Diagnostic exome sequencing in children: A survey of parental understanding, experience and psychological impact.

Clinical exome sequencing (CES) is increasingly being used as an effective diagnostic tool in the field of pediatric genetics. We sought to evaluate the parental experience, understanding and psychological impact of CES by conducting a survey study of English-speaking parents of children who had diagnostic CES. Parents of 192 unique patients participated. The parent's interpretation of the child's result agreed with the clinician's interpretation in 79% of cases, with more frequent discordance when the clinician's interpretation was uncertain. The majority (79%) reported no regret with the decision to have CES. Most (65%) reported complete satisfaction with the genetic counseling experience, and satisfaction was positively associated with years of genetic counselor (GC) experience. The psychological impact of CES was greatest for parents of children with positive results and for parents with anxiety or depression. The results of this study are important for helping clinicians to prepare families for the possible results and variable psychological impact of CES. The frequency of parental misinterpretation of test results indicates the need for additional clarity in the communication of results. Finally, while the majority of patients were satisfied with their genetic counseling, satisfaction was lower for new GCs, suggesting a need for targeted GC training for genomic testing.

Pediatric laryngeal carcinoma in a heterozygous carrier of Fanconi anemia.

A case of invasive, keratinizing squamous cell carcinoma of the larynx in an 8-year-old female treated with laryngectomy is presented. Perinatal exposure to human papilloma virus and constitutional heterozygosity for a FANCC mutation were identified, though FANCC heterozygosity is not known to be cancer predisposing. An additional tumor-associated mutation in NOTCH1 was also identified potentially contributing to oncogenesis. This case illustrates an exceedingly rare type of cancer in the pediatric population and discusses diagnostic workup, evaluation of risk factors for head and neck cancer, and treatment options.

The effect of deprivation on the incidence of mandibular fractures in a British city.

AIM: To examine the relationship between social and material deprivation and mandibular fractures. METHOD: Three hundred and forty three consecutive patients who underwent mandibular fracture fixation were selected for the study. After exclusions, 290 were divided into age groups and ranked according to their Index of Multiple Deprivation (IMD) score. Rankings were determined using postcodes, and divided into quintiles for statistical analysis. RESULTS: Ages ranged from 7 to 82 with 146 (50%) patients aged between 20 and 29. Males accounted for 85% of cases. The most common site of fracture was the angle (n = 195) and assault was shown to be the most common mechanism of injury (63.3%). A strong relationship was demonstrated between fractures of the mandible and worsening deprivation, with the most striking relationship seen with fractures sustained as a consequence of assault. Females were less likely than males to sustain a fracture of the mandible as a consequence of assault; however, when assault was the mechanism of injury they were also likely to be from a deprived background. CONCLUSION: This study has demonstrated that a strong relationship exists between deprivation and the incidence of mandibular fractures in our catchment area. Fractures that resulted from interpersonal violence were shown to have a particularly strong correlation with deprivation.

Enhancement of neonatal innate defense: effects of adding an N-terminal recombinant fragment of bactericidal/permeability-increasing protein on growth and tumor necrosis factor-inducing activity of gram-negative bacteria tested in neonatal cord blood ex vivo.

Innate defense against microbial infection requires the action of neutrophils, which have cytoplasmic granules replete with antibiotic proteins and peptides. Bactericidal/permeability-increasing protein (BPI) is found in the primary granules of adult neutrophils, has a high affinity for lipopolysaccharides (or "endotoxins"), and exerts selective cytotoxic, antiendotoxic, and opsonic activity against gram-negative bacteria. We have previously reported that neutrophils derived from newborn cord blood are deficient in BPI (O. Levy et al., Pediatrics 104:1327-1333, 1999). The relative deficiency in BPI of newborns raised the possibility that supplementing the levels of BPI in plasma might enhance newborn antibacterial defense. Here we determined the effects of addition of recombinant 21-kDa N-terminal BPI fragment (rBPI(21)) on the growth and tumor necrosis factor (TNF)-inducing activity of representative gram-negative clinical isolates. Bacteria were tested in citrated newborn cord blood or adult peripheral blood. Bacterial viability was assessed by plating assay, and TNF-alpha release was measured by enzyme-linked immunosorbent assay. Whereas adult blood limited the growth of all isolates except Klebsiella pneumoniae, cord blood also allowed logarithmic growth of Escherichia coli K1/r and Citrobacter koseri. Bacteria varied in their susceptibility to rBPI(21)'s bactericidal action: E. coli K1/r was relatively susceptible (50% inhibitory concentration [IC(50)], approximately 10 nM), C. koseri was intermediate (IC(50), approximately 1,000 nM), Klebsiella pneumoniae was resistant (IC(50), approximately 10,000 nM), and Enterobacter cloacae and Serratia marcescens were highly resistant (IC(50), >10,000 nM). All isolates were potent inducers of TNF-alpha activity in both adult and newborn cord blood. In contrast to its variable antibacterial activity, rBPI(21) consistently inhibited the TNF-inducing activity of all strains tested (IC(50), 1 to 1,000 nM). The antibacterial effects of rBPI(21) were additive with those of a combination of conventional antibiotics typically used to treat bacteremic newborns (ampicillin and gentamicin). Whereas ampicillin and gentamicin demonstrated little inhibition of bacterially induced TNF release, addition of rBPI(21) either alone or together with ampicillin and gentamicin profoundly inhibited release of this cytokine. Thus, supplementing newborn cord blood with rBPI(21) potently inhibited the TNF-inducing activity of a variety of gram-negative bacterial clinical pathogens and, in some cases, enhanced bactericidal activity. These results suggest that administration of rBPI(21) may be of clinical benefit to neonates suffering from gram-negative bacterial infection and/or endotoxemia.

Life after a stroke: coping with change.

Individuals who have had a stroke must cope with many changes in their lives. Initially, the focus is on the physical changes and functional abilities; however, coping with the emotional and cognitive changes also requires attention. Changes in mental status can affect a person's rehabilitation outcomes. This study describes the predominant themes related by stroke survivors that affected their recovery. Eleven right-hemisphere stroke patients (6 women and 5 men) were interviewed four times (at 1 week, 1 month, 3 months, and 6 months) after their stroke. The descriptions of personal changes, feelings, and experiences were categorized and analyzed for recurrent themes. The major mental changes were in mood, judgment, memory, and personality. At 6 months, the predominant themes were depression, memory loss, nervousness, irritability, frustration, lack of energy, and decreased initiative. These mental changes are important for nurses to consider when planning rehabilitation goals.

Cognitive status as a predictor of right hemisphere stroke outcomes.

The care of stroke patients continues to present a challenge to health care professionals. There is evidence that the quality of life following a stroke is related to functional status and also emotional, behavioral and cognitive abilities. The purpose of this study was to examine the relationship between emotional, behavioral and cognitive status and functional activity status of stroke survivors. The sample of 15 right hemisphere stroke patients was seen at four time periods after the stroke and they were assessed using the Neurobehavioral Rating Scale (NRS) and the Barthel Functional Index (BFI). The most frequently occurring mental status changes at six months were somatic concern, memory deficit, depressive mood and mental fatigue. There was a correlation between cognitive ability and functional ability. Although there was improvement over time in the scores of the NRS and BFI, there remained sufficient cognitive impairment to affect functional ability. Findings indicated the need for nurses to assess mental status when planning rehabilitation to establish realistic goals. Further research is needed with larger samples to examine the effects of stroke outcomes on functional ability.

Comparison of the holding power of 3.5-mm cortical versus 4.0-mm cancellous orthopedic screws in the pelvis of immature dogs (cadavers).

A 3.5-mm cortical orthopedic screw was compared with a 4.0-mm cancellous screw for maximal load to failure in the pelvis of immature dogs. The pelvis from young cadavers (7 to 13 months old) was divided into hemipelves and used for testing of the 2 screw types. Two sites in each hemipelvis were used, mid-shaft of the ilium and mid-sacrum, including the wing of the ilium. The screws were extracted, and maximal load to failure and mode of failure were recorded. Maximal load to failure per millimeter of engaged thread was calculated. In either pelvic site, the 4.0-mm cancellous screw required a significantly (P < 0.05) higher pullout force per millimeter of engaged screw threads than did the 3.5-mm cortical bone screw.

Effects of auditory stimuli on comatose patients with head injury.

This descriptive study was a pilot effort to determine the effect of specific sensory input on the cortical activity of a selected population of young adults with a closed head injury. The specific research questions were (1) Does the comatose patient demonstrate a response on an electroencephalogram (EEG) to a specific auditory stimulus? (2) Does the comatose patient demonstrate other types of responses to a specific auditory stimulus? The subjects were three male and two female young adults 15 to 29 years of age who had a closed head injury as the result of an automobile accident. A similarity in depth of coma was established by using the Glasgow Coma Scale. Cortical activity was recorded by EEG at the same time that auditory stimulation was introduced to the subject. Data obtained by observation during the period of EEG recording were also included by an additional measure of the subject's response to stimulation. The findings indicate that persons in a coma do respond to auditory stimulation. The responses were varied in this small sample, but some type of response did occur. Two patients demonstrated a response on EEG and the other responded by eye opening or extremity movement. The EEG alone does not appear to be useful as a measure of response to auditory stimulus. Further work needs to be done to determine what other methods measure the response of comatose patients to auditory stimulation.

The Neurobehavioral Rating Scale: an interrater reliability study in the HIV seropositive population.

The Neurobehavioral Rating Scale (NRS) has been used in the rapid bedside assessment of closed head-injured and stroke patients in the past and has been found to be highly predictive of long-term outlook. The NRS consists of 27 items in a Likert-type scale and measures cognition and behavioral parameters of brain disease. The NRS was administered to nine human immunodeficiency virus (HIV) positive individuals in a pilot interrater reliability study. Highly significant correlations (r .94 and r .97; p less than .001) were found between interviewers. Content and construct validity had already been established in prior research. To date, no quick, easy assessment tool measuring both cognitive and behavioral manifestations in this population has been widely used. Therefore, it becomes imperative that such a tool be available to nursing staff to aid in monitoring of neurologic deterioration, assist in appropriate placement of acquired immunodeficiency syndrome (AIDS) dementia complex patients and planning of care.

Psychoneuroimmunology and AIDS.

Although PNI is a relatively new field, basic research has demonstrated the interconnectedness of immune and neurological systems, alerting nurses to the need to conduct multisystem assessments and provide holistic nursing care to persons with AIDS. Although the burden of research does not support the notion that the mind can cure AIDS, preliminary studies suggest that under certain circumstances the psychogenic and physiological conditions of the host alter rates of progression of HIV infection. Nursing research is needed to determine circumstances under which immunomodulating events alter disease progression in this population.

The neurobehavioural rating scale: assessment of the behavioural sequelae of head injury by the clinician.

To investigate the inter-rater reliability and validity of the Neurobehavioural Rating Scale at various stages of recovery after hospitalisation for closed head injury, we studied 101 head trauma patients who had no antecedent neuropsychiatric disorder. The results demonstrated satisfactory inter-rater reliability and showed that the Neurobehavioural Rating Scale reflects both the severity and chronicity of closed head injury. A principal components analysis revealed four factors which were differentially related to severity of head injury and the presence of a frontal lobe mass lesion. Although our findings provide support for utilising clinical ratings of behaviour to investigate sequelae of head injury, extension of this technique to other settings is necessary to evaluate the distinctiveness of the neurobehavioural profile of closed head injury as compared with other aetiologies of brain damage.

Family-member involvement to initiate and promote treatment of problem drinkers.

The present study evaluated a method of teaching distressed family members of problem drinkers how to minimize their own distress, reduce the drinking, increase the motivation of the alcoholic to obtain formal treatment and assist in the treatment program. Twelve concerned family members were given either community-reinforcement counseling or a traditional type of counseling (control group). The reinforcement counseling resulted in more alcoholic persons obtaining treatment than did the traditional type and a greater reduction in drinking before the formal treatment was obtained; drinking was reduced further during the joint treatment of the family members and problem drinkers. These results suggest that the drinking of unmotivated alcoholic persons can be reduced by counseling concerned family members in the use of appropriate reinforcement procedures and can lead to the initiation of formal treatment.

Alcoholism treatment by disulfiram and community reinforcement therapy.

Traditional disulfiram treatment has often been ineffective because of a failure to maintain usage. The present study with 43 alcoholics compared: (1) a traditional disulfiram treatment, (2) a socially motivated Disulfiram Assurance program and (3) a Disulfiram Assurance program combined with reinforcement therapy. About five sessions were given for each program. At the 6-month follow-up, the traditional treatment clients were drinking on most days and no longer taking the medication. The Disulfiram Assurance treatment resulted in almost total sobriety for married or (cohabitating) clients but had little benefit for the single ones. The combined program produced near-total sobriety for the single and married clients. These results indicate a promising integration of chemical, psychological and social treatment of alcoholism.

Socialization to violence among the aged.

This paper addresses the issue of the attitudinal consequences of fear and victimization by focusing on the degree to which people of different ages expresses approval of violent behavior. It is our argument that the experience of victimization socializes the individual to a view as constituting an effective strategy for resolving interpersonal conflict. Data from a national sample of the noninstitutionalized adult population of the United States support this argument, at least for respondents under 60. Older people are less likely to be victims of crime than younger persons, more likely to report fear of crime, and more disapproving of violent behavior. Older victims, however, do not evidence the same attitudinal response as younger victims. Younger victims are generally less disapproving of violence than youthful non-victims; the difference between older victims and non-victims, however, is in the opposite direction. This finding is explained as a specific instance of the lesser impact across the life cycle of period effects on attitudes.

The use of systematic encouragement and community access procedures to increase attendance at Alcoholic Anonymous and Al-Anon meetings.

A difficulty in the treatment of alcoholism is that many alcoholics referred to treatment programs never reach the referral destination, or if they do, they seldom remain involved in those programs. The present study attempted to increase participation in Alcoholics Anonymous and Al-Anon meetings. Twenty clients were selected from an outpatient mental health alcoholism treatment program and randomly assigned to either a standard referral procedure which involved giving the client information about Alcoholics Anonymous or Al-Anon; encouraging the client to attend; and providing information concerning time, date, and location of weekly meetings; or to a systematic encouragement and community access procedure which involved a phone call being made in the counseling session to a local Alcoholics Anonymous or Al-Anon member in which the member briefly talked to the client about the meeting, offered to give a ride to the client and to meet the client before the meeting and having the Alcoholics Anonymous or Al-Anon member call the client the night of the meeting to remind them of it and to encourage them to come. The results of this study showed that 100% of the experimental group attended Alcoholics Anonymous or Al-Anon within 1 week of referral and continued to attend, whereas none of the control group ever attended. The results of this study suggest that the systematic encouragement and community assess procedure are significantly more effective than standard referral systems.

Spironolactone and acute mountain sickness.

Thirteen adults trekking in Nepal in 1974 to altitudes between 4,300 m and 5,500 m remained free from acute mountain sickness while taking spironolactone as a prophylactic measure. Two years previously five of these adults trekking at similar altitudes, but without treatment, had suffered from acute mountain sickness. The regime used was spironolactone in a dosage of 25 mg three times a day for two days preceding and during the periods spent at altitudes above 3,000 m.