Growth hormone signalling: sprouting links between pathways, human genetics and therapeutic options.

Our molecular understanding of growth hormone-induced signal transduction has improved significantly over the past decades. At the same time, human population genetics and the analysis of genetically engineered animals have led to the discovery of genes that control specific aspects of the overall growth process. Although, currently, growth disorders are still diagnosed and treated on empirical bases, it might soon be possible to stratify patients predominantly by genetic defect, with treatment based on our molecular understanding of the role of the affected gene in the disease.     

Sympathetic skin response in scleroderma.

Examination of the sympathetic skin response (SSR) was performed in 32 patients with systemic sclerosis, morphea and mixed connective tissue disease displaying scleroderma-like features. The control group consisted of 26 healthy subjects and 12 patients with other skin diseases and asymmetrical cutaneous changes. Right and left median and tibial nerves were stimulated successively and the responses were recorded from the palms and soles simultaneously. SSR abnormalities (delayed latency, decrease and/or asymmetry of amplitude, absent response) were observed in 68.8% of the patients, most frequently in linear scleroderma. An amplitude asymmetry of the responses from upper extremities was the most characteristic pattern of abnormalities. There was no correlation between the SSR and the localization, degree and character (inclurated oedema, atrophy, sclerosis) of skin changes, the duration of the disease, symptoms of the disorder of the autonomic nervous system symptoms (vasomotor and/or sudomotor) and the changes in capillaroscopy. All patients with slow motor conduction and sensor conduction velocities (MCV and SCV) had lower SSR amplitude and the patients with prolonged skin sensory chronaxy had more often delayed latency. The results revealed presence of disturbances of the autonomic nervous system in all varieties of scleroderma, both systemic and localized forms, even without any other signs of autonomic dysfunction.     

Pentobarbital in tobacco.

The spectrometric analysis of extracts from tobacco and tobacco smoke revealed the presence of pentobarbital in the analyzed substances. Tobacco samples and tobacco smoke were extracted with chloroform, determinations were performed with the Perkin-Elmer Autosystem XL system, on a Turbo Mass spectrometer. Subject to analysis were 4 cigarette brands manufactured in Poland and raw, unprocessed tobacco. The presence of pentobarbital in the analyzed samples was confirmed by the analysis of the mass spectrum of the substance, as well as by comparison of retention time with standard of pentobarbital. The determined pentobarbital concentrations in tobacco amounted to 3-6 microg/cigarette, and in tobacco smoke they were approximately 45% lower. In case of tobacco extracts it can with high probability be excluded that pentobarbital is synthesized during chromatographical analysis. The presence of pentobarbital in tobacco is thus beyond question.     

Transfer of the distal phalange of the ring finger as a method of reconstruction of the partially amputated thumb--preliminary report]

Loss of a thumb accounts for 60% decrease of functional value of the hand, thus any attempt of it's reconstruction is a priority in the field of hand surgery. Optimal reconstructive solution for subtotal thumb amputations has not been settled. The results of partial pollicization of ring finger in 5 adult men is presented. Four patients sustained distal subtotal thumb amputation (MCP joint level), one total amputation. In three patients the distal phalange of the ring finger was transferred with the DIP joint, FDP tendon and a fragment of extensor tendon. An effective movement of a newly created thumb's IP joint was achieved in two patients. In one patient with a total thumb amputation the transfer was followed by a pollicization of the second metacarpal with remnants of proximal phalange. The postoperative course was uneventful in all of the patients. The sensitivity tested on the pulp of the transferred finger equalized to the preoperative value, the hand strength was not diminished. The cosmetic result was excellent.     

Brain uptake of radiolabeled N‐oleoyl‐dopamine in the rat

N‐acyl‐dopamines are a novel class of biologically active lipids that have recently been identified in the brain and have the potential to interact with neural signaling pathways. This study seeks to determine the ability of N‐oleoyl‐dopamine, a synthetic amide of oleic acid and dopamine, to cross the blood brain barrier. We determined the tissue content of radioactivity in selected brain regions, in a short‐run study design, following injections of [³H]N‐oleoyl‐dopamine (0.4 µCi) into the internal carotid artery in the rat. These results were compared with intracarotid injections of [³H]dopamine and with intravenous injections of both radiolabeled compounds. The level of radioactivity was determined using liquid scintillation and was expressed as the percentage of its total dose injected per gram of tissue. We found that the 15‐min brain uptake of radioactivity, with no distinct regional variations, amounted to about 6% following the intracarotid [³H]N‐oleoyl‐dopamine, which was a significant 3–4‐fold increase over that following similar administration of [³H]dopamine. Intravenous injections of [³H]N‐oleoyl‐dopamine gave a much smaller yield of radioactivity in brain tissue samples which was still severalfold greater than that for intravenous [³H]dopamine. Qualitative thin‐layered chromatography screening showed the presence of unchanged N‐oleoyl‐dopamine in the brain following injections. We conclude that N‐oleoyl‐dopamine has an appreciable ability to cross the blood‐brain barrier, which contrasts the limited transfer of dopamine alone. N‐oleoyl‐dopamine might exert physiological effects due to its known affinity for the central vanilloid receptors or to better satisfying the brain tissue demand for dopamine. The study suggests a potential pharmacological role for N‐oleoyl‐dopamine delivered exogenously in helping regulate the brain function. Drug Dev. Res. 60:217–224, 2003. © 2003 Wiley‐Liss, Inc.     

Retinal detachment in pseudophakia

Retinal detachment in an aphakic eye is a grave therapeutical problem. There exists some fears that cataract extraction with implantation of an artificial lens may increase the number of these complications. Three hundred and seventy cases of cataract extraction with implantation of an artificial lens performed in our department were analysed from the point of view of the incidence of retinal detachment. The cataract was extracted extra- and intracapsularly and the artificial lens was implanted in the anterior as well as in the posterior chamber. During the period of observation--4 months to 3 years--it was established that the number of the retinal detachment in pseudophakia was not larger than in aphakic eyes without implant.     

Effects of montelukast treatment on clinical and inflammatory variables in patients with cystic fibrosis.

BACKGROUND: In cystic fibrosis (CF), the inflammatory process contributes to progressive lung tissue damage. Cysteinyl leukotrienes have been found in the sputum of patients with CF at high concentrations sufficient to cause potent biological effects. OBJECTIVE: To evaluate the effect of anti-inflammatory treatment with montelukast sodium in patients with CF. METHODS: Twenty-six patients aged 6 to 18 years were recruited to this 20-week, randomized, double-blind, placebo-controlled, crossover trial. Patients received montelukast or placebo for 8 weeks in addition to their regular CF treatment. Before and after treatment, findings from spirometry, whole-body plethysmography, and the clinical wheezing and cough scales were evaluated. At the same time, serum and sputum samples were obtained for the measurement of eosinophil cationic protein, interleukin 10 (IL-10), IL-8, and myeloperoxidase levels. RESULTS: Twenty-three patients completed the study. Compared with placebo use, montelukast treatment significantly improved forced expiratory volume in I second, peak expiratory flow, and forced expiratory flow between 25% and 75% and significantly decreased cough and wheezing scale scores (P < .001 for all). There were no significant changes in vital capacity, thoracic gas volume, airway resistance, and residual volume after treatment. Compared with placebo use, montelukast treatment decreased serum and sputum levels of eosinophil cationic protein and IL-8, decreased sputum levels of myeloperoxidase, and increased serum and sputum levels of IL-10 (P < .001 for all). CONCLUSIONS: Montelukast may have measurable anti-inflammatory properties in patients with CF.     

Plasma levels of alpha beta peptides are altered in amnestic mild cognitive impairment but not in sporadic Alzheimer's disease

Plasma alpha beta levels have been examined in sporadic Alzheimer's disease yielding conflicting results; both no difference and an increase in plasma concentrations of alpha beta42 and alpha beta40 in sporadic cases of AD as compared to controls have been reported. Elevated plasma alpha beta42 levels may be detected several years before the onset of symptoms (in mild cognitive impairment stadium). Levels of alpha beta40 and alpha beta42 were measured in plasma from 54 patients with AD, 39 subjects with MCI and 35 controls using a commercially available ELISA. Mean plasma alpha beta42 levels were significantly higher in MCI as compared to both AD (P < 0.001) and control subjects (P < 0.001), while alpha beta40 did not differ between the groups. No correlations were observed between alpha beta levels and age, MMSE scores or gender. According to ROC curve analysis the maximum accuracy in discriminating MCI versus both controls and AD subjects has been achieved using a cut-off value of 3.8.