Reporting of coronary artery calcification on chest CT studies in patients with interstitial lung disease.

AIM: To evaluate the prevalence of coronary artery calcification (CAC) on non-contrast computed tomography (CT) of the thorax in patients with interstitial lung disease (ILD), assess consistency of CAC reporting and assess incidence of subsequent cardiac events. MATERIALS AND METHODS: Patients with known interstitial lung disease who underwent a CT thorax over a 2-year period were retrospectively reviewed. Presence of CAC was assessed using a visual scale for CAC reporting and graded as mild, moderate, or severe by two cardiothoracic radiologists. CT reports were reviewed to determine if presence of CAC had been described. Electronic medical records were reviewed for any subsequent cardiothoracic events from the date of the CT thorax to present. RESULTS: 254 patients were included in the analysis (54.7% men; mean age 59.9 yo). 43.7% had CAC on their CT thorax; however, in 87.3% of those, reports did not comment on its presence. 8 patients had cardiac events; 7 of them had CAC on CT although only in 1 case this was reported. Global CAC and LAD CAC Patients with cardiac events had a significantly higher global CAC (p=0.016) and LAD CAC (p=0.048) when compared to patients without. CONCLUSION: We demonstrated a high prevalence of CAC in ILD patients and its significant association with adverse cardiac events. Unfortunately, CAC on CT thorax is still largely unreported. As per recent BSCI/BSCCT and BSTI guidelines, reporting of CAC should become part of routine practice, as may prompt prevention and impact on patients outcome.

Anal trauma caused by bull-horn injury.

BACKGROUND: Bullfighting festivals are commonly performed at Spain. Perineal trauma due to bull-horn injury is associated with high morbidity due to sphincteric associated lesions METHODS: We report a case of 37-year-old male patient with anal trauma due to a bull-horn injury involving the sphincter complex, treated in our Emergency department RESULTS: Urgent surgery was performed with primary sphincteroplasty, without performing a colostomy. The associated complication was a partial dehiscence of the surgical wound (Clavien-Dindo I). No transfusions, re-interventions or readmissions were registered. The degree of incontinence at discharge and after 12 month follow-up, according to the Wexner scale was 8 points and 2 points, respectively. CONCLUSIONS: The main treatment of bull-horn injuries is extensive surgical debridement, antibiotic therapy, and lavage of the area. In cases involving the anal sphincter, primary sphincteroplasty is recommended. The modern trend does not include the systematic performance of a colostomy however, it has been described in cases with catastrophic wounds and urological lesions associated.

Pulmonary ischaemia without pulmonary arterial thrombus in COVID-19 patients receiving extracorporeal membrane oxygenation: a cohort study.

AIM: To evaluate the incidence of pulmonary ischaemia in COVID-19 patients on extracorporeal membrane oxygenation (ECMO), and its correlation with pulmonary artery thrombosis. MATERIALS AND METHODS: Computed tomography (CT) thorax of all patients receiving ECMO with proven COVID-19 pneumonitis between March and May 2020 were analysed for the presence and extension of pulmonary thromboembolic disease. RESULTS: Fifty-one patients were reviewed. The mean (range) age of 45 (26-66) years; 38/51 (74.5%) were men. All patients had severe COVID-19 pneumonitis, and 18/51 (35.3%) had macroscopic thrombosis (15 with associated ischaemia); however, 13/51 (25.5%) patients had ischaemia without associated thrombus. CONCLUSION: The majority of patients with COVID-19 who received ECMO had areas of ischaemia within consolidated lungs, almost half of these without subtending pulmonary artery thrombosis. Although the prognostic significance of these findings is unclear, they are highly suggestive of lung ischaemia due to isolated microvascular immune thrombosis.

Approach and management of patients injured by bullfighting trauma. / Abordaje y manejo médico-quirúrgico del paciente herido por traumatismo taurino.

INTRODUCTION: Bullfighting festivals are attributed to the cultural idiosyncrasies of the Ibero-American people, posing an extreme risk to the physical integrity of the participants. Spain is considered the country with the highest number of bull-related celebrations worldwide and, therefore, with the highest number of patients injured by bullfighting trauma treated, thus justifying a public health problem. The generalities associated with this type of trauma define the people injured as polytraumatised patients. In addition, it is important to know the kinematics of the injuries and their specific characteristics, in order to implement quality medical-surgical care. METHODS: scientific review of the literature to promote a comprehensive guide for the medical-surgical management of patients injured by bullfighting trauma. RESULTS: We described the guidelines to standardise protocols for in-hospital approach of patients injured by bullfighting trauma. CONCLUSIONS: Bullfighting trauma is considered a real health problem in the emergency departments of the ibero-Americans countries, especially in Spain, where bullfighting is part of the national culture. The inherent characteristics of these animals cause injuries with special aspects, so it is important to know the generalities of bullfighting trauma. Because of the multidisciplinary approach, this guidelines are adressed to all healthcare providers involved in the management of these patients. It is essential to establish particular initial care for this type of injury, specific therapeutic action and follow-up based on the medical-surgical management of the trauma patient in order to reduce the associated morbidity and mortality.

Traumatic abdominal wall hernia as a component of the seatbelt syndrome: A case report of complete abdominal wall muscle transection.

INTRODUCTION AND IMPORTANCE: Seat belt syndrome (SBS) is a rare condition described as injuries sustained due to thoracic, abdominal, and pelvic compression in the context of traffic accidents. These injuries can range from minor skin abrasions to large lesions of internal organs and spinal cord involvement. Traumatic abdominal wall hernias (TAWH) are one of the injuries that can be associated. CASE PRESENTATION: A 21-year-old male suffered a severe injury, resulting in complete transection of all abdominal wall musculature due to SBS, with associated visceral injury. Emergency surgery included intestinal and sigmoid colon resection, along with cava vein repair. After a prolonged recovery, a second-stage surgery for abdominal wall reconstruction was planned. Prehabilitation involved botulinum toxin and pneumoperitoneum, with surgical planning utilizing CT scan and 3D reconstruction. The second-stage surgery included transversus abdominis release and placement of double mesh. CLINICAL DISCUSSION: Managing traumatic abdominal wall hernias in polytrauma patients necessitates emergent surgery for vital injuries, while reconstructive surgery timing is crucial, with patient preparation being essential. Surgical planning, including 3D reconstructions, enhances accuracy, and safety, with repair technique selection depending on anatomical features. Given our patient's athletic background and preoperative vascular CT findings, flapless reconstructive surgery was chosen to mitigate vascular risks. CONCLUSION: The therapeutic approach to traumatic abdominal wall injuries should be individualized to each patient, with a focus on addressing vital injuries first and considering abdominal wall reconstruction surgery at a subsequent stage. Utilizing CT scan with 3D reconstruction can be a valuable tool for preoperative planning in cases involving significant abdominal wall defects.

Inhaler technique knowledge and skills before and after an educational program in obstructive respiratory disease patients: A real-life pilot study.

INTRODUCTION AND OBJECTIVE: Patients present poor knowledge and skills about their respiratory disease and inhaler device. We aimed to: (1) evaluate COPD and asthmatic patients... ability to manage inhaled drugs (2) identify differences among devices and (3) correlate clinical data with patient ability. MATERIAL AND METHODS: Patients (n=134) admitted for pulmonary rehabilitation (PR) were given an ad-hoc questionnaire covering 0% as the worst and 100% the best value of global ability (indicating the sum of knowledge and skills in managing inhaled drugs) at baseline (T0) and discharge (T1). Educational program was provided during PR. Setting of rehabilitation, age, sex, diagnosis, spirometry, CIRS score, level of autonomy to use medications, if na..ve about PR, educational level, and number/type of prescribed inhaled drugs were recorded. RESULTS: Most patients used 1 drug while 37% used 2 drugs. DPIs were the main device prescribed. At baseline, patients... mean level of knowledge and skills were 73% and 58%, respectively. There was a significant difference in level of skills (p=0.046) among device families, DPIs resulting worst and pMDIs best. Global ability, skills and knowledge improved after educational support (p<0.001) but did not reach the optimal level, 88%, 87% and 89%, respectively. Baseline global ability was positively correlated to female gender, younger age, previous PR access, outpatient status, higher education level and GOLD D class. CONCLUSIONS: At hospital admission, global ability was not optimal. Education may improve this, irrespective of the type of device used, in particular in male, elderly, na..ve to PR, low educational level patients.

Surgical management of peripheral pulmonary artery pseudoaneurysm.

Pulmonary artery pseudoaneurysm is rare and may cause life-threatening haemoptysis. Coil or stent is the main treatment option. We present a case of intrapulmonary pseudoaneurysm located in the fissure between left upper and lower lobes surgically repaired due to the location and the broad base of the pseudoaneurysm.

Non-invasive assessment of ventriculo-arterial coupling using aortic wave intensity analysis combining central blood pressure and phase-contrast cardiovascular magnetic resonance.

BACKGROUND: Wave intensity analysis (WIA) in the aorta offers important clinical and mechanistic insight into ventriculo-arterial coupling, but is difficult to measure non-invasively. We performed WIA by combining standard cardiovascular magnetic resonance (CMR) flow-velocity and non-invasive central blood pressure (cBP) waveforms. METHODS AND RESULTS: Two hundred and six healthy volunteers (age range 21-73 years, 47% male) underwent sequential phase contrast CMR (Siemens Aera 1.5 T, 1.97 × 1.77 mm2, 9.2 ms temporal resolution) and supra-systolic oscillometric cBP measurement (200 Hz). Velocity (U) and central pressure (P) waveforms were aligned using the waveform foot, and local wave speed was calculated both from the PU-loop (c) and the sum of squares method (cSS). These were compared with CMR transit time derived aortic arch pulse wave velocity (PWVtt). Associations were examined using multivariable regression. The peak intensity of the initial compression wave, backward compression wave, and forward decompression wave were 69.5 ± 28, -6.6 ± 4.2, and 6.2 ± 2.5 × 104 W/m2/cycle2, respectively; reflection index was 0.10 ± 0.06. PWVtt correlated with c or cSS (r = 0.60 and 0.68, respectively, P < 0.01 for both). Increasing age decade and female sex were independently associated with decreased forward compression wave (-8.6 and -20.7 W/m2/cycle2, respectively, P < 0.01) and greater wave reflection index (0.02 and 0.03, respectively, P < 0.001). CONCLUSION: This novel non-invasive technique permits straightforward measurement of wave intensity at scale. Local wave speed showed good agreement with PWVtt, and correlation was stronger using the cSS than the PU-loop. Ageing and female sex were associated with poorer ventriculo-arterial coupling in healthy individuals.

Identifying exceptional malaria occurrences in the absence of historical data in South Sudan: a method validation.

BACKGROUND: Detecting unusual malaria events that may require an operational intervention is challenging, especially in endemic contexts with continuous transmission such as South Sudan. Médecins Sans Frontières (MSF) utilises the classic average plus standard deviation (AV+SD) method for malaria surveillance. This and other available approaches, however, rely on antecedent data, which are often missing. OBJECTIVE: To investigate whether a method using linear regression (LR) over only 8 weeks of retrospective data could be an alternative to AV+SD. DESIGN: In the absence of complete historical malaria data from South Sudan, data from weekly influenza reports from 19 Norwegian counties (2006-2015) were used as a testing data set to compare the performance of the LR and the AV+SD methods. The moving epidemic method was used as the gold standard. Subsequently, the LR method was applied in a case study on malaria occurrence in MSF facilities in South Sudan (2010-2016) to identify malaria events that required a MSF response. RESULTS: For the Norwegian influenza data, LR and AV+SD methods did not perform differently (P > 0.05). For the South Sudanese malaria data, the LR method identified historical periods when an operational response was mounted. CONCLUSION: The LR method seems a plausible alternative to the AV+SD method in situations where retrospective data are missing.

Short-course treatment outcomes and adverse events in adults and children-adolescents with MDR-TB in Niger.

Niger National Tuberculosis Programme. To describe the outcomes and adverse events (AEs) in a cohort of adults, children and adolescents with multidrug-resistant tuberculosis (MDR-TB) who were treated with the 'short-course regimen'. The regimen comprised an intensive phase of 4-6 months with kanamycin, medium-high dose of isoniazid and prothionamide, and high doses of gatifloxacin, clofazimine, ethambutol and pyrazinamide throughout. Sixty-five patients were treated with a regimen of 12-14 months and 55 patients with a regimen of 9-11 months. Of the 120 patients evaluated, 110 (92%) were adults (median age 31 years) and 10 (8%) were children or adolescents (median age 17 years). The treatment success rate was respectively 88% and 83% with the 9-month regimen, and 90% and 75% with the 12-month regimen in adults and children/adolescents. Initial resistance to ethambutol and prothionamide did not affect treatment success rates but resistance to fluoroquinolones did, although this was not statistically significant. Vomiting was the most frequently encountered AE, followed by ototoxicity and hepatotoxicity. AEs experienced were mild or moderate in severity in most patients, and did not lead to treatment interruption. These results confirm the programmatic effectiveness and tolerability of the shorter regimen in second-line drug-naïve patients. .

A study of the presence of B. burgdorferi, Anaplasma (previously Ehrlichia) phagocytophilum, Rickettsia, and Babesia in Ixodes ricinus collected within the territory of Belluno, Italy.

In the years 2000 and 2001, we sampled ticks in order to establish the distribution of Ixodes ricinus in the province of Belluno; 5987 tick samples from 244 sites throughout the province were gathered, by dragging for a 5-min period. In 40 sites, seasonal variations and cycle stages of the parasites were studied at monthly intervals from March to September. A polymerase chain reaction (PCR) technique was used to identify the tick-infected sites. Of 1931 individual ticks, 8.23% were positive for Borrelia burgdorferi, 4.4% were positive for Ehrlichia, 1.6% were positive for Rickettsia, and 1.6% were positive for Babesia. The co-presence of Borrelia and Ehrlichia (1.2%) and Babesia (0.5%), Borrelia, Ehrlichia and Rickettsia (0.1%) was also found.

Sparks creating light? Strengthening peripheral disease surveillance in the Democratic Republic of Congo.

SETTING: The Democratic Republic of Congo suffers from an amalgam of disease outbreaks and other medical emergencies. An efficient response to these relies strongly on the national surveillance system. The Pool d'Urgence Congo (PUC, Congo Emergency Team) of Médecins Sans Frontières is a project that responds to emergencies in highly remote areas through short-term vertical interventions, during which it uses the opportunity of its presence to reinforce the local surveillance system. OBJECTIVE: To investigate whether the ancillary strengthening of the peripheral surveillance system during short-term interventions leads to improved disease notification. DESIGN: A descriptive paired study measuring disease notification before and after 12 PUC interventions in 2013-2014. RESULTS: A significant increase in disease notification was observed after seven mass-vaccination campaigns and was sustained over 6 months. For the remaining five smaller-scaled interventions, no significant effects were observed. CONCLUSION: The observed improvements after even short-term interventions underline, on the one hand, how external emergency actors can positively affect the system through their punctuated actions, and, on the other hand, the dire need for investment in surveillance at peripheral level.

Contexte : La République Démocratique du Congo souffre d'un amalgame de flambées épidémiques et d'autres urgences médicales. Une réponse efficace à ces problèmes est basée sur le système national de surveillance. Le Pool d'Urgence Congo (PUC) de Médecins Sans Frontières est un projet répondant aux urgences dans les zones très reculées grâce à des interventions verticales à court terme, pendant lesquelles le projet met à profit l'opportunité de sa présence pour renforcer le système de surveillance local.Objectif : Vérifier si le renforcement complémentaire du système de surveillance périphérique pendant des interventions à court terme amène une amélioration de la notification des maladies.Schéma : Une étude descriptive par paires mesurant la notification des maladies avant et après 12 interventions PUC en 2013­2014.Résultats : Une augmentation significative de la notification des maladies a été observée après sept campagnes de vaccination de masse et elle s'est maintenue pendant 6 mois. En ce qui concerne les cinq interventions restantes à plus petite échelle, aucun effet significatif n'a été observé.Conclusion : Les améliorations observées, même après des interventions à court terme, soulignent d'un côté comment des acteurs externes de l'urgence peuvent affecter positivement le système à travers leurs actions ponctuelles et, d'un autre côté, le besoin pressant d'investir dans la surveillance au niveau périphérique.

Marco de referencia: La República Democrática del Congo adolece de una amalgama de brotes epidémicos y otras urgencias médicas y la eficiencia de la respuesta a esta situación depende en gran medida del sistema nacional de vigilancia. El proyecto 'Pool d'Urgence Congo' (PUC, en francés) de Médecins Sans Frontières responde a las situaciones de urgencia en zonas muy remotas, mediante intervenciones verticales a corto plazo, durante las cuales se aprovecha la presencia en el terreno con el fin de reforzar el sistema local de vigilancia sanitaria.Objetivo: Investigar si el fortalecimiento complementario del sistema periférico de vigilancia sanitaria durante las intervenciones de corta duración contribuye a mejorar la notificación de las enfermedades.Método: Un estudio descriptivo emparejado, en el cual se midió la notificación de las enfermedades antes y después de 12 intervenciones del PUC del 2013 al 2014.Resultados: Se observó un aumento estadísticamente significativo de la notificación de las enfermedades después de siete campañas de vacunación colectiva, el cual se mantuvo durante 6 meses. En las cinco intervenciones restantes de menor escala no se observaron efectos considerables.Conclusión: El progreso observado incluso después de intervenciones a corto plazo, por una parte, pone de manifiesto que los actores externos en situaciones de emergencia pueden inducir modificaciones positivas del sistema mediante sus actividades puntuales y, en segundo lugar, destaca la necesidad urgente de invertir en el sistema de vigilancia sanitaria a nivel periférico.

First genetic analysis of lattice corneal dystrophy type I in a family from Bulgaria.

PURPOSE: To report a new family belonging to a previously non-investigated geographic are a with a rare form of lattice corneal dystrophy (LCD). METHODS: Detailed ophthalmologic analysis was carried out on a Bulgarian woman, enrolled for perforating keratoplasty. In order to obtain a final diagnosis both histology and genetic analysis were performed. RESULTS: Upon transplantation, histologic analysis of the dystrophic cornea revealed the typical staining pattern and amyloid deposits of lattice corneal dystrophies. Genetic analysis of the subject and her daughter confirmed the presence of an autosomal dominant R124C mutation within exon 4 of the BIGH3 gene, encoding for keratoepithelin, while showing no abnormalities in her son. CONCLUSIONS: The identification of this mutation allows the unambiguous classification of this corneal dystrophy as LCD type I. A first case of LCD I in a family from Eastern Europe could help to better clarify the molecular epidemiology of the disease.

Selection and characterization of early hematopoietic progenitors using an anti-CD71/S06 immunotoxin.

Most recently reported methods to select early hematopoietic cells basically rely on the depletion of committed progenitors. This task is generally accomplished by laborious procedures, which are sometimes difficult to reproduce. To simplify the selection method, we took advantage of the expression of the transferrin receptor (CD71) by proliferating committed progenitors and the lack of CD71 on noncycling immature progenitors. A monoclonal antibody (MAB) reactive with CD71 has been conjugated to the Saponaria officinalis seed ribosome-inactivating protein (SO6). The immunotoxin (IT) complex was used at increasing concentrations on normal non-phagocytizing bone marrow cells. A complete and reproducible killing effect on myeloid (colony-forming unit-granulocyte/macrophage [CFU-GM]) and erythroid (burst-forming unit-erythroid [BFU-E]) progenitors was observed for IT concentrations of 1 x 10(-7) M. Unconjugated SO6 or anti-CD71 MAB had no effect on cell growth and viability. IT-resistant cells were able to generate CFU-GM after 7, 14, and 21 days of suspension culture in the presence of 5637 CM. Maximal CFU-GM values were obtained at day 21 and nearly approached the pretreatment values (mean 2587 vs. 3877 CFU-GM/mL). Growth factor enhancement of CFU-GM yield was obtained only by stem cell factor (SCF) at day 7; SCF, as well as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3), had an enhancing effect at days 14 and 21. IT toxicity on highly immature progenitors was ruled out by evaluating the growth of long-term culture-initiating cells (LTC-IC) from IT-treated cultures. LTC-IC frequency was found to be 1 out of 1506 seeded cells, which is within the range of normal untreated BM cells. In conclusion, anti-CD71 IT allows a simple and complete depletion of committed progenitors while sparing immature hematopoietic cells. The high CD71 expression by leukemic cells makes the procedure potentially suitable for in vitro purging.

Elevated diet-induced thermogenesis and lipid oxidation rate in Crohn disease.

BACKGROUND: Although malnutrition is frequently observed in Crohn disease (CD), its cause is not clear. Regulation of energy metabolism and diet-induced thermogenesis (DIT) have not been adequately studied in CD. OBJECTIVE: The aim was to study DIT and substrate oxidation in patients with inactive ileal CD. DESIGN: After a test meal providing 50.2 kJ/kg body wt, DIT was assessed by indirect calorimetry performed over 360 min in 18 CD patients and 12 healthy volunteers matched for age, sex, weight, and height. Body composition was evaluated with the labeled-water-bolus injection technique. RESULTS: Fat-free mass did not differ significantly between groups, but CD patients had markedly lower fat mass than control subjects (13.8+/-5.63 compared with 19.0+/-3.49 kg; P < 0.001). Nonprotein respiratory quotient was lower in CD patients than control subjects (0.80+/-0.04 compared with 0.86+/-0.03; P < 0.001). Average respiratory quotient between 75 and 150 min after the test meal was 0.85+/-0.03 in CD patients and 0.91+/-0.02 in control subjects (P < 0.001). Lipid oxidation rate was higher in CD patients than in control subjects (2.26+/-1.13 compared with 1.50+/-0.75 kJ/min; P < 0.05). DIT was higher in CD patients than in control subjects (9.89+/-1.93% compared with 5.67+/-0.91% of energy intake; P < 0.001). CONCLUSIONS: Patients with inactive ileal CD had significantly higher DIT and lipid oxidation rate than do healthy volunteers. These results may explain why CD patients have difficulty maintaining adequate nutritional status, and the findings also suggest that a diet relatively rich in fat may attain better energy balance.

Twenty-four-hour energy balance in Crohn disease patients: metabolic implications of steroid treatment.

Several hypotheses have been proposed to explain the nutritional deficiencies seen in Crohn disease patients, including inadequate food intake, decreased assimilation and increased loss of nutrients, and increased energy expenditure. To assess the effect of steroid therapy on body composition, energy expenditure, and fuel selection in Crohn disease, we compared 12 patients (6 men and 6 women) with biopsy-proven ileal Crohn disease with 11 healthy volunteers (6 men and 5 women). Five patients [Crohn's disease activity index (CDAI) = 98.4 +/- 3.78] took no medication and seven patients (CDAI = 283.9 +/- 22.5) were administered 29 +/- 18 mg prednisone/d. Body composition was evaluated by isotopic dilution and bioelectrical impedance analysis, and 24-h energy expenditure and basal metabolic rate were measured in a respiratory chamber. Fat-free mass was not significantly different among groups, whereas fat mass was lower in patients than in control subjects. Energy intake was higher in treated patients than in both untreated patients (P = 0.004) and control subjects (P = 0.005). Fecal losses were not significantly different between untreated patients and control subjects, but were higher (and proportional to the CDAI) in treated patients than in control subjects (P = 0.001). Metabolizable energy was not significantly different among groups, whereas energy balance was significantly higher in treated patients than in both control subjects (P = 0.0057) and untreated patients (P = 0.018). Nitrogen balance was mildly negative in treated patients compared with both control subjects and untreated patients, but not significantly so. In conclusion, prednisone treatment in Crohn disease patients stimulates food intake, promoting an overall positive energy balance despite large fecal nutrient losses.

Physiological roles of neuronal nicotinic receptor subtypes: new insights on the nicotinic modulation of neurotransmitter release, synaptic transmission and plasticity.

Nicotinic acetylcholine receptors (nAChRs) are widely expressed in the mammalian central nervous system (CNS). Despite this, very little was known, until recently, about their physiological role. In the periphery, nicotinic receptors mediate vital excitatory fast synaptic cholinergic transmission at both the neuromuscular junction and ganglia. In the brain, this role has been mainly "delegated" to glutamate receptors. The very broad cholinergic innervations of most brain areas, including the cortex, have implicated this system, and brain nicotinic receptors in particular, in a unique "modulatory" role of other transmitters systems. Recent evidence confirms, on one hand, that brain nicotinic receptors have a dominant "presynaptic" modulatory function, controlling the release of both acetylcholine (auto-receptors) and other neurotransmitters (hetero-receptors). On the other hand, more experimental data support the idea that a variable component of fast synaptic transmission in the brain can also be mediated by "postynaptic" nicotinic receptors, which, in turn, can control cell excitability. A challenging goal is to identify which one of the plethora of nicotinic receptor subtypes is mediating each effect in different brain areas, and which of these receptors and functions are lost or affected in different human neuro-psychiatric disorders. Needless to say, a better understanding of the physiological role of brain nicotinic receptors will drive our quest for more selective and efficacious nicotinic receptor targeted therapeutic agents.

Comparison of insulin response to intravenous glucose in healed myocardial infarction, in "cooled-off" unstable and stable angina pectoris, and in healthy subjects.

Fasting and postglucose hyperinsulinemia are recognized risk factors for acute coronary events. The insulin reactivity of patients with acute coronary syndromes, however, has not been carefully compared with that of patients with chronic stable angina. We used Bergman's minimal model to analyze the insulin response to intravenous glucose in 21 subjects: 8 patients with previous (>3 months) acute coronary syndrome but no effort-related angina; 6 patients with stable effort angina but no prior acute event; and 7 healthy controls. Diabetes mellitus, systemic hypertension, dyslipidemias, and obesity were excluded. All patients underwent coronary angiography. Insulin sensitivity, glucose effectiveness, and glucose tolerance were determined from insulin and glucose concentrations measured frequently up to 3 hours after a 0.33 g/kg intravenous glucose bolus. Patients with previous unstable angina or acute myocardial infarction had less extensive disease at angiography than patients with stable angina (p = 0.007). Both patient groups had higher basal and 180-minute insulinemia than controls (p <0.0007). However, patients with stable angina did not differ significantly from controls with regard to early and late insulinemic response to glucose. In contrast, patients with previous acute onset of ischemia had significantly greater 180-minute integrated insulinemia (p = 0.04) and reduced insulin sensitivity (p = 0.05) after the glucose challenge than did the stable angina group. These data suggest that patients with acute presentation of coronary artery disease, compared with patients with uncomplicated chronic stable angina, have an impaired insulin response to glucose despite less extensive coronary disease at angiography.

Safety and efficacy of procainamide infusions.

Thirty-four patients who were resistant to conventional doses of lidocaine received procainamide intravenously according to a pharmacokinetically designed two infusion technique. A mean peak serum concentration of 7.1 mg/liter was achieved with an average loading dose of 989 mg administered over 1 hour. A mean steady state serum concentration of procainamide of 6.5 mg/liter was achieved with a mean dose of 64.4 mg/kg body weight for the first 24 hours of treatment. Dose, renal impairment, the degree of congestive heart failure and acetylator status influenced the steady state serum concentration of procainamide. Dangerous ventricular arrhythmias were abolished in 74% of the patients at a steady state level of 6.9 +/- 3.7 mg/liter (mean +/- standard deviation). Nonresponders to procainamide had a mean steady state serum concentration of procainamide of 4.2 +/- 2.1 mg/liter (P less than 0.05). Systolic and diastolic blood pressures decreased moderately (10 and 8%, respectively), and heart rate decreased 11%. The infusion was interrupted in one patient because of hypotension. The duration of electrocardiographic conduction intervals was increased slightly in some patients. It is concluded that procainamide administered by this two infusion method is effective and well tolerated by most patients.

Renoprotection by nitric oxide donor and lisinopril in the remnant kidney model.

Previous studies showed a renoprotective effect of l-arginine in experimental uremia. Whether this was caused by an increased nitric oxide (NO) release or depended on l-arginine per se is not clear. Here, we evaluated whether chronic administration of an NO donor, molsidomine, controlled systemic blood pressure and renal disease progression and prolonged survival in rats with renal mass reduction (RMR). Rats with RMR received the following daily in the drinking water: group 1 (n = 21), no specific therapy (vehicle); group 2 (n = 12), molsidomine, 120 mg/L; group 3 (n = 9), lisinopril, 25 mg/L; and group 4 (n = 12), reserpine, 5 mg/L, hydralazine, 80 mg/L, and hydrochlorothiazide, 25 mg/L, from day 21 after surgery, when rats had hypertension and proteinuria, until the death of the vehicle-treated rats. Molsidomine normalized systemic hypertension, only partially reduced proteinuria and serum creatinine levels, but significantly prolonged animal survival, particularly in the early stage of the disease. Lisinopril at a similar systemic blood pressure was even better than molsidomine in limiting proteinuria, preserving renal function, and prolonging survival, but triple therapy, despite being effective on blood pressure, offered no renoprotection or prolonged survival. Endothelin-1 (ET-1) levels, formed in excessive amounts by the kidneys of these animals, were reduced by molsidomine and lisinopril, but not by triple therapy. The prolongation of survival by NO donor could be attributed to its effect of reducing ET levels, which in turn may limit the smooth muscle cell proliferation and matrix accumulation responsible for organ and, especially, myocardial fibrosis in uremia.