A 5-year experience of benign pancreatic hyperenzymemia.

OBJECTIVE: Benign pancreatic hyperenzymemia is characterized by a long-term increase of serum pancreatic enzymes in otherwise healthy subjects. This study was designed to determine (a) whether all pancreatic enzymes are elevated, (b) the extent of each enzyme increase, (c) the relative frequency of the familial form, and (d) the relative frequencies of pancreatic and salivary hyperamylasemia and macroamylasemia. METHODS: Two hundred seven asymptomatic subjects with benign pancreatic hyperenzymemia were studied during the 5-year period. Serum amylase, isoamylase, and lipase levels were assessed by immunoenzymatic assays. RESULTS: Most (n = 183; 88.4%) patients had benign pancreatic hyperenzymemia; 155 (74.9%) patients had an abnormal increase of all 3 enzymes, 15 (7.2%) patients of only lipase, and 13 (6.3%) patients of only amylase and pancreatic isoamylase. Lipase levels were the highest (1.1-21 times above upper limit). Of the 183 subjects, 72 were members of 35 different families, 15 (7.2%) had increased salivary amylase, and 9 (4.3%) had macroamylasemia. Wide day-to-day fluctuations of pancreatic enzymes, including falls within the reference ranges, were recorded. CONCLUSIONS: All enzymes were increased in benign pancreatic hyperenzymemia, with lipase showing the highest elevation. Doctors should reassure patients about the benign nature of this condition and limit repeating useless examinations.

Poor glycaemic control and arrhythmias.

OBJECTIVE: To evaluate number, type, and complexity of arrhythmias in diabetics compared with controls and, among diabetics, comparing good glycaemic control (GGC) and poor glycaemic control (PGC) patients. METHODS: We compared Ambulatory Electrocardiogram recordings of 92 diabetics and 100 controls. The glycaemic profile of 50 diabetics, taken the same day as the Ambulatory ECG recording, was subdivided into GGC (gluco-stick mean values between 100 and 140 mg/dL) or PGC (gluco-stick values ≤99 mg/dL in 3-of-4 daily determination or gluco-stick values ≥140 mg/dL in 3-of-4 daily determination). RESULTS: Diabetics show a higher prevalence of either ventricular ectopic beats (VEBs) (93.47% vs. 82% controls, p < 0.05) and heart rate (both in sinus rhythm and in atrial fibrillation) (98.35 ± 10 beats/min in diabetics vs. 78.10 ± 8.1 in controls, p < 0.001). Moreover, diabetics with PGC show either a higher prevalence of VEBs (96.42% vs 77.27% in GGC, p < 0.05) and of supraventricular ectopic beats (SVEBs) (96.42% vs. 68.18 in GGC, p < 0.05); furthermore, diabetics with PGC show more severe and complex atrial and ventricular arrhythmias (SVEBs 32.14% vs 0%, p < 0.05; VEBs 39.28% vs 9.09%, p < 0.05). CONCLUSIONS: The analysis of our sample shows that the arrhythmogenic condition is not only provided from diabetic condition per se but it is enhanced in PGC. Infact PGC patients showed higher number of VEBs, often polymorphic, expression of more severe arrhythmic and cardiovascular outcome. This could be partially explained by hyperactivation of autonomic nervous system during metabolic stress (which increases mean heart rate). Moreover more severe diabetic patients may present coronary microangiopathy that can further explain their arrhythmogenic tendency.

SPINK1 and PRSS1 mutations in benign pancreatic hyperenzymemia.

UNLABELLED: The aim of this study was to determine whether mutations in SPINK1/PRSS1 genes are associated with benign pancreatic hyperenzymemia (BPH). METHODS: Sixty-eight subjects with BPH (including 13 familial cases) were studied. In all, we sequenced germline DNA for all the exons and intro-exon boundaries of PRSS1 and SPINK1. RESULTS: Nine (13.2%) of the 68 subjects harbored PRSS1 or SPINK1 mutations. As to PRSS1, no hereditary pancreatitis-associated variant was detected, whereas previously undescribed mutations (p.Ala148Val and c.40+1G>A) were respectively found in 2 subjects (2.9%). SPINK1 mutations were detected in 7 subjects (10.3%). Five of them exhibited known mutations (3 p.Asn34Ser, 1 p.Pro55Ser, and 1 c.88-23A>T), whereas 2 had a newly found variant (p.Arg67Gly and c.*32C>T, respectively). Only 2 familial BPH, belonging to 2 different families, were found to carry a mutation (1 with p.Ala148Val for PRSS1 and 1 with p.Asn34Ser for SPINK1). CONCLUSIONS: No known mutations of PRSS1 have been found in BPH, whereas the frequency of known SPINK1 variants is similar to that reported in the general population. No segregation of PRSS1/SPINK1 variants occurs in BPH families. Benign pancreatic hyperenzymemia cannot be explained by mutations in genes whose variants are known to be associated with pancreatitis or by mutations in other PRSS1/SPINK1 genes.

Endogenous sex hormones as risk factors for dementia in elderly men and women.

BACKGROUND: The associations of endogenous sex hormones with risk of dementia in the elderly population are not well known. METHODS: The relationship of baseline serum total estradiol (E2) and free testosterone (FT) to 4-year risk of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD) was examined in a dementia-free, population-based cohort of 433 women (mean age 74 years) and 376 men (mean age 73 years). Multivariable proportional hazards regression was used to adjust for sociodemographic and lifestyle variables, body mass index, apolipoprotein E genotype, cardiovascular conditions, and homocysteinemia. RESULTS: Dementia developed in 71 women (46 AD, 21 VaD) and 39 men (23 AD, 12 VaD). In women with high E2 (serum E2 >or= 10 pg/mL), the multivariable-adjusted hazard ratio (HR) for dementia was 1.75 (95% confidence interval [CI], 1.06-2.89). The corresponding multivariable-adjusted HR for AD was 1.94 (95% CI, 1.04-3.61), whereas no association was found for VaD. No association with dementia was found for serum FT in women and for either serum E2 or FT in men. CONCLUSION: High serum E2 is an independent predictor for dementia and AD in elderly women.

Can pancreatic steatosis explain the finding of pancreatic hyperenzymemia in subjects with dyslipidemia?

OBJECTIVE: It has been proposed by some investigators that benign pancreatic hyperenzymemia could result from pancreatic steatosis that they believe would have been caused by dyslipidemia; their diagnosis of steatosis was based on the finding of a hyperechogenic pancreas at ultrasound. The aim of this study was to assess the validity of this proposed model. METHODS: The study group was composed of 18 subjects with benign pancreatic hyperenzymemia, 12 men and 6 women; mean age, 55 years; range, 38 to 68 years. All 18 had dyslipidemia and 9 had hyperechogenic pancreas at ultrasound. In addition, 6 subjects with benign pancreatic hyperenzymemia but who did not have dyslipidemia or hyperechogenic pancreas and 10 healthy subjects with none of these conditions were also studied as controls. In each of these subjects, magnetic resonance imaging of the pancreas was performed to assess the presence of pancreatic steatosis. RESULTS: Magnetic resonance imaging showed normal pancreas with no signs of fatty infiltration in all 18 subjects with dyslipidemia, including those with both dyslipidemia and hyperechogenic pancreas at ultrasound. A similar result was found in all control subjects. CONCLUSION: The finding of a completely normal pancreas at magnetic resonance imaging does not support the proposed model in which pancreatic hyperenzymemia in subjects with dyslipidemia is attributed to pancreatic steatosis.

Metabolic Syndrome: prevalence and prediction of mortality in elderly individuals.

OBJECTIVE: Little is known about the prevalence of the metabolic syndrome among elderly people in Italy, its association with all-cause mortality, and whether measurement of serum C-reactive protein (CRP) and interleukin (IL)-6 affects this association. RESEARCH DESIGN AND METHODS: The baseline prevalence of metabolic syndrome, diagnosed according to the National Cholesterol Education Program (NCEP) criteria, and all-cause mortality at 4 years were recorded in an Italian population-based cohort (981 subjects, 55% women, aged 65-97 years). A Cox model adjusted for sociodemographic, lifestyle, and medical variables was used to investigate 1) whether metabolic syndrome was a predictor of mortality and 2) how the association was affected by baseline high CRP (>3 mg/l) and IL-6 (>1.33 pg/ml). RESULTS: Overall, metabolic syndrome prevalence was 27.2% [95% CI 24.0-30.5] and higher in women (33.3% [28.7-38.0]) than in men (19.6% [15.5-24.2]). During follow-up, 137 deaths occurred. Using the no metabolic syndrome/no high IL-6 group as the reference, mortality was not associated with the metabolic syndrome alone (multivariable-adjusted hazard ratio 1.24 [0.60-2.59]), only weakly associated with high IL-6 alone (1.66 [1.04-2.63]), but strongly associated with the concurrent presence of metabolic syndrome and high IL-6 (3.26 [2.00-5.33]). High CRP was not a mortality predictor (0.83 [0.58-1.20]) nor did it affect the association of the other variables with mortality. CONCLUSIONS: Metabolic syndrome by NCEP criteria is highly prevalent in the Italian elderly population. It is not itself associated with mortality but may improve the usefulness of IL-6 as a mortality predictor in older age.

A search for acute necrotic pancreatitis in early stages of alcoholic chronic pancreatitis.

OBJECTIVES: Various investigators believe that alcoholic chronic pancreatitis is the result of recurrent episodes of acute necrotic pancreatitis. The aim of this work is to study pancreatic histology in early stages of the disease to search for evidence of these acute episodes. STUDY: Of about 650 patients with alcoholic pancreatitis seen during the 30-year period from 1972 to 2002, 45 underwent surgery for this disease, all within 2 years of clinical onset. Of these 45, tissue samples adequate for study were obtained from 42, and this was the study material. Tissue samples were prepared for histologic examination by standard procedures. RESULTS: Areas of pancreatic necrosis were seen in tissue samples of only three (7%) of the 42 patients, and in all three cases chronic lesions were also present. No evidence of localized scarring that could be attributed to prior episodes of focal necrotic pancreatitis was found. A typical feature was the patchy distribution of the lesions in largely normal pancreatic tissue. The main lesions observed were perilobular and intralobular fibrosis, dilation of acini and ducts, and protein plugs in dilated ducts surrounded by periductal fibrosis. CONCLUSIONS: This study shows that, in the early stages of alcoholic chronic pancreatitis, signs of acute necrotic pancreatitis are very infrequent and, when present, they are associated with chronic lesions. These findings suggest that alcoholic pancreatitis begins as a chronic disease.

Interleukin-1beta and interleukin-6 gene polymorphisms as risk factors for AD: a prospective study.

Risk of incident dementia from any cause and Alzheimer's disease (AD) in relation to the IL-1beta-511 (C-->T) and IL-6-174 (G-->C) polymorphisms was investigated in an Italian elderly cohort (n=791) with 4 years of follow-up. Analyses were adjusted for socio-demographic confounders (age, gender, education), presence of the Apolipoprotein E-epsilon4 allele, and plasma total homocysteine (tHcy), a newly proposed AD risk factor. No significant association was found for the IL-1beta-511 and IL-6-174 polymorphisms with either dementia or AD. However, in the baseline dementia-free cohort considered as a whole, independently of other confounders, IL-1beta-511 T/T homozygotes had lower plasma tHcy than both heterozygotes (P=0.036) and wild-types (P=0.004). These data do not support the hypothesis that the IL-1-beta-511 and IL-6-174 polymorphisms affect dementia or AD risk. The relationship between the AD risk factor plasma tHcy and the IL-1beta-511 polymorphism was never reported before and might explain previous cross-sectional reports of an association between this polymorphism and AD.

Folate, but not homocysteine, predicts the risk of fracture in elderly persons.

BACKGROUND: Recent prospective studies reported that increased plasma homocysteine levels are an independent predictor of osteoporotic fracture in elderly persons. These studies, however, did not take into account folate and vitamin B12, which are the major nutritional determinants of homocysteinemia. METHODS: Incident osteoporotic fractures were assessed in 702 Italian participants aged 65-94 years with a mean follow-up of 4 years (1999/2000-2003/2004). A multivariable logistic regression model was used to study the relation of baseline plasma homocysteine, serum folate, and serum vitamin B12 with risk of fracture. RESULTS: After adjustment for sociodemographic and clinical confounders, the odds ratio (OR) for each increase of 1 standard deviation in log-transformed plasma homocysteine was 1.39 (95% confidence interval [CI], 1.01-1.91), but decreased to 1.22 (95% CI, 0.85-1.74) after further adjustment for serum folate and vitamin B12. The corresponding multivariable-adjusted OR for hyperhomocysteinemia (plasma total homocysteine [tHcy] > 15 micromoL) was 1.58 (95% CI, 0.71-3.53). Participants in the lowest serum folate quartile (< or =9.3 nmol/L) had an increased risk of fracture than did those in higher quartiles (multivariable-adjusted OR = 2.06; 95% CI. 1.02-4.18), but no dose-related protective effect for increasing serum folate levels was found (multivariable-adjusted OR = 0.84 for each increase of 1 standard deviation in log-transformed serum folate, 95% CI, 0.59-1.19). No independent association was found for serum vitamin B12. CONCLUSIONS: Low serum folate is responsible for the association between homocysteine and risk of osteoporotic fracture in elderly persons.

Mutations of the CFTR gene in idiopathic pancreatic hyperenzymemia.

OBJECTIVES: Idiopathic pancreatic hyperenzymemia is a new syndrome that is characterized by a chronic increase of serum pancreatic enzymes in the absence of pancreatic disease. The aim of this study was to assess whether mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene may have a role in the etiology of this hyperenzymemia. METHODS: Seventy subjects with idiopathic pancreatic hyperenzymemia, 44 men and 26 women (mean age, 48 years; range, 8-74 years), were studied. Thirteen of these 70 subjects had the familial form of the syndrome. The mutation analysis of the CFTR gene was carried out using diagnostic commercial kits for the simultaneous detection of 29 mutations and Tn polymorphism. RESULTS: Among the 70 subjects studied, 7 (10.0%) had CFTR gene mutations. None of these 7 subjects had the familial form of pancreatic hyperenzymemia. These mutations were DeltaF 508 in 1 subject, 2789 + 5 G > A in another subject, and T5 allele in the remaining 5. All these mutations were heterozygous, with the exception of 1 T5 allele that was homozygous in 1 subject. CONCLUSIONS: The frequencies of the mutations of the CFTR gene found in these subjects are similar to the carrier frequencies in the general Italian population. This finding does not support a role for CFTR gene mutations in the etiology of idiopathic pancreatic hyperenzymemia.

Obesity and the risk of pancreatic cancer: an italian multicenter study.

OBJECTIVE: The purpose of this work was to determine whether obesity is a risk factor for pancreatic cancer. METHODS: We studied 400 patients with this tumor and 400 controls matched for sex and age from various Italian cities. We used a standardized questionnaire that was compiled at personal interview, with particular attention to body weight at the time of the interview, and for those with the tumor, their weight before onset of the disease. Body mass index (BMI) was calculated as the patient's weight in kilograms divided by their height in meters squared. RESULTS: The risk of pancreatic cancer adjusted for smoking was 5-fold higher (P < 0.001) in patients with a BMI less than 23 kg/m2 after diagnosis compared with patients with a BMI ranging from 23 to 29.9 kg/m2, whereas the risk in patients with BMI of at least 30 kg/m2 was not significant (P = 0.689). Taking into account BMI before diagnosis, smoking was confirmed as a significant risk factor (odds ratio = 1.68; P = 0.001) for pancreatic cancer, whereas no significant relationship was found between BMI classes and the risk of pancreatic cancer (P = 0.984). CONCLUSIONS: These findings indicate that obesity is not a risk factor for pancreatic cancer.

Serum C-reactive protein and cognitive function in healthy elderly Italian community dwellers.

BACKGROUND: Chronic low-grade inflammation, as measured with the peripheral serum marker C-reactive protein (sCRP), may be a risk factor for dementia in elderly persons. METHODS: The relationship between sCRP and score on the Mini-Mental State Examination (MMSE), a commonly used screening cognitive measure, was investigated in 540 well functioning, healthy, and cognitively normal elders (age 73 +/- 6 years). Sociodemographic status, lifestyle, health status, traditional and nontraditional cardiovascular risk factors including plasma total homocysteine (tHcy), and other peripheral blood markers of vascular inflammation (leukocyte count, serum albumin, and plasma fibrinogen) were also assessed. RESULTS: Risk for having sCRP in the highest decile (>0.7 mg/dl) was significantly higher in individuals with MMSE score 24-25 (odds ratio = 3.07, 95% confidence interval, 1.2-7.9) and 26-28 (odds ratio = 2.10, 95% confidence interval, 1.1-3.9) compared with those scoring above 28 (reference group). Results were unaffected by adjustment for all potential confounders. No association was found between MMSE and peripheral markers of vascular inflammation other than sCRP, but lower MMSE scores were also independently associated with hyperhomocysteinemia (plasma tHcy > 15 mmol/L). CONCLUSION: In healthy, cognitively normal elderly community dwellers, increased sCRP levels are associated with concurrent cognitive impairment as measured by MMSE. The association is independent of sociodemographic status, lifestyle, health status, and traditional and nontraditional cardiovascular risk factors including hyperhomocysteinemia. Results support the hypothesis that chronic low-grade inflammation may be involved in age-related cognitive impairment.

Effects of weight loss and risk factor treatment in subjects with elevated serum C3, an inflammatory predictor of myocardial infarction.

BACKGROUND: Serum C3 is an inflammatory predictor of myocardial infarction and a covariate of fasting insulin and several endogenous risk factors. This study was performed to ascertain whether risk factor control may reduce elevated C3 concentrations. METHODS: After traditional risk factor and C3 assessment in 1100 unselected men aged 55-64 years, 238 men with persistently elevated C3 levels (>=1.19 g/l, high tertile) were randomised into 2 groups: 43 controls, who were referred to their general practitioner, and 195 subjects who were intensively treated with diet, and anti-hypertensive or antidiabetic drugs according to specific indications, without anti-dyslipidemic drugs. RESULTS: After three months in the treated subjects significant decrements of body weight, blood pressure, blood glucose and serum lipids were obtained, with stable C3 levels (while in controls a 3.3% increase occurred, P=0.02). The factors associated with a C3 decrement >5% were a high baseline C3 level, a recent acute inflammation, physical activity, belonging to the treated group, and a significant reduction in body weight, triglycerides or blood glucose. However, in multivariate analysis only an elevated baseline C3 (P<0.0001), a weight loss >2% (P=0.0009) and physical activity (P=0.02) remained independently associated with a C3 decrement >5% (R(2)=0.14). CONCLUSIONS: Only weight loss and physical activity, but not traditional risk factor lowering, could independently induce a significant C3 decrease. Thus, C3 elevation is associated with, but probably not caused by, traditional risk factors.

Screening for mild cognitive impairment in elderly ambulatory patients with cognitive complaints.

BACKGROUND AND AIMS: Identification of patients with Mild Cognitive Impairment (MCI) is strongly recommended because of their increased risk of dementia. Two brief global cognitive instruments, the Mini Mental State Examination (MMSE) and the Clock Drawing Test (CDT), were examined as useful screening methods for MCI. METHODS: The sensitivity and specificity of MMSE and CDT, scored using the Sunderland and Wolf-Klein methods, were evaluated in 113 elderly individuals with three different MCI subtypes: amnestic, multiple domain impairments, and single non-memory domain. Diagnoses were made on the basis of extensive clinical and neuropsychometric assessment. RESULTS: Used alone, MMSE and CDT at standard cut-offs were highly specific (about 0.80) but rather insensitive (less than 0.50) to all MCI subtypes. By contrast, when used in combination, an abnormal result on either MMSE or CDT scored by the Sunderland method had a specificity of 0.69 [0.57-0.81] and a sensitivity of 0.75 [0.64-0.87] for multiple domain impairments MCI. Results were similar for MMSE in combination with CDT scored by the Wolf-Klein method (specificity 0.71 [0.59-0.83]; sensitivity 0.68 [0.56-0.80]). CONCLUSIONS: MMSE and CDT alone are not valid screening methods for MCI detection. In combination, they reach fair sensitivity and specificity for the multiple domain impairment MCI subtype. However, some theoretical concerns relating to this subtype, together with the uncertainty that still lingers about its prognostic value, caution against routine use of MMSE and CDT as MCI screening instruments.