The multidimensional prognostic index (MPI) predicts long-term mortality in old type 2 diabetes mellitus patients: a 13-year follow-up study.

PURPOSE: The Multidimensional Prognostic Index (MPI) is a tool capable of holistically frame older patients in different settings and affected by different pathologies, establishing a risk of adverse events. Among them, type 2 diabetes mellitus (T2DM), a common metabolic disease in the elderly, is responsible for complications and deaths. Few previous works have focused specifically on MPI and DM, and none have followed up the patients for more than 3 years. The aim of the present study is to analyze MPI accuracy in predicting mortality in a cohort of T2DM patients followed-up for 13 years. METHODS: The enrolled subjects were evaluated with MPI, identifying three levels of risk: MPI1 (low risk, 0.0-0.33), MPI2 (moderate risk, 0.34-0.66), and MPI3 (severe risk, 0.67-1.0), and with glycated hemoglobin, and years since T2DM diagnosis. RESULTS: One hundred and seven patients met the inclusion criteria. MPI3 was excluded by further analysis since it was made up of only three patients. Overall, cognitive performances, autonomies in daily living, nutritional status, risk of pressure injuries, comorbidities, and taken drugs were better (p ≤ 0.0077) in MPI1 than MPI2; moreover, the story of T2DM was shorter (p = 0.0026). Cox model showed an overall 13-year survival of 51.9%, and survival rates were significantly smaller in MPI2 (HR: 4.71, p = 0.0007). Finally, increased age (HR: 1.15), poorer cognitive abilities (HR: 1.26), vascular (HR: 2.15), and kidney (HR: 2.17) diseases were independently associated with death. CONCLUSION: Our results prove that MPI predicts short-, mid-, and even long-term mortality in T2DM patients, whose death seems to be related to age and cognitive status, and even more to vascular and kidney diseases.

The single-point insulin sensitivity estimator (SPISE) index is a strong predictor of abnormal glucose metabolism in overweight/obese children: a long-term follow-up study.

PURPOSE: To investigate the relationship between the single-point insulin sensitivity estimator (SPISE) index, an insulin sensitivity indicator validated in adolescents and adults, and metabolic profile in overweight/obese children, and to evaluate whether basal SPISE is predictive of impaired glucose regulation (IGR) development later in life. METHODS: The SPISE index (= 600 × HDL0.185/Triglycerides0.2 × BMI1.338) was calculated in 909 overweight/obese children undergoing metabolic evaluations at University of Cagliari, Italy, and in 99 normal-weight, age-, sex-comparable children, selected as a reference group, together with other insulin-derived indicators of insulin sensitivity/resistance. 200 overweight/obese children were followed-up for 6.5 [3.5-10] years, data were used for longitudinal retrospective investigations. RESULTS: At baseline, 96/909 (11%) overweight/obese children had IGR; in this subgroup, SPISE was significantly lower than in normo-glycaemic youths (6.3 ± 1.7 vs. 7 ± 1.6, p < 0.001). The SPISE index correlated positively with the insulin sensitivity index (ISI) and the disposition index (DI), negatively with age, blood pressure, HOMA-IR, basal and 120 min blood glucose and insulin (all p values < 0.001). A correlation between SPISE, HOMA-IR and ISI was also reported in normal-weight children. At the 6.5-year follow-up, lower basal SPISE-but not ISI or HOMA-IR-was an independent predictor of IGR development (OR = 3.89(1.65-9.13), p = 0.002; AUROC: 0.82(0.72-0.92), p < 0.001). CONCLUSION: In children, low SPISE index is significantly associated with metabolic abnormalities and predicts the development of IGR in life.

Presence of diabetes-specific autoimmunity in women with gestational diabetes mellitus (GDM) predicts impaired glucose regulation at follow-up.

PURPOSE: Gestational diabetes mellitus (GDM) is the most frequent complication of pregnancy; around 10% of GDM cases may be determined by autoimmunity, and our aims were to establish the role of autoimmunity in a population of Sardinian women affected by GDM, to find predictive factors for autoimmune GDM, and to determine type 1 diabetes (T1D) auto-antibodies (Aabs) together with glucose tolerance after a mean 21.2 months of follow-up. METHODS: We consecutively recruited 143 women affected by GDM and 60 without GDM; clinical data and pregnancy outcomes were obtained by outpatient visit or phone recall. T1D auto-antibodies GADA, IA2-A, IAA, ZnT8-A were measured in the whole population at baseline, and in the Aab-positive women at follow-up. RESULTS: The overall prevalence of autoimmunity was 6.4% (13/203). No significant difference was found in the prevalence of auto-antibodies between GDM (5.6%) and control (8.3%) women, neither in antibody titres. Highest titres for GADA and ZnT8-A were observed in the control group; no phenotypic factors were predictive for autoimmune GDM. Diabetes-related autoantibodies were still present in all the GDM women at follow-up, and their presence was associated with a 2.65 (p < 0.0016) relative risk (RR) of glucose impairment. CONCLUSION: We observed a low prevalence (5.6%) of diabetes-related autoimmunity in our GDM cohort, consistent with the prevalence reported in previous studies. It was not possible to uncover features predictive of autoimmune GDM. However, given the significant risk of a persistent impaired glycemic regulation at follow-up, it is advisable to control for glucose tolerance in GDM women with diabetes-related autoimmunity.

High prevalence of diabetes-specific autoimmunity in first-degree relatives of Sardinian patients with type 1 diabetes.

BACKGROUND: The incidence of type 1 diabetes mellitus (T1DM) in Sardinia is among the highest in the world (44.8 cases/100,000 person-years). Recommendations of the Immunology of Diabetes Society advise evaluating autoantibody positivity in first-degree relatives (FDRs) of patients with T1DM, for their higher risk to develop the disease. The aim of this study was to determine the prevalence of beta-cell autoimmunity in FDRs of T1DM patients in Sardinia. METHODS: A total of 188 Sardinian families were recruited in collaboration between diabetes and pediatric units of university and district hospitals in Sardinia. The recruitment involved 188 patients with diagnosed T1DM and all their available FDRs (n = 447). Autoantibodies (Aabs) against GAD, IA2, insulin, and ZnT8 were measured in all subjects. Human leukocyte antigen (HLA) risk genotypes (HLA-DR and DQ loci) were analyzed in 43 Aabs-positive FDR. RESULTS: The prevalence of Aabs (any type of autoantibody, single or multiple) in FDR was 11.9% (53/447). Of those with autoantibodies, 62.3% (33/53) were positive to only 1 autoantibody, 22.6% (12/53) had 2 autoantibodies, 7.55% (4/53) had 3 autoantibodies, and 7.55% (4/53) had all 4 autoantibodies. Typing of HLA-DR and DQ loci showed that 89% of FDR carried moderate- to high-risk genotypes, with only 5 FDR with low-risk genotypes. CONCLUSIONS: The prevalence of T1DM autoantibodies in FDRs of T1DM patients was very high (11.9%) in the Sardinian population, higher than in other populations from the United States and Europe, and similar to that observed in Finland. Autoantibody positivity strongly associated with HLA risk. This study provides evidence of the high risk of T1DM in FDR of T1DM patients in Sardinia and warrants longitudinal follow-up to estimate the risk of progression to T1DM in high-risk populations.

The vitamin D receptor (VDR) gene rs11568820 variant is associated with type 2 diabetes and impaired insulin secretion in Italian adult subjects, and associates with increased cardio-metabolic risk in children.

BACKGROUND AND AIMS: 1α,25-dihydroxyvitamin-D3, the biologically active vitamin D, plays a central role in several metabolic pathways through the binding to the vitamin D receptor (VDR). VDR has been shown to be involved in cardiovascular diseases, cancer, autoimmunity and type 2 diabetes mellitus (T2DM). Several polymorphisms in the VDR gene have been described. Among these, the rs11568820 G-to-A nucleotide substitution was found to be functional, modulating the transcription of the VDR gene. Objective of this study was to perform an association study between rs11568820 polymorphism and T2DM in a cohort of Italian adults with T2DM and in non-diabetic controls. To add further insight into the role of VDR gene we explored whether this association begins early in life in overweight/obese children, or becomes manifest only in adulthood. METHODS AND RESULTS: As many as 1788 adults and 878 children were genotyped for the rs11568820 polymorphism. All participants underwent oral glucose tolerance tests (OGTT), with measurement of glucose and insulin levels. Indices of insulin-resistance and secretion were also calculated. The AA genotype was significantly more frequent in adults with T2DM compared to controls (7.5% vs. 4.6%, P = 0.037), and conferred a higher risk of T2DM (ORHom = 1.69C.I. = [1.13-2.53], P = 0.011). In the adult cohort, rs11568820 was also associated with reduced indices of ß-cell insulin secretion. In children, the AA genotype was associated with 2 h high-normal glucose, a marker of cardio-metabolic risk. CONCLUSIONS: Our study demonstrates for the first time that VDR gene AA carriers have higher risk of T2DM and impaired insulin secretion. In children, the association between AA homozygous and high-normal 2h glucose suggests that mild alterations associated with this genotype may appear early in life.

Anterior pituitary autoantibodies in patients with type 1 diabetes mellitus: methodological problems and clinical correlations.

BACKGROUND: Anti-pituitary antibodies (APA) were described in patients with Type 1 Diabetes (T1D) but their prevalence and relevance remain controversial. MATERIALS AND METHODS: We evaluated the APA prevalence in Sardinian sera from 100 T1D patients, 70 Type 2 Diabetes (T2D) patients and 62 healthy controls, using indirect immunofluorescence on bovine pituitary sections. To compare two different substrates, we tested using bovine sections, further T1D patient sera (n = 11, from Pisa) previously analysed for APA on monkey sections, while some T1D Sardinian patient sera (n = 22) were tested on monkey sections. According to preliminary experiments, positivity were considered ≥1:200 and ≥1:20 for bovine and monkey substrates, respectively. RESULTS AND DISCUSSION: Using bovine sections, APA were detected in 7/100 Sardinian T1D patients (at 1:200 titer) and in none of the other Sardinian sera tested. When the T1D sera from Pisa were tested on bovine and the T1D Sardinian sera were tested on monkey, none of these sera showed corresponding positivity for APA. Pituitary hormone dysfunctions were not found in the 7 APA-positive Sardinian T1D patients. The present study shows that the presence of APA at low-titer is highly related to T1D but not associated with any pituitary dysfunction while the animal species used as substrate appears crucial. CONCLUSION: Further studies are needed to ascertain whether APA detected by different animal species may have different pathological relevance in T1D and/or whether APA in the long run may predict future anterior pituitary dysfunction.

Breast MRI artefacts: evaluation and solutions in 630 consecutive patients.

AIM: To evaluate the problems that may arise in breast magnetic resonance imaging (MRI) related to the presence of artefacts and pitfalls, in order to improve its accuracy, sensitivity, and specificity. MATERIALS AND METHODS: Six hundred and thirty breast MRI examinations performed using a 1.5 T magnet were analysed retrospectively. Each type of artefact that may have affected the correct interpretation of the acquired images was considered and analysed. In particular, the presence of technical artefacts, which are related to patient-dependent factors or to the examination itself, and non-technical artefacts, which are the result of inadequate and incorrect image interpretation occurring in absence of technical issues, were examined. In every case of suspicious findings, doubtful lesions were subjected to histological characterization for appropriate therapeutic planning. In the remainder of cases, patients underwent follow-up for at least 18 months. RESULTS: Artefacts were found in 33% of all examinations, among those 48.6% were caused by movement, 33.6% were due to non-homogeneous or failed fat saturation, 8.7% to incorrect positioning of the patient, 7.2% to metallic artefacts, 1.4% to aliasing, and 0.5% were "zebra artefacts". When the artefact was identified in a sequence, the sequence was performed a second time after corrective measures. No artefacts affected diagnostic interpretation of the obtained images. CONCLUSION: The present study provides a specific and precise review of the most frequent artefacts with a discussion of possible and practical solutions. A highly qualified team is required to perform accurate diagnostic tests and to limit or remove the possibility of misinterpretation.

Cost-effectiveness of two breast biopsy procedures: surgical biopsy versus vacuum-assisted biopsy.

PURPOSE: The aim of this study was to compare the cost-effectiveness of two breast biopsy procedures: surgical biopsy and vacuum-assisted biopsy (VAB). MATERIALS AND METHODS: Between November 2008 and September 2009, 200 patients with suspicious breast lesions underwent biopsy procedures at our radiology department: 100 underwent VAB and 100 underwent surgical biopsy. 66 lesions were sampled under sonographic guidance, 109 under mammographic guidance and 25 under magnetic resonance guidance. RESULTS: All procedures were successfully completed. No significant differences in diagnostic efficacy were found between the biopsy procedures. Surgical biopsy has a higher unit cost compared with VAB. CONCLUSIONS: Our analysis emphasises the benefits of VAB compared with surgical biopsy in terms of both cost-effectiveness, and less invasiveness from a psychological and aesthetic point of view.

Value of the correct diagnostic pathway through conventional imaging (mammography and ultrasound) in evaluating breast disease.

PURPOSE: This study evaluated the role of the correct diagnostic pathway through conventional imaging in evaluating breast disease. MATERIALS AND METHODS: Six hundred patients aged between 35 and 75 years were enrolled in the study. All patients underwent detailed history and clinical examination, ultrasound (US) and mammography. US scans were repeated after mammography. All suspicious lesions were studied by cytological and histological characterisation and magnetic resonance (MR) imaging. RESULTS: The first US scan showed 147 solid lesions, 67 lesions characterised by posterior acoustic shadowing and 193 areas of heterogeneous echostructure. The second US scan, performed after mammography, confirmed 123/147 solid nodular lesions, 53/67 lesions characterised by posterior acoustic shadowing and 183/193 areas of heterogeneous echostructure; it also showed 13 nodular lesions not seen on the first scan and two cases of nodular lesions with irregular calcifications. CONCLUSIONS: Our experience suggests that US not performed in conjunction with mammography gives rise to incorrect diagnostic interpretations (either false positive or false negative results). The detection rate of the US scan performed after mammography increases from 4.16% to 5.5%.

Pathological classification of DCIS and planning of therapeutic management.

BACKGROUND: Ductal intraepitelial neoplasia (DIN) represents a spectrum of disease that may progress from usual hyperplasia to ductal carcinoma in situ (DCIS) grade 3. The aim of the study was to asses the correlation between the DIN classification and the surgical treatment including sentinel lymph node biopsy (SLNB). PATIENTS AND METHODS: In this retrospective study, 229 patients with DIN had undergone conservative or radical surgical treatment and SLNB in cases of DIN1C-DIN3. RESULTS: Breast conservative surgery was the definitive treatment in 80% of the cases. The H&E evaluation of excised sentinel nodes was negative for metastatic disease; nevertheless the immunohistochemical (IHC) evaluation revealed the presence of metastatic cells in 6 patients (3.7%). CONCLUSION: In cases of DIN lesions SLNB is not indicated. The only reason SLNB should be considered is when there is an evidence of invasive foci at definitive histology or when radical mastectomy is proposed.

ANGPTL4 gene E40K variation protects against obesity-associated dyslipidemia in participants with obesity.

OBJECTIVE: ANGPTL4 inhibits lipoprotein lipase in adipose tissue, regulating plasma triglycerides levels. In persons with obesity plasma ANGPTL4 levels have been positively correlated with body fat mass, TG levels and low HDL. A loss-of-function E40K mutation in ANGPTL4 prevents LPL inhibition, resulting in lower TGs and higher HDLc in the general population. Since obesity determines metabolic alterations and consequently is a major risk factor for cardiovascular disease, the aim was to explore if obesity-related metabolic abnormalities are modified by the ANGPTL4-E40K mutation. METHODS: ANGPTL4-E40K was screened in 1206 Italian participants, of which 863 (71.5%) with obesity. All subjects without diabetes underwent OGTT with calculation of indices of insulin-sensitivity. RESULTS: Participants with obesity carrying the E40K variant had significantly lower TG (p = 0.001) and higher HDLc levels (p = 0.024). Also in the whole population low TGs and high HDLc were confirmed in E40K carriers. In the obese subpopulation it was observed that almost all E40K carriers were within the lowest quartile of TGs (p = 1.1 × 10-9). E40K had no substantial effect of on glucose metabolism. Finally, none of the obese E40K carriers had T2D, and together with the favourable lipid profile, they resemble a metabolically healthy obese (MHO) phenotype, compared to 38% of E40E wild-type obese that had diabetes and/or dyslipidaemia (p = 0.0106). CONCLUSIONS: In participants with obesity the ANGPTL4-E40K variant protects against dyslipidemia. The phenotype of obese E40K carriers is that of a patient with obesity without metabolic alterations, similar to the phenotype described as metabolic healthy obesity.

FEM analysis of RF breast ablation: multiprobe versus cool-tip electrode.

BACKGROUND: Radio-frequency ablation (RFA) has recently received much attention as an effective minimally invasive strategy for the local treatment of tumors. The purpose of this study was to evaluate the efficacy of single-needle cool-tip RF breast ablation in terms of temperature distribution and duration of the procedure as compared to multiprobe RF breast ablation. MATERIALS AND METHODS: Two different commercially available radiofrequency ablation needle electrodes were compared. Finite-element method (FEM) models were developed to simulate the thermoablation procedures. A series of ex vivo radiofrequency thermal lesions were induced to check the response of the FEM calculations. RESULTS: Data obtained from FEM models and from ex vivo procedures showed that cool-tip RF breast ablation assures better performances than multiprobe RF breast ablation in terms of temperature distribution and duration of the procedure. Histopathological analysis of the cool-tip RF thermoablated specimens showed successful induction of coagulation necrosis in the thermoablated specimens. CONCLUSION: Data obtained from FEM models and from ex vivo procedures suggest that the proposed cool-tip RF breast ablation may kill more tumor cells in vivo with a single application than the multiprobe RF breast ablation.

Relationship between nocturnal serum thyrotropin peak and metabolic control in diabetic patients.

Circadian variations in serum TSH, especially its nocturnal rise, are often blunted in nonthyroidal illness. We analyzed TSH secretion in 15 diabetic patients (7 with type I and 8 with type II diabetes mellitus). Patients were evaluated when diabetes was poorly controlled (fasting blood glucose ranging from 13.7-19.2 mmol/L with absence of ketoacidosis) and after achieving glycemic control. Before correction of hyperglycemia, the nocturnal serum TSH peak (2230-0200 h) was abolished in 11 of 15 patients (73%); the mean (+/- SE) night TSH/morning TSH x 100 was 109.0 +/- 9.5 (range, 66.7-166.7) vs. a mean of 216.5 +/- 27.0 (range, 139.8-462.5) in normal controls. The mean morning TSH value in diabetics (1.9 +/- 0.4 mU/L) did not differ from that in normal age- and sex-matched controls. The mean TSH increase after iv administration of TRH was only slightly reduced (8.4 +/- 1.2 mU/L pretreatment vs. 10.8 +/- 1.6 mU/L posttreatment), with the TRH test blunted in 3 cases. No differences were found between type I and type II patients. Correction of hyperglycemia was associated with the reappearance of a nocturnal TSH peak in all but 1 patient (mean TSH peak, 198.2 +/- 13.0; P = NS vs. controls). This change paralleled the normalization of serum total T3 and rT3, which were reduced and increased, respectively, when diabetes was poorly controlled. An inverse relationship was found between serum fructosamine levels and the nocturnal TSH peak, suggesting that metabolic decompensation accounts for the abolishment of the latter.

The effect of altered thyroid function on serum fructosamine concentrations.

The effect of altered thyroid function on serum fructosamine concentrations was investigated in 31 untreated hyperthyroid patients, 18 short-term hypothyroid patients (i.e., 20 days after withdrawal of thyroid hormone suppressive therapy for thyroid cancer), 7 untreated long-term hypothyroid patients, and 25 age-matched normal controls. No differences in serum fructosamine concentrations were observed between hyperthyroid patients and normal controls; conversely, serum fructosamine concentrations were significantly higher both in short-term and in long-term hypothyroid patients than those found in normal controls. Furthermore, long-term hypothyroid patients showed significantly higher serum fructosamine concentrations than short-term hypothyroid patients. L-Thyroxine (L-T4), replacement therapy in two hypothyroid patients, resulted in a marked decrease in serum fructosamine concentrations. In seven hyperthyroid patients, the restoration of euthyroidism with antithyroid drug therapy was associated with no significant changes in serum fructosamine concentrations. The results of the present study indicate that hypothyroidism is associated with a marked increase in serum fructosamine concentrations. This alteration does not appear to be the consequence of gross abnormalities in plasma protein or glucose metabolism. The duration of hypothyroidism seems to be an important factor, even though the mechanism underlying this alteration remains at present unexplained. These results also suggest that caution must be used in the interpretation of elevated serum fructosamine concentrations as an index of the metabolic control of diabetes mellitus in the presence of hypothyroidism.

Is the imbalance between thrombin and plasmin activity in diabetes related to the behaviour of antiplasmin activity?

The aim of this study was to evaluate the balance between thrombin and plasmin activity in a group of 79 diabetic patients (IDDM and NIDDM). For this purpose we determined fibrinopeptide A (FPA) and B beta 15-42, specific products of thrombin and plasmin activity. Moreover we investigated the behaviour of antithrombin III and alpha 2 antiplasmin, important inhibitors of blood coagulation and fibrinolysis. Results show an increase both in FPA and B beta 15-42 in IDDM and NIDDM patients when compared to healthy controls. However the ratio between B beta 15-42 and FPA was lower than in controls indicating an imbalance between thrombin and plasmin activity. Antithrombin III levels were not different from the controls and no correlation was found with Hb A1c. alpha 2 antiplasmin was found to be higher in IDDM when compared both with NIDDM and controls. A non linear correlation was found between Hb A1c and alpha 2 AP in both diabetic groups. We conclude that the imbalance between thrombin and plasmin activity may have a role in determining fibrin deposition. These subclinical abnormalities, unrelated to vascular complications and duration of the disease, may progressively contribute to the development of the vascular complications in diabetes.

GAD65 and IA-2 autoantibodies are common in a subset of siblings of Sardinian Type 2 diabetes families.

UNLABELLED: Type 1 diabetes in Sardinia is very common in children, and we hypothesized that Latent Autoimmune Diabetes of Adult (LADA) might constitute a significant proportion of diabetes in adult Sardinian subjects. Since Type 2 diabetes is a familial disorder, we tested this hypothesis by investigating the prevalence of GAD65 and IA-2 autoantibodies (Ab) in Type 2 diabetes multiplex families of Sardinian ancestry enrolled in the Study Group for the Genetics of Diabetes in Sardinia. METHODS: A total of 684 individuals were ascertained from 252 Sardinian Type 2 diabetes multiplex families with 2.4 affected siblings per family comprising 190 families with two affected, 37 with three, 15 with four, 7 with five, and 3 with six, in addition to 80 unaffected siblings. Controls were household contacts representing 204 healthy spouses of affected siblings. Diagnosis was at 35-69 years of age and insulin was not given in the first 4 years after diagnosis. GAD65Ab and IA-2Ab were determined in standard radioligand binding assays. RESULTS: Among affected siblings GAD65Ab were positive in 8.8% of insulin-treated (n = 137; P = 0.0006), in 2.5% of non-insulin-treated (n = 467), and in 1.2% of non-diabetic siblings (n = 80) compared with 0.5% of controls (n = 204). IA-2Ab was positive in 6.6% insulin-treated (P = 0.04), 2.1% non-insulin-treated, and 2.5% non-diabetic siblings compared with 1.5% of controls. CONCLUSION: A high frequency of GAD65Ab and IA-2Ab as markers of Type 1 diabetes was found among Type 2 diabetes siblings from Sardinian multiplex families despite excluding those who had been treated with insulin during the first 4 years of disease. Our data support the hypothesis that LADA may be common in Sardinian Type 2 diabetes and stress the importance of investigating markers of Type 1 diabetes in studies of Type 2 diabetes.

Radioguided-surgery of early breast lesions.

BACKGROUND: Radioguided-surgery has been recently proposed in patients with clinically occult breast lesions. This study aimed to evaluate the feasibility of correctly locating and eradicating, by a single intralesional injection of a radiotracer, any breast lesion and, in the case of malignancy, to perform simultaneous sentinel lymph node (SLN) biopsy procedure. PATIENTS AND METHODS: Sixty-three women with early breast lesions were enrolled: 42 were invasive carcinomas, 16 in situ ductal carcinomas (DCIS) and 5 fibroadenomas. RESULTS: Scintigraphic images clearly identified the lesions in all patients while SLN/s were evident in 88% of them. At surgery all the breast lesions were easily radiolocalized and eradicated with minimum surgical trauma and, for those patients with invasive carcinomas, the SLN technique was performed in 86% of them. No skip metastases were found. CONCLUSION: A single intralesional administration of radiotracer is an easy and reliable procedure to simultaneously locate and remove both the non-palpable breast lesion and the SLN when primary malignancy was intraoperatively confirmed.

What's new in mammography.

Early diagnosis of breast cancer plays the leading role in reducing mortality rates and improving the patients' prognosis: mammography is the most sensitive technique currently available for the detection of nonpalpable lesions and therefore the method of choice. However, mammography has some limitations and the technique must be improved with technological devices without affecting image quality. This could be the target to increase diagnostic accuracy. Mammography sensitivity and specificity are now improved with the digital computer assisted technique, teleradiology, digital tomosynthesis or digital angiography--used to study microvascularization--3D imaging or synchrotron light, and laser mammography. Such other technological devices as Mammospot reduce breast thickness and provide better breast compression. Digital mammography can be carried out with film or direct digitization. The advantages of the digital technique are a shorter examination time, less storage space, electronic image recording, with image 'adjustments' made by the radiologist, and especially computerized analysis. The computer aided diagnosis can be defined as the diagnosis made by the radiologist who considers the results of computerized analysis as a 'second opinion'. In this way incidental mistakes made by radiologists, can be corrected by the computer analysis. Computers are a basic element also in teleradiology, which needs immediate and simultaneous admittance to the patient's history and permits radiology optimization in rural areas too. As for tomosynthesis, it permits to study a single slice of the breast without glandular tissue overlapping, which is useful in dense breasts where the diagnosis can be made with a lower X-ray dose. Moreover, this method fits the current mammographic systems easily. 3D imaging is still a work in progress. Synchrotron mammography is used only on surgery specimens, where it exhibits high resolution and contrast, depicting structures and details missed by conventional mammography. Breast DSA allows the study of vessels < 0.20 mm in diameter and of fine microvascular details; it can also demonstrate neoangiogenesis. Laser mammography permits bilateral examinations of the breast in 10-15 mins and is currently used also for breast cancer therapy, although only in animal trials. To conclude, after reviewing new techniques and evaluating the real cost/benefit ratio for each of them, conventional mammography remains the most sensitive tool for breast cancer diagnosis.

[Low levels of dehydroepiandrosterone sulfate in adult males with insulin-dependent diabetes mellitus]. / Bassi livelli di deidroepiandosterone solfato in maschi adulti affetti da diabete insulino dipendente.

UNLABELLED: Studies on animals and humans have suggested that dehydroepiandrosterone sulphate (DHEAS) has antiatherogenic effects. It has been hypothesized that insulin may have an atherogenic role and it has been reported recently that, surprisingly, DHEAS levels decreased in normal men and women during the hyperinsulinemic-euglycemic technique. Since a hyperinsulinemia frequently occurs during insulin therapy in patients with insulin dependent diabetes mellitus (IDDM), the present work was undertaken to determine whether DHEAS serum concentrations were decreased in IDDM patients as compared to controls and if so, to discover the possible causes. To this, purpose, out of 805 outpatients afferent to our Diabetes Centre from 1989 to 1992, three groups were selected on the basis of the criteria described below. Known interferences with the DHEAS serum concentrations such as gender (all males), age (aged 20-40 years) and Body Mass Index (BMI < 30) were excluded. Group A (cross-sectional study) was made up of 15 IDDM patients on insulin treatment with good metabolic control (HbA1C < 8%); group B (control study) was made of 18 healthy subjects (these patients were selected also on the basis of their normal oral glucose tolerance test) and group C (longitudinal study) was made up of 7 IDDM patients who had been examined previously and who were on insulin treatment. METHODS: In all three groups serum concentrations of DHEAS, 17 OH progesterone (17 OHP), delta 4 androstenedione (A4) and cortisol (F) were measured. In 10 patients from group A and in 9 patients from group B the ACTH test (9.25 mg IM Synacthen) was administered and the same hormonal pattern was measured after 60 min. In group C the same hormonal evaluation was performed 5 +/- 2.8 months after commencement of insulin therapy. RESULTS: DHEAS serum concentrations were significantly decreased in group A (median 2.9; range 1.1-5.2 mumol/l) with respect to group B (median 5.7; range 3.0-9.5 mumol/l) (p < 0.0012). However, the serum concentrations of 17 OHP (median 3.9 nm/l; range 2.9-6.9 nm/l and A4 (median 5.2 nm/l; range 1.8-10.2 nm/l) were also significantly reduced, while cortisol levels and the 17 OHP/A4 ratio were comparable to group B. After administration of ACTH, the delta increment in cortisol percentage showed a frank increase (55.1%) in group A with respect to group B (33.1%) (p < 0.01). The rise in DHEAS showed a lower increase in group A (10.2%) with respect to group B (65.5%) even though not statistically significant, while the other hormones showed an overlap between the two groups. In group C the serum concentrations of hormones before insulin therapy did not show any statistical differences with respect to the values in group B. A second evaluation, which was performed during insulin therapy, showed that only the 17 OHP/A4 ratio tended towards higher values with respect to pretherapy values (1.1 and 0.6 respectively; p = 0.07). In conclusion our data confirm low DHEAS levels during chronic insulin administration therapy. The underlying mechanism could be a general aspecific reduction in the activity of P 450 C 21 SCC enzymes in contrast with the specific inhibition of 17.20-lyase obtained during insulin bolus. Whether the low serum concentrations of DHEAS can determine an atherogenic effect of insulin needs further investigation, but the hormone could constitute a new parameter for the follow-up of patients affected by diabetes mellitus.