Lifestyle and high density lipoprotein cholesterol in postmenopause.

OBJECTIVES: Menopause is characterized by hormonal and metabolic changes. These are linked to increased risk of cardiovascular disease, for which low blood plasma levels of high density lipoprotein (HDL) cholesterol are an independent risk factor. The present study investigated variables linked with basal plasma HDL cholesterol levels and the effects of aerobic training, on their variations, in 40 postmenopausal women. METHODS: We assessed body composition, dietary habits and maximal aerobic capacity of participants. Characteristics of daily physical activity and plasma lipoproteins were measured. The women walked on 4 days/week, for 14 weeks, at moderate intensity, and they were grouped according to the resulting tertiles of basal plasma HDL cholesterol levels. RESULTS: Logistic regression analysis showed that waist-to-hip ratio and number of daily bouts of moderate-intensity physical activity, held for at least 10 consecutive minutes (B10m/day), are predictive variables of basal plasma HDL cholesterol levels. After the training period, the first and second tertiles increased plasma HDL cholesterol levels, while the third tertile decreased plasma HDL cholesterol levels. The tertiles showed different remodelling of spontaneous physical activity: the third tertile reduced B10m/day, while the others did not. CONCLUSIONS: This study provides knowledge about the relationships of plasma HDL cholesterol levels with characteristics of physical activity. Furthermore, it shows that physical exercise engagement can result in negative compensation of spontaneous physical activity that could counteract or reduce the positive effects of the aerobic training on plasma HDL cholesterol levels.

Characteristics of spontaneous physical activity and executive functions in postmenopause.

AIM: Executive functions are susceptible to age-related changes, and menopause has also been shown to be linked with their decline. The aim of the present study was to investigate the variables related to executive functions in postmenopausal women not involved in controlled dietary and physical exercise programs and without hormone-replacement therapy. METHODS: Fifty-seven women (58.39 ±4.16 yr) were investigated for their medical history, blood lipids, insulin resistance (HOMA-IR), body composition, blood pressure, executive functions (Digit Span and Trail Making tests), maximal aerobic capacity, dietary habits, and spontaneous physical activity. RESULTS: Cluster analysis performed on the basal data of the Digit Span scores and Trail Making tests identified two subgroups: Group A (N.=24) that showed better executive functions than Group B (N.=33). Although these subgroups differed across several variables of body composition, plasma lipids, dietary habits, spontaneous physical activity, aerobic fitness, and insulin resistance, logistic regression models showed B10m/die as the only predictive variable for subgroup membership. CONCLUSION: In the absence of a physical exercise program, the knowledge of how spontaneous physical activity is organized (B10m/die) is important for executive functions of post-menopausal women. It is the specific moderate to intense physical activity characteristic of B10m/die, rather than generic physical activity, that seems to determine the maintenance or attainment of cognitive health through body movement.

[Determinants of short-term memory: is there a difference between young adults and postmenopausal women?]. / Fattori determinanti la memoria a breve termine: esiste una differenza tra giovani donne e donne in postmenopausa?

AIM: The literature indicates that several variables are influencing cognitive health. The aim of the study was to investigate the main determinants of the short-term memory among anthropometric, dietary and performance variables in a sample of healthy women. The role played by the age was also investigated. METHODS: Forty-five healthy overweight women were recruited through general physicians: 23 were young adults (24.63±4.17 years) and 22 were postmenopausal (53.30±2.95 years). Overweight condition was assessed according to the age-adjusted reference values. Participants were analyzed for Digit Span, blood pressure, body composition, aerobic fitness and dietary habits. RESULTS: Young adults and postmenopausal women did not differ either in Digit Span or in dietary habits. In postmenopausal women Digit Span was positively correlated with body weight, body mass index, body fat, waist circumference and daily intake of vitamin D. Linear regression model indicated vitamin D as the only significant predictor variable of Digit Span. In young adults Digit Span had no correlations with the others investigated variables. CONCLUSION: In postmenopause, vitamin D daily intake is important not only for skeletal, but also for cognitive health. Even though young adults and post-menopausal women did not differ for health status, short-term memory in young adulthood seems to be differently linked with the investigated variables than during post-menopause.

Relationships between physical exercise practice, dietary behaviour and body composition in female university students.

AIM: The relationship between female body composition, total energy expenditure and physical exercise energy expenditure is not very strong because women can compensate by increasing their energy intake. The aim of this study was to investigate the relationship between total minutes of exercise per week, dietary habits and body composition in female university students using physical activity and the habit to cook as covariates. METHODS: Fifty-one female university students were investigated for body composition, dietary habits, aerobic fitness, physical activity and physical exercise practice. Participants were grouped in three sub-samples (1, 2 and 3) according to the 33rd and 66th percentiles of weekly minutes (min/wk) of training. RESULTS: Group 1 had 0.00 min/wk, group 2 had 95±35.59 min/wk and group 3 had 231.66±85.97 min/wk of training. Sub-samples did not differ for IPAQ parameters while differed for aerobic fitness (P=0.001). Group 3 had a higher energy intake (EI) (P=0.008), a higher intake of lipids (P=0.017), saturated (P=0.042) and monounsaturated fat (P=0.024) and a lower intake of carbohydrates (P=0.007). Group 3 maintained the higher EI and the worse composition of lipid intake considering the habit to cook as covariate. Group 3 also had higher muscle mass. CONCLUSION: In order to positively affect body composition, in the sedentary women it is enough to control the energy balance, whereas in those that trained regularly it is necessary to control both energy balance and composition of daily meals.

Effects of the time of day of walking on dietary behaviour, body composition and aerobic fitness in post-menopausal women.

AIM: Post-menopause is linked to an increased risk of death from cardiovascular disease. Physical exercise and healthy dietary habits are normally suggested to enhance health. The aim of this study was to verify whether the time of day of walking had different effects on both spontaneous dietary intake and body composition modification in overweight and sedentary post-menopausal women. METHODS: Forty-two sedentary post-menopausal women (53.46+/-3.32 yrs) were recruited. Thirty-three completed the study: 29 were suitable for statistical analysis. Of those, 14 walked in the morning (MG) and 15 in the early evening (EG). Body composition, dietary habits and predicted VO2max were investigated. Food intake was analysed for energy, macronutrients and daily distribution. RESULTS: The Mann-Whitney test showed that according to the time of day of walking there were different fat mass (FM) reductions and dietary behaviour responses. EG reduced FM greater than MG and showed a major increase in morning energy intake (EI). Sub-samples did not differ in total EI, daily macronutrient portioning and daily meals variations. The variation of FM was correlated with that of proteins (r=-0.352), morning EI (r=-0.367) and aerobic performance (r=0.369). Both MG and EG improved their aerobic performance. CONCLUSION: The positive effects of walking on health could be optimised by its evening execution because it could also be linked to spontaneous dietary habit modification.

[Clinical study of the imaging validity in detecting infiltration of the mesenteric-portal axis in pancreatic carcinoma]. / Studio clinico sulla validità dell'"imaging" nel riconoscere l'infiltrazione dell'asse mesenterico-portale nei carcinomi pancreatici.

The authors examine the value of different imaging techniques (CT, MRI) in the diagnosis of the involvement of the mesenteric-portal vessels in the pancreatic cancer. In 20 jaundiced patients they obtained in all cases a correct diagnosis about the etiology of the jaundice. The correspondence of the preoperative imaging study with the involvement of the mesenteric-portal vessels was respectively 73% for the CT and 78% for the MRI. In all cases the intra-operative echography allowed a correct diagnosis of the vascular involvement.

Leucine zipper domain of 52 kDa SS-A/Ro promotes protein dimer formation and inhibits in vitro transcription activity.

Two forms of the human 52 kDa SS-A/Ro protein autoantigen, 52alpha and 52beta, are products of alternative mRNA splicing. The 52alpha form is ubiquitously expressed whereas 52beta, lacking the central leucine zipper domain, has been detected at higher levels than 52alpha during certain stages of fetal development. Because 52alpha has sequence similarity with macromolecules associated with transcriptional regulation and the two forms differ only in that 52beta does not contain the leucine zipper, their roles in protein dimer formation and in transcriptional activity were examined. Employing the yeast two-hybrid system, 52alpha was shown to interact with itself but not 52beta. The homodimerization of 52alpha was independently confirmed in gel filtration chromatography using in vitro cDNA template derived translation products and in HL-60 cell extracts; two peaks were observed corresponding to dimer and monomer of 52alpha, while in vitro the translation product of 52beta exhibited only a single monomer peak. In addition, dimer formation was also demonstrated in a chemical cross-linking experiment using HeLa cells transfected with 52alpha. To evaluate effects on transcription, eukaryotic expression plasmids encoding 52alpha or 52beta fused with the GAL4 DNA binding (DB) domain were co-transfected into 293 cells together with a luciferase reporter vector. A 6-fold increase in transcription activity of the reporter was detected with the GAL4-DB-52beta fusion constructs compared to GAL4-DB-52alpha or the empty vector control. We speculate that the ratio of cellular 52alpha and 52beta may play an important role in regulating gene expression as potential repressor and activator respectively.

Interaction between 52 kDa SSA/Ro and deubiquitinating enzyme UnpEL: a clue to function.

The detection of isolated heart block in utero strongly predicts the presence of maternal autoantibodies reactive with 52 kDa SSA/Ro. The mechanisms that underlie this observation may be elucidated by defining the function of the target antigen. The initial approach was to identify proteins interactive with 52Ro using transcriptional activity in the yeast 2-hybrid system. A cDNA library was constructed using RNA isolated from human fetal hearts (12-23 weeks) and cloned into the HybriZAP vector encoding the activation domain of GAL4(AD) as target. Approximately 7 x 10(6) cDNAs were cotransformed with the bait into YRG-2. Plasmids from five interactive colonies were sequenced and three identified as the specific human deubiquitinating enzyme, UnpEL. UnpEL did not interact with bait plasmid encoding 52 beta, an alternative leucine zipper-minus form of 52 kDa SSA/Ro which is maximally expressed in fetal life. The mammalian 2-hybrid assay confirmed the interaction between full-length 52Ro and UnpEL. Further support for a biologic interaction was the marked redistribution in cellular localization of UnpEL following cotransfection of the two proteins into cultured human cardiocytes, human renal carcinoma cells (293 cells), and monkey kidney fibroblasts (COS-1). In conclusion, the interaction of full-length 52Ro and UnpEL implies that the former may also be involved in the ubiquitin pathway, an observation of particular interest since 52Ro contains a RING finger domain, a motif common to several recently reported proteins involved in modulating ubiquitination. The absence of an interaction with 52 beta raises the consideration that regulation of protein ubiquitination might differ in fetal life.

[Study of the possibility of an effect of biliary disease on the occurrence of chronic pancreatitis]. / Studio sulla possibilità di una influenza della patologia biliare nell'insorgenza di una pancreatite cronica.

The authors report a series of patients suffering from chronic pancreatitis and underline the high frequency of biliary pathology in these subjects. The authors remind, then a research performed, some years ago, by one of them. In such a research the performing of an anastomosis between the pancreatic duct and the biliary common duct in a series of experimental animals caused an acute pancreatitis or in the surviving animals a chronic pancreatitis. The authors believe that a biliary pathology may be responsible not only of an acute pancreatitis but also of a chronic pancreatitis.

Anti-SSA/Ro and anti-SSB/La autoantibodies bind the surface of apoptotic fetal cardiocytes and promote secretion of TNF-alpha by macrophages.

Despite the near universal association of congenital heart block and maternal Abs to SSA/Ro and SSB/La, the intracellular location of these Ags has made it difficult to substantiate their involvement in pathogenicity. To define whether components of the SSA/Ro-SSB/La complex, which translocate during apoptosis, are indeed accessible to extracellular Abs, two approaches were taken: immunoprecipitation of surface biotinylated proteins and scanning electron microscopy. Human fetal cardiocytes from 16-24-wk abortuses were cultured and incubated with staurosporine to induce apoptosis. Surface biotinylated 48-kDa SSB/La was reproducibly immunoprecipitated from apoptotic, but not nonapoptotic cardiocytes. Surface expression of SSA/Ro and SSB/La was further substantiated by scanning electron microscopy. Gold particles (following incubation with gold-labeled sera containing various specificities of anti-SSA/Ro-SSB/La Abs and murine mAb to SSB/La and 60-kDa SSA/Ro) were consistently observed on early and late apoptotic cardiocytes. No particles were seen after incubation with control antisera. To evaluate whether opsonized apoptotic cardiocytes promote inflammation, cells were cocultured with macrophages. Compared with nonapoptotic cardiocytes or apoptotic cardiocytes incubated with normal sera, apoptotic cardiocytes preincubated with affinity-purified Abs to SSB/La, 52-kDa SSA/Ro, or 60-kDa SSA/Ro increased the secretion of TNF-alpha from cocultured macrophages. In summary, apoptosis results in surface accessibility of all SSA/Ro-SSB/La Ags for recognition by circulating maternal Abs. It is speculated that in vivo such opsonized apoptotic cardiocytes promote an inflammatory response by resident macrophages with damage to surrounding conducting tissue.

mRNA and protein expression of SSA/Ro and SSB/La in human fetal cardiac myocytes cultured using a novel application of the Langendorff procedure.

Irreversible congenital heart block (CHB) and the transient rash of neonatal lupus are strongly associated with maternal antibodies to SSA/Ro and SSB/La proteins; however, the precise mechanism by which these antibodies mediate organ-specific injury is not yet defined. Culturing of keratinocytes has provided critical insights. Accordingly, successful culturing of human fetal cardiac myocytes at high yield would constitute a powerful tool to directly examine conditions that promote expression of the target autoantigens. To accomplish this aim, fetal cardiac myocytes from 18- to 22-wk abortuses were established in culture using a novel technique in which cells were isolated after perfusion of the aorta with collagenase in a Langendorff apparatus. After preplating to decrease fibroblast contamination, cardiocytes were grown in flasks and slide chambers. Staining with monoclonal anti-sarcomeric alpha-actinin revealed the expected striations typical of cardiac myocytes in 70-90% of the cells after 4 d in culture. Furthermore, the cells were observed to beat at rates varying between 25-75 beats per minute (bpm) after the addition of 1.8 mM CaCl2. An average yield of 45-60 x 10(6) cells was obtained from a 3- to 5-g heart. Cellular localization of SSA/Ro and SSB/La by indirect immunofluorescence and demonstration of mRNA expression by reverse transcriptase polymerase chain reaction supports the feasibility of cultured cardiac myocytes for the study of congenital heart block. In contrast to the increased expression of SSA/Ro reported for keratinocytes, incubation of cultured human cardiac myocytes with either 17beta-estradiol or progesterone did not alter mRNA expression or cellular localization of 48 kD SSB/La, 52 kD SSA/Ro, or 60 kD SSA/Ro. In summary, we describe a novel method to successfully culture human fetal cardiac myocytes that should provide a valuable resource for investigation of the molecular mechanism(s) contributing to the development of congenital heart block. Differential constitutive and estradiol-induced expression of 52 and 60 kD SSA/Ro in human cardiac myocytes compared with keratinocytes may be a factor contributing to the marked discordance of clinically detectable injury in these two target tissues.

Accessibility of SSA/Ro and SSB/La antigens to maternal autoantibodies in apoptotic human fetal cardiac myocytes.

Access of intracellular Ags SSA/Ro and SSB/La to cognate maternal autoantibodies is unexplained despite their strong association with congenital heart block. To investigate the hypothesis that apoptosis facilitates surface accessibility of these Ags, human fetal cardiac myocytes from 16- to 22-wk abortuses were established in culture using a novel technique in which cells were isolated after perfusing the aorta with collagenase. Confirmation of cardiac myocytes included positive staining with antisarcomeric alpha-actinin and contractility induced by 1.8 mM calcium. Incubation with 0.5 microM staurosporine or 0.3 mM 2,3-dimethoxy-1,4-naphthoquinone induced the characteristic morphologic and biochemical changes of apoptosis. The cellular topology of Ro and La was evaluated with confocal microscopy and determined in nonapoptotic and apoptotic cardiocytes by indirect immunofluorescence. In permeabilized nonapoptotic cardiocytes, Ro and La were predominantly nuclear, and propidium iodide (PI) stained the nucleus. In early apoptotic cardiocytes, condensation of the PI- and Ro- or La-stained nucleus was observed, accompanied by Ro/La fluorescence around the cell periphery. In later stages of apoptosis, nuclear Ro and La staining became weaker, and PI demonstrated nuclear fragmentation. Ro/La-stained blebs emerged from the cell membrane, a finding observed in nonpermeabilized cells, supporting an Ab-Ag interaction at the cell surface. In summary, induction of apoptosis in cultured cardiocytes results in surface translocation of Ro/La and recognition by Abs. Although apoptotic cells are programmed to die and do not characteristically evoke inflammation, binding of maternal Abs and subsequent influx of leukocytes could damage surrounding healthy fetal cardiocytes.

The 52-kd protein as a target of intermolecular spreading of the immune response to components of the SS-A/Ro-SS-B/La complex.

OBJECTIVE: To determine whether immunization of healthy non-autoimmune mice with 52-kd SS-A/Ro induces a secondary antibody response to other components of the 48-kd SS-B/La-60-kd SS-A/Ro RNP complex and vice versa, since anti-52-kd antibodies have been invariably linked to these antigens in patients with Sjogren's syndrome and in mothers whose children have neonatal lupus. METHODS: Female BALB/c mice were immunized with 100 microg of 6xHis recombinant human 48-kd SS-B/La, 52-kd SS-A/Ro, or 60-kd SS-A/Ro proteins, or the 6xHis polypeptide control, each purified by Ni2+ affinity chromatography. Mice subsequently received booster injections with 50 microg of the same antigen every 10-21 days. Immune responses were measured by enzyme-linked immunosorbent assay (ELISA), immunoblotting of recombinant antigens, and immunoprecipitation of 35S-methionine-labeled in vitro translation products. RESULTS: Immunization with 48-kd SS-B/La resulted in anti-48-kd SS-B/La antibodies within 45 days, followed 10 days later by a secondary response to 52-kd SS-A/Ro, as measured by ELISA. Antibody spreading to 60-kd SS-A/Ro was not detected. Immunization with 52-kd SS-A/Ro resulted in rapid high-titer anti-52-kd SS-A/Ro responses within 27 days. Spreading to 48-kd SS-B/La occurred in only 1 mouse and 60-kd SS-A/Ro was detected in a minority of the mice after prolonged antigen exposure. Immunization with 60-kd SS-A/Ro led to anti-60-kd SS-A/Ro responses within 37 days, followed 3 months later by low-titer anti-48-kd SS-B/La and anti-52-kd SS-A/Ro antibodies. All primary immune responses were confirmed by immunoblotting and immunoprecipitation. While immunoblotting of the recombinant proteins revealed reciprocal intermolecular spreading in the majority of mice, immunoprecipitation clearly demonstrated that predominant spreading was generated after immunization with 48-kd SS-B/La, which consistently resulted in antibodies to 52-kd SS-A/Ro. CONCLUSION: The murine responses observed in the present study, demonstrating reciprocal intermolecular spreading to 48-kd SS-B/La, 52-kd SS-A/Ro, and 60-kd SS-A/Ro, support the linkage of 52-kd SS-A/Ro with the other proteins, despite their as-yet-undetected association in vivo. The marked recruitment of anti-52-kd SS-A/Ro responses elicited by 48-kd SS-B/La may provide a lead to exploring the physical interaction, direct or indirect, of 52-kd SS-A/Ro with the SS-A/Ro-SS-B/La RNP particle and its presentation to the immune system. These data should facilitate the establishment of a murine model of neonatal lupus.

Cardiac expression of 52beta, an alternative transcript of the congenital heart block-associated 52-kd SS-A/Ro autoantigen, is maximal during fetal development.

OBJECTIVE: Congenital heart block (CHB), associated with antibodies to SS-A/Ro and SS-B/La, is most often detected between 18 and 24 weeks of gestation, yet the maternal heart is unaffected. We recently described an alternatively spliced 52-kd SS-A/Ro messenger RNA (mRNA) derived from the skipping of exon 4 which encodes a smaller protein, 52beta (MW 45 kd), recognized by CHB maternal antisera. This study was designed to identify whether cardiac expression of 52beta and full-length 52alpha relates to the development of CHB. METHODS: Reverse transcriptase-polymerase chain reaction was performed using primers flanking exon 4 and mRNA from 22 human fetal hearts (age 11-25 weeks) and 3 adult hearts. The brain, kidney, liver, lung, and spleen were similarly evaluated in a 15-week, an 18-week, and a 24-week fetus. RESULTS: Expression of 52beta was greatest and 52alpha lowest between 14 and 16 weeks of gestation. In fetal hearts ages 22-25 weeks and adult heart, the 52beta transcript was markedly diminished and 52alpha clearly dominated. The 52beta mRNA was observed in a 15-week brain, kidney, lung, and spleen; however, its expression relative to 52alpha was greatest in the heart. CONCLUSION: Since expression of the alternative product 52beta is maximal at the time of cardiac ontogeny when maternal antibodies gain access to the fetal circulation, just prior to the clinical detection of bradyarrhythmia, a role for 52beta in the development of CHB is implicated. Although other fetal tissues express 52beta, there may be differences in accessibility of antigen or regenerative capacities.

Stability of immunoblot profile of anti-SSA/Ro-SSB/La antibodies over time in mothers whose children have neonatal lupus.

Neonatal lupus is strongly associated with antibodies reactive with SSA/Ro-SSB/La proteins, independent of maternal disease activity or classification. We sought to determine whether the fine specificity of antibody profiles remains stable or evolves over time and whether these findings relate to clinical status. Sera from 23 mothers whose children had neonatal lupus (22 heart block, one skin) were evaluated by SDS-immunoblot. For each mother two samples were available at least 13 months apart; the mean duration of time between testing was 45 months +/- 27 S.D. (range 13-108 months). Twenty-two of the 23 initial profiles were identical to the results obtained in a later sample. The health status of seven (30%) of 23 mothers changed after the birth of the affected infant but the immunoblot specificity of the antibodies remained unchanged. SLE was the initial and final diagnosis in the only mother whose profiles differed, with development of weak reactivity to 48 kD SSB/La in addition to the 52kD SSA/Ro after 14 months. In conclusion, the fine specificity of anti-SSA/Ro-SSB/La antibodies as assessed by immunoblot is highly stable for years. Progression of clinical status was not associated with a concomitant change in antibody profile.

52-kD SS-A/Ro: genomic structure and identification of an alternatively spliced transcript encoding a novel leucine zipper-minus autoantigen expressed in fetal and adult heart.

The 52-kD SS-A/Ro protein is one of the antigenic targets strongly associated with the autoimmune response in mothers whose children have manifestations of neonatal lupus. In addition to the cDNA clone we previously reported for the full-length 52-kD SS-A/Ro protein, an interesting MOLT-4 cDNA clone, p52-2, was found to have an internal deletion of 231 nucleotides including the domain encoding the leucine zipper motif. To further investigate the nature of this deletion, genomic DNA clones were isolated from a lambda FIXII library. The complete gene for the full-length 52-kD protein (alpha form, 52 alpha) spans 10 kb of DNA and is composed of seven exons. Exon 1 contains only the 5' untranslated sequence, while the translation initiation codon is located 3 kb downstream in exon 2, which also encodes the three zinc finger motifs. Exon 4 encodes amino acids 168-245, including the coiled coil/leucine zipper domain. Exon 7 is the longest and encodes the rfp-like domain and the 3' untranslated region. The cDNA p52-2 can now be accounted for as a product of alternative messenger RNA (mRNA) derived from the splicing of exon 3 to exon 5, skipping exon 4, which results in a smaller protein (52 beta) with a predicted molecular weight of 45,000. An initial approach to identifying this alternatively spliced form in the human heart used a ribonuclease protection assay. Using an RNA probe corresponding to bases 674-964 of the full-length cDNA, two protected mRNA fragments were identified, a 290-bp fragment corresponding to expression of 52 alpha and a smaller fragment of 144 bp, the predicted size of 52 beta. Using reverse transcription followed by polymerase chain reaction, cDNAs from a 16-wk fetal heart, 24-wk heart, and adult heart were amplified with primers flanking exon 4. Two polymerase chain reaction products were observed in each tissue, one 1.0 kb likely representing 52 alpha and a second 0.78 kb, consistent with 52 beta. The 0.78-kb fragment identified in the 16-wk heart was cloned, and DNA sequencing confirmed the 52 beta type. Immunoprecipitation of in vitro-translated 35S-labeled 52 beta form was performed to evaluate the antigenicity of this novel form of 52-kD SS-A/Ro. 26 (87%) of 30 sera tested from mothers whose children were known to have neonatal lupus immunoprecipitated the 52 beta form.(ABSTRACT TRUNCATED AT 400 WORDS)

Increasing incidence of childhood celiac disease in Sicily: results of a multicenter study.

By screening the patient list of four Sicilian centers of gastroenterology and those with gluten-free product consumption, 1074 patients (607 females and 467 males) with celiac disease, diagnosed between 1975 and 1989, were identified. A maximum cumulative incidence rate by birth cohort was reached in 1986 (1.65/1000). When the incidence rate was adjusted for the years of follow-up, the actual standardized rate was 3 cases per 1000 live births. Growth failure and chronic diarrhea were the most common symptoms, but a diminishing trend for chronic diarrhea was observed when symptoms were distributed by year of diagnosis. Even though 61.1% of all cases were diagnosed within six months from the onset of symptoms, mean age at diagnosis showed an increasing trend, from less than two years to approximately four years of age. The results of our study showed an increasing incidence of celiac disease due to diagnosis of less typical cases at an older age and also to a steady increase in the rate of diagnosis of cases with a classic clinical picture.

Pulsatile growth pattern during catch-up growth in childhood coeliac disease.

Catch-up growth in coeliac disease was thought to be a continuous process and hence linear models have been proposed to interpret the pattern of catch-up growth. Observed longitudinal data do not fit a linear model adequately. The aim of this study is to clarify the pattern of short-term catch-up growth in coeliac patients. Twenty-one coeliac children (aged 6-24 months) entered the study and were monitored at short-time intervals. All showed a "pulsatile" pattern of growth velocity for height, weight, leg length, subscapular and triceps skinfolds. Peaks alternated with troughs at a mean time of 62 days for the whole set of measurements. The periodicity was remarkably stable. The size of the peaks decreased with time on a gluten-free diet. Catch-up growth is a discontinuous process made up of a sequence of bursts of growth followed by a resting phase. This provides strong evidence for the possibility that short-term growth may be pulsatile.

[Anti-platelet-aggregation drugs and atherosclerosis]. / Antiaggreganti piastrinici ed aterosclerosi.

The relationship between hyperlipidaemia and thrombophilic state in atherosclerosis was appraised by evaluation of platelet aggregation according to Breddin in 20 patients with clinically established atherosclerosis, 10 normal controls, and 22 subjects taken from the average population of a medical department aged 12-58 yr with no history of atherosclerosis. Normal screening for the disease was carried out in all patients. Drugs inhibiting platelet-aggregation were given to all subjects in Breddin's 3rd or 4th stage. A relationship was noted between Breddin stage and the seriousness of atherosclerosis, while the former was a pointer to thrombophilic states. The drugs administered were able to reverse the aggregation stage.