Homocysteine predicts increased NT-pro-BNP through impaired fatty acid oxidation.

BACKGROUND: The deficiency in methyl donors, folate and vitamin B12, increases homocysteine and produces myocardium hypertrophy with impaired mitochondrial fatty acid oxidation and increased BNP, through hypomethylation of peroxisome-proliferator-activated-receptor gamma co-activator-1α, in rat. This may help to understand better the elusive link previously reported between hyperhomocysteinemia and BNP, in human. We investigated therefore the influence of methyl donors on heart mitochondrial fatty acid oxidation and brain natriuretic peptide, in two contrasted populations. METHODS: Biomarkers of heart disease, of one carbon metabolism and of mitochondrial fatty acid oxidation were assessed in 1020 subjects, including patients undergoing coronarography and ambulatory elderly subjects from OASI cohort. RESULTS: Folate deficit was more frequent in the coronarography population than in the elderly ambulatory volunteers and produced a higher concentration of homocysteine (19.3 ± 6.8 vs. 15.3 ± 5.6, P<0.001). Subjects with homocysteine in the upper quartile (≥ 18 µmol/L) had higher concentrations of NT-pro-BNP (or BNP in ambulatory subjects) and of short chain-, medium chain-, and long chain-acylcarnitines, compared to those in the lower quartile (≤ 12 µmol/L), in both populations (P<0.001). Homocysteine and NT-pro-BNP were positively correlated with short chain-, medium chain-, long chain-acylcarnitines and with acylcarnitine ratios indicative of decreased mitochondrial acyldehydrogenase activities (P<0.001). In multivariate analysis, homocysteine and long chain acylcarnitines were two interacting determinants of NT-pro-BNP, in addition to left ventricular ejection fraction, body mass index, creatinine and folate. CONCLUSIONS: This study showed that homocysteine predicts increased NT-pro-BNP (or BNP) through a link with impaired mitochondrial fatty oxidation, in two contrasted populations.

A single question for the rapid screening of restless legs syndrome in the neurological clinical practice.

The purposes of this study were to validate the use of a single standard question for the rapid screening of restless legs syndrome (RLS) and to analyze the eventual effects of the presence of RLS on self-assessed daytime sleepiness, global clinical severity and cognitive functioning. We evaluated a group of 521 consecutive patients who accessed our neurology clinic for different reasons. Beside the answer to the single question and age, sex, and clinical diagnosis, the following items were collected from all patients and normal controls: the four criteria for RLS, the Epworth Sleepiness Scale (ESS), the Clinical Global Impression of Severity (CGI-S), and the Mini-Mental State evaluation. RLS was found in 112 patients (70 idiopathic). The single question had 100% sensitivity and 96.8% specificity for the diagnosis of RLS. ESS and CGI-S were significantly higher in both RLS patient groups than in normal controls. RLS severity was significantly higher in idiopathic than in associated/symptomatic RLS patients. RLS can be screened with high sensitivity and good reliability in large patient groups by means of the single question; however, the final diagnosis should always be confirmed by the diagnostic features of RLS and accompanied by a careful search for comorbid conditions.

Low total cholesterol predicts mortality in the nondemented oldest old.

Several studies have demonstrated the importance of hypercholesterolemia as a cardiovascular risk factor and a direct correlation between the reduction in cholesterolemia and the reduction in cardiovascular mortality in populations younger than 65 years. This correlation is controversial in the elderly and, particularly, in the oldest old. The aim of our study was to evaluate the total cholesterol in the oldest old and to assess the eventual presence of correlation between total cholesterol levels and mortality in a group of nondemented oldest old. A subsample of 40 subjects was extracted from the 103 subjects aged over 84 years living in Troina, a rural village in Sicily. We excluded all subjects under therapy with lipid-lowering drugs, demented, with malnutrition or affected by acute or chronic diseases which might cause death in the short term. At the end, 23 subjects (15 males and 8 females) were included in the study. After 2 years, mortality data of all subjects included in the study were obtained from official registers. The statistical analysis was performed by means of the X(2) test. In all subjects the mean of total cholesterol was of 182+/-32 mg/dl (mean+/-SD) and the body mass index was above 20; 17 subjects were in the normal range, 3 were moderately over-weighed and 3 were severely over-weighed. Overall, mortality rate after 2 years was 30% (7 subjects, 4 males and 3 females). We evaluated the relationship between mortality and 4 factors: sex, age, body mass index (BMI) and serum total cholesterol. Mortality was significantly correlated (p<0.002) only with a low level of total serum cholesterol

Colposcopy vs Hybrid Capture II assay in detection of cervical human papilloma virus infection.

PURPOSE OF INVESTIGATION: Considering the relationship between high-risk human papillomavirus types and the presence or subsequent development of cervical high-grade preinvasive lesions, the aim of the study was to determine if the Hybrid Capture II test can be used to triage women with atypical colposcopic findings. METHODS: The study was carried out on 100 patients with suspicious colposcopy findings (suggestive of human papillomavirus infection) who underwent a cervical smear for human papillomavirus testing DNA Hybrid Capture II and direct biopsies for histopathological analysis. RESULTS: Sixteen patients were negative for human papillomavirus. Of the eight patients positive for high-risk HPV type, seven presented an abnormal transformation zone grade 2 (high-grade squamous intraepithelial lesion of the cervix at histopathology). There was a significant positivity of medium-high risk virus types in the cases with more abnormal colposcopy (chi2 = 7.44; p < 0.005). Histopathological findings of high-grade squamous intraepithelial lesions were registered in the patients positive for medium-high risk human papillomavirus types (chi2 = 7.66; p < 0.025). CONCLUSIONS: Based on these results it can be concluded that if a diagnosis of a high-grade squamous intraepithelial lesion has been made on the basis of colposcopic and histopathological findings, there is a high probability that the infection was due to one or more types of human papillomavirus. There are necessary further studies to interpretate both the advantages and disadvantages of intermediate triage procedures, like Hybrid Capture II testing, compared with immediate colposcopy.

Ischemic stroke and fibrinogen in the elderly.

Senescence is accompanied by an important increase in prevalence and incidence of ischemic stroke. The plasma level of fibrinogen tends to increase with age in the elderly similarly to the prevalence of stroke. The aim of our study was to evaluate the age-related increase in fibrinogen plasma level in the elderly and to assess the presence of eventual differences between normal subjects and patients with previous ischemic stroke associated with precerebral atherosclerosis. Eighty inpatients (41 males and 39 females), consecutively admitted to our Geriatric Unit, were included to this study. The patient group was formed 32 subjects (20 males and 12 females) aged 50-79 years, suffering from cerebrovascular disease with one or several previous ischemic stroke episodes, having occurred at least 1 year earlier. The control group consisted of 48 normal subjects (21 males and 27 females) aged 50-79 years. Both control and patient groups were subdivided into three subgroups, according to their age: Group 1 (50-59 years), Group 2 (60-69 years)and Group 3 (70-79 years). The statistical comparison was carried out by means of the Mann-Whithney nonparametric test. In normal controls, a mild age effect is evident because only Group 3 shows fibrinogen levels significantly higher than those of Group 1. On the contrary, in patients with ischemic stroke, an age effect is already evident between Group 2 and Group 1; of course, also the comparison between patient Group 3 and Group I shows a statistically significant difference. Moreover, the levels of fibrinogen were significantly increased in patient Group 2 and 3 when compared to those of their respective age-matched controls. Our data are in agreement with those already available in the literature and demonstrate that fibrinogen in normal aging changes with age and shows a 19 %increase between age Group 1 and Group 3. Patients with ischemic stroke show an earlier and more evident age-related increase in fibrinogen than normal controls. Even if it is not possible to know, if the increase in fibrinogen is a consequence or not of the ischemic stroke, we can affirm that certainly the increased levels of fibrinogen should be considered as an important risk factor in the elderly for cerebrovascular disease and deserve treatment.

Association of IL-1 RN*2 allele and methionine synthase 2756 AA genotype with dementia severity of sporadic Alzheimer's disease.

BACKGROUND: Genetic polymorphisms of APO-E, homocysteine, and the IL-1 gene cluster (IL-1A, IL-1B, receptor antagonist IL-1RN) are associated with sporadic Alzheimer's disease and may involve interdependent pathways of neuronal toxicity. OBJECTIVE: To determine whether these polymorphisms and the genetic determinants of homocysteine (methylenetetrahydrofolate reductase, MTHFR; methionine synthase, MTR; transcobalamin, TC) are associated with an increased risk of severe dementia in Alzheimer's disease. METHODS: 152 patients with Alzheimer's disease and 136 controls were studied. The association of occurrence and dementia severity (Reisberg score <6 and >or=6) of Alzheimer's disease with APO-E, IL-1A, IL-1B, IL-1RN, MTHFR677 C-->T and 1298A-->C, MTR 2756 A-->G, and TC 776 C-->G polymorphisms was evaluated by multivariate logistic regression analysis after adjustment for age, sex, and age of onset of Alzheimer's disease. RESULTS: IL-1A TT and IL-1B CT/TT associated genotypes were at risk of Alzheimer's disease (odds ratio 4.80 (95% confidence interval, 1.32 to 17.40), p = 0.017); the MTR 2756 AA genotype was at risk of severe dementia (OR 2.97 (1.23 to 7.21), p = 0.016); IL-1 RN*2 was protective (OR 0.28, (0.11 to 0.69), p = 0.006). Allele epsilon4 of the APO-E and IL-1B CC genotypes increased the risk of severe Alzheimer's disease associated with the MTR 2756 AA genotype by 3.3-fold and 1.5-fold, respectively. CONCLUSIONS: Distinct determinants of the IL-1 gene cluster are related to the generation and progression of Alzheimer's disease. MTR only influences progression of the disease, which may be enhanced by carriage of allele epsilon4 of APO-E.

Biomphalaria tenagophila: genetic variability within intermediate snail hosts susceptible and resistant to Schistosoma mansoni infection.

DNA analysis by molecular techniques has significantly expanded the perspectives of the study and understanding of genetic variability in molluscs that are vectors of schistosomiasis. In the present study, the genetic variability of susceptible and resistant B. lenagophila strains to S. mansoni infection was investigated using amplification of their genomic DNA by RAPD-PCR. The products were analyzed by PAGE and stained with silver. The results showed polymorphism between tested strains with four different primers. We found two bands of 1,900 and 3,420 bp that were characteristic of the susceptible strains with primer 2. The primers 9 and 10 identified a single polymorphic band that was also characteristic of (3,136 and 5,041 bp, respectively) susceptible snails. Two polymorphic bands were detected by primer 15: one with 1,800 bp was characteristic of the resistant strain and the other with approximately equal to 1,700 bp in the susceptible one. These results provide additional evidence showing that the RAPD-PCR technique is adequate for the study of polymorphisms in intermediate hosts snails of S. mansoni. The obtained results are expected to expand the knowledge about the genetic variability of the snails and to permit the future identification of genomic sequences specifically related to the resistance/susceptibility of Biomphalaria to the larval forms of S. mansoni.

Isolated monolateral neurosensory hearing loss as a rare sign of neuroborreliosis.

Lyme disease, or borreliosis, is a zoonosis transmitted by Borrelia burgdorferi which also involves the central nervous system (CNS), in 15% of affected individuals, with the occurrence of aseptic meningitis, fluctuating meningoencephalitis, or neuropathy of cranial and peripheral nerves. Encephalopathy with white matter lesions revealed by magnetic resonance imaging (MRI) scans in late, persistent stages of Lyme disease has been described. In this report, we describe a patient with few clinical manifestations involving exclusively the eighth cranial nerve, monolaterally and diffuse bilateral alterations of the white matter, particularly in the subcortical periventricular regions at cerebral MRI. This single patient study shows that the search for antibodies against Borrelia burgdoferi should always be performed when we face a leukoencephalopathy of unknown origin. An isolated lesion of the eighth cranial nerve can be the only neurologic sign in patients with leukoencephalopathy complicating Lyme disease.

Genetic markers between Biomphalaria glabrata snails susceptible and resistant to Schistosoma mansoni infection.

The analysis of the genetic variability related to susceptibility to Schistosoma mansoni infection in the vector of the genus Biomphalaria is important in terms of a better understanding of the epidemiology of schistosomiasis itself, the possible pathological implications of this interaction in vertebrate hosts, and the formulation of new strategies and approaches for disease control. In the present study, the genetic variability of B. glabrata strains found to be resistant or susceptible to S. mansoni infection was investigated using DNA amplification by random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR). The amplification products were analyzed on 8% polyacrylamide gel and stained with silver. We selected 10 primers, since they have previously been useful to detect polymorphism among B. glabrata and/or B. tenagophila. The results showed polymorphisms with 5 primers. Polymorphic bands observed only in the susceptible strain. The RAPD-PCR methodology represents an adequate approach for the analysis of genetic polymorphisms. The understanding of the genetic polymorphisms associated to resistance may contribute to the future identification of genomic sequences related to the resistance/susceptibility of Biomphalaria to the larval forms of S. mansoni and to the development of new strategies for the control of schistosomiasis.

Genetic markers between Biomphalaria glabrata snails susceptible and resistant to Schistosoma mansoni infection

The analysis of the genetic variability related to susceptibility to Schistosoma mansoni infection in the vector of the genus Biomphalaria is important in terms of a better understanding of the epidemiology of schistosomiasis itself, the possible pathological implications of this interaction in vertebrate hosts, and the formulation of new strategies and approaches for disease control. In the present study, the genetic variability of B. glabrata strains found to be resistant or susceptible to S. mansoni infection was investigated using DNA amplification by random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR). The amplification products were analyzed on 8 percent polyacrylamide gel and stained with silver. We selected 10 primers, since they have previously been useful to detect polymorphism among B. glabrata and/or B. tenagophila. The results showed polymorphisms with 5 primers. Polymorphic bands observed only in the susceptible strain. The RAPD-PCR methodology represents an adequate approach for the analysis of genetic polymorphisms. The understanding of the genetic polymorphisms associated to resistance may contribute to the future identification of genomic sequences related to the resistance/susceptibility of Biomphalaria to the larval forms of S. mansoni and to the development of new strategies for the control of schistosomiasis

Somatosensory evoked potentials in patients affected by unilateral cerebrovascular lesions with onset during the perinatal period or adulthood.

Unilateral cerebrovascular lesions occurring during adulthood have been reported to be accompanied by high-amplitude somatosensory evoked potentials over the nonaffected hemisphere; however, the mechanisms by which somatosensory evoked potential amplitude increases over the nonaffected hemisphere are still unclear. To investigate the eventual presence of similar amplitude abnormalities in children, we recorded somatosensory evoked potentials in three groups of patients: one with unilateral cerebrovascular lesions that occurred during the perinatal period and another two with unilateral cerebrovascular lesions occurring during late adulthood or old age. Group 1 was comprised of 12 children and young adults (age range 2 3/12-31 years, 6 males and 6 females) who suffered from unilateral cerebrovascular lesion with perinatal onset. Four control groups were arranged with age matched to that of the patients. Adult patients were subdivided into two subgroups (group 2: n = 10, all males; group 3: n = 18, 12 males and 6 females) on the basis of the presence or absence of sensory impairment over the hemiplegic side. In group 1, the four youngest subjects, aged less than 6 years, were found to show somatosensory evoked potentials of abnormally high amplitude over the nonaffected hemisphere, with a "giant" main negative wave at around 45 ms (range 38.7-49.2), strictly localized over the central areas contralateral to the lesion; in normal controls, there was no such wave. All patients in group 2 were found to be affected by large infarctions in the territory of the middle cerebral artery, whereas patients in group 3 presented with subcortical lesions of the internal capsule isolated or in association with an involvement of the frontal and/or temporal cortex. Regarding somatosensory evoked potential parameters measured over the nonaffected hemisphere in adult/elderly subjects, a significant difference was observed for N20 and P22 latency, which was longer in both groups of patients than in controls. There is a significant difference in the neurophysiologic consequences of unilateral cerebrovascular lesion, as well as over the nonaffected hemisphere, if it occurs during early infancy or during adulthood. Our findings show a new type of "giant" somatosensory evoked potentials in some children affected by unilateral cerebrovascular lesion with perinatal onset.

Nail pathology in patients with hemiplegia.

BACKGROUND: It is well known that nails can be involved in some diseases of the central nervous system; however, no systematic study has been carried out in order to evaluate the incidence and the possible mechanisms of these nail changes in hemiplegia. OBJECTIVES: To study the presence of nail pathology specifically associated with hemiplegia and to evaluate its incidence and its temporal relationship with the onset of the neurological deficit. METHODS: In an open study, fingernails and toenails were examined by a dermatologist; 108 were patients with hemiplegia due to a stroke, consecutively admitted to our Department of Neurology between 1995 and 1998, and 121 were normal controls. RESULTS: Onychodystrophy of fingernails and onychomycosis of toenails were found in both patients with hemiplegia and normal controls. However, three conditions (longitudinal reddish striation, neapolitan nails and unilateral clubbing) were only observed in some patients, always affecting fingernails of the limb affected by hemiplegia. Neapolitan nails were present in three (3%) patients with hemiplegia which had its onset 3-14 months earlier. Hemiplegia had occurred approximately 40 months earlier, on average, in six patients (6%) with longitudinal reddish striation, and 60-120 months prior to unilateral clubbing in another two patients (2%). CONCLUSIONS: In this study we were able to assess the presence of three different fingernail conditions that were characteristically associated with hemiplegia (longitudinal reddish striation, neapolitan nails and unilateral clubbing), to evaluate their incidence and to study the delay with which these changes occur after a stroke.

Treadmill exercise-induced release of endothelin-1 in patients with peripheral arterial occlusive disease at Fontaine stage IIb.

BACKGROUND: Endothelin-1 (ET-1) is an endothelial vasoconstrictor mitogenic peptide which is thought to be a marker of endothelial damage and a potential participant in the pathophysiological processes of the development of atherosclerotic lesions and disease states associated with vasoconstriction and vasospasm. METHODS: To investigate the endothelin-1 release in response to dynamic exercise in patients with peripheral arterial occlusive disease (PAOD), plasma concentrations were determined by radioimmunoassay in 16 patients (14 men, 2 women, mean age 56.2 +/- 8.1 years) with peripheral arterial occlusive disease at Fontaine stage IIb and in 10 control subjects (8 men, 2 women, mean age 58.1 +/- 7.2 years) in normal health during treadmill testing (slope 5%, speed 3 km/hr). Blood samples were collected at rest from an antecubital vein, at the onset of claudication pain, and 10 minutes after exercise. RESULTS: Mean plasma endothelin-concentrations during the stress test increased significantly in the patients with arterial disease, rising from basal values of 4.4 +/- 0.6 pmol/L to values of 8.9 +/- 0.7 pmol/L at the end of the test (p < 0.0001), whereas it did not change significantly in control subjects (rising from 2.6 +/- 0.4 pmol/L to 2.7 +/- 0.5 pmol/L). Further, plasma endothelin- in the patients with arterial disease was at all times higher than in the control subjects (p < 0.0001). CONCLUSIONS: In conclusion, this study shows that in patients with peripheral arterial occlusive disease, plasma endothelin-1 increases after treadmill exercise performed until claudication pain supervenes. Raised endothelin-1 could be a marker of ischaemic acute endothelial damage and/or could contribute to increase the vascular resistance in ischaemic limbs of these patients during dynamic exercise by promoting arterial/arteriolar vasoconstriction or vasospasm.

Allopregnanolone and dehydroepiandrosterone response to corticotropin-releasing factor in patients suffering from Alzheimer's disease and vascular dementia.

OBJECTIVE: Neurosteroids have been suggested to be involved in the regulation of cognitive performances. A major neurosteroid gamma-aminobutyric acid (GABA) agonist is allopregnanolone: the main source of circulating allopregnanolone is the adrenal cortex. Studies indicated that a disturbance of the central regulation of the hypothalamic-pituitary-adrenocortical axis occurs in both senile (Alzheimer's disease: AD) and vascular dementia (VD). DESIGN: The aim of the present study was to evaluate the levels of circulating allopregnanolone, dehydroepiandrosterone (DHEA) and cortisol and their response to corticotropin-releasing factor (CRF) test in AD and VD. METHODS: Three groups of 12 subjects were included in the study: AD, VD and age-matched control subjects. CRF test was performed in all subjects and allopregnanolone, DHEA and cortisol levels were measured every 15min for 2h. RESULTS: Mean +/- s.e.m. allopregnanolone and DHEA basal levels were significantly lower in AD and VD than in controls, while cortisol levels were significantly higher than in controls (P<0.01). Allopregnanolone and DHEA levels increase in response to CRF test in all subjects but the area under curve (AUC) in patients was significantly lower than in controls (P<0.01). Cortisol secretion appeared to be very sensitive in response to CRF stimulation: in fact, cortisol response to CRF test in AD and VD subjects was higher (both as AUC and as % max increase) than in controls (P<0.01). CONCLUSIONS: The present study firstly showed that allopregnanolone levels are reduced both in AD and in VD and that dementia has a preserved stimulated response of allopregnanolone to CRF. Overall, however, the total response of allopregnanolone to CRF remains reduced in respect to controls. Further studies are necessary for a better understanding of the role of neurosteroids in the regulation of cognitive function.

Skin pathology findings in a cohort of 1500 adult and elderly subjects.

BACKGROUND: No extensive studies are available in the literature on the eventual skin pathology induced by neurologic or systemic diseases in elderly individuals. Other factors, such as health and hygiene, socioeconomic status, and climate can also play an important role. METHODS: Fifteen-hundred subjects (886 women and 614 men; mean age, 67.8 years; range, 39-90 years) were admitted to the Department of Geriatrics at the Oasi Institute between 1992 and 1997; all these subjects were carefully evaluated from a dermatologic point of view. Each subject underwent specialist examinations, routine blood analyses, thoracic X-rays, cerebral computerized tomography (CT) scan, and magnetic resonance imaging (MRI) when appropriate. A group of subjects without significant neurologic or systemic disease, comprising 116 women and 60 men (mean age, 64.5 years; range, range, 40-90 years), was selected and used as a normal control group. Subsequently, our attention was focused on the eventual presence of the following neurologic diseases: Alzheimer-type dementia, vascular dementia, mixed-type dementia, subcortical dementia, Parkinson's disease, vascular brain disease, hemiplegia, etc. Thus, different subgroups were formed on the basis of such diagnostic categories and the frequency of skin pathology in each subgroup was evaluated. RESULTS: Of the 1500 subjects, 1439 stated that they had never been affected by dermatologic disease. No statistically significant difference in frequency of skin pathology was found between normal controls and the different patient subgroups. Unsuspected and singular dermatoses were found, however, such as paraneoplastic syndromes, idiopathic tripe palms, white fibrous papulosis of the neck as an expression of photoaging, conditions induced by former popular traditions of Sicilian culture (anetoderma secondary to the application of Hirudo medicinalis and erythema ab igne), pigmented dermatoses never described before in Italy (prurigo pigmentosa and friction amyloidosis), and nail abnormalities (atypical half-and-half nail, and dyschromic nail changes in multiple system atrophy and in hemiplegia). CONCLUSIONS: The dermatologic screening performed in 1500 patients revealed several unexpected diagnoses and some original observations. Some rare dermatoses were described and certain hypotheses were suggested to explain the peculiar dyschromic changes of the fingernails in multiple system atrophy, the atypical cases of half-and-half nail, and the so-called idiopathic tripe palms associated with psoriasis.

Serum leptin concentrations in obese women with Down syndrome and Prader-Willi syndrome.

We have evaluated serum leptin concentrations in two forms of genetic obesity. The subjects examined were eight women with Down syndrome and eight women with Prader-Willi syndrome. All patients were in the reproductive age range and were obese (body mass index > or = 27 kg/m2). Plasma leptin values, analyzed as a function of body mass index showed a statistically significant correlation in both Prader-Willi (r = 0.985; p < 0.001) and Down syndrome patients (r = 0.943; p < 0.001). Obese Down syndrome women exhibited significantly lower leptin values (10.8 +/- 1.1) as compared to patients with Prader-Willi syndrome (31 +/- 2.6; p < 0.01). The linear correlation between leptin and insulin in the two groups of patients was not statistically significant. The data suggested that obesity in Prader-Willi subjects could be caused by failure of leptin to reach its target in the brain, as a consequence of defects in the receptor or in postreceptor processing, whereas data on obese patients with Down syndrome could be due to a different pathogenetic origin.