Diagnostic performance of chest CT average intensity projection (AIP) reconstruction for the assessment of pleuro-parenchymal abnormalities.

AIM: The comparison between chest x-ray (CXR) and computed tomography (CT) images is commonly required in clinical practice to assess the evolution of chest pathological manifestations. Intrinsic differences between the two techniques, however, limit reader confidence in such a comparison. CT average intensity projection (AIP) reconstruction allows obtaining "synthetic" CXR (s-CXR) images, which are thought to have the potential to increase the accuracy of comparison between CXR and CT imaging. We aim at assessing the diagnostic performance of s-CXR imaging in detecting common pleuro-parenchymal abnormalities. MATERIALS AND METHODS: 142 patients who underwent chest CT examination and CXR within 24 hours were enrolled. CT was the standard of reference. Both conventional CXR (c-CXR) and s-CXR images were retrospectively reviewed for the presence of consolidation, nodule/mass, linear opacities, reticular opacities, and pleural effusion by 3 readers in two separate sessions. Sensitivity, specificity, accuracy and their 95% confidence interval were calculated for each reader and setting and tested by McNemar test. Inter-observer agreement was tested by Cohen's K test and its 95%CI. RESULTS: Overall, s-CXR sensitivity ranged 45-67% for consolidation, 12-28% for nodule/mass, 17-33% for linear opacities, 2-61% for reticular opacities, and 33-58% for pleural effusion; specificity 65-83%, 83-94%, 94-98%, 93-100% and 79-86%; accuracy 66-68%, 74-79%, 89-91%, 61-65% and 68-72%, respectively. K values ranged 0.38-0.50, 0.05-0.25, -0.05-0.11, -0.01-0.15, and 0.40-0.66 for consolidation, nodule/mass, linear opacities, reticular opacities, and pleural effusion, respectively. CONCLUSION: S-CXR images, reconstructed with AIP technique, can be compared with conventional images in clinical practice and for educational purposes.

Intracranial complications of sinogenic and otogenic infections in children: an ESPN survey on their occurrence in the pre-COVID and post-COVID era.

BACKGROUND: COVID-19 pandemic is thought to have changed the epidemiology of some pediatric neurosurgical disease: among them are the intracranial complications of sinusitis and otitis (ICSO). According to some studies on a limited number of cases, both streptococci-related sinusitis and ICSO would have increased immediately after the pandemic, although the reason is not clear yet (seasonal changes versus pandemic-related effects). The goal of the present survey of the European Society for Pediatric Neurosurgery (ESPN) was to collect a large number of cases from different European countries encompassing the pre-COVID (2017-2019), COVID (2020-2021), and post-COVID period (2022-June 2023) looking for possible epidemiological and/or clinical changes. MATERIAL AND METHODS: An English language questionnaire was sent to ESPN members about year of the event, patient's age and gender, presence of immune-deficit or other favoring risk factors, COVID infection, signs and symptoms at onset, site of primary infection, type of intracranial complication, identified germ, type and number of surgical operations, type and duration of medical treatment, clinical and radiological outcome, duration of the follow-up. RESULTS: Two hundred fifty-four cases were collected by 30 centers coming from 14 different European countries. There was a statistically significant difference between the post-COVID period (129 children, 86 cases/year, 50.7% of the whole series) and the COVID (40 children, 20 cases/year, 15.7%) or the pre-COVID period (85 children, 28.3 cases/year, 33.5%). Other significant differences concerned the presence of predisposing factors/concurrent diseases (higher in the pre-COVID period) and previous COVID infection (higher in the post-COVID period). No relevant differences occurred as far as demographic, microbiological, clinical, radiological, outcome, morbidity, and mortality data were concerned. Paranasal sinuses and middle ear/mastoid were the most involved primary site of infection (71% and 27%, respectively), while extradural or subdural empyema and brain abscess were the most common ICSO (73% and 17%, respectively). Surgery was required in 95% of cases (neurosurgical and ENT procedure in 71% and 62% of cases, respectively) while antibiotics in 99% of cases. After a 12.4-month follow-up, a full clinical and radiological recovery was obtained in 85% and 84% of cases, respectively. The mortality rate was 2.7%. CONCLUSIONS: These results suggest that the occurrence of ICSO was significantly increased after the pandemic. Such an increase seems to be related to the indirect effects of the pandemic (e.g., immunity debt) rather than to a direct effect of COVID infection or to seasonal fluctuations. ICSO remain challenging diseases but the pandemic did not affect the management strategies nor their prognosis. The epidemiological change of sinusitis/otitis and ICSO should alert about the appropriate follow-up of children with sinusitis/otitis.

Primary mediastinal large B-cell lymphoma: Outcome of a series of pediatric patients treated with high-dose methotrexate and cytarabine plus anti-CD20.

Between 2007 and 2013, 13 children diagnosed with primary mediastinal large B-cell lymphoma (PMLBL) were treated according to a modified version of AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) LNH-97 protocol based on high-dose methotrexate, anthracyclines, and addition of anti-CD20. Ten patients achieved a continuous complete remission with front-line therapy. The overall 5-year survival was 91.7%, and event-free survival was 83.9%, with only one patient dying of progressive disease. Despite the few cases, these results demonstrate that this therapy, which includes anti-CD20, given in a multicenter setting, is feasible with acceptable toxicity in children with PMLBL.

Metastatic neuroblastoma in infants: are survival rates excellent only within the stringent framework of clinical trials?

INTRODUCTION: SIOPEN INES protocol yielded excellent 5-year survival rates for MYCN-non-amplified metastatic neuroblastoma. Patients deemed ineligible due to lack or delay of MYCN status or late registration were treated, but not included in the study. Our goal was to analyse survival at 10 years among the whole population. MATERIALS AND METHODS: Italian and Spanish metastatic INES patients' data are reported. SPSS 20.0 was used for statistical analysis. RESULTS: Among 98 infants, 27 had events and 19 died, while 79 were disease free. Five- and 10-year event-free survival (EFS) were 73 and 70 %, and overall survival (OS) was 81 and 74 %, respectively. MYCN status was significant for EFS, but not for OS in multivariate analysis. CONCLUSIONS: The survival rates of patients who complied with all the inclusion criteria for INES trials are higher compared to those that included also not registered patients. Five-year EFS and OS for INES 99.2 were 87.8 and 95.7 %, while our stage 4s population obtained 78 and 87 %. Concerning 99.3, 5-year EFS and OS were 86.7 and 95.6 %, while for stage 4 we registered 61 and 68 %. MYCN amplification had a strong impact on prognosis and therefore we consider it unacceptable that many patients were not studied for MYCN and probably inadequately treated. Ten-year survival rates were shown to decrease: EFS from 73 to 70 % and OS from 81 to 74 %, indicating a risk of late events, particularly in stage 4s. Population-based registries like European ENCCA WP 11-task 11 will possibly clarify these data.

Five to ten years follow-up after coiling of 241 patients with acutely ruptured aneurysms. A single centre experience.

Endovascular treatment has assumed a role of first choice in the management of ruptured intracranial aneurysms. We describe the clinical and morphological data after the treatment of 258 ruptured intracranial aneurysms in 241 patients, in order to evaluate the safety and the efficacy of the endovascular treatment. Two hundred and forty-one patients with saccular ruptured aneurysms were treated at our institution between 2000 and 2005. After the endovascular treatment a clinical and angiographic follow-up was conducted. The clinical follow-up was carried out with a medical examination and telephonic interviews and mRS was used for evaluation. Two hundred and forty-nine acutely ruptured aneurysms were successfully treated and immediately after the endovascular procedure 81.9% of the aneurysms resulted completely occluded, 12.1% had a residual neck and 6% revealed a residual sac. The evolution of each grade was evaluated at six months and two years. During the follow-up we observed five early and one late re-bleedings. Twenty-four patients underwent a second procedure. After the discharge and up to ten years 73.1% of patients had a good clinical outcome (mRS0-1), 8.9% died and the remainder showed moderate-severe disability (mRS2-3). The long-term stability of the anatomical result is a critic-al issue of this approach because eventual re-bleedings may occur even after several months or years. A careful clinical and radiological follow-up for up to two years after the embolization may prevent recurrences but may not be sufficient.

El acceso vascular sigue siendo un problema a resolver / Vascular access is still an unresolved problem

El acceso vascular para el tratamiento endovascular de los aneurismas de aorta puede ser una limitante o una causa grave de morbilidad o mortalidad. La presunción, la posibilidad de realizarmaniobras adyuvantes o la combinación con cirugía abierta pueden ser determinantes al momento de planear o finalizar el procedimiento. Se describen una variedad de procedimientos utilizados para modificar la anatomía desfavorable de las arterias ilíacas. La angioplastía con dilatadores o balón, la utilización de ciertas guías y accesos o la realización de conductos pueden ser claves al momento de realizar la cirugía.

O acesso vascular para o tratamento endovascular dos aneurismas da aorta pode ser uma limitante ou uma causa grave de morbilidade ou mortalidade. Como presunção, a possibilidade derealizar manobras adjuvantes ou a combinação com cirurgia aberta podem ser determinantes no momento de planejar ou finalizar o procedimento. Descrevem-se uma variedade de procedimentos utilizados para modificar a anatomia desfavorável das artérias ilíacas. A angioplastia com dilatadores ou balão, a utilização de certas guias e acessos ou a realização de canais podem ser fundamentais no momento de realizar a cirurgia.

The vascular access in the treatment of aortic aneurysms may be a limiting factor or a severe cause of morbidity and mortality. The possibility of carrying out adjuvant procedures or combiningthem with open surgery may be determining factors at the moment of planning or completing the procedure. A series of procedures used to modify the unfavourable anatomy of the iliac arteries are here in described. Dilator or balloon angioplasty, the use of certain guidewires and routes of access or the carrying out of conduits may be key at the moment of carrying out the surgery.

Muscle metastasis from hepatocellular carcinoma in a patient treated with TACE.

The authors describe a rare case of hepatocellular carcinoma that metastasized to the pectineal muscle of the right thigh. The patient had been treated with surgical procedures and with multiple sessions of transarterial chemoembolization, one of which was complicated by a right femoral artery hematoma at the catheter insertion site. It is unclear whether the muscle metastasis was caused by blood-borne spread or by tumor-cell seeding caused by the TACE procedure.

A highly accurate method for monitoring histological recovery in patients with celiac disease on a gluten-free diet using an endoscopic approach that avoids the need for biopsy: a double-center study.

BACKGROUND AND STUDY AIM: Endoscopy with duodenal biopsy is often performed in order to assess histological recovery in patients with celiac disease who are on a gluten-free diet. Use of the "immersion" technique during upper endoscopy allows visualization of duodenal villi or detection of total villous atrophy. In this two-center study, we investigated the accuracy of the immersion technique in predicting histological recovery in patients on a gluten-free diet whose initial diagnosis of celiac disease had been made on the basis of total villous atrophy. PATIENTS AND METHODS: The immersion technique was performed in 62 patients with celiac disease who were being treated and who had been referred for follow-up (26 patients at the Rome center and 36 patients at the Vicenza center). All these patients had an initial diagnosis based on positive antibodies and biopsy-proved duodenal total villous atrophy. At the follow-up examination, the duodenal villi were re-evaluated as present or absent by one endoscopist at each center, and the results were compared with the histology. RESULTS: At the follow-up endoscopy, the duodenal villi were found to be present in 51 patients and absent in 11. The sensitivity, specificity, positive predictive value, and negative predictive value of the immersion technique for detecting the presence or absence of villi were all 100 %. CONCLUSIONS: This study demonstrated the feasibility and the high level of accuracy of the immersion technique in predicting the histological recovery of duodenal villi in patients with celiac disease who are following a gluten-free diet. An endoscopy-based approach that avoids the need for biopsy could be useful for monitoring the dietary adherence and/or response of patients with an initial diagnosis of celiac disease based on total villous atrophy.

Comparative follow up of patients with implanted cardioverter-defibrillators after induction of sustained monomorphic ventricular tachycardias or ventricular fibrillation by programmed stimulation.

OBJECTIVE: To investigate the prognostic value of induced monomorphic ventricular tachycardia (VT) and ventricular flutter or fibrillation (VF) during programmed electrical stimulation in patients with a high risk for sudden arrhythmogenic cardiac death. DESIGN: Prospective cohort study. PATIENTS: 102 patients at high risk for arrhythmogenic sudden cardiac death who received an automated implantable cardioverter-defibrillator (AICD) were evaluated. 56 patients received the AICD for primary prevention and 46 for secondary prevention. 58 patients had induction of a monomorphic VT (VT group) and 44 had induction of a polymorphic VT, ventricular flutter, or ventricular fibrillation (VF group) during programmed electrical stimulation. Average follow up was 20 months in both groups. MAIN OUTCOME MEASURES: Appropriate AICD protocol. RESULTS: In patients who received the AICD for primary prevention, 16 of 32 patients in the VT group, compared with only four of 24 patients in the VF group, received an appropriate AICD protocol (p = 0.02). In the entire study population, 479 appropriate AICD protocols were recorded in 28 (48%) patients in the VT group and 28 appropriate protocols in 11 (25%) patients in the VF group. Cumulative Kaplan-Meier event-free survival curves were significantly different (p = 0.02). CONCLUSION: Induction of VF during programmed electrical stimulation is of no prognostic value even in high risk patients without previously documented ventricular fibrillation.

Intra-aneurysmal pressure after incomplete endovascular exclusion.

PURPOSE: An endoleak results from the incomplete endovascular exclusion of an aneurysm. We developed an experimental model to analyze hemodynamic changes within the aneurysm sac in the presence of an endoleak, with and without a simulated open collateral branch. METHODS: With a latex aneurysm model connected to a pulsatile pump, pressures were measured simultaneously within the system (systemic pressure) and the aneurysm sac (intrasac pressure). The experiments were performed without endoleak (control group) and after creating a 3.5-mm (group 1), 4.5-mm (group 2), and 6-mm (group 3) diameter orifice in the endograft, simulating an endoleak. Pressures were also registered with and without a patent aneurysm side branch. RESULTS: In each endoleak group, the intrasac diastolic pressure (DP) and mean pressure (MP) were significantly higher than the systemic DP and MP (P =.01, P =.006, and P =.001, respectively), although the pressure curve was damped. The presence of an open side branch significantly reduced the intrasac DP and MP. CONCLUSION: In this model, intrasac pressures were significantly higher than systemic pressures in the presence of all endoleaks, even the smallest ones. Intrasac pressures higher than systemic pressure may pose a high risk for aneurysm rupture. Although patent side branches significantly reduce these pressures, the aggressive management of an endoleak should be pursued.

Increased activity of membrane-associated nucleoside diphosphate kinase and inhibition of cAMP synthesis in failing human myocardium.

OBJECTIVE: Chronic heart failure is associated with a decreased responsiveness of the heart to beta-adrenergic receptor agonists. We recently demonstrated a receptor-independent activation of G proteins and modulation of cardiac adenylyl cyclase activity by sarcolemmal membrane-associated nucleoside diphosphate kinase. We wondered whether changes in the activity of nucleoside diphosphate kinase occur in heart failure and contribute to or compensate for the impairment in myocardial receptor-mediated cAMP generation. METHODS: Sarcolemmal membranes were purified from non-failing and failing human left ventricular myocardium. The protein level and activity of nucleoside diphosphate kinase were quantified. The influence of nucleoside diphosphate kinase on adenylyl cyclase activity was determined by measuring the effect of GDP on adenylyl cyclase activity in the absence and presence of nucleoside diphosphate kinase inhibitors. RESULTS: The amount and activity of nucleoside diphosphate kinase in sarcolemmal membranes from failing hearts (n=13) were increased 3- to 4-fold compared to levels in membranes from non-failing myocardium (n=5). This increase in sarcolemmal nucleoside diphosphate kinase activity resulted in a 50% inhibition of adenylyl cyclase activity over a range of GDP and ATP concentrations. CONCLUSION: The amount and activity of nucleoside diphosphate kinase are increased in sarcolemmal membranes of failing human myocardium, resulting in a substantial receptor-independent inhibition of adenylyl cyclase activity.

Initial evaluation of carotid angioplasty and stenting with three different cerebral protection devices.

OBJECTIVE: The purpose of the study was to assess the effectiveness of cerebral protection devices during carotid artery angioplasty and stent placement. METHODS: Between September 1998 and September 1999, carotid angioplasty and stenting were performed in 46 patients with symptomatic (39.1%) or asymptomatic (60.9%) severe carotid artery stenosis. Wallstents were used in all patients with selective predilatation. Cerebral protection devices were used in 25 of these patients. Primary end points were perioperative neurologic complications and mortality. Data were collected prospectively. RESULTS: The overall combined end point of all neurologic deficits and death rate was 4.34%. Two neurologic events (one transient ischemic attack and one minor stroke) occurred in the unprotected group (9.53%) versus none in the group with cerebral protection. This difference is not statistically significant. The mortality rate was 0% for both groups. On an intention to treat basis, the overall technical success rate for carotid angioplasty was 97.8%, and for placement of cerebral protection devices it was 100%. An important number of particles of different sizes were captured in all cases in which cerebral protection devices were used. CONCLUSION: Experience has shown that cerebral protection during carotid angioplasty and stenting is technically feasible and appears to be effective in preventing procedure-related neurologic complications. Further investigation is warranted.

Bloodstream infections in children with cancer: a multicentre surveillance study of the Italian Association of Paediatric Haematology and Oncology. Supportive Therapy Group-Infectious Diseases Section.

A one-year prospective, multicentre surveillance study on aetiology, main clinical features and outcome of bloodstream infections in children with cancer was conducted in 18 paediatric haematology centres belonging to the Italian Association for Paediatric Haematology and Oncology. A total of 191 bloodstream infections were reported during the study period. Of them, 123 (64%) occurred in neutropenic and 68 (36%) in non-neutropenic patients. Gram-positive cocci caused 45% (85/191) of the episodes, gram-negative rods 41% (78/191), and fungi 9% (18/191). The remaining 5% (10/191) of the episodes were poly-microbial infections. A total of 204 pathogens were isolated (46% gram-positive cocci; 44% gram-negative rods; and 10% fungi). The aetiologic distribution was similar among neutropenic and non-neutropenic patients. A correlation between the infection and the presence of an indwelling central venous catheter was found in 20% (23/114) of the episodes among neutropenic patients and in 55% (23/62) among non-neutropenic patients. Gram-negative micro-organisms were isolated in an unusually high proportion of catheter-related infections (48%). The overall mortality rate from any cause within 30 days from the first positive blood culture was 11%, and was higher among patients who were neutropenic at the onset of the infection than among those who were not neutropenic (15 versus 4%, P = 0.03). In addition, the mortality was significantly higher in recipients of bone marrow transplantation than in patients with acute leukaemia or solid tumour (21, 11 and 6%, respectively) and was also higher in fungaemias and poly-microbial infections (22 and 30%) than in single gram-positive and gram-negative bacteraemias (11 and 6%).

Receptor-independent activation of cardiac adenylyl cyclase by GDP and membrane-associated nucleoside diphosphate kinase. A new cardiotonic mechanism?

Regulation of adenylyl cyclase activity by guanine nucleoside tri- and diphosphates as well as by stimulatory and inhibitory receptors was studied in canine cardiac sarcolemmal membranes. Guanosine triphosphate (GTP) increased adenylyl cyclase activity by a maximum of 80%, with an EC50 value of 0.7 mumol/l. The addition of the beta-adrenoceptor agonist, isoprenaline (100 mumol/l), caused a further, about 100%, increase in GTP-stimulated activity. The nucleoside diphosphate (GDP) also activated cardiac adenylyl cyclase, but in a biphasic manner. At low concentrations (EC50 0.12 mumol/ l). GDP increased enzyme activity by about 80%, followed by a plateau at 0.5-2 mumol/l and a second increase to a maximum of 60% with an EC50 value of 14 mumol/l. The stable GDP analog, guanosine 5'-O-(2-thio)diphosphate (GDP beta S), also increased cardiac adenylyl cyclase activity, but in a monophasic manner, by a maximum of 150%, with an EC50 of 0.4 mumol/l. Addition of uracil diphosphate (UDP) (3 mmol/l), which completely inhibited transphosphorylation of GDP to GTP, did not reduce adenylyl cyclase stimulation by low concentrations of GDP, whereas enzyme stimulation by high GDP concentrations was almost completely attenuated. Furthermore, pretreatment of the membranes with cholera toxin led to an increased stimulation of adenylyl cyclase activity by high concentrations of GDP. These findings suggest that the second phase of adenylyl cyclase stimulation by GDP is due to transphosphorylation of GDP to GTP, associated with activation of Gs proteins, and that stimulation by GDP itself (first phase) and endogenously formed GTP (second phase) is additive. However, in contrast to exogenously added GTP, beta-adrenoceptor activation did not enhance GDP-stimulated adenylyl cyclase activity. Furthermore, in the presence of 1 mumol/l GDP, the addition of GTP did not cause any further increase in enzyme activity. On the other hand, the muscarinic acetylcholine receptor agonist carbachol inhibited both GTP- and GDP-activated adenylyl cyclase. The inhibition of GDP-stimulated activity was lost when formation of GTP from GDP was blocked. The contrasting effects of endogenously formed GTP and exogenous GTP suggest that the formation of GTP from GDP is closely linked to the activation site of adenylyl cyclase, i.e. the stimulatory Gs protein. This receptor-independent activation can apparently bypass beta-adrenoceptor-dependent activation of cardiac adenylyl cyclase.

Opioid receptor agonists activate pertussis toxin-sensitive G proteins and inhibit adenylyl cyclase in canine cardiac sarcolemma.

Although both opioid receptors and endogenous opioids are abundant in cardiac tissues, the signal transduction pathways of opioids in cardiac sarcolemmal membranes have yet to be identified. In highly purified canine cardiac sarcolemmal membranes, binding of the opioid receptor antagonist [3H]diprenorphine and effects of mu, delta and kappa agonists on low Km GTPase and adenylyl cyclase were measured. Equilibrium binding of [3H]diprenorphine revealed a maximal binding capacity of 7.2 pmol/mg protein and a Kd of 1.3 nmol/l. In the presence of GTP, (D-Pen2,5, p-Cl-Phe4) enkephalin and (D-Arg6) dynorphin A 1-13 fragment both inhibited adenylyl cyclase by 20-25% (from 206 +/- 30 to 164 +/- 28 pmol.min-1.mg protein-1, EC50 6 mumol/L, and from 254 +/- 109 to 204 +/- 90 pmol.min-1.mg protein-1, EC50 8 mumol/L, respectively; P < 0.001). Both substances stimulated low Km GTPase by 20% and 13%, respectively (from 12.7 +/- 3.0 to 15.2 +/- 3.7 pmol.min-1.mg protein-1, EC50 12 mumol/L, P < 0.01, and from 9.1 +/- 2.8 to 10.4 +/- 3.2 pmol.min-1.mg protein-1, EC50 6 mumol/L, P < 0.05, respectively). These effects were blocked by the opioid receptor antagonist naltrexone and by pretreatment of sarcolemmal membranes with pertussis toxin. The mu opioid receptor agonists (D-Ala2, Me Phe4, Gly-[ol]5)enkephalin and morphiceptin had no effect on either adenylyl cyclase or low Km GTPase activities. These data suggest that in cardiac sarcolemma, opioid receptors are coupled to pertussis toxin sensitive G proteins and mediate inhibition of adenylyl cyclase activity.

Stable GDP analog-induced inactivation of G(i) proteins promotes cardiac adenylyl cyclase inhibition by guanosine 5'-(beta gamma-imino)triphosphate and muscarinic acetylcholine receptor.

Low concentrations of GDP and its stable analog guanosine 5'-O-(2-thio)diphosphate (GDP beta S) have been shown to stimulate adenylyl cyclase activity in canine cardiac sarcolemmal membranes independent from a phosphate transfer reaction. The mechanism of this stimulation was further examined. The stable GTP analog guanosine 5'-(beta gamma-imino)triphosphate (Gpp(NH)p) increased basal adenylyl cyclase activity and inhibited forskolin-stimulated activity with EC50 (half-maximal effective concentration) values of 0.7 mumol/l and 10 nmol/l, respectively. In the presence of GDP beta S (5 mumol/l), which increased basal activity by about 150%, addition of Gpp(NH)p inhibited adenylyl cyclase activity by up to 50% with an EC50 value of 40 nmol/l. Activation of cardiac muscarinic acetylcholine receptors by carbachol amplified this Gpp(NH)p-induced inhibition of GDP beta S-stimulated adenylyl cyclase activity. The stimulatory effect of GDP beta S and the inhibitory effect of Gpp(NH)p on GDP beta S-stimulated adenylyl cyclase activity were both attenuated by increasing the Mg2+ concentration or substituting Mn2+ for Mg2+ in the assay. Furthermore, both effects were strongly reduced or abolished upon pretreatment of the sarcolemmal membranes with a low concentration of the SH reagent N-ethylmaleimide (10 mumol/l). These results suggest that the stimulatory effect of GDP beta S on basal adenylyl cyclase activity in canine cardiac sarcolemmal membranes is caused by inactivation of G(i) proteins, which are then rendered susceptible to activation by Gpp(NH)p and inhibitory receptors.