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Biomedical subjects

A Simone

Publications and source records attributed to A Simone.

15 recordsLinked to original sources

Depression is the main determinant of quality of life in multiple sclerosis: a classification-regression (CART) study.

PURPOSE: Quality of life in multiple sclerosis has been often measured through the SF-36 questionnaire. In this study, validation of the SF-36 summary scores, its 'physical' component, and its 'mental' component was attempted by exploring the joint predictive power of disability (EDSS score), of anxiety and depression (HADS-A and -D scores, respectively), and of disease duration, progression type, age, gender and marital status. METHOD: The sample consisted of 75 patients suffering from multiple sclerosis admitted to an inpatient rehabilitation unit. The interplay between potential predictors was assessed through a particular regression model (classification and regression tree, CART). Two main advantages of this technique are its robustness with respect to distributional assumptions (rarely met by scores coming in from questionnaires) and its sensitivity to high-order interactions, between independent variables, difficult to detect through conventional multiple regression. RESULTS: Predictive variables for physical component of the SF-36 were EDSS and HADS-D (36.8% variance explanation). The only predictive variable for mental component of SF-36 was HADS-D (39.1% variance explanation). CONCLUSION: Results confirm previous findings showing that in patients with multiple sclerosis quality of life is heavily determined by person's mood, whatever his/her neurological or functional severity. The usefulness and validity of the SF-36 as an index representative of quality of life is debatable, as long as depression explains much of its variance. Further refinement of quality of life definition and measurement is worth further psychometric and statistical research.

Adult↗

Single sperm cell isolation by laser microdissection.

In 1996, Van Oorschot and Jones firstly reported in scientific correspondence that short tandem repeat (STR) profiles could be obtained from cells left on different objects. Since then, forensic scientists have focused their efforts in isolating single cells as it can be extremely helpful in solving case works where sexual violence was concerned. Laser microdissection is a micromanipulation procedure allowing to cut off precisely the cells of interest from tissue samples or smears by a laser beam fitted with an optical microscope. We have harvested single sperm cells by laser microdissection using a Leica AS LMD (Leica Microsystems, Germany); laser setting, pulse laser intensity and laser alignment as well as recovery of the specimen have been properly fitted to the samples we were dealing with. Different tissue preservation, fixation, histological staining (Papanicolau, Nuclear Fast Red-Picroindigocarmine) methods and number of harvested cells for each sample have been evaluated as well. Finally, the genotype of sperm cells has been determined by STR typing, evaluating the sensibility of this forensic technique according to instrumental and biological above-mentioned variables.

DNA↗

Laser microdissection and DNA typing of cells from single hair follicles.

Isolation and identification of single cells from tissue samples or smears assume a great relevance in pathological and forensic applications; in this latter field, the possibility to identify a specific genetic profile can be obtained by short tandem repeat (STR) typing, allowing to achieve a scientific proof important in law courts. It is well known that DNA extraction may be performed from several tissue fragments, blood traces, spermatozoa as well as telogen hair. However, in the last case, few follicle cells are coupled to a great amount of keratin reducing the efficiency of DNA amplification. Recently, the introduction of laser microdissection technique has greatly improved the capability to select single cells without any cross-contamination. In the present report, we have performed a laser microdissection using a Leica AS LMD (Leica Microsystems, Germany), utilized on cutting the telogen hair in order to exclusively collect the lower part of the follicle and reduce keratin contamination. In this way we can accurately extract an adequate amount of DNA, successfully typed by STR profile.

DNA↗

Co-expression of interleukin-6 (IL-6) and interleukin-6 receptor (IL-6R) in thyroid nodules is associated with co-expression of CD30 ligand/CD30 receptor.

Data on the expression of interleukin 6 (IL-6)/interleukin 6 receptor (IL-6R) in thyroid nodules is scarce. Based on our recent data of CD30 ligand (CD30L)/CD30 receptor (CD30) in these nodules and on the knowledge that this signal stimulates IL-6 production in non-thyroid neoplasms, we wanted to evaluate the immunocytochemical expression of these 2 ligand/receptor systems in a large archival series of paraffin-embedded specimens. These specimens included 6 normal thyroids and 130 thyroid nodules. Co-expression of IL-6 and IL-6R in the epithelial (follicular) cells was observed solely in CD30L/CD30 positive nodules: 5/15 (33%) oncocytic adenomas; 6/30 (20%) follicular adenomas which belonged to 2 variants (4/4 microfollicular toxic and 2/2 hyalinizing trabecular); 9/30 (30%) papillary thyroid cancers (PTC), all belonging to the conventional variant. In PTC the proportion of tumor epithelial cells that were IL6 positive was inversely correlated with the pTNM staging (r=-0.549, p=0.01). All 15 follicular cancers (FTC), all 6 anaplastic cancers (ATC) were IL-6/lL-6R negative; 14/15 FTC and 5/6 ATC were CD30L/CD30 negative. In another oncocytic adenoma, another 4 conventional PTC and another 7 non-conventional PTC CD30L/CD30 expression was associated to expression of IL-6 only. IL-6 staining associated to absent expression of CD30L and CD30 was observed in 7 follicular adenomas (all belonging to variants different from toxic and hyalinizing trabecular), 2 oncocytic adenomas, 5 of the 30 colloid nodules and 2 normal thyroids. Of the 6 tumors arising from the parafollicular C cells (medullary thyroid cancer, MTC), all 3 that had metastasized were CD30L/CD30/IL-6 positive and IL-6R negative; only IL-6 expression was lost in both the local and distant metastases. This finding matched the loss of IL-6 expression in one PTC metastasis. All 3 non-metastasized MTC were IL-6/IL-6R negative, and 1/3 was CD30L positive/CD30 negative. We conclude that only in a subset of both benign and malignant thyroid nodules the IL-6/IL-6R signal could be induced by the CD30L/CD30. IL-6 expression is related with aggressiveness in both PTC and MTC. In the normal thyroid tissue, colloid nodules, and another subset of benign and malignant thyroid nodules, IL-6 expression is under control of signals other than CD30L/CD30.

Adenocarcinoma, Follicular↗

Immunohistochemical evidence of lactoferrin in hepatic biopsies of patients with viral or cryptogenetic chronic liver disease.

Lactoferrin (Lf) expression has been immunohistochemically investigated in 117 formalin-fixed paraffin-embedded liver bioptic samples obtained from an equal number of patients affected by chronic hepatitis (HCV = 76; HBV = 17; HBV + HDV = 14; cryptogenetic = 10); in addition, 10 autoptic specimens of normal liver were studied as control. The Lf immunoreactivity was evaluated by an intensity-distribution (ID) score. The Lf immunoexpression was observed in 88 out of 117 (75%) cases of chronic hepatitis; interestingly, all liver specimens from HBV hepatitis showed a constant Lf reactivity with the highest ID-score, whereas the evidence of Lf was encountered in 54/76 (71.1%) HCV as well as in 11/14 (78.6%) HDV chronic hepatitis, thus documenting a variable degree of Lf immunostaining in relation to different viruses. Moreover, in 6/10 (60%) cases of cryptogenetic hepatitis Lf immunoexpression was documented, whereas all normal liver controls were unreactive. In HCV specimens, the Lf nuclear immunoreactivity appeared to increase with the progression of the disease, with a greater expression in genotype 1. In contrast, no relationship among Lf ID-scores and different stages or grades of HBV, HDV or cryptogenetic hepatitis was encountered. This fact may suggest a role for Lf as an unspecific defensive agent in chronic inflammatory liver diseases, similarly to that elsewhere reported in other inflammatory tissue injuries.

Adult↗

Expression of CD30 ligand and CD30 receptor in normal thyroid and benign and malignant thyroid nodules.

Because the CD30 ligand (CD30L)/CD30 receptor (CD30) system is expressed in certain malignancies, but has not been studied in thyroid nodules, we investigated its immunohistochemical expression in 6 normal thyroids (NT) and 131 thyroid nodules: 28 colloid nodules (CN), 45 adenomas (15 oncocytic [OA], 30 follicular [FA]) and 58 carcinomas (15 follicular [FTC], 1 insular [ITC], 6 anaplastic [ATC], 30 papillary [PTC], and 6 medullary [MTC]). NT and CN expressed neither CD30L nor CD30 (CD30L-/CD30-). Forty percent of OA and 20% of FA showed epithelial coexpression of CD30L and CD30, and interstitial expression of CD30L, which was also observed in the surrounding normal tissue. Within malignancies, epithelial coexpression of CD30L and CD30 was observed in 7% of FTC, 33% of ATC, 67% of PTC, and 67% of MTC. Only PTC and MTC showed epithelial expression of CD30L in the perinodular tissue with similar frequency (80% PTC, 75% MTC). PTC and MTC had the highest proportion of CD30L+ or CD30+ cells, and together with OA, a thus far unreported nuclear location of CD30L. In PTC, the proportion of CD30L+ cells and the prevalence of nuclear location of CD30L correlated inversely and directly, respectively, with aggressiveness. In conclusion, CD30L/CD30 signaling is activated only past the colloid nodule stage, most frequently in an autocrine fashion.

CD30 Ligand↗

Expression of the hepatocyte growth factor and c-met in normal thyroid, non-neoplastic, and neoplastic nodules.

We have examined the coexpression of hepatocyte growth factor (HGF) and its receptor (HGF-R or c-met) in an archival series of 63 paraffin-embedded thyroid specimens plus one lymph node metastasis. By immunocytochemistry, we found undetectable expression of both the ligand and the receptor in 10 normal thyroids and 9 nonpapillary malignant nodules [5 follicular carcinomas, 1 poorly differentiated (insular) carcinoma, 3 undifferentiated (anaplastic) carcinomas]. Of 10 non-neoplastic nodules (colloid nodules) and 17 benign neoplastic nodules, 3 of 10 colloid nodules, 2 of 10 follicular adenomas, and 2 of 7 oncocytic adenomas showed a weak but distinct staining (1+ score in a scale from 0 to 4+) of both HGF and c-met in a modest proportion of cells (1% to 3%). In these 7 cases, expression of HGF was always stromal and expression of c-met limited to the membrane of the follicular cells. Of 3 malignant nodules derived from aberrant growth of the parafollicular C cells (medullary thyroid cancer or MTC), 2 were positive (6% of cells). In these 2 cases, the expression of HGF (3+) was not stromal, but in both the membrane and cytoplasm of the parafollicular cells, while that of c-met (3+) was restricted to the membrane. In contrast to all of the above, of 14 papillary carcinomas (PTC) encompassing 5 histological variants (conventional; follicular; oncocytic; with foci of solid growth; diffuse sclerosing) plus 1 neck lymph node metastasis of 1 conventional PTC, 12 (86%) expressed HGF, and 13 (93%) expressed c-met. With the exception of 2 negative cases, HGF was detected in 15% to 46% of the cells. The highest percentage (46%) pertained to conventional PTC cases with abundant peritumoral lymphocyte infiltration, indicating that some lymphokine(s) may recruit PTC cells for HGF expression in a paracrine fashion. With the exception of one negative case, c-met was found in 43% to 80% of the cells, both at levels from intense (3+) to very intense (4+). The immunostaining for HGF was stromal in 25%, membranous in 8%, cytoplasmic in 8%, and both membranous and cytoplasmic in 59% of the PTC-positive cases. The immunostaining for c-met was membranous in 43% and both membranous and cytoplasmic in 57% of the PTC-positive cases. In the lymph node metastasis and in the diffuse sclerosing variant of PTC (the most aggressive variant), the coexpression of HGF/c-met was lost, in that only c-met was expressed on membranes in both cases. We conclude that the HGF/c-met system is activated (by overexpression of both components) in the vast majority of PTC. In most PTC the interaction of HGF and its receptor (c-met) is autocrine, not paracrine.

Carcinoma↗

Cariostatic effects of a xylitol/NaF dentifrice in vivo.

Xylitol has been shown to reduce plaque acids, but its topical cariostatic effect has been equivocal. The purpose of the studies reported here was to optimise the xylitol/NaF combination in dentifrices for an improved anticaries activity. In the first study, the combination of 10 per cent xylitol with 1100 ppm F (NaF), 1100 ppm F (NaF), and placebo dentifrices were tested in a rat caries model to assess the cariostatic effect. The combination was significantly more effective than fluoride by itself (P = 0.05). The xylitol/NaF combination provided significantly more remineralisation of dentine than fluoride by itself. Collectively, results of these investigations confirm the improved anticaries effectiveness of the xylitol/NaF combination in a variety of animal and intra-oral models. A three-year clinical study confirmed these findings.

Acids↗

Reduction in accumulation of plaque, stain, and calculus in dogs by dietary means.

We conducted 215 evaluations for plaque, stain, and calculus in 120 dogs at two research sites. Dogs were balanced in groups of five according to baseline plaque index scores; groups were randomly assigned to treatment or control dietary regimens. Dental cleanings were done on Day 0. Dogs in the treatment group were fed a food formulated to reduce accumulation of plaque, stain, and calculus. Control group dogs were fed a commercially available dry dog food. No other foods, treats, or snacks were given to either group. We graded 22 teeth for plaque accumulation on Day 7 and for stain and calculus accumulation on Day 21. Six trials were conducted and the results reported as a combined mean for all treatment and control groups. Dogs fed the treatment food had significantly less plaque, stain, and calculus accumulation (p = 0.001) than dogs fed the control food. Plaque, stain, and calculus accumulation can be reduced by dietary means.

Analysis of Variance↗

Assessment of oral malodor in dogs.

This paper describes a methodology for measuring and assessing changes in canine oral malodor with the intent that it can be used to evaluate products designed to make pets' breath more acceptable to their owners. Ten judges, able to discriminate and rank malodorous chemical compounds, were trained as a formal sensory panel by an expert in sensory evaluation techniques. The panel was assembled to determine changes in oral malodor resulting from dietary manipulation. A dry experimental food served as the test food, and a commercial dry dog food as the reference food. Dogs fed the experimental food developed significantly less oral malodor (p < 0.01) than when they were fed the control food.

Animal Feed↗

Controlled trial of enalapril and hydrochlorothiazide in 200 hypertensive patients.

In a multicenter, multinational study, 200 patients with essential hypertension were treated with a fixed dose of Enalapril (E) 20 mg/day after a 2- to 4-week placebo period. All had diastolic blood pressure (DBP) 100 to 120 mm Hg at the end of the placebo period. They were then given E for 6 weeks. If DBP after this was greater than 90 mm Hg they were randomized double-blind to added therapy with hydrochlorothiazide (H) either 25 mg/day (E + H 25) or 12.5 mg/day (E + H 12.5) or placebo (E + P) for 4 weeks. Blood pressure was measured approximately 24 hours after taking the medication. In the whole group, BP fell from 171/107 to 156/97 mm Hg during monotherapy with E (P less than 0.001). Sixty-six patients reached DBP less than or equal to 90 mm Hg on E alone. Of the remainder, 42 were randomized to E + P. In these, BP fell by 5.9/3.4 mm Hg (P less than 0.05). Forty-two patients received E + H 12.5 and BP fell by 9.0/6.9 mm Hg (P less than 0.001). Forty-one patients received E + H 25 and BP fell by 5.6/6.3 mm Hg (P less than 0.05/0.01). The proportion of patients who reached DBP less than or equal to 90 mm Hg was 26% in the E + P group, 48% in the E + H 12.5 group (P less than 0.05 compared to E + P group), and 38% in the E + H 25 group. There were no other significant differences between the E + H 12.5 and E + H 25 groups except that S-potassium fell significantly (-0.2 mmol/L) in E + H 25. Both regimens were remarkably well tolerated. It can be concluded that H 12.5 mg/day potentiates the effect of Enalapril 25 mg/day at least as well as H 25 mg/day and better than placebo.

Adult↗

Role of brain lactic acidosis in hypoxic depression of respiration.

The role of lactic acidosis of progressive brain hypoxia (PBH) as both a central chemoreceptor stimulant and a general respiratory depressant was assessed by preventing lactate formation both locally and globally with dichloroacetate (DCA). Phrenic nerve activity (PN) and ventral medullary pH (Vm pH) responses to PBH (1% CO-40% O2-balance N2) were determined in anesthetized, paralyzed, peripherally chemodenervated, vagotomized cats while fraction of end-tidal CO2 (FETCO2) and mean arterial blood pressure (MABP) were maintained constant. Topical DCA near the central chemoreceptors prevented the progressive Vm acidosis of PBH and was associated with a slightly greater depression of PN for any given level of brain hypoxia [75 +/- 12% base-line mock cerebrospinal fluid compared with 63 +/- 11% base-line topical DCA at O2 content of arterial blood (CaO2) of 7.5 ml O2/dl]. Systemic DCA also prevented the progressive acidosis of PBH and significantly altered the profile of depression with PBH. Before DCA, PBH produced a progressive reduction in PN after reducing CaO2 by 20%. After DCA, PN was not significantly depressed until CaO2 was reduced to very low levels, whereupon there was a sharp decline in PN. Before DCA, reducing CaO2 to 6 ml O2/dl reduced PN by 41 +/- 16%, whereas after DCA there was no significant reduction in PN (4 +/- 5%). We conclude that 1) lactic acidosis near the central chemosensitive regions does produce a small stimulation of respiration during PBH but that 2) the overwhelming response to central lactic acidosis of PBH is respiratory depression.

Acidosis, Lactic↗

Immunolocalization of lactoferrin in surgically resected pigmented skin lesions.

Lactoferrin (Lf) expression was determined immunohistochemically in 57 formalin-fixed paraffin-embedded bioptic samples obtained from an equal number of patients treated by surgery to remove pigmented skin lesions (nevi = 23; melanoma = 12; vulgaris and seborrhoeic warts = 12; basal cell carcinoma = 10); in addition, 10 specimens of normal skin were studied as control. On 3 mm thick sections, depigmentation and antigen retrieval procedures were performed. The Lf immunoreactivity was revealed by a rabbit anti-human Lf. Quantification of Lf immunoreactivity was performed using an intensity-distribution (ID) score. Melanocytic cells, regardless of their benign or malignant nature, were consistently stained, with no significant differences in the Lf ID-score between melanomas or nevi. A different intensity of Lf immunoreactivity was encountered in superficial portions of warts, exclusively inside squamous epithelial cells arranged in sheets or whorls of keratin. On the contrary, basal cell carcinomas were always unstained, while a slight Lf positivity was found in focal keratinized areas present in two tumours showing baso-squamous differentiation. The Lf immunoreactivity was localized in the cytoplasm and only occasionally in the nucleus. The biological meaning of Lf in these cases of human skin specimens remains unexplained, although it cannot be ruled out that Lf might be involved in the defense system against tumours, or alternatively, may be used by cells requiring iron availability for their turnover. Moreover, the immunohistochemical expression of Lf in melanocytic lesions might be also related to a Lf-melanin interaction. Finally, the involvement of Lf in skin squamous non-neoplastic elements could be related to its role as one of the molecules modulating an unspecific inflammatory or anti-oxidant response.

Adult↗

Free to total prostatic specific antigen ratio as a new diagnostic tool in prostatic carcinoma.

One hundred seventy-one patients with clinical suspicion of prostate cancer were initially selected and underwent total and free PSA determination, digital rectal examination and transrectal ultrasonography. Sixty-five had total PSA values between 4 to 20 ng/ml. In these patients in addition to the free to total PSA ratio, the sensitivity, specificity, positive predictive value, true and false negative predictive value were evaluated, comparing these findings with histopathological characterization. Receiver Operating Characteristic Analysis was also performed. No statistically significant differences were evidenced between benign and neoplastic prostates comparing total PSA values, while significant differences were found by comparing both free PSA and the free to total PSA ratio (p < 0.01). Our experience demonstrates that using a 0.20 free to total PSA ratio cut-off, it is possible avoid 44.4% of following clinical tests, and biopsies could be saved in almost 40% of patients with a considerable cost-benefit ratio.

Aged↗