Cyclic analogues of Thr6-bradykinin,N8-Lys-bradykinin and endo-Lys8a-vespulakinin 1

Syntheses are described of the endo-Lys^8a-vespulakinin 1 and of cyclo-Thr⁶- and cyclo-N^ε-Lys-bradykinin. The linear peptides covering the entire sequences of endo-Lys^8a-VSK-1 and Thr⁶-BK, and the decapeptide containing all residues constituting Lys-BK, with a Arg-Lys peptide bond involving the ε-amino function of lysine, were prepared by the solid-phase procedure based on Fmoc chemistry. Cyclization was carried out by the diphenylphosphorazide method. The amino-terminal octapeptide sequence of vespulakinin 1, Fmoc-Thr(tBu)-Ala-Thr(tBu)-Thr(tBu)-Arg(Pmc)-Arg(Pmc)-Arg(Pmc)-Gly-OH, and its N^α-Boc-[(Gal β)Thr³, (Gal β)Thr⁴]-analogue, were used to prepare N^α-(1–8 VSK 1)-cyclo-N^ε-kallidin and N^α-[(Gal β)Thr³, (Gal β)Thr⁴, 1–8 VSK 1]-cyclo-N^ε-kallidin. Peptides and glycopeptides were characterized by amino-acid analysis, optical rotation, analytical HPLC and FAB-MS. Consistent with previous findings, preliminary pharmacological experiments on smooth muscle preparations showed that the cyclic, or partially cyclic, analogues were significatively less potent than the linear ones. © Munksgaard 1995.     

Can infant mortality be reduced by promoting breastfeeding? Evidence from Sao Paulo city

An ambitious breastfeeding promotion programme was launchedin Brazil in 1981 which included the use of mass media, healthpersonnel training and re-organization of health service routines.A comparison of two health surveys carried out in Greater SãoPaulo before (1981) and after (1987) the implementation of theprogramme showed an important increase in the median durationof breastfeeding from 84 to 146 days, respectively. The potentialimpact of the programme on infant mortality rates has been estimated,using the relative risks associated with breastfeeding obtainedin a case-control study in a similar urban population in southernBrazil. During this period the infant mortality rate in SãoPaulo fell by 49%. The observed change in feeding practicesmay have been responsible for a reduction of 12% of this 49%or, expressed another way, for one-quarter of the observed declinein infant mortality. The calculations suggest that the programmemay have led to reductions in deaths caused by diarrhoea of32%, in respiratory infections of 22% and in deaths due to otherinfections of 17%.     

Asystole with Syncope Secondary to Hyperventilation in Three Young Athletes

We describe three athletes who had syncope after (case 1) or during (cases 2, 3) hyperventilation. During the episode, ECG showed prolonged sinus arrest. Clinical data and noninvasive investigations were normal and the phenomenon was not reproducible. Electrophysiological study after autonomic blockade allowed a prolonged intrinsic heart rate in case 1, and abnormal corrected sinus node recovery time in cases 1 and 2. During follow-up, symptomatic sinus arrest provoked by deep inspiration occurred in case 3. These cases document prolonged asystole of unknown etiology, secondary to hyperventilation, and probably caused by different vagally-mediated mechanisms.     

The Effect of DDD Pacing on Ergospirometric Parameters and Neurohormonal Activity in Patients with Hypertrophic Obstructive Cardiomyopathy

This study examined the acute and long-term effects of DDD pacing on ergospirometric parameters and neurohormonal activity in patients with hypertrophic obstructive Cardiomyopathy (HOCM). We studied eight patients (five males), aged 56 ± 7 years, with HOCM refractory to drugs. In all patients a DDD pacemaker was implanted and programmed with an atrioventricular (AV) delay that insured full ventricular activation. The patients underwent echocardiographic examination and exercise stress testing before and 3 days, 3 months, and 12 months after pacemaker implantation. Oxygen consumption was measured at the anaerobic threshold (VO_2AT) and peak exercise (pVO₂). Atrial natriuretic peptide (ANP) and cyclic adenosine monophosphate (c-AMP) levels were measured concomitantly. Left ventricular outflow tract (LVOT) pressure gradient decreased significantly from 70 ± 18 to 25 ± 12 mmHg (P < 0.05) 3 days after pacing and remained unchanged at 3 and 12 months. pVO₂ and VO_2AT increased significantly, from 20.1 ± 3 to 23.4 ± 3 mL/kg/min and from 16 ± 3 to 17.8 ± 2 mL/kg/min, respectively (P < 0.05). This improvement continued up to 3 months, and then remained stable until the end of the 12-month follow-up period. ANP levels decreased at 3 days from 85.4 ± 5.7 to 75.4 ± 7.3 fmol/mL (P < 0.05), and remained unchanged over the 12 months. c-AMP levels did not change significantly after the onset of pacing. DDD pacing in patients with HOCM not only reduces the LVOT pressure gradient but also causes a significant early and long-term improvement in exercise capacity and neurohormonal profile.     

Technical and Clinical Problems in Patients with Simultaneous Implantation of a Cardiac Pacemaker and Spinal Cord Stimulator

Spinal cord stimulators are used to relieve pain associated with peripheral ischemia and angina pectoris. In patients with both a permanent pacemaker (PPM) and a spinal cord stimulator (SCS), electromagnetic signals from the SGS may inhibit the PPM. A bipolar PPM configuration is preferred to minimize myopotential or electromagnetic interference but patients have safely had unipolar devices implanted. We report ten patients (six males and four females; median age 73.3 years) with both a SCS and a PPM implanted between 1987–1991. Intermittent interference with one PPM (Ela Medical Model Opus 3001)was noted after an increase in the output voltage of the SCS for continued clinical efficacy. Inhibition was output voltage dependent, and reversion to the noise mode was frequency dependent. Sensitivity to both could he managed by changing the pacemaker sensitivity. Interference with pocemaker function occurred if the SCS output was set above a voltage and pulse duration which resulted in a product of these values above 1.9–2 mVs. Seven VVI, one VDD, and two DDD PPM had been implanted. In five potients hoth PPM and SCS were unipolar. In two patients the SCS was bipolar and the PPM unipolar, in two potients a bipolar PPM was associated with a bipolar SCS and with one patient, a unipolar SCS. Multiprogrammable and/or bipolar PPMs should be implanted in a patient with a SCS to allow reprogramming of the PPM and to minimize the risk of inter-device interference. Inhibition of the PPM may occur at different SCS stimulation frequencies. The frequency at which inhibition occurs varies with different models of implanted pacemaker     

Soluble interleukin-6 receptor (sIL-6R), a new prognostic factor in multiple myeloma

sIL-6R is a 55 kD soluble molecule mediating the interleukin-6 (IL-6) signal through the IL-6 receptor-associated transmembrane signal transducer, gp130. It has recently been suggested that sIL-6R serum levels may reflect disease severity in multiple myeloma (MM). We determined sIL-6R serum levels in 25 normal controls (NC) and in 80 MM patients at diagnosis and during the course of the disease. Measurements were done by ELISA. In NC, sIL-6R levels ranged from 14 to 40 ng/ml (median 28 ng/ml) whereas in MM patients the range was 10–200 ng/ml (median 38 ng/ml) ( P  < 0.01). 61 patients entered remission and 19 were resistant. Median sIL-6R value at diagnosis was 36 ng/ml (10–120) in responding patients, and 82 ng/ml (20–200) in non-responding patients ( P  < 0.001). During a follow-up from 12 to 89 months, sIL-6R values remained more or less stable in most patients. High sIL-6R levels correlated with poor survival.     

Musical preference as an indicator of adolescent drug use

Aims. This paper aims to demonstrate whether a relationship exists between adolescent drug use and identification with styles of music linked to specific youth culture. Design. Survey data were collected by researchers, under exam conditions, from two contrasting samples of Scottish secondary schoolchildren. Setting. Fieldwork was conducted in five comprehensive schools in the city of Dundee in 1994 and five comprehensive schools in the rural area of Perth and Kinross District in 1996. Participants. Questionnaires were administered to two randomly selected mixed ability classes in each of the four compulsory school years (S1 to S4), at each participating school. The eventual sample ( n= 1523) was approximately 10% of all children in these school years from the geographical areas surveyed. Measurements. Comparisons were made between life-time measures of legal and illegal drug use and current favourite style of music. Findings. Although few children in this study had ever taken the drug ecstasy (MDMA), 'fans' of rave music were more likely to have used drugs than those who preferred other styles of music. This relationship held true across a range of drugs used, across two geographical areas, over time and controlling for age, gender and parental social class. Conclusions. The paper is one of the first to quantify a possible relationship between drug use and music style. On the basis of the evidence presented, a significant relationship was found between identification with rave music and life-time drug use.