Neonatal hypoglycemia, Part I: Background and definition

Hypoglycemia in the neonate remains a common problem. The association of low blood glucose concentrations and abnormal development has prompted extensive research into the anticipation, evaluation, and treatment of neonatal hypoglycemia. Glucose homeostasis in the fetus and neonate is a developmentally regulated dynamic process involving a number of intricate physiologic mechanisms. In addition, the determination of glucose concentrations is dependent upon both the type of tissue analyzed and the limitations of the specific method employed. The complexity of glucose metabolism makes it difficult to precisely define "normal" and "abnormal" glucose levels in preterm and term neonates.     

Tuberculous tenosynovitis of the flexor tendons of the wrist: MR imaging with pathologic correlation

A 3-year-old child with a patent arterial duct underwent percutaneous transcatheter occlusion using Rashkind's "double umbrella" technique. The procedure, using a 17 mm device, was uncomplicated. An echocardiogram done 6 hr later showed a mobile 5 x 3 mm thrombus on the pulmonary aspect of the device. The thrombus resolved after 24 hr of intravenous heparin.     

What's new: the AHCPR guideline update on urinary incontinence

The Agency for Health Care Policy and Research (AHCPR) released their first updated guideline in March, 1996. Three documents were released: the Clinical Practice Guideline, Urinary Incontinence in Adults: Acute and Chronic Management; the Quick Reference Guide, Managing Acute and Chronic Urinary Incontinence; and the Patient Guide, Understanding Incontinence. The new areas are outlined and addressed. Unlike the 1992 version, the update emphasizes the problem of urinary incontinence (UI) in a specific population, those with chronic "intractable" incontinence. It provides an algorithm in the Quick Reference Guide for selecting appropriate behavioral, pharmacologic, and surgical treatments and supportive devices for use in managing UI. The concept of "prevention" of UI and the promotion of healthy bladder habits is introduced. The updated guideline developed recommendations for each assessment and treatment method. Specific interventions that can impact individuals with chronic "intractable" incontinence are discussed including toileting assistance programs, physical and environmental alterations, fluid and dietary management, management of nighttime voiding, and other measures and supportive care. Skin care and social and organizational environmental factors are also discussed. In August, 1996 the AHCPR released two additional, original documents, the Caregiver Guide, Helping People with Incontinence, and Alert for Directors of Nursing, which are briefly discussed.     

Factors associated with sexual behavior problems in young sexually abused children

OBJECTIVE: To identify variables associated with the presence of sexual behavior problems in young sexually abused children. METHOD: Data were gathered from the clinical records of 100 sexually abused boys and girls ages 3-7 years enrolled in two treatment programs. Information was coded systematically on approximately 350 areas related to the child and family's history and functioning, the sexual abuse experience, and treatment outcome. The children were grouped and compared according to their presenting sexual behavior into three categories: (1) developmentally "expected"; (2) "sexualized/self-focused"; and (3) problematic "interpersonal" sexual behavior. RESULTS: Bivariate and multivariate analyses highlighted five variables which were predictive of sexual behavior problems among sexually abused children. Sexual arousal of the child during his/her sexual abuse, the perpetrator's use of sadism, and a history of physical and emotional abuse differentiated between those children with and without "interpersonal" sexual behavior problems. Who the child blamed for his/her sexual abuse further contributed to the distinction between children whose sexual behavior was exclusively "self-focused" (sexualized) versus "interpersonal." CONCLUSIONS: The five major predictor variables, as well as other variables identified in this study, have potential utility in assessing child risk for negative outcomes and determining referral priorities for sexual abuse treatment. Given that sexual arousal and who the child blames for the abuse are prominent variables associated with sexual problems and self-blame, clinicians will need to ensure that sexually abused children and their caregivers are given specific opportunities to deal with these areas in the supportive context of treatment. Children with sexual behavior problems differ not only in the type and level of sexual behavior they exhibit but in most other areas as well, suggesting a need for differential assessment and individualized treatment approaches.     

Instrumented measurement of patellar mobility

To provide an objective analysis of medial and lateral patellofemoral laxity, we examined 94 uninjured athletic subjects and 22 patients with unilateral lateral patellar dislocation. We developed an instrument to measure the compliance of the medial and lateral patellar restraints. The instrument recorded the force-displacement relationship as the patella was pushed medially and laterally. Subtracting the medial displacement from the lateral displacement at a given force level allowed the tester to assess the peripatellar soft tissue "balance." The results for both the 2.5- and the 5-pound tests were significant. Paired comparisons differentiated the three groups, with significant differences between control and affected (P = 0.0001), control and contralateral (P = 0.0036), and affected and contralateral (P = 0.0157) knees. The mean result of the lateral minus medial displacement test for our sample population of control subjects was -2.1 mm for the 5-pound test. A negative value in this test indicates that medial displacement exceeds lateral displacement. This finding was present in 81% of control subjects. In contrast, the mean result for the patients' affected knees was +3.2 mm for the 5-pound test. Using the value of 0.0 mm as the diagnostic determinant for peripatellar imbalance, we found a test sensitivity of 91% and a specificity of 81%.     

Scrubbing ions with molecules: kinetic studies of chemical noise reduction in mass spectrometry using ion-molecule reactions with dimethyl disulfide

The kinetics and product distributions of the reactions of dimethyl disulfide (DMDS) have been investigated with a group of chemical background ions commonly observed in atmospheric pressure ionization (API) mass spectrometry (MS) in order to assess the value of this molecule in filtering (or "scrubbing") these ions by changing their mass/charge (m/z) ratio. The measurements were taken with a novel electrospray ionization/selected ion flow tube/QqQ tandem mass spectrometer. The background ions studied include those with m/z 42 (protonated acetonitrile, ACN), 83 (protonated ACN dimer), 99 (protonated phosphoric acid), 117 (water cluster of m/z 99), 131 (methanol cluster of m/z 99), 149 (protonated phthalic anhydride, formed from the phthalates), and 327 (protonated triphenyl phosphate). In addition, reactions of DMDS have been studied with two model analytes--protonated caffeine and doubly protonated bradykinin--in order to assess the selectivity of DMDS reactivity. All the measurements were taken at 295 +/- 2 K in helium buffer gas at a pressure of 0.35 +/- 0.01 Torr. DMDS was observed to react efficiently with m/z 42 (ACNH+), 149 (from phthalates), and 99 (protonated phosphoric acid), with k/kc=0.91, 0.47, and 0.38, respectively. Only proton transfer was observed with ACNH+, followed by the secondary reaction of [DMDSH]+ with DMDS to yield [CH3S-S(CH3)-SCH3]+. Ligation of DMDS was the dominant primary channel observed for the reaction of the m/z 149 background ion; however, some proton transfer also was observed. Both of these primary product ions react further with DMDS to yield [CH3S-S(CH3)-SCH3]+, the structure of which we have determined computationally using DFT calculations. Only the sequential ligation with two DMDS molecules was observed for the reaction of the m/z 99 ion. Reactions of DMDS with m/z 117 [H3PO4 + H + H2O]+ and m/z 131 [H3PO4 + H + MeOH]+ were observed to proceed with k/kc=0.71 and 0.058, respectively. Ligand substitution of DMDS for H2O predominated ( approximately 94%) over DMDS ligation ( approximately 6%) in the reaction with m/z 117, while only DMDS ligation was observed for the reaction of m/z 131 with DMDS. In contrast, the reactions of DMDS with ions of m/z 83 (protonated dimer of ACN) and 327 (protonated triphenyl phosphate) were extremely inefficient, with k/kc=0.0042 and 0.0079, respectively. The higher reactivity of DMDS toward ACNH+ (m/z 42) compared to (ACN)2H+ (m/z 83) is attributed to the lower proton affinity of the unsolvated ACN. The reactivity of DMDS toward the two model analyte ions studied-protonated caffeine and doubly protonated bradykinin-was negligible, with k/kc=0.0073 and 0.010, for the respective reactions. These results suggest that, under appropriate reagent pressure conditions, DMDS can be an appropriate reagent for chemically filtering out many common API-MS background ions, without significantly affecting the observed intensity of analyte peaks.     

Characterization of the signal transduction pathway activated in human monocytes and dendritic cells by MPIF-1, a specific ligand for CC chemokine receptor 1

The receptor specificity and signal transduction pathway has been identified and characterized for a truncated form of myeloid progenitor inhibitory factor-1 (MPIF-1(24-99)). MPIF-1 binds specifically to sites, in particular CCR1, shared with macrophage inflammatory protein-1alpha (MIP-1alpha) on the surface of human monocytes and dendritic cells, as inferred by its ability to compete for [125I]MIP-1alpha, but not for [125I]MIP-1beta or [125I]monocyte chemotactic protein-1(MCP-1) binding to intact cells. Based on calcium flux, MPIF-1 is an agonist on CCR1-transfected HEK-293 cells, monocytes, and dendritic cells, but not on CCR5-, CCR8-, or CX3CR1-transfected cells. The inhibitory effect of guanosine 5'-O-(3-thio-triphosphate) (GTP-gammaS) or pertussis toxin pretreatment on MPIF-1 binding and calcium mobilization, respectively, indicates the involvement of G proteins in the interaction of MPIF-1 and its receptor(s). The increase in intracellular free calcium concentration following MPIF-1 treatment is mainly due to the influx of calcium from an extracellular pool. However, a portion of the intracellular free calcium concentration is derived from a phospholipase C inhibitor-sensitive intracellular pool. MPIF-1 induces a rapid dose-dependent release of [3H]arachidonic acid from monocytes that is dependent on extracellular calcium and is blocked by phospholipase A2 (PLA2) inhibitors. Furthermore, PLA2 activation is shown to be necessary for filamentous actin formation in monocytes. Thus, the MPIF-1 signal transduction pathway appears to include binding to CCR1; transduction by G proteins; effector function by phospholipase C, protein kinase C, calcium flux, and PLA2; and cytoskeletal remodeling.     

Identification and reconstitution of an isoform of the 116-kDa subunit of the vacuolar proton translocating ATPase

We have identified a cDNA encoding an isoform of the 116-kDa subunit of the bovine vacuolar proton translocating ATPase. The predicted protein sequence of the new isoform, designated a2, consists of 854 amino acids with a calculated molecular mass of 98,010 Da; it has approximately 50% identity to the original isoform (a1) we described (Peng, S.-B., Crider, B. P., Xie, X.-S., and Stone, D.K. (1994) J. Biol. Chem. 269, 17262-17266). Sequence comparison indicates that the a2 isoform is the bovine homologue of a 116-kDa polypeptide identified in mouse as an immune regulatory factor (Lee, C.-K., Ghoshal, K., and Beaman, K.D. (1990) Mol. Immunol. 27, 1137-1144). The bovine a1 and a2 isoforms share strikingly similar structures with hydrophilic amino-terminal halves that are composed of more than 30% charged residues and hydrophobic carboxyl-terminal halves that contain 6-8 transmembrane regions. Northern blot analysis demonstrates that isoform a2 is highly expressed in lung, kidney, and spleen. To determine the possible role of the a2 isoform in vacuolar proton pump function, we purified from bovine lung a vacuolar pump proton channel (VO) containing isoform a2. This VO conducts bafilomycin-sensitive proton flow after reconstitution and acid activation, and supports proton pumping activity after assembly with the catalytic sector (V1) of vacuolar-type proton translocating ATPase (V-ATPase) and sub-58-kDa doublet, a 50-57-kDa polypeptide heterodimer required for V-ATPase function. These data indicate that the a2 isoform of the 116-kDa polypeptide functions as part of the proton channel of V-ATPases.     

Activation of protein kinase C by oxytocin inhibits the biological activity of the human myometrial corticotropin-releasing hormone receptor at term

The role of placental CRH in human pregnancy is currently unknown. The myometrium expresses CRH receptors that during pregnancy become coupled to adenylate cyclase. Oxytocin (OT) is one of the main regulators of uterine activity, acting via activation of the inositol triphosphate pathway. In view of the possible cross-talk between the CRH and OT signal transduction pathways we have sought to examine in more detail the second messenger mechanisms involved. CRH receptor binding affinity for CRH and activation of adenylate cyclase were reduced in the presence of OT in pregnant (at term, but not preterm) human myometrium. OT action was mediated via pertussis toxin-sensitive G proteins, which directly inhibit adenylate cyclase and, via activation of protein kinase C, phosphorylate the CRH receptor, leading to desensitization. Activation of protein kinase C by OT could be partially inhibited in human pregnant myometrial cells by OT antagonists (F327 and CAP476; 1 microM) or phospholipase C inhibitors (U73122; 10 microM). These results suggest that in term myometrium, CRH receptor function is modulated by OT, leading to reduced biological activity, lower cAMP levels, and a subsequent shift in favor of contractility rather than relaxation.     

Daily injections of fluoxetine induce dose-dependent desensitization of hypothalamic 5-HT1A receptors: reductions in neuroendocrine responses to 8-OH-DPAT and in levels of Gz and Gi proteins

BACKGROUND: Overall and left temporal scalp area reductions of P300 have been demonstrated in schizophrenia. P300 amplitude and topography in psychotic affective disorder, a crucial comparison in assessing the specificity of P300 abnormalities to schizophrenia, are not well studied. METHODS: P300 was recorded from 35 schizophrenic, 20 psychotic manic, and 30 control subjects. All were right-handed men. RESULTS: P300 was reduced in both psychotic groups relative to control subjects. Anteroposterior P300 topography differed between patient groups, with schizophrenic subjects showing posterior reduction and bipolar subjects showing anterior reduction. Schizophrenic subjects showed an abnormal asymmetry, with smaller P300 over the left temporal scalp site than the right. Both bipolar and control subjects showed a left greater than right asymmetry. CONCLUSIONS: Widespread auditory P300 reductions were present in schizophrenia and bipolar disorder with psychosis, but subtle topographic differences were present in the two diseases. Although unequivocal knowledge of neural generators cannot be derived from topography alone, differences in topography imply different generator configurations. Based on previous studies, the posterior P300 reductions in schizophrenia may reflect abnormalities of a generator located in the left superior temporal gyrus. The frontal reductions in bipolar psychosis may reflect abnormalities in a hypothetical frontal generator, consonant with reports of altered frontal lobe function in mania.