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Biomedical subjects

A Di Nardo

Publications and source records attributed to A Di Nardo.

At least 19 recordsLinked to original sources

Characteristics of Type 2 diabetic patients cared for by general practitioners either with medical nutrition therapy alone or with hypoglycaemic drugs.

The essential role of medical nutrition therapy (MNT) for people with diabetes is widely recognised, and its exclusive use is recommended in mild diabetes according to a stepwise therapeutic approach. We describe the characteristics of MNT-treated Type 2 diabetic patients (vs drugs) cared for by general practitioners (GPs) in order to check that appropriate differences did exist between the two groups, by auditing the data from our local shared-care program for diabetes. We had 16,000 diabetic patients (out of 630,000 inhabitants); 6,800 of them (42.5%) cared for by GPs. Thirty-one percent (2,079 out of 6,800 patients cared for by GPs) were treated with MNT and 69% with drugs. The MNT-treated patients (vs drugs) were younger (66.1 +/- 10.7 vs 67.7 +/- 11.0 yr, p<0.01), had shorter disease duration (8.2 +/- 6.6 vs 11.2 +/- 7.6 yr, p<0.01), lower HbA1c (7.0 +/- 1.1 vs 7.8 +/- 1.6%, p<0.01) and body mass index (BMI) (28.6 +/- 4.6 vs 29.0 +/- 4.9 kg/m2, p<0.01). They had less prevalence of high blood triglycerides (25.4% vs 29.0%, p<0.01). MNT-treated patients had less micro-albuminuria (5.3% vs 8.8%, p<0.01); less retinopathy both non-proliferant (6.5% vs 11.1%, p<0.01), and pre-proliferant (6.8% vs 12.7%, p<0.01), and proliferant (7.0% vs 12.9%, p<0.01); less peripheral neuropathy (3.9% vs 8.3%, p<0.01); and diabetic foot (1.0% vs 2.0%, p<0.01). They had less chronic heart failure (2.7% vs 4.6%, p<0.01), and claudicatio intermittens (3.3% vs 5.3%, p<0.01). In conclusion, the Type 2 diabetic patients cared for by GPs using MNT appropriately had a less severe form of diabetes.

Age Factors↗

Pelvic exenterative procedures for locally advanced or recurrent colorectal carcinoma in a community hospital.

BACKGROUND: We describe our experience with exenterative pelvic surgery for colorectal cancer in a small community hospital. METHODS: We retrospectively evaluated 26 consecutive patients (14 women) with locally advanced (n=16) or recurrent (n=10) colorectal adenocarcinomas who underwent pelvic exenterations between August 1990 and December 2001 in our service. RESULTS: Seventeen patients had posterior pelvic exenteration (PPE), eight had total pelvic exenteration (TPE) and one had TPE with internal hemipelvectomy. Major morbidity occurred in 12 patients (46%), causing 3 deaths (11%) in the immediate postoperative period. Fourteen of 23 patients who survived the immediate postoperative period have relapsed (61%). At a median follow-up of 42 months, the 5-year survival is 38%. CONCLUSION: Pelvic exenterative procedures can be offered to patients with bulky or recurrent colorectal carcinomas with adequate results and satisfactory palliation, even in a community setting.

Adenocarcinoma↗

[Sentinel lymph node for breast cancer: remove less to know more].

BACKGROUND: Our aim was to study the value of sentinel lymph node (SLN) biopsy in patients with breast cancer seen at a community hospital. METHODS: Consecutive cases receiving primary treatment for unicentric breast cancer less than 3 cm in diameter were prospectively studied from January 1999 to July 2000. All patients signed a detailed informed consent. The majority of patients (89%) underwent a combined technique of intradermal injection of 0.3-1.2 mCi of (99)Tc and 1-3 cc of Patent Blue at the biopsy site. Intraoperative localization was performed with a hand-held gamma probe. The first 15 patients underwent routine back-up lymphadenectomy. Thereafter, only patients with positive SLN, suspicious findings, or personal preference underwent formal axillary dissection. RESULTS: One hundred eight cases were included in the study with a median age of 61 years and a median diameter of the breast tumor of 1.5 cm. Success rate for identification of SLN was 94% (101/108 cases). A total of 917 additional lymph nodes were removed after SLN biopsy (median 6.5 lymph nodes/patient). Correlation between SLN and the final axillary status was 98%. In 20/36 patients (61%) with positive axillary status the sentinel lymph node was the only positive one. Ten patients had only microscopic foci of cancer found in the SLN. Sixty-seven patients (62%) could have avoided axillary dissection becouse the SLN was found, it was negative, and there were no other intraoperative suspicious findings. CONCLUSIONS: SLN biopsy is accurate and easily reproduced. Our data confirms that the majority of breast cancer patients may no longer need routine axillary lymphadenectomy.

Adult↗

Ceramide 2 (N-acetyl sphingosine) is associated with reduction in Bcl-2 protein levels by Western blotting and with apoptosis in cultured human keratinocytes.

BACKGROUND: Ceramides produced by sphingomyelin hydrolysis activate a cycle that is followed by three different major cellular responses: downregulation of cell proliferation, induction of cell differentiation and apoptosis. In the skin, the generation of intracellular ceramide may also provide a link between an extracellular signal and the induction of the apoptosis programme for the elimination of damaged cells. OBJECTIVES: We investigated the effect of ceramides capable of entering cells on cultured keratinocytes. METHODS: Human keratinocytes from neonatal skin were cultured in serum-free medium with or without increasing concentrations of ceramide 2 (CER-2; N-acetyl sphingosine) (5, 10, 20 and 40 micromol L-1). Proliferative effects were studied either by cell counts or by 3H-thymidine incorporation and flow cytometric analysis. Apoptosis was studied by TUNEL staining and Western blot analysis of Bcl-2 protein. RESULTS: Cell counts and DNA synthesis were reduced in a dose-dependent manner following CER-2 treatment. TUNEL staining showed CER-2-induced apoptosis at 48, 72 and 96 h. Western blot analysis showed that CER-2 induces downregulation of Bcl-2 at 24-96 h. CONCLUSIONS: These results demonstrate that CER-2 inhibits cell proliferation and induces apoptosis, possibly via a Bcl-2-dependent mechanism.

Apoptosis↗

Alternative splicing of the mouse profilin II gene generates functionally different profilin isoforms.

Profilins are a conserved family of proteins participating in actin dynamics and cell motility. In the mouse, two profilin genes are known. Profilin I is expressed universally at high levels, while profilin II is expressed mainly in the brain. Here we describe the occurrence of two mouse profilin II isoforms, A and B, which are derived by alternative splicing. They are identical through residue 107 of the protein, but then have distinct C-terminal sequences. Profilin IIA binds to poly-L-proline and actin with high affinity similar to profilin I. Profilin IIB on the other hand does not bind to actin and the affinity for poly-L-proline is greatly diminished. However, tubulin was found to bind to GST-profilin IIB, and in vivo GFP-profilin IIB was recruited to spindles and asters during mitosis in HeLa cells. Our results indicate unexpected diversity in the functions of the profilin family of proteins, and suggest that in mouse profilin IIA is intimately involved in actin dynamics, while profilin IIB associates with other cytoskeletal components.

Alternative Splicing↗

In mouse brain profilin I and profilin II associate with regulators of the endocytic pathway and actin assembly.

Profilins are thought to be essential for regulation of actin assembly. However, the functions of profilins in mammalian tissues are not well understood. In mice profilin I is expressed ubiquitously while profilin II is expressed at high levels only in brain. In extracts from mouse brain, profilin I and profilin II can form complexes with regulators of endocytosis, synaptic vesicle recycling and actin assembly. Using mass spectrometry and database searching we characterized a number of ligands for profilin I and profilin II from mouse brain extracts including dynamin I, clathrin, synapsin, Rho-associated coiled-coil kinase, the Rac-associated protein NAP1 and a member of the NSF/sec18 family. In vivo, profilins co-localize with dynamin I and synapsin in axonal and dendritic processes. Our findings strongly suggest that in brain profilin I and profilin II complexes link the actin cytoskeleton and endocytic membrane flow, directing actin and clathrin assembly to distinct membrane domains.

Actins↗

Supracricoid partial laryngectomies: oncologic and functional results.

BACKGROUND: The authors present their study on oncologic and functional results of supracricoid partial laryngectomies (SPL) performed on 149 patients between January 1984 and December 1995. METHODS: Cricohyoidopexy (CHP) was carried out on 98 patients and cricohyoidoepiglottopexy (CHEP) on 51 patients. The patients were divided into two groups. The first group included those operated on between January 1984 and December 1992 and who therefore had a minimum follow-up period of 3 years. The second group included those operated on after December 1992 and who therefore had a follow-up period of less than 3 years. The statistical evaluation of this second group was carried out using an actuarial method according to Kaplan-Meier. RESULTS: In the first group, survival rate (regarding disease-related deaths) was 94% (95/101), whereas in the second group, survival rate was 95%. There were 9 recurrences in the 149 patients (6.71%), B of which occurred after CHP (6 for tumor [T] and 2 for node [N]) and 1 (for T) after CHEP. Three of the 6 recurrences for T after CHP occurred in the hypopharynx, 2 in the peristomal area, and 1 in the arytenoid area. The only recurrence for T after CHEP occurred in the paraglottic area. Decannulation was carried out in 85.7% of CHP patients (84/98) and in 98% of CHEP patients (50/51). The nasogastric tube was kept in position for an average of 28 days (range, 15-90 days) in the CHP patients and 15 days (range, 9-90 days) in the CHEP patients. Swallowing was excellent; only a small number of patients (n = 21) were forced to assume a particular posture during meals. Phoniatric controls performed on 104 patients also showed adequate speech recovery. CONCLUSIONS: If the indications are applied scrupulously, CHEP is a valid alternative to partial laryngeal surgery and CHP is a possible alternative to total laryngectomy in the treatment of glottic and supraglottic tumors.

Adult↗

Ceramide and cholesterol composition of the skin of patients with atopic dermatitis.

Atopic dermatitis skin tends to be easily irritated and appears dry. These clinical peculiarities correspond to impaired barrier function and to increased transepidermal water loss (TEWL) values. A few studies suggest that a reduced amount of total ceramides (especially of ceramide 1) is responsible for functional abnormalities of the skin of atopic dermatitis patients. The aim of this study was to analyze the relationship between epidermal lipids and barrier impairment in the skin of patients with atopic dermatitis. The quantity of ceramides, cholesterol sulphate and free cholesterol of 47 patients with atopic dermatitis and 20 age- and sex-matched healthy subjects was assessed by cyanoacrylate stripping and thin layer chromatography. Capacitance and TEWL were recorded at the same site of the lipid sample. In patients with atopic dermatitis, the levels of ceramide 1 and 3 were significantly lower and values of cholesterol significantly higher with respect to healthy subjects. Moreover, the CER/CH ratio was significantly lower with respect to normal skin. Patients with active signs of eczema also had higher TEWL values and lower capacitance values. By contrast, patients with no active signs of atopic dermatitis had a normal barrier function and intermediate values of ceramides and cholesterols, when compared to patients with atopic dermatitis with active lesions and normal subjects. The quantity of ceramide 3 was significantly correlated with TEWL impairment. These findings suggest that a decrease in ceramides in the stratum corneum is involved in barrier impairment in atopic dermatitis skin. Our data confirm those of other authors and support the view that impaired metabolism of ceramides may be the cause of dry skin and impaired barrier function in atopic dermatitis.

Adolescent↗

In vitro selection of dopamine RNA ligands.

RNA aptamers that specifically bind dopamine have been isolated by in vitro selection from a pool of 3.4 x 10(14) different RNA molecules. One aptamer (dopa2), which dominated the selected pool, has been characterized and binds to the dopamine affinity column with a dissociation constant of 2.8 microM. The specificity of binding has been determined by studying binding properties of a number of dopamine-related molecules, showing that the interaction with the RNA might be mediated by the hydroxyl group at position 3 and the proximal aliphatic chain in the dopamine molecule. The binding domain was initially localized by boundary experiments. Further definition of the dopamine binding site was obtained by secondary selection on a pool of sequences derived from a partial randomization of the dopa2 molecule. Sequence comparison of a large panel of selected variants revealed a structural consensus motif among the active aptamers. The dopamine binding pocket is built up by a tertiary interaction between two stem and loop motifs, creating a stable framework in which five invariant nucleotides are precisely arrayed. Minimal active sequence and key nucleotides have been confirmed by the design of small functional aptamers and mutational analysis. Enzymatic probing suggests that the RNA might undergo a conformational change upon ligand binding that stabilizes the proposed tertiary structure.

Base Sequence↗

Parallel intraindividual evaluation of the vasoconstrictory action and the anti-allergic activity of topical corticosteroids.

The human skin blanching assay is a well established method for ranking the efficacy of corticosteroids after epicutaneous application. Vasoconstriction is a pharmacological activity, which correlates well with the clinical efficacy, the intensity of skin blanching after a single application under occlusion corresponding, generally, to the clinical efficacy after repeated application without occlusion. However, in studies dealing with the comparison between the vasoconstriction assay and the evaluation of the clinical effects on inflammatory skin diseases, some exceptions to this correlation have been reported. Therefore, in a pre-clinical phase, it would be useful to combine the blanching assay with at least one anti-inflammatory assay. In the present study the blanching assay and the allergic contact dermatitis inhibition test were performed in parallel, in order to compare the two testing procedures in the same group of subjects, utilizing standardized study designs supported by objective means of evaluation. Three commercial preparations of corticosteroids containing clobetasol propionate (CP), clobetasone butyrate (CB) and hydrocortisone acetate (HA), respectively, were employed both to treat nickel-induced positive patch test responses on the volar forearms, and to perform a vasoconstrictor assay on normal forearm skin in 16 nickel-sensitized healthy volunteers. For evaluating skin blanching, we employed colorimetric measurements, whereas for the quantitative determination of the inhibition of the intensity of allergic patch test reactions, 20 MHz B-scanning supported by image analysis was used. Both colorimetric and echogenicity values enabled us to distinguish between the three corticosteroids (at the 17 h evaluation and the 64 h assessment, respectively). A fair correlation was noted between colorimetric and echogenicity values. Both testing procedures ranked the three corticosteroids in the expected order. Corticosteroid preparations should be compared using methods which allow different effects to be simultaneously monitored, without involving a high number of patients. We are proposing this double procedure for the parallel intraindividual evaluation of the vasoconstrictory action and the anti-allergic activity of topical steroids.

Administration, Topical↗

Inhibition of elicitation of contact dermatitis in humans by mometasone furoate: evaluation by means of 20-MHz B scanning associated with image analysis.

BACKGROUND: Mometasone furoate (MF) is a new strongly lipophilic steroid which has an anti-inflammatory effect as evaluated by in vivo and in vitro studies. OBJECTIVE: The objective of the present study was to investigate the degree of inhibition of experimental allergic contact dermatitis induced by the treatment with MF. METHODS: The therapeutic effect was evaluated by an echographic method associated with image analysis. MF activity was compared to that of hydrocortisone acetate 0.5% (Cortaid Cream, Lachifarma), clobetasone butyrate 0.05% (Eumovate Cream, Glaxo) and clobetasol propionate 0.05% (Clobesol Cream, Glaxo), classified respectively as weak, moderately potent and very potent steroids. RESULTS: The different corticosteroid formulations employed for inhibiting experimentally induced contact dermatitis reflect the expected rank order of efficacy. CONCLUSION: MF behaves like clobetasol butyrate ranking as a moderately potent corticosteroid.

Administration, Topical↗

No alteration of biophysical parameters in the skin of subjects with respiratory atopy.

BACKGROUND: Skin hyperreactivity to environmental factors in patients with atopic dermatitis has been extensively studied. Conversely, little is known on the biophysical parameters of the skin in patients with respiratory allergy. OBJECTIVE AND METHODS: Functional characteristics of the skin in subjects with allergic asthma and/or rhinitis were studied using evaporimetry, capacitance and pHmetry. Data were compared to those of healthy subjects and patients with atopic dermatitis (AD). RESULTS AND CONCLUSIONS: Our results suggest that the skin of patients with atopic respiratory allergy does not show altered biophysical parameters when compared to normal skin, confirming that the functional alterations in AD skin are linked to the expression of the atopic diathesis in the skin.

Adolescent↗

Sodium hydroxide-induced irritant dermatitis as assessed by computerized elaboration of 20 MHz B-scan images and by TEWL measurement: a method for investigating skin barrier function.

Sodium hydroxide-induced irritation was studied in 34 volunteers, by means of 24-h patch testing at different concentrations, and by a 10-min testing procedure employing 0.1 mol/l NaOH. As a supplement to subjective evaluation of skin changes, assessments of test areas by TEWL measurement and sonography were performed at 24, 48 and 72 h. After 24-h patch testing, instrumental evaluations showed an increase in the extension of the hypo-echogenic dermal area and in TEWL, whereas a 10-min NaOH application induced a decrease of the dermal and epidermal reflectivity and an increase in TEWL. Twenty-four hour patch testing with 4% NaOH allowed a classification of subjects into two categories: subjects who reacted normally and hyper-reactors. Hyper-reactors showed an enhanced inflammatory response and a more pronounced barrier function damage, as assessed clinically and instrumentally by decreased dermal reflectivity, and by higher postexposure TEWL. Subjects with a more marked inflammatory response to 4% NaOH also showed greater TEWL increases during the short-term testing procedure employing 0.1 mol/l NaOH. Moreover, these subjects were characterized by higher baseline TEWL values, indicating that cutaneous reactivity to NaOH is at least partly correlated to impaired stratum corneum function, which is inadequate to effectively prevent compounds from penetrating the skin.

Adolescent↗

Echographic evaluation with image analysis of normal skin: variations according to age and sex.

In order to identify and characterize the sonographic variations between different age groups, 48 subjects, 24 aged 27-30, and 24 over 60, were studied with a 20-MHz B scanner on six skin sites. Images were evaluated by the instrument's standard programme and by a new image analysis software package enabling the characterization of steady structures or transitory functional aspects of skin reactions, by highlighting areas in which the echo amplitudes are included within selected values, and by calculating their extension. Three bands were selected as intervals of interest, respectively, highlighting hyporeflecting parts of the dermis, tissue reflecting with intermediate amplitude values and hyperreflecting epidermis and dermis. This method was employed to assess skin thickness, demonstrating its decrease in elderly skin, to characterize and quantify the hypoechogenic subepidermal band appearing in the elderly at volar and dorsal forearm skin, and to evaluate echogenicity of the upper and lower dermis. Our data show that there is a great regional variation in the behaviour of ultrasound reflection of elderly skin in respect to the skin of young subjects. However, a general trend can be identified, consisting in a shift from low-intensity ultrasound echoes, characteristic in the dermis of young subjects, to intermediate or high reflection amplitudes, which are more frequent in elderly skin. Thus, the echographic method provides two parameters for the evaluation of skin aging.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[ANP in the cirrhotic patient. A clinical contribution].

Pathogenesis of ascites in patients affected by liver cirrhosis is still debated; humoral and haemodynamic factors can play a role. Plasmatic renin activity (PRA), plasmatic aldosterone (PA), atrial natriuretic peptide (ANP) plasma levels, blood Na, K, urea, urinary K and Na were evaluated in 14 patients affected by liver cirrhosis (11 males and 3 females, aged from 38 to 62 years), 8 of them with ascites. The results were compared with those obtained in a control group poised to age and sex to the experimental group. 4 out of 14 patients suffering from ascites unresponsive to medical treatment were submitted to peritoneal venous jugular shunt (PVGS) and blood samples for PRA, PA and ANP were withdrawn immediately before, 4, 8 hours following surgery. The patients affected by liver cirrhosis without ascites showed PRA and PA levels similar to those observed in the control group, while ANP plasma levels were significantly higher (50.6 + 9.6 vs. 39.7 + 9.5 Pg/ml) (p < 0.02). In patients with ascites ANP, PA and PRA levels were higher than those observed in non ascites patients (ANP = 147.8 + 97.3 vs. 50.6 + 9.6 pg/ml; PA = 20.6 + 2.7 vs 7.8 + 0.8 ng/dl; PRA = 4.48 + 0.5 vs 1.9 + 0.34 ng/ml/h). In patients submitted to PVGS, PA and PRA levels were reduced 4 and 8 hours following the surgery, while ANP levels showed significant increase. A natriuretic and diuretic response has been observed even in the absence of ANP plasma levels variations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Echographic evaluation with image analysis of histamine-induced wheals.

10 healthy, non-atopic women, aged 20-30, underwent histamine prick tests, performed in duplicate on the volar surface of the forearm with progressively increasing histamine concentration, from elbow to wrist on the left arm and from wrist to elbow on the right. Histamine wheal assessments were performed with the following methods at 5, 10, 15 and 20 min from challenge: planimetry for wheal area determination, A-scanning for skin thickness evaluation and echographic image analysis for assessing skin edema corresponding to the hypoechogenic area in the dermis. Wheal extension, skin thickness and edema of the dermis increase in time according to the histamine concentration. However, in response to the same concentration, regional variations consisting in greater wheal extension and dermis hypoechogenic areas were observed on proximal than on distal sites. Conversely, statistically significant differences were found between tests carried out on the right arm compared to those on the left regarding skin thickness. These variations have to be considered when interpreting data derived from pharmacological studies on the inhibition of histamine-induced reactions.

Adult↗

Assessment of topical corticosteroid activity on experimentally induced contact dermatitis: echographic evaluation with binary transformation and image analysis.

A new echographic evaluation method employing a B scanner and a dedicated software (Dermavision 2D, Cortex Technology, Hadsund, Denmark) was used in assessing the potency of three different corticosteroids. Experimental lesions were induced by patch tests with nickel sulfate 5% in petrolatum in 10 sensitized subjects and treated with two medications of different steroids (clobetasol propionate, fluocinolone acetonide or clobetasone butyrate) performed 16 and 40 h after the application of the nickel patch tests. Clinical and echographic evaluations were carried out at the beginning of the experiment and 64 h after the induction of the reactions. After obtaining echographic images, these were processed by software, enabling the selection of amplitudes of interest, the highlighting of parts of images and their assessment by a value corresponding to the number of pixels (picture elements). For evaluations a low reflecting band was chosen, marking edema and inflammatory infiltration. At positive patch test sites we observed a progressive increase in the number of low reflecting pixels, in accordance with the intensity of the reaction. Therapeutic response was assessed as the difference between values of treated and untreated test sites. The rank order of the efficacy of test substances as determined echographically was identical to the rank order generally accepted for these steroids. This evaluation method of topical corticosteroid activity could be usefully employed besides traditional evaluation methods.

Administration, Topical↗