Association of raised titres of antibodies to Chlamydia pneumoniae with a history of pre-eclampsia

OBJECTIVE: To establish the prevalence of Chlamydia pneumoniae (C. pneumoniae) infection in a pregnant UK population and to investigate whether C. pneumoniae infection is more common in women with a previous history of pre-eclampsia. DESIGN: Prospective study. SETTING: Academic Hospital. POPULATION: Ninety-one pregnant women (54 parous and 37 nulliparous) at 16-22 weeks of gestation were studied. Of the parous women, 32 had a previous history of pre-eclampsia. METHODS: Peripheral blood was drawn for C. pneumoniae antibodies between 16-22 and 28-40 weeks of gestation. C. pneumoniae antibodies were measured using a solid-phase enzyme immunoassay. According to pregnancy outcome, women were categorised into normal, gestational hypertension and pre-eclampsia groups. MAIN OUTCOME MEASURES: Serum levels of IgG, IgA and IgM C. pneumoniae antibodies. RESULTS: Prevalence of seropositivity to C. pneumoniae was 77%. Parous women had significantly higher levels of IgA and IgM C. pneumoniae antibodies than nulliparous women (P < 0.04). Parous women with previous pre-eclampsia were found to have higher levels of antibodies than parous women with a normal obstetric history (P< or = 0.003). There was no difference in the antibody levels in women with different pregnancy outcomes. CONCLUSIONS: The longitudinal data do not indicate an association between C. pneumoniae infection and pre-eclampsia. However, the subgroup analysis of parous women demonstrated raised C. pneumoniae antibodies in the women with previous pre-eclampsia, and therefore suggests that there may be an association between C. pneumoniae and the disease in this group.     

Risk factors and stroke subtypes: results of five consecutive years of the Perugia Stroke Registry

To understand the etiopathogenetic mechanisms of stroke and to target prevention, we need to know how risk factors differ among etiological subtypes. Our aims were to determine the different profile of risk factors for ischemic and hemorrhagic stroke subtypes in our cohort from the Perugia Hospital-Based Stroke Registry. We analyzed the characteristics and the different risk factors of 2,395 first-ever consecutive stroke patients admitted to the Perugia Hospitals in the period between January 1, 1998 and December 31, 2002. The prevalence of cerebrovascular risk factors in each stroke subtype was analyzed independently and compared with other subtypes of stroke pooled together by means of univariate analysis and logistic regression models. Hypertension occurred in 61% of patients; familial history of stroke in 41.6%; vascular disease in 27.2%; embolic heart disease in 22.3%; cigarette smoking in 21.6%. Different potentially modifiable risk factors profiles were identified for each ischemic subtype of stroke, while in hemorrhagic lobar stroke subtypes, only male gender was an independent risk factor.     

Efficacy of thrombolytic (rt-PA) therapy in old stroke patients: the Perugia Stroke Unit experience

The use of intravenous recombinant tissue plasminogen activator (rt-PA) administered within 3 hrs from symptom onset is beneficial in selected patients independent of age; although oldest patients (> or = 80 years) are excluded a priori. We report an experience relative to rt-PA treatment in the oldest patients including outcome at 3 months. Data were from the hospital-based Perugia Stroke Registry. Seventy-two consecutive acute stroke patients, fulfilling NINDS and EUSI-criteria were treated with rt-PA of these 23 patients (30.5%) were > or = 80 years. The median and mean age were, respectively, 72.5 and 71.1 +/- 12.7 years (range 35-94). The proportion of favorable outcome at 3-months did not differ between groups (55% elderly versus 51.1% of younger patients). Proportions of unfavorable outcome and death from baseline were similar in both groups of patients. Age did not influence prognosis in patients treated with rt-PA. The oldest stroke patients should not be excluded from rt-PA treatment on the basis of age per se.     

Folate supplementation during pregnancy improves offspring cardiovascular dysfunction induced by protein restriction

Dietary protein restriction in the rat compromises the maternal cardiovascular adaptations to pregnancy and leads to raised blood pressure and endothelial dysfunction in the offspring. In this study we have hypothesized that dietary folate supplementation of the low-protein diet will improve maternal vascular function and also restore offspring cardiovascular function. Pregnant Wistar rats were fed either a control (18% casein) or protein-restricted (9% casein) diet +/-5 mg/kg folate supplement. Function of isolated maternal uterine artery and small mesenteric arteries from adult male offspring was assessed, systolic blood pressure recorded, and offspring thoracic aorta levels of endothelial nitric oxide (NO) synthase mRNA measured. In the uterine artery of late pregnancy dams, vasodilatation to vascular endothelial growth factor was attenuated in the protein-restricted group but restored with folate supplementation, as was isoprenaline-induced vasodilatation (P<0.05). In male offspring, protein restriction during pregnancy led to raised systolic blood pressure (P<0.01), impaired acetylcholine-induced vasodilatation (P<0.01), and reduced levels of endothelial NO synthase mRNA (P<0.05). Maternal folate supplementation during pregnancy prevented this elevated systolic blood pressure associated with a protein restriction diet. With folate supplementation, endothelium-dependent vasodilatation and endothelial NO synthase mRNA levels were not significantly different from either the control or protein-restricted groups. Maternal folate supplementation of the control diet had no effect on blood pressure or vasodilatation. This study supports the hypothesis that folate status in pregnancy can influence fetal development and, thus, the risks of cardiovascular disease in the next generation. The concept of developmental origins of adult disease focuses predominately on fetal life but must also include a role for maternal cardiovascular function.     

Influences of maternal nutritional status on vascular function in the offspring

Fetal growth restriction leading to low birthweight is associated with increased risk of ischaemic heart disease and hypertension in later life. Increasingly, it is recognised that cardiovascular risk may also be initiated in early life when the fetus and neonate are exposed to maternal nutritional excess. This review summarises the studies in man and animals that have investigated the potential role of vascular disorders in the aetiology of atherosclerosis and hypertension arising from early life nutritional deprivation or excess. Malfunction of the arterial endothelial cell layer in the offspring has been frequently described in association with both maternal under and overnutritional states and may play a permissive role in the origin of these disorders. Also prevalent is evidence for increased stiffness of the large arteries which may contribute to systolic hypertension. Further investigation is required into the intriguing suggestion that early life nutritional imbalance may adversely influence vascular angiogenesis leading to rarefaction and increased peripheral vascular resistance.     

Effect of normalization of fasting glucose by intensified insulin therapy and influence of eNOS polymorphisms on the incidence of restenosis after peripheral angioplasty in patients with type 2 diabetes: a randomized, open-label clinical trial

Primary objective was to evaluate whether an intensified insulin therapy (IIT) incorporating the target of normal fasting glucose and HbA1c levels could halve the incidence of restenosis/amputation/SCA/death at 6 months after peripheral angioplasty compared with standard care (SC) in patients with type 2 diabetes (DMT2) affected by critical limb ischemia (CLI). Forty-six consecutive patients with DMT2 and CLI were randomly assigned to a parallel, open-label study with IIT (basal-bolus glulisine + glargine administrations) or SC (glargine administration + oral antidiabetic drugs). A SNP of eNOS (rs753482-A>C) and circulating CD34⁺ and CD34⁺KDR⁺ progenitor cells were determined. At the end of the study, although HbA1c levels were lower in IIT than in SC (6.9 ± 1.3 % vs. 7.6 ± 1.2 %, p < 0.05), IIT did not reduce the cumulative incidence of restenosis/amputation/SCA/death (52 and 65 %, respectively, odd ratio 0.59; CI 95 %: 0.21–1.62, p = 0.59). rs753482AC+CC as compared with rs753482AA increased the cumulative incidence of restenosis/amputation/SCA/death (79 and 42 %; odd ratio 5.3; CI 95 %: 1.41–19.5, p < 0.02). Baseline CD34⁺KDR⁺ were higher in rs753482AA (166.2 ± 154.0 × 10⁶ events) than in rs753482AC+CC (63.1 ± 26.9 × 10⁶ events, p < 0.01). At the end of the study, the highest circulating CD34⁺KDR⁺ were found in IIT rs753482AA (246.9 ± 194.0 × 10⁶ events) while the lowest levels were found in SC rs753482AC+CC (70.9 ± 45.0 × 10⁶ events). IIT did not decrease the cumulative incidence of restenosis/amputation/SCA/death in DMT2 and CLI patients. These patients correspond to a class of fragile subjects at high risk of cardiovascular events, and new predictors of restenosis should be contemplated, such as of eNOS polymorphism, (rs753482-A>C SNP) and circulating endothelial progenitor cells.     

Topical treatment of chronic venous ulcers with sucralfate: a placebo controlled randomized study

Venous leg ulcers are an important medical issue due to their high incidence in the elderly and the lack of a standard curative approach. Apart from surgical therapy, different medical treatments to effect ulcer wound repair and regeneration are currently being investigated. Sucralfate is a cytoprotective agent employed to prevent or treat several gastrointestinal diseases such as gastroesophageal reflux, gastritis, peptic ulcer, stress ulcer and dyspepsia. In this study we evaluated the efficacy, safety and tolerability of topical sucralfate (SUC-LIS 95) on the healing of chronic venous leg ulcers in 50 patients by a double-blind, placebo-controlled, randomized study. Our results indicated that the daily application of SUC-LIS 95 to non-infected post-phlebitis/vascular ulcers, for a median period of 42.0 days, led to complete healing in 95.6% of patients, against only 10.9% of cases with a matched placebo. A significant improvement was obtained in the SUC-LIS 95-treated patient group with regard to local tissue inflammation as well as pain and burning, and consequently, in ulcer size and the evolution of granulation tissue. Our findings were corroborated for selected patients by the morphological analysis of biopsies obtained before and after treatment. Using ultrastructural analysis we demonstrated that the topical use of SUC-LIS 95 was able to affect neoangiogenesis, increase wound contraction, promote re-epithelialization of the wound area and diminish the inflammatory reaction. Overall, our results indicated that patients with chronic venous ulcers show improvement after the use of topical sucralfate.     

Effect of nutritional restriction in early pregnancy on isolated femoral artery function in mid-gestation fetal sheep

Unbalanced maternal nutrition affects fetal endocrine and cardiovascular systems, sometimes accompanied by changes in growth, although this is usually in late gestation. We determined the effect of moderate restriction for the first half of gestation of maternal dietary protein, or of total calorific intake on isolated resistance artery function of mid-gestation fetal sheep. Welsh Mountain ewes were nutritionally restricted by 30 % of the recommended nutrient intake (globally restricted) or 30 % of the recommended protein intake (protein-restricted), compared to control ewes fed 100 % of recommended nutrient intake, for ~12 days prior to conception and for the subsequent 70 days of gestation. At mid-gestation, fetal and placental weights were similar in all dietary groups. In isolated femoral arteries, the response curve to noradrenaline was reduced in protein-restricted group fetuses (   P < 0.05  ). Maximal relaxation (   P < 0.01  ) and sensitivity (   P < 0.05  ) to acetylcholine were markedly reduced in protein-restricted group fetuses, and to a smaller extent in globally restricted group fetuses (response curve,   P < 0.05  ). The dilator response (   P < 0.05  ) and sensitivity (   P < 0.05  ) to the α₂ agonist UK14304 was lower in protein-, but not in globally restricted group fetuses. The response (   P < 0.05  ) and sensitivity (   P < 0.05  ) to the nitric oxide donor sodium nitroprusside were reduced in protein-restricted group fetuses compared to controls. Our data show that dietary imbalance, in particular restricted protein, of the ewe can produce blunting of endothelial-dependent and -independent relaxation in systemic arteries from the mid-gestation fetus. These changes may precede perturbed late-gestation fetal and postnatal cardiovascular control.