Intravenous repletion of phosphorus deficiency in the chronic renal failure patients with severe hypophosphatemia

Severe hypophosphatemia is a potentially life-threatening medical condition and might lead to a fatal outcome in critically ill patients. The situation is further complicated by the co-morbid renal failure. We evaluated the efficacy and safety of the intravenous phosphate repletion in 15 renal failure patients with severe hypophosphatemia. Six patients with advanced renal failure and nine patients under maintenance hemodialysis, 7 males and 8 females, aged between 42 and 83 years old, were found to have serum phosphate level < 1.2 mg/dL from various medical conditions and were treated with intravenous phosphate infusion. The phosphate solution prepared from sodium dihydrogen phosphate (NaH2PO4), containing 13 mg/ml phosphate and 0.5 meq/ml sodium, in the dosage 2.5-3.0 mg phosphate/Kg body weight, was administered through the central venous lins every 6-8 hours. The infusion was discontinued once serum phosphate level reached 5.0-5.5 mg/dL. Serum ionized calcium, phosphate and intact parathyroid hormone levels were serially followed at different intervals, respectively. The hemodialyzed uremic patients received their dialysis treatment as scheduled. All patients survived the hypophosphatemic period and regained normal phosphate levels after repletion. The amount of phosphate administered to reach the target level ranged between 3438 and 9150 mg and the duration of treatment varied between six and seventeen days. Hypocalcemia (< 4.2 mg/dL) was noted at eight occasions during the whole treatment period but none was symptomatic. Eleven patients recovered from the offending illness. However, four patients expired due to reasons not directly consequent to and temporally remote from hypophosphatemia. We conclude that prompt repletion of severe hypophosphatemia and phosphate deficiency with relatively slower rate of NaH2PO4 solution intravenous infusion is a safe and effective mode of treatment for renal failure and uremic patients. The longer treatment period allowed the administered minerals full equilibration. The risk of hyperkalemia is avoided and the sodium/volume load can be eliminated by dialysis.     

Differential activation of NAD kinase by plant calmodulin isoforms. The critical role of domain I

NAD kinase is a Ca2+/calmodulin (CaM)-dependent enzyme capable of converting cellular NAD to NADP. The enzyme purified from pea seedlings can be activated by highly conserved soybean CaM, SCaM-1, but not by the divergent soybean CaM isoform, SCaM-4 (Lee, S. H., Kim, J. C., Lee, M. S., Heo, W. D., Seo, H. Y., Yoon, H. W., Hong, J. C., Lee, S. Y., Bahk, J. D., Hwang, I., and Cho, M. J. (1995) J. Biol. Chem. 270, 21806-21812). To determine which domains were responsible for this differential activation of NAD kinase, a series of chimeric SCaMs were generated by exchanging functional domains between SCaM-4 and SCaM-1. SCaM-4111, a chimeric SCaM-1 that contains the first domain of SCaM-4, was severely impaired (only 40% of maximal) in its ability to activate NAD kinase. SCaM-1444, a chimeric SCaM-4 that contains the first domain of SCaM-1 exhibited nearly full ( approximately 70%) activation of NAD kinase. Only chimeras containing domain I of SCaM-1 produced greater than half-maximal activation of NAD kinase. To define the amino acid residue(s) in domain I that were responsible for this differential activation, seven single residue substitution mutants of SCaM-1 were generated and tested for NAD kinase activation. Among these mutants, only K30E and G40D showed greatly reduced NAD kinase activation. Also a double residue substitution mutant, K30E/G40D, containing these two mutations in combination was severely impaired in its NAD kinase-activating potential, reaching only 20% of maximal activation. Furthermore, a triple mutation, K30E/M36I/G40D, completely abolished NAD kinase activation. Thus, our data suggest that domain I of CaM plays a key role in the differential activation of NAD kinase exhibited by SCaM-1 and SCaM-4. Further, the residues Lys30 and Glu40 of SCaM-1 are critical for this function.     

TNF-alpha receptor knockout mice are protected from the fibroproliferative effects of inhaled asbestos fibers

We performed a prospective observational cohort study of the epidemiology and etiology of nosocomial pneumonia in 358 medical ICU patients in two university-affiliated hospitals. Protected bronchoscopic techniques (protected specimen brush and bronchoalveolar lavage) were used for diagnosis to minimize misclassification. Risk factors for ventilator-associated pneumonia were identified using multiple logistic regression analysis. Twenty-eight cases of pneumonia occurred in 358 patients for a cumulative incidence of 7.8% and incidence rates of 12.5 cases per 1, 000 patient days and 20.5 cases per 1,000 ventilator days. Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Hemophilus species made up 65% of isolates from the lower respiratory tract, whereas only 12.5% of isolates were enteric gram-negative bacilli. Daily surveillance cultures of the nares, oropharynx, trachea, and stomach demonstrated that tracheal colonization preceded ventilator-associated pneumonia in 93.5%, whereas gastric colonization preceded tracheal colonization for only four of 31 (13%) eventual pathogens. By multiple logistic regression, independent risk factors for ventilator- associated pneumonia were admission serum albumin <= 2.2 g/dl (odds ratio [OR] 5.9; 95% confidence interval [CI] 2.0-17.6; p = 0.0013), maximum positive end-expiratory pressure >= 7.5 cm H2O (OR, 4.6; 95% CI, 1.4 to 15.1; p = 0.012), absence of antibiotic therapy (OR, 6.7; 95% CI, 1.8 to 25.3; p = 0.0054), colonization of the upper respiratory tract by respiratory gram-negative bacilli (OR, 3.4; 95% CI, 1.1 to 10.1; p = 0.028), pack-years of smoking (OR, 2.3 for 50 pack-years; 95% CI, 1. 2 to 4.2; p = 0.012), and duration of mechanical ventilation (OR, 3. 4 for 14 d; 95% CI, 1.5 to 7.8; p = 0.0044). Several of these risk factors for ventilator-associated pneumonia appear amenable to intervention.     

The capsule biosynthetic locus of Pasteurella multocida A:1

OBJECTIVES: The purpose of this study was to investigate the progression of autonomic dysfunction in patients with Duchenne-type progressive muscular dystrophy (DMD) over time by using heart rate variability. BACKGROUND: Although previous studies suggest the presence of autonomic dysfunction in patients with DMD, the precise cause is not known. On the other hand, it is well known that analysis of heart rate variability provides a useful, noninvasive means of quantifying autonomic activity. High frequency power is determined predominantly by the parasympathetic nervous system, whereas low frequency power is determined by both the parasympathetic and sympathetic nervous systems. METHODS AND RESULTS: Frequency and time domain analyses of heart rate variability during ambulatory electrocardiographic monitoring were performed in 17 patients with DMD over a 9-year period. At the time of entry, the mean patient age was 11 years and the mean Swinyard-Deaver stage was 4. In the first year, high frequency power was significantly lower and the ratio of low frequency to high frequency was significantly higher in patients with DMD than in the normal control subjects. These differences become significantly greater as the disease progressed. At the time of entry, low and high frequency powers increased at night in both groups. However, over time, high and low frequency powers at night tended to decrease. All of the time domain parameters were significantly lower in the patients with DMD at all time points compared with the normal control subjects. CONCLUSIONS: We concluded that DMD patients have either a decrease in parasympathetic activity, an increase in sympathetic activity, or both as their disease progresses.     

The nature of antigen in the eye has a profound effect on the cytokine milieu and resultant immune response

The eye is endowed with a number of mechanisms that protect it from immune-mediated injury. One such mechanism, termed anterior chamber-associated immune deviation (ACAID), evokes the antigen-specific, systemic down-regulation of Th1 responses to antigen inoculated into the anterior chamber of the eye. ACAID has been correlated with the selective production of IL-10 by the antigen-presenting cells (APC) and the development of a cross-regulatory Th2-like response. A small subset of antigens do not induce ACAID, but instead provoke IL-12 and normal Th1 immunity. Remarkably, all soluble antigens tested are capable of inducing ACAID; only cell-associated antigens do not induce ACAID. We hypothesized that the nature of antigen plays a decisive role in the resultant immune response. This hypothesis was tested with two well-characterized antigens, ovalbumin (OVA) and SV40 large T antigen (SV40 Lg T Ag). The soluble forms of OVA and SV40 Lg T Ag induced ACAID in both in vivo and in vitro models of the eye. In contrast, the particulate forms of these antigens, i.e. OVA passively absorbed onto inert latex beads (OVA-latex) and SV40 Lg T Ag expressed in two different cell lines, 99E1 and SV-T2, did not induce ACAID in either in vivo or in vitro models of the eye. In addition, the cytokine profiles of ocular APC pulsed with OVA or OVA-latex showed that soluble OVA induced the production of IL-10, whereas OVA-latex induced the production of IL-12. These data suggest that the nature of the antigen in the eye, whether soluble or particulate, is a crucial determinant in the resultant immune response. Moreover, they suggest a mechanism in which soluble antigens preferentially induce the release of ACAID-inducing IL-10 whereas particulate antigens preferentially induce the release of Th1-inducing IL-12 by responding APC.     

Acute sensory neuronopathy: identified with electrodiagnosis and magnetic resonance imaging

We report on a 13-year-old female with idiopathic acute sensory neuronopathy mimicking a sensory form of Guillain-Barré syndrome, which was identified by using electrodiagnosis and spine magnetic resonance imaging. Motor conduction results were normal, but no sensory nerve action potentials were seen in the four limbs. On magnetic resonance imaging of the whole spine, the diffuse gadolinium enhancement of the dorsal roots in the spinal canal was detected, without evidence of intramedullary lesions. The clinical symptoms and electrodiagnostic findings had persisted for more than 18 months of follow-up.     

Chemotherapy of primary malignant brain tumors in adults

Chemotherapy of primary malignant brain tumors (PMBT) is palliative, except for germinomas. It is used as adjuvant therapy or alone at recurrence. The chemosensitivity of PMBT differs among tumors of different histological types. The role of chemotherapy in the treatment strategy will be reviewed by tumor type (malignant astrocytic gliomas, anaplastic oligodendrogliomas and mixed gliomas, anaplastic ependymomas, medulloblastomas, germinomas, primary malignant cerebral lymphoma).     

Targeted disruption of the ubiquitous CNC-bZIP transcription factor, Nrf-1, results in anemia and embryonic lethality in mice

The CNC-basic leucine zipper (CNC-bZIP) family is a subfamily of bZIP proteins identified from independent searches for factors that bind the AP-1-like cis-elements in the beta-globin locus control region. Three members, p45-Nf-e2, Nrf-1 and Nrf-2 have been identified in mammals. Expression of p45-Nf-e2 is largely restricted to hematopoietic cells while Nrf-1 and Nrf-2 are expressed in a wide range of tissues. To determine the function of Nrf-1, targeted disruption of the Nrf-1 gene was carried out. Homozygous Nrf-1 mutant mice are anemic due to a non-cell autonomous defect in definitive erythropoiesis and die in utero.