Antiviral effect of high-pressure nasal stimulation.

OBJECTIVE: In a previous study, we reported an increase of nasal nerve growth factor (NGF) in patients treated with high-pressure administration of sterile saline isotonic solution (HPpSIS). Herein we characterized the nasal mucosa in terms of innate immune response and cytokine signature, including antiviral properties. Potential NGF and antiviral benefits of HPpSIS were also discussed. PATIENTS AND METHODS: Twenty (20) patients (11 males, 9 females; age range 30-75 years old) underwent HPpSIS and nasal samples were collected before and after treatment. Nasal scraping was used for morphological (smears and Quick May-Grunwald Giemsa staining, MGG), biochemical (Histamine, Serotonin; ELISA) and molecular (messenger RNA, mRNA) analyses. Amplification of transcripts specific for Toll-like receptor (TLR) 3 (TLR3), TLR7, TLR9, Interleukin-(IL) 18 (IL18), IL13, IL12, eosinophil-derived neurotoxin (EDN), Eosinophil Cationic Protein (ECP), γ Interferon (γIFN), tryptase and serotonin was performed using the 2-step real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR). Clinical and laboratory data were analyzed and compared. RESULTS: The clinical evaluation showed a protective effect of our therapy. Smears showed the presence of leucocytes, eosinophils (EOs) and mast cells (MCs), and increased immunoreactivity for ECP/RNase3 and EDN after HPpSIS. ELISA showed increased levels of Serotonin and EDN associated with unchanged levels of substance P(SP) and histamine. Increased eosinophil-derived neurotoxin eosinophil-derived neurotoxin (EDN) levels were confirmed by in situ fluorescent analysis. HPpSIS induced the upregulation of TLR3, TLR7 and TLR9 transcripts, while no changes were observed for Intercellular Adhesion Molecule 1 (ICAM1), IL18, Interleukin-15 (IL15) and IL12 transcripts nor for Interleukin-6 (IL6) and IL13. No changes were also observed for γIFN and EDN/RNase2 transcripts, while ECP/RNase3 transcripts were significantly upregulated after HPpSIS. Finally, tryptase transcripts were unchanged while serotonin transcripts were significantly increased after HPpSIS. CONCLUSIONS: The clinical and biomolecular changes observed at the nasal mucosa due to HpSS treatment suggest the activation of an innate surveillance, by means of TLR transcription, and a possible anti-viral response due to EDN upregulation. It remains to be verified if NGF, known to be released locally upon HpSIS treatment, might in part be responsible for this local activation.

Minimal influence of traditional surgical risk factors on mortality in contemporary aortic valve replacement.

AIM: Transcatheter aortic valve implantation is increasingly presented as an alternative to aortic valve replacement in the high risk surgical candidate. We review the outcomes of isolated aortic valve replacement to identify contemporary results of aortic valve replacement in such high risk patients. METHODS: Retrospective analysis of 846 patients (mean age 68.7 ± 11.8 years) who underwent aortic valve replacement in a single institution from 1999 to 2008. We considered 10 risk factors as follows: female gender (395 patients, 46.7%), age, left ventricular ejection fraction, New York Heart Association Class, preoperative creatinine clearance, body mass index, peripheral vascular disease (49 patients, 5%), cerebrovascular disease (42 patients, 4.9%), chronic obstructive pulmonary disease (87 patients,10.2%), and redo surgery (53 patients, 6.2%). RESULTS: Twenty-five patients died (2.9%). Age (P=0.032; OR 1.07 per each year increase) was the only significant independent predictor of mortality. Length of stay in the hospital was correlated with age (P<0.0001), New York Heart Association Class (P<0.0001) creatinine clearance (P=0.005) and redo surgery (P=0.006). CONCLUSION: Contemporary aortic valve replacement is a low risk procedure for most patients. Historical risk factors which have been used to define high risk and inoperability, such as pulmonary disease, reoperations, decreased left ventricular ejection fraction and vascular disease, may not be relevant in the current era. This observation should be considered if such criteria are used to define patients for transcatheter aortic valve implantation.

A ruptured right sinus of Valsalva diverticled aneurysm: echocardiographic diagnosis and surgical repair.

Aneurysms of sinus of Valsava (SV) are uncommon heart lesions resulting from either a congenital deficiency or an acquired degeneration of the aortic wall. Usually these lesions are asymptomatic and incidentally diagnosed by echocardiography. Therefore when rupture occurs, they might require a prompt surgical operation. We report the case of a 58-year-old man who suddenly developed chest pain. On physical examination a new finding of sistodyastolic murmur was detected. On two-dimensional echocardiography was evidenced an aneurysm of the right SV ruptured in the right atrium. The patient was submitted to urgent surgery. Surgical aneurysm exclusion was achieved through a double access either transaortic and trans-right atrium approach. The right SV was obliterated by suturing a dacron patch on the aortic site while complete exclusion of the aneurysm expanding in the right atrium, was acquired through the right atrium itself, by 5/0 continous prolene suture line. The postoperative course was uneventful and the patient was discharged on 6th postoperative day. Transesophageal echocardiography represent the gold standard technique to assess this disease and to plan the adequate surgical treatment. The management of an asymptomatic, non ruptured aneurysm is not clear, however surgery is advisable when the aneurysm is complicated by rupture with an acceptably low operative risk and good long-term outcome.

[Bentall-DeBono intervention: 8 years of clinical experience]. / Intervento di Bentall-DeBono: otto anni di esperienza clinica.

BACKGROUND: Annulo-aortic ectasia is a dilation of the aortic root with the involvement of the Valsalva sinuses. In 1968 Bentall and DeBono proposed to replace the aortic valve, the Valsalva sinuses and the ascending aorta with a composite tube graft containing aortic valve prosthesis. Consequently coronary ostia had to be reimplanted on the prosthetic tube. Recently the use of new materials has resulted in a more acceptable operative risk, and postoperative bleeding and late mortality have been reduced. METHODS: From January 1991 to December 1998, 44 out of 241 patients were operated on with the Bentall-DeBono procedure, affected by dissecting or expansive aneurysm of the ascending aorta. Of the 44 patients (35 males, 9 females, mean age 53.7 years), 3 presented with acute aortic dissection, 5 were asymptomatic, 10 were in NYHA functional class II, 14 in class III, 9 in class IV, and 2 in CCS class 4; 1 patient had dysphonia; 37 patients presented with isolated aortic regurgitation, and 7 associated aortic valvular stenosis. The diagnosis of acute dissection was made by transesophageal echocardiography and that of expansive aneurysm by thorax helical computed tomographic scanning and/or magnetic resonance imaging and cardiac catheterization. Follow-up was obtained in 100% of the patients for an average of 23 +/- 20.9 months (range 4-79 months). RESULTS: Four patients (9%) died; in 4 patients (9%) postoperative bleeding needed reoperation, in 5 (11.4%) a permanent pacemaker for atrioventricular block was implanted, and 1 patient (2.3%) had transient hemiparesis. At univariate analysis predictive factors for operative risk were NYHA functional class IV (p < 0.005) and atherosclerotic etiology (p < 0.05). At follow-up 7 late deaths occurred for an actuarial survival at 24 months of 75 +/- 9%. Causes were sudden death in 3 patients, cardiac failure in 3 and stroke in 1 patient; 31 surviving patients (94%) were in NYHA functional class I and 2 patients in class II (6%). CONCLUSIONS: The Bentall-DeBono procedure involves moderate risk with good results; clinical presentation and associated valvular pathology influence early and mid-term results.

Patient with large 17p11.2 deletion presenting with Smith-Magenis syndrome and Joubert syndrome phenotype.

We report on a 22-year-old woman carrying a del(17)(p11.2p12) and presenting with the clinical manifestations of both Smith-Magenis syndrome (SMS) and Joubert syndrome (JS). Her facial anomalies, brachydactyly, severe mental retardation, and self-injuring behavior could be attributed to SMS, whereas the cerebellar vermis hypoplasia, hypotonia, ataxic gait, developmental delay, and abnormal respiratory pattern were suggestive of JS. By fluorescent in situ hybridization analyses with Yeast Artificial Chromosomes (YAC) mapping to the 17p11.2 region, as well as locus-specific probes generated through a novel procedure, we could establish that the deletion encompasses a 4-Mb interval with centromeric and telomeric breakpoints at loci D17S793 and D17S953, the latter close to the locus Charcot Marie Tooth 1A (CMT1A)-REP. The deletion differs from that commonly found in SMS in its telomeric boundary, which is more distal than usually observed. The presence of JS phenotype in our patient and the detection of an unusual SMS deletion might suggest the presence of a JS gene in close proximity to the SMS locus.

New case of the Richieri-Costa/Guion-Almeida syndrome.

We describe a boy with multiple congenital anomalies/mental retardation (MCA/MR) syndrome. He has growth retardation, microbrachycephaly, coloboma of the iris, and typical facial anomalies including cleft lip/palate. This phenotype overlaps with that described by Richieri-Costa and Guion-Almeida in three Brazilian brothers. The new patient provides further evidence of the existence of this rare clinical entity.

Early postoperative myocardial ischemia after coronary artery bypass grafting. Detrimental effects of nitroglycerine infusion.

This study was aimed at assessing the incidence and mechanisms of myocardial ischemia early after coronary artery bypass grafting and the effects of treatment with nitroglycerine. The electrocardiogram of 35 patients (29 males and 6 females, mean age 61 +/- 8 years) with stable angina and multivessel coronary disease, was monitored continuously for 24 hours after uncomplicated coronary artery bypass grafting. Patients were randomized to receive nitroglycerin infusion or placebo. Fourteen of the 35 patients (40%) had 24 transient ischemic episodes (mean duration 11.8 +/- 3.5 min; range 6-20 min with ST segment elevation in 6, ST segment depression in 7 and both ST segment elevation and depression in 1. Seventy-five per cent of the ischemic episodes occurred within the first 6 postoperative hours. The mean ejection fraction prior to surgery and the mean number of stenosed vessels and of the implanted grafts were similar in patients with and without postoperative ischemia (57 +/- 5 vs 57 +/- 6%, p = 0.86; 2.7 +/- 0.5 vs 2.8 +/- 0.4, p = 0.52 and 3.0 +/- 0.9 vs 3.2 +/- 0.7, p = 0.51, respectively) as well as total bypass time and cross-clamp time (123 +/- 38 vs 124 +/- 18 min, p = 0.89 and 67 +/- 20 vs 70 +/- 14 min, p = 0.68, respectively). The values of heart rate and systolic blood pressure at the onset of the ischemic episodes were similar to those recorded 15 min before (103 +/- 16 vs 106 +/- 18 b/min, p = 0.36 and 119 +/- 12 vs 121 +/- 14 mmHg, p = 0.48). Ischemic episodes were recorded in 9 of the 16 patients (56%) randomized to receive nitroglycerine and in 5 only of the 19 patients (26%) randomized to receive placebo (p = 0.05). Thus, transient ischemic episodes occurring early after coronary artery bypass grafting are not preceded by an increase in myocardial oxygen consumption; they appear to be due, therefore, to a primary reduction in coronary blood flow. Treatment with nitroglycerine is associated with a higher prevalence of ischemic episodes, thus suggesting that myocardial ischemia is unlikely to be caused by spasm of large epicardial vessels or grafts. Myocardial ischemia may be caused, instead, by extracorporeal circulation-induced alterations enhanced by the hypotensive effects of nitroglycerine.

Intraoperative antifibrinolysis and blood-saving techniques in cardiac surgery. Prospective trial of 3 antifibrinolytic drugs.

Sixty consecutive patients undergoing elective open-heart surgery were prospectively enrolled in a study to compare the efficacy of 3 different antifibrinolytic drugs to reduce postoperative bleeding and to reduce homologous blood requirements in combination with blood-saving techniques and restrictive indications for blood transfusion. The patients were randomized to 1 of 4 intraoperative treatment regimens: 1) control (no antifibrinolytic therapy); 2) epsilon-aminocaproic acid (10 g IV at induction of anesthesia, followed by infusion of 2 g/h for 5 hours); 3) tranexamic acid (10 mg/kg IV within 30 minutes after induction of anesthesia, followed by infusion of 1 mg/kg per hour for 10 hours); or 4) high-dose aprotinin (2 million KIU IV at induction of anesthesia and 2 million KIU added to the extracorporeal circuit, followed by infusion of 500 thousand KIU/h during surgery). Hemoconcentration and reinfusion of blood drained from the operative field and the extracorporeal circuit after operation were used in all patients. Indications for blood transfusion were hypotension, tachycardia, or both, with hemoglobin values < 8.5 g/dL; or severe anemia with hemoglobin values < 7 g/dL. Compared with the blood loss in the control group, patients receiving aprotinin and epsilon-aminocaproic acid showed significantly less postoperative blood loss at 1 hour (control, 128 +/- 94 mL; aprotinin, 54 +/- 47 mL, p = 0.01; and epsilon-aminocaproic acid, 69 +/- 35 mL, p = 0.03); this trend continued at 24 hours after operation (control, 724 +/- 280 mL; aprotinin, 344 +/- 106 mL, p < 0.0001; and epsilon-aminocaproic acid, 509 +/- 148 mL, p = 0.01). Aprotinin was significantly more efficient than epsilon-aminocaproic acid (p=0.002). Tranexamic acid did not have a statistically significant effect on blood loss. Homologous blood requirements were not significantly different among the groups; postoperative hematologic values and coagulation times were also comparable. Despite the efficacy of aprotinin and epsilon-aminocaproic acid shown in the present study, the blood requirements were not significantly different from those that are found when transfusions are restricted, autotransfusions are used, and blood from the operative field and extracorporeal circuit is concentrated and reinfused. Therefore, intraoperative antifibrinolysis may not be indicated in routine cardiac surgery when other blood-saving techniques are adopted.

[Esthetic suture of the lower limbs after a saphenous vein graft in cardiac surgery. Polydioxanone vs Vicryl]. / Sutura estetica degli arti inferiori dopo prelievo della vena safena in cardiochirurgia. Polidiossanone vs Vicryl.

The vena saphena magna is widely used as a passage during myocardial revascularisation surgery (CABG). The preparation of the vein involves a long incision on the thigh and leg which is routinely closed using a continuous suture thread in Vicryl of the subcutis and continuous intradermal suture of the cutis. The authors retrospectively evaluated the functional and esthetic results of intradermal suture performed using two different types of reabsorbable thread: PDS II and Vicryl. A total of 178 patients underwent CABG surgery at the Heart Surgery Division of Tor Vergata University of Rome during the period January-September 1992. Mean age was 63 year +/- 7 (SD), 140 were males and 38 females. PDS II 3/0 was used for intradermal suture in 88 patients, whereas Vicryl 3/0 was used in 90. There were no significant differences between the two groups with regard to age, sex, number of grafts, associated pathologies or wound length. After 1-9 months (mean 5.6 months) the surgical wound on the saphenectomized limb was evaluated. It was found that compared to Vicryl the use of PDS II presented a higher incidence of keloids (p > 0.05). This was probably due to the greater reaction provoked in the dermis by the monofilament compared to twisted thread. The authors conclude that the use of a reabsorbable twisted thread, such as Vicryl or Vicryl Rapid, is preferable owing to the higher rate of compliance and lower incidence of complications.

Evaluation of suspected deep venous thrombosis in oncologic patients.

Impedance plethysmography (IPG) and duplex scanning with color flow Doppler were performed in 100 consecutive high-risk patients with clinically suspected deep venous thrombosis. Risk factors included recent surgery (< three weeks) in 23%, malignant disease in 91%, clotting abnormalities in 32%, and limited activity in 70%. Lower limb findings of either edema, calf tenderness, or both occurred in 92%. There was agreement between the two tests in 76 patients (29 positive and 47 negative). In 12 patients the IPG was positive and the duplex negative. Four of these had extensive pelvic disease, 2 had lung cancer with an obstructive profile, and 2 had heart failure, all of which are known to cause false-positive IPG results. In the other 12 patients the IPG was negative and the duplex positive; however, 3 of these patients had nonocclusive thrombi, 5 had pelvic disease, and 1 had a hemiparesis of the involved lower limb. In 15 patients (11 with positive duplex studies and 4 with negative) a venogram was obtained and confirmed the results. All patients were followed up clinically and none developed complications suggesting inaccurate duplex results. In conclusion, the IPG is of limited utility in this population with a sensitivity of 71%, specificity of 80%, and false-negative rate of 29% when duplex Doppler and clinical outcome are used as the standard. Where available, duplex Doppler should be preferred for evaluation of suspected deep venous thrombosis in patients with extensive medical disease.

Kinking of internal carotid artery: is it a risk factor for cerebro-vascular damage in patients undergoing cardiac surgery?

The incidence of carotid artery kinking is reported from 4% to 25% in different studies. During cardiopulmonary by-pass (CPB) in cardiac surgery the hemodynamic effects related to the kinking could produce hypoperfusion especially if associated with atherosclerotic lesions of the carotid arteries. We report our experience of 653 patients (538 males, 115 females, mean age 58.3 years) studied by coronaroangiography and internal carotid artery duplex scanning during the period January 1991-December 1992. Thirty-seven patients (22 males, 15 females, mean age 64.9 years), revealed anomalies of the internal carotid artery classificated as tortuosity (9 patients; 24.4%), and kinking (28 patients; 75.6%). All but 4 patients underwent cardiac surgery isolated or associated with carotid thrombo-endarterectomy (TEA) with Dacron patch arterioplasty. Three patients died (8.1%), one of them from cerebrovascular accident. He was a patient who had thromboembolism from the ascending aorta but without associated atherosclerotic lesions of carotid arteries. Asymptomatic isolated internal carotid artery kinking does not seem to be a risk factor for neurological complications during CPB. If carotid kinking is symptomatic and associated with atherosclerotic plaque producing internal carotid artery stenosis greater than 75%, we strongly suggest surgical treatment before cardiac operation.

[Unstable angina: the point of view of the surgeon]. / L'angina instabile: il parere del chirurgo.

Unstable angina is a serious condition with high risk of early coronary events; coronary revascularization in these patients gives good results but carries higher operative risk than in stable angina patients. Full medical therapy with antiischemic agents may be effective in controlling symptoms and preventing death and is therefore the first treatment of choice; as in stable angina, further treatment is indicated in stabilized patients according to non invasive tests results and coronary angiograms. Non responsive unstable patients have a poor outcome and are candidates for revascularization: angioplasty may be preferred in single or double vessel disease and bypass operation in multivessel disease. However, surgical revascularization in single and double vessel disease with critical proximal stenosis of a large anterior descending gives optimal results in our experience and may be the treatment of choice also in these patients. Because of the higher operative risk in multivessel disease in unstable ischemia, a combined procedure with angioplasty of the "culprit" lesion followed by full revascularization at a later time may be a more favourable option in some patients with multivessel disease.

Clinical cardiotoxicity of 5-fluorouracil.

5-Fluorouracil is widely known to be toxic to the hematopoietic and gastrointestinal systems. It also has cardiac toxicity, but this is perceived to be rare. During a 16-month period from January 1990 through April 1991, approximately 910 patients were treated with 5-fluorouracil. Five of these developed life-threatening toxicity consistent with coronary artery spasm for an incidence of .55%. The acute events occurred on the third or fourth day of the 5-day infusion and after the fourth intravenous bolus in the patient on bolus therapy. Each of the patients had ST elevation and ventricular arrhythmias, four had acute myocardial infarction, and two had cardiac arrests. In these cases and those previously reported, cardiac toxicity is consistent with drug- or metabolite-mediated increases in coronary vasomotor tone and spasm, leading to the full spectrum of signs and symptoms of myocardial ischemia in susceptible individuals.

Isoflurane versus fentanyl: hemodynamic effects in cancer patients treated with anthracyclines.

Cancer patients treated with anthracycline derivatives are at risk for perioperative cardiovascular decompensation. The authors studied hemodynamic performance before, during, and after laparotomy in 14 anthracycline-treated patients with ovarian carcinoma. General anesthesia was maintained with 70% N2O in O2, and patients were randomized to receive supplementation with either isoflurane, 0.59% end-tidal +/- 0.04 (mean +/- SE), or fentanyl, 2.67 micrograms/kg +/- 0.49 as a loading dose, and a total dose of 7.16 micrograms/kg +/- 0.71. The degree of hemodynamic stability relative to the baseline was assessed. There was no obvious superiority of either technique prior to the skin incision. However, during and immediately after surgery, a clearer tendency for isoflurane-N2O to result in better hemodynamic stability was found. Isoflurane-N2O demonstrated significantly smaller change scores in systemic vascular resistance (SVR) and cardiac index (CI). At the start of surgery, the isoflurane-N2O change in SVR was 228.08 dyne.sec.cm-5 compared to 479.58 for the fentanyl patients, (P = 0.002); at the end of surgery the corresponding means were -12.09 and 703.14 dyne.sec.cm-5, respectively, (P = 0.002). Isoflurane-N2O was associated with significantly greater CI stability in the early postoperative period: the isoflurane-N2O mean change was -0.081 L/min/m2, versus -0.993 for the fentanyl-N2O patients, (P = 0.005). The authors conclude that anthracycline-treated patients who do not have overt evidence of cardiomyopathy can be safely anesthetized with either anesthetic technique. However, during surgery and in the early postoperative period, an isoflurane-N2O technique appears to offer better hemodynamic stability.

Tricuspid valve thromboembolus with recurrent pulmonary embolism--a case report.

The authors describe a fifty-one-year-old man with multiple pulmonary emboli in whom two-dimensional echocardiography clearly showed a large mobile thrombus transiently entrapped in the chordal apparatus of the tricuspid valve, a location rarely noted except in autopsy specimens. Subsequent lung scan and echocardiograms documented clinically silent nonfatal embolization of this large thrombus to the lungs. Whereas most patients with this form of thromboembolic disease come to either surgery or autopsy, this case demonstrates how the combination of echocardiography and lung scanning can be used to differentiate the etiology of some right-heart masses.

Clinical performance of low-profile bioprostheses: results at 10 years.

The purpose of this retrospective study is to evaluate the long-term performance of the Liotta minimally intrusive bioprosthesis (MIB) and to identify its most important risk factors. From January 1980 to March 1982, 73 patients (30 males and 43 females; mean age 45.5 years +/- 11.7 standard deviation; range 11 to 64) underwent operation for heart valve replacement with an MIB. Fifty-two mitral valve replacements (MVR), 16 aortic valve replacements (AVR), 4 mitral and aortic valve replacements (MAVR), and 1 mitral and tricuspid valve replacement (MTVR) have been performed (78 MIBs implanted). Global operative mortality has been 8.2% (6/73): 9.6% (5/52) for MVR and 6.2% (1/16) for AVR. The 10-year follow-up reaches 519 patient-years and 581 valve-years, and is 96.5% and 93.9% complete, respectively. Actuarial freedom from any patient- or valve-related event has been calculated at one time with its hazard function and its incidence normalized per 100 patient- and/or valve-years; statistical significance of difference between curves has been assessed. In this report, overall actuarial survival at 10 years is 79.4% +/- 5.3% SEM (standard error of the mean), including operative deaths (incidence = 2.6% per patient-year). Two patients experienced periprosthetic leakage (PL) at 4 and 9 years, respectively (incidence = 0.4% per valve-year). One patient underwent reoperation because of otherwise untreatable prosthetic valve endocarditis (PVE) at 5 years (0.2% per valve-year).(ABSTRACT TRUNCATED AT 250 WORDS)