Hypertension and paroxysmal atrial fibrillation: a novel predictive role of high sensitivity C-reactive protein in cardioversion and long-term recurrence.

The role of inflammation in maintenance of paroxysmal atrial fibrillation (PAF) in patients with hypertension and no other heart disease has not been fully elucidated yet. We investigated the association of various inflammatory markers with cardioversion and recurrence of PAF in patients with hypertension. We studied 75 patients (44 male, mean age 67.9+/-9.9 years) with PAF (duration from onset of symptoms<24 h) secondary to hypertension. None had heart failure or any other ongoing inflammatory process. All patients received anticoagulation and intravenous amiodarone for cardioversion. High sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and tumour necrosis factor (TNF)-alpha were measured on admission and 48 h later. By 48 h from admission 61/75 patients (81.3%) regained sinus rhythm (cardioverted), whereas 14/75(18.7%) remained in AF (non-cardioverted). hsCRP, IL-6 and TNF-alpha serum levels on admission were similar between groups. hsCRP at 48 h was the most significant factor correlated with cardioversion outcome (OR: 0.06, 95% CI: 0.01-0.47, P=0.008). During a 1-year follow-up, AF recurred in 28/61(45.9%) patients. The strongest factor associated with AF recurrence was hsCRP at 48 h > or =2.27 mg l(-1) (hazard ratio: 6.2, 95% CI: 2.2-17.6, P=0.001). hsCRP at 48 h after admission correlates with cardioversion outcome and may predict long-term AF recurrence.

Anatomical study and colour Doppler assessment of the skin perforators of the anterior tibial artery and possible clinical applications.

BACKGROUND: Traumatic or trophic defects of the soft tissue of the lower leg are quite often very difficult to manage, especially in the distal third of the leg. Fasciocutaneous flaps are a relatively simple option for covering small- and medium-sized defects of the lower leg. The aim of this study is to investigate the distribution of septocutaneous perforators of the anterior tibial artery and their possible clinical applications. METHODS: An anatomical study was performed on 50 fresh adult cadaveric lower extremities. Using coloured contrast materials, the location of septocutaneous perforators, originating from the anterior tibial artery, were mapped. These findings were then compared with colour Doppler imaging (CDI) data in 20 living volunteers. RESULTS: The septocutaneous perforators of the anterior tibial artery follow a reproducible pattern all over the lower leg (septa I, II and III). In the distal segment, we found relatively few perforators. There was a marginal difference between cadaveric and CDI data for perforators with diameter >or=1mm. The average number of anterior tibial artery septocutaneous perforators in anatomical dissections was 6.6+/-2.4, while CDI revealed 8.2+/-3.2 perforators in living volunteers (P=0.053). In five areas of the lower leg, there is a >50% chance that a septocutaneous perforator with diameter >or=1mm is coming off the anterior tibial artery. Anatomical dissections for a cutaneous territory 5 cm above the lateral maleollus, and 10 cm in width, revealed 6.1+/-2.2 septocutaneous perforators (range 4 to 12). CONCLUSIONS: CDI, paired with knowledge of anatomical details, is a reliable tool for preoperative identification of septocutaneous perforators of 1mm or larger outer diameter, thus providing critical information for planning and harvesting safe fasciocutaneous flaps of the lower leg. Additionally, according to our anatomical study, a new transverse fasciocutaneous flap (Type B according to the Nahai-Mathes classification), located over the distal anterolateral third of the lower leg and based on perforators of the anterior tibial artery, may be successfully used for covering selected defects of the distal third of the lower leg.

Optimizing the interventional cardiology facility: services integration in routine workflow.

OBJECTIVES: Integration of administrative and clinical data, imaging, and expert services, although challenging,is a key requirement in contemporary interventional cardiology facilities (ICF). We propose a workflow-oriented hybrid system to support the ICF and investigate its feasibility and effectiveness ina referral medical center. METHODS: We have developed a Java-powered hybrid system (NetCARDIO), able to support over web synchronous and asynchronous data management, realtime multimedia data telemonitoring and continuous telementoring. Data regarding procedural rates, treatment planning and radiation exposure were collected over a two-year period of routine NetCARDIO implementation(July 2002 to June 2004) and compared with data from an immediately preceding period of equal duration (January 2000 to December 2001). RESULTS: During the NetCARDIO period, 163 +/- 17 coronary procedures per month were performed vs.77 +/- 15 during the control period (p <0.001). Percutaneous coronary intervention was delivered 'ad hoc' in 88% of eligible patients vs. 45% (p <0.001). Mean fluoroscopy time per coronary lesion treated decreased from 594 +/- 82 s to 540 +/- 94 s(p < 0.001). Annual radiation exposure of expert interventionists was decreased by 22%. Electronic storage significantly reduced archiving costs. CONCLUSIONS: Real-time multimodal services sharing combined with powerful database capabilities is feasible through a web-based structure, significantly enhancing performance and cost-effectiveness of ICF. Further research is needed to promote integration of additional data sources and services.

The predictive value of external continuous lumbar drainage, with cerebrospinal fluid outflow controlled by medium pressure valve, in normal pressure hydrocephalus.

BACKGROUND: Although sporadic studies have described temporary external cerebrospinal fluid (CSF) lumbar drainage as a highly accurate test for predicting the outcome after ventricular shunting in normal pressure hydrocephalus (NPH) patients, a more recent study reports that the positive predictive value of external lumbar drainage (ELD) is high but the negative predictive value is deceptively low. Therefore, we conducted a prospective study in order to evaluate the predictive value of a continuous ELD, with CSF outflow controlled by medium pressure valve, in NPH patients. METHOD: Twenty-seven patients with presumed NPH were admitted to our department and CSF drainage was carried out by a temporary (ELD) with CSF outflow controlled by a medium pressure valve for five days. All patients received a ventriculoperitoneal shunt using a medium pressure valve based upon preoperative clinical and radiographic criteria of NPH, regardless of ELD outcome. Clinical evaluation of gait disturbances, urinary incontinence and mental status, and radiological evaluation with brain CT was performed prior to and after ELD test, as well as three months after shunting. FINDINGS: Twenty-two patients were finally shunted and included in this study. In a three-month follow-up, using a previously validated score system, overall improvement after permanent shunting correlated well to improvement after ELD test (Spearman's rho = 0.462, p = 0.03). When considering any degree of improvement as a positive response, ELD test yielded high positive predictive values for all individual parameters (gait disturbances 94%, 95% CI 71%-100%, urinary incontinence 100%, 95% CI 66%-100%, and mental status 100%, 95% CI 66%-100%) but negative predictive values were low (< 50%) except for cognitive impairment (85%, 95% CI 55%-98%). CONCLUSION: This study suggests that a positive ELD-valve system test should be considered a reliable criterion for preoperative selection of shunt-responsive NPH patients. In case of a negative ELD-valve system test, further investigation of the presumed NPH patients with additional tests should be performed.

Quantitative evaluation of magnetic resonance imaging (MRI) abnormalities in subclinical hepatic encephalopathy.

BACKGROUND/AIMS: Cirrhotic patients often demonstrate high signal intensity on T1-weighted magnetic resonance (MRI) images in basal ganglia with accumulation of manganese being the predominant causing factor. In these patients, electrophysiological tests and especially electroencephalogram (EEG) are considered to be the most sensitive methods in detection of subclinical hepatic encephalopathy. The aim of this study is to correlate MRI findings with biochemical parameters and EEG alterations in cirrhotic patients without clinically overt encephalopathy. METHODOLOGY: Twenty-two cirrhotic patients (16 males and 6 females, mean age of 65.2 +/- 9.5 years), classified according to Child-Pugh score, were submitted to brain MRI, neurological assessment (including psychometric tests and EEG) and complete biochemical testing. None of them had any clinical signs of brain dysfunction. MRI findings were evaluated both qualitatively (normal, mild, moderate and severe) and quantitatively with the ROI method. EEG alterations were also classified as normal, mild, moderate and severe. RESULTS: Statistical analysis revealed a significant linear association between EEG grading and MRI signal intensity (r2=0.248, p=0.035). Among clinical and biochemical parameters, overall Child-Pugh score and albumin levels were identified as significant predictors of the MRI signal intensity (p=0.006 and p=0.021 respectively). CONCLUSIONS: Although further investigation must be performed to confirm the clinical impact of brain MRI in hepatic cirrhosis, our study strongly suggests that MRI alterations are good predictors of liver and brain dysfunction in cirrhotic patients.

Single high dose of local methotrexate for the management of relatively advanced ectopic pregnancies.

OBJECTIVE: To evaluate the limits of the conservative management of relatively advanced ectopic pregnancies (EPs) with local methotrexate given at a higher than standard dose. DESIGN: Nonrandomized prospective study. SETTING: A tertiary teaching hospital and an affiliated infertility center. PATIENT(S): We treated 118 EPs of up to 56 days' gestation (8 weeks) regardless of the presence of fetal heart activity, the size of the gestational mass, and the initial beta-hCG levels. INTERVENTION(S): Transvaginal intraamniotic or laparoscopic intratubal injection of 100 mg of methotrexate as a single dose. MAIN OUTCOME MEASURE(S): beta-hCG levels, red and white blood cell count, and liver function tests before and after methotrexate injection, followed by repeat transvaginal color Doppler assessments. RESULT(S): Treatment was successful in 105 (88.98%) of the 118 patients included in the study. In 7 of them with persistent fetal cardiac activity after the methotrexate injection, treatment was concluded with a complementary intracardiac injection of 10% KCl. No grade 3 or important clinical, hematologic, or biochemical toxicities occurred. CONCLUSION(S): Local administration of a single high dose of methotrexate (100 mg) proved safe and effective in the medical management of relatively advanced and unselected EPs, including cases with fetal heart activity, with high initial beta-hCG levels, and with a gestational mass beyond the standard maximum of 3.5 cm. Complementary hypertonic KCl proved to be effective in cases with persistent cardiac activity.

Evolution of the lambda or twin-chorionic peak sign in dichorionic twin pregnancies.

OBJECTIVE: To study the sonographic evolutaion of the chorionic tissue projection at the intertwin membrane-placental junction, or lambda sign, or twin-chorionic peak sign, in dichorionic twin pregnancies and to determine the effect of placental location on its prevalence during the first half of pregnancy. METHODS: We prospectively recruited women with twin pregnancies undergoing sonographic screening for chromosomal abnormalities at 10-14 weeks' gestation for this study. The presence or absence of the lambda sign and the position of the placenta(s) were recorded in all cases. The presence of the lambda sign was evaluated prospectively at 16 and 20 weeks' gestation. RESULTS: There were 101 twin pregnancies with a lambda sign identified at 10-14 weeks' gestation, 67 with fused placentas and 34 with separate placentas. At 16 weeks, the lambda sign was present in all 67 pregnancies with fused placentas (100%) and in 31 of 34 (91%) pregnancies with separate placentas. At 20 weeks, the lambda sign was present in 25 of the 34 (74%) pregnancies with separate placentas and in 62 of the 67 (93%) with fused placentas. The lambda sign was identified subsequently in none of the 53 pregnancies in which it was absent at 10-14 weeks' gestation. CONCLUSIONS: At 10-14 weeks' gestation, twin pregnancies with the lambda sign can be classified as dichorionic and pregnancies with absent lambda sign can be classified as monochorionic and therefore monozygotic. At 16-20 weeks, the lambda sign is indicative of dichorionicity but its absence does not exclude dizygosity.

Fear of falling revisited.

OBJECTIVE: To evaluate the measurement properties of an expanded version of the Falls Efficacy Scale (FES)-a measure of fear of falling. The original FES measures fear on almost exclusively indoor activities, which may limit the usefulness of the scale in identifying early stages of fear of falling in active community-dwelling older people. DESIGN: Two-group convenience sample. SETTING: An outpatient referral clinic, and community-dwelling older people recruited from various sources. SUBJECTS: A volunteer sample of 111 healthy community-dwelling elderly (mean age 74.0 years) and a sample of 68 older people referred to a Falls and Balance Clinic (FBC) (mean age 79.2). Twenty-one subjects (9 healthy elderly and 12 FBC patients) were tested twice 1 week apart to investigate retest reliability. MAIN OUTCOME MEASURES: A 14-activity questionnaire (the Modified Falls Efficacy Scale [MFES]) was used that incorporated the original 10-activity FES and four additional activities. Falls efficacy was rated on a 10-point visual analogue scale for each activity. RESULTS AND CONCLUSIONS: The MFES demonstrated high internal consistency (Cronbach's alpha.95) and less skew than the original FES (-2.4 and -3.3, respectively). Factor analysis of the MFES revealed two factors accounting for 75% of the sample variance, grouping into an "indoor type activity" factor and an "outdoor type activity" factor. Retest reliability for the MFES was high (intraclass correlation coefficients = .93). Significant differences were evident between the FBC group and the healthy older group on all items of the MFES and on the total MFES score (p < .05). On the basis of these preliminary findings, the MFES appears to be a reliable and valid measure of falls self-efficacy, and could be a useful addition in the comprehensive assessment of older people with balance disturbance or falls.

Approaching the function of new genes by detection of their potential upstream activation sequences in Saccharomyces cerevisiae: application to chromosome III.

The systematic sequencing of the yeast genome reveals the presence of many potential genes of unknown function. One way to approach their function is to define which regulatory system controls their transcription. This can also be accomplished by the detection of an upstream activation sequence (UAS). Such a detection can be done by computer, provided that the definition of a UAS includes sufficient and precise rules. We have established such rules for the UASs of the GAL4, RAP1 (RPG box), GCN4, and the HAP2/HAP3/HAP4 regulatory proteins, as well as for a motif (PAC) frequently found upstream of the genes of the RNA polymerase A and C subunits. These rules were applied to the chromosome III DNA sequence, and gave precise predictions.

Sequencing of a 35.71 kb DNA segment on the right arm of yeast chromosome XV reveals regions of similarity to chromosomes I and XIII.

In a shotgun approach we sequenced the cosmid pEOA284 containing a fragment derived from the right arm of chromosome XV of Saccharomyces cerevisiae. An analysis of the sequence revealed that it contained open reading frames (ORFs) corresponding to the known genes SLY41, SPS4, COT1, FAA1, PMT3, PRO2 and MYO2. Of the 18 unknown ORFs, five are contained totally within, and two, O6105 and O6163, partially overlap other ORFs. ORF O6116 and O6139 have putative introns. Regions of similarity with chromosomes I and XIII have been uncovered. Interestingly, most of the paired ORFs encode proteins of the same gene family. The relatedness of these ORFs suggests gene duplication.

A computer filtering method to drive out tiny genes from the yeast genome.

The authors of the first yeast chromosome sequence defined a minimum threshold requirement of 100 codons, above which an open reading frame (ORF) is retained as a putative coding sequence. However, at least 58 yeast genes shorter than 100 codons have an assigned protein function. Therefore, the yeast genome may contain other tiny but functionally important genes that are discarded from analyses by this simple filtering rule. We have established discriminant functions from the in-phase hexamer frequencies of functional genes and of simulated ORFs derived from a stationary Markov chain model. Fifty-two out of the 58 genes were recognized as coding ORFs by our discriminating method. The test was also applied to all the small ORFs (36 to 100 codons) found in the intergenic regions of published chromosomes. It retained 140 new potential tiny coding sequences, among which we identified seven new genes by similarity searches. Our method, used conjointly with similarity searches, can also highlight sequencing errors resulting from the disruption of the coding frame of longer ORFs. This method, by its ability to detect potential coding ORFs, can be a very useful tool for functional analysis.

The evaluation of morphological abnormalities of human spermatozoa in fertile and infertile men.

Spermatozoal morphology in semen from 114 fertile men, 107 infertile men with varicocele and 35 infertile men with infection of the accessory genital organs, aged from 18 to 53 years were evaluated by Papanicolaou-stained smears in order to investigate: (a) the frequency of abnormalities in the neck and tail of spermatozoa with an abnormal head and (b) the ability of prediction of the morphology of one sperm part when the morphology of another part is known. The investigation showed that: (1) morphological abnormalities in the neck are significantly higher (P < 0.001, P < 0.01), when the head was abnormal, compared to spermatozoa with a normal head in fertile men and in men with varicocele, respectively; (2) morphological abnormalities in the tail are also higher (0.05 < P < 0.1) in spermatozoa with an abnormal head in men with infection; (3) the proportional reduction of error (PRE) was low in all cases. Our results show that spermatozoa with abnormal heads more often present morphological abnormalities of their counterparts compared to spermatozoa with normal heads. Nevertheless, no prediction can be made on the nature of the morphology of a part of a spermatozoon on the basis of knowledge of its morphology of another part.

Discrimination between fortuitous and biologically constrained open reading frames in DNA sequences of Saccharomyces cerevisiae.

The systematic sequencing of the yeast genome has raised the problem of the biological significance of the open reading frames (ORFs) revealed: it is possible that some of these are fortuitous. To avoid the analysis of such fortuitous ORFs, a minimum length of 100 sense codons was adopted. Nevertheless, the presence of fortuitous ORFs of more than 100 codons cannot be excluded. Thus, in the context of functional analysis, a method for discrimination between fortuitous and biologically active ORFs may be useful. The discrimination method described here is based on multiple criteria: ORF length, codon bias, and both amino-acid and dipeptide composition of the corresponding polypeptide. The thresholds for each criterion are based on the comparison between two learning sets: one drawn from random DNA sequences and the second from known genes. The method was validated by two test sets (one random and one biological) and then applied to the ORFs of chromosomes I, II, III, V, VIII, IX and XI. This method predicts 123 fortuitous ORFs among the 1773 identified on these chromosomes.

A 29.425 kb segment on the left arm of yeast chromosome XV contains more than twice as many unknown as known open reading frames.

The nucleotide sequence of a 29.425 kb fragment localized on the left arm of chromosome XV from Saccharomyces cerevisiae has been determined. The sequence contains 13 open reading frames (ORFs) of which four encode the known genes ADH1, COQ3, MSH2 and RCF4. Predictions are made concerning the functions of the unknown ORFs. Some of the ORFs contain sequences similar to expressed sequence tags (EST) found in the database made available by TIGR. In particular, the highly expressed ADH1 gene is represented in this database by no less than 20 EST sequences. Two ARS sequences and a putative functional GCN4 motif have also been detected. One ORF (O0953) containing nine putative transmembrane segments is similar to a hypothetical membrane protein of Arabidopsis thaliana. Characteristic features of the other ORFs include ATP/GTP binding sites, a fungal Zn(2)-Cys(6) binuclear centre, an endoplasmic reticulum targeting sequence, a beta-transducin repeat signature and in two instances, good similarity to the prokaryotic lipoprotein signal peptide motif.

Automatic intron detection in nuclear DNA sequences of Saccharomyces cerevisiae.

The goal of the present work is the construction of software (EXPLORA) which automatically detects Open Reading Frames (ORF), intron-containing or not, in the nuclear sequences of the yeast Saccharomyces cerevisiae. In order to detect introns within (or preceding) ORFs, one must define precise rules of how an intron is identified. These rules are described here. The software is able to detect correctly an intron-associated ORF in at least 88% of cases. We tested all yeast nuclear entries of the EMBL database with the software, and found, in addition to the known intron-associated ORFs, some others which may include an intron. Finally the software was applied to the DNA sequences of chromosomes III and XI, in which it detected eight new intron-associated ORFs.

Hypothalamic-pituitary deficiency after Weil's syndrome: a case report.

A case of male hypogonadism after Weil's syndrome is described. Hypogonadism was the result of complete hypothalamic-pituitary deficiency. The relationship between leptospirosis and the endocrinopathy, the incidence that leptospira attacks hypothalamic-pituitary axis, and the mechanism with which the microorganism may cause damage to the pituitary and/or the hypothalamus are discussed.

Familial blepharophimosis with ovarian dysfunction.

Three cases including two sisters and one brother with blepharophimosis are described. Their father also had blepharophimosis. Moreover, the elder sister initially presented with resistant ovary syndrome and thereafter true premature menopause, while the younger one presented with resistant ovary syndrome. The explanation for the association of blepharophimosis with primary ovarian dysfunction is unknown, but the possibility of a microdeletion of genetic material containing two geographically associated, but independent genes could not be confirmed or excluded. All families affected by blepharophimosis should be counselled about the high incidence of ovarian dysfunction and female infertility, at least in one form of the syndrome.

Danazol influences gonadotropin secretion acting at the hypothalamic level.

OBJECTIVES: The purpose of the study was to determine the influence of danazol on gonadotropin secretion. METHODS: Ten endometriotic patients were treated with danazol for 6 months. To evaluate gonadotropin and estradiol secretion, a gonadotropin-releasing hormone (GnRH) test and a clomiphene citrate (CC) challenge test were carried out in the follicular phase before treatment, during the sixth month of treatment and after the reappearance of the second menses. The same tests were also performed, only once, in the follicular phase of ten normal women. RESULTS: GnRH-stimulated gonadotropin response during danazol treatment was significantly higher than that in the same group of women before and after danazol treatment, as well as in controls. Gonadotropin increase after clomiphene citrate administration during danazol treatment was not significant; moreover, LH response was significantly lower than that in the same group of patients before and after danazol treatment, as well as in controls. CONCLUSIONS: Our results suggest that danazol exerts a suppressive effect on gonadotropin secretion acting at the hypothalamic level.

Approaching the function of new genes by detection of their potential upstream activation sequences in Saccharomyces cerevisiae: application to chromosome III.

The systematic sequencing of the yeast genome reveals the presence of many potential genes of unknown function. One way to approach their function is to define which regulatory system controls their transcription. This can also be accomplished by the detection of an upstream activation sequence (UAS). Such a detection can be done by computer, provided that the definition of a UAS includes sufficient and precise rules. We have established such rules for the UASs of the GAL4, RAP1 (RPG box), GCN4, and the HAP2/HAP3/HAP4 regulatory proteins, as well as for a motif (PAC) frequently found upstream of the genes of the RNA polymerase A and C subunits. These rules were applied to the chromosome III DNA sequence, and gave precise predictions.

Linguistic analysis of chromosome III DNA sequence of Saccharomyces cerevisiae.

The analysis of the Saccharomyces cerevisiae chromosome III DNA sequence by computer ('in silico') permits the definition of its linguistic characteristics. These characteristics include the designation of non-randomly occurring oligonucleotides, their distribution along the chromosome, and the distribution of some particular homopolymers. All these elements may contribute to the understanding of the organization of information on the chromosome.