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S Squatrito

Publications and source records attributed to S Squatrito.

At least 19 recordsLinked to original sources

Insulin aspart improves meal time glycaemic control in patients with Type 2 diabetes: a randomized, stratified, double-blind and cross-over trial.

AIMS: This randomized, multi-centre, double-blind, stratified, two period, cross-over trial was undertaken to assess the pharmacokinetics and pharmacodynamics of insulin aspart injected immediately before compared with regular human insulin injected 30 min before a Mediterranean-style meal in 37 (23 M, 14 F) patients with Type 2 diabetes. METHODS: Insulin aspart or regular human insulin was given subcutaneously (0.15 U/kg) in random sequence, using a double-dummy technique (at one visit: human regular insulin at t=-30 min and placebo at t=0; at the other visit: placebo at t=-30 min and aspart insulin at t=0). Serum glucose and insulin concentrations (15 points) were measured after each meal for 240 min. RESULTS: Post-prandial glycaemic excursions were 20% lower with insulin aspart (IAsp) compared with regular human insulin (HI) treatment [ratio (Iasp/HI)=0.80, CI=(0.66-0.98), P=0.034]. The maximum serum glucose (SG) concentration was similar for the two treatments (P=NS). The (median) time to maximum SG was 25 min shorter for IAsp compared with HI (P=0.048). Maximum serum insulin concentration was higher after IAsp compared with HI (P=0.023) as well as the area under the 4-h serum insulin curve (P=0.006). Furthermore, the time to maximum serum insulin concentration was 27 min shorter after IAsp (P=0.039), even though IAsp was injected 30 min after HI. No adverse events occurred during the trial. CONCLUSIONS: In patients with Type 2 diabetes a more favourable insulin profile and a better glycaemic control were found with IAsp injected immediately before compared with HI injected 30 min before a Mediterranean-style meal.

Aged↗

Validation of the Italian version of the WHO-Well-Being Questionnaire (WHO-WBQ) and the WHO-Diabetes Treatment Satisfaction Questionnaire (WHO-DTSQ).

AIM: To validate the Italian version of the World Health Organization (WHO)-Well-Being Questionnaire (WBQ) and the WHO-Diabetes Treatment Satisfaction Questionnaire (DTSQ) in Type 1 and Type 2 diabetic patients. METHODS: The cultural adaptation of the questionnaires was performed by using standard forward/backward techniques. Internal consistency reliability was estimated by Cronbach's alpha coefficient. Construct validity was evaluated using the Short Form-36 (SF-36) Health Status Questionnaire. Finally, the discriminative properties of the questionnaires were evaluated relative to the patients' characteristics. The questionnaires were administered to a random sample of patients identified in twelve outpatient diabetes clinics. RESULTS: Overall, 412 subjects were recruited, of whom 96 (23%) with Type 1 diabetes. Item-scale correlations were >0.40 for all the items. Cronbach's alpha coefficient was 0.86 for the WHO-DTSQ and ranged between 0.79 and 0.91 for the WHO-WBQ. High correlations were found between WHO-WBQ scales and the mental dimensions of the Short Form-36 (SF-36) questionnaire, but not between WHO-DTSQ and SF-36 scores. Women, obese subjects, those with longer diabetes duration and multiple complications showed a worse quality of life in all of the four areas of the WHO-WBQ. In Type 2 diabetic subjects, SF-36 scores, but not WHO-WBQ scores, were able to discriminate the population according to the treatment modalities. Lower levels of treatment satisfaction were related to female gender, longer diabetes duration, insulin treatment, presence of diabetes complications and HbA1c levels >7.0%. The flexibility of the treatement was perceived as a major problem even among patients treated with oral agents. CONCLUSIONS: The WHO-DTSQ can be considered as a valuable instrument to be used internationally for the description of diabetes treatment satisfaction. The WHO-WBQ also shows adequate psychometric properties, but additional data are needed to clarify whether it is more sensitive than SF-36, the most widely used generic instrument.

Adult↗

Metastasis to the thyroid gland: a case report and review of the literature.

Metastatic cancer to the thyroid is uncommon. Although the thyroid is richly supplied with blood, there are a few reports of metastatic cancer spreading to this gland. The overall incidence in autopsy series has been quite varied, with rates from 1.2 to 24% of malignant tumors. Most of this metastases are not detected in clinical practice. The majority of these patients had widespread metastases and, as a result, had very short survival times. Although detection of metastases to the thyroid gland often indicates poor prognosis, aggressive surgical and medical treatment may be effective, especially for renal carcinoma. In this report, we present a case of renal carcinoma with thyroid metastases and a review of the literature.

Aged↗

Diabetic mastopathy: a case report.

Diabetic mastopathy, although reported since 1984, is a poorly recognized diabetes complication. It more frequently affects pre-menopausal women with Type 1 diabetes mellitus and microvascular complications. The pathogenesis of this condition is believed to involve mammary tissue autoimmune reaction to the accumulation of abnormal matrix proteins, caused by hyperglycemia. The lesion often simulates breast cancer; its recognition, therefore, is important to avoid unnecessary diagnostic procedures and surgical treatments. We now report a case of diabetic mastopathy which clinically simulated breast cancer in a young pre-menopausal diabetic woman who, after sonography and mammography, was suggested surgery under suspicion of breast cancer. Histopathological examination by core-biopsy ruled out malignancy.

Adult↗

Alternative site blood glucose testing: a multicenter study.

The aim of this study was to compare glucose measurements between fingertip and forearm using the blood glucose (BG) monitoring system One Touch Ultra (LifeScan), an electrochemical sensor that requires only a very small drop of blood (1 microL). Patients with type 1 or type 2 diabetes were identified in five outpatient diabetes clinics. Participants were requested to use the One Touch Ultra at home for 1 week for the measurement of BG levels from both sites. Patients filled in a questionnaire about their experience with testing blood samples from fingertip and forearm. The agreement between the measurements from the two sites was assessed using linear regression analysis, mean absolute relative error (MARE), the Bland-Altman method, and Error Grid Analysis (EGA). Overall, 112 patients were recruited, of whom 58% had type 1 diabetes. Linear regression analysis showed an intercept of 17.7, statistically different from 0 (p<0.0001). The slope was 0.956, and the Pearson correlation coefficient was 0.95. A MARE of 12.1% (SD=11.8%) was obtained, with a greater deviation of the forearm values from the fingertip ones in the hypoglycemic range (MARE=22.3%; SD=21.7%). The Bland-Altman bias plot showed a mean bias of 10.2 mg/dL (SD=23.1), with no correlation between mean difference and average BG levels (r=0.02). The EGA showed that 89.2% of the values fell in zone A, 10.4% in zone B, and 0.4% in zone C. The vast majority of patients (71%) declared that the collection of blood from the forearm caused no pain or less pain than the traditional site. Only 17% of the patients declared that it was impossible to obtain any blood from the forearm, while 63% reported with satisfaction that the quantity requested was small. At the end of the study period, 32% of the participants indicated the forearm as the preferred test site. Alternative site testing on the arm, with a BG meter that requires only a very small drop of blood, is feasible and reliable under routine clinical conditions. When testing with the express purpose of detecting hypoglycemia, the finger still remains the recommended test site.

Adolescent↗

A ten-year (1989-1998) perspective study of the incidence of Type 1 diabetes in the district of Catania (Sicily) in a 0-14 year age group.

The aim of this report was to evaluate the incidence of Type 1 diabetes mellitus (T1DM) in the district of Catania (eastern Sicily) in children under 15 yr of age over a ten-yr period (01/01/1989 - 31/12/1998) in relation to age, sex, monthly-seasonal variability, calendar yr and spatial clustering. The estimated completeness of our register was 99.2%. The overall incidence rate was 12.38 per 100,000 during the period of the study. Twenty-four percent of cases were 0-4 yr at diagnosis, 42% were 5-9 yr and 34% were 10-14 yr. More males (no. 148) than females (no. 125) were newly diagnosed with a male/female ratio similar to the base population ratio in the range 0-14 yr and within age groups. The study revealed a non-random spatial distribution of T1DM incidence in children not accounted for by known demographic factors. A significant seasonal pattern and temporal trend of incidence were also detected.

Adolescent↗

Similarities and differences in the phenotype of members of an Italian family with hereditary non-autoimmune hyperthyroidism associated with an activating TSH receptor germline mutation.

Constitutively activating germline mutations of the TSH receptor (TSH-R) are considered the cause of hereditary non-autoimmune hyperthyroidism. In this study, 10 members (8 affected and 2 unaffected) of an Italian family with hereditary non-autoimmune hyperthyroidism were investigated for the presence of mutations in the TSH-R gene. The clinical features of the disease were also analyzed. PCR-amplified fragments of the TSH-R gene were obtained from genomic DNA extracted from peripheral blood leukocytes of each family member and analyzed by direct nucleotide sequencing and restriction analysis. An identical germline TSH-R mutation was detected in all the patients with hyperthyroidism but in none of the unaffected family members. The mutation was heterozygotic and determined the substitution of valine for methionine (codon 463; ATG-->GTG) in the second transmembrane domain of the TSH-R. When expressed in chinese hamster ovary (CHO) cells, the Val463 mutant TSH-R induced constitutive activation of the TSH receptor. Analysis of the clinical features of our family and those of other families with hereditary non-autoimmune hyperthyroidism, including one with the same Val463 mutation, revealed wide variability in the phenotypical expression of the disease. Our findings indicate that an activating germline mutation in the TSH-R gene plays a key role in hereditary non-autoimmune hyperthyroidism although the onset of clinical manifestations and the evolution of the disease seem to depend heavily on other factors, thus far unidentified. The absence of a clear correlation between mutant genotypes and phenotypic expression of the disease currently limits the prognostic value of genetic testing in families with hereditary non-autoimmune hyperthyroidism.

Adult↗

Visual motion responses of neurons in the caudal area pe of macaque monkeys.

Area PE of macaques has traditionally been considered a somatosensory association cortex. Recent studies, however, suggest that neurons of this and neighboring areas are involved in the visual control of movement, especially arm movement. We investigated the neuronal sensitivity to local visual stimuli of this region by recording neuronal activity in two behaving macaque monkeys trained in a simple visual fixation task. Recordings were performed from the dorsal surface of the caudal pole of the superior parietal lobule (SPL). Classical receptive fields (RFs) were mapped by using conventional static or moving luminous figures. We found that many neurons in this area were selectively activated by moving visual stimuli. Cell responses were tuned to the movement direction. RFs were usually large; their mean surface covered some 30 x 30 degrees of the visual field. The fovea was often included into RF, in many cases it was along a RF side. The center of RFs was mainly located in the contralateral hemifield, although RFs having the center ipsilaterally sited were also found. No evident retinotopy was found. Visual neurons were especially concentrated in a region of the SPL likely corresponding to area PEc. These results suggest that the caudal part of area PE contains neuronal populations specifically signaling local visual motion, possibly encoding the direction of moving objects. These signals might well be suited for sensorimotor integration mechanisms aimed at motor acts.

Animals↗

Usefulness of recombinant human thyrotropin in the radiometabolic treatment of selected patients with thyroid cancer.

Treatment of persistent/recurrent differentiated thyroid cancer is based on surgery, when feasible, and malignant tissue ablation by 131I administration. This procedure requires levothyroxine withdrawal to obtain high levels of endogenous thyrotropin (TSH) to stimulate radioactive iodine uptake by the malignant tissue. Levothyroxine withdrawal may cause severe adverse effects and complications in patients with concomitant illness or advanced metastatic disease. The recent availability of recombinant human thyrotropin (rhTSH) allows diagnostic whole-body scan (WBS) and thyroglobulin testing without levothyroxine withdrawal. We describe six patients with metastatic differentiated thyroid cancer (DTC) and concomitant illness in whom the use of rhTSH was effective in preventing the complications that patients had previously experienced during hypothyroidism consequent to levothyroxine withdrawal. Our results indicate that rhTSH can be particularly advantageous to avoid signs and symptoms of hypothyroidism and complications because of associated diseases in view of 131I treatment of DTC metastases in selected cases in which levothyroxine withdrawal may be dangerous. Its efficacy to treat advanced metastatic disease should be further investigated.

Adult↗

Eye-hand coordination during reaching. I. Anatomical relationships between parietal and frontal cortex.

The anatomical and physiological substrata of eye-hand coordination during reaching were studied through combined anatomical and physiological techniques. The association connections of parietal areas V6A and PEc, and those of dorso-rostral (F7) and dorso-caudal (F2) premotor cortex were studied in monkeys, after physiological characterization of the parietal regions where retrograde tracers were injected. The results show that parieto-occipital area V6A is reciprocally connected with F7, and receives a smaller projection from F2. Local parietal projections to V6A arise from areas MIP and, to a lesser extent, 7m, PEa and PEC: On the contrary, parietal area PEc is strongly and reciprocally connected with the part of F2 located close to the pre-central dimple (pre-CD). Local parietal projections to PEc come from a distributed network, including PEa, MIP, PEci and, to a lesser extent, 7m, V6A, 7a and MST. Premotor area F7 receives parietal projections mainly from 7m and V6A, and local frontal projections mainly from F2. On the contrary, premotor area F2 in the pre-CD zone receives parietal inputs from PEc and, to a lesser extent, PEci, while in the peri-arcuate zone F2 receives parietal projections from PEa and MIP. Local frontal projections to F2 pre-CD mostly stem from F4, and, to a lesser extent, from F7 and F3, and CMAd; those addressed to peri-arcuate zone of F2 arise mainly from F5 and, to a lesser extent, from F7, F4, dorsal (CMAd) and ventral (CMAv) cingulate motor areas, pre-supplementary (F6) and supplementary (F3) motor areas. The distribution of association cells in both frontal and parietal cortex was characterized through a spectral analysis that revealed an arrangement of these cells in the form of bands, composed of cell clusters, or 'columns'. The reciprocal connections linking parietal and frontal cortex might explain the presence of visually related and eye-position signals in premotor cortex, as well as the influence of information about arm position and movement direction in V6A and PEC: The association connections identified in this study might carry sensory as well motor information that presumably provides a basis for a re-entrant signaling. This might be necessary to match retinal-, eye- and hand-related information underlying eye-hand coordination during reaching.

Animals↗

Eye-hand coordination during reaching. II. An analysis of the relationships between visuomanual signals in parietal cortex and parieto-frontal association projections.

The relationships between the distribution of visuomanual signals in parietal cortex and that of parieto-frontal projections are the subject of the present study. Single cell recording was performed in areas PEc and V6A, where different anatomical tracers were also injected. The monkeys performed a variety of behavioral tasks, aimed at studying the visual and motor properties of parietal cells, as well as the potential combination of retinal-, eye- and hand-related signals on cell activity. The activity of most cells was related to the direction of movement and the active position of the hand. Many of these reach-related cells were influenced by eye position information. Fewer cells displayed relationships to saccadic eye movements. The activity of most neurons related to a combination of both hand and eye signals. Many cells were also modulated during preparation for hand movement. Light-dark differences of activity were common and interpreted as related to the sight and monitoring of hand motion and/or position in the visual field. Most cells studied were very sensitive to moving visual stimuli and also responded to optic flow stimulation. Visual receptive fields were generally large and extended to the periphery of the visual field. For most neurons, the orientation of the preferred directions computed across different epochs and tasks conditions clustered within a limited sector of space, the field of global tuning. This can be regarded as an ideal frame to combine spatially congruent eye- and hand-related information for different forms of visuomanual behavior. All these properties were common to both PEc and V6A. Retinal, eye- and hand-related activity types, as well as parieto-frontal association cells, were distributed in a periodic fashion across the tangential domain of areas PEc and V6A. These functional and anatomical distributions were characterized and compared through a spectral and coherency analysis, which revealed the existence of a selective 'match' between activity types and parieto-frontal connections. This match depended on where each individual efferent projection was addressed. The results of the present and of the companion study can be relevant for a re-interpretation of optic ataxia as the consequence of the breakdown of the combination of retinal-, eye- and hand-related directional signals within the global tuning fields of parietal neurons.

Animals↗

The IGF system in thyroid cancer: new concepts.

In recent years, the activation of the insulin-like growth factor (IGF) system in cancer has emerged as a key factor for tumour progression and resistance to apoptosis. Therefore, a variety of strategies have been developed to block the type I IGF receptor (IGF-I-R), which is thought to mediate the biological effects of both IGF-I and IGF-II. However, recent data suggest that the IGF signalling system is complex and that other receptors are involved. To unravel the complexity of the IGF system in thyroid cancer, IGF-I and IGF-II production, and the expression and function of their cognate receptors were studied. Both IGFs were found to be locally produced in thyroid cancer: IGF-I by stromal cells and IGF-II by malignant thyrocytes. Values were significantly higher in malignant tissue than in normal tissue. IGF-I-Rs were overexpressed in differentiated papillary carcinomas but not in poorly differentiated or undifferentiated tumours, whereas insulin receptors (IRs) were greatly overexpressed in all tumour hystotypes, with a trend for higher values in dedifferentiated tumours. As a consequence of IR overexpression, high amounts of IR/IGF-I-R hybrids (which bind IGF-I with high affinity) were present in all thyroid cancer histotypes. Because of recent evidence that isoform A of IR (IR-A) is a physiological receptor for IGF-II in fetal life, the relative abundance of IR-A in thyroid cancer was measured. Preliminary data indicate that overexpressed IRs mainly occur as IR-A in thyroid cancer. These data indicate that both IR/IGF-I-R hybrids and IR-A play an important role in the overactivation of the IGF system in thyroid cancer and in IGF-I mitogenic signalling in these tumours. J Clin PATHOL: Mol Pathol

Carcinoma, Papillary↗

Addition of low-dose rosiglitazone to sulphonylurea therapy improves glycaemic control in Type 2 diabetic patients.

AIMS: This study was designed to test the efficacy and safety of low-dose rosiglitazone, a potent, insulin-sensitizing thiazolidinedione, in combination with sulphonylurea in Type 2 diabetic patients. METHODS: For the intention-to-treat analysis, 574 patients (59% male, mean age 61 years) were available, randomized to receive 26 weeks of twice-daily placebo (n = 192), rosiglitazone 1 mg (n = 199) or rosiglitazone 2 mg (n = 183) in addition to existing sulphonylurea treatment with gliclazide (47.6% of patients), glibenclamide (41.8%) or glipizide (9.4%) (two patients were taking carbutamide or glimepiride). Change in haemoglobin A1c (HbA1c), fasting plasma glucose (FPG), fructosamine, insulin, C-peptide, albumin, and lipids were measured, and safety was evaluated. RESULTS: Mean baseline HbA1c was 9.2% and FPG was 11.4 mmol/l. Rosiglitazone at doses of 1 and 2 mg b.d. plus sulphonylurea produced significant decreases, compared with sulphonylurea plus placebo, in HbA1c (-0.59% and -1.03%, respectively; both P<0.0001) and FPG (1.35 mmol/l and 2.44 mmol/l, respectively; both P<0.0001). Both HDL-cholesterol and LDL-cholesterol increased and potentially beneficial decreases in non-esterified fatty acids and gamma glutamyl transpeptidase levels were seen in both rosiglitazone groups. The overall incidence of adverse experiences was similar in all three treatment groups, with no significant cardiac events, hypoglycaemia or hepatotoxicity. CONCLUSIONS: Overall, the combination of rosiglitazone and a sulphonylurea was safe, well tolerated and effective in patients with Type 2 diabetes.

Adult↗

Insulin/IGF-I hybrid receptors play a major role in IGF-I signaling in thyroid cancer.

The insulin-like growth factor-I (IGF-I) plays an important role in determining the biological behavior of a variety of malignancies. We measured IGF-I, its receptor and related receptors in thyroid cancer. IGF-I was present both in normal thyroid tissue and in thyroid cancer tissue and it was produced by stromal cells but not by thyrocytes. Values were significantly higher in malignant than in normal tissue. IGF-I receptors (IGF-I-Rs) and the homologous insulin receptors (IRs) were found overexpressed in both thyroid cancer cell lines (n = 4) and specimens (n = 17) as compared to normal values. In addition, high levels of hybrid IGF-I/insulin receptors (IR/IGF-I-Rs) were present in both thyroid cancer specimens and cell lines. IR/IGF-I-R hybrids were the most represented type of receptor in 14/17 specimens and exceeded the IGF-I-R content in all cases. Hybrid content correlated with the IR and IGF-I-R content, suggesting that in thyroid tissue hybrid formation occurs by random assembly of IR and IGF-I-R half receptors. Hybrid receptor autophosphorylation was stimulated by IGF-I with high affinity. In cells with a high IR/IGF-I-Rs content, blocking antibodies specific to these receptors substantially inhibited IGF-I induced cell growth. These data indicate that the IGF-I system is overactivated in thyroid cancer and that IR/IGF-I-R hybrid receptors play an important role in IGF-I mitogenic signaling in these tumors.

Cell Line↗

Early coding of reaching: frontal and parietal association connections of parieto-occipital cortex.

The ipsilateral association connections of the cortex of the dorsal part of the rostral bank of the parieto-occipital sulcus and of the adjoining posterior part of the superior parietal lobule were studied by using different retrograde fluorescent tracers. Fluoro-Ruby, Fast blue and Diamidino yellow were injected into visual area V6A, and dorso-caudal (PMdc, F2) and dorso-rostral (PMdr, F7) premotor cortex, respectively. The parietal area of injection had been previously characterized physiologically in behaving monkeys, through a variety of oculomotor and visuomanual tasks. Area V6A is mainly linked by reciprocal projections to parietal areas 7m, MIP (medial intraparietal) and PEa, and, to a lesser extent, to frontal areas PMdr (rostral dorsal premotor cortex, F7) and PMdc (F2). All these areas project to that part of the dorsocaudal premotor cortex that has a direct access to primary motor cortex. V6A is also connected to area F5 and, to a lesser extent, to 7a, ventral (VIP) and lateral (LIP) intraparietal areas. This pattern of association connections may explain the presence of visually-related and eye-position signals in premotor cortex, as well as the influence of information concerning arm position and movement direction on V6A neural activity. Area V6A emerges as a potential 'early' node of the distributed network underlying visually-guided reaching. In this network, reciprocal association connections probably impose, through re-entrant signalling, a recursive property to the operations leading to the composition of eye and hand motor commands.

Animals↗

Corticocortical connections between frontal periarcuate regions and visual areas of the superior temporal sulcus and the adjoining inferior parietal lobule in the macaque monkey.

In macaque monkeys, corticocortical connections between distinct parietotemporal visual areas (areas MST-FST, DP, and 7a) and frontal periarcuate areas are studied using tritiated aminoacids and WGA-HRP. While labeling within the banks of the principal sulcus, the dorsal part of the arcuate concavity, and the banks of the upper arcuate limb were present in both 7a and MST-FST injected animals; in the latter cases, additional projections were found towards frontal regions including the dorsomedial frontal cortex and the posterior bank of the arcuate ventral limb. Our results point to widespread frontal connections of the MST-FST complex, involving both prefrontal and premotor cortical regions.

Animals↗

Encoding of smooth pursuit direction and eye position by neurons of area MSTd of macaque monkey.

The spike activity of neurons was recorded from the dorsal bank of the superior temporal sulcus (area MSTd) of alert behaving macaque monkeys performing visual fixation or target tracking tasks, with the aim of studying the tuning features of these neurons with both the direction of slow eye movement and the position of gaze. One hundred thirty-two neurons were tested for several fixation points and tracking directions. Many of them (43%) tuned to the direction of pursuit, regardless of the angle of gaze. Some (18%) showed a tonic discharge modulated by the static position of the eyes without pursuit direction specificity. A substantial number of cells (22%) were characterized by a discharge rate tuned to pursuit direction but influenced also by angle of gaze. Tuning curves for eye movement direction presented an average bandwidth of 130 degrees and turned out to be continuously overlapping, suggesting a sort of vector coding of smooth pursuit direction. Gaze fields of eye position (EP) neurons were mostly ramp-like, with center of ramps shifted away from the straight ahead, implying a form of scalar coding of gaze eccentricity. The different categories of cells were intermingled and close to each other, suggesting possible reciprocal interactions within the same cortical area. These results show that EP and pursuit direction are signaled mainly by separate neuronal elements in area MSTd. Moreover, some cells can integrate both signals. Taking into account the visual responses of MSTd neurons to large, textured, moving fields, it is suggested that this area could be the site of interaction between visuo-oculomotor signals related to visual motion detection, slow eye movement direction, and EP. This signal interaction may be important for integrative functions such as analysis of external or self-induced visual motion, cortical control of pursuit eye movements, and eye/head coordination.

Animals↗