Antitoxin use and pediatric intensive care for viper bites in Rome, Italy.

In Italy viper bites represent an uncommon event, though envenomation can cause severe complications, more in children than adults, because of dose/body size ratio. We present a case series within a selected population: 10 Italian cases (from Rome surroundings) of viperbites requiring PICU admission, over a 5-year interval. Five children showed a systemic involvement, whereas the remaining patients showed a damage. All were managed and closely monitored in an ICU setting. Relevant clinical findings and therapeutic approach, ICU course and complications have been recorded. Age range was 3-15 years with mean age of 6,9 (SD±4,58) years; 2 patients needed respiratory support beyond oxygen supplementation. Most patients underwent fluid loading, while hemodynamic support was given to4/10. Median PICU stay was 60 hours (IQR=24.0-75.5). No mortality was reported. Indications and precautions for administration of antivenom in the last years have been reviewed: early treatment seems to reduce mortality/morbidity, though representing a threat for children. Current recommendations for the treatment of viper envenomation have been described, based on a literature's review and the application of these knowledges to clinical reality of our PICUs. Therefore, paediatric patients with systemic or rapidly evolving symptoms should be monitored carefully for the development of bite-related complications in an ICU setting mostly in younger children.

Predictive factors of left ventricular mass changes after treatment of primary aldosteronism.

A variety of abnormalities that occur in patients with primary aldosteronism indicate the capability of elevated aldosterone to induce cardiac damage over that induced by hypertension itself. This study investigates factors that can predict structural and functional changes of the heart after treatment of primary aldosteronism in a post-hoc analysis of 54 patients who were enrolled in a long-term follow-up study that was conducted after either adrenalectomy or treatment with spironolactone. Cardiac ultrasound assessment was performed before treatment and after with an average follow-up of 6.4 years. During follow-up, blood pressure decreased significantly and comparably in both treatment groups. In both treatment groups, left ventricular mass decreased significantly with a trend to improved diastolic filling profile and no changes in ventricular geometry. At univariate analysis, changes in left ventricular mass induced by treatment of primary aldosteronism were directly related with changes in systolic blood pressure and pretreatment plasma aldosterone levels measured both at baseline and after an intravenous saline load. This relationship was maintained when patients treated with adrenalectomy and spironolactone were analyzed separately. Multivariate regression analysis showed that changes in systolic blood pressure and pretreatment aldosterone levels were independent predictors of left ventricular mass changes after treatment. This study strongly supports a role of aldosterone in promoting left ventricular hypertrophy that is independent of the hypertension-related hemodynamic load and suggests a practical way to predict left ventricular mass changes following surgical and medical treatment of primary aldosteronism.

Aldosterone and the heart: from basic research to clinical evidence.

Recent views suggest that long-term exposure to elevated aldosterone concentrations might result in cardiac, vascular, renal, and metabolic sequelae that occur independent of the blood pressure level. Indirect evidence of the untoward effects of aldosterone on the heart has been clearly established in clinical studies that have tested the effects of mineralocorticoid receptor antagonists in the treatment of systolic heart failure. As it has become clear in recent years, the interaction between aldosterone and the heart has to deal with additional actions of the hormone on specific cell types, cellular mechanisms, and molecules that are involved in regulation of tissue responses, leading to hypertrophy, remodeling, and fibrosis. The majority of these effects are mediated by activation of the mineralocorticoid receptors that are expressed in cardiomyocytes and cardiac fibroblasts, and mediate the genomic effects of the hormone. Evidence of interactions between aldosterone and the heart that occur independent of the renal effects of aldosterone, however, is not limited to the context of systolic heart failure and observations obtained in other disease states have led, together with findings of animal studies, to a better understanding of the potential benefits of aldosterone antagonists. In this narrative overview, we highlight the most recent findings that have been obtained in experimental animal models and in clinical conditions that include, in addition to systolic heart failure, primary aldosteronism, essential hypertension, diastolic heart failure, and arrhythmia.

Mineralocorticoid antagonists treatment versus surgery in primary aldosteronism.

Recent evidence indicates a greater frequency of primary aldosteronism (PA) among patients with hypertension than the previously accepted prevalence. PA was once considered a relatively benign form of hypertension associated with low incidence of organ complications. Recent views, however, suggest that long-term exposure to increased aldosterone levels might result in cardiovascular, renal, and metabolic sequelae that occur independently of the blood pressure level. Cross-sectional comparisons with patients with essential hypertension have demonstrated that patients with PA are at higher risk of cardiovascular events, have more frequent left ventricular hypertrophy and diastolic dysfunction, have greater urinary albumin losses as a marker of a hemodynamic intrarenal adaptation, and are insulin resistant. Some of these findings have been corroborated by the results of short-term, follow-up studies where it was shown that unilateral adrenalectomy or treatment with mineralocorticoid receptor (MR) antagonists are effective in correcting hypertension and hypokalemia. Normalization of blood pressure and correction of hypokalemia, however, are not the only goals in managing PA and effective prevention of organ complications is mandatory in these patients. The relative efficacy of adrenalectomy and MR antagonists, in the long-term, on the cardiovascular, renal, and metabolic outcomes still needs evaluation, being the aldosterone-induced tissue damage the main factor that could justify the cost of increasing efforts in screening of disease and differentiation of subtypes. In this narrative review, we summarize the results obtained with either surgical or medical treatment of PA and outline the findings of long-term, prospective studies on the effects of treatment on cardiovascular and renal outcomes and on insulin sensitivity.

Measles-induced respiratory distress, air-leak and ARDS.

Young infants with measles requiring respiratory support have a significant risk for death and long-term complications. Even in developed countries, the occurrence of spontaneous air-leaks and acute respiratory distress syndrome (ARDS) still represent the most severe clinical presentation in early childhood, with a high fatality rate. A clinical series review from a tertiary university paediatric intensive care unit (PICU) was undertaken. During the 2006-2007 outbreak in Rome, Italy, a young infant presented with ARDS/spontaneous air-leak and needed aggressive ventilatory management and haemodynamic support. Both nebulised iloprost and intravenous pentoxifylline were administered during the acute hypoxaemic phase; the role of this pharmacologic approach in critically ill patients is still under debate. We observed four further cases of respiratory impairment requiring a non-invasive approach. Clinical-radiological findings ranged from interstitial pneumonia to bronchiolitis-like pictures. All patients were imported cases, representing an important epidemiological factor and future medical issue, though they were not malnourished nor affected by chronic diseases. We conclude that early respiratory assessment and timely PICU referral is of mainstem importance in the youngest infants with measles-induced respiratory failure. The protean nature of clinical presentation and the possibility of rapid respiratory deterioration should be highlighted, and infants from immigrant families may represent a susceptible high-risk group.

Surgical treatment of differentiated thyroid carcinoma: a retrospective study.

INTRODUCTION: We carried out a retrospective analysis of our experience in the management of Differentiated Thyroid Carcinoma (DTC), in order to better define prognostic factors (age, gender, histological type, stage) and outline a standard procedure, where it's possible, for surgical treatment. PATIENTS AND METHODS: Patient population consisted of 432 cases, operated from 1978 to 2003. We carried out 285 operations of total thyroidectomy of which 39 associated to some kind of lymphadenectomy, 66 totalization (21 pts had been operated in other institutes), 60 subtotal thyroidectomies and 21 lobo-isthmectomies. Survival and mortality curves for age, sex, histological type, grading and staging have been calculated. Kaplan-Meyer statistical elaboration for disease-free interval and Mann-Whitney test for the comparison of different clinical and pathological data have been employed. RESULTS: The statistical analysis puts in evidence that on 432 cases examined, with a follow-up from 1 to 25 ys (median = 6.33 ys) and with a drop-out of 60 cases (13.8 %), total mortality for cancer has been of 24 cases (6,4%), with a median interval free by disease of 4.2 ys (range 5 months to 25 ys), and a probability to stay free by disease at 12 and 24 months respectively of 95.1% and 91.6%. The median survival is resulted of 5.8 ys (range 1 to 25 ys) with a probability of survival at 24 and 48 months respectively of 97.5% and 94.3%. The multivariate analysis evidences the most important variables, i.e. age > 45 ys, tumor of intermediate malignancy, with size 1.5 cm, operative M+, significantly condition the prognosis, noticeably getting worse it, independently by the kind of carried out operation. CONCLUSION: Our present therapeutic choices are: 1. total thyroidectomy in the treatment of the apparently benign pathology when bilaterally with spread; the checking at the final histological exam of a cancer makes however think adequate the carried out operation; 2. lobo-isthmectomy in the treatment of unilateral benign pathology or with suspect FNAB for follicular neoplasm; the histological checking of a cancer makes think the operation adequate only in presence of favourable prognostic parameters, but in presence even of just one unfavourable variable, we consider necessary the totalization; 3. total thyroidectomy in presence of a certain or strongly suspected preoperative diagnosis of cancer.

Large idiopathic unilateral adrenal hematoma in a young woman.

This is a case report on a young woman with a large idiopathic unilateral adrenal hematoma (AH). Only few cases of AH which were not associated with any trauma, previous surgery, coagulative or any other systemic disorders have been described. The mass was discovered by abdominal ultrasound which was performed for a recent flank pain. Magnetic resonance imaging (MRI) confirmed the presence of a 13-cm sized lesion in the right hemi-abdomen; T1 and T2 weighed imaging was compatible with subacute-to-chronic adrenal hematoma. The lesion dislocated the liver and right kidney. Positron emission tomography (PET) did not show any significant radiotracer uptake by the mass. Serum cortisol, aldosterone, renin activity and DHEA-S were normal. Urinary catecholamines and free cortisol excretion were within the normal range too. The lesion was removed by transabdominal laparoscopic adrenalectomy without any complication. The histological exam confirmed a large subacute- to-chronic organized AH. In conclusion, in the absence of known risk factors, differential diagnosis of a large AH may not be easy. The possibility of an underlying pheochromocytoma, malignant adrenal or metastatic tumor must always be considered. In our patient, computed tomography (CT) scan and MRI suggested the presence of a large subacute-to-chronic AH, and PET excluded metabolic activity of the mass. Laparoscopic adrenalectomy can be the surgical treatment of choice in organized symptomatic AH. The correct diagnosis, early recognition and treatment of complications including adrenal insufficiency may decrease patient morbidity and mortality.

[Video-assisted appendectomy]. / Appendicectomia videoassistita.

BACKGROUND: The acceptability of the classic laparoscopic technique in the treatment of acute appendicitis is slow, probably due to the higher costs of this method compared to the cheaper, efficacious, safe and rapid discharge associated with traditional surgery. METHODS: In order to combine the advantages of the laparoscopic technique with those of traditional surgery, we performed a retrospective study of the safety, efficacy, rapid discharge with return to normal working activities, and the costs in 70 patients referred to our attention with a diagnosis of acute appendicitis and who underwent one trocar appendectomy. This technique consists of positioning a single trocar in an umbilical site and using a 10 mm telecamera with a 5 mm operating canal. Having visualised the appendix and freed it from any synechiae, the distal end is grasped and it is removed through the umbilical trocar. Appendectomy is performed outside using a technique that is similar to traditional surgery. The diagnosis of acute appendicitis was made on the basis of clinical data (pain, leucocytosis, fever, possible resistance in the right iliac fossa).

Role of different dialysis membranes in the release of interleukin-6-soluble receptor in uremic patients.

BACKGROUND: Interleukin-6 (IL-6) exerts its actions through a cell-surface receptor system that consists of two transmembrane subunits: the IL-6 binding glycoprotein gp 80 (IL-6R) and the signal-transducing component (gp 130). Soluble forms of the IL-6R (sIL-6R) are generated by shedding of the membrane-associated proteins. The sIL-6R binds the ligand IL-6 with comparable affinity as the membrane-associated IL-6R and enhances the actions of IL-6. METHODS: Our aim was to evaluate the role of both uremia and different dialysis membranes on peripheral blood mononuclear cell (PBMC) release (either in absence or in presence of mitogen stimulation) and plasma levels of sIL-6R. Ten patients chronically dialyzed with cuprophan membranes (CU), eight patients on regular dialysis treatment with polymethylmethacrylate (PMMA) membranes, 11 uremic nondialyzed patients (UR), and 12 healthy subjects (CON) were included in the study. RESULTS: PBMCs harvested from CU spontaneously released significantly (P < 0.01) greater amounts of sIL-6R (881.8 +/- 80.1 pg/mL), as compared with CON (267.5 +/- 26.5 pg/mL), UR (258.4 +/- 38.1 pg/mL), and PMMA (288.4 +/- 24.6 pg/mL). Under mitogenic stimulation, the sIL-6R release was significantly (P < 0.01) increased in all groups. The greater PBMC production of sIL-6R in CU was followed by significantly (P < 0.01) higher levels of circulating soluble receptors (48.7 +/- 2.5 ng/mL, 60%), as compared with CON (30.5 +/- 1.9 ng/mL). UR also showed high circulating levels of sIL-6R (53.3 +/- 5.9 ng/mL), probably secondary to an impaired urinary excretion. Circulating levels of sIL-6R in PMMA were comparable to CON (30.3 +/- 3.3 ng/mL). Either the absence of monocyte activation or the adsorption of sIL-6R on the hydrophobic PMMA surface could explain this finding. CONCLUSIONS: These results suggest an important role for poor dialysis biocompatibility of CU on the release of sIL-6R, which increases sIL-6R plasma levels, thereby enhancing the inflammatory effects of IL-6.

Serum withdrawal-induced apoptosis in thyroid cells is caused by loss of fibronectin-integrin interaction.

In some cell types, including a fetal thyroid cell line, denial of adhesion to extracellular matrix induces a type of apoptosis called anoikis. Serum withdrawal in dog and transformed rat thyroid cells also induces programmed cell death. Because serum can stimulate cells to produce some components of the extracellular matrix, it was of interest to determine the role of the matrix in the apoptosis induced by serum withdrawal in normal human thyroid cells in primary culture. The present report demonstrates that thyroid cells selectively produce and deposit insoluble fibronectin (FN) only when stimulated by serum. Adhesion in the presence of serum is dependent upon integrin-FN interaction. Serum withdrawal determines a degradation of the insoluble FN deposited and a detachment of the cells from the plates. In these conditions, cells undergo anoikis, demonstrated by DNA fragmentation and annexin V staining. Apoptosis was prevented by exogenous FN immobilized onto the plates. These results indicate that serum withdrawal induces apoptosis in human thyroid cells, determining FN degradation and loss of cell-matrix adhesion.

Hemodialysis-related lymphomononuclear release of interleukin-12 in patients with end-stage renal disease.

Interleukin-12 (IL-12) is a cytokine produced by peripheral blood mononuclear cells (PBMC) that causes interferon-gamma (IFN-gamma) production and enhancement of cell-mediated cytotoxicity. To clarify the role of hemodialysis biocompatibility on IL-12 production and uremic immunodeficiency, we have studied the IL-12 and IFN-gamma release by PBMC harvested from 12 patients dialyzed with cuprophan membrane (CU), eight patients dialyzed with polymethylmethacrylate membrane (PMMA), and eight nondialyzed uremic patients (UR). Ten healthy subjects constituted the control group (CON). PBMC were cultured for 48 h with and without nonspecific mitogen stimulation. In unstimulated conditions, CU showed an IL-12 PBMC production higher than CON, UR, and PMMA (46.67 +/- 30.13 versus 2.56 +/- 1.38, 6.16 +/- 7.09, and 4.62 +/- 4.76 pg/ml, respectively; P < 0.01). IL-12 production was correlated with C3a concentration measured at the outlet of hemodialyzer after 15 min of dialysis (r = 0.69, P < 0.01). IL-12 release in CU remained unchanged under mitogen stimulation (44.34 +/- 23.86 pg/ml) and was lower than in CON, UR, and PMMA (66.0 +/- 12.41, 68.37 +/- 25.78, and 67.75 +/- 22.61 pg/ml, respectively; P < 0.05). IFN-gamma production was similar, in unstimulated conditions, in all groups. Under stimulation, IFN-gamma release was lower in CU (13.42 +/- 12.04 IU/ml) than in CON, UR, and PMMA (51.84 +/- 30.74, 32.16 +/- 13.86, and 32.16 +/- 13.86 IU/ml, respectively; P < 0.01). These results demonstrate that hemodialysis with CU induces monocyte activation with an enhanced release of IL-12. On the contrary, stimulated PBMC production of both IL-12 and IFN-gamma is lower in these patients than in CON, UR, and PMMA. The altered release of these cytokines could play a role in cell-mediated immunodeficiency of the uremic patients dialyzed with CU.

Surgical management of benign thyroid disease.

The most recent surgical approaches to benign uninodular, multinodular, normo and/or hyperfunctioning thyroid disease are considered.

Expression of integrins of the beta1 family in thyroid cells from patients with Graves' disease in vivo and in vitro.

The expression of the beta1 family of integrins was determined in thyroid follicular cells from patients with Graves' disease (GD). Integrin expression was quantitated by flow fluorocytometry of single cell suspensions with antibodies against the common beta1 chain and the alpha1-alpha6 subunits. Results indicated that also in thyroid glands of GD, as previously observed in nodular goiters, two follicular cell populations with different patterns of beta1 integrin expression coexist (VLAalpha3beta1 and VLAalpha1,3,5,6beta1). The VLAalpha1,3,5,6beta1 thyrocyte population in GD was more abundant than in nodular goiters, ranging from 40 to 70% of the total follicular cells and the overall expression of the beta1 integrins was a two-fold higher. In thyrocytes from patients with GD cultured in vitro, alpha3 and alpha2 expression was regulated by cell-to-cell contact as previously described in normal thyroid cells, while the expression of alpha1, alpha5 and alpha6 was quickly lost during the culture. Our data suggest that the integrin profile of the VLAalpha1,3,5,6beta1 thyrocyte population in GD is induced by micro-environmental conditions rather than being the expression of a constitutive phenotype.

[Non-palpable lesions of the breast. Preoperative location techniques with vegetable charcoal]. / Lesioni non palpabili della mammella. Tecnica di localizzazione preoperatoria con carbone vegetale.

PURPOSE: Mammography and US increase the rate of early breast cancer diagnoses. The difficult intraoperative location of nonpalpable lesions has led to the development of various techniques suitable to this purpose. We investigated the effectiveness of free-hand vegetable charcoal lesion marking during both mammography and US and compared this technique with other more commonly used methods. MATERIAL AND METHODS: Our series consisted of 485 consecutive charcoal markings of nonpalpable breast lesions submitted to histologic examination. Marking was carried out free-hand under mammographic guidance in 392 cases and under US guidance in 93 cases. The technique, presented in the paper with schematic drawings, was successful because the surgeon correctly identified the charcoal tracing in all 485 cases. There were no complications, neither during charcoal introduction nor during surgery. RESULTS: The comparison with other marking techniques showed the following advantages of our method: 1) it is rapid and easy to perform; 2) patient discomfort is minimal and no local anesthesia is needed; 3) it is accurate and there are no risks of charcoal displacement or spread; 4) the tracing charcoal is easy to find; 5) the most appropriate surgical route can be followed, with consequently better cosmetic results in the patients not undergoing quadrantectomy; 6) surgery can be performed on an outpatient basis under local anesthesia; 7) a minimal amount of glandular tissue is removed; 8) there are absolutely no side-effects; 9) cost is low; 10) surgery can be planned over time; 11) there is no risk of cutting the wire with an electrotome; 12) no particular equipment or instruments are needed; 13) there are no problems in very superficial lesions. CONCLUSIONS: To conclude, on account of our results and of so many advantages, we believe that free-hand vegetable charcoal marking during mammography and US is now the best possible solution to the problem of surgical identification of nonpalpable breast lesions.

[Splenomegaly and hypersplenism in cirrhotic patients before and after orthotopic liver transplantation]. / Splenomegalia e ipersplenismo nei pazienti cirrotici prima e dopo trapianto ortotopico del fegato.

PURPOSE: To measure the spleen length in patients with cirrhosis and portal hypertension with US and compare the measurements before and after orthotopic liver transplantation. To correlate splenic measures with laboratory data and Doppler flowmetry (mean portal vein flow velocity). MATERIALS AND METHODS: May, 1993, to January, 1997, fifteen patients with cirrhosis, portal hypertension and splenomegaly were examined and underwent orthotopic liver transplantation. The spleen length was measured before and after transplantation in 15/15 patients and it was also measured twice after transplantation in 10/15 patients. The mean portal venous flow velocity was measured before and after transplantation in 10/15 patients. The results were analyzed using the Student's t-test for paired and unpaired data; the association between the variables was evaluated by linear regression analysis; two-tailed p values were used. RESULTS: At the first control after orthotopic liver transplantation (mean time from transplantation 5.5 +/- 2.6 months; range 2.5-12.5 months) a significant decrease was found in spleen length (179 +/- 32 to 149 +/- 30 mm, p = .0001; mean percent decrease = 16.7 +/- 9.9%), hypersplenism disappeared in 9/13 cases, mean portal venous flow velocity, measured in 10/15 patients, showed an increasing trend (16.0 +/- 9.0 to 22.3 +/- 9.0 cm/s). At the first control the correlation between the values of mean portal flow velocity measured before and after transplantation was not significant (r = .558, p = .0939); the same was true for the correlation between mean portal flow velocity and spleen length. The second measurement of the spleen length after transplantation (mean time from the first follow-up 18.1 +/- 7.8 months; range 6.4-32.8 months) in 10/15 subjects demonstrated no significant changes in the spleen dimensions relative to the first examination (139 +/- 24 mm to 138 +/- 26 mm), and in 1/10 case hypersplenism disappeared. CONCLUSIONS: The measurement of the spleen length is proposed for the follow-up of the patients with cirrhosis and hypersplenism before and after orthotopic liver transplantation. In our study, the mean decrease in spleen length was 17% in the period from transplantation to the first US examination. In the patients who underwent a second measurement after transplantation no significant change in spleen length was observed.

Germline and somatic mutations of the RET proto-oncogene in apparently sporadic medullary thyroid carcinomas.

Medullary thyroid carcinomas (MTC) occur sporadically or as part of inherited multiple endocrine neoplasia (MEN) type 2 syndromes. To recognize misdiagnosed familial cases and to establish the frequency of somatic mutations, a series of 50 patients, clinically diagnosed with sporadic MTC, were analyzed for mutations in the RET proto-oncogene. The clinical management of the patient and of the family is different in the two cases. Germline mutations were detected in three independent cases, demonstrating that they were associated to familial MTC. The mutations affected exon 11 in two cases and exon 14 in one case. Somatic mutations were detected in eight patients (30%) and they were indicative of sporadic MTC. In seven cases the mutation affected codon 918 of exon 16 and in one case codon 634 in exon 11. No RET mutations were detected in the remaining patients. A different genetic and clinical management is proposed for individuals with a diagnosis of familial or sporadic MTC.

[Non-palpable lesions of the breast. Retrospective analysis of mammographic and ultrasonographic indications for surgery]. / Lesioni non palpabili della mammella. Analisi retrospettiva delle indicazioni mammografiche ed ecografiche all'intervento chirurgico.

INTRODUCTION: The differential diagnosis of malignancy in small foci of microcalcifications or in extremely small nodes can be difficult. We carried out a retrospective analysis of integrated mammographic and US results, correlated with histologic data, to assess the limitations of each method and to optimize and benign/malignant ratio. MATERIALS AND METHODS: Our series consisted of 485 nonpalpable breast lesions submitted to histologic examination after vegetable charcoal marking. We gave each lesion an 0-5 score according to the degree of diagnostic doubt/suspicion after mammography and US, which results were correlated with histologic data to assess the carcinoma frequency in the various groups identified. RESULTS: The analysis of mammographic and US images showed that the most frequent mammographic alteration in the lesions submitted to biopsy was an isolated cluster of microcalcifications (40.99%): of these, 36.86% were neoplastic. The nodules submitted to biopsy, which were 29.81% of the total, showed a cancer rate (36.80%) very similar to that of the microcalcifications. The carcinoma rate rose to 37.93% when the microcalcifications were associated with nodes. The highest carcinoma rates, i.e., 52.94% and 66.66%, respectively, were found in parenchymal distortions, either isolated or associated with microcalcifications, which however were only 7.03% and 3.10%, respectively, of the total number of cases. DISCUSSION AND CONCLUSIONS: Our study showed that: 1) a highly suspicious US result must be seriously considered when a negative mammography has poor intrinsic contrast; 2) a highly suspicious US image with a little suspicious good contrast mammography requires further confirmation before surgery is planned; 3) when the mammographic finding is mid-to-highly suspicious, further investigations are needed even if US is negative. To conclude, even though the histologic examination of nonpalpable breast lesions involves performing a biopsy, we believe this is acceptable when performed on an outpatient basis, under local anesthesia and removing a limited amount of tissue only. The benign/malignant ratio ranges 2 to 1.5: if it is further reduced (below 1.5), there will be the risk of missing some early neoplastic lesions.