosine kinase activity was identified in an alkalophile, Exiguobacterium aurantiacum ATCC 35652, and the gsk gene encoding it was isolated as a homologous fragment of the Brevibacterium acetylicum gsk. The cloned chromosomal fragment contained an open reading frame which encodes a polypeptide of 308 amino acids with a molecular mass of 33349 Da. The Ex. aurantiacum Gsk shows strong sequence similarity to B. acetylicum Gsk, but possesses five additional amino acids at the C-terminus. An Mr 39200 protein synthesized in Escherichia coli harboring plasmids carrying Ex. aurantiacum gsk was purified and characterized. A 0.9 kb transcript revealed by Northern blot analysis and the presence of a factor-independent terminator structure suggest that Ex. aurantiacum gsk is monocistronic, although B. acetylicum gsk has been shown to be bicistronic. The striking alterations in the 3'-untranslated region resulted in a different gene organization.

Understanding the Relationship between Social Cognition and Word Difficulty. A Language Based Analysis of Individuals with Autism Spectrum Disorder.

BACKGROUND: Few quantitative studies have been conducted on the relationship between society and its languages. Individuals with autistic spectrum disorder (ASD) are known to experience social hardships, and a wide range of clinical information about their quality of life has been provided through numerous narrative analyses. However, the narratives of ASD patients have thus far been examined mainly through qualitative approaches. OBJECTIVES: In this study, we analyzed adults with ASD to quantitatively examine the relationship between language abilities and ASD severity scores. METHODS: We generated phonetic transcriptions of speeches by 16 ASD adults at an ASD workshop, and divided the participants into 2 groups according to their Social Responsiveness Scale(TM), 2nd Edition (SRS(TM)-2) scores (where higher scores represent more severe ASD): Group A comprised high-scoring ASD adults (SRS(TM)-2 score: ≥ 76) and Group B comprised low- and intermediate-scoring ASD adults (SRS(TM)-2 score: < 76). Using natural language processing (NLP)-based analytical methods, the narratives were converted into numerical data according to four language ability indicators, and the relationships between the language ability scores and ASD severity scores were compared. RESULTS AND DISCUSSION: Group A showed a marginally negative correlation with the level of Japanese word difficulty (p < .10), while the "social cognition" subscale of the SRS(TM)-2 score showed a significantly negative correlation (p < .05) with word difficulty. When comparing only male participants, Group A demonstrated a significantly lower correlation with word difficulty level than Group B (p < .10). CONCLUSION: Social communication was found to be strongly associated with the level of word difficulty in speech. The clinical applications of these findings may be available in the near future, and there is a need for further detailed study on language metrics designed for ASD adults.

Pulmonary endocrine cell hyperplasia and papilloma in rats induced by intratracheal injections of extract from particulate air pollutants.

We investigated the effect of intratracheal injections of an extract of suspended particulate matter (SPM) obtained from the urban ambient air of Tokyo, upon the development of proliferative lesions of pulmonary endocrine cells (PECs) in the rat. We also examined the modification effects of nitrogen dioxide, sulfur dioxide, or both of them on the PEC lesions. Male F344 rats were divided into six experimental groups of 5 animals each. Twenty animals were treated with intratracheal instillations of SPM admixed with carbon once a week for 4 weeks with or without additional gaseous exposure (6 ppm nitrogen dioxide or 4 ppm sulfur dioxide) 16 hrs a day for 11 months. Five animals were given intratracheal injections of carbon suspended in saline and the other five were untreated. The subcardiac lobes of the right lung were fixed with 4% paraformaldehyde, and embedded in paraffin. PEC hyperplasias and papillomas were counted in 200 serial sections, 4 microns thick. The average incidences of PEC hyperplasia in the untreated animals and in those treated with carbon were 194 and 200/cm3, respectively. The average incidences of PEC hyperplasia in the animals exposed to SPM tar only, SPM tar plus nitrogen dioxide and sulfur dioxide, SPM tar with nitrogen dioxide and SPM tar with sulfur dioxide were 376, 378, 372 and 349/cm3, respectively. These were significantly higher than the levels of the control animals, and additional gaseous stimuli had no effect on the incidence of PEC hyperplasia. Besides PEC hyperplasia, a few PEC papillomas were found in the animals treated with SPM tar, regardless of gaseous exposure, but in the control animals no papilloma was evident. Thus, compounds in airborne particulates are considered to be responsible for the development of PEC hyperplasias and papillomas.

Effect of prostaglandin E1 on arterial ketone body ratio in hepatectomy.

We evaluated the effect of prostaglandin E1 (PGE1) administration during hepatectomy on arterial ketone body ratio (AKBR), which is an indicator of liver function, and on other liver functions in the postoperative period. Eighteen patients were divided into two groups: Continuous intravenous administration of PGE1 (0.02 µg·kg-1·h-1) was started immediately before hepatic resection and ceased at the end of operation in nine patients (PGE1 group); the other nine did not receive PGE1 (control group). After hepatic resection, a significant increase in AKBR was observed in the PGE1 group. However, no change was observed in the control group. In the PGE1 group, total bilirubin and SGOT recovered more rapidly to the preoperative level than in the control group. These findings suggested that PGE1 might have a protective effect on the liver.

[A trial of clinical application of sparfloxacin for treating mycobacterial infections].

Sparfloxacin seems to be a good candidate for antimycobacterial treatment. However, there have been no clinical studies. We experienced 2 SPFX-treated cases, who could not use other antimycobacterial agents because of side effect, we tried SPFX-treatment on these cases. Good results were obtained, however, for long time use to prevent side effects, we tried SPFX every second day and monitored the serum levels of SPFX. SPFX-every second day treatment gave good clinical results and adequate serum levels of SPFX were observed.

[Cefaclor dosage change with renal dysfunction].

Serum and/or urine levels of cefaclor (CCL) were studied in 4 patients during the therapy with CCL. In patients with severely impaired renal function, moderately higher serum and urine levels of CCL persisted, serum half-lives of CCL were moderately prolonged and urinary excretion of CCL slightly decreased. Although dosage modification of CCL is necessary in patients with renal dysfunction, multiple doses of 250 mg every 8 hours may be safe and effective even in patients with impaired renal function.

Clinical studies on ampicillin-cloxacillin for intravenous injection (Rectocillin 'Kyowa') (author's transl).

(1) Ampicillin-cloxacillin for intravenous injection (Rectocillin 'Kyowa') was administered to 9 patients 1 g or 2 g daily for protection of postoperative infections, and good result was obtained in all cases. Eight out of 9 cases were with renal insufficiency. No side effect was encountered. (2) Rectocillin was administered to 14 patients with infections. The treatment was remarkably effective in 4 cases, and effective in 6 cases. In the cases with renal insufficiency, a daily dose of 1 g was effective. The dose administered to the patients with normal renal function was 2 g or 4 g daily. Neither clinical nor laboratory findings showed evidence of side effect.

[Pharmacokinetic study of sparfloxacin in patients receiving regular hemodialysis].

We investigated the in vivo kinetics of sparfloxacin (SPFX), an oral quinolone, in the hemodialytic patients. SPFX was orally administrated in a single dose of 200 mg to each of five hemodialytic patients, on a day that they were not receiving hemodialysis therapy. After dosing, the blood samples were collected periodically at 2, 4, 6, 8, 12, 24, 25, 27, 29, 48, 72 hours. Concentration of the unchanged SPFX in the plasma samples were measured by HPLC. The peak plasma levels of SPFX in the hemodialytic patients did not differ greatly from patients with renal failure (5 < Ccr<20 ml/min). Average T 1/2 beta of SPFX was 25.7 hours, and it was prolonged compared to the patients with renal failure (who were not receiving hemodialysis) and a group of young healthy volunteers. Based on these results, we believe those hemodialytic patients may be administrated with the drug once every other day, as long as normal doses are used.

[Studies on cephradine for intravenous injection (author's transl)].

1) The half-life of serum concentration of cephradine (CED) in patients with normal renal function, was 30 minutes and it prolonged to 83 minutes when combined with probenecid. 2) In the patients with severely impaired renal function, mean serum concentration of CED was 33 mcg/ml 24 hours after 1 g intravenous injection. 3) In clinical observations of 17 cases with infections of lung, urinary tract, and bile duct, the treatment with CED showed excellent results in 5 cases, good in 6, undetermined in 1. No remarkable side effect was observed.

[Clinical studies with minocycline intravenous instillation. Chemotherapy in patients with renal impairment (author's transl)].

In the present studies, we had an opportunity to review the effects of minocycline intravenous instillation for the treatment of moderate disorder of renal functions. No accumulation of minocycline was observed in the repeated administration of this drug instilled intravenously up to 7 days in the patients with moderate disorder of the renal functions. Also, no particular abnormality was observed in the tests of the liver, kidney and hematology. For patients with moderate Ccr 30 approximately 60 ml/min, as entered into the present study, the usual dosage of minocycline intravenous instillation for less than 7 days would not cause adverse reaction on renal functions.

[Clinical pharmacology and efficacy of levofloxacin in elderly patients].

We studied a newly developed oral quinolone antimicrobial agent, levofloxacin (LVFX, DR-3355), and obtained the following results. 1. Serum and urine levels of LVFX were determined after oral administration of LVFX 100 mg to 11 elderly patients with various degrees of renal function insufficiencies. The patients were classified according to creatinine clearance (Ccr) values into Group I (n = 1, Ccr greater than or equal to 70 ml/min), Group II (n = 4, 40 less than or equal to Ccr less than 70 ml/min), and Group III (n = 6, Ccr less than 40 ml/min). The peak levels of LVFX did not differ greatly among the 3 groups, but in patients with severely impaired renal functions, serum concentrations decreased more slowly than in those with slightly and moderately impaired renal functions, and high serum levels were maintained over a long period. Urinary excretion of LVFX diminished in relation to degrees of renal failure. 2. LVFX was administered to treat 13 elderly patients with respiratory tract infections. Clinical responses were good in all patients with a high efficacy rate of 100%. Laboratory tests revealed eosinophilia in 1 case. The symptom was mild, however, and no severe side effects due to the drug were observed.

[Clinical evaluation and pharmacology of DQ-2556 in the patients with compromised renal function].

We studied the pharmacokinetics of a new cephem antibiotic, DQ-2556, in patients with impaired kidney function. The peak concentrations of the compound in the serum were observed irrespective of the degree of kidney failure 5 minutes after its bolus administration of 1.0 g intravenously, and no significant difference was observed in the concentrations among the patients. On the other hand, the decrease in its concentrations in the serum was impeded in proportion to degrees of kidney failure and, in particular, hemodialysis patients showed markedly delayed clearance of the drug from the serum; the half-lives in the serum (beta phase) were prolonged to ca. 6 hours in patients with severe kidney failure (Ccr ca. 20 ml/min) and did so markedly to ca. 17 to 21 hours in patients with hemodialysis as compared with ca. 2.5 hours in patients with slight kidney failure (Ccr ca. 50 ml/min). Urinary excretion rates (0-to-24 hours values) were ca. 70% in patients with slight kidney failure, ca. 60% in patients with moderate kidney failure and ca. 40% in patients with severe kidney failure, showing a tendency toward a decline in relation to increasing degrees of kidney failure. The compound showed a satisfactory dialytic property. The clinical efficacy and safety of DQ-2556 were evaluated upon administering if at daily doses of 0.5 g b.i.d. and 1.0 g b.i.d. for 7 and 14 consecutive days respectively, in patients with lower respiratory tract infections. The clinical efficacies were excellent in 2 patients, good in 11 and poor in 2, yielding a efficacy rate of 86.7%. No side effects were observed, though, a neutrophil sedimentation ratio decreased in a patient, and a down-shift of prothrombin activities was observed in another. These results suggest that DQ-2556 is useful for lower respiratory tract infections, but in patients with kidney failures it is required to seek the most suitable regimen since the excretion rates of the compound decrease as degrees of kidney failure become severer.

[Clinical pharmacology and efficacy of S-1108].

We studied the pharmacokinetics of a new cephem antibiotic, S-1108, in patients with impaired kidney functions. Serum and urinary levels of S-1006 were determined after oral administration of S-1108 at 150 mg to 9 patients with renal dysfunction. In patients with severe renal impairment, high serum levels were maintained over long periods of time. Urinary excretion rates of S-1006 were lower as degrees of kidney failure were severer. S-1108 was administered to treat 27 patients with respiratory tract infections, and its clinical efficacy and safety were evaluated. The clinical efficacies were good in 26 patients, but poor in 1, yielding an efficacy rate of 96.3%. As to adverse reactions; diarrhea was observed in one case. Laboratory tests revealed elevated GOT and GPT in 1, and elevated gamma-GTP in another. These abnormalities, however, were slight and no severe side effects were caused by the drug.

[Usefulness of positron emission tomography to STA-MCA anastomosis for the case with cerebral infarction].

The ischemic area surrounding the cerebral infarction in the eloquent area was salvaged by STA-MCA bypass surgery. Both the misery perfusion area evaluated by positron emission tomography (PET) using the [15O] gas inhalation steady-state method and clinical symptoms improved within a year after surgery. To confirm the ischemic area and select the suitable recipient artery was important for successful bypass surgery, because only an artery covering the ischemic area is expected to have low resistance. In this case a large ischemic area with disturbed, vasodilatation by Diamox was detected on the SPECT. However, PET clearly exposed the localized misery perfusion area in the overestimated ischemic area by SPECT. We describe our experience and discuss the technique and efficacy of PET for STA-MCA anastomosis surgery.

[Lessons from experience of bertrand's selective peripheral denervation for splenius type torticollis].

A 23-year-old male with splenius type torticollis underwent selective denervation of C1 and C2 roots and C3-C6 spinal posterior rami, with excellent results. Based on this experience, we stress the importance of dynamic EMG and thorough review of video recording for identifying the involved neck muscles. In the operative procedures, the nerve rami are identified under the semispinalis muscle. To dissect the correct plane under the semispinalis muscle, the key point to keep in mind is to follow the great occipital nerve to the proximal part. An ultrasonic blood flow meter is useful to locate the vertebral artery in the spaces between the occiput and the C1 lamina and between C1-C2 laminae. Because fine nerve branches run in the soft tissues over the laminae, to avoid transient neuroapraxia, dissection around the C1, C2 arches should not be carried out under the periosteum, as is usually done in case of laminectomy. Dissection of C1 and C2 rami as far as the very medial part is rather difficult because of bleeding from the venous plexus and the presence of the vertebral artery. Therefore, the intradural approach might be easier for sectioning the C1 and C2 roots. We would like to add these points to the original description by Bertrand.

[Acute appendicitis caused by mucorales in a patient with severe aplastic anemia: report of an autopsy case].

A male patient with severe aplastic anemia was admitted for bone marrow transplantation. While waiting for a donor, high doses of methylprednisolone, anabolic steroid and granulocyte colony stimulating factor were given without response. Deferoxamine was administered for prophylaxis of hemochromatosis because of high level of ferritin. Acute right lower abdominal pain and pyrexia developed. A diagnosis of acute appendicitis was made and appendectomy was performed. The histopathological examination of the resected appendix revealed necrotizing hemorrhagic appendicitis with numerous hyphae of Mucorales. Though anti-fungal agent (amphotericin B) administration was continued, he subsequently developed ileo-cecal abscess and eventually died due to myoglobinuric nephropathy caused by extensive necrosis of the iliopsoas muscle. Autopsy revealed dissemination of hyphae of Mucorales in lungs, kidneys, large vessels and muscle of the bilateral lower limbs. Systemic vascular invasion and embolization of fungal hyphae were also observed. However, culture of exudate sampled from ileocecum yielded no Mucorales. It was emphasized that antemortem diagnosis and effective anti-fungal treatments are essential for the management of intestinal mucormycosis. The relation ship between mucormyocosis and deferoxamine was also discussed.

[Which factors affect the liver function most after gastrectomy in the gastric cancer patients?].

We examined the factors which influence the postoperative liver function in the gastric cancer patients who received gastrectomy by a particular surgeon. One hundred and five patients had no history of liver diseases, no blood transfusions, and no infection after the operation. They also had normal liver function preoperatively. They were anesthetized with halothane-nitrous oxide oxygen or enflurane-nitrous oxide oxygen with epidural anesthesia by the same group of anesthesiologists. GOT was followed for one month after the operation to evaluate the liver function. In 44 patients, GOT went up to above 50 IU.l-1. The maximal GOT correlated with low hemoglobin level on the 1st postoperative day, the duration of hypotension below 80 mmHg of the systolic blood pressure, and duration of the operation. These results suggest that special attention should be paid to correct hemoglobin level and to avoid hypotension during anesthesia.