Synthesis of a potent agonist of substance P by modifying the methionyl and glutaminyl residues of the C-terminal hexapeptide of substance P

Analogues of [Orn⁶]-SP_6-11 have been synthesized in which the Met¹¹ residue is replaced by glutamate γ-alkylesters. These analogues were tested in three in vitro preparations representative of NK-1, NK-2, and NK-3 receptor types. Substitution of the SCH₃ group of the Met¹¹ side chain by a COOR (R = methyl, ethyl, n-propyl, n-butyl, cyclohexyl) group results in analogues which are full agonsists in NK-1 and NK-2 preparations but show little agonist activity in the NK-3 preparation. When the SCH₃ group is replaced by a t-butyl ester group and the resulting analogue is a full agonist in all the above preparations and more active than the parent hexapeptide and SP-OCH₃ at NK-1 receptors. It is concluded that for activity at NK-1 receptors methionine can be replaced by γ-t-butyl glutamate without loss of activity, whilst at NK-2 and NK-3 receptors the above substitution increases the activity of [Orn₆]-SP_6-11. Other γ-alkyl esters of the glutamic acid reduce its biological activity.     

A possible explanation for the increased referral of atopic dermatitis from the Asian community in Leicester

The population of the city of Leicester contains, in addition to the ‘native’ popuiation. a large immigrant ‘Asian’ community originating from the Indian subcontinent. Among referrals to our department, atopic dermatitis (AD) was 3·3 times more common in Asians. We therefore performed a study based on a cohort of consecutive births in Leicester hospitals to investigate the possible ethnic difference in prevaience and to examine possible reasons for an ethnic difference in referral pattern. Parents of 1800 children were asked at the time of the birth to allow their child to be entered on a register. A year later, parents of a sample of 499 of these children, 158 Asian and 341 non-Asian, were invited for interview and for examination of the children. A total of 413 children were examined. The overall point prevalence of AD was 10.7% (95% confidence interval, 7·7%–13·7%). There was no significant ethnic difference. However, a history of eczema in a first degree relative was found in 14·2% of Asian subjects and 35·1% of non-Asians (P < 0.0001, chi-square test). The data suggest the increased referrals to our clinic from the Asian community may result from a lower level of familiarity with AD.     

Malposition of Transvenous Pacing Lead in the Left Ventricle

Malposition of pacemaker leads has been described in several locations but rarely in the left ventricle. The incidence and clinical course of this pacemaker complication are unknown. We describe clinical, electrocardiographic, chest X ray, and echocardiographic findings in four patients in whom the transvenous pacing lead was inadvertendy placed through the interatrial septum and mitral valve into the left ventricle, in these patients, lead misplacement was not recognized at the time of implantation and lead malposition was diagnosed a mean of 2 years later. All four patients had right bundle branch block configuration paced complexes. In retrospect, chest X rays suggested atypical lead position in all, but the initial posterioranterior and lateral chest X rays were misinterpreted and contributed to the delay in diagnosis. When lead misplacement in the left ventricle was considered it was confirmed by two-dimensional echocardiography. One patient subsequently presented with a stroke and the remainder were diagnosed when they presented with other unrelated problems. Pacing thresholds were normal at the time of implantation and behaved normally during follow-up. The patient presenting with stroke was anticoagulated and the other three have been managed expectantly without anticoagulafion. Diagnosis of left ventricular lead malposition is not difficult but requires a high index of suspicion. A 12-lead ECC and posterior-anterior and lateral chest X rays after implantation can be diagnostic. Patients with pacing lead in the left ventricle may remain asymptomatic with normal lead function during long-term follow-up. Anticoagulation should be considered when this problem comes to attention for the first time during follow-up.     

Treatment of Patients with Prior Exit Block Using a Novel Steroid-Eluting Active Fixation Lead

An increased interest has developed in active fixation leads for several reasons. Exit block is an uncommon complication that is seen with both active and passive fixation leads. Exit block has not been a significant problem with passive fixation steroid-eluting leads and has been treated with these leads. A new steroid-eluting active fixation lead was examined for its performance in patients in whom exit block had previously occurred. The lead function was evaluated prospectively in 24 patients with a history of exit block (15 ventricular and 9 atrial). The results in patients with atrial exit block are encouraging with an average chronic stimulation threshold of 0.19 msecs at 2.5 volts. Results in the ventricle are less encouraging with 3 occurrences of recurrent exit block in 15 patients; however, the remaining patients had a good mean threshold of 0.21 ±0.11 msecs at 2.5 volts. There were a remarkable number of non–lead related complications suggesting that this is a substantially different group than routine implantations.     

An Esophageal and Gastric Approach to Ventricular Pacing

Using a unipolar esothoracic pacing system (where current passes from a point source positioned in the distal esophagus to a chest wall pad) and pulse duration of 50 msec, satisfactory 1:1 ventricular capture was obtained in57 (86%) of 66 patients, with a mean threshold current of 27.7 mA at an optimal depth of 40.3 cm from the lower lip. When the unipolar esothoracic and bipolar transesophageal ventricular pacing systems were compared, the bipolar system was associated with a lower success rate and higher threshold current. When unipolar esothoracic pacing and gastrothoracic pacing (where current passes from a point source positioned in the stomach to a chest wall pad) were compared in 23 patients with bradyarrhythmia, ventricular capture was achieved using gastrothoracic pacing in 22 patients (96%) and esothoracic pacing in 21 (91%): gastrothoracic pacing required less current (16.0 mA ± SD 7.2 vs25.8 mA± SD 8.6). Optimal ventricular capture occurred using a unipolar gastrothoracic pacing electrode inserted to an average depth of 44.3 cm together with a high impedance chest pad (250 Ω) placed in the fourth interspace at the left sternal edge, with 50-msec current pulses and a mean threshold of 16.0 mA. Thus, using a gastroesophageal electrode system, ventricular pacing can be achieved successfully, and the availability of such a system could play a major role in resuscitation of patients from severe bradyarrhythmias.     

Impact of Adaptive Rate Pacing Controlled by a Right Ventricular Impedance Sensor on Cardiac Output in Response to Exercise

COOK, L., et al. : Impact of Adaptive Rate Pacing Controlled by a Right Ventricular Impedance Sensor on Cardiac Output in Response to Exercise. This study examined the effects of adaptive rate pacing controlled by closed-loop right ventricular impedance sensing on exercise hemodynamics. Twelve patients in whom Biotronik INOS²⁺ pacemakers had been implanted 4–6 weeks earlier participated in the study. All patients completed two graded, symptom-limited exercise tests. The pacemaker was programmed to DDDR with an upper rate limit of 75–85% of the age-predicted maximum heart rate and a lower rate limit of 45–60 ppm. Heart rate was recorded continuously. An average of 5 beats during the last 10 seconds of each exercise stage was used in the analysis. Oxygen uptake (VO₂) was measured using open circuit spirometry. The VO₂ values from the final 15 seconds of each exercise stage were used for analysis. Stroke volume and cardiac output were measured during the last minute of each stage using impedance cardiography. The test-retest reliability of heart rate and cardiac output responses to graded exercise was assessed using repeated measures analysis of variance, for which the reliability coefficients were r = 0.993 and r = 0.954, respectively (P < 0.01). There were significant correlations (P < 0.01) between VO₂ and heart rate and between VO₂ and cardiac output, with correlation coefficients of r = 0.907 and r = 0.824, respectively. This method of adaptive rate pacing produced reliable, positive hemodynamic responses to graded exercise on a test-retest basis. (PACE 2003; 26:[Pt. II]:244–247)     

Celiac Disease with Jejunal Ulceration

A patient with celiac disease with ulceration of the jejunum, an infrequent association, is reported. Patient underwent surgery for resection of the ulcerated segment. The frequency of such an association, possible complications and an approach to therapy is reviewed.