Rocco Micciolo

Intimal-Medial Thickness of the Carotid Artery in Nondiabetic and NIDDM Patients: Relationship with insulin resistance

OBJECTIVE The aim of this study was 1) to compare intimal-medial thickness (IMT) of the carotid artery in nondiabetic and NIDDM patients and 2) to evaluate the association of this early marker of atherosclerosis with several cardiovascular risk factors, including plasma insulin and insulin resistance. RESEARCH DESIGN AND METHODS A total of 58 nondiabetic and 56 NIDDM patients, randomly selected among those attending the outpatient Diabetes Clinic or the Clinic for Internal Medicine were examined. BMI, waist-to-hip ratio (WHR), blood pressure, glycohemoglobin (HbA1c), and fasting concentrations of plasma glucose, serum lipids (total and HDL cholesterol, triglycerides), and serum insulin were measured. Insulin resistance was assessed by computing glucose disappearance rate from plasma after intravenous insulin injection (Kitt). IMT of the carotid artery was measured by ultrasonography. RESULTS IMT was significantly higher in diabetic patients, and the difference remained highly significant after adjusting for sex, age, BMI, WHR, presence of hypertension and dyslipidemia, and smoking status (1.39 vs. 1.24 mm, common SD 0.12, P < 0.001). Univariate regression analyses showed that IMT was negatively correlated with Kitt in either nondiabetic (r = −0.348, P < 0.01) or diabetic patients (r = −0.492, P < 0.001). However, multiple regression analyses showed that IMT was independently associated with age and WHR in nondiabetic subjects, whereas in diabetic patients, IMT was independently predicted by Kitt and hypertension. These two variables explained ∼ 62% and ∼35% of the variability of IMT in nondiabetic and diabetic patients, respectively. Plasma insulin was not independently associated with IMT in either groups. CONCLUSIONS These results indicate that 1) diabetes is characterized by a greater thickness of the carotid artery independently of other established risk factor of atherosclerosis, 2) early atherosclerosis is independently associated with insulin resistance in diabetic but not in nondiabetic patients, 3) central adiposity is an independent predictor of IMT in nondiabetic individuals.

Suicide and unemployment in Italy: Description, analysis and interpretation of recent trends

This paper assesses the relationship between suicide and unemployment in Italy during the period 1977-1987, taking into account variations by gender and region. The first objective of the study is to provide descriptive longitudinal and cross-sectional aggregate-level analyses and also trends in individual-level and population risks for suicide in relation to unemployment. Our second objective is to use the Italian data to help discriminate between rival interpretations of the unemployment-suicide link, i.e. the operation of health selection or causal (susceptibility) mechanisms. Evidence for an association between suicide and unemployment among women was not convincing. The annual rate of female unemployment was negatively correlated with the female suicide rate and unrelated to the suicide rate among the unemployed, the relative risk or population attributable risk. Individual-level analyses for each year confirmed that unemployed women were more likely to commit suicide than their employed counterparts, although the overall relative risk was low (1.5) and conference intervals for six of the eleven annual risk ratios included unity (1). Among men, the unemployment rate was positively correlated over time with the suicide rate. However, change in the suicide rate across 18 geographic regions of Italy was unrelated to change in the unemployment rate, a finding which did not appear to be invalidated by a regression to the mean effect. Unemployment was also positively related to the suicide rate among the employed and population attributable risk, but unrelated to the rate among the unemployed or the relative risk. Comparison of suicide rates among the employed and unemployed revealed an excess of suicide among the latter in each year, with an overall relative risk of 3.4. On the basis of this contradictory and inconsistent evidence, we are cautious about offering definitive interpretations concerning the nature of the unemployment-suicide link among men. We conclude by suggesting the need for further individual-level studies using retrospective case-control methods.

The relationship between body composition and physical performance in older women.

BACKGROUND: The relationship between age‐associated change in body composition and physical disability is still unknown. Skeletal muscle mass declines with age in both sexes; however, since women have less muscle mass per unit of weight than men, these changes may be more debilitating in women.

Ki-67 immunostaining in 322 primary breast cancers: Associations with clinical and pathological variables and prognosis

Cell‐proliferation markers are very important in the clinical management of cancer patients, and the identification of Ki‐67 (a monoclonal antibody that recognizes proliferating cells) can make it easier to define the level of proliferative activity. This study investigated the associations between the Ki‐67 levels measured by means of immunohistochemistry, and other clinical and pathological variables and prognosis in 322 breast‐cancer patients. A significant association was found (p < 0.001) between Ki‐67 values and tumor size, nodal status, estrogen and progesterone receptor status; multivariate analysis showed that Ki‐67 levels were associated with disease‐free and overall survival, thus confirming that it is an independent prognostic variable. Various statistical approaches were used in an attempt to establish the best cut‐off point for dividing patients into groups at high or low risk of relapse but, in this series, we could find no evidence leading to a single “best” cut‐off point. We conclude that the quantitative level of Ki‐67 could be used as a prognostic factor in breast‐cancer patients. Int. J. Cancer 74:433–437, 1997.

Leptin/HER2 crosstalk in breast cancer: in vitro study and preliminary in vivo analysis

BackgroundObesity in postmenopausal women is associated with increased breast cancer risk, development of more aggressive tumors and resistance to certain anti-breast cancer treatments. Some of these effects might be mediated by obesity hormone leptin, acting independently or modulating other signaling pathways. Here we focused on the link between leptin and HER2. We tested if HER2 and the leptin receptor (ObR) can be coexpressed in breast cancer cell models, whether these two receptors can physically interact, and whether leptin can transactivate HER2. Next, we studied if leptin/ObR can coexist with HER2 in breast cancer tissues, and if presence of these two systems correlates with specific clinicopathological features.MethodsExpression of ObR, HER2, phospo-HER2 was assessed by immonoblotting. Physical interactions between ObR and HER2 were probed by immunoprecipitation and fluorescent immunostaining. Expression of leptin and ObR in breast cancer tissues was detected by immunohistochemistry (IHC). Associations among markers studied by IHC were evaluated using Fishers exact test for count data.ResultsHER2 and ObR were coexpressed in all studied breast cancer cell lines. In MCF-7 cells, HER2 physically interacted with ObR and leptin treatment increased HER2 phosphorylation on Tyr 1248. In 59 breast cancers, the presence of leptin was correlated with ObR (the overall association was about 93%). This result was confirmed both in HER2-positive and in HER2-negative subgroups. The expression of leptin or ObR was numerically more frequent in larger (> 10 mm) tumors.ConclusionCoexpression of HER2 and the leptin/ObR system might contribute to enhanced HER2 activity and reduced sensitivity to anti-HER2 treatments.

Seasonal variation in suicide: is there a sex difference?

Seasonal variation in suicide in Italy for the years 1969-81 has been assessed in males and females by means of harmonic analysis. Cyclical fluctuations in the number of suicides, reasonably consistent over the 13 years of the study, have been observed in both sexes. Seasonal harmonics accounted for 65.3 and 48.4% of the variance in male and female suicides respectively. While in males the only important seasonal harmonic was the first (one cycle per year), in females there was an important first harmonic and a second harmonic (two cycles per year). In both sexes the peak of the first harmonic occurred in May, while in females the subsidiary peak occurred in October-November.

Cough threshold in reflux oesophagitis: influence of acid and of laryngeal and oesophageal damage

BACKGROUND Gastro-oesophageal reflux is often associated with cough. Patients with reflux show an enhanced tussive response to bronchial irritants, even in the absence of respiratory symptoms. AIM To investigate the effect of mucosal damage (either oesophageal or laryngeal) and of oesophageal acid flooding on cough threshold in reflux patients. PATIENTS We studied 21 patients with reflux oesophagitis and digestive symptoms. Respiratory diseases, smoking, and use of drugs influencing cough were considered exclusion criteria. METHODS Patients underwent pH monitoring, manometry, digestive endoscopy, laryngoscopy, and methacholine challenge. We evaluated the cough response to inhaled capsaicin (expressed as PD5, the dose producing five coughs) before therapy, after five days of omeprazole therapy, and when oesophageal and laryngeal damage had healed. RESULTS In all patients spirometry and methacholine challenge were normal. Thirteen patients had posterior laryngitis and eight complained of coughing. Twenty patients showed an enhanced cough response (basal PD5 0.92 (0.47) nM; mean (SEM)) which improved after five and 60 days (2.87 (0.82) and 5.88 (0.85) nM; p<0.0001). The severity of oesophagitis did not influence PD5 variation. On the contrary, the response to treatment was significantly different in patients with and without laryngitis (p=0.038). In patients with no laryngitis, the cough threshold improved after five days with no further change thereafter. In patients with laryngitis, the cough threshold improved after five days and improved further after 60 days. Proximal and distal oesophageal acid exposure did not influence PD5. Heartburn disappeared during the first five days but the decrease in cough and throat clearing were slower. CONCLUSIONS Patients with reflux oesophagitis have a decreased cough threshold. This is related to both laryngeal inflammation and acid flooding of the oesophagus but not to the severity of oesophagitis. Omeprazole improves not only respiratory and gastro-oesophageal symptoms but also the cough threshold.

Bone marrow micrometastases in 109 breast cancer patients: correlations with clinical and pathological features and prognosis

Background: The presence in bone marrow of cells which react with monoclonal antibodies against tumor-associated antigens has been proposed over the last few years as a new prognostic factor in breast cancer patients. Patients and methods: Bone marrow aspirates were obtained from 109 stage I and II breast cancer patients during or 2–4 weeks after primary surgery. The samples were processed for leukocyte separation on a Ficoll-Hypaque gradient and then used to prepare cytospin slides for immunocytochemical analysis. The slides were stained with a pool of monoclonal antibodies (MoAbs) which recognize tumor associated antigens, using the alkaline phosphatase anti-alkaline phosphatase method. The median follow-up was 36 months (range 15–62); 22 patients relapsed and 7 died. Results: Thirty-four of the 109 patients (31.1%) had MoAb positive bone marrow cells. The bone marrow was positive in 28/74 (37.9%) patients who had the aspirate taken during surgery and in 6/35 (17.1%) who had it taken after surgery (p = 0.055). No association was found between bone marrow positivity and tumour size, nodal status, menopausal status, estrogen receptor positivity or the proliferative index. No association was found between bone marrow and prognosis: the log-rank test was 0.291 (p > 0.5) for OS and 0.023 for DFS; the hazard ratio (positive vs negative) was 1.51 for OS (95% CI: 0.33–6.86) and 0.93 for DFS (95% CI: 0.35–2.45). Conclusions: In our series, bone marrow positivity did not correlate with prognostic parameters or prognosis. Of interest is the relative excess of positivity when the bone marrow was obtained during surgery.

Glucose tolerance and blood lipids in bran-fed patients with impaired glucose tolerance.

Thirty-eight patients (13 men and 25 women) with impaired glucose tolerance, aged 33–70 yr, underwent a dietary program adding 20 g of raw bran to their usual diet without changing their dietary habits. After 1 mo of treatment, the areas under the curves for glucose and insulin were reduced from 26,214 ± 5618 to 24,529 ± 5207 g/min (P < 0.001) and from 15,893 ± 9714 to 12,440 ± 7377 mU/min (P < 0.001), respectively, cholesterol was reduced from 234 ± 40 to 212 ± 29 mg/dl (P < 0.001), and triglycerides were reduced from 108 ± 56 to 97 ± 50 mg/dl (P < 0.05). Body weight (initially 128.44% relative body weight) decrease 0.8% (P < 0.02). After the first month, 14 subjects were studied for a further 2 mo. Six patients continued bran feeding, and eight, who stopped bran, were used as controls. Patients who took bran maintained metabolic improvement over the 3-mo treatment period, while those who stopped bran did not.

Geographical and urban—rural variation in the seasonality of suicide: Some further evidence

The seasonal variation of the suicides (n = 57,007) that occurred in Italy during the years 1969-1984 was evaluated using harmonic analysis, according to the method described by Pocock (1974). Monthly data were analyzed, separately for males and females, taking into account the setting (urban or rural) and the geographical location (Northern, Central or Southern regions). As compared with a previous study by our research group, a more precise (less aggregated) index of the urban-rural continuum was used. Rates for males were greater than those for females; urban were higher than rural rates; the seasonality was greater in the rural than in the urban settings and generally greater in males than in females in the Southern as well as in the Northern regions.