Insomnia and menopause: a narrative review on mechanisms and treatments.

The menopausal transition is associated with an increased frequency of sleep disturbances. Insomnia represents one of the most reported symptoms by menopausal women. According to its pathogenetic model (3-P Model), different predisposing factors (i.e. a persistent condition of past insomnia and aging per se) increase the risk of insomnia during menopause. Moreover, multiple precipitating and perpetuating factors should favor its occurrence across menopause, including hormonal changes, menopausal transition stage symptoms (i.e. hot flashes, night sweats), mood disorders, poor health and pain, other sleep disorders and circadian modifications. Thus, insomnia management implies a careful evaluation of the psychological and somatic symptoms of the individual menopausal woman by a multidisciplinary team. Therapeutic strategies encompass different drugs but also behavioral interventions. Indeed, cognitive behavioral therapy represents the first-line treatment of insomnia in the general population, regardless of the presence of mood disorders and/or vasomotor symptoms (VMS). Different antidepressants seem to improve sleep disturbances. However, when VMS are present, menopausal hormone therapy should be considered in the treatment of related insomnia taking into account the risk-benefit profile. Finally, given its good tolerability, safety, and efficacy on multiple sleep and daytime parameters, prolonged-released melatonin should represent a first-line drug in women aged ≥ 55 years.

The evolution of multigene panel testing for hereditary cancers.

A thorough family history evaluation remains a critical tool that helps identify those patients who are at risk for hereditary cancer. The American College of Obstetricians and Gynecologists (ACOG) recommends that all women receive a family history evaluation to screen for inherited risk, and that this information be regularly updated. Patients with an abnormal cancer family history need additional follow-up that may include hereditary cancer testing. Multigene panel testing provides comprehensive profiling for hereditary cancer patients by identifying more health risks than single genome testing. If hereditary cancer is established, patients should be counseled about management options, including increased surveillance, chemoprevention, and/or surgery. Establishing workflow protocols may help clinicians integrate hereditary cancer risk assessment into their practice.

Long term clinical outcomes in DES implantation for unprotected left main disease.

AIM: Generate a long term follow-up and evaluate the impact of clinical and procedural characteristics on long term events in percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation for unprotected left main coronary artery (ULMCA) disease. METHODS: Ninety-seven consecutive patients who underwent PCI with DES, either sirolimus (SES) or paclitaxel-eluting stent (PES), for de novo lesions in ULMCA were analyzed. No patients were excluded. Mean follow-up was 3 years (range 1-6.7 years). RESULTS: Technical and procedural success rate were 100% and 95.9%. According to the Academic Research Consortium definitions, cardiac death occurred in 6.1% of patients, reinfarction, target vessel revascularization (TVR) and target lesion revascularization (TLR) occurred in 6.1%, 17.5% and 4.2% of patients respectively. Definite stent thrombosis (ST) incidence was 1%, whereas possible ST occurred in 4.2% of patients. Postdilation was performed in 49.5% of patients and was, among all clinical and procedural characteristics, the only factor at multivariate analysis significantly related to lower MACE (25% vs. 46.9%, P=0.024, CI: 0.202 to 0.889) and TVR (8.3% vs. 26.5%, P=0.03 CI: 0.096-0.895). CONCLUSION: Long term follow-up in PCI of ULMCA disease shows favorable clinical results. Stent postdilation seems to have a protective role in DES PCI for ULMCA disease.

Effects of EPC capture stent and CD34+ mobilization in acute myocardial infarction.

AIM: Percutaneous coronary intervention (PCI) is the gold standard for the treatment of acute myocardial infarction (AMI), with the main limitation of in-stent restenosis for BMS and late stent thrombosis (ST) for both BMS and DES. Endothelial progenitor cells (EPC) CD34+ capture stents, promoting vascular healing, may be advantageous in preventing ST. Aim of the study is to evaluate the outcomes of AMI patients treated with EPC CD34+ capture stent and describe the mobilization kinetics of CD34+ and their clinical correlation. METHODS: Fifty AMI patients underwent primary PCI with EPC CD34+ capture stent. Serial assays of CD34+ were performed by flow-cytometric analysis. RESULTS: Procedural success rate was 100%. At six-months follow-up cardiac death, myocardial infarction, target lesion revascularization (TLR) and target vessel revascularization (TVR) occurred respectively in 2%, 4%, 10% and 12% of patients. No case of ST was observed. The MACE-free survival was 81,2%. The mean peak value of plasmatic CD34+ was 4.69±3.76 cells/µL. A positive correlation was found between CD34+ concentration, age and infarct area. No correlation was detected between CD34+ concentration and occurrence of TVR, TLR and MACE. CONCLUSION: EPC capture stent implantation seems to be safe and effective in the clinical setting of AMI, representing a possible alternative to BMS and DES. CD34+ cells plasmatic concentration seems not to correlate to coronary restenosis and atheromasic disease progression.

Rationale and results of percutaneous coronary revascularization with endothelial progenitor cell capture stent in high-risk patients requiring undeferrable non-cardiac surgery.

AIM: Drug eluting stents (DES) are currently the gold standard for the treatment of significant coronary artery stenosis in high risk patients. In case of undeferrable non-cardiac surgery their use is still a challenge, due to the need of a prolonged dual antiplatelet therapy. We aimed to prospectively evaluate the efficacy and safety of the implantation of endothelial progenitor cells (EPC) capture stent followed by a short dual anti-platelet therapy (DAT) period in a high risk population of patients undergoing undeferrable non-cardiac surgery. METHODS: We examined all consecutive patients who received EPCs capture stents and underwent non-cardiac surgery within 60 days of percutaneous coronary intervention. Our primary outcome was the occurrences of cardiac death, myocardial infarction (MI), stent thrombosis (ST), target vessel revascularization (TVR) and major adverse cardiac events (MACE). RESULTS: Twenty-six patients underwent PCI and were enrolled, but only 20 underwent surgical intervention. Technical and procedural success rates were both 100%. No perioperative MACE was detected. After a mean long term follow-up of 15.4±10.3 months, 2 cases of cardiac death (10%), were recorded. No case of stent thrombosis was reported; no case of ischemia driven TLR was detected. The total MACE-free survival probability was 66.5%. CONCLUSION: EPC capture stent implantation in high-risk patients requiring undeferrable non-cardiac surgery seems to allow early cand safe discontinuation of DAT, and may be an attractive alternative to conventional stents.

Evaluation of the topical hemostatic efficacy and safety of TISSEEL VH S/D fibrin sealant compared with currently licensed TISSEEL VH in patients undergoing cardiac surgery: a phase 3, randomized, double-blind clinical study.

AIM: TISSEEL VH is the only commercially available fibrin sealant indicated as an adjunct to conventional methods of hemostasis during cardiac surgery. A next generation fibrin sealant (TISSEEL VH S/D) has been developed in frozen, ready-to-use form with an added virus inactivation step (solvent/detergent [S/D] treatment) to provide added safety and convenience to the currently licensed product. This study was performed to compare efficacy and safety of the two products. METHODS: Phase 3, prospective, randomized, double-blind, multicenter study to compare TISSEEL VH S/D to TISSEEL VH during cardiac surgery. The primary efficacy endpoint was the proportion of patients who achieved hemostasis at the primary treatment site within 5 min, and maintained hemostasis until surgical closure. RESULTS: The proportion of patients who achieved hemostasis at the primary treatment site within 5 min, and maintained hemostasis until surgical closure was 88.2% for TISSEEL VH S/D and 89.6% for TISSEEL VH in the intent-to-treat population. The difference in proportions, TISSEEL VH S/D minus TISSEEL VH, was 1.4% with a standard error of 3.70%. The lower 97.5% confidence bound of this difference was 8.6%, which is above the predefined noninferiority margin of 15%. Therefore, TISSEEL VH S/D is at least as efficacious as TISSEEL VH. The safety profile of TISSEEL VH S/D was very similar to that of currently licensed TISSEEL VH as assessed by the safety endpoints. CONCLUSION: TISSEEL VH S/D is safe and effective for use as an adjunct to hemostasis in patients undergoing cardiac surgery.

Intravenous catecholamine administration affects mouse intestinal lymphocyte number and apoptosis.

The purposes of this study were to determine plasma and intestinal epinephrine (E) and norepinephrine (NE) concentrations in mice after exercise stress and, the effect of intravenous injection of E and NE (at concentrations during exercise) on viability of intestinal lymphocytes (IL). Exhaustive exercise significantly elevated plasma E and NE, and intestinal E, compared with sedentary animals. Twenty-four hours after intravenous NE administration, IL counts were higher (p<0.001) and % apoptotic IL were lower (p<0.001) than saline conditions. E resulted in fewer apoptotic IL at 24 h compared to saline controls. E and NE differentially influence IL numbers at 24 h after injection although both result in fewer % apoptotic IL relative to mice given saline only.

Neurofibromatosis: caso clínico presentación poco habitual. oportunidad diagnostica familiar

Resumen La Neurofibromatosis (NF) es una genodermatosis autosómica dominante. La literatura reconoce varios síndromes clínicos diferentes dentro de los cuáles se describen tres formas principales: Neurofibromatosis tipo 1, Neurofibromatosis tipo 2 y Schwanomatosis. La más común de las tres es la NF1. Con una incidencia de 1 en 3000 y una penetrancia del 100% presenta amplio espectro de manifestaciones clínicas. Nosotros presentamos un caso de sexo femenino que consulta inicialmente por dolor relacionado a una lesión compatible con neuro fibroma con componente epidérmico y subcutáneo. Sin diagnóstico previo de la enfermedad a los 33 años, logramos la correspondiente captación de todos los integrantes de su familia quienes tampoco tenían diagnóstico.

Summary Neurofibromatosis is an autosomal dominant genodermatosis. The literature recognizes several different clinical syndromes within which three main forms are described: Neurofibromatosis type 1, Neurofibromatosis type 2 and Schwanomatosis. The most common of the three is NF1. With an incidence of 1 in 3000 and a penetrance of 100%, it presents a broad spectrum of clinical manifestations. We present a female case that initially consulted for pain related to a lesion compatible with neurofibroma with an epidermal and subcutaneous component. Without previous diagnosis of the disease at 33 years, we were able to diagnose all the members of his family, who also had no diagnosis.

18F-FDG uptake and calcifications on positron emission tomography/computed tomography in octogenarians with severe aortic stenosis.

AIM: The degree of inflammation within the atherosclerotic plaque can be detected non-invasively by positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG). The incidence of aortic plaques with 18F-FDG increased uptake in octogenarians with aortic stenosis is unknown. Aim of this study was to evaluate the frequency of inflamed aortic atherosclerotic plaques in octogenarians with or without severe aortic stenosis and their correlations with calcifications. METHODS: The study group comprised 27 patients older than 80 years who underwent a 18FDG PET/CT. Nine patients with severe symptomatic aortic stenosis, eligible to TAVI procedure (TAVI Group), and 18 patients age and sex matched, without clinical evidence of aortic stenosis (No TAVI Group), were selected and analysed. RESULTS: In the whole population 4/27 patients (9.3%) had a significant focal aortic vessel wall 18F-FDG increased uptake: 1 patient (11.1%) in TAVI group and 3 in non-TAVI Group (16.7%). Overall 81 aortic segments were analysed. 18F-FDG uptake rates were similar in the two groups (1/27, 3.7% in TAVI Group and 3/54, 5.5% in No TAVI Group, P=0.7). At CT scan calcifications were significantly more frequent in the TAVI Group compared to non-TAVI Group (23/27, 85.2% and 28/54, 51.8% P=0.005). None of the sites of arterial calcification had an increased focal 18F-FDG uptake. CONCLUSION: Irrespectively to the presence of aortic stenosis, a significant FDG plaque uptake in octogenarians is rare while calcifications are extremely frequent.

Effect of tumor bulk on local control and survival of patients with T1 glottic cancer.

PURPOSE: To evaluate the effect of tumor bulk in relation to various tumor-related prognostic factors and treatment-related variables on local control and survival of patients with T1 N0 M0 squamous cell carcinoma of the glottis. MATERIALS AND METHODS: In 114 patients with T1 squamous cell carcinoma of the glottic larynx who were irradiated with curative intent, we determined the effect of tumor bulk in relation to mucosal extent (stage and anterior commissure involvement), histologic differentiation and various radiation factors, especially overall treatment time on local control and survival. Tumors were classified retrospectively as small surface lesions or bulky tumors. Seventy-seven patients had small lesions and 37 had bulky tumors. The anterior commissure was involved with cancer in 43 patients. The overall duration of irradiation ranged from 39 to 64 days. The median follow-up time was 6 years (range 5-24 years). RESULTS: The 5-year actuarial local control rate for all patients was 82% after radiotherapy and 92% after salvage laryngectomy. On univariate analysis, bulky tumors and tumors involving the anterior commissure showed an adverse effect on local control, whereas the overall duration of irradiation had a borderline significance. The actuarial local control rate was 91% for small tumors and 58% for bulky tumors (P = 0.0002), 88% when the anterior commissure was not involved and 67% when the anterior commissure was involved (P = 0.01) and 89% when radiation was given in less than 50 days and 73% when irradiation exceeded 50 days (P = 0.06). On multivariate analysis. tumor bulk was the only significant factor that affected local control (P = 0.02). The 5-year actuarial survival for all patients was 73% and the disease-free survival was 92%. CONCLUSION: This study shows that tumor bulk has a highly significant effect on the radiation control of T1 glottic cancer. Patients who had bulky tumors had lower local control and disease-free survival rates than those patients who had small tumors.

Sodium nitroprusside in the treatment of Prinzmetal's variant angina.

A patient had attacks of Prinzmetal's angina, resistant to sublingual nitrates in high doses and to a calcium antagonist. All the crises wee resolved by sodium nitroprusside therapy. This report suggests that nitroprusside merits further evaluation in the treatment of Prinzmetal's angina, particularly in cases resistant to usual therapy in which the evolution towards myocardial infarction is very likely.

Acute effects of chewable nifedipine on hemodynamic responses to upright exercise in patients with prior myocardial infarction and effort angina.

To evaluate the hemodynamic effects of nifedipine on anginal patients during exercise in the upright position, a placebo (P) and 20 mg of nifedipine were administered in a double-blind random sequence to ten patients presenting with exertional angina and a healed myocardial infarction. All patients had previously undergone coronary angiography. The effects of nifedipine in the upright position at rest, at the anginal threshold, and at the maximal level of exercise were studied. Nifedipine decreased systemic vascular resistances in upright position and increased the cardiac index. It reduced the severity of angina and allowed a higher physical work capacity without anginal symptoms. The most important beneficial effect of nifedipine appears to be the reduction in afterload, but an improvement of left ventricular function cannot be ruled out.

Hemangioma of the right ventricular outflow tract.

Obstruction of the right ventricular outflow tract by a primary cardiac tumor is rare. Six cases of right ventricular outflow tract obstruction by a primary cardiac hemangioma have been reported; all but one were detected before the age of 25 years. In this report, we review the literature and describe what we believe to be only the second reported case of right ventricular outflow tract obstruction produced by a cardiac hemangioma that presented in late adulthood.

BioGlue surgical adhesive for thoracic aortic repair during coagulopathy: efficacy and histopathology.

BACKGROUND: We hypothesized that induction of coagulopathy in sheep would model clinical needle hole and surgical bleeding from synthetic graft anastomoses, and that a new tissue bioadhesive (BioGlue) would control postoperative blood loss during surgical repair of the thoracic aorta. METHODS: Sheep were anticoagulated with aspirin and heparin. A bypass was made using end-to-side anastomoses of a graft to a partially occluded descending thoracic aorta. Experimental anastomoses (EXP, n = 9) were treated with BioGlue, and control anastomoses (CON, n = 5) were treated with Surgicel to gain intraoperative hemostasis. RESULTS: EXP animals exhibited significantly reduced postsurgical bleeding (CON median 955 mL versus EXP median 470 mL, p < 0.003), a reduced rate of blood loss over the first 2 postoperative hours (CON median 210 mL/hr versus EXP median 92.5 mL/hr, p < 0.006), and over the entire recovery period (CON median 158 mL/hr versus EXP median 86 mL/hr, p < 0.05), and reduced total blood loss (CON mean 1,497 +/- 691 mL versus EXP mean 668 +/- 285 mL, p < 0.008). On histologic examination of tissues explanted after 3 months, BioGlue was relatively inert and demonstrated a minimal inflammatory response. CONCLUSIONS: The use of BioGlue significantly reduced the volume and rate of postsurgical bleeding in a coagulopathic sheep model for thoracic aortic operations. Histopathologically, BioGlue generated only a minimal inflammatory response. This new surgical tissue bioadhesive should prove extremely beneficial for coagulopathic patients undergoing thoracic aortic or vascular procedures.

Changes in mu opiate receptors following inescapable shock.

Rats exposed to inescapable shock exhibit profound hypoalgesia. Pharmacological evidence has suggested that changes in endogenous opiate activity may be responsible for the hypoalgesic response. We measured the binding of [3H]DAGO, a selective mu-opiate receptor agonist, in brains of rats exposed to no shock, inescapable shock, or escapable shock. Binding of [3H]DAGO in the midbrains of rats in the inescapable shock group was decreased relative to the other two groups. The decrease in binding appeared to result from a decrease in number of mu-receptors and not a change in affinity. These results support the hypothesis that inescapable shock produces long-term changes in endogenous opiate systems.

Gonadal steroids and opioid control of gonadotropin secretion in man.

The aim of this study was to ascertain whether there was an interrelationship between gonadal steroids and endogenous opioid peptides. The effects of naloxone (20 mg, intravenously) and of a met-enkephalin analog (DAMME) (250 micrograms, intravenously) on gonadotropin secretion in three castrated men (18 to 23 years of age) and in five age-matched normal men were studied. Normal subjects were studied before and after treatment with a specific nonsteroidal estrogen receptor antagonist, clomiphene. Naloxone caused a significant increase in luteinizing hormone (LH) (P less than 0.05); in these subjects, clomiphene treatment significantly increased LH and follicle-stimulating hormone plasma levels but totally suppressed the naloxone-induced rise in LH. In castrated men, naloxone failed to increase plasma LH levels. However, DAMME significantly reduced plasma LH levels in normal, in castrated, and in clomiphene-treated normal subjects. The results demonstrate that in castrated subjects who lack gonadal steroids and in normal subjects with blocked estrogen receptors there is a reduced opioid inhibitory tone on gonadotropin secretion. The effect of DAMME on gonadotropin secretion, however, is not influenced by the gonadal steroid environment.

The influence of gonadal steroids on the dopamine inhibitory effect on gonadotropin release in men.

The aim of this study was to ascertain whether an interrelationship exists between gonadal steroids and the inhibition of gonadotropin secretion by dopamine. The effect of dopamine infusion (4 micrograms/kg/minute intravenously) on gonadotropin plasma levels in four castrated men (18 to 23 years of age) and in four age-matched normal men was studied. Normal subjects were studied before and after treatment with a specific nonsteroidal estrogen receptor antagonist, CC. LH plasma levels in normal subjects receiving CC had a maximum decrease percentage and a net decrease significantly greater (P less than 0.005 and P less than 0.012, respectively) than those before CC treatment. In castrated subjects the maximum decrease percentage was significantly greater (P less than 0.005) than in control subjects, but it did not show any difference from that of normal subjects receiving CC. In none of the group were significant changes in FSH concentration observed. The findings suggest that whenever there is a gonadal steroid deficiency, dopamine infusion causes an increased sensitivity to LH inhibition. This may be due to a lower endogenous dopaminergic influence on LH secretion.

Organization and connections of the dorsal descending nucleus and other presumed acoustic areas in the brainstem of the teleost fish, Astronotus ocellatus.

This study provides new information on brainstem areas, assumed to be auditory based on observations in other species, in the oscar, Astronotus ocellatus. The primary goal of the study was to explore the morphology of the dorsal descending octaval nucleus, which contains a population of neurons that receives acoustic afferents from the inner ear. Using cytoarchitectonic and connectional criteria, we revised the previously defined dorsal boundary of the descending octaval nucleus, such that the most dorsomedial neurons in this nucleus are positioned ventral to the cerebellar crest and medial to nucleus medialis. At some levels, these dorsomedial cells are continuous with another part of the dorsal descending nucleus that underlies nucleus medialis. The terminal fields of the saccule and lagena are located within this latter, more ventral part of the dorsal descending nucleus. However, the dorsomedial cells that are proximate to the cerebellar crest have long ventral dendrites that extend into these terminal fields, and therefore likely receive saccular and lagenar input. In contrast to a previous report, saccular afferents terminate more medially within the dorsal descending nucleus than do lagenar inputs. Injections of horseradish peroxidase in nucleus centralis of the torus semicircularis revealed that many descending nucleus neurons that lie within the saccular and lagenar terminal fields, including the dorsomedial neurons proximate to the cerebellar crest, project to this acoustic midbrain area. These injections also revealed a secondary octaval population like that described in otophysan fishes.

Age-adjusted outcomes in traumatic flail chest injuries in the elderly.

Severe chest trauma does not independently predict poor outcome in elderly patients. We chose a specific injury, flail chest, to determine whether age factored into outcome of these patients. A retrospective chart review of all trauma admissions to our Level I trauma center between January 1994 and January 1998 sustaining flail chest was undertaken. Sixty-eight patients were identified, but ten patients were excluded because of death on arrival. Fifty-eight patients were included in the study and separated into groups. The first group comprised those under the age of 55 (n = 32) and the second comprised those over age 55 (n = 26). Parameters evaluated were age, Injury Severity Score (ISS), neurologic injury, the need for mechanical ventilation, need for tracheostomy, length of stay, and death. Statistical analysis was performed with Wilcoxon t test, chi2, and logistic regression where appropriate. A 95 per cent confidence interval was sought as determinant of significance. Of the 58 surviving patients analyzed there was no significant difference between the groups regarding ISS, length of stay, days on the ventilator, head injury, tracheostomy, or development of pneumonia or adult respiratory distress syndrome. The likelihood of death was shown to increase by 132 per cent for every 10 years starting at the second decade and continuing to the eighth decade of life. The likelihood of death also increased by 30 per cent for each unit increase in ISS. The likelihood of death decreased by 23 per cent for every day survived in the hospital. Blunt chest trauma directly impacts respiratory mechanics. Elderly patients are more likely to have comorbid conditions and less likely to tolerate traumatic respiratory compromise. Age (and its effects on the body) is the strongest predictor of outcome with flail chest and is associated with an increased mortality (P < or = 0.05).