Specific gene blockade shows that peptide nucleic acids readily enter neuronal cells in vivo

Peptide nucleic acids (PNAs) are DNA analogs that can hybridize to complementary sequences with high affinity and stability. Here, we report the first evidence of intracellular delivery of PNAs in vivo. Two CNS receptors, an opioid (mu) and a neurotensin (NTR-1), were targeted independently by repeated microinjection of PNAs into the periaqueductal gray. Behavioral responses to neurotensin (antinociception and hypothermia) and morphine (antinociception) were lost in a specific manner. Binding studies confirmed a large reduction in receptor sites. The loss of behavioral responses was long lasting but did fully recover. The implications of specifically and readily turning off gene expression in vivo are profound.     

Dermatomyositis with subclinical myositis and spontaneous pneumomediastinum with pneumothorax: case report and review of the literature

Dermatomyositis (DM) is a clinical entity characterized by a distinctive cutaneous rash and inflammatory myopathy. Besides skin and muscle, the disease can also involve other internal organs, especially the lungs. We describe a patient with dermatomyositis and incomplete signs of myositis who developed pneumomediastinum, pneumothorax and massive subcutaneous emphysema. This case illustrates a rare pulmonary complication of DM, and underscores that muscular involvement in this disease is not always reflected in laboratory and/or histological abnormalities.     

Personality traits and the development of nicotine, alcohol, and illicit drug disorders: Prospective links from adolescence to young adulthood.

The personality traits constraint (CN) and negative emotionality (NE) have been more (CN) or less (NE) consistently associated with alcoholism. The authors examined the association of personality at age 17 with timing of onset and with prospective prediction of nicotine, alcohol, and illicit drug disorders 3 years later in a twin sample (569 females; 432 males). Earlier onset of alcohol and drug disorders (by age 17) was related to significantly lower CN compared with later onsets (by age 20); high NE was related to either onset. NE, as well as CN, uniquely predicted new onsets of all 3 types of substance use disorders by follow-up, with preexisting substance disorders taken into account. Personality traits confer generalized risk for developing any substance disorder, though some traits are more strongly linked with some substance disorders than with others. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Frequency, causes, and outcome of home ventilator failure

STUDY OBJECTIVES: The safety of home ventilators has been questioned. We collected data to study the following: frequency of home ventilator failure, apparent causes for the failure or malfunction, and adverse consequences following the failure. STUDY DESIGN: Information on all requests to correct home ventilator failures reported to a home respiratory equipment vendor was collected prospectively between November 1991, and November 1992. PATIENTS: There were 150 ventilator-assisted patients aged 2 to 77 years; 44 were < or = 18 years. They received 841,234 h of home mechanical ventilation (average, 15.4 h/d per ventilator-assisted patient). RESULTS: There were 189 reports of home ventilator failure. Defective equipment or mechanical failure was found in only 39% (73 reports), equivalent to one home ventilator failure for every 1.25 years of continuous use. Other causes of ventilator failure included the following: improper care, damage, or tampering with the ventilator by caregivers (13%), functional equipment improperly used by caregivers (30%), and equipment functional but the patient's condition changed, mimicking ventilator failure (3%). No problem could be identified in 16%. The following actions were required: ventilator replacement (44%), repair of a defective part (6%), replacement of a functioning ventilator for psychological comfort (14%), ventilator adjustments made (21%), caregiver reeducation (7%), caregiver anxiety or distress reduced (3%), and no action required (4%). Hospitalization was required only in two cases (1%). No adverse outcomes, deaths, or serious injuries were associated with home ventilator failure. CONCLUSIONS: We conclude that in 150 patients requiring home mechanical ventilation, ventilator failure occurred relatively infrequently, and there were no adverse outcomes as a result of equipment failure at home. We speculate that equipment failure is not a frequent or serious problem for ventilator-assisted patients treated at home.     

Biochemical hallmarks of tyrosine hydroxylase deficiency

We report the biochemical hallmarks of tyrosine hydroxylase deficiency with emphasis on reliable diagnostic strategies of four new cases of an inborn error of tyrosine hydroxylase (TH). Three of our patients from different parts of the Netherlands were found homozygous for a mutation in exon 6 (G698A) of the TH gene, and one patient was found compound heterozygous for the same mutation and an additional mutation in exon 3. The first clinical symptoms of hypokinesia, rigidity of arms and legs and axial hypotonia, developed between 3 and 7 months of age. Cerebrospinal fluid investigations revealed a characteristic metabolite constellation in every case: low homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylethyleneglycol concentrations in the presence of normal reference range 5-hydroxyindolacetic acid concentrations. Strict adherence to a standardized lumbar puncture protocol and adequate age-related reference values are essential for diagnosis of this "new" treatable neurometabolic disorder. Urinary measurements of HVA, vanillylmandelic acid, and catecholamines can lead to false-negative conclusions. All patients showed a remarkable clinical improvement on a low dose of L-dihydroxyphenylalanine/ (S)-2-(3,4-dihydroxybenzyl)-2-hydrazinpropionic acid. During treatment, cerebrospinal fluid HVA, and 3-methoxy-4-hydroxy-phenylethyleneglycol increased substantially.     

Bone healing capacity of titanium plasma-sprayed and hydroxylapatite-coated oral implants

The authors report preliminary results of Brief Supportive Psychotherapy (BSP) in the Beth Israel Brief Psychotherapy Program for a sample with primarily Cluster C Axis II disorders. This study compares 24 patients treated with BSP with 25 patients treated with Short-Term Dynamic Psychotherapy (STDP). STDP was chosen because its confrontational methods contrast dramatically to BSP, which emphasizes building self-esteem, reducing anxiety, and enhancing coping mechanisms. Videotaped therapies were based on manualized 40-session protocols. Similar degrees of improvement were seen in BSP and STDP at termination and at 6-month follow-up. A study of therapeutic alliance in BSP showed stable and high levels of alliance in good-outcome cases and more variability in poor-outcome cases. These preliminary findings are consistent with other studies and suggest supportive psychotherapy may be effective for many patients, leading to significant and lasting change.     

The prevalence of antibiotic-resistant faecal Escherichia coli in healthy volunteers in Venezuela

Faecal samples were collected from healthy volunteers in two regions in Venezuela, the village of Grulla (n = 195) and the city of Mérida (n = 181), and analysed for the prevalence of antibiotic resistant faecal Escherichia coli as well as the antibiotic susceptibility of the strains isolated. The highest prevalences of resistance were observed for amoxicillin, oxytetracycline, sulfamethoxazole and trimethoprim. The percentages found for Grulla were 46, 38, 44 and 30%, respectively; for Mérida 39, 65, 56 and 36%, respectively. In Mérida, a significantly higher prevalence of resistance for oxytetracycline was found (P < 0.05). Significant differences in the distribution of the MIC values between Grulla and Mérida were observed for amoxicillin, chloramphenicol and oxytetracycline (P < 0.05). In Grulla, the most frequent pattern was resistance to amoxicillin only and in Mérida to oxytetracycline only. Amoxicillin resistance was due to production of TEM1 beta-lactamase.     

A new subtype of diabetes mellitus: maternally inherited diabetes and deafness (MIDD)

Diabetes mellitus comprises many subtypes, the pathogenesis of each of which involves a combination of inherited and environmental factors. Recently a new subtype of diabetes mellitus was recognized in a Dutch pedigree, designated as 'maternally inherited diabetes and deafness' (MIDD). Impaired hearing is an associated phenomenon of the disease. Approximately 1.3% of all diabetic cases in the Netherlands exhibit the MIDD subtype. MIDD shows a strictly maternal heredity. In MIDD there is a guanine-for-adenine substitution at position 3243 in mitochondrial DNA. Mitochondria carrying this mutation exhibit a decreased functionality. In carriers of the MIDD mutation the insulin secretion by the pancreas in response to stimulation by glucose is impaired.     

Fear, Conditioning, and Aging: Theoretical Comment on LaBar et al. (2004).

Age-related impairments in associative learning have been found in studies using classical conditioning of motor responses. However, it is as yet unclear whether conditioning of fear responses is similarly affected by aging. K. S. La Bar et al. (2004; see record 2004-19432-004) aimed to address this issue by studying age effects on fear conditioning applying a discrimination paradigm. Considering these results, this commentary discusses methodological issues in investigating fear conditioning as well as similarities and differences between associative learning of motor and autonomic responses with respect to neuronal substrates, susceptibility to aging, and the role of awareness of stimulus contingencies in mediating aging effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)