Uptake of meta-iodobenzylguanidine by bovine chromaffin granule membranes

meta-Iodobenzylguanidine, an adrenal imaging agent used for the scintigraphic detection of human pheochromocytoma, is a substrate for the monoamine uptake system of chromaffin granules. It is accumulated by bovine chromaffin granule membrane vesicles in the presence of ATP, and it can be released by an osmotic shock. The uptake is dependent upon the generation of an H+-electrochemical gradient by an ATP-dependent H+ pump since it is blocked by an H+ ionophore and since meta-iodobenzylguanidine uptake can be driven by imposing an artificial pH gradient (inside acidic) on the membrane vesicles. The transport is saturable and its Km value (2.0 microM at pH 8.0) is similar to that of noradrenaline (5.3 microM). Transport occurs through the monoamine transporter since it is blocked by the same inhibitors, tetrabenazine and reserpine, and also by the transporter substrates noradrenaline and serotonin. Noradrenaline inhibits meta-iodobenzylguanidine uptake competitively (Ki = 13 microM). In addition, meta-iodobenzylguanidine displaces dihydrotetrabenazine and reserpine from their binding sites on chromaffin granule membranes. It is thus likely that, after in vivo administration, [131I] meta-iodobenzylguanidine is ultimately stored in chromaffin granules and that it is translocated by the monoamine transporter.     

Comparison of stress-only vs. stress/rest with technetium-99m methoxyisobutylisonitrile myocardial perfusion imaging

Unlike conventional thallium-201 myocardial imaging, technetium-99m methoxyisobutylisonitrile (MIBI) requires separate stress and rest injections. We prospectively studied 148 consecutive patients referred for myocardial perfusion studies to determine the diagnostic value of rest images once normal exercise or dipyridamole tomographic images had been obtained. In patients referred with no history of previous myocardial infarction in whom the diagnosis of coronary artery disease was suspected, 45 of 109 (41%) patients had normal stress tomographic images. Obtaining rest images did not alter the final interpretation in any of these cases. From this we infer that in patients with normal images after exercise or dipyridamole administration and no past history of myocardial infarction, ^99mTc-MIBI rest images are not required. This provides several advantages including increased speed of diagnosis, decreased patient radiation exposure, improved cost efficiency and decreased demand on tomographic camera time. Offprint requests to: A.Y. Fung     

The effects of shivering on oxygen consumption and carbon dioxide production in patients rewarming from hypothermic cardiopulmonary bypass

Oxygen consumption (VO2), carbon dioxide production (VCO2), end-tidal carbon dioxide partial pressure (PETCO2), mixed venous oxygen saturation (SvO2) and haemodynamic variables were recorded every 30 min for four hours in 15 patients recovering from hypothermic cardiopulmonary bypass (CPB). All patients had been anaesthetised with fentanyl 40 micrograms.kg-1, supplemented with isoflurane, and pancuronium 0.15 mg.kg-1 for muscle relaxation. Three of the 15 patients (20 per cent) shivered, defined as intermittent or continuous, vigorous movements of chest or limb muscles. Patients who shivered had a VO2 of 159 +/- 16.4 ml.min-1.m-2 on arrival in the ICU which rose to a maximum value of 254 +/- 28.3 ml.min-1.m-2 by 150 min post-CPB. In contrast, patients who did not shiver had a significantly lower VO2 of 93.1 +/- 6.9 ml.min-1.m-2 on arrival in the ICU which rose to a maximal value of only 168 +/- 11.5 ml.min-1.m-2 by 180 min post-CPB. Maximal VO2 in both groups was reached when the nasopharyngeal temperature (NPT) was approaching normal. VCO2 paralleled the increase in VO2 in both groups. By four hours there was no significant difference between the two groups; however, the VO2 in both groups (160.5 +/- 21.3 ml.min-1.m-2 and 173.9 +/- 12.3 ml.min-1.m-2 respectively) was approximately twice values commonly measured in anaesthetized patients. Patients who shivered had a significantly higher heart rate and cardiac index and significantly lower SvO2. We conclude that the high VO2 and VCO2 associated with shivering causing increased myocardial work may be detrimental to patients who have impaired cardiac function post-coronary artery surgery (CAS).     

Stability of regional cerebral glucose metabolism in the normal brain measured by positron emission tomography

Cerebral glucose utilization (LCMRGI) was measured using the [18F]fluorodeoxyglucose method with PET in two groups of ten healthy young volunteers, each scanned in a resting state under different methodological conditions. In addition, five subjects had a second scan within 48 hr. Mean hemispheric values averaged 45.8 +/- 3.3 mumol/100 g/min in the right cerebral hemisphere and 47.0 +/- 3.7 mumol/100 g/min in the left hemisphere. A four-way analysis of variance (group, sex, region, hemisphere) was carried out on the results using three different methods of data manipulation: (a) the raw values of glucose utilization, (b) LCMRGI values "normalized" by the mean hemispheric gray matter LCMRGI value, and (c) log transformed LCMRGI values. For all analysis techniques, significantly higher LCMRGI values were consistently seen in the left mid and posterior temporal area and caudate nucleus relative to the right, and in the right occipital region relative to the left. The coefficient of variation of intrasubject regional differences (9.9%) was significantly smaller than the coefficient of variation for regions between subjects (16.5%). No differences were noted between the sexes and no effect of repeat procedures was seen in subjects having multiple scans. In addition, inter-regional LCMRGI correlations were examined both in values from the 20 normal subjects, as well as in a set of hypothetical "abnormal" values. Results were compared with those reported from other PET centers; despite certain methodological differences, the intersubject and inter-regional variation of LCMRGI is fairly constant.     

Ontogeny of B lymphocytes in mice. Quantification of surface membrane immunoglobulins by immunoperoxidase assay.

Surface membrane immunoglobulins (SmIg) of splenic lymphocytes were investigated by immunoperoxidase assay in newborn Swiss mice, their mothers and adult controls. The mean number of SmIg + cells in adult mice was 45-8% and the mean number of antigenic sites per positive cells was 108,500. In newborn mice during the first 7 days of life, values for both parameters were low (24-25--28-5% and 38,000-45,773 respectively) and began to rise after the 10th day to reach adult levels between the ages of 2 and 3 weeks. A peak above adult levels for the mean number of sites per cell was observed on day 21 with a subsequent drop to adult levels on day 28. Post-partum females were found to have consistently fewer sites per positive cell (69,000-86,600) during the 14 days following delivery than their adult control counterparts, though the difference was not statistically significant.     

Personal protective equipment related skin reactions in healthcare professionals during COVID‐19

Since the outbreak of COVID‐19 pandemic, clinicians have had to use personal protective equipment (PPE) for prolonged periods. This has been associated with detrimental effects, especially in relation to the skin health. The present study describes a comprehensive survey of healthcare workers (HCWs) to describe their experiences using PPE in managing COVID‐19 patients, with a particular focus on adverse skin reactions. A 24‐hour prevalence study and multi‐centre prospective survey were designed to capture the impact of PPE on skin health of hospital staff. Questionnaires incorporated demographics of participants, PPE type, usage time, and removal frequency. Participants reported the nature and location of any corresponding adverse skin reactions. The prevalence study included all staff in intensive care from a single centre, while the prospective study used a convenience sample of staff from three acute care providers in the United Kingdom. A total of 108 staff were recruited into the prevalence study, while 307 HCWs from a variety of professional backgrounds and demographics participated in the prospective study. Various skin adverse reactions were reported for the prevalence study, with the bridge of the nose (69%) and ears (30%) being the most affected. Of the six adverse skin reactions recorded for the prospective study, the most common were redness blanching (33%), itchiness (22%), and pressure damage (12%). These occurred predominantly at the bridge of the nose and the ears. There were significant associations (P < .05) between the adverse skin reactions with both the average daily time of PPE usage and the frequency of PPE relief. The comprehensive study revealed that the use of PPE leads to an array of skin reactions at various facial locations of HCWs. Improvements in guidelines are required for PPE usage to protect skin health. In addition, modifications to PPE designs are required to accommodate a range of face shapes and appropriate materials to improve device safety.     

Increased dopamine receptor sensitivity in the rat following acute administration of sufentanil,U50,488H and d-Ala2-d-Leu5-enkephalin

Summary The effects of acutely administered opioid receptor agonists sufentanil, U50,488H and [d-Ala², d-Leu⁵]-enkephalin (DADL) were observed upon dopamine D₁ and D₂ binding site density in the striatum of the rat. In addition, the functional implications of opioid-induced changes in dopamine receptor sensitivity were studied using the behavioural profile elicited by apomorphine in the rat. The -agonist sufentanil (1 or 20 Erg/kg, i. p.), the -agonist U50,488H (10 mg/kg, i. p.) and DADL (1 g/animal, i. c. v.) all significantly elevated D₂ but not D₁ binding site density in rat striatum. Pretreatment with sufentanil (1 g/kg, i. p.) induced an elevation in apomorphine-induced sterotyped behaviour, but attenuated locomotor activity. Following administration of U50,488H (10 mg/kg, i. p.), both the degree of stereotypy and the intensity of the locomotor activity were enhanced. Contralateral rotation was observed in animals pretreated with DADL (1 g/animal, i. c. v.) following challenge with apomorphine. It is concluded that the opioid agonists studied induce a significant elevation in functional D₂ sites to the exclusion of D₁ sites. However, the precise mechanism by which this effect is elicited remains to be established. Send offprint requests to R. D. E. Sewell at the above address