Hyperventilation and seizures in an adolescent female.

A 16 year-old girl was admitted after suffering from recurrent episodes of dyspnea and stridor, cyanosis, loss of contact, stiffening of all four limbs, clenching of the jaw and eye retroversion that lasted for a few seconds to a minute, followed by slow recovery of consciousness without any loss of sphincter control. These symptoms began at the age of 11 and worsened over time. Prolonged rate corrected QT intervals was observed with an ECG. Two cardio-respiratory monitorings were performed (one during daytime hours while the patient was awake, and one at night time while the patient slept). Daytime recordings showed 17 central apnoeas and 97 central hypopneas, with an apnea-hypopnea index (AHI) of 13.2 events/hour, that were associated with severe oxyhemoglobin desaturation. In contrast, night time recordings were normal (AHI=1.1 events/hour). The patient underwent diurnal monitoring of transcutaneous pCO2(PtcCO2), transcutaneous O2(PtcO2), SpO2 and end tidal CO2 (PETCO2), with simultaneous monitoring of regional cerebral oxymetry (rSO2) which showed values of PtcCO2 between 8 and 15 mmHg, suggesting several episodes of marked hyperventilation. Twenty-nine episodes of severe arterial desaturation (SpO2<50%) were registered, all after the same number of apnea events, with ascent of PtcO2 up to 28 mmHg at the end of apnea. During the final phase of apnea, the patient showed cyanosis, contact disturbance, grimaces, oral movements of rhyme, and, on three occasions, partial seizures. A mask was packaged and applied daytime to the face of the patient during episodes of hyperventilation to prevent, together with a psychiatric follow up, rapid falls of PaCO2 levels determining central apnoeas.

Predictors of survival within 2 years of inpatient rehabilitation among older adults.

BACKGROUND: Restoring functional independence in elderly people with disabilities is one of the main purposes of a geriatric rehabilitation unit. However, the rehabilitation period may also represent a useful circumstance to identify predictors of long-term health outcomes. The aim of this study was to evaluate a broad spectrum of characteristics in geriatric patients admitted to a rehabilitation unit in order to identify possible predictors of long-term survival. METHODS: This cross-sectional and prospective study was carried out in an Evaluation and Rehabilitation unit in Northern Italy. 243 persons aged 65 or older were enrolled over a period of 12 months (2007-8) and followed for 2 years. Possible predictors of survival were identified among a large spectrum of demographic, clinical (Charlson Index, lab data), nutritional (Mini-Nutritional Short-Form, bio-impedance analysis), and respiratory (spirometry) features. Logistic regression models were used to evaluate the association between patients' characteristics and survival. RESULTS: 189 (86.3%) participants were alive after 2 years of follow-up. Younger age, better functional status at discharge, a lower Charlson Index score, higher hemoglobin and albumin values at discharge, lower basal fasting glucose, creatinine, TNF-α levels, and extra-cellular water, as well as higher cholesterol, vital capacity (VC), and inspiratory capacity were significantly associated with survival. In the multivariate model, higher VC (OR=6.2; 95%CI=1.6-24.6) and albumin (OR=3.7; 95%CI=1.2-11.8) were associated with survival, whereas the Charlson Index and male gender showed an inverse correlation (OR=0.77; 95%CI=0.60-0.99 and OR=0.23; 95%CI=0.10-0.95, respectively). CONCLUSION: VC was identified as one of the best predictors of survival along with higher albumin and lower Charlson Index score within 2 years of inpatient rehabilitation among older adults.

Inspiratory capacity predicts mortality in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) severity is usually graded upon the FEV(1) reduction and FEV(1) has been considered the most important mortality predictor with age in COPD. Recent studies suggest other factors as more powerfully related to mortality than FEV(1) in COPD patients. AIM: To assess the impact of inspiratory capacity (IC) on mortality and morbidity in COPD patients during a 5-year follow-up period. METHODS: We recruited 222 patients with mild-to-moderate COPD from January 1995 to December 2001 with an average follow-up period of 60 months (range 30-114 months). Among different respiratory parameters measured in stable conditions FEV(1), FEV(1)/FVC%, IC and PaO(2), PaCO(2) and BMI were chosen and their relationships with all-cause and respiratory mortality and with morbidity were assessed. RESULTS: All these variables were associated with mortality at the univariate analysis. However, in a multivariate regression analysis (Cox proportional hazards model) for all-cause mortality age (year), IC (%pred.) and PaO(2) (mmHg) remained the only significant, independent predictors (HR=1.056, 95%CI: 1.023-1.091; HR=0.981, 95%CI: 0.965-0.998; HR=0.948, 95%CI: 0.919-0.979, respectively). According to the same analysis, IC (%pred.) and PaO(2) (mmHg) were significant independent predictors for respiratory mortality (HR=0.967, 95%CI: 0.938-0.997; HR=0.919, 95%CI: 0.873-0.969) together with FEV(1)/FVC% and BMI (kg/m(2)) (HR=0.967, 95%CI: 0.933-1.022; HR=0.891, 95%CI: 0.807-0.985, respectively). IC (%pred.), FEV(1)/FVC%, and PaO(2) (mmHg) were also significantly related to morbidity, as independent predictors of hospital admissions because of exacerbations (OR=0.980, 95%CI: 0.974-0.992; OR=0.943, 95%CI: 0.922-0.987; OR=0.971, 95%CI: 0.954-0.996, respectively). CONCLUSION: IC (%pred.) is a powerful functional predictor of all-cause and respiratory mortality and of exacerbation-related hospital admissions in COPD patients.

Wernicke's encephalopathy in a malnourished surgical patient: clinical features and magnetic resonance imaging.

We report a clinical and neuroradiological description of a severe case of Wernicke's encephalopathy in a surgical patient. After colonic surgery for neoplasm, he was treated for a long time with high glucose concentration total parenteral nutrition. In the early post-operative period, the patient showed severe encephalopathy with ataxia, ophthalmoplegia and consciousness disorders. We used magnetic resonance imaging (MRI) to confirm the clinical suspicion of Wernicke's encephalopathy. The radiological feature showed hyperintense lesions which were symmetrically distributed along the bulbo-pontine tegmentum, the tectum of the mid-brain, the periacqueductal grey substance, the hypothalamus and the medial periventricular parts of the thalamus. This progressed to typical Wernicke-Korsakoff syndrome with ataxia and memory and cognitive defects. Thiamine deficiency is a re-emerging problem in non-alcoholic patients and it may develop in surgical patients with risk factors such as malnutrition, prolonged vomiting and long-term high glucose concentration parenteral nutrition.

Frontotemporal dementia: impact of P301L tau mutation on a healthy carrier.

Frontotemporal dementia (FTD) is the second commonest form of dementia after Alzheimer's disease, but its clinical and biological features are less well known. To uncover its earliest signs, we studied the main clinical, neuroimaging, and biochemical findings in an asymptomatic carrier from a three generation FTD family, bearing the P301L pathogenic mutation in the tau gene. Except for selective impairment on the Verbal Fluency Test for letters, all cognitive tests were normal. The brain computed tomography scan was normal, but the brain single photon emission computed tomography and statistical parametric mapping (SPECT-SPM) scan revealed bilateral frontal lobe hypoperfusion. Levels of total tau, 181P-tau, and Abeta1-42 in the cerebrospinal fluid were increased compared with control values. We conclude that detection of these distinctive abnormalities should improve early diagnostic accuracy for FTD and help distinguish it from Alzheimer's disease.

Inhibition of energy metabolism down-regulates the Alzheimer related presenilin 2 gene.

Defects in energy metabolism and oxidative stress play an important role in the pathogenesis of Alzheimer's Disease (AD). In sporadic AD cases, presenilin 2 (PS2) mRNA levels are decreased in brain areas affected by the disease. The aim of the present study was to investigate whether mitochondrial dysfunction might influence PS2 gene expression. We demonstrated that the inhibition of energy metabolism by sodium azide down-regulates PS2 gene expression through modification of promoter activity. No one of the analyzed transcription factors, sensitive to redox status of the cell, could explain this effect. Azide effect on PS2 expression was completely inhibited by the addition of an antioxidant suggesting that the imbalance of the cellular redox homeostasis modulates the expression of this gene.

BACE-2 is overexpressed in Down's syndrome.

Brain deposition of the amyloid-beta protein (Abeta) is a frequent complication of Down's syndrome (DS) patients. Abeta peptide is generated by endoproteolytic processing of Abeta precursor protein by gamma and beta secretases. Recently a transmembrane aspartyl protease, BACE, has been identified as the beta-secretase, and its homologous BACE-2 has also been described. BACE-2 gene resides on chromosome 21 in the obligate DS region. It cleaves Abeta precursor protein at its beta site and more efficiently at a different site within Abeta. In the present study we characterized the BACE-2 gene and protein expression in the DS patients and healthy control. We analyzed, by using a nonradioactive ribonuclease protection assay, the levels of BACE-2 mRNA expression in primary skin fibroblasts. The analysis revealed a 2.6-fold increase in BACE-2 mRNA levels in the DS group compared to the levels observed in the control group. Western blot analysis revealed no difference between DS and control in BACE-2 protein levels in the intracellular compartment. In the medium conditioned by fibroblast, we revealed an evident secretion of BACE-2 protein, represented by two different molecular weights, remarkably increased in DS fibroblasts. BACE-2 overexpression was also confirmed in the DS fetal brains and human neural embryonic DS stem cells in which conditioned media BACE-2 was secreted. These data highlight the importance of the extracellular compartment where BACE-2 overexpression could play a role in plaque formation in DS patients.

Detection of the presenilin 1 COOH-terminal fragment in the extracellular compartment: a release enhanced by apoptosis.

Mutations in gene encoding presenilin 1 (PS1) are responsible for the majority of familial Alzheimer's disease (FAD) cases. We studied PS1 localization in HEK293 cells and in primary neurons obtained from rat cortex and hippocampus. We first demonstrated that PS1-CTF, but neither PS1-FL nor PS1-NTF, is released into the medium as a soluble and membrane-associated form. After induction of apoptosis with staurosporine (Sts), we observed a dramatic increase in the level of PS1-CTF in the medium, both in HEK293 and in primary neurons. Immunocytochemical analysis suggested that the release of PS1-CTF might occur via membrane shedding. Abeta(1-42) treatment reduced PS1-CTF extracellular levels. This decrease was strongly associated to an impaired secretion of sAPP fragments, thus suggesting a role of PS1-CTF in the control of trafficking and generation of APP fragments.

Analysis of alpha-2-macroglobulin-2 allele as a risk factor in Alzheimer's disease.

A correlation between a 5-nucleotide deletion polymorphism in the A2M gene and an enhanced risk of developing Alzheimer's disease (AD) was reported. We studied this polymorphism in sporadic AD patients and patients with frontotemporal dementia (FTD) by using an electrophoretical separation of PCR products on a Metaphor gel. Our results did not show any significant difference between A2M-2 allelic frequency (p = 0.89) or genotype frequency (p = 0.97) in the two different clinical series and in control subjects. The frequencies were not significantly different after stratification by APOE epsilon4 status.

Peptic ulcer bleeding: comparison of two hemostatic procedures.

OBJECTIVE: Bleeding is a serious complication of peptic ulcer. Endoscopic injection therapy is accepted as a homeostatic endoscopic treatment in acute nonvariceal of upper GI hemorrhages, particularly in bleeding peptic ulcers. The risk of rebleeding is predicted by the endoscopic appearance of ulcer features classified according to Forrest's criteria. METHODS: Two hundred twenty-three patients were selected from 1,003 emergency upper endoscopies for GI bleeding. According to Forrest's criteria, 99 well-matched patients with ulcers F1 and F2 were considered at risk of rebleeding; 54 patients (group A) received local ulcer injection of epinephrine solution 1:10,000, whereas (group B) patients were treated with local epinephrine injection and then with endoscopic Hemoclips. (1) We considered the control of bleeding, the number of rebleeding episodes, the need for emergency surgery, and mortality. RESULTS: Bleeding ulcers stopped completely in 83.3% group A patients, and in 95.6% group B patients (p = not significant). In a subset of F1b patients the rebleeding rate was 31 % for group A and 0% for group B (p < 0.05). There was no mortality as a result of the procedure. There was a trend toward reducing surgery in favor of the combined therapy (0% vs 7.4%). No differences were found in transfusion requirements or mean hospitalization days. CONCLUSIONS: We conclude that endoscopic injection of l:10,000 epinephrine solution alone and epinephrine solution plus application of Hemoclips are equivalent therapies in treating bleeding and rebleeding from peptic ulcers. There was no difference between therapies in terms of need for surgery or mortality. Possibly combination therapy is more effective in treating ulcers that are actively oozing.

Diagnosis and therapy of intrathecal bleeding.

AIM: Define pathophysiology, epidemiology, diagnosis and therapy in case of spinal bleeding after central neural blockade (CNB). METHODS: Spinal epidural hematoma (SEH) following CNB may occur due to vascular trauma from needle/catheter placement and can occur in subdural and epidural spaces. Epidural artery bleeding seems the source of SEH: the damage mechanism depends on compression and neural vascular ischemia of cord, nerve roots, ganglion and toxicity from blood cell lysis products. Incidence varies (1:150.000 - 1:500.000) but SEH may be asymptomatic. CONCLUSIONS: SEH starts with acute severe low back and/or radicular pain and neurologic signs that may progress to paraparesis, sensory loss and sphincter disturbances. After CNB, the only sign of SEH may be an unusually prolonged motor and sensory block. Symptoms may start even 96 hours after CNB and/or removal of the epidural catheter. Neurological recovery is related to severity and speed of preoperative deficits development and surgical decompression. MR imaging features (diagnostic tool of choice), including degree of cord compression, are useful to establish or confirm the diagnosis of SEH but do not influence the management or predict outcome. Hematoma resolution and severity of neurologic impairment has the greatest impact on management and outcome. Preoperative MRI information and intraoperative evidence of subarachnoid hemorrhage (SAH) and CSF leakage is important: SAH worsens outcome for its negative effect on spinal cord and cauda equina. Conservative therapy may be successful in cases with minimal neurologic deficits, despite cord compression.

[Postoperative pain management. Aims and organization of a strategy for postoperative acute pain therapy]. / La gestione del dolore postoperatorio. Obiettivi, identificazione e organizzazione delle procedure di sviluppo di un programma di terapia del dolore acuto postoperatorio.

The Health Services, not only the Italian one, is under pressure because of request for improving treatment quality and the financial need for reorganization and cost-saving. It's required a rationalization of intervention, together with a careful choice of the best and cheapest techniques and the demonstration of their efficacy. The anaesthesia service activity, in a period of cost rationalization and funds restriction should be aimed to appropriate outcome measures corrected by both patient's risk factors and surgical-anaesthesiological case-mix. The development of a complete strategy for surgical pain management might run into two phases. The first phase, internal and mono-specialistic, should develop like the creation of an Acute Pain Team. The main processes are: focusing the problem (charge of the care), training, information, teaching methodology (timing, methods, drugs, techniques, etc.) and the audit (before and after changes). The main aims are the evaluation of the level of analgesia and pain relief or patient's satisfaction which are partial endpoints useful to demonstrate the improvement and the efficacy of the new pain management strategies. The second phase, multidisciplinary, is directed toward the creation of a Postoperative Evaluation Team. The main objective is to set up a collaborative clinical group able to identify the criteria for quality, efficacy and safety. The major purpose is the evaluation of major outcome measures: surgical outcome, morbidity, mortality and length of hospitalization. The improvement in the quality of postoperative pain treatment goes through a better organization and a progressive increase of the already available therapy. The achievement of the result and the quality projects depend on the interaction among staff members with different behaviours and settings. Internal teaching and training, continuous education for doctors and nurses, and external information, marketing and improvement of attractive capability of Institution, are the procedures of a growing integrated program for postoperative pain treatment. The organizational processes should interact effectively with a plan of education, updating, revision and information in a definite development timing. It should be emphasized a collaborative, interdisciplinary approach to pain control, assessment and treatment, including all the members of the health care team, with an input from the patient and a protective collaboration from the Institution. The development of a postoperative care team must be considered as part of the largest project for "a Painfree Hospital". It represents a keystone of a Institutional Quality Assurance Plan for health care providers, patients (customs) and Institution.

Do pipecuronium and rocuronium affect human bronchial smooth muscle?

BACKGROUND: Muscle relaxants affect nicotinic and muscarinic receptors. Interaction of muscle relaxants with muscarinic receptors of human airways has been studied incompletely. METHODS: The effects of pipecuronium bromide (long-acting, nondepolarizing) and rocuronium bromide (intermediate-acting, nondepolarizing) on prejunctional and postjunctional muscarinic receptors were studied in 96 isolated human bronchial rings from 12 patients. Contractile isometric responses to electric field stimulation of pilocarpine-stimulated and nonstimulated M2 muscarinic receptors were compared before and after incubation with the two muscle relaxants. The effect on postjunctional muscarinic receptors was studied by comparing acetylcholine concentration-response curves before and after incubation with the two muscle relaxants. RESULTS: Pipecuronium bromide, but not rocuronium bromide, inhibited pilocarpine-stimulated prejunctional M2 muscarinic receptors. Neither pipecuronium bromide nor rocuronium bromide had significant inhibitory effects on nonstimulated M2 muscarinic receptors and on postjunctional M3 muscarinic receptors. CONCLUSIONS: The inhibitory effect of pipecuronium bromide on pilocarpine-stimulated prejunctional M2 muscarinic receptors occurred at clinical concentrations.

Celiac plexus block: a reappraisal.

BACKGROUND AND OBJECTIVES: The neurolytic celiac plexus block is an established, well-developed procedure and the most widely applicable of all the neurolytic pain blocks. It optimizes palliative treatment for cancer of the upper abdominal viscera. Several techniques have been proposed in an attempt to increase success rates, reduce morbidity, and enhance technical accuracy. However, the assessment of the results and effectiveness of the block have been controversial. METHODS: A survey was made of pertinent English language literature on the anatomic and technical problems, indications, advantages, complications, and outcomes related to the neurolytic celiac plexus block as well as the neurolytic solutions and radiologic guidance used. RESULTS: The successful relief of the pain of pancreatic cancer and other abdominal malignancies can be expected in 85% and 73% of patients, respectively. Following the block, many patients can be weaned from opioids or at least have their dose reduced. The half-life of the celiac plexus block seems to be more than 4 weeks. The probability of patients remaining completely pain-free diminishes with increases survival time. The technique selected should be appropriate to the available and the extent of malignancy, since the analgesic results seem to be independent of the principal techniques used. Serious complications are extremely rare. However, critical analysis revealed major deficiencies in all of the reports reviewed. CONCLUSION: Neurolytic celiac plexus block alone is capable of providing complete pain relief until death in a few cases and, therefore, should be considered as an adjuvant treatment in the analgesic strategy. Combination palliative therapy is necessary in most cases. Failure of the block may be attributed to tumor metastasizing beyond the nerves that conduct pain via the celiac plexus and the component nerves that form it. Concomitant pain of somatic origin (frequently observed in upper gastrointestinal cancer because of significant peritoneal involvement) requires other therapeutic measures.

Inhibition of airway constriction by opioids is different down the isolated bovine airway.

BACKGROUND: Opioid agonists attenuate in isolated airways contractile responses to electrical field stimulation (EFS), and this attenuation is mediated by opioid receptors. Differences exist in the density of muscarinic and beta-adrenergic receptors between large and small airways. The authors hypothesized that the density of opioid receptors may also be different down the airway. METHODS: The effects of three selective opioid agonists (mu, kappa, delta) on EFS-induced contractions were compared between isolated bovine sublobar (4- or 5-mm inner diameter) and segmental (2- or 3-mm inner diameter) bronchial rings and between trachealis strips and bronchial rings. RESULTS: D-Ala2-N-MePhe4-Gly-ol5 enkephalin (DAMGO; 10(-5) M), a mu-opioid agonist, attenuated EFS-induced contractions of isolated sublobar and segmental bronchial rings at low stimulating frequencies of 0.5 Hz (P < 0.001), 2 Hz (P < 0.001), and 8 Hz (P < 0.001), but not at 32 Hz (P = 0.071). The inhibitory effect of DAMGO was antagonized by naloxone (10(-5) M) (P = 0.025). The selective kappa-opioid agonist U-50488 H (10(-5) m) attenuated EFS-induced contractions at 32 Hz (P = 0.008) and 8 Hz (P = 0.045), but not at 2-Hz (P = 0.893) or 0.5-Hz (P = 0.145) contractions. The inhibitory effects of 10(-5) M U-50488 H were not antagonized by the highly selective kappa-antagonist 2,2'-[1,1'-biphenyl] 4,4'-diyl-bis [2-hydroxy-4,4-dimethyl]-morpholinium (nor-BNI; 10(-5) M; P = 0.216) or naloxone (10[-5]) M; P = 0.065). The selective delta-agonist D-penicillamine2-D-penicillamine5-enkephalin (DPDPE) (10(-5) M) had no inhibitory effects (P = 0.256). The inhibitory effects of the selective mu-opioid agonist DAMGO were smaller (P < 0.001) and those of U-50488 H larger (P < 0.001) in trachealis strips compared with bronchial rings. CONCLUSIONS: The attenuation of EFS-induced contractions by DAMGO in isolated bovine bronchi was mediated by prejunctional opioid receptors. In contrast, the inhibitory effect of U-50488 H was probably not mediated by opioid receptors in the bronchi.

Postoperative analgesia in Italy. National survey on the anaesthetist's beliefs, opinions, behaviour and techniques in postoperative pain control in Italy.

BACKGROUND: Using a personal, anonymous questionnaire developed ad hoc, we tried to document the role, the problems and the activities of Italian anaesthetists in postoperative pain control. METHODS: A random selection-stratified by region-was made from a list of 971 hospitals. The final sample was made up of 395 departments of anaesthesia and intensive care from 369 hospitals. The completeness and consistency of each questionnaire were assessed. RESULTS: The response rate achieved was 78.9% (312 centres in 293 hospitals) with 2435 evaluable questionnaires corresponding to 30% of all Italian anaesthesia departments and 25% of Italian anaesthetists. Only 15.2% of anaesthetists are completely responsible for the postoperative analgesia (POA) (prescriptions and evaluations) and an established attitude for POA (protocols/guidelines) exists in 18 departments only. 60% of anaesthetists use routinely the intramuscular route, 55.2% the intravenous route (infusion plus bolus), and 23.7% the spinal/epidural route. Only 6.2% of the anaesthetists use the patient-controlled analgesia system. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used agents (47% NSAID vs 37.9% opioids; NSAID-opioid association 14.7%). A local anesthetics-opioids association is preferred for the spinal/epidural route (15.1%) only (local anaesthetic 4.9% only; opioids alone 2.7%). Lack of time, work organization, technique knowledge/training, trust in nursing-ward staff, difficulty in monitoring the patient on the ward, concern about opioid use leading to ventilatory depression, and administration errors are reported to be the main factors that limit an appropriate approach to postoperative pain (POP), the correct use of analgesics and a free choice of POA technique. CONCLUSION: This survey shows that Italian anaesthetists do not consider the postoperative period to be their own personal work area and that POA is to be considered as a matter of individual choice.

Salvage chemotherapy with paclitaxel in platinum-resistant advanced ovarian cancer patients.

Encouraging results with Paclitaxel are reported in ovarian cancer patients relapsing and progressing after platinum-based chemotherapy; however, the two populations have different probabilities of a response to a second-line treatment. Here we report the results achieved in 39 patients with platinum-refractory ovarian cancer, treated with Paclitaxel 175 mg/qm2 (or 135 mg/m2 if heavily pretreated) using 3-hour intravenous infusion every 3 weeks, in an attempt to verify the activity of this drug in platinum-resistant patients. The toxicity was mild to moderate and primarily hematologic and neurologic. The objective response rate is 12.8% with no complete responses. The response duration was brief and the median survival 6 (range 1-17) months. An accurate cost-benefit balance is necessary before routinely use of Paclitaxel in platinum-refractory patients. Further research is needed to determine the optimal role of Paclitaxel in the whole therapeutic strategy for ovarian cancer.