Conformational investigation of α, β-dehydropeptides. VIII.*N-Acetyl-α, β-dehydroamino acid N'-methylamides: conformation and electron density perturbation from infrared and theoretical studies

The Fourier transform infrared spectra are analyzed in the regions of v_s(N-H), amide I, amide II and v_s(C^α=C^β) bands for a series of Ac-ΔXaa-NHMe, where ΔXaa =ΔAla, (Z)-ΔAbu, (Z)-ΔLeu, (Z)-ΔPhe and AVal, to determine the predominant solution conformation of these α, β-dehydropeptide-related molecules and the electron distribution perturbation in their amide bonds. The measurements were performed in dichloromethane (DCM). To confirm and rationalize the assignments, the spectra of the respective series of saturated Ac-Xaa-NHMe, recorded in DCM, and the spectra of these two series of unsaturated and saturated compounds, recorded in acetonitrile, were examined. To help interpret the spectroscopic results, the equilibrium geometrical parameters for some selected amides were used. These were optimized with ab initio methods in the 6-31G** basis set. Each of the dehydroamides studied adopted a C₅ structure, which in Ac-ΔAla-NHMe is fully extended and accompanied by the strong C₅ hydrogen bond. Interaction with the C^α=C^β bond lessened the amidic resonance within each of the flanking amide groups. The N-terminal C=O bond was noticeably shorter, both amide bonds were longer than the corresponding bonds in the saturated entities and the N-terminal amide system was distorted. Ac-ΔAla-NHMe constituted an exception. Its C-terminal amide bond was shorter than the standard one and both amide systems were prototypically planar.     

Aggravating Process Induced by Indomethacin on Chronic Gastric Lesion in Rat. Role of Polymorphonuclear Leucocytes

The present study examines the indomethacin-provoked aggravation of chronic ulceration induced by acetic acid in rats. The drug was administered in a single dose, 7 and 14 days after provocation of ulceration. The changes induced by indomethacin in other groups of animals that had been treated for 7 and 14 days with hydroxyurea (which provokes a marked leucopenia) were also studied. The results obtained demonstrate that indomethacin does not significantly modify the macroscopic index of ulceration nor vascular permeability in the majority of the groups tested. Only in the group that received hydroxyurea for 14 days was there an increase in both parameters. Myeloperoxidase activity was assayed and used as an index of leucocyte infiltration in an attempt to relate the increase in this activity with a gastrolesive effect. Application of acetic acid produced a significant increase in this activity 7 days after induction of chronic injury. Administration of hydroxyurea intraperitoneally was associated with a decrease in the severity of chronic ulceration and neutrophil infiltration into the gastric mucosa. This effect was detectable enzymatically and microscopically. The groups that received indomethacin showed an increase in myeloperoxidase activity, although this increase was only significant in the animals treated with hydroxyurea for 7 and 14 days. The results suggest that the aggravation provoked by indomethacin is greater when the ulcer curing process is more advanced.     

Review article The use of botulinum toxin in the alimentary tract

New and future indications for the treatment of disorders of the alimentary tract using local injections of botulinum toxin are reviewed. Clinical experience shows that overactive smooth muscle sphincters may be weakened to treat disorders such as achalasia or chronic anal fissure. By contrast, injections placed into the sphincter of Oddi have proven less effective for post-cholecystectomy pain syndrome. Experimental evidence suggests that food intake may be reduced by weakening the distal stomach with botulinum toxin. This approach may possibly lead to the treatment of obesity. There are some new possible indications for the use of botulinum toxin on the alimentary tract, and infantile hypertrophic pyloric stenosis seems to be the most promising new development.     

Improvement of survival in Duchenne Muscular Dystrophy: retrospective analysis of 835 patients

Duchenne Muscular Dystrophy (DMD) is the most common muscle disease in children. Historically, DMD results in loss of ambulation between ages 7 and 13 years and death in the teens or 20s. In order to determine whether survival has improved over the decades and whether the impact of nocturnal ventilation combined with a better management of cardiac involvement has been able to modify the pattern of survival, we reviewed the notes of 835 DMD patients followed at the Naples Centre of Cardiomyology and Medical Genetics from 1961 to 2006. Patients were divided, by decade of birth, into 3 groups: 1) DMD born between 1961 and 1970; 2) DMD born between 1971 and 1980; 3) DMD born between 1981 and 1990; each group was in turn subdivided into 15 two-year classes, from 14 to 40 years of age. Age and causes of death, type of cardiac treatment and use of a mechanical ventilator were carefully analyzed.The percentage of survivors in the different decades was statistically compared by chi-square test and Kaplan-Meier survival curves analyses. A significant decade on decade improvement in survival rate was observed at both the age of 20, where it passed from 23.3% of patients in group 1 to 54% of patients in group 2 and to 59,8% in patients in group 3 (p < 0.001) and at the age of 25 where the survival rate passed from 13.5% of patients in group 1 to 31.6% of patients in group 2 and to 49.2% in patients in group 3 (p < 0.001).The causes of death were both cardiac and respiratory, with a prevalence of the respiratory ones till 1980s. The overall mean age for cardiac deaths was 19.6 years (range 13.4-27.5), with an increasing age in the last 15 years. The overall mean age for respiratory deaths was 17.7 years (range 11.6-27.5) in patients without a ventilator support while increased to 27.9 years (range 23-38.6) in patients who could benefit of mechanical ventilation.This report documents that DMD should be now considered an adulthood disease as well, and as a consequence more public health interventions are needed to support these patients and their families as they pass from childhood into adult age.Key words: Duchenne, survival, cardiomyopathy     

THE INCIDENCE OF SKIN DISEASES IN THE WEST OF SCOTLAND

SUMMARY. A survey of dermatological out-patients in 2 large Glasgow hospitals from 1955ndash;64 is reported.
The incidence of common diseases is analyzed in detail and changes in incidence are indicated and discussed. *
Earlier surveys in Glasgow and comparable recent surveys in other cities are reviewed.
The need for an internationally acceptable nomenclature for common diseases, without unproven aetiological implications, is emphasized.     

Dermoscopic Features of Difficult Melanoma

BACKGROUND: The dermoscopic diagnosis of cutaneous melanoma (CM) may be difficult because some CM lack specific dermoscopic features for melanoma diagnosis. OBJECTIVE: To evaluate whether a diagnosis of CM could be achieved using the classic dermoscopic melanoma-specific criteria, we conducted a retrospective multicenter study of 508 CM samples. METHODS: All the dermoscopic images were analyzed to identify the dermoscopic criteria found in dermoscopically difficult melanomas (DDM) and to examine the possible relation of dermoscopic diagnosis with respect to the difficulty of the dermoscopic diagnosis and the melanoma thickness. RESULTS: A significant percentage of melanomas, 89 of 508 (17.5%), were DDM. The criteria leading to a significant increased risk of DDM were presence of streaks [odds ratio (OR), 2.26; 95% confidence interval (CI), 1.15-4.47), absence or presence of regular pigmentation (OR, 3.41; 95% CI, 1.70-6.85), absence of a blue-whitish veil (OR, 4.04; 95% CI, 2.33-6.99), absence of regression structures (OR, 4.31; 95% CI, 2.42-7.66), and the presence of hypopigmentation (OR, 2.61; 95% CI, 1.49-4.58). CONCLUSION: A significant number of melanomas defy even dermoscopic diagnosis. Only a meticulous comparative and interactive process based on an assessment of all the individual's other nevi ("ugly ducking" sign) and a knowledge about recent changes can lead to the recognition of DDM.     

Systematic reviews of psychosocial interventions for autism: an umbrella review

Aim  A wide range of psychosocial interventions for the treatment of individuals with autism-spectrum disorders (ASDs) have been evaluated in systematic reviews. We conducted an umbrella review of systematic reviews of the effectiveness of psychosocial interventions for ASD.
Method  Comprehensive searches were conducted in 25 bibliographic databases, relevant journals and reference lists up to May 2007. Studies included were systematic reviews on any psychosocial intervention for individuals with ASDs. Two reviewers independently assessed study relevance and quality.
Results  Thirty systematic reviews were included. The majority of reviews evaluated interventions based on behavioural theory ( n =9) or communication-focused ( n =7) therapies. Positive intervention outcomes were reported in the majority of the reviews. Methodological quality of the reviews was generally poor.
Interpretation  The reviews reported positive outcomes for many of the interventions, suggesting that some form of treatment is favourable over no treatment. However, there is little evidence for the relative effectiveness of these treatment options. Many of the systematic reviews had methodological weaknesses that make them vulnerable to bias. There is a need for further systematic reviews that adhere to strict scientific methods and for primary studies that make direct comparisons between different treatment options.