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Objective: The aim of this study was to compare cardiac output measurements of the non-invasive cardiac output and the pulmonary artery catheter during repeat surgery for hip replacement., Methods: In this prospective observational study, patients undergoing repeat hip surgery who needed a pulmonary artery catheter were included. A standard protocol was followed for induction, endotracheal intubation and maintenance of anaesthesia (sufentanil, etomidate, sevoflurane, cisatracurium). After endotracheal intubation, the non-invasive cardiac output was connected and a pulmonary artery catheter was inserted. Data were collected every 3 min until patients were extubated., Results: Ten patients were included and 2455 points of comparison recorded. Cardiac output from the pulmonary artery catheter varied from 1.7 to 8.9 L min(-1) (mean 4.1 L min(-1)) and the non-invasive cardiac output (using averaging mode) from 1.7 to 8.0 L min(-1) (mean 3.7 L min(-1)). There was a significant correlation between them (P < 0.01; bias 0.3 L min(-1); limits of agreement +1.9 and -2.5 L min(-1)), although these differed between patients., Conclusion: The perioperative bias was small and the non-invasive cardiac output slightly underestimated cardiac output intraoperatively compared to the pulmonary artery catheter. The bias was smaller when mean cardiac output was below 3 L min(-1). Core temperature between 34.4 degrees C and 37.6 degrees C had no influence on the differences.

Whey acidic protein (WAP), a major whey protein present in milk of a number of mammalian species has characteristic cysteine-rich domains known as four-disulfide cores (4-DSC). Eutherian WAP, expressed in the mammary gland throughout lactation, has two 4-DSC domains, (DI-DII) whereas marsupial WAP, expressed only during mid-late lactation, contains an additional 4-DSC (DIII), and has a DIII-D1-DII configuration. We report the expression and evolution of echidna (Tachyglossus aculeatus) and platypus (Onithorhynchus anatinus) WAP cDNAs. Predicted translation of monotreme cDNAs showed echidna WAP contains two 4-DSC domains corresponding to DIII-DII, whereas platypus WAP contains an additional domain at the C-terminus with homology to DII and has the configuration DIII-DII-DII. Both monotreme WAPs represent new WAP protein configurations. We propose models for evolution of the WAP gene in the mammalian lineage either through exon loss from an ancient ancestor or by rapid evolution via the process of exon shuffling. This evolutionary outcome may reflect differences in lactation strategy between marsupials, monotremes, and eutherians, and give insight to biological function of the gene products. WAP four-disulfide core domain 2 (WFDC2) proteins were also identified in echidna, platypus and tammar wallaby (Macropus eugenii) lactating mammary cells. WFDC2 proteins are secreted proteins not previously associated with lactation. Mammary gland expression of tammar WFDC2 during the course of lactation showed WFDC2 was elevated during pregnancy, reduced in early lactation and absent in mid-late lactation.

Plaque psoriasis is a chronic inflammatory disorder of the skin. It is inherited as a multifactorial trait, with a strong genetic component. Linkage studies have identified a large number of disease loci, but very few could be replicated in independent family sets. In this study, we present the results of a genome-wide scan carried out in 14 French extended families. Candidate regions were then tested in a second set of 32 families. Analysis of the pooled samples confirmed linkage to chromosomes 6p21 (Z(MLB) score=3.5, P=0.0002) and 20p13 (Z(MLB) score=2.9, P=0.002), although there was little contribution of the second family set to the 20p13 linkage signal. Moreover, we identified four additional loci potentially linked to psoriasis. The major histocompatibility complex region on 6p21 is a major susceptibility locus, referred to as PSORS1, which has been found in most of the studies published to date. The 20p13 locus segregates independently of PSORS1 in psoriasis families. It has previously been thought to be involved in the predisposition to psoriasis and other inflammatory disorders such as atopic dermatitis (AD) and asthma. Although psoriasis and AD rarely occur together, this reinforces the hypothesis that psoriasis is influenced by genes with general effects on inflammation and immunity.

We report clinical and molecular findings in 20 patients from 11 families with autosomal recessive congenital ichthyosis (ARCI) linked to chromosome 17p13, and attributed to mutations in the ALOX gene cluster, which includes three lipoxygenase genes, ALOXE3, ALOX12B, and ALOX15B. We identified six novel missense mutations and one novel deletion leading to a premature stop codon in ALOX12B in only six out of the 11 families which led us to investigate a possible implication of ALOX15B. Mutation analysis of this gene, as well as ALOXE3, which is known to be mutated in some cases of ARCI, failed to reveal causative mutations in the five remaining ARCI families, indicating that other genes on chromosome 17p13 may be involved in this disease. However, by adding new variants to the repertoire of ALOX12B mutations in non-bullous congenital ichthyosiform erythroderma, our data contribute to an enlargement of the spectrum of mutations for the development of efficient molecular genetic tests for analysis of at risk individuals whose carrier status is unknown.

Neutral lipid storage disease comprises a heterogeneous group of autosomal recessive disorders characterized by systemic accumulation of triglycerides in cytoplasmic droplets. Here we report a neutral lipid storage disease subgroup characterized by mild myopathy, absence of ichthyosis and mutations in both alleles of adipose triglyceride lipase (PNPLA2, also known as ATGL). Three of these mutations are predicted to lead to a truncated ATGL protein with an intact patatin domain containing the active site, but with defects in the hydrophobic domain. The block in triglyceride degradation was mimicked by short interfering RNA directed against ATGL. NLSDM is distinct from Chanarin-Dorfman syndrome, which is characterized by neutral lipid storage disease with ichthyosis, mild myopathy and hepatomegaly due to mutations in ABHD5 (also known as CGI-58).

During the excavations of the XIX century Meadowlark cemetery (Manhattan, Kansas, US), samples of sediments were taken from around five skeletons, and analyzed to detect intestinal parasites. No helminth eggs were found, but immunological ELISA tests for Entamoeba histolytica were positive in three samples. The immunological techniques have been successfully used in paleoparasitology to detect protozoan infections. Amoebiasis could have been a severe disease in the past, especially where poor sanitary conditions prevailed, and there is evidence that this cemetery may have been used in a situation where poor sanitary conditions may have prevailed. The presence of this protozoan in US during the late XIX century gives information on the health of the population and provides additional data on the parasite's evolution since its appearance in the New World.

With the decreasing cost of DNA sequencing technology and the vast diversity of biological resources, researchers increasingly face the basic challenge of annotating a larger number of expressed sequences tags (EST) from a variety of species. This typically consists of a series of repetitive tasks, which should be automated and easy to use. The results of these annotation tasks need to be stored and organized in a consistent way. All these operations should be self-installing, platform independent, easy to customize and amenable to using distributed bioinformatics resources available on the Internet. In order to address these issues, we present EST-PAC a web oriented multi-platform software package for expressed sequences tag (EST) annotation. EST-PAC provides a solution for the administration of EST and protein sequence annotations accessible through a web interface. Three aspects of EST annotation are automated: 1) searching local or remote biological databases for sequence similarities using Blast services, 2) predicting protein coding sequence from EST data and, 3) annotating predicted protein sequences with functional domain predictions. In practice, EST-PAC integrates the BLASTALL suite, EST-Scan2 and HMMER in a relational database system accessible through a simple web interface. EST-PAC also takes advantage of the relational database to allow consistent storage, powerful queries of results and, management of the annotation process. The system allows users to customize annotation strategies and provides an open-source data-management environment for research and education in bioinformatics.

The authors report a serial of 17 patients with complex trauma of the forearm treated in emergency by means of compound tissue reconstruction. Every patient present a cutaneous defect associated with multiple lesions or defects of the subjacent tissues. The management consisted of a large debridement with excision of all contuse tissues, a stable osteosynthesis witch permit an early mobilization of the hand and fingers, a revascularization of the hand by a by-pass procedure or a vascular bridge free flap, reconstruction of the muscles, tendons, and the nerves at the same time as possible, a coverage of the tissues by free flaps or forearm pedicle flaps and a physiotherapy by a specialized team undertaken immediately after surgery. The functional results have been evaluated satisfying in the whole serial. The authors conclude that the compound tissue reconstruction of the forearm in emergency with an early physiotherapy permits an optimal functional recovery within short period. It authorizes a rapid socioprofessional return of these patients with complex trauma of the forearm.

We report the identification of mutations in a non-syndromic autosomal recessive congenital ichthyosis (ARCI) in a new gene mapping within a previously identified locus on chromosome 19p12-q12, which has been defined as LI3 in the OMIM database (MIM 604777). The phenotype usually presents as lamellar ichthyosis and hyperlinearity of palms and soles. Seven homozygous mutations including five missense mutations and two deletions were identified in a new gene, FLJ39501, on chromosome 19p12 in 21 patients from 12 consanguineous families from Algeria, France, Italy and Lebanon. FLJ39501 encodes a protein which was found to be a cytochrome P450, family 4, subfamily F, polypeptide 2 homolog of the leukotriene B4-omega-hydroxylase (CYP4F2) and could catalyze the 20-hydroxylation of trioxilin A3 from the 12(R)-lipoxygenase pathway. Further oxidation of this substrate by the fatty alcohol:nicotinamide-adenine dinucleotide oxidoreductase (FAO) enzyme complex, in which one component, ALDH3A2, is known to be mutated in Sjögren-Larsson syndrome (characterized by ichthyosis and spastic paraplegia), would lead to 20-carboxy-(R)-trioxilin A3. This compound could be involved in skin hydration and would be the essential missing product in most forms of ARCI. Its chiral homolog, 20-carboxy-(S)-trioxilin A3, could be implicated in spastic paraplegia and in the maintenance of neuronal integrity.

Purpose of the Study: We report our experience with vascularized fibular transplant using the technique described by Urbaniak for the treatment of avascular necrosis of the femoral head., Material and Methods: Sixteen patients, mean age 39 years 4 months at surgery, were evaluated at mean 3 years 6 months follow-up (minimum 15 months). Mean pain score (analog visual scale) was 6.25/10. Mean Postel-Merle-d'Aubigné (PMA) function score was 12. The Ficat classification was grade 2A (n=9) or grade 2B (n=7)., Results: There were no cases of infection or migration of the fibula. The only complication at the donor site was one case of paresia of the long extensor of the hallux which resolved spontaneously. There were five failures which required a hip prosthesis (31%). Three failures occurred early during the first 18 months. Two were late. These patients had grade 2B (n=4) or grade 2A (n=1) necrosis. At last follow-up, eleven hips had not required prosthetic revision (69%). The pain score improved in 81% of patients: mean score=2.3. Nine patients were satisfied or very satisfied (81%). Among these eleven hips, function was good or excellent in eight (72%). Walking distance was improved in nine patients, unchanged in one and worse in one. Joint motion improved in nine patients, was unchanged in one and decreased in one. Nine patients resumed their full-time job. Mean sick leave was 13.3 months. Radiographically, only two of the initial Ficat grade 2A hips remained at this stage. Likewise only one of the three hips initially rated grade 2B remained at this stage. Overall radiographic results were: failure (n=5), worsening (n=9), stabilization and no improvement (n=2). Among the nine 2A hips, one was converted to a total hip prosthesis and five femoral heads remained spheric. Among the seven 2B hips, four were converted to a total hip prosthesis and two femoral heads collapsed., Discussion: At mean follow-up (3.5 years), 69% of the hips had not required total hip arthroplasty. The grade 2A hips did better but the small sample size did not allow statistical comparison. There was a clear discordance between the clinical presentation and the radiographic findings among the hips which were not treated with a prosthesis: good function score, maintained occupational and daily life activities contrasting with unfavorable radiographic evolution. Results could be improved by detailed quantification of the lesion using 3D imaging and by associating intraoperative navigation.

Introduction: Neuromyotonia is a late and rare complication of radiation therapy, consisting of involuntary sustained muscle contractions with a delay in relaxation., Observation: We report the case of a 68-year-old man who developed neuromyotonia of the masseter muscle 6 years after irradiation for tonsil carcinoma., Conclusion: This observation underlines the importance of a correct diagnosis that can lead to an efficient treatment by carbamazepine.

We report the genomic localization by homozygosity mapping and the identification of a gene for a new form of non-syndromic autosomal recessive congenital ichthyosis. The phenotype usually presents as non-bullous congenital ichthyosiform erythroderma with fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs. A few patients presented a more generalized lamellar ichthyosis. Palmoplantar keratoderma was present in all cases, whereas only 60% of the patients were born as collodion babies. Six homozygous mutations including one nonsense and five missense mutations were identified in a new gene, ichthyin, on chromosome 5q33 in 23 patients from 14 consanguineous families from Algeria, Colombia, Syria and Turkey. Ichthyin encodes a protein with several transmembrane domains which belongs to a new family of proteins of unknown function localized in the plasma membrane (PFAM: DUF803), with homologies to both transporters and G-protein coupled receptors. This family includes NIPA1, in which a mutation was recently described in a dominant form of spastic paraplegia (SPG6). We propose that ichthyin and NIPA1 are membrane receptors for ligands (trioxilins A3 and B3) from the hepoxilin pathway.

Intracellular symbiosis is widespread in the insect world where it plays an important role in evolution and adaptation. The weevil family Dryophthoridae (Curculionoidea) is of particular interest in intracellular symbiosis evolution with regard to the great economical and ecological features of these invasive insects, and the potential for comparative studies across a wide range of host plants and environments. Here, we have analyzed the intracellular symbiotic bacteria of 19 Dryophthoridae species collected worldwide, representing a wide range of plant species and tissues. All except one (Sitophilus linearis) harbor symbiotic bacteria within specialized cells (the bacteriocytes) assembled as an organ, the bacteriome. Phylogenetic analysis of the 16S rDNA gene sequence of the Dryophthoridae endosymbionts revealed three endosymbiotic clades belonging to gamma3-Proteobacteria and characterized by different GC contents and evolutionary rate. The genus name Candidatus Nardonella was proposed for the ancestral clade infesting Dryophthoridae 100 MYA and represented by five of nine bacterial genera studied. For this clade showing low GC content (40.5% GC) and high evolutionary rate (0.128 substitutions/site per 100 Myr), a single infection and subsequent cospeciation of the host and the endosymbionts was observed. In the two other insect lineage endosymbionts, with relatively high GC content (53.4% and 53.8% GC), competition with ancestral pathogenic bacteria might have occurred, leading to endosymbiont replacement in present-day last insects.

Mal de Meleda is a recessive, transgressive palmoplantar keratoderma for which we previously identified mutations in the gene encoding secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related protein-1 (SLURP-1). In this report we describe two new mutations: (i) a founder mutation, which changes a conserved cysteine residue to tyrosine (C99Y) in a large inbred Tunisian pedigree, and (ii) a signal sequence mutation (W15R), which was homozygous in a German family and heterozygous in a Scottish patient. Four ancestral haplotypes were observed in 69 patients from countries around the Mediterranean basin, and an additional haplotype was found in the German and Scottish patients.

During the 1998 field season, the Western Aleutians Archaeological and Paleobiological Project (WAAPP) team located a cave in the Near Islands, Alaska. Near the entrance of the cave, the team identified work areas and sleeping/sitting areas surrounded by cultural debris and animal bones. Human burials were found in the cave interior. In 2000, with permission from The Aleut Corporation, archaeologists revisited the site. Current research suggests three distinct occupations or uses for this cave. Aleuts buried their dead in shallow graves at the rear of the cave circa 1,200 to 800 years ago. Aleuts used the front of the cave as a temporary hunting camp as early as 390 years ago. Finally, Japanese and American military debris and graffiti reveal that the cave was visited during and after World War II. Russian trappers may have also taken shelter there 150 to 200 years ago. This is the first report of Aleut cave burials west of the Delarof Islands in the central Aleutians.

Osteoblasts are cells responsible for matrix deposition during bone development and although temporal expression of many genes has been related to osteoblast differentiation, a complete description of osteoblast-specific gene regulation will lead to a better understanding of osteoblast function. In this study, microarray technology was used to analyze gene expression on a broad scale during osteoblast differentiation. Expression analysis of 9596 sequences revealed 342 genes and expressed sequence tags (ESTs) to be modulated differentially during a time course experiment in which murine C2C12 mesenchymal progenitor cells were induced to differentiate into mature osteoblasts by treatment with bone morphogenetic protein 2 (BMP-2). By means of hierarchical clustering, these genes were grouped by similarities in their expression profiles, resulting in subsets of early, intermediate, and late response genes, which are representative of the distinct stages of osteoblast differentiation. To identify new bone markers, the bone specificity of the late response genes was determined by comparing BMP-induced expression in C2C12 and MC3T3 osteoblasts with that in NIH3T3 fibroblasts. This resulted in the identification of nine novel genes and ESTs that were induced specifically in osteoblasts, in addition to the well-known markers ALP and osteocalcin. For at least one of these novel genes, Wnt inhibitory factor 1, and two of the ESTs, expression in developing bone was verified in vivo by in situ hybridization of E16.5 mouse embryos. In conclusion, by a combination of in vitro and in vivo screening approaches, a set of new genes related to osteoblast differentiation and skeletal development has been identified.

We report the identification of mutations in lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) genes in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17. Linkage disequilibrium analysis of six families affected by NCIE permitted us to reduce a recently reported interval of 8.4 cM on chromosome 17p13.1 to a 600 kb region around the marker D17S1796, which contains LOX genes. LOX products have long been implicated in skin disorders. Two point mutations and one deletion were found in ALOXE3 and three point mutations were found in ALOX12B in these consanguineous families from the Mediterranean basin. ALOXE3 and ALOX12B are two genes which are physically linked and functionally related. They are separated by 38 kb, have one more exon than the other LOX genes and are mainly expressed in epithelial cells including keratinocytes. Although the main substrate(s) of the two enzymes is (are) still unknown, the products of ALOX12B obtained in experimental systems have been demonstrated to be of R-chirality. It seems likely that the product of one of these enzymes may be the substrate of the other, and that they belong to the same metabolic pathway.

Papillon-Lefèvre syndrome is an autosomal recessive disorder characterized by palmoplantar keratoderma, periodontitis, and premature loss of dentition. Mutations in the CTSC gene that encodes cathepsin C have been described in families affected with Papillon--Lefèvre syndrome. Cathepsin C is the least understood of the lysosomal cysteine proteases; it has been reported to participate in both intracellular and extracellular cleavage of proteins and activation of serine proteases in immune and inflammatory cells. We report here eight new mutations in Papillon-Lefèvre syndrome families: four deletions and four point mutations, including a missense mutation in the propeptide chain that could help elucidate structure-function relationships in this protein. We also found that the 458C > T mutation, first reported in two families by Hart et al (2000c), was a neutral polymorphism in our families, as suggested by Allende et al (Cathepsin C gene: first compound heterozygous patient with Papillon--Lefèvre syndrome and novel symptomless mutation. Hum Mutat 17:152-153, 2001).

Chanarin-Dorfman syndrome (CDS) is a rare autosomal recessive form of nonbullous congenital ichthyosiform erythroderma (NCIE) that is characterized by the presence of intracellular lipid droplets in most tissues. We previously localized a gene for a subset of NCIE to chromosome 3 (designated "the NCIE2 locus"), in six families. Lipid droplets were found in five of these six families, suggesting a diagnosis of CDS. Four additional families selected on the basis of a confirmed diagnosis of CDS also showed linkage to the NCIE2 locus. Linkage-disequilibrium analysis of these families, all from the Mediterranean basin, allowed us to refine the NCIE2 locus to an approximately 1.3-Mb region. Candidate genes from the interval were screened, and eight distinct mutations in the recently identified CGI-58 gene were found in 13 patients from these nine families. The spectrum of gene variants included insertion, deletion, splice-site, and point mutations. The CGI-58 protein belongs to a large family of proteins characterized by an alpha/beta hydrolase fold. CGI-58 contains three sequence motifs that correspond to a catalytic triad found in the esterase/lipase/thioesterase subfamily. Interestingly, CGI-58 differs from other members of the esterase/lipase/thioesterase subfamily in that its putative catalytic triad contains an asparagine in place of the usual serine residue.

Mal de Meleda (MDM) is a rare autosomal recessive skin disorder, characterized by transgressive palmoplantar keratoderma (PPK), keratotic skin lesions, perioral erythema, brachydactyly and nail abnormalities. We report the refinement of our previously described interval of MDM on chromosome 8qter, and the identification of mutations in affected individuals in the ARS (component B) gene, encoding a protein named SLURP-1, for secreted Ly-6/uPAR related protein 1. This protein is a member of the Ly-6/uPAR superfamily, in which most members have been localized in a cluster on chromosome 8q24.3. The amino acid composition of SLURP-1 is homologous to that of toxins such as frog cytotoxin and snake venom neurotoxins and cardiotoxins. Three different homozygous mutations (a deletion, a nonsense and a splice site mutation) were detected in 19 families of Algerian and Croatian origin, suggesting founder effects. Moreover, one of the common haplotypes presenting the same mutation was shared by families from both populations. Secreted and receptor proteins of the Ly-6/uPAR superfamily have been implicated in transmembrane signal transduction, cell activation and cell adhesion. This is the first instance of a secreted protein being involved in a PPK.

Bothriocephalid (Diphyllobothrium pacificum) and Ascarid (Ascaris lumbricoides) eggs have been identified in a sample taken in the abdominal cavity of a child skeleton found in Zeto Point (ADK-011), an archaeological site on Adak Island in the Central Aleutian Islands (Alaska).

Weakness of the pinch grip between index finger and thumb, in ulnar nerve palsy, leads to severe loss of hand function. The first dorsal interosseous plays a major rôle as it abducts and flexes the index finger at its base and stabilizes the MP joint of this finger. Replacement of this muscle is therefore important. The authors report the results of eight clinical cases of replacement of the first dorsal interosseous by extensor pollicis brevis. They obtained good improvement of hand function, in terms of objective and subjective results, in all cases.

Excavations on Buldir Island, Aleutian Islands, Alaska, have revealed the remains of several features dated between the 13th and 17th centuries A.D. Soil from an open-air workshop, represented by 2 excavated pits, and a structure built of whale bones were sampled for evidence of parasites and microfloristic remains. Two groups of helminth eggs (Diphyllobothrium and Ankylostomidae) were identified in samples from the open-air pits; microfloristical remains were found in all samples. This is the first paleoparasitological analysis conducted on an Aleutian midden.

Using a specifically designed diagnostic PCR assay with nested primers the following could be achieved: (1) a group of 22 clinically indistinguishable women attending an infertility clinic, 18 with repeated embryo transfer failure, and asymptomatic for HSV-1 could be divided into two subgroups after testing their menstrual blood. An HSV-DNA positive (50%) and HSV-DNA negative group (50%) could be distinguished. None of the four controls were positive; (2) semen from 154 infertile and 24 fertile men was tested in relation to infertility. In the group of infertile men 37 (24%) were HSV-DNA positive but none of the fertile control (0%) was positive; (3) treatment of both partners with an antiviral drug resulted in two pregnancies; (4) HLA data on four of the couples in which the wife's menstrual blood was HSV positive was compared to seven HSV negative couples and 22 infertile, as well as 22 fertile couples. Clustering of class I HLA (B61 and Cw3) was found with a significant increase in Cw3 in both partners.

A sensitive and selective high-performance liquid chromatographic method with native detection of fluorescence was developed and validated for the quantitation of ivabradine and its N-demethylated metabolite in plasma (rat, dog, human) and human urine. The procedure involves the use of an analogue as internal standard, solid-phase extraction on cyano cartridges, separation on a Nova-Pak C8 column and fluorescence detection. Calibration curves are linear in the concentration ranges from 0.5 to 100 ng/ml in plasma and 2.0 to 500 ng/ml in urine with a limit of quantitation set at 0.5 and 2.0 ng/ml in plasma and urine, respectively. The analysis of plasma and urine samples (spiked with the analytes at low, medium and high concentrations of the calibration range) demonstrates that both analytes can be measured with precision and accuracy within acceptable limits. Quality controls spiked with analyte concentrations up to 10000 ng/ml can also be analysed with excellent precision and accuracy after dilution of the samples. The parent drug and its metabolite are stable in plasma and urine after short-term storage (24 h at room temperature and after three freeze-thaw cycles) as well as after long-term storage at -20 degrees C (at least 6 months in animal plasma and 12 months in human plasma and urine). The method has been used to quantify both compounds in plasma and urine samples from clinical and non-clinical studies with ivabradine.

Purpose of the Study: Extensive cervical laminectomy has been widely used in the treatment of progressive myelopathies secondary to stenotic conditions. Complications of this procedure such as spinal instability, accelerated spondylotic changes, postoperative spinal deformity and constriction of the dura mater by extradural scar tissue formation have been recognized. However, the frequency of these complications is probably overestimated and their consequences on the clinical outcome remain unknown. The purpose of this report was to describe the incidence and consequences of cervical spinal deformity and instability after multilevel laminectomy in adult patients with myelopathy caused by cervical spondylosis and to determine the usefulness of preoperative dynamic films in the prevention of postoperative destabilization., Materials and Methods: 30 patients older than 30 years who underwent a laminectomy of more than 3 levels without fusion for myelopathy secondary to cervical spondylosis were reviewed retrospectively with an average follow-up of 5 years. Functional results were evaluated according to the Japanese Orthopaedic Association scoring system. Lateral views in neutral position, in flexion and in extension of the preoperative cervical roentgenograms were analyzed in comparison with the last follow-up one in order to identify the changes in the curvature of the cervical column, in the range of motion of the neck, in the intervertebral angular mobility and antero-posterior displacement of the vertebral bodies, and finally to identify the incidence of spinal instability., Results: 18 patients (31 per cent) developed postoperative changes in cervical spine curvature. 15 patients (25 per cent) had one or more destabilized levels. Deformities of the cervical spine occurring after surgery do not appear to cause any symptom or neurologic abnormalities. Destabilization required repeat surgery in 3 patients. All the levels found destabilized on the postoperative films were hypermobile on the preoperative dynamic radiographs. A preoperative olisthesis without hypermobility was not a risk factor for postoperative destabilization., Conclusion: The use of preoperative dynamic radiographs should improve the selection of patients undergoing laminectomy for the treatment of multilevel cervical cord compression. Dynamic X-rays may also reinforce the need for possible adjunctive procedures such as fusion and instrumentation, in order to prevent a postoperative destabilization. A preoperative olisthesis with a hypermobility in sagittal or horizontal planes must be fused and instrumented.

The authors report the results of a series of 59 microdissections of the region of the foramen magnum. These dissections were made under the strict conditions of a surgical approach using an operating microscope. The major anatomic structures of the medullo-spinal junction are arranged mainly at its lateral aspect. The customary surgical approaches to the posterior cranial fossa give ready access to the cerebello- and latero-medullary cisterns. The description of the neurovascular structures contained therein assumes a particular importance because of the relative frequency of lesions developing at this level. This study deals particularly with the vertebral a. (VA), the inferior posterior cerebellar a. (IPCA), the cranial nn. IX (glossopharyngeal n.), X (vagus n.), XIc and XIs (cranial and spinal accessory n.) and XII (hypoglossal n.). The anatomy of this posterior and lateral region is characterised by the contrast between the relatively uniform course of the VA and the variable course of the IPCA, a true guideline whose very irregular arrangement accounts for the diversity of its relations with the last four cranial nn.

Objective: To determine a possible link between herpes simplex virus 1 (HSV) and infertility., Method: A specifically designed polymerase chain reaction with nested primers, was developed and used to test for HSV in 153 men and 20 women attending an infertility clinic., Results: HSV DNA was detected in 37 (24%) out of 153 semen samples and in 11 (55%) out of 20 menstrual blood samples. However, HSV DNA (0%) was not detected in the semen of 16 males with children. A significant association between the evidence for infertility and an HSV positive test was observed in men (Fisher's exact test, p = 0.024), and a stronger effect was found in females after failed in vitro fertilization (Fisher's exact test p = 0.0086)., Conclusion: This is the first report of the detection of herpes simplex virus DNA in semen and menstrual blood. Encouraging preliminary results justify antiviral therapy in case of a positive test.

A number of models have been proposed to describe the spread of infectious diseases of the S-I-R type. Most of them account for variable infectivity levels, and very few incorporate variable susceptibility levels. In the present work, a new epidemic model, called a collective model, is constructed that combines both variabilities in a general way. It is then established how to determine the exact distribution of the final state and the severity of the epidemic when the infection process stops.

The distally based lateral supramalleolaire flap with a retrograde blood flow on the perforating branch of the peroneal artery is a good flap to treat loss of skin involving the ankle, the region behind the Achilles tendon, and the foot. Based on the results of an anatomical study, the authors describe a modification of this flap which can be raised on the infero-lateral collateral artery, with an anterograde blood flow. In fact, clinical experience of six cases shows that vascular pedicle component (perforating branch of the peroneal artery, infero-lateral collateral artery) and blood flow (anterograde, retrograde) can be calculated according to the regional vascular network, arc of rotation and the type of flap. Because of the many possible combinations, it can be considered to be a flap with variable vascular pedicle raised "à la carte". However, according to our clinical cases, the anterograde blood flow does not seem to have resolved the problems of venous congestion of this flap.

Dynamics of the backbone and some side chains of apo-neocarzinostatin, a 10.7 kDa carrier protein, have been studied from 13C relaxation rates R1, R2 and steady-state 13C-(1H) NOEs, measured at natural abundance. Relaxation data were obtained for 79 nonoverlapping C alpha resonances and for 11 threonine C beta single resonances. Except for three C alpha relaxation rates, all data were analysed from a simple two-parameter spectral density function using the model-free approach of Lipari and Szabo. The corresponding C-H fragments exhibit fast (tau e < 40 ps) restricted libration motions (S2 = 0.73 to 0.95). Global examination of the microdynamical parameters S2 and tau e along the amino acid sequence gives no immediate correlation with structural elements. However, different trends for the three loops involved in the binding site are revealed. The beta-ribbon comprising residues 37 to 47 is spatially restricted, with relatively large tau e values in its hairpin region. The other beta-ribbon (residues 72 to 87) and the large disordered loop ranging between residues 97-107 experience small-amplitude motions on a much faster (picosecond) time scale. The two N-terminal residues, Ala1 and Ala2, and the C-terminal residue Asn113, exhibit an additional slow motion on a subnanosecond time scale (400-500 ps). Similarly, the relaxation data for eight threonine side-chain C beta must be interpreted in terms of a three-parameter spectral density function. They exhibit slower motions, on the nanosecond time scale (500-3000 ps). Three threonine (Thr65, Thr68, Thr81) side chains do not display a slow component, but an exchange contribution to the observed transverse relaxation rate R2 could no be excluded at these sites. The microdynamical parameter (S2, tau e and R2ex) or (S(slow)2, S(fast)2 and tauslow) were obtained from a straightforward solution of the equations describing the relaxation data. They were calculated assuming an overall isotropic rotational correlation time tau c for the protein of 5.7 ns, determined using standard procedures from R2/R1 ratios. However, it is shown that the product (1-S2) x tau e is nearly independent of tau c for residues not exhibiting slow motions on the nanosecond time scale. In addition, this parameter very closely follows the heteronuclear NOEs, which therefore could be good indices for local fast motions on the picosecond time scale.

Representation of sequence similarity by dot matrix plots is a method widely used for comparing biological sequences. The user is presented with an overall view of similarity between two sequences. Computation of this plot has been reconsidered here. An improvement is proposed through the preprocessing of the data into an automation recognizing the word structure of a sequence. The main advantage of this approach is to systematically eliminate the repetitions during word comparison. Simple heuristics are also considered to greatly speed up pattern matching. As a result, large sequences are handled very efficiently. This is illustrated by a comparison of large genomic DNA. The algorithm has been implemented in an interactive application on a microcomputer.

Based on coordinates derived from three series of anatomic sections, the authors propose a view for tomographic investigation, applicable in MRI and ultrasound, which reconstructs the ideal image of the suprarenal gland in its quadrilateral as described by Testut. This "anatomic" view is 45 degrees vertical and oblique, intermediate between the sagittal and frontal views, which it can advantageously replace. A new aspect of suprarenal tomography, recalling the image of a triskele, is described in the context of this view.

A new epidemic model is developed that describes the spread of an infectious disease with fatal risk. The model includes as extreme cases the standard general epidemic process (for diseases that confer immunity after infection) and the fatal epidemic process (for diseases that lead inevitably to death). Both deterministic and stochastic versions are examined. First, attention is paid to the temporal and final states of the epidemic. Then the existence of a threshold phenomenon and the qualitative effect of the fatal risk are investigated.

This paper addresses two important issues of three-dimensional (3D) natural shape analysis. The first concerns the segmentation of these shapes into 3D primitives and the second deals with their geometric characterisation by means of intrinsic features. Restricting ourselves to 3D objects formed from two-dimensional (2D) cross-sectional adjacent slices (i.e., long bones), we present a method of contextual classification and results concerning the ulnar bone. With respect to the second issue, a curvature-torsion analysis of the medullar axis is introduced and the results are represented by means of torsion images. A first application to ulnar structures is given. It is shown that radius bones have zero torsion and that their curvatures can be studied in 2D. A preliminary statistical study of the 2D curvature of the radius is also presented.

We consider the basic function which locates a specific string of symbols within a longer sequence. When one is expecting to do many substring searches it is worthwhile to build an auxiliary index to the sequence to aid in the search. We propose a method to generate a compact index that can be viewed as a small (partial) deterministic finite automaton recognizing the subword structure of a sequence. We present an algorithm for its construction on-line in linear time. Such a data structure permits the efficient localization of subwords in a sequence and can be used in the development of interactive sequence analysis software.

We consider the problem of comparing several nucleic acid sequences to identify words occurring imperfectly (patterns with no gap) with unusual frequency. Methods for computing, representing, and inspecting interactively the structure of such repeating motifs in nucleic acids and more generally any text are described. Multiple sequences are treated as one large concatenate. In a preprocessing step, a lexical index is created to provide rapid string matching for the enumeration of the words matching a pattern. For given word features (word length, minimal frequency), a sequence profile is displayed. The profile can be inspected interactively with on-line algorithms. Applications to the identification of regulatory elements in DNA regions involved in the control of gene expression are presented. Our program ('DNA-Lexemics') runs on the Macintosh.

A method for pattern analysis of DNA sequence data is considered. A space economical automaton for word recognition was presented elsewhere together with an algorithm for its compilation in linear time. An algorithm for the localization of words including imperfect matches (motif search) was developed. A program was implemented on the Macintosh and used extensively for the representation of the word composition of DNA data. We explore different sets of regulatory sequences to illustrate the performance of this method. In mammalian DNA, this analysis reveals "consensus motifs" corresponding to functional (or putative) cis-acting elements mediating the regulation of gene expression.

A distally based posterior calf fasciocutaneous flap was successfully used to reconstruct a major ankle defect with exposed bones and joints. The flap, which reaches easily this region, can also be used as a free flap for coverage of heel and ankle when the forefoot is not involved in the injury.

Tango [Biometrics 40:15 (1984)] proposed an index for detecting disease clustering in time applicable to grouped data obtained from a population that remains fairly stable over the study period. This index has received considerable attention in the literature including the suggestion that it be used to detect the space-time clustering of diseases and the suggestion to use similar test statistics to detect disease clustering in space and/or time while accounting for a changing population size over the study period. This paper concerns the related question of measuring the severity of the disease clustering once it has been determined that cases are not randomly distributed over space and/or time. A family of alternatives to randomness is proposed in which space and/or time versions of Tango's index are sufficient statistics for the parameters measuring the severity of the clustering. For the special case of temporal clustering, an unbiased estimator of the clustering parameter and its sampling variance is derived, and a particularly simple interpretation of this estimator is suggested. These latter results are based on some asymptotic approximations due to Tango [Biometrics 46:351 (1990)]. An application to the trisomy data given by Wallenstein [Am. J. Epidemiol. 111:367 (1980)] is discussed.

A generalized Reed-Frost epidemic process is discussed in which variability among susceptible individuals is incorporated by randomizing the levels of resistance of the individuals to the infection. Our purpose is to derive the exact distribution of the ultimate number of susceptibles surviving the disease. This is achieved by a simple conditional argument and by using a particular family of polynomials defined recursively. The results can be viewed as a continuation of those obtained by the authors for the alternative situation with randomized infectivity levels.

A mathematical model for the epidemiology of rinderpest was developed, starting from a simplified descriptive analysis of the disease. A formula for the calculation of the probability of infection of a susceptible animal was first established. A deterministic failure threshold of the infection was then deduced. Deterministic and stochastic approaches were adopted using iterative methods on a computer. These allowed a description of the spread and the variability of an infection process in a population to be made. An illustration of the use of this model showed that, in some cases, variability effects due to stochastic factors were very important. In these particular conditions, the use of the deterministic model alone was not adequate for a good description of the infection. Consequently, improvements of the model were proposed in order to make it more realistic and to allow its use for the evaluation of the efficiency of field operations.

In 21 cases of acetabulum fractures of 19 patients, the authors compare the findings given by three dimensional reconstructions of axial CT scan cuts with the plain films. The number of CT scan cuts is reasonable for each patient. Working time is about 20 to 30 minutes for the technician. In the cases of complex and displaced fractures, three dimensional imaging brings often decisive informations for the therapeutic management of these patients. Unusual views are often allowed but completely adapted to each type of fracture.

The present paper is concerned with a chain-binomial deterministic model for an infectious disease of the S-I-S type. The model extends the Cooke et al. (1977) and Longini (1980) model in the sense that it accounts for the distribution of the number of contacts made by each susceptible during an infectious period and for the probabilities of infection at the different contacts with infectives. The aim of the work is to investigate under which conditions the disease becomes endemic or not. Some partial results are first derived, but a complete analysis of the threshold behaviour seems very intricate. A more detailed discussion is then presented for the specific case where at least K + 1 contacts with infectives, K greater than or equal to 1 fixed, are required to make a susceptible infected.