The investigation of factors underlying deficits in self-awareness and self-regulation

Primary objective : To examine a theoretical model which suggests that a contribution of both psychological and neuropsychological factors underlie deficits in self-awareness and self-regulation.

Research design : Multivariate design including correlations and analysis of variance (ANOVA).

Methods : Sixty-one subjects with acquired brain injury (ABI) were administered standardized measures of self-awareness and self-regulation. Psychological factors included measures of coping-related denial, personality-related denial and personality change. Neuropsychological factors included an estimate of IQ and two measures of executive functioning that assess capacity for volition and purposive behaviour.

Main outcomes and results : The findings indicated that the relative contribution of neuropsychological factors to an outcome of deficits in self-awareness and self-regulation had a more direct effect than psychological factors. In general, measures of executive functioning had a direct relationship, while measures of coping-related and personality-related denial had an indirect relationship with measures of self-awareness and self-regulation.

Conclusion : The findings highlighted the importance of measuring both neuropsychological and psychological factors and demonstrated that the relative contribution of these variables varies according to different levels of self-awareness and self-regulation.     

Tone burst-evoked myogenic potentials in human neck flexor and extensor

Vestibular evoked myogenic potential (VEMP) has been proposed to be a manifestation of sacculocollic reflex. In a recent study using intracellular recording from neck flexor and extensor motoneurons, the neuronal connections and pathways underlying sacculocollic reflexes were determined in cats. The results showed that sacculocollic reflex displayed inhibitory connection to bilateral neck flexors and excitatory connection to bilateral neck extensors. A total of 16 normal young adults were tested with bilateral recordings of sternocleidomastoid (SCM) and splenius capitis (SC) muscles by acoustic stimulus of 500 Hz short tone burst. The results revealed that polarity of the wave I/II of VEMP on SC was the reverse of that on SCM. This implied that VEMP from ipsilateral SCM showed inhibitory neural activity; whereas VEMP from ipsilateral SC was an excitatory response. Using this non-invasive technique, the sacculocollic reflexes in human neck flexor and extensor were studied. The results in humans were consistent with the previous findings in cats.     

Early and prolonged intravenous immunoglobulin replacement therapy in childhood agammaglobulinemia: a retrospective survey of 31 patients

OBJECTIVE: To evaluate the outcome of children who received prolonged intravenous immunoglobulin (IVIg) replacement therapy early in life for X-linked agammaglobulinemia (XLA). STUDY DESIGN: We performed a retrospective study of the clinical features and outcome of patients with genetic and/or immunologic results consistent with XLA. Patients receiving IVIg replacement therapy within 3 months of the diagnosis and for at least 4 years between 1982 and 1997 were included. RESULTS: Thirty-one patients began receiving IVIg replacement therapy at a median age of 24 months and were followed up for a median time of 123 months. IVIg was given at doses >0.25 g/kg every 3 weeks, and mean individual residual IgG levels ranged from 500 to 1140 mg/dL (median, 700 mg/dL). During IVIg replacement, the incidence of bacterial infections requiring hospitalization fell from 0.40 to 0.06 per patient per year (P <. 001). However, viral or unidentified infections still developed, including enteroviral meningoencephalitis (n = 3) causing death in one patient, exudative enteropathy (n = 3), and aseptic arthritis (n = 1). At last follow-up, 30 patients were alive at a median age of 144 months (range, 58 to 253 months). Among 23 patients who were evaluated by respiratory function tests and computed tomography, 3 had an obstructive syndrome, 6 had bronchiectasis, and 20 had chronic sinusitis. CONCLUSION: Early IVIg replacement therapy achieving residual IgG levels >500 mg/dL is effective in preventing severe acute bacterial infections and pulmonary insufficiency. More intensive therapy may be required to fully prevent the onset of bronchiectasis, chronic sinusitis, and nonbacterial infections, particularly enteroviral infections, in all cases.     

Ask, advise, assist: pediatricians and passive smoke exposure.

The objectives of this study were to determine: (1) how frequently pediatricians obtain a history of passive smoke exposure (PSE), (2) what type of advice regarding PSE they offer and how frequently they offer it, and (3) what methods and what assistance they believe would be useful to reduce PSE. A random sample of 1,000 US members (GEN) of the American Academy of Pediatrics (AAP) and all 724 members of the AAP sections of pulmonology, otolaryngology, and allergy (SPECS) were sent a questionnaire. Seven hundred fifty-five usable questionnaires were returned. Ninety-six percent of 321 general pediatricians obtained a PSE history at least "sometimes" but were much more likely to "always" do so when seeing a patient with asthma (87%) or recurrent otitis media (56%) than during well-child visits (41%) (p < 0.0001). Ninety-eight percent of pulmonologists and 95% of allergists "always" obtained a PSE history from parents of their asthmatic patients as compared with generalists who reported doing so 87% of the time (p = 0.0004). Fifteen percent of GEN gave specific assistance to parents with smoking cessation such as referral to an internist or family practitioner or a community agency or initiating a smoking cessation program themselves, whereas 85% gave only nonspecific advice such as, "don't smoke around the child," or "quit smoking." Reasons for not initiating a cessation program included lack of skills (38%) or time (36%) or a belief that it was "not their responsibility" (13%). Pediatricians indicated that brochures for parents that describe the hazards of PSE and contain specific information regarding how to refer to community smoking cessation programs would be of most use to them in helping parents reduce PSE to their children. Pediatricians frequently ask about PSE and advise reducing it but seldom assist parents with specific advice regarding effective methods to quit smoking.     

Clinical utility of liver biopsy in children with acquired immunodeficiency syndrome

BACKGROUND: Little is known about hepatic histology in children with AIDS, although the liver is frequently involved in the course of HIV infection. The clinical utility of liver biopsy in these patients is not well-defined. We reviewed retrospectively the results of this procedure in a group of infected children better to delineate its indications. PATIENTS AND METHODS: Eighteen children with AIDS underwent liver biopsy in our institution. The indications were unexplained fever in eight children, six of whom had an elevated erythrocyte sedimentation rate and clinical suspicion of mycobacterial infection; jaundice in four; suspicion of drug toxicity (dideoxyinosine) in two; discussion of treatment for chronic hepatitis B in three; suspicion of cytomegalovirus infection in one who had also AIDS cholangiopathy. RESULTS: Of the six children thought to have mycobacterial infection, two had the disease on biopsy, both of whom had abnormal liver enzymes. The children with unexplained fever had nonspecific findings, except for one with lymphoid interstitial pneumonitis who had a dense lymphoid infiltrate. Of the four with jaundice two had extensive necrosis caused by adenovirus infection in one and suspected herpes simplex infection in the other. The other two with jaundice had unexplained findings, severe necrosis and fibrosis in one case and hemophagocytosis in the other one; both improved clinically. Both children with suspected dideoxyinosine hepatotoxicity had nonspecific findings. The three children with chronic hepatitis B had mild lesions that were not an indication for treatment. CONCLUSIONS: Liver biopsy appeared to be useful in two groups of selected children with AIDS: when there is strong clinical suspicion of mycobacterial infection; and when the child is jaundiced.     

Late events in pediatric patients with Ewing sarcoma/primitive neuroectodermal tumor of bone: the Dana-Farber Cancer Institute/Children's Hospital experience

The outcome for 82 pediatric patients with Ewing sarcoma (ES) and primitive neuroectodermal tumor (PNET) of bone is reported; the patients were treated at the Dana-Farber Cancer Institute (DFCI) and Children's Hospital (CH) in Boston, MA (USA) from 1971-1988. The charts of all patients with ES/PNET of bone treated during this period were reviewed for disease status, therapy, sites of relapse, information on second malignancies, and survival status. Eighty-two patients with ES/PNET of bone treated at DFCI/CH were identified. The 10-year event-free survival (EFS) rates were 12% (95% confidence interval [CI] 0, 27%) and 38% (95% CI 26, 51%) for patients with and without metastases, respectively (P = 0.002); the overall survival (OS) rates were 17% (95% CI 1, 33%) and 48% (95% CI 35, 61%) for patients with and without metastases (P = 0.001). Median follow-up for surviving patients is 10.2 years. Primary site in the pelvis also was associated with a poor outcome for patients with no metastatic disease (P = 0.006 OS, P = 0.03 EFS). Thirty-one patients survived in first remission at least 5 years from diagnosis, and of these, five experienced relapse of original disease, and five experienced secondary malignancies. Pediatric patients treated for ES/PNET of bone remain at risk for life-threatening events into the second decade of follow-up. After 5 years, the risk of second malignant neoplasm is at least as high as the risk of late relapse. Prolonged follow-up of patients with ES and PNET of bone is indicated.     

Variations in genetic assessment and recurrence risks quoted for childhood deafness: a survey of clinical geneticists

We report here the results of a questionnaire survey of consultant clinical geneticists in the United Kingdom to which we had an 81% response rate. In this questionnaire we asked about: (1) the nature of services currently offered to families with hearing impaired children, (2) what recurrence risks they quoted in isolated non-syndromic cases, and (3) what they might suggest for improving the range of genetic services available at present. We noted great variation both in these services and in the recurrence risks quoted in isolated cases. Based on the results of the questionnaire, we have proposed a protocol for the investigation of permanent childhood hearing impairment, which we believe to be both comprehensive and practical in an outpatient clinic setting. It is only by improving existing clinical and social understanding and knowledge of childhood hearing impairment that it will become possible to use recent molecular advances to develop comprehensive and consistent services for these families.     

The effects of oxidizing and cysteine-reactive reagents on the inward rectifier potassium channels Kir2.3 and Kir1.1

The inwardly rectifying potassium channel Kir2.3 possesses extracellular cysteine residues at positions 113, 140, and 145, as well as at position 79 near the outer membrane boundary. In this study, we have investigated the roles of these extracellular cysteine residues in mediating inhibition of the Kir2.3 channel by the cysteine-reactive reagents para-chloromercuribenzenesulphonate (PCMBS) and thimerosal, and the oxidizing agent hydrogen peroxide (H2O2). We have also compared the effects of these reagents with those on Kir1.1 channels (which do not possess cysteine residues equivalent to 140 and 79 in Kir2.3 channels). Mutant channels were made in which cysteine residues were mutated to serine by site-directed mutagenesis. Wild-type or mutant cRNA was injected into Xenopus oocytes and voltage-clamp recordings made 1-2 days later. Wild-type Kir2.3 currents were significantly inhibited by PCMBS, thimerosal and H2O2. Currents for mutants Kir2.3 C79S and C140S were also inhibited by PCMBS, thimerosal and H2O2. These mutations affected the time course of inhibition by all three reagents. For PCMBS, a slow component of inhibition was absent for the C79S mutation, and a fast component was absent for C140S. For the double mutation C79S/C140S, PCMBS no longer had any effect. For thimerosal, there was a slower time course for C140S, a faster time course for C79S, and a delayed onset for C79S/C140S. For H2O2, the main effect was a delayed onset for the double mutant. The reducing agent dithiothreitol (DTT) reversed the inhibition by both PCMBS and thimerosal of wild-type and mutant currents, but not the inhibition due to H2O2. Finally, wild-type Kir1.1 currents were not significantly inhibited by the applications of either PCMBS or thimerosal, while H2O2 produced small inhibition. The results taken together indicate that inhibition by the cysteine-reactive reagent PCMBS is mediated through cysteine residues 79 and 140 in Kir2.3 channels, with C79 mediating a slow component of inhibition and C140 a faster component, and that both residues are extracellularly exposed. The data indicate that these two cysteine residues are also main sites for inhibition by thimerosal and H2O2 but, unlike for PCMBS, an additional non-extracellular inhibitory site(s) must also be involved.