Hematuria recidivante como síntoma guía del síndrome del desfiladero aortomesentérico / Recurrent hematuria as a guiding symptom of aortomesenteric gorge síndrome

INTRODUCCIÓN: Este síndrome define la compresión de la vena renal izquierda entre la aorta y la arteria mesentérica superior, provocando una presión elevada de dicha vena renal con posible desarrollo de venas colaterales. Clínicamente, aparece hematuria intermitente, proteinuria con o sin dolor abdominal o en hemiabdomen izquierdo. CASOS CLÍNICOS: Presentamos 15 niños de entre 7 y 13 años, la mayoría con examen físico normal y clínica de dolor abdominal o del flanco izquierdo con presión arterial normal (46,6%); hallazgos urinarios: hematuria no glomerular (20%) y proteinuria de rango no nefrótico (20%), con microalbúmina inferior a 300 mg en orina de 24 horas. Un paciente (6,7%) presentó proteinuria asociada a glucosuria e hipertensión. Las mediciones de ultrasonografía Doppler del diámetro anteroposterior (AP) y las velocidades máximas de la vena renal izquierda son diagnósticas: dilatación y enlentecimiento del flujo proximal a la pinza aortomesentérica, disminución del calibre con flujo acelerado a nivel distal y ángulo de la pinza menor de 30º. En dos casos precisó angio-TAC, mostrando la vena renal izquierda comprimida entre la aorta y la arteria mesentérica superior. La angiografía por RM ofrece una excelente definición anatómica. El tratamiento es conservador. Puede ser necesario tratamiento con inhibidores de la enzima convertidora de la angiotensina, intervenciones quirúrgicas o procedimientos extravasculares. CONCLUSIÓN: Sospechar SHVR ante la presencia de hematuria, proteinuria, dolor abdominal recurrente, diagnóstico que requiere alto índice de sospecha. Precisa ecografía. En casos seleccionados, angio-TAC, RM o flebografía, siendo esta última el gold standard para el diagnóstico, que no suele precisarse

INTRODUCTION: This syndrome defines the compression of the left renal vein between the aorta and the superior mesenteric artery, causing an elevated pressure of said renal vein with possible development of collateral veins. Clinically, intermittent hematuria, proteinuria appears with or without abdominal pain or in the left abdomen. CLINICAL CASES: We present 15 children between 7 and 13 years old. Most with normal physical and clinical examination of abdominal or left flank pain with normal blood pressure (46.6%); urinary findings: non-glomerular hematuria (20%) and non-nephrotic range proteinuria (20%), with microalbumin less than 300 mg in 24-hour urine. One patient (6.7%) presented proteinuria associated with glucosuria and hypertension. Doppler ultrasound measurements of the anteroposterior diameter (AP) and the maximum velocities of the left renal vein are diagnostic: dilatation and slowing of the flow proximal to the aortomesenteric clamp, decrease in caliber with accelerated flow at the distal level and angle of the clamp less than 30º. In two cases, angio-TAC was required, showing the compressed left renal vein between the aorta and the superior mesenteric artery. MR angiography offers excellent anatomical definition. The treatment is conservative. Treatment with angiotensin-converting enzyme inhibitors, surgery, or extravascular procedures may be necessary. CONCLUSION: Suspect RVS, in the presence of hematuria, proteinuria, recurrent abdominal pain, a diagnosis that requires a high index of suspicion. Requires ultrasound. In selected cases, CT angiography, MRI or phlebography, the latter being the gold standard for diagnosis, which is not usually required

Negative Refraction in Time-Varying Strongly Coupled Plasmonic-Antenna-Epsilon-Near-Zero Systems.

Time-varying metasurfaces are emerging as a powerful instrument for the dynamical control of the electromagnetic properties of a propagating wave. Here we demonstrate an efficient time-varying metasurface based on plasmonic nano-antennas strongly coupled to an epsilon-near-zero (ENZ) deeply subwavelength film. The plasmonic resonance of the metal resonators strongly interacts with the optical ENZ modes, providing a Rabi level spitting of ∼30%. Optical pumping at frequency ω induces a nonlinear polarization oscillating at 2ω responsible for an efficient generation of a phase conjugate and a negative refracted beam with a conversion efficiency that is more than 4 orders of magnitude greater compared to the bare ENZ film. The introduction of a strongly coupled plasmonic system therefore provides a simple and effective route towards the implementation of ENZ physics at the nanoscale.

Corrigendum: Controlling hybrid nonlinearities in transparent conducting oxides via two-colour excitation.

This corrects the article DOI: 10.1038/ncomms15829.

Controlling hybrid nonlinearities in transparent conducting oxides via two-colour excitation.

Nanophotonics and metamaterials have revolutionized the way we think about optical space (ɛ,µ), enabling us to engineer the refractive index almost at will, to confine light to the smallest of the volumes, and to manipulate optical signals with extremely small footprints and energy requirements. Significant efforts are now devoted to finding suitable materials and strategies for the dynamic control of the optical properties. Transparent conductive oxides exhibit large ultrafast nonlinearities under both interband and intraband excitations. Here we show that combining these two effects in aluminium-doped zinc oxide via a two-colour laser field discloses new material functionalities. Owing to the independence of the two nonlinearities, the ultrafast temporal dynamics of the material permittivity can be designed by acting on the amplitude and delay of the two fields. We demonstrate the potential applications of this novel degree of freedom by dynamically addressing the modulation bandwidth and optical spectral tuning of a probe optical pulse.

Enhanced Nonlinear Refractive Index in ε-Near-Zero Materials.

New propagation regimes for light arise from the ability to tune the dielectric permittivity to extremely low values. Here, we demonstrate a universal approach based on the low linear permittivity values attained in the ε-near-zero (ENZ) regime for enhancing the nonlinear refractive index, which enables remarkable light-induced changes of the material properties. Experiments performed on Al-doped ZnO (AZO) thin films show a sixfold increase of the Kerr nonlinear refractive index (n_{2}) at the ENZ wavelength, located in the 1300 nm region. This in turn leads to ultrafast light-induced refractive index changes of the order of unity, thus representing a new paradigm for nonlinear optics.

Experimental demonstration of titanium nitride plasmonic interconnects.

An insulator-metal-insulator plasmonic interconnect using TiN, a CMOS-compatible material, is proposed and investigated experimentally at the telecommunication wavelength of 1.55 µm. The TiN waveguide was shown to obtain propagation losses less than 0.8 dB/mm with a mode size of 9.8 µm on sapphire, which agree well with theoretical predictions. A theoretical analysis of a solid-state structure using Si(3)N(4) superstrates and ultra-thin metal strips shows that propagation losses less than 0.3 dB/mm with a mode size of 9 µm are attainable. This work illustrates the potential of TiN as a realistic plasmonic material for practical solid-state, integrated nano-optic and hybrid photonic devices.

On-chip CMOS-compatible all-optical integrator.

All-optical circuits for computing and information processing could overcome the speed limitations intrinsic to electronics. However, in photonics, very few fundamental 'building blocks' equivalent to those used in multi-functional electronic circuits exist. In this study, we report the first all-optical temporal integrator in a monolithic, integrated platform. Our device--a lightwave 'capacitor-like' element based on a passive micro-ring resonator--performs the time integral of the complex field of an arbitrary optical waveform with a time resolution of a few picoseconds, corresponding to a processing speed of ∼200 GHz, and a 'hold' time approaching a nanosecond. This device, compatible with electronic technology (complementary metal-oxide semiconductor), will be one of the building blocks of next-generation ultrafast data-processing technology, enabling optical memories and real-time differential equation computing units.

La eficacia clínica de la carga convencional, precoze inmediata en sobredentaduras mandibulares con implantes dentales. Un estudio comparativo a cinco años / The clinical efficacy of conventional, early and immediate in mandibular overdentures with dental implants. A 5-year comparative study

Introducción. El estudio muestra la evaluación de los pacientes edéntulos totales tratados con sobredentaduras mandibulares con implantes dentales mediante diferentes tipos de carga funcional. Métodos. 33 pacientes edéntulos totales fueron tratados con 127 implantes en la mandíbula para su rehabilitación prostodóncica con sobredentaduras. Todos los implantes fueron insertados en la cirugía y fueron cargados de forma convencional, precoz o inmediata. Resultados. Después de un seguimiento clínico medio de 67,5 meses (rango: 36-108 meses), los resultados indican un éxito de los implantes del 96,9% porque 4 implantes fracasaron. El 100% delos pacientes fueron tratados con una sobredentadura implantosoportada, el 60,9% con retenedores de bolas y el 31,9% mediante barras .Conclusiones. El estudio indica que la rehabilitación oral de los pacientes edéntulos con sobredentaduras mandibulares implantosoportadas mediante su carga convencional, precoz o inmediata pueden obtener la oseointegración y representar una terapéutica odontológica con éxito (AU)

Introduction. This study reports the evaluation of edentulous patients treated with overdentures in the mandible by different loading protocols of dental implants. Patients and Methods. 33 edentulous patients were treated with 127 implants for prosthodontics rehabilitation with overdentures in the mandible. All implants were inserted in one-stage and were loaded with conventional, early and immediate protocols. Results. After a mean follow-up of 67,5 months (range: 36-108 months), clinical results indicate a success rate of implants of 96,9%. Four implants were lost. 100% of patients were treated with overdentures, 60,9% with ball attachments and 39,1% with bar retained. Conclusions. This study indicate that oral rehabilitation in the mandible of edentulous patients with overdentures supported by implants can achieve osseo integration and were loaded conventionally, early and immediately as a successful dental treatment (AU)

Melatonin in diseases of the oral cavity.

BACKGROUND: Melatonin is the principal secretory product of the pineal gland. It has immunomodulatory and antioxidant activities, stimulates the proliferation of collagen and osseous tissue and acts as a protector against cellular degeneration associated with aging and toxin exposure. Arising out of its antioxidant actions, melatonin protects against inflammatory processes and cellular damage caused by the toxic derivates of oxygen. As a result of these actions, melatonin may be useful as a co-adjuvant in the treatment of certain conditions of the oral cavity. METHODS: An extensive review of the scientific literature was carried out using PubMed, Science Direct, ISI Web of Knowledge and the Cochrane base. RESULTS: Melatonin, which is released into the saliva, may have important implications for oral diseases. Melatonin may have beneficial effects in certain oral pathologies including periodontal diseases, herpes viral infections and Candida, local inflammatory rocesses, xerostomia, oral ulcers and oral cancer. CONCLUSIONS: Melatonin may play a role in protecting the oral cavity from tissue damage caused by oxidative stress. The experimental evidence suggests that melatonin may have utility in the treatment of several common diseases of the oral cavity. However, more specific studies are necessary to extend the therapeutic possibilities to other oral diseases.

Low power four wave mixing in an integrated, micro-ring resonator with Q = 1.2 million.

We demonstrate efficient, low power, continuous-wave four-wave mixing in the C-band, using a high index doped silica glass micro ring resonator having a Q-factor of 1.2 million. A record high conversion efficiency for this kind of device is achieved over a bandwidth of 20 nm. We show theoretically that the characteristic low dispersion enables phase-matching over a tuning range > 160 nm.

Polarization proximity effect in isolator crystal pairs.

We experimentally study the polarization dynamics (orientation and ellipticity) of near-infrared light transmitted through magneto-optical yttrium iron garnet isolator crystal pairs using a modified balanced detection scheme. When the pair separation is in the submillimeter range, we observed a proximity effect in which the saturation field is reduced by up to 20%. One-dimensional calculations suggest that the proximity effect originates from magnetostatic interactions between the dipole moments of the isolator crystals.

High prevalence of apical periodontitis amongst smokers in a sample of Spanish adults.

AIM: To study the prevalence of apical periodontitis in smoker and nonsmoker patients. METHODOLOGY: In a cross-sectional study, the records of 180 subjects, 109 smokers and 71 nonsmokers, were examined. All participants underwent a full-mouth radiographic survey incorporating 14 periapical radiographs. The periapical region of all teeth, excluding third molars, was examined. Periapical status was assessed using the Periapical Index score. Statistical analyses were conducted using the Cohen's Kappa test, analysis of variance and logistic regression. RESULTS: Apical periodontitis in at least one tooth was found in 74% of smokers and in 41% of nonsmokers (P < 0.01; odds ratio = 4.2; 95% C. I. = 2.2-7.9). Amongst smoker patients 5% of the teeth had apical periodontitis, whereas in nonsmoker subjects 3% of teeth were affected (P = 0.008; odds ratio = 1.5; 95% C. I. = 1.1-2.1). The percentage of root filled teeth in smoker and nonsmoker patients was 2.5% and 1.5%, respectively (P < 0.05; odds ratio = 1.7; C. I. 95% = 1.0-2.6). CONCLUSIONS: In this study population, smoking was significantly associated with a greater frequency of root canal treatment and with an increased prevalence of apical periodontitis.

El tratamiento con implantes dentales postextracción / Treatment with postextraction dental implants

Introducción. El objetivo del presente estudio era mostrar los resultados de del tratamiento con implantes dentales insertados inmediatamente después de la extracción. Métodos. 22 pacientes con pérdida dental unitaria, parcial o total fueron tratados con 82 implantes Microdent® con superficie con chorreado de arena y grabada con ácidos. Todos los implantes fueron insertados inmediatamente después de la extracción correspondiente. Los implantes fueron cargados después de un periodo de cicatrización de 3 meses en la mandíbula o 6 meses en el maxilar superior. Resultados. Los hallazgos clínicos indican una supervivencia y éxito de los implantes del 97,6%. 2 implantes se perdieron durante el periodo de cicatrización. El 73,2% de los implantes fueron insertados en el maxilar. superior mientras que el 26,8% en la mandíbula. Después de un periodo medio de carga funcional de 12 meses, no ha habido complicaciones tardías. Conclusiones. Este estudio indica que los implantes dentales insertados de forma inmediata después de la extracción pueden constituir una alternativa implantológica predecible y exitosa (AU)

Introduction. The aim of this study was to report the outcome of treatment with implant inserted immediately after tooth extraction. Methods. 22 patients with single, partially or totally tooth loss were treated with 82 Microdent® sandblasted etched surface implants. All implants were inserted immediately after tooth extraction. Implants were loaded after a healing free-loading period of 3 months in mandible or 6 months in maxilla. Results. Clinical results indicate a survival and success rate of implants of 97,6%. 2 implants were lost during the healing period. 73.2% of implants were inserted at maxilla while 26.8% were inserted at mandible. After a functioning period of 12 months, no late complications were reported. Conclusions. This study indicate that dental implants inserted immediately after tooth extraction may constitute a successful, predictable alternative implant treatment (AU)

High prevalence of apical periodontitis amongst type 2 diabetic patients.

AIM: To study the prevalence of AP in patients with and without type 2 diabetes mellitus. METHODOLOGY: In a retrospective cohort study, the records of 38 subjects with diabetes and 32 control subjects were examined. All participants underwent a full-mouth radiographic survey incorporating 14 periapical radiographs. The periapical region of all teeth, excluding third molars, was examined. Periapical status was assessed using the periapical index score. Statistical analyses were conducted using the Cohen's kappa test, analysis of variance and logistic regression. RESULTS: Apical periodontitis in at least one tooth was found in 81.3% of diabetic patients and in 58% of control subjects (P = 0.040; OR = 3.2; 95% CI = 1.1-9.4). Amongst diabetic patients 7% of the teeth had AP, whereas in the control subjects 4% of teeth were affected (P = 0.007; OR = 1.8; 95% CI = 1.2-2.8). CONCLUSIONS: Type 2 diabetes mellitus is significantly associated with an increased prevalence of AP.

La carga inmediata de implantes transicionales en sobredentaduras mandibulares en adultos mayores / Inmediate loading of transitional implants in mandible overdentures of older adults

Introducción. La implantología oral constituye una importante modalidad terapéutica en el tratamiento prostodóncico de los pacientes con pérdida dental total. El estudio muestra la evaluación de los pacientes edéntulos totales tratados con sobredentaduras mandibulares mediante la carga inmediata de los miniimplantes de titanio con superficie grabada con ácidos. Métodos. 18 pacientes edéntulos totales fueron tratados con 72 mini implantes transicionales Sendax® en la mandíbula para su rehabilitación prostodóncica con sobredentaduras. Todos los implantes fueron insertados en 1 cirugía y fueron cargados inmediatamente en la misma sesión. Los hallazgos clínicos (implantológicos y prostodóncicos) se han seguido al menos durante 12 meses. Resultados. Después de un seguimiento clínico medio de 20,8 meses (rango: 12-48 meses), los resultados indican un éxito de los implantes del 97,3 por ciento porque 2 implantes fracasaron. El 100 por ciento de los pacientes fueron tratados con una sobredentadura implantosoportada con retenedores de bolas sobre 4 implantes. Conclusiones. Los resultados del presente estudio indican que la rehabilitación prostodóncica de la mandíbula con sobredentaduras implantosoportadas de los pacientes edéntulos mediante la carga inmediata de implantes transicionales de titanio pueden obtener la oseointegración y representar una terapéutica odontológica con éxito (AU)

Introduction. Oral implantology constitute an important therapeutic modality in the prosthodontic treatment of patients with total tooth loss. This study reports the evaluation of edentulous patients treated with overdentures in the mandible by immediate loading of titanium miniimplants with acid-etched surface. Patients and Methods. 18 edentulous patients were treated with 72 Sendax® transitional mini implants for prosthodontic rehabilitation with overdentures in the mandible. All implants were inserted in one-stage and were loaded immediately. Clinical findings (implant and prosthodontics) were followed during 12 months at least. Results. After a mean follow-up of 20.8 months (range: 12-48 months), clinical results indicate a success rate of implants of 97,3%.Twoimplants were lost. 100% of patients were treated with overdentures with ball attachments retained with 4 implants. Conclusions. Clinical results of this study indicate that prosthodontic rehabilitation in the mandible of edentulous patients with overdentures supported by transitional titanium implants can achieve osseointegration and were loaded immediately as a successful dental treatment (AU)

Periapical status and quality of root fillings and coronal restorations in an adult Spanish population.

AIM: To investigate the quality of root fillings and coronal restorations and their association with periapical status in an adult Spanish population. METHODOLOGY: A total of 180 subjects, aged 37.1 +/- 15.7 years, who presented as new patients at the Faculty of Dentistry, Seville, Spain, were examined. All participants underwent a full-mouth radiographic survey incorporating 14 periapical radiographs. The periapical region of all root filled teeth, excluding third molars, were examined. The technical quality of root fillings was evaluated in terms of length in relation to the root apex and lateral adaptation to the canal wall. Radiographic signs of overhang or open margins associated with coronal restorations were also evaluated. Periapical status was assessed using the Periapical Index score. Statistical analyses were conducted using the Cohen's kappa test and logistic regression. RESULTS: The total number of root filled teeth was 93, and 60 (64.5%) had apical periodontitis (AP). Presence of AP in root filled teeth was associated with inadequate adaptation of the filling (OR = 2.29; P = 0.06), inadequate length of the root filling (OR = 2.44; P = 0.048), and with poor radiographic quality of the coronal restoration (OR = 2.38; P = 0.054). Only 34.4% of the root fillings were adequate from a technical perspective. When both root fillings and coronal restorations were adequate the incidence of AP decreased to 31.3% (OR = 5.50; P < 0.01). CONCLUSIONS: The incidence of AP in root filled teeth was high. Many root fillings were technically unsatisfactory. Adequate root fillings and coronal restorations were associated with a lower incidence of AP; an adequate root filling had a more substantial impact on the outcome of treatment than the quality of the coronal restoration.

Prevalence of apical periodontitis and frequency of root-filled teeth in an adult Spanish population.

AIM: To estimate the prevalence of teeth with apical periodontitis (AP) and root-filled teeth in an adult Spanish population. METHODOLOGY: A total of 180 subjects, aged 37.1 +/- 15.7 years, presenting as new patients to the Faculty of Dentistry, Seville, Spain, were examined. All participants underwent a full-mouth radiographic survey (14 periapical radiographs). The frequency of root canal treatment and the periapical status of all teeth, using the periapical index (PAI) score, were assessed. An intraobserver agreement test on PAI scores produced a Cohen's kappa of 0.77 (substantial agreement). Results were analysed statistically using the Chi-square test. RESULTS: Apical periodontitis in one or several teeth was found in 110 subjects (61.1% prevalence), and 73 (40.6% prevalence) had at least one root-filled tooth. Among subjects with root-filled teeth, 48 (65.8%) had AP affecting at least one root-filled tooth. A total of 4453 teeth were examined, of these 186 (4.2%) had AP. The total number of root-filled teeth was 93 (2.1%), of which 60 (64.5%) had AP. Among non-root filled teeth, only 2.9% had AP. The prevalence of AP in connection with molar teeth was higher (5.5%) than for premolar (4.5%) and anterior teeth (3.2%; P < 0.01). More premolar and molar teeth were root-filled (2.8 and 2.7%, respectively) than anterior teeth (1.3%; P < 0.01). The prevalence of AP increased with age. CONCLUSIONS: The prevalence of AP in root-filled and untreated teeth, and the frequency of root-filled teeth were comparable to those reported in previous similar studies carried out in European countries. The prevalence of root-filled teeth with AP was found to be higher compared to that demonstrated in other epidemiological studies.

Comparison of modified Bass technique with normal toothbrushing practices for efficacy in supragingival plaque removal.

OBJECTIVES: This study was designed to compare the efficacy in supragingival plaque removal of normal toothbrushing practices and a particular toothbrushing technique, the modified Bass method. SUBJECTS AND METHODS: The research consisted of two identical experiments with two toothbrushing methods: the normal toothbrushing practices and the modified Bass technique. Forty-six secondary, non-dental students (10 males and 36 females) with ages ranging from 18 to 30 years were selected. Dental plaque was assessed according to the Turesky modification of Quigley-Hein Index. Subjects were requested not to brush their teeth 48 h prior to the baseline record of plaque index. Participants were instructed to brush twice daily during 3 min for the duration of the 3-week trial using their usual toothpaste. Plaque index was recorded at 2, 7 and 21 days. RESULTS: The modified Bass (Mod-Bass) technique was significantly (P < 0.05) more effective in removing supragingival plaque than normal toothbrushing practices both in all, buccal and lingual sites. After 21 days, the normal practices did not significantly decrease mean plaque indices compared to the scores calculated after 7 days (P > 0.05), but did so with the modified Bass technique (P < 0.05). The modified Bass technique was specially efficient at the lingual sites where it was 2.9-fold more effective than normal practices in reducing plaque scores (P < 0.01). CONCLUSION: The results show that a particular toothbrushing technique as modified Bass method is significantly superior to normal toothbrushing practices in supragingival plaque removal. The introduction of a specific toothbrushing technique, such as modified Bass technique represents an important improvement in the oral hygiene of the patients.

The rise and fall of democratic universalism: health care reform in Italy, 1978-1994.

In 1978, a sweeping reform created the first national health service of continental Europe: Italy's Servizio Sanitario Nazionale. This new scheme was based on the principle of "full democratic universalism": The state would provide free and equal benefits to every citizen and the organization of public health would subject to popular control, essentially through political parties. However, the severe problems encountered in implementing the reform design and rapidly increasing health expenditures soon eroded any consensus on this principle. Thus the 1980s and early 1990s witnessed a gradual shift to "conditional and well managed universalism." These latter principles stress the need to differentiate access to care according to some criterion to regulate demand and the need for efficient use of scarce resources through adequate valorization of managerial skills and the use of "market-type" incentives. An elaborated system of user copayments was introduced gradually, and in 1992 a "reform of the reform" profoundly changed the organizational framework of the Servizio Sanitario Nazionale. The new government elected in the spring of 1994 announced ambitious plans to partially dismantle public universal insurance. Although these plans may prove difficult, the potential to form an anti-universalistic coalition seems strong in the contemporary Italian health care arena.

Novel hirudin variants from the leech Hirudinaria manillensis. Amino acid sequence, cDNA cloning and genomic organization.

Novel hirudin variants isolated from the leech Hirudinaria manillensis, a leech more specialized for mammalian parasitism, are described. Isolation of antithrombin polypeptides was performed by ion-exchange chromatographies followed by an affinity chromatography step on immobilized thrombin. The major active component, antithrombin polypeptide peak 2 (HM2) and a second polypeptide, named HM1, were purified to homogeneity and their complete amino acid sequences were determined. The protein structure of the two hirudin variants include 64 amino acids with 6 cysteine residues at highly conserved positions. Comparison of the amino acid sequences of HM1 and HM2 with other known hirudins shows differences mainly in the central part and in the C-terminal region of the polypeptides. Particularly significant is the lack of a sulfated tyrosine residue in the C-terminal portion of the molecule which is replaced by aspartic acid. Polymerase chain reaction cloning techniques were used to isolate and characterize the cDNAs and determine the genomic structures of these hirudin-like polypeptides. The cDNA clones coding for the two variants indicate the expression of pre-hirudins of 84 amino acids where the first 20 residues constitute the signal peptide required for extracellular secretion. The leader sequence appears to be highly conserved for both isoforms and shares a complete similarity with the partial hirudin variant 2 (HV2) signal peptide sequence previously reported. The HM1 and HM2 gene fragments show the presence of four exons: the first one corresponding to a 20-amino-acid signal peptide while the other three exons share the full primary structure of the antithrombin polypeptides. HM2 was also efficiently produced in recombinant Escherichia coli by expressing a periplasmic construction containing the synthetic gene.