Growth hormone releasing activity by intranasal administration of a synthetic hexapeptide (hexarelin)

OBJECTIVE Hexarelin is a new synthetic growth hormone releasing peptide. We have tested the efficacy of intranasal (i.n.) administration of hexarelin to stimulate plasma GH and have compared this to the intravenous (i.v.) administration of the peptide. PATIENTS Ten children with familial short stature (FSS) aged 5·5-15·5 years and two known GH deficient patients aged 24 and 28 years without GH treatment. METHODS All 12 subjects were submitted to i.v. (1 μg/kg) and i.n. (20 μg/kg) hexarelin tests with a one-week interval between tests. Blood samples for GH, TSH, fT4 and T3 were obtained at 0, 15, 30, 60, 90 and 120 minutes. The hormone determinations were made by standard radio-immunoassays (RIA). RESULTS Both the i.n. and i.v. administration of hexarelin induced a large GH response, the mean (±SD) being 72·2± 35·5 mU/l for the i.n. test and 79·6 ± 53·0 mU/l for the i.v. test. The peak GH in the i.v. test occurred at 15–30 minutes and in the i.n. test between 30 and 60 minutes. The GH deficient patients showed no GH response In either test. Plasma TSH decreased in the FSS children from a mean (±SD) of 1.0 ± 0·26 to 0·64±0 2 mU/l (P<0 005) during the i.n. test and from 1·0±0·3 to 0·7±0·3mU/l (P> 0 05) during the I.v. test. In the isolated GH deficient patient, plasma TSH decreased from 1·06±0·38 mU/l to 0·86±0·17 during the i.v. test and from 1·60±0·01 to 1·11±0·06mU/l during the i.n. test. There were no significant changes in plasma fT4 or T3 in any of the tests. CONCLUSIONS The synthetic hexapeptide hexarelin is a potent pituitary GH stimulator when administered intra-nasally. The GH response was similar to that observed after intravenous hexarelin. Simultaneously, there was a significant decrease in plasma TSH but the concentrations remained in the normal range. These findings appear to be of theoretical and practical relevance to the investigation and management of short children.     

Functional outcome and general health status in patients after arthroscopic release in adhesive capsulitis

Frozen shoulder is said to be a self-limiting entity but full recovery often takes more than 2 years. For that, most patients are unwilling to tolerate painful restriction while awaiting resolution. We prospectively investigated 30 patients (16 women, 14 men) for the outcome of arthroscopic capsular release in idiopathic frozen shoulder. Results were determined by the assessment of subjective and objective parameters to estimate both shoulder function and general health status. Symptoms persisted without improvement for a minimum of 6 months of conservative treatment. Preoperative average American shoulder and elbow surgeons score (ASES) was 35, visual analog scale (VAS) to measure pain was 7, and simple shoulder test (SST) was 4. Mean scores of the physical component of SF-36 were considerably reduced. Mean forward elevation was 85°, average abduction was 70°, mean internal rotation was 15°, and mean external rotation was 10°. Patients were followed-up at 6 weeks, 3, 6, 12 months and by a mean of 36 months. Range of motion for all planes improved (P < 0.05). Median VAS reduced to 2, average ASES increased to 91, and SST enhanced to a mean of 10 (P < 0.05). We stated improvement of the physical components in the SF-36 questionnaire in particular bodily pain and the role-physical score. There were no significant differences between the measurements in the early postoperative phase compared to the mid-term follow-up (P > 0.05). Our results demonstrate that arthroscopic release of refractory idiopathic frozen shoulder combined with a gentle manipulation provides reliable expectations for improvement in both clinical and general health status for most patients. We recommend the use of a limb-specific and a general-health-status questionnaire to conclude the benefit of the surgical intervention and contribute the optimization of a therapy concept more effectively.     

The relationship of schools to emotional health and bullying

Objectives:  

To examine the extent to which school climate and school pressure could predict other aspects of adolescents’ lives, most particularly their emotional health and bullying. Furthermore, the study sought to investigate if these relationships were consistent across countries.     

Qualitätssicherung in der Therapie chronischen Schmerzes

Ohne Zusammenfassung The online version of the original article can be found at     

Direct automated EMIT d.a.u. analysis of N,N-dimethylformamide-modified serum, plasma, and postmortem blood for benzodiazepines, benzoylecgonine, cannabinoids, and opiates

Serum, plasma, and postmortem blood treated with two volumes of N,N-dimethylformamide (DMF) and centrifuged, were directly analyzable by means of the EMIT d.a.u. reagents on the Syva Autocarousel in the same manner as urine. Cutoff values in milligrams (immunochemically cross-reactive analyte equivalents)/L are 0.05 for morphine (MOR), 0.15 for benzoylecgonine (BZE), 0.20 for oxazepam (OX), and 0.02 for 11-nor-delta 9-tetrahydrocannabinol carboxylic acid (THCC). The relationship of concentrations (micrograms/mL serum) to absorbance changes (delta A) were S-shaped up to greater than 3.0 for MOR, 4.0 for BZE, greater than 5.0 for OX, and 0.2 for THCC. Beyond these maximal concentrations, delta A values declined. Thus, negatives should be repeated on substantially diluted aliquots to avoid missing extraordinarily high positives. "False" quantitative negative/positive noncongruence between total EMIT cross-reactives and free-drug analyses by gas chromatography/mass spectrometry (GC/MS) were 0/17 (N = 75) for opiates, 8/0 (N = 119) for cocaine products, and 19/5 (N = 103) for cannabinoids. For benzodiazepines (N = 58) the "false" negative/"false" positive ratio of EMIT (total)/high performance liquid chromatography (HPLC) (free) was 4/4. Within-day precision as coefficient of variation (CV) of quantitative estimates was 8-18%. For between-day precision, quantitative estimates varied by 8% for MOR, 15% for BZE, 18% for OX, and 34% for THCC.     

In vitro inhibition of lymphocyte proliferation by Pseudomonas aeruginosa phenazine pigments.

Human lymphocyte proliferation is inhibited in vitro in the presence of killed Pseudomonas aeruginosa or cell-free P. aeruginosa culture supernatants. A comparison of culture supernatants obtained under similar conditions from Staphylococcus aureus, Escherichia coli, P. aeruginosa, and Pseudomonas cepacia strains demonstrated that all P. aeruginosa supernatants were strongly inhibitory, whereas supernatants from other bacteria were mildly inhibitory or not inhibitory at all. These P. aeruginosa inhibitors prevent proliferative responses of resting cells upon mitogen activation and decrease [3H]thymidine uptake when added to human lymphocytes undergoing active proliferation in culture. The inhibitory effect is reversible and not due to cytotoxicity. Most of the inhibitory activity present in crude supernatants was detected in ultrafiltrates of molecular weights below 2,000. Purified P. aeruginosa pyocyanine, a low-molecular-weight phenazine pigment present in culture supernatant, was strongly inhibitory for lymphocyte proliferation. Extraction of pyocyanine and phenazine pigments from inhibitory P. aeruginosa supernatants eliminated their inhibitory activity. Inhibitors were recovered from reverse-phase chromatographic cartridges by both chloroform and methanol elution, indicating that pyocyanine and other phenazine pigments present in P. aeruginosa supernatants are responsible for the inhibition of lymphocyte proliferation. In addition to the identification of phenazine pigments as lymphocyte proliferation inhibitors, several criteria ruled out major contributions of P. aeruginosa polysaccharide, exotoxin A, and proteases to this phenomenon. P. aeruginosa strains selected for very low protease production or for very low exotoxin A production produced supernatants as inhibitory for lymphocyte proliferation as supernatants obtained from clinical P. aeruginosa isolates. Purified P. aeruginosa lipopolysaccharide and protease preparations failed to induce reversible lymphocyte proliferation inhibition. Finally, heat inactivation of P. aeruginosa supernatants at 100 degrees C for 60 min inactivates exotoxin A and proteases but produced only a moderate decrease of the inhibitory activity for lymphocyte proliferation.     

Multicolor fluorescence in situ hybridization for the simultaneous detection of probe sets for chromosomes 13, 18, 21, X and Y in uncultured amniotic fluid cells.

The most frequent aneuploidies in newborns involve the autosomes 13, 18 and 21 as well as both sex chromosomes. Fluorescence in situ hybridization readily allows the detection of numerical chromosomal aberrations throughout all stages of the cell cycle. Using a multicolor fluorescence in situ hybridization approach based on combinatorial probe labeling and digital imaging microscopy we demonstrate the simultaneous visualization of probe sets specific for chromosomes 13, 18, 21, X and Y. This approach enables one to evaluate aberrations of multiple chromosomes in a single hybridization experiment using metaphase chromosomes and interphase nuclei from a variety of cell types, including lymphocytes and amniocytes.     

Physiological Correlates of Mental Activity: Eye Movements, Alpha, and Heart Rate During Imagining, Suppression, Concentration, Search, and Choice

Rapid eye movements (REMs), EEG alpha, and tonic heart rate (HR) were measured during 6 types of cognitive tasks—imagining a liked person, suppressing thoughts of the person, searching one's mind for alternative solutions, arithmetic involving little concentration, problems involving high concentration, and choosing a preferred activity. The latter 3 required verbalization, the former 3 did not. Only suppression and search did not differ significantly from each other on at least one physiological variable. Imagining, suppression, and search yielded few REMs, high alpha, and low HR. High concentration yielded many REMs, low alpha, and high HR. Choice yielded many REMs, low alpha, and intermediate HR. Low concentration yielded few REMs, low alpha, and high HR. Suppression produced somewhat less alpha than imagining but did not differ significantly in REMs.