Doctor-patient communication tricks. Oncological study at Campus Bio-Medico University of Rome.

OBJECTIVE: Doctor-patient relationship is a very important variable in the oncological clinical consultation. METHODS: We have analyzed 100 outpatients oncological visits (first visits and follow up visits). We conducted an observational study of the extra verbal communication (non-verbal and para-verbal) with a structured observation grid. We have analyzed the three stages of the visit: 1. Patient's admission, 2. Communication flows and 3. Information exchange between doctor and patient. RESULT: In the first visit doctor introduce himself (85%). In the follow-up visit the doctor has received the patient with a handshake (86%) while in the first examination in 100%. In the follow-up visit the short phase of pleasantries was present in 61% of cases, while in the first examination in 45% of cases. Doctor drawn an outline, a design or wrote a note in 45% of first examination and 25% of the follow up. CONCLUSION: Extra verbal communication is more important than the verbal. We suggest useful tips on what "do not" and what "do better" during clinical consultations. CONCLUSION: Against what it is often believed eye contact is not always necessary or useful in establishing a good doctor-patient relationship it depends on the patient's preferred representational system.

Colloids for fluid resuscitation: what is their role in patients with shock?

BACKGROUND: Fluid therapy is widely used in critically ill patients to restore effective intravascular volume and improve organ perfusion. Recent studies have questioned the administration of colloid-based solutions, especially if containing hydroxyethyl starch (HES), in different ICU populations; however, there is still uncertainty on the use of colloids as initial fluid therapy for early resuscitation. METHODS: The aim of this study was to investigate the effect of two different resuscitation fluid strategies on the mortality of patients with shock. In a multicentric (57 ICUs), controlled, open-label trial (from February 2003 to August 2012), the authors randomized patients with signs of acute hypovolemia, defined by the combination of hypotension, evidence of low filling pressures or cardiac index and at least two signs of tissue hypoperfusion (such as altered consciousness, mottled skin, oliguria, lactate levels > 2 mmol/L), to received either a colloid- or crystalloid-based therapy. Both cohorts received maintenance fluids consisting in isotonic crystalloids and albumin in case of severe hypoalbuminemia (<2 g/dL). Exclusion criteria included previous fluid therapy, pregnancy, brain death, extended burns, chronic hemodialysis or liver disease, known coagulopathy, acute anaphylaxis, dehydration and hypotension due to sedative drugs. RESULTS: Among the 6498 eligible patients, 2857 were eventually randomized in one of the two groups. The 28-day mortality was 25.4% in the colloid and 27.0% in the crystalloid group (P=0.26). In the sub-group analysis, similar mortality rates were reported for shock due to hypovolemia, sepsis or trauma. Also, the use of continuous renal replacement therapy was similar between groups (11.0% vs. 12.5%, P=0.19). There were more days alive without mechanical ventilation or vasopressors during the first 7 and 28 days and a lower 90-day mortality in the colloid group. CONCLUSION: These data suggest that mortality was not increased and probably decreased with the use of colloids in different forms of shock requiring early fluid resuscitation. We discussed herein some methodological issues that may explain the discrepancies of this trial with the other studies developed in the same field.

How to target temperature after cardiac arrest: insights from a randomized clinical trial.

Implementation of treatments able to improve survival and neurological recovery of cardiac arrest (CA) survivors is a major clinical challenge. More than ten years ago, two pivotal trials showed that application of therapeutic hypothermia (TH, 32-34 °C) to patients resuscitated from an out-of-hospital CA (OHCA) with an initial shockable rhythm significantly ameliorated their outcome. Since then, TH has been used also for non-shockable rhythms and for in-hospital CA to some extent, even if the quality of evidence supporting TH in such situations remained very low. The objective of this randomized, controlled, multicenter study (named "Targeted Temperature Management" TTM study) was to compare two different strategies of temperature control after CA; patients were randomized to be treated either at 33 °C or at 36 °C for 24 hours, while fever was accurately avoided for the first 3 days since randomization. Inclusion criteria were: Glasgow Coma Score <8, presumed cardiac origin of arrest, randomization occurring within the first 4 hours from the return of spontaneous circulation. Patients were excluded if they had an unwitnessed arrest with asystole as the initial rhythm, suspected or known acute intracranial hemorrhage or stroke, and a body temperature of less than 30 °C. A specific algorithm was used to decide for withdrawal of care in patients remaining comatose after 72 hours since normothermia was achieved. The primary outcome was 6-month mortality. After the enrollment of 939 patients, the authors did not find any significant difference between groups in primary outcome (235/473 [50%] and 225/466 [48%] of patients died in 33 °C and 36 °C group, respectively; HR for death if in the 33 °C group, 1.06 [95% CI 0.89 to 1.28; P=0.51]). Similarly, the analysis of the composite outcome of death or poor neurologic function yielded similar results between the two groups. This is the largest study evaluating the effects of two different strategies of temperature management after CA. Some important concerns have been raised on the real benefit of keeping CA patients at 33 °C and major changes in clinical practice are expected. We discussed herein the main differences with previous randomized trials and tried to identify possible explanations for these findings.

Intraoperative prophylactic and therapeutic non-invasive ventilation: a systematic review.

Non-invasive ventilation (NIV) has been used to prevent or to treat perioperative acute respiratory failure (ARF). Intraoperative prophylactic and therapeutic use of NIV could be of interest to patients with anticipated difficulty in postoperative weaning from mechanical ventilation or to patients refusing tracheal intubation. Intraoperative NIV might also be useful when deep sedation is required, as this can cause respiratory depression. PubMed, Embase, Google Scholar, and Cochrane Library were searched for pertinent studies. Inclusion criteria were NIV use during surgery and adult patients; the exclusion criteria were NIV application only in the preoperative or postoperative periods, paediatric patients, NIV applied as negative pressure ventilation. Thirty papers including 618 patients were included for final analysis. Intraoperative therapeutic NIV to treat ARF was reported for 92 patients and in all those cases, including six Caesarean sections, surgery was completed uneventfully. Intraoperative prophylactic NIV to avoid ARF was described in 24 patients with severe respiratory limitation and in 502 healthy patients during deep sedation. Three patients could not be successfully ventilated due to upper airway obstruction, but no further complication was reported. Intraoperative NIV appears feasible, safe, and potentially useful, particularly when tracheal intubation is best avoided. However, high-quality, randomized studies are required.

Non-invasive ventilation in cardiac surgery: a concise review.

Mild to severe respiratory dysfunction is still a common issue after cardiac surgery. Postoperative respiratory complications are associated with prolonged hospitalization and worse survival. In this high-risk surgery, non-invasive ventilation could have relevant positive effects. The present narrative concise review aims to summarize available data on the role of non-invasive ventilation before and after cardiac surgery. Non-invasive ventilation exerts its main effects on the pulmonary and on the cardiovascular systems.  Non-invasive ventilation can be applied to prevent acute respiratory failure; it can also be prescribed as a curative tool to treat an established postoperative acute respiratory failure. Non-invasive ventilation could also be applied to wean patients from mechanical ventilation. When applied as a preventive tool, the main scope is the prevention of pneumonia by resolving or preventing atelectasis. So far, limited (but encouraging) data are available: its routine use in all patients to prevent postoperative acute respiratory failure cannot be recommended. Non-invasive ventilation to treat postoperative acute respiratory failure has been evaluated more extensively. A failure rate from 10 to 55% was reported. Safety appears preserved, with no relevant hemodynamic complication reported. Non-invasive ventilation has also been applied during percutaneous aortic valve implant in patients unable to lie supine due to severe respiratory limitation and orthopnea. In conclusion, non-invasive ventilation has the potential to be very useful before and after cardiac surgery. So far, results are promising but available data are limited. Training and experience are essential to obtain positive results and to avoid complications.

Non-invasive ventilation during upper endoscopies in adult patients. A systematic review.

BACKGROUND: Upper endoscopies (UE) are widely performed. Non-invasive ventilation (NIV) during UE has been used to avoid respiratory complications, mainly in high-risk or sedated patients. We performed a systematic review on this topic. METHODS: BioMedCentral, PubMed, Embase and the Cochrane Central Register of Clinical Trials were searched (updated September 1, 2012). Further searches involved conference proceedings. RESULTS: We included in this systematic review 27 papers out of 405 publications retrieved. Ten studies reported the use without complications of NIV to assist fiberoptic bronchoscopy (FOB) and broncho-alveolar lavage (BAL). Ten studies described the use of NIV in fiberoptic-guided tracheal intubations. The authors reported no complications, even in hypoxemic patients and they observed only one failure (0.4%). Three studies evaluated the effectiveness of NIV during placement of percutaneous endoscopic gastrostomy in patients with neuromuscular diseases. In this group the failure rate was 4.4%. One study described the successful use of NIV in sedated patients undergoing gastroscopy. Three studies reported the successful application of NIV during trans-esophageal echocardiography. Overall, the procedure could not be performed due to inability of NIV to maintain safe intra-procedural ventilation in four out of total 515 cases of NIV-aided UE, suggesting a success rate higher than 99.2%. CONCLUSION: This is the first systematic review addressing the use of NIV during upper endoscopies. Its use seems feasible, and based on the limited data available NIV appears safe and likely effective. The patients who would benefit the most are: high-risk and patients undergoing sedation.

Non-invasive ventilation after cardiac surgery outside the Intensive Care Unit.

BACKGROUND: Non-invasive ventilation (NIV) can prevent or treat postoperative acute respiratory failure. NIV after discharge from the Intensive Care Unit (ICU) has never been described in the setting of cardiac surgery. METHODS: This study enrolled 85 patients who received NIV in the main ward as treatment for respiratory failure. The patients had the following conditions: atelectasis (45 patients), pleural effusion (20 patients), pulmonary congestion (13 patients), diaphragm hemiparesis (6 patients), pneumonia (4 patients) or a combination of these conditions. RESULTS: Eighty-three patients were discharged from the hospital in good condition and without need for further NIV treatment, while two died in-hospital. Four of the 85 patients had an immediate NIV failure, while eight patients had delayed NIV failure. Only one patient had a NIV-related complication represented by hypotension after NIV institution. In this patient, NIV was interrupted with no consequences. Major mistakes were mask malpositioning with excessive air leaks (7 patients), incorrect preparation of the circuit (one patient), and oxygen tube disconnection (one patient). Minor mistakes (sub-optimal positioning of the face mask without excessive air leaks) were noted by the respiratory therapists for all patients and were managed by slightly modifying the mask position. CONCLUSION: In our experience, postoperative NIV is feasible, safe and effective in treating postoperative acute respiratory failure when applied in the cardiac surgical ward, preserving intensive care unit beds for surgical activity. A respiratory therapy service managed the treatment in conjunction with ward nurses, while an anesthesiologist and a cardiologist served as consultants.

A unique carboxy-terminus truncation mutant of the retinoic acid receptor alpha gene associated with a variant marker chromosome in a retinoic acid resistant HL-60 subline.

In order to contribute to the study of the molecular basis of leukemic cellular resistance to the induction of differentiation by all-trans retinoic acid (RA) we have generated and analyzed a mutant, RA-resistant HL-60 cell line. Molecular analysis of the retinoic acid receptor alpha (RARalpha) cDNA disclosed, in one of the two alleles, a novel mutation consisting of a 7-base deletion in the ligand binding domain that includes part of a FokI restriction endonuclease site previously described. As a consequence of this deletion and translational frame-shift, a stop signal is created that truncates the protein at codon 421, disrupting an essential functional component of the receptor. Transducing an epitope tagged RARalpha into the mutant is sufficient to inhibit clonal growth in the presence of RA. Standard cytogenetic analysis, fluorescent in situ hybridization (FISH) and comparative genomic hybridization (CGH) analysis revealed the presence of two RARalpha loci, and showed a composite karyotype with additional abnormalities with respect to the parental line, including a chromosome 8 insertion in a chromosome previously known as marker three.

Leukemic cellular retinoic acid resistance and missense mutations in the PML-RARalpha fusion gene after relapse of acute promyelocytic leukemia from treatment with all-trans retinoic acid and intensive chemotherapy.

This study evaluated whether relapse of acute promyelocytic leukemia (APL) patients from clinical remissions achieved and/or maintained with all-trans retinoic acid (RA) in combination with intensive chemotherapy is associated with leukemic cellular resistance to RA and with alterations in the PML-RARalpha fusion gene. We studied matched pretreatment and relapse specimens from 12 patients who received variable amounts of RA, primarily in nonconcurrent combination with daunorubicin and cytarabine (DA) on Eastern Cooperative Oncology Group (ECOG) protocol E2491, and from 8 patients who received DA only on protocol E2491. Of 10 RA-treated patients evaluable for a change in APL cell sensitivity to RA-induced differentiation in vitro, 8 showed diminished sensitivity at relapse, whereas, of 6 evaluable patients treated with DA alone, only 1 had marginally reduced sensitivity. From analysis of sequences encoding the principal functional domains of the PML and RARalpha portions of PML-RARalpha, we found missense mutations in relapse specimens from 3 of 12 RA-treated patients and 0 of 8 DA-treated patients. All 3 mutations were located in the ligand binding domain (LBD) of the RARalpha region of PML-RARalpha. Relative to normal RARalpha1, the mutations were Leu290Val, Arg394Trp, and Met413Thr. All pretreatment analyses were normal except for a C to T base change in the 3'-untranslated (UT) region of 1 patient that was also present after relapse from DA therapy. No mutations were detected in the corresponding sequences of the normal RARalpha or PML (partial) alleles. Minor additional PML-RARalpha isoforms encoding truncated PML proteins were detected in 2 cases. We conclude that APL cellular resistance occurs with high incidence after relapse from RA + DA therapy administered in a nonconcurrent manner and that mutations in the RARalpha region of the PML-RARalpha gene are present in and likely mechanistically involved in RA resistance in a subset of these cases.

Expression of the lymphotoxin beta receptor on follicular stromal cells in human lymphoid tissues.

The lymphotoxin beta receptor (LTbetaR), and its ligand, LTalpha1beta2, have been proposed to play a key role in the development and organization of lymphoid tissues. The LTbetaR is expressed on a variety of human primary and transformed cells, but strikingly absent on T or B lymphocytes and primary monocytes or peripheral dendritic cells, although LTbetaR is detected on some myeloid leukemic lines. In the developing thymus LTbetaR is prominent along the trabeculae and into the medulla upto corticomedullary junction. In the spleen, LTbetaR is prominently expressed by cells in the red pulp and along the borders of red and white pulp which colocalizes with reticular stromal cells. The LTbetaR is expressed on a human follicular dendritic cell line, FDC-1, and signals expression of CD54 when ligated with the LTalpha1beta2 complex. These results support the concept that directional interactions between LTalpha1beta2 bearing lymphocytes and LTbetaR bearing stromal cells are involved in the organization of lymphoid tissue.

Autoantibody production and cytokine profiles of MHC class I (beta2-microglobulin) gene deleted New Zealand black (NZB) mice.

We established a colony of MHC class I deleted (knockout) NZB mice, which lack the beta2 microglobulin gene (NZB.beta2m-/-), to characterize the contribution of MHC class I to the thymic microenvironment abnormalities, autoantibody production and lupus-like disease of NZB mice. Using an extensive panel of well characterized monoclonal antibodies defining thymic epithelial and other stromal elements, we demonstrated that deletion of MHC class I molecules does not change the thymic abnormalities, including the presence of a cortical epithelial cell free region, ectopic expression of medullary epithelial antigens, and the irregular shape of the medullary epithelial network of NZB mice. Moreover, the decreased staining of MTS 33(+) cells, a marker of premature thymocyte maturation, was also seen in NZB.beta2m-/-. However, although NZB.beta2m-/- mice had approximately the same levels of IgM and IgG anti-ss and dsDNA antibodies when compared to control NZB mice, there were significant alterations in the incidence and onset of anti-erythrocyte antibody levels. NZB.beta2m-/- had a lower incidence and a delayed onset of anti-erythrocyte autoantibody production compared to that seen in NZB mice. We also compared constitutive and PHA-P-driven levels of IFN-gamma, IL-4, IL-6, and IL-12 in cells from NZB, NZB.beta-/-2, and control C57BL/6 mice. Mitogen stimulated cells showed a decreased IFN-gamma, and a marked increase in IL-6 and IL-12 in NZB and NZB.beta2m-/- mice.

Extractive spectroscopic insulin determination in pharmaceutical formulations.

Two methods are proposed, one spectrophotometric and one spectrofluorimetric, for the determination of insulin in several pharmaceutical formulations. The methods were found to be fairly simple, sensitive and accurate, and thus suitable for this purpose. Both methods involve an extractive step with diethyl ether for the elimination of excipient interference, and subsequent direct spectrometric analysis. Spectrophotometric determinations were carried out at lambda = 276 nm; spectrofluorimetric determinations were carried out at lambda em = 306 nm with lambda exc = 277 nm.

Experimental analysis of tensile properties of some suturing materials.

The aim of the investigation is to quantitatively evaluate the failure load of several suture materials currently used in dentistry surgery. No chromic catgut, silk, Prolene, Ethilon, Ethibond, Vicryl and Vicryl Rapid, obtained from Ethicon s.p.a., in the sizes 3-0, 4-0, and 5-0 have been tested. The analysis has been carried out measuring the diameter of each suture with an optical microscope to determine the accuracy of manufacturers' data. Tensile testing has been performed to evaluate the failure load of each material. Finally, sutures of the same effective diameter class have been compared relative to failure load. Results show that monofilament sutures present a failure load remarkably superior to that of multifilament sutures. Using SEM analysis monofilament sutures present less surface irregularities than multifilament sutures. Only monofilaments Ethilon 4-0 and 5-0, Prolene 4-0, and multifilament no chromic catgut 4-0 and 5-0 meet the requirements of the Italian Pharmacopeia. In contrast, Prolene 5-0 and the other multifilaments, silk, Ethibond, Vicryl and Vicryl rapid, have a larger diameter than that declared on the label by the producer.

[The choleretic effects of licorice: identification and determination of the pharmacologically active components of Glycyrrhiza glabra]. / Studio dell'effetto coleretico della liquirizia: identificazione e determinazione di componenti della Glycyrrhiza glabra farmacologicamente attivi.

Recent studies indicate that licorice extract, when administered per os or i.v., causes an evident choleretic effect in rats. Aim of this research is to identify and quantify those licorice constituents which are responsable for the observed choleresis. The quali-quantitative analysis of umbelliferon (7-idroxycoumarin), was at first performed by a fluorimetric method, subsequently by a more selective HPLC method. Moreover, this HPLC method allows the determination of glycyrrhizin, an important licorice constituent. Unlike the glycyrrhizin, which is present in a fairly large amount, umbelliferon resulted to be present at a very low concentration (at trace level), both in licorice and in bile. Research is in progress, aiming to determine the substances, beyond glycyrrhizin, which are responsable for the choleretic effect of licorice.

HPLC determination of glycyrrhizin and glycyrrhetic acid in biological fluids, after licorice extract administration to humans and rats.

Simple and sensitive HPLC methods were developed for the determination of glycyrrhyzin (G) and its main metabolite glycyrrhetic acid (GA) in biological samples, in order to investigate the pharmacokinetic behaviour of G after oral administration of licorice extract (LE) or G to humans and rats. The analysis have been carried out by HPLC with UV detector (251 nm), after a careful pretreatment of the samples. These methods are suitable in terms of precision and accuracy for the G and GA determination in plasma and urine of human volunteers and in bile, plasma ad urine of rats.

Homeostasis and narcolepsy.

Narcolepsy is characterized by irresistible daytime sleep episodes and cataplectic attacks. Because of the finding of an ultradian rhythmicity of slow-wave sleep in narcolepsy, an alteration of nonrapid eye movement sleep homeostatic regulation has been hypothesized to explain the impairment of the sleep-wakefulness cycle. This hypothesis was tested by two different methods: 1) a sleep-deprivation method (16 or 24 hours) increasing the prior sleep wakefulness and 2) a bed-rest method shortening the prior sleep wakefulness. In both studies normal subjects, sex- and age-matched to narcoleptic subjects, served as controls. Although some differences could be evidenced between the two groups, it was clearly shown that the homeostatic process was functional in narcolepsy and that narcoleptics seemed to be more sensitive to homeostatic regulation of sleep than normal subjects.

Characterization of TNF receptors on human thymocytes.

Although tumor necrosis factor-alpha (TNF) is constitutively expressed in human and mouse thymus, the effects of TNF on thymocyte proliferation, differentiation and survival suggest that its influence in the thymus is complex. To determine if this complexity results from changes in the expression of the two TNF receptors during thymocyte differentiation, we examined the expression of the 55 kDa TNF receptor (TNF-R1) and the 75 kDa TNF receptor (TNF-R2) on postnatal human thymocytes. Both TNF-R1 and TNF-R2 mRNA were found in resting human thymocytes by reverse transcriptase-polymerase chain reaction (RT-PCR). Using mAb which specifically react with the respective TNF receptors and a highly sensitive, three-step method of immunofluorescence, cell surface TNF-R1 was detected on the vast majority of thymocytes. In contrast, detectable cell surface TNF-R2 was present on a mean of only 12.9% of thymocytes. TNF conjugated to phycoerythrin (TNF-PE) also reacted with a small population of thymocytes and was found to specifically block binding of the TNF-R2 mAb and not the TNF-R1 mAb, implicating preferential binding of TNF-PE to TNF-R2. Using dual-color immunofluorescence with TNF-PE we found that the population of cells which express TNF-R2 also express high levels of the TCR alpha, beta-CD3 complex, CD4 or CD8, and IL-2 receptor alpha chain. Thus, immature (TCRneg/low) thymocytes express TNF-R1 while mature (TCRhigh) thymocytes can also express TNF-R2. This differential expression of TNF receptors provides a mechanism for distinct effects of TNF on immature vs. mature thymocytes.