Objective reduction in adenoid tissue after mometasone furoate treatment

Objective: Chronic rhinitis and adenoid hypertrophy are the main causes of nasal obstruction in children and proper treatment of these factors seem essential for controlling nasal obstructive symptoms. This study aims to evaluate the effects of topical mometasone treatment on symptoms and size of adenoid tissue in children with complaints of nasal obstruction and to compare this approach to continuous nasal saline douching plus environmental control alone. Methods: Fifty-one children with nasal obstructive complaints were submitted to a semi-structured clinical questionnaire on nasal symptoms, prick test and nasoendoscopy. Nasoendoscopic images were digitalized, and both adenoid and nasopharyngeal areas were measured in pixels. The relation adenoid/nasopharyngeal area was calculated. Patients were subsequently re-evaluated in two different periods: following 40 days of treatment with nasal douching and environmental prophylaxis alone; and after an subsequent 40 day-period, when topical mometasone furoate (total dose: 100 mu g/day) was superposed. Results: Nasal symptoms and snoring significantly improved after nasal douching, and an additional gain was observed when mometasone furoate was included to treatment. Saline douching did not influence the adenoid area, whereas a significant reduction on adenoid tonsil was observed after 40 days of mometasone treatment (P < 0.0001). Conclusion: Nasal saline douching significantly improved nasal symptoms without interfering in adenoid dimension. In contrast, mometasone furoate significantly reduced adenoid tissue, and led to a supplementary improvement of nasal symptoms. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Craniofacial morphology and sleep apnea in children with obstructed upper airways: Differences between genders

Objective: To correlate sleep apnea with craniofacial characteristics and facial patterns according to gender. Methods: In this prospective survey we studied 77 male and female children (3-12 years old) with an upper airway obstruction due to tonsil and adenoid enlargement. Children with lung problems, neurological disorders and syndromes, obstructive septal deviation, previous orthodontic treatment, orthodontic surgeries or oral surgeries, or obesity were excluded. Patients were subjected to physical examinations, nasal fiberoptic endoscopy, teleradiography for cephalometric analysis, and polysomnography. Methods: Cephalometric analysis included the following skeletal craniofacial measurements: facial axis (FA), facial depth (FD), mandibular plane angle (MP), lower facial height (LFH), mandibular arch (MA), and vertical growth coefficient (VERT) index. Results: The prevalence of sleep apnea was 46.75% with no statistical difference between genders. Among children with obstructive sleep apnea (Apneia Hypopnea Index - AHI >= 1) boys had higher AHI values than girls. A predominance of the dolichofacial pattern (81.9%) was observed. The following skeletal craniofacial measurements correlated with AHI in boys: FD (r(s) = -0.336/p = 0.020), MP (r(s) = 0.486/p = 0.00), and VERT index (r(s) = -0.337/p = 0.019). No correlations between craniofacial measurements and AHI were identified in girls. Conclusions: Craniofacial morphology may influence the severity of sleep apnea in boys but not in girls. (C) 2012 Elsevier B.V. All rights reserved.

Double-chambered right ventricle in an adult patient diagnosed by transthoracic echocardiography

Abstract Background Double-chambered right ventricle is a rare congenital disease frequently misdiagnosed in the adult patient. An anomalous muscle band divides the right ventricle in two cavities causing variable degree of obstruction. Although echocardiography is considered a useful method for the diagnosis of this pathology in children, it has been recognized the transthoracic scanning limitation in adults. Case presentation A 29 year-old patient with double-chambered right ventricle presenting mild exercise intolerance referred for follow up of a known ventricular septal defect in whom a complete diagnosis was obtained based only on transthoracic two dimensional echocardiography without the needing of cardiac catheterization. Conclusion Based on non invasive echocardiographic diagnosis, patient was referred to surgical correction, which was completely successful.

Dyspeptic symptoms and delayed gastric emptying of solids in patients with inactive Crohn’s disease

Background Patients with Crohn’s disease (CD) have been shown to present dyspeptic symptoms more frequently than the general population. Some of these symptoms could be related to motility disorders to some degree. Then, we propose to investigate whether gastric emptying of solids in patients with inactive CD is delayed and to determine the relationships between gastric emptying and dyspeptic symptoms in inactive CD. Methods Twenty-six patients with inactive Crohn’s disease, as defined by a Crohn’s Disease Activity Index (CDAI) < 150, underwent a gastric emptying test by breath test using 13C octanoic acid coupled to a solid meal and answered a validated questionnaire (The Porto Alegre Dyspeptic Symptoms Questionnaire) to assess dyspeptic symptoms. Patients with scores ≥ 6 were considered to have dyspepsia. The control group was composed by 19 age- and sex-matched healthy volunteers. Results Patients with CD had a significantly longer t 1/2 and t lag (p<0.05) than the controls. CD patients with dyspepsia had significantly (p<0.05) prolonged gastric emptying when compared to patients without dyspeptic symptoms. When the individual symptom patterns were analyzed, only vomiting was significantly associated with delayed gastric emptying (p<0.05). There was no difference between the subgroups of patients with respect to gender, CDAI scores, disease location, clinical behavior (obstructive/obstructive) or previous gastrointestinal surgery. Conclusion Delayed gastric emptying in inactive Crohn’s disease patients seems to be associated with dyspeptic symptoms, particularly vomiting, even without any evidence of gastrointestinal obstruction.

Analysis of the biofilm proteome of Xylella fastidiosa

Abstract Background Xylella fastidiosa is limited to the xylem of the plant host and the foregut of insect vectors (sharpshooters). The mechanism of pathogenicity of this bacterium differs from other plant pathogens, since it does not present typical genes that confer specific interactions between plant and pathogens (avr and/or hrp). The bacterium is injected directly into the xylem vessels where it adheres and colonizes. The whole process leads to the formation of biofilms, which are considered the main mechanism of pathogenicity. Cells in biofilms are metabolically and phenotypically different from their planktonic condition. The mature biofilm stage (phase of higher cell density) presents high virulence and resistance to toxic substances such as antibiotics and detergents. Here we performed proteomic analysis of proteins expressed exclusively in the mature biofilm of X. fastidiosa strain 9a5c, in comparison to planktonic growth condition. Results We found a total of 456 proteins expressed in the biofilm condition, which correspond to approximately 10% of total protein in the genome. The biofilm showed 37% (or 144 proteins) different protein than we found in the planktonic growth condition. The large difference in protein pattern in the biofilm condition may be responsible for the physiological changes of the cells in the biofilm of X. fastidiosa. Mass spectrometry was used to identify these proteins, while real-time quantitative polymerase chain reaction monitored expression of genes encoding them. Most of proteins expressed in the mature biofilm growth were associated with metabolism, adhesion, pathogenicity and stress conditions. Even though the biofilm cells in this work were not submitted to any stress condition, some stress related proteins were expressed only in the biofilm condition, suggesting that the biofilm cells would constitutively express proteins in different adverse environments. Conclusions We observed overexpression of proteins related to quorum sensing, proving the existence of communication between cells, and thus the development of structuring the biofilm (mature biofilm) leading to obstruction of vessels and development of disease. This paper reports a first proteomic analysis of mature biofilm of X. fastidiosa, opening new perspectives for understanding the biochemistry of mature biofilm growth in a plant pathogen.

Sensitivity, specificity and predictive values of linear and nonlinear indices of heart rate variability in stable angina patients

Abstract Background Decreased heart rate variability (HRV) is related to higher morbidity and mortality. In this study we evaluated the linear and nonlinear indices of the HRV in stable angina patients submitted to coronary angiography. Methods We studied 77 unselected patients for elective coronary angiography, which were divided into two groups: coronary artery disease (CAD) and non-CAD groups. For analysis of HRV indices, HRV was recorded beat by beat with the volunteers in the supine position for 40 minutes. We analyzed the linear indices in the time (SDNN [standard deviation of normal to normal], NN50 [total number of adjacent RR intervals with a difference of duration greater than 50ms] and RMSSD [root-mean square of differences]) and frequency domains ultra-low frequency (ULF) ≤ 0,003 Hz, very low frequency (VLF) 0,003 – 0,04 Hz, low frequency (LF) (0.04–0.15 Hz), and high frequency (HF) (0.15–0.40 Hz) as well as the ratio between LF and HF components (LF/HF). In relation to the nonlinear indices we evaluated SD1, SD2, SD1/SD2, approximate entropy (−ApEn), α1, α2, Lyapunov Exponent, Hurst Exponent, autocorrelation and dimension correlation. The definition of the cutoff point of the variables for predictive tests was obtained by the Receiver Operating Characteristic curve (ROC). The area under the ROC curve was calculated by the extended trapezoidal rule, assuming as relevant areas under the curve ≥ 0.650. Results Coronary arterial disease patients presented reduced values of SDNN, RMSSD, NN50, HF, SD1, SD2 and -ApEn. HF ≤ 66 ms2, RMSSD ≤ 23.9 ms, ApEn ≤−0.296 and NN50 ≤ 16 presented the best discriminatory power for the presence of significant coronary obstruction. Conclusion We suggest the use of Heart Rate Variability Analysis in linear and nonlinear domains, for prognostic purposes in patients with stable angina pectoris, in view of their overall impairment.

Body packing by rectal insertion of cocaine packets: a case report

Background: Body packing is used for international drug transport, immediate drug concealment during a police searching or introducing drugs inside prisons. Despite the high level of specialization of dealers who have started to manufacture more complex packs, up to 5% of patients could develop intoxication due to pack rupture. Bowel obstruction is another acute complication. Case presentation: A 27-year-old black male patient was sent to the hospital by court order for clinical evaluation and toxicological examination. The patient was conscious, oriented, had good color, normal arterial pressure and heart rate, and no signs of acute intoxication. Abdominal examination revealed discrete pain upon deep palpation and a small mass in the left iliac fossa. A plain abdominal radiograph revealed several oval structures located in the rectum and sigmoid. Fasting and a 50 g dose of activated charcoal every six hours were prescribed. After three days, the patient spontaneously evacuated 28 cocaine packs. Conclusion: Adequate clinical management and prompt identification of potential complications are of fundamental importance in dealing with body packing.

Midgut volvulus after laparoscopic appendectomy

The authors report a case of a 13-year old child who was submitted to a laparoscopic appendectomy and developed, during the postoperative period, an intestinal obstruction caused by small bowel volvulus in the absence of a congenital malrotation.

Cisto nasolabial bilateral como causa de obstrução nasal: relato de caso e revisão de literatura

INTRODUÇÃO: O cisto nasolabial é uma doença rara, normalmente unilateral, benigna, de origem embrionária, localizada em partes moles da região do sulco nasolabial e asa nasal. O diagnóstico é essencialmente clínico, levando em consideração a topografia do cisto, que geralmente é assintomático. OBJETIVO: Este artigo tem como objetivo principal à descrição de um caso incomum de cisto nasolabial bilateral com obstrução nasal, seu tratamento, aspectos anatomopatológicos e acompanhamento, além de revisão de literatura. RELATO DO CASO: Paciente do sexo feminino, parda, 24 anos de idade, apresentando abaulamento em região nasolabial e obstrução nasal. Exames físico e complementares compatíveis com cisto nasolabial. Indicado tratamento cirúrgico para exérese da lesão. CONSIDERAÇÕES FINAIS: O cisto nasolabial bilateral, apesar de raro, é uma possível causa de obstrução nasal, com boa resposta à terapia cirúrgica.

Renal papillary necrosis

In 1877, Dr. Nikolaus Friedreich (1825- 1882; student of Virchow who became Professor of Pathology at Heidelberg and who also described Friedreich’s ataxia) first described renal papillary necrosis (RPN) in patients with prostatic hypertrophy and secondary hydronephrosis. Thereafter in 1937, Froboese and Günther emphasized the association of this entity with diabetes mellitus. These authors also observed renal papillary necrosis in cases of urinary tract obstruction even in the absence of diabetes mellitus.

Effects of ischemia and reperfusion on subpopulations of rat enteric neurons expressing the P2X7 receptor

BACKGROUND: Intestinal ischemia followed by reperfusion (I/R) may occur following intestinal obstruction. In rats, I/R in the small intestine leads to structural changes accompanied by neuronal death. AIM: To analyze the impact of I/R injury on different neuronal populations in the myenteric plexus of rat ileum. METHODS: The ileal artery was occluded for 35 min and animals were euthanized 6, 24, and 72 h, and 1 week later. Immunohistochemistry was performed with antibodies against the P2X7 receptor as well as nitric oxide synthase (NOS), calbindin, calretinin, choline acetyltransferase (ChAT), or the pan-neuronal marker anti-HuC/D. RESULTS: Double immunolabeling demonstrated that 100% of NOS-, calbindin-, calretinin-, and ChAT-immunoreactive neurons in all groups expressed the P2X7 receptor. Following I/R, neuronal density decreased by 22.6% in P2X7 receptor-immunoreactive neurons, and decreased by 46.7, 38, 39.8, 21.7, and 20% in NOS-, calbindin-, calretinin-, ChAT-, and HuC/D-immunoreactive neurons, respectively, at 6, 24, and 72 h and 1 week following injury compared to the control and sham groups. We also observed a 14% increase in the neuronal cell body profile area of the NOS-immunoreactive neurons at 6 and 24 h post-I/R and a 14% increase in ChAT-immunoreactive neurons at 1 week following I/R. However, the average size of the calretinin-immunoreactive neurons was reduced by 12% at 6 h post-I/R and increased by 8% at 24 h post-I/R. CONCLUSIONS: This work demonstrates that I/R is associated with a significant loss of different subpopulations of neurons in the myenteric plexus accompanied by morphological changes, all of which may underlie conditions related to intestinal motility disorder

Metachronic malignant transformation of small bowel and rectal endometriosis in the same patient

[ES] Background: Malignant transformation of intestinal endometriosis is a rare event with an unknown rate of incidence. Metachronous progression of endometriosis to adenocarcinoma from two distant intestinal foci happening in the same patient has not been previously reported. Case presentation: We describe a case of metachronic transformation of ileal and rectal endometriosis into an adenocarcinoma occurring in a 45-year-old female without macroscopic pelvic involvement of her endometriosis. First, a right colectomy was performed due to intestinal obstruction by an ileal mass. Pathological examination revealed an ileal endometrioid adenocarcinoma and contiguous microscopic endometriotic foci. Twenty months later, a rectal mass was discovered. An endoscopic biopsy revealed an adenocarcinoma. En bloc anterior rectum resection, hysterectomy and bilateral salpingectomy were performed. A second endometrioid adenocarcinoma arising from a focus of endometriosis within the wall of the rectum was diagnosed. Conclusion: Intestinal endometriosis should be considered a premalignant condition in premenopausal women.

Importanza prognostica delle citochine e loro ruolo nell'immunomodulazione: risultati di studi sperimentali in vivo e in vitro

Citokines are proteins produced by several cell types and secreted in response to various stimuli. These molecules are able to modify the behaviour of other cells inducing activities like growth, differentiation and apoptosis. In the last years, veterinary scientists have investigated the role played by these factors; in fact, cytokines can act as intercellular communicative signals in immune response, cell damage repair and hematopoiesis. Up to date, various cytokines have been identified and in depth comprehension of their effects in physiology, pathology and therapy is an interesting field of research. This thesis aims to understand the role played by these mediators during natural or experimentally induced pathologies. In particular, it has been evaluated the genic and protein expressions of a large number of cytokines during several diseases and starting from different matrix. Considering the heterogeneity of materials used in experimentations, multiple methods and protocols of nucleic acids and proteins extractions have been standardized. Results on cytokines expression obtained from various in vitro and in vivo experimental studies have shown how important these mediators are in regulation and modulation of the host immune response also in veterinary medicine. In particular, the analysis of inflammatory and septic markers, like cytokines, has allowed a better understanding in the pathogenesis during horse Recurrent Airway Obstruction, foal sepsis, Bovine Viral Diarrhea Virus infection and dog Parvovirus infection and the effects of these agents on the host immune system. As experimentations with mice have shown, some pathologies of the respiratory and nervous system can be reduced or even erased by blocking cytokines inflammatory production. The in vitro cytokines expression evaluation in cells which are in vivo involved in the response to exogenous (like pathogens) or endogenous (as it happens during autoimmune diseases) inflammatory stimuli could represent a model for studying citokines effects during the host immune response. This has been analyzed using lymphocytes cultured with several St. aureus strains isolated from bovine mastitic milk and different colostrum products. In the first experiment different cytokines were expressed depending on enterotoxins produced, justifying a different behaviour of the microrganism in the mammal gland. In the second one, bone marrow cells derived incubated with murine lymphocytes with colostrum products have shown various cluster of differentiation expression , different proliferation and a modified cytokines profile. A better understanding of cytokine expression mechanisms will increase the know-how on immune response activated by several pathogen agents. In particular, blocking the cytokine production, the inhibition or catalyzation of the receptor binding mechanism and the modulation of signal transduction mechanism will represent a novel therapeutic strategy in veterinary medicine.

Revisione critica dei risultati e nuovi algoritmi decisionali sulla chirurgia dell'OSAS

Obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is the periodic reduction or cessation of airflow during sleep. The syndrome is associated whit loud snoring, disrupted sleep and observed apnoeas. Surgery aims to alleviate symptoms of daytime sleepiness, improve quality of life and reduce the signs of sleep apnoea recordered by polysomnography. Surgical intervention for snoring and OSAHS includes several procedures, each designed to increase the patency of the upper airway. Procedures addressing nasal obstruction include septoplasty, turbinectomy, and radiofrequency ablation (RF) of the turbinates. Surgical procedures to reduce soft palate redundancy include uvulopalatopharyngoplasty with or without tonsillectomy, uvulopalatal flap, laser-assisted uvulopalatoplasty, and RF of the soft palate. More significant, however, particularly in cases of severe OSA, is hypopharyngeal or retrolingual obstruction related to an enlarged tongue, or more commonly due to maxillomandibular deficiency. Surgeries in these cases are aimed at reducing the bulk of the tongue base or providing more space for the tongue in the oropharynx so as to limit posterior collapse during sleep. These procedures include tongue-base suspension, genioglossal advancement, hyoid suspension, lingualplasty, and maxillomandibular advancement. We reviewed 269 patients undergoing to osas surgery at the ENT Department of Forlì Hospital in the last decade. Surgery was considered a success if the postoperative apnea/hypopnea index (AHI) was less than 20/h. According to the results, we have developed surgical decisional algorithms with the aims to optimize the success of these procedures by identifying proper candidates for surgery and the most appropriate surgical techniques. Although not without risks and not as predictable as positive airway pressure therapy, surgery remains an important treatment option for patients with obstructive sleep apnea (OSA), particularly for those who have failed or cannot tolerate positive airway pressure therapy. Successful surgery depends on proper patient selection, proper procedure selection, and experience of the surgeon. The intended purpose of medical algorithms is to improve and standardize decisions made in the delivery of medical care, assist in standardizing selection and application of treatment regimens, to reduce potential introduction of errors. Nasal Continuous Positive Airway Pressure (nCPAP) is the recommended therapy for patients with moderate to severe OSAS. Unfortunately this treatment is not accepted by some patient, appears to be poorly tolerated in a not neglible number of subjects, and the compliance may be critical, especially in the long term if correctly evaluated with interview as well with CPAP smart cards analysis. Among the alternative options in Literature, surgery is a long time honoured solution. However until now no clear scientific evidence exists that surgery can be considered a really effective option in OSAHS management. We have design a randomized prospective study comparing MMA and a ventilatory device (Autotitrating Positive Airways Pressure – APAP) in order to understand the real effectiveness of surgery in the management of moderate to severe OSAS. Fifty consecutive previously full informed patients suffering from severe OSAHS were enrolled and randomised into a conservative (APAP) or surgical (MMA) arm. Demographic, biometric, PSG and ESS profiles of the two group were statistically not significantly different. One year after surgery or continuous APAP treatment both groups showed a remarkable improvement of mean AHI and ESS; the degree of improvement was not statistically different. Provided the relatively small sample of studied subjects and the relatively short time of follow up, MMA proved to be in our adult and severe OSAHS patients group a valuable alternative therapeutical tool with a success rate not inferior to APAP.

Development of Clinical Decision Support Systems based on Mathematical Models of Physiological Systems

In the last years of research, I focused my studies on different physiological problems. Together with my supervisors, I developed/improved different mathematical models in order to create valid tools useful for a better understanding of important clinical issues. The aim of all this work is to develop tools for learning and understanding cardiac and cerebrovascular physiology as well as pathology, generating research questions and developing clinical decision support systems useful for intensive care unit patients. I. ICP-model Designed for Medical Education We developed a comprehensive cerebral blood flow and intracranial pressure model to simulate and study the complex interactions in cerebrovascular dynamics caused by multiple simultaneous alterations, including normal and abnormal functional states of auto-regulation of the brain. Individual published equations (derived from prior animal and human studies) were implemented into a comprehensive simulation program. Included in the normal physiological modelling was: intracranial pressure, cerebral blood flow, blood pressure, and carbon dioxide (CO2) partial pressure. We also added external and pathological perturbations, such as head up position and intracranial haemorrhage. The model performed clinically realistically given inputs of published traumatized patients, and cases encountered by clinicians. The pulsatile nature of the output graphics was easy for clinicians to interpret. The manoeuvres simulated include changes of basic physiological inputs (e.g. blood pressure, central venous pressure, CO2 tension, head up position, and respiratory effects on vascular pressures) as well as pathological inputs (e.g. acute intracranial bleeding, and obstruction of cerebrospinal outflow). Based on the results, we believe the model would be useful to teach complex relationships of brain haemodynamics and study clinical research questions such as the optimal head-up position, the effects of intracranial haemorrhage on cerebral haemodynamics, as well as the best CO2 concentration to reach the optimal compromise between intracranial pressure and perfusion. We believe this model would be useful for both beginners and advanced learners. It could be used by practicing clinicians to model individual patients (entering the effects of needed clinical manipulations, and then running the model to test for optimal combinations of therapeutic manoeuvres). II. A Heterogeneous Cerebrovascular Mathematical Model Cerebrovascular pathologies are extremely complex, due to the multitude of factors acting simultaneously on cerebral haemodynamics. In this work, the mathematical model of cerebral haemodynamics and intracranial pressure dynamics, described in the point I, is extended to account for heterogeneity in cerebral blood flow. The model includes the Circle of Willis, six regional districts independently regulated by autoregulation and CO2 reactivity, distal cortical anastomoses, venous circulation, the cerebrospinal fluid circulation, and the intracranial pressure-volume relationship. Results agree with data in the literature and highlight the existence of a monotonic relationship between transient hyperemic response and the autoregulation gain. During unilateral internal carotid artery stenosis, local blood flow regulation is progressively lost in the ipsilateral territory with the presence of a steal phenomenon, while the anterior communicating artery plays the major role to redistribute the available blood flow. Conversely, distal collateral circulation plays a major role during unilateral occlusion of the middle cerebral artery. In conclusion, the model is able to reproduce several different pathological conditions characterized by heterogeneity in cerebrovascular haemodynamics and can not only explain generalized results in terms of physiological mechanisms involved, but also, by individualizing parameters, may represent a valuable tool to help with difficult clinical decisions. III. Effect of Cushing Response on Systemic Arterial Pressure. During cerebral hypoxic conditions, the sympathetic system causes an increase in arterial pressure (Cushing response), creating a link between the cerebral and the systemic circulation. This work investigates the complex relationships among cerebrovascular dynamics, intracranial pressure, Cushing response, and short-term systemic regulation, during plateau waves, by means of an original mathematical model. The model incorporates the pulsating heart, the pulmonary circulation and the systemic circulation, with an accurate description of the cerebral circulation and the intracranial pressure dynamics (same model as in the first paragraph). Various regulatory mechanisms are included: cerebral autoregulation, local blood flow control by oxygen (O2) and/or CO2 changes, sympathetic and vagal regulation of cardiovascular parameters by several reflex mechanisms (chemoreceptors, lung-stretch receptors, baroreceptors). The Cushing response has been described assuming a dramatic increase in sympathetic activity to vessels during a fall in brain O2 delivery. With this assumption, the model is able to simulate the cardiovascular effects experimentally observed when intracranial pressure is artificially elevated and maintained at constant level (arterial pressure increase and bradicardia). According to the model, these effects arise from the interaction between the Cushing response and the baroreflex response (secondary to arterial pressure increase). Then, patients with severe head injury have been simulated by reducing intracranial compliance and cerebrospinal fluid reabsorption. With these changes, oscillations with plateau waves developed. In these conditions, model results indicate that the Cushing response may have both positive effects, reducing the duration of the plateau phase via an increase in cerebral perfusion pressure, and negative effects, increasing the intracranial pressure plateau level, with a risk of greater compression of the cerebral vessels. This model may be of value to assist clinicians in finding the balance between clinical benefits of the Cushing response and its shortcomings. IV. Comprehensive Cardiopulmonary Simulation Model for the Analysis of Hypercapnic Respiratory Failure We developed a new comprehensive cardiopulmonary model that takes into account the mutual interactions between the cardiovascular and the respiratory systems along with their short-term regulatory mechanisms. The model includes the heart, systemic and pulmonary circulations, lung mechanics, gas exchange and transport equations, and cardio-ventilatory control. Results show good agreement with published patient data in case of normoxic and hyperoxic hypercapnia simulations. In particular, simulations predict a moderate increase in mean systemic arterial pressure and heart rate, with almost no change in cardiac output, paralleled by a relevant increase in minute ventilation, tidal volume and respiratory rate. The model can represent a valid tool for clinical practice and medical research, providing an alternative way to experience-based clinical decisions. In conclusion, models are not only capable of summarizing current knowledge, but also identifying missing knowledge. In the former case they can serve as training aids for teaching the operation of complex systems, especially if the model can be used to demonstrate the outcome of experiments. In the latter case they generate experiments to be performed to gather the missing data.