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Biomedical subjects

C Cracco

Publications and source records attributed to C Cracco.

At least 19 recordsLinked to original sources
PubMed2005

Reassessing the current TNM lymph node staging for renal cell carcinoma.

OBJECTIVE: The most commonly used staging system for renal cell carcinoma (RCC) is the tumor-node-metastasis (TNM) system. In the most recent TNM edition, lymph node (LN) involvement is defined as pN0, pN1, or pN2, depending on the number of metastatic LNs (none, 1, or >1). This study evaluated the prognostic value of this classification and tried to improve its clinical impact by considering an additional parameter, that is, LN density (ratio between number of positive LNs and total number of LNs retrieved). METHODS: All pathologic reports of radical nephrectomies performed for RCC in two urologic centers between November 1983 and December 1999 were reviewed. For each patient, complete clinical and pathologic data, number of LNs removed, location and number of positive LNs, and LN density were recorded. The Kaplan-Meyer method and the log-rank test were used to calculate cause-specific survival rates and to compare survival curves, respectively. RESULTS: A total of 735 patients underwent radical nephrectomy. Lymphadenectomy was performed in 618 cases, and the rate of positive LNs was 14.2%. The 5-yr cause-specific survival rate of pN+ patients was 18%, with no statistically significant difference between pN1 and pN2. The average number of LNs removed was 13 (range, 1-35). The median number of LNs involved was 3 (range, 1-18). LN density ranged between 3.7% and 100% (median, 22.9%). The number of LNs removed had no impact on survival in pN+ patients. The only significant unfavorable prognostic factors were >4 LNs involved (p = 0.02) and LN density >60% (p = 0.01). CONCLUSION: The results show that in RCC the current TNM stratification of positive LNs is not significantly correlated with prognosis. From our data it appears that classification as < or =4 or >4 LNs involved, supported by LN density, better reflects the impact of the disease on survival.

Adult↗
PubMed2005

[Tracheostomy in intensive care: impact on prognosis and the influence of underlying chronic respiratory insufficiency].

INTRODUCTION: Numerous uncertainties remain concerning the place of tracheostomy in intensive care. Reluctance to perform tracheostomy is common, particularly in the presence of pre-existing chronic respiratory insufficiency (CRI), but some data suggest there may be benefits. The objective of this study was to evaluate the influence of tracheostomy on mortality in both intensive care and hospital, and to study the role of pre-existing CRI. MATERIAL AND METHODS: In a retrospective study of the records of 2901 patients admitted over a period of 5 years 882 were identified who had been intubated and ventilated. 127 patients who had had tracheostomies (T+) were compared with 755 who had not (T-), and with a sub-group of T- patients (T-app) matched for severity on admission (SAPSII). RESULTS: ICU and hospital mortality were significantly less in the T+ than the T-patients (28 vs 52% and 42 vs 59%) and the duration of stay was longer. This was equally true when matched for severity on admission when T+ were compared with T app (28 vs 49% and 42 vs 59%). Pre-existing CRI did not influence the outcomes of the tracheostomised patients, regardless of whether the CRI was obstructive, restrictive or neuro-muscular. CONCLUSIONS: Tracheostomy can, in certain groups of artificially ventilated patients and in certain care settings, be associated with a reduction in hospital mortality.

Female↗
PubMed2005

Independent prognostic role of circulating chromogranin A in prostate cancer patients with hormone-refractory disease.

The presence of neuroendocrine (NE) differentiation in the context of predominantly exocrine prostate cancer may play a key role in androgen-independent tumor growth. The prognostic significance of plasma chromogranin A (CgA) was assessed in a series of consecutive prostate cancer patients with hormone-refractory disease. One hundred and eight patients with newly diagnosed hormone-refractory prostate cancer entered the study. Plasma CgA levels and other biochemical parameters, such as serum prostate specific antigen, serum alkaline phosphatase, serum lactate dehydrogenase, serum albumin and hemoglobin concentration, were measured at baseline (i.e. when hormone refractoriness occurred) and their prognostic role was evaluated together with patient performance status, Gleason score (at diagnosis of prostate cancer) and the presence of visceral metastases. Furthermore, plasma CgA was prospectively evaluated in 50 patients undergoing chemotherapy. At baseline, 45 patients (43.3%) showed elevated CgA values. Plasma CgA negatively correlated with survival, either in univariate analysis (P=0.008) or in multivariate analysis, after adjusting for previously mentioned prognostic parameters (P<0.05). In the patient subset undergoing chemotherapy, median CgA (range) values were 13.3 (3.0-141.0) U/l at baseline, 19.1 (3.0-486.0) U/l after 3 months, 20.8 (3.0-702.0) U/l after 6 months and 39.4 (3.0-414.0) U/l after 9 months (P<0.01). The corresponding supranormal rates were 17/50 (34%), 23/50 (46%), 26/50 (52%) and 34/50 (68%) respectively (P<0.005). Elevated plasma CgA levels are frequently observed in prostate cancer patients with hormone-refractory disease and correlate with poor prognosis. NE differentiation in hormone-refractory patients is a time-dependent phenomenon and is not influenced by conventional antineoplastic treatments.

Aged↗
PubMed2004

Prognostic value of the involvement of the urinary collecting system in renal cell carcinoma.

OBJECTIVES: The prognostic role of the invasion of the urinary collecting system (UCS) by renal cell carcinoma (RCC) has not attracted a notable amount of attention. The aim of this study was to investigate incidence and prognostic value of UCS involvement in RCC. MATERIAL AND METHODS: All pathological reports of radical nephrectomies performed in two centres of urology from November 1983 to December 1999 were reviewed in order to evaluate the invasion of the UCS (calices, renal pelvis, ureter). Patients were divided into two groups according to presence (Group 1) or absence (Group 2) of UCS invasion. The stage was determined according to the TNM 6th edition. Overall and cause-specific survival rates were evaluated. Univariate and multivariate analyses were performed. RESULTS: The evaluable specimens were 671 from the 735 examined; in 64 cases it was not possible to ascertain or to exclude UCS involvement. Invasion of the UCS was found in 59 cases (8.8%). Median follow-up was 59.0 months (range 0-216). Tumours invading the UCS were usually symptomatic, with high nuclear grade and predominantly high stage. At univariate analysis the 5 year overall and cause-specific survival rates of tumours invading the UCS were significantly lower when compared to those without UCS invasion (42.8% versus 60.8% and 45.5% versus 64.7%, respectively). When groups were stratified, according to the pT category, the 5-year cause-specific survival rate was only significantly different for the pT2 category (33.3% versus 76.9%). At the multivariate analysis TNM staging, symptoms at diagnosis and tumour grade were the only independent prognostic factors. CONCLUSION: The invasion of the UCS by RCC is unusual, particularly in small tumours. UCS involvement does not represent an independent prognostic factor. However, in organ-confined tumours (i.e. pT2) UCS involvement has an influence on the prognosis and should be taken into account when planning adjuvant treatments and follow-up.

Adult↗
PubMed2004

[Initiation and management of home mechanical ventilation].

INTRODUCTION: Effective initiation and optimal monitoring of treatment are essential elements for successful home mechanical ventilation (HMV). STATE OF KNOWLEDGE: Ventilation is best initiated in a hospital setting. There is an enormous range of equipment available but there is little evidence pointing to the superiority of one device over another. Many problems can arise that lead to an interruption in HMV but often these can be resolved simply as discussed in this article. PERSPECTIVES: Unfortunately a number of pitfalls in management remain, the main one being the absence of accurate data about the sleep of patients on ventilators, which hinders optimal nocturnal management. Another problem is the lack of adaptation of equipment for use by handicapped patients. Finally the transfer of responsibility and workload to home carers including family members with disengagement by the hospital can also be a major milestone. CONCLUSION: Successful initiation and supervision is the key to effective home mechanical ventilation. Treatment is often abandoned because of pitfalls, mistakes and lack of knowledge. This article proposes means to improve these two important areas.

Decision Trees↗
PubMed2001

Accuracy of pulse oximetry in the intensive care unit.

OBJECTIVE: Pulse oximetry (SpO2) is a standard monitoring device in intensive care units (ICUs), currently used to guide therapeutic interventions. Few studies have evaluated the accuracy of SpO2 in critically ill patients. Our objective was to compare pulse oximetry with arterial oxygen saturation (SaO2) in such patients, and to examine the effect of several factors on this relationship. DESIGN: Observational prospective study. SETTING: A 26-bed medical ICU in a university hospital. PATIENTS: One hundred two consecutive patients admitted to the ICU in whom one or serial arterial blood gas analyses (ABGs) were performed and a reliable pulse oximeter signal was present. INTERVENTIONS: For each ABG, we collected SaO2, SpO2, the type of pulse oximeter, the mode of ventilation and requirement for vasoactive drugs. MEASUREMENTS AND RESULTS: Three hundred twenty-three data points were collected. The mean difference between SpO2 and SaO2 was -0.02% and standard deviation of the differences was 2.1%. From one sample to another, the fluctuations in SpO2 to arterial saturation difference indicated that SaO2 could not be reliably predicted from SpO2 after a single ABG. Subgroup analysis showed that the accuracy of SpO2 appeared to be influenced by the type of oximeter, the presence of hypoxemia and the requirement for vasoactive drugs. Finally, high SpO2 thresholds were necessary to detect significant hypoxemia with good sensitivity. CONCLUSION: Large SpO2 to SaO2 differences may occur in critically ill patients with poor reproducibility of SpO2. A SpO2 above 94% appears necessary to ensure a SaO2 of 90%.

Bias↗
PubMed2000

Multiple organ failure complicating probable scrub typhus.

This report describes a case of life-threatening acute respiratory distress syndrome with multiple organ failure complicating probable scrub typhus. Favorable outcome was associated with fluoroquinolone therapy. Scrub typhus should be suspected in travelers returning from Southeast Asia presenting with unexplained respiratory manifestations.

Adult↗
PubMed1999

Novel mutation in the ATP-binding site of the MET oncogene tyrosine kinase in a HPRCC family.

Germline mutations in the tyrosine-kinase domain of the MET proto-oncogene were found in patients suffering from the hereditary predisposition to develop multiple papillary renal-cell carcinomas (hereditary PRCC, HPRCC). PRCCs are often multiple and bilateral even in patients without a family history. We analyzed the germline of patients carrying multiple or single papillary tumors with and without family history. One patient had a familial cancer and carried a novel (V1110I) germline MET mutation, located in MET gene exon 16. This mis-sense mutation was found in affected members of this patient's family. Interestingly, the V1110I mutation is located in the ATP-binding site of the MET kinase and is homologous to the V157I mutation that triggers the sarcomagenic potential of the v-erbB oncogene. The V1110I mutated MET receptor is an active kinase and transforms NIH-3T3 fibroblasts in the in vitro assays. Patients without familiality did not show germline mutations in the MET kinase domain, showing that multiple and bilateral papillary kidney tumors develop in the absence of these mutations. In conclusion, we describe a new mutation in the MET oncogene kinase domain, associated to HPRCC, affecting an amino-acid residue critical for kinase activation in different oncogenes.

Adenosine Triphosphate↗
PubMed1998

Coexistence of orbital and retroperitoneal involvement in multifocal fibrosclerosis: case report.

OBJECTIVE: To report a rare case of multifocal fibrosclerosis involving the retrobulbar tissue and the retroperitoneum. METHODS: A 59-year-old man presented with bilateral exophthalmos, more serious in the right eye. Right orbital biopsy showed fibrous tissue with inflammatory cells. After the failure of the radiation therapy, a right orbital exenteration was required. Radiological examinations demonstrated a retroperitoneal mass involving the perirenal fat, the aorta, the presacral and the perivesical tissue. Renal function impaired. A left inferior calycoureterostomy and a surgically placement of a right JJ stent were performed. Histological examination of the retroperitoneal biopsies revealed fibrous connective tissue. RESULTS: After 9 years of follow up, there was no change in left visual or renal function (last creatinine: 1.3 mg/dl), and no symptoms or signs of recurrences. CONCLUSION: This case is the ninth to document the association of orbital pseudotumor and retroperitoneal fibrosis. It is important that both the ophthalmologist and the urologist are aware of the existence of this association, so that suitable treatment can be initiated without delay.

Humans↗
PubMed1997

Sex steroids modulate NADPH-diaphorase expression in the postnatal adrenal neurons of the rat.

The rat adrenal gland contains nitric oxide-producing ganglion cells, contributing to its innervation. In a previous study postnatal number and morphology of these adrenal neurons were analyzed by NADPH-diaphorase histochemistry in the two sexes. A transient sex-related difference in the number of NADPH-diaphorase positive neurons per adrenal gland was found at postnatal day 10, when the number of stained neurons in males was nearly twice that found in females. In the present work we studied the effects of perinatal hormonal manipulation on the number of adrenal NADPH-diaphorase-positive neurons during the second postnatal week. The number of labeled adrenal neurons at postnatal day 10 was higher in females receiving perinatal androgen treatment than in control untreated females, and was similar to that of control untreated males. In contrast, in males that underwent perinatal deprivation of testosterone the number of labeled adrenal neurons was lower than in control males, and similar to that of control females. These differences were found in both the adrenal cortex and medulla. In males and in testosterone-treated females there was a higher proportion of stained multipolar neurons than in females and in androgen-deprived males. No intergroup differences were found in the size of stained neurons. Thus, we demonstrated that the postnatal difference in the number of NADPH-diaphorase-positive adrenal neurons in the two sexes is related to the epigenetic action of gonadal hormones during perinatal maturation.

Adrenal Cortex↗
PubMed1997

In vitro correction of iduronate-2-sulfatase deficiency by adenovirus-mediated gene transfer.

Hunter syndrome is a lethal lysosomal storage disorder caused by the deficiency of iduronate-2-sulfatase and characterized by severe skeletal and neurological symptoms. Only symptomatic treatments are available and, although bone marrow transplantation has been suggested, no encouraging results have been obtained so far. Therefore, gene therapy might be a route to be pursued for treatment of the disease. In this respect, one major goal to achieve is the generation of an overexpressing vector able to correct, in particular, central nervous system (CNS) cells. Adenoviruses have been shown to infect CNS cells efficiently with minor or even absent immunological response. We describe the generation of a replication-defective adenoviral vector, AdRSVIDS, which is able to express in vitro high levels of iduronate-2-sulfatase. After infection, accumulation of mucopolysaccharides in treated Hunter cells was normalized. Furthermore, endocytosis of the transduced IDS did occur via the mannose-6-phosphate (M6P) receptor. Since no animal model for the disease is available, we developed a system based on the generation of derma-equivalents which enabled us to verify the expression of high levels of sulfatase up to 30 days after infection.

Adenoviridae↗
PubMed1997

Chemotherapy with FUDR in the management of metastatic renal cell carcinoma.

SUMMARY: Metastatic renal cell carcinoma has a poor prognosis, requiring systemic therapy, in addition to radical nephrectomy. Since August 1989, 50 patients were treated with continuous, systemic, chronobiological infusion of FUDR (floxuridine) at our Institution. We reported 11.7% of objective responses, a long period of stable disease and low toxicity. We also compared our actuarial survival with the results obtained with recombinant IL-2 treatment.

Actuarial Analysis↗
PubMed1995

Conjunctiva and subconjunctival tissue in primary open-angle glaucoma after long-term topical treatment: an immunohistochemical and ultrastructural study.

BACKGROUND: Primary open-angle glaucoma is commonly treated with long-term hypotensive medical therapy. When this approach becomes inadequate, therapy proceeds with surgery. The present study investigates morphological changes in the conjunctival and subconjunctival tissues induced by short- and long-term topical medical therapy of primary open-angle glaucoma. METHODS: Comparisons were made between biopsy specimens from glaucomatous patients, who received specific eyedrop therapy (timolol and pilocarpine) for various periods of time, and control patients with no conjunctival pathology or topical treatment. Histological, immunohistochemical and ultrastructural parameters were investigated. RESULTS: The morphometric analysis of histological sections and immunohistochemistry (anti-fibronectin antibody) in medium- and long-term therapy patients showed: (a) significant increases in the thickness and number of epithelial cell layers; (b) significant increases in the fibroblast density in both subepithelial and deep connective tissue; and (c) a more compact connective tissue, richer in collagen fibers arranged in whirls, with some inflammatory elements. These findings were confirmed by the ultrastructural analysis. In the same patients, the other immunohistochemical parameters investigated (anti-HLA-DR, anti-CD1a, anti-CD4, anti-CD8, anti-IL2 and C3b antibodies) revealed a tendency to chronic inflammation. Following specific surgery, this tendency manifested itself in a diffuse immune response, especially in those patients who underwent medium- and long-term medical therapy. CONCLUSION: According to these results, antiglaucomatous surgery should be rehabilitated and considered as an alternative to long-term medical therapy in the first-instance treatment of primary open-angle glaucoma.

Administration, Topical↗
PubMed1995

Models of neuronal plasticity and repair in the enteric nervous system: a review.

In the Fifties we developed an experimental model of neuronal plasticity in adulthood, involving the intestinal myenteric plexus. Causing an incomplete stenosis of the gut, the thickness of the wall and the diameter of the lumen underwent a massive increase on the oral side of the obstruction. The myenteric neurons innervating such hypertrophic and hyperplastic smooth muscle became hypertrophic and increased their number per ganglion, in absence of mitoses. Therefore we hypothesized the existence of a reserve pool of morphologically undifferentiated elements within the plexus, undergoing differentiation under conditions of functional hyperactivity. Some recent experiments suggest once again the existence in adulthood of a reserve pool of potential neurons. In fact, we put in evidence a subpopulation of NADPH-diaphorase positive myenteric neurons, very small in size orally to the stenosis and even smaller in the control gut. Following experimental ablation of the myenteric plexus in an intestinal segment and induction of hypertrophy in its smooth muscle layers, we found a two-five-fold increase in neuronal density along mesenteric nerves. This increase is probably due to the recruitment of cells, not readily identifiable as neurons, along mesenteric nerves in an attempt to reinnervate the damaged ileum. Moreover, it is demonstrated that hypertrophic smooth muscle cells may induce neuronal differentiation of transplanted PC12 cells. Finally, we explain the decreased total number of myenteric neurons in advanced age with the exhaustion of this reserve pool: in fact, NADPH-diaphorase positive small neurons in the myenteric plexus of old rats could not be found.

Animals↗
PubMed1994

Quantitative study of the NADPH-diaphorase-positive myenteric neurons of the rat ileum.

The subpopulation of myenteric neurons able to synthesize nitric oxide was studied quantitatively in the adult rat, using the NADPH-diaphorase histochemical method on whole-mount preparations of distended distal ileum. The spatial density of NADPH-diaphorase-positive myenteric neurons was 2388 +/- 193/cm2 (S.D.; five rats), comprising about 27% of the nerve cell bodies per ganglion. Most neurons were intensely stained and displayed predominantly a Dogiel type I morphology; about 8% of the labelled nerve cells were ovoid neurons, exhibiting a pale cytoplasmic reaction product. The mean somatic size of all NADPH-diaphorase-positive myenteric neurons was 446 +/- 40 microns2, with a mean nuclear size of 96 +/- 18 microns2 (mean values +/- S.D.; five rats). Such values fell exactly within the range of neuronal sizes of the total myenteric population, marked by means of NADH-diaphorase histochemistry. Therefore, the morphometric analysis did not identify any peculiar cell size feature, characterizing this specific nerve cell subpopulation. Thus, the present study provides quantitative data on the size, density and proportion of those myenteric neurons that may synthesize nitric oxide in the distal ileum of the rat.

Animals↗
PubMed1993

Mesenteric neurons in the adult rat are responsive to ileal treatment with benzalkonium chloride.

The application of a 2 mM solution of the cationic surfactant benzalkonium chloride (BAC) to an ileal segment produced a selective and extensive myenteric denervation. The aim of the present study was to investigate whether such a selective unbalance of the enteric nervous system in the adult rat elicited any plastic response within the mesenteric nervous structures contacting it. Acetylcholinesterase (AChE) staining, beta-nicotinamide adenine dinucleotide (NADH) and beta-nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry and glyoxylic acid-induced fluorescence were performed on whole-mount preparations of myenteric plexus and mesenteric nerves. In both control and BAC-treated animals nervous elements were detected along the mesenteric nerves. Although rather similar in position, shape and size, these neurons displayed striking differences with regard to their arrangement and density per nerve. In the controls, few small aggregates of neurons could be detected; more commonly, isolated nerve cell bodies were scattered along the nerve trunks. In the BAC-treated animals, numerous spherical or spindle-shaped clusters of neurons were located along the nerves; the mean neuronal density per nerve displayed a two-five-fold increase over the control values. The observed changes within the mesenteric nerves might be involved in an attempt at reinnervation of the BAC-treated intestinal segments from extra-enteric sources.

Acetylcholinesterase↗
PubMed1992

Comparative study of Langerhans cells in normal and pathological human scars. I. Atrophic scars.

In the present study, we investigated Langerhans cells (LCs) in the epidermal component of human atrophic scars, comparing them with those in control skin and normotrophic scars. A preliminary analysis of the histological features was first carried out on vertical serial sections, stained with hematoxylin and eosin. The total epidermal thickness and the thickness of the single epidermal layers were then measured, by means of a digitizing tablet and a morphometric program run on an Apple IIe computer. These parameters were found to be significantly lower (40%) in atrophic scars, if compared to control skin and normotrophic scars (p less than 0.05). CDla-positive and HLA-DR-positive LCs were marked by indirect immunofluorescence. Their position among the epidermal layers, their dimensions, their density and their morphology were examined. In atrophic scars, LCs were densely and evenly distributed in all the epidermal layers. Their density was increased (about 1200 cells/mm2 of epidermal area), if compared to control skin and normotrophic scars (both 300-400 cells/mm2 of epidermal area; p less than 0.001). The CDla-positive definite cell bodies, exhibiting an unstained nucleus, were as large as those evidentiated in the normotrophic scars and twice as much the control skin values (p less than 0.001). The present results provide morphological data that distinguish atrophic scars from control skin and normotrophic scars, and suggest an involvement of the Langerhans cells in this particular case of pathological scarring.

Adolescent↗