Predictors of Rod Length Gain and Sagittal Alignment Change After Magnetically Controlled Growing Rod Lengthening.

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: There are preoperative characteristics that predict rod lengthening of magnetically controlled growing rods (MCGR). The lengthening of MCGR will lead to increased kyphosis. SUMMARY OF BACKGROUND DATA: The amount of length gained by MCGR is variable, and predictors are lacking. Similarly, sagittal plane changes over the MCGR lengthening period have not been investigated. MATERIALS AND METHODS: Patients with MCGR and a minimum 2-year follow-up were identified and those with previous spine surgery were excluded. Preimplantation, postimplantation, and last follow-up postlengthening radiographs were examined. Multiple linear regression analyses were used for rod length gain predictors. RESULTS: Fifty-six patients with early-onset scoliosis met inclusion criteria: nine idiopathic, five congenital, 14 neuromuscular, 20 syndromic, and eight skeletal dysplasia patients. No difference was seen between subtypes of early-onset scoliosis for rod length gain ( P =0.62). Shorter preoperative T1-T12 height and higher curve correction rate after implantation were significant predictors for rod length gain ( P <0.001). Preoperative major curve magnitude and kyphosis were not significant predictors. Flattening of the spine around the actuator and compensative increase in T1-T5 kyphosis were seen secondarily after MCGR implantation. Maximum sagittal kyphosis, T1-T5 kyphosis, and T5-T12 kyphosis did not change during lengthening. Lumbar lordosis significantly decreased postimplantation (first erect) but then increased during lengthening. Pelvic incidence and sacral slope both increased during lengthening, but this may be age related. CONCLUSION: Patients who gained the most rod length with MCGR were those with an initially shorter T1-T12 height and better initial curve correction at implantation, likely representing that implants work best in small patients with flexible curves. Diagnosis, preoperative curve magnitude, and thoracic kyphosis were not related to rod length gain. Thoracic kyphosis did not deteriorate over the lengthening phase. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

Molecular characterization of phenylketonuria patients from the North Region of Brazil: State of Pará.

BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive disease resulting from a deficiency of the enzyme phenylalanine hydroxylase (PAH). Hyperphenylalaninemias (HPA) due to PAH deficiency are accompanied by a wide variety of clinical, biochemical, and molecular features. To identify and characterize pathogenic variants in the PAH gene and establish a correlation between genotype and biochemical phenotype in patients with PKU from state of Pará in the North Region of Brazil. METHODS: All 13 exons of the PAH gene from 32 patients (21 PKU and 11 non-PKU HPA) were amplified by PCR and submitted to DNA sequencing (Sanger). Biochemical data were obtained from the patients' medical records. RESULTS: Molecular analysis identified 17 pathogenic variants and 3 nonpathogenic variants. The most frequent pathogenic variants were IVS10-11G>A (7.9%), p. Arg261Gln (7.9%), p. Val388Met (6.3%) and p. Ile65Thr (4.7%). Was observed correlations and inconsistencies between genotype and biochemical phenotype. CONCLUSION: In PKU patients from state of Pará, North Region of Brazil, a heterogeneous mutation spectrum was revealed, in which the most frequent mutations are variants commonly observed in other Brazilian studies and in the region of the Iberian Peninsula.

Growth Modulation by Tension Band Plate in Achondroplasia With Varus Knee Deformity: Comparison of Gait Analysis Measurements.

BACKGROUND: Limited evidence exists concerning growth modulation by tension band plate (TBP) to correct varus deformity in patients with achondroplasia with limited growth due to FGFR3 gene mutation. We evaluated the efficacy of TBP in children with achondroplasia with genu varum and reported the static radiographic and dynamic motion data to determine parameters that impact the rate of deformity correction. METHODS: Patients with achondroplasia with genu varum who underwent TBP surgery for growth modulation were studied. Those with at least 1 year of follow-up with TBP were included. Radiographic parameters were measured. Growth velocity of femoral/tibial length was calculated separately. Patients were deemed successful or unsuccessful. Spearman correlation analysis and Student t test were used to describe statistical results. RESULTS: Twenty-two patients (41 limbs; 12 girls) fulfilled our criteria. Mean age at TBP surgery was 7.6±2.4 years. Thirty-six femoral TBP and 41 tibial TBP were in place for 24.5±9.7 months. Mean mechanical axis deviation, mechanical lateral distal femoral angle, and medial proximal tibial angle preoperatively were 30.1±7.6 mm, 97.2±6.4, and 80.3±4.3 degrees, and 11±15.6 mm, 87.4±5.9, and 84.7±5.3 degrees at last follow-up ( P <0.001). Fifteen limbs were successfully straightened; 4 limbs were in more varus than the initial deformity. Twenty-four limbs with TBP were still undergoing correction. In successful limbs, mean age at surgery was 6.5±1.7 years and duration of TBP was 29.9±7.8 months. In 4 unsuccessful limbs, mean age at surgery was 11.7±1.2 years. Analysis in the gait laboratory included physical examination with the measurement of knee varus and kinematic varus based on a posterior view static standing photograph. Photographic measurement of varus was higher than the radiographic measurement. CONCLUSIONS: Growth modulation by TBP surgery is a reliable and simple technique to correct genu varum in achondroplasia. An early age at TBP implementation (mean: 6.5 y) is crucial to successfully correct the varus knee deformity. Furthermore, we recommend early and regular surveillance of achondroplasia for progressive varus knee deformity. LEVEL OF EVIDENCE: Level IV-cohort study.

Construction of exact minimal parking garages: nonlinear helical motifs in optimally packed lamellar structures.

Minimal surfaces arise as energy minimizers for fluid membranes and are thus found in a variety of biological systems. The tight lamellar structures of the endoplasmic reticulum and plant thylakoids are comprised of such minimal surfaces in which right- and left-handed helical motifs are embedded in stoichiometry suggesting global pitch balance. So far, the analytical treatment of helical motifs in minimal surfaces was limited to the small-slope approximation where motifs are represented by the graph of harmonic functions. However, in most biologically and physically relevant regimes the inter-motif separation is comparable with its pitch, and thus this approximation fails. Here, we present a recipe for constructing exact minimal surfaces with an arbitrary distribution of helical motifs, showing that any harmonic graph can be deformed into a minimal surface by exploiting lateral displacements only. We analyse in detail pairs of motifs of the similar and of opposite handedness and also an infinite chain of identical motifs with similar or alternating handedness. Last, we study the second variation of the area functional for collections of helical motifs with asymptotic helicoidal structure and show that in this subclass of minimal surfaces stability requires that the collection of motifs is pitch balanced.

The Genetic Landscape and Epidemiology of Phenylketonuria.

Phenylketonuria (PKU), caused by variants in the phenylalanine hydroxylase (PAH) gene, is the most common autosomal-recessive Mendelian phenotype of amino acid metabolism. We estimated that globally 0.45 million individuals have PKU, with global prevalence 1:23,930 live births (range 1:4,500 [Italy]-1:125,000 [Japan]). Comparing genotypes and metabolic phenotypes from 16,092 affected subjects revealed differences in disease severity in 51 countries from 17 world regions, with the global phenotype distribution of 62% classic PKU, 22% mild PKU, and 16% mild hyperphenylalaninemia. A gradient in genotype and phenotype distribution exists across Europe, from classic PKU in the east to mild PKU in the southwest and mild hyperphenylalaninemia in the south. The c.1241A>G (p.Tyr414Cys)-associated genotype can be traced from Northern to Western Europe, from Sweden via Norway, to Denmark, to the Netherlands. The frequency of classic PKU increases from Europe (56%) via Middle East (71%) to Australia (80%). Of 758 PAH variants, c.1222C>T (p.Arg408Trp) (22.2%), c.1066-11G>A (IVS10-11G>A) (6.4%), and c.782G>A (p.Arg261Gln) (5.5%) were most common and responsible for two prevalent genotypes: p.[Arg408Trp];[Arg408Trp] (11.4%) and c.[1066-11G>A];[1066-11G>A] (2.6%). Most genotypes (73%) were compound heterozygous, 27% were homozygous, and 55% of 3,659 different genotypes occurred in only a single individual. PAH variants were scored using an allelic phenotype value and correlated with pre-treatment blood phenylalanine concentrations (n = 6,115) and tetrahydrobiopterin loading test results (n = 4,381), enabling prediction of both a genotype-based phenotype (88%) and tetrahydrobiopterin responsiveness (83%). This study shows that large genotype databases enable accurate phenotype prediction, allowing appropriate targeting of therapies to optimize clinical outcome.

Insights on chemical-biological correlations learned from investigations on the sulfated galactan from the marine alga Bothryocladia occidentalis.

Marine organisms have been proven to be a valuable source of bioactive compounds. Among them, we highlight the sulfated galactans (SGs) from seaweeds, which besides being massively exploited as industrial thickening and gelling agents (agarans and carrageenans), have also shown promising pharmacological properties. Investigations on the non-agaran/-carrageenan SG from the red algae Bothryocladia occidentalis (SGBo) have demonstrated clear correlations between physical-chemical features and biological activities. SGBo is composed of 2,3-disulfated (~33%) or 2-sulfated (33%) α-D-galactose linked to non- or 2-sulfated ß-D-galactose repetitive disaccharide units. The notable serpin-dependent/-independent anticoagulant activity of SGBo (~130 international units [IU]/mg) is higher than those of other SGs containing less 2,3-disulfated α-D-galactose units and their low-molecular-weight derivatives, and thus is directly correlated to its high molecular mass (>200 kDa) and sulfation pattern. Although SGBo has antithrombotic efficacy equivalent to heparin and decreased bleeding potential at low-doses, high-doses substantially increase thrombus formation in animal models. Such an odd dose-dependent dual antithrombotic/prothrombotic activity has been attributed to the ability of SGBo to activate factor XII. In addition to anticoagulant properties, SGBo also exerts antimalarial, antileishmanial and antiophidic activities, and, therefore, has a remarkable potential for the research and development of novel drugs.

Columella Elongation Surgery Outcome in Complete Bilateral Cleft Lip and Palate.

BACKGROUND: The evaluation of surgical outcomes is needed to achieve excellence in nasal reconstruction of patients with complete bilateral cleft lip and palate (BCLP). The study objective is to evaluate the quality of nasal aesthetics after the columella elongation surgery. METHODS: The sample of this study consisted of 70 patients with complete BCLP, operated on columella elongation surgery and analyzed at 6 to 12 years. The system for evaluation of nasal appearance after the columella elongation surgery was performed by objective and subjective analyses. ANTHROPOMETRIC MEASUREMENTS: Four anthropometric nose measurements were performed directly on the faces, and the same was performed in control group (60 children without oral clefts), paired by age and sex with the experimental group. The measurements were repeated 3 times (triplicate). SUBJECTIVE ANALYSIS: Scores to evaluate nasal width, nasal tip projection, and length of the columella were applied before and after the columella elongation surgery by 5 raters from the rehabilitation team. Interrater and intrarater agreement was calculated by means of the kappa test. RESULTS: Nasal width in BCLP group was higher when compared to the control group (P < 0.05). Nasal tip projection (subnasal-pronasal) and columella length (subnasal-columella) were decreased in BCLP group compared to that of the controls (P < 0.05). Columella width was similar in both study groups (P > 0.05). All scores of nasal aesthetics significantly improved after the columella elongation surgery. CONCLUSIONS: Nose of the patients with BCLP is wider, is less projected, and has the shorter columella compared to that of the noncleft subjects. After secondary columella elongation surgery in BCLP, nasal width, nasal projection, and columella length significantly improved.

Diagnosis and Management of Classica Homocystinuria in Brazil: A Summary of 72 Late-Diagnosed Patients

Abstract This study described a broad clinical characterization of classical homocystinuria (HCU) in Brazil. This was a cross-sectional, observational study including clinical and biochemical data from 72 patients (60 families) from Brazil (South, n = 13; Southeast, n = 37; Northeast, n = 8; North, n = 1; and Midwest, n = 1). Parental consanguinity was reported in 42% of families. Ocular manifestations were the earliest detected symptom (53% of cases), the main reason for diagnostic suspicion (63% of cases), and the most prevalent manifestation at diagnosis (67% of cases). Pyridoxine responsiveness was observed in 14% of patients. Only 22% of nonresponsive patients on treatment had total homocysteine levels <100 mmol/L. Most commonly used treatment strategies were pyridoxine (93% of patients), folic acid (90%), betaine (74%), vitamin B12 (27%), and low-methionine diet + metabolic formula (17%). Most patients diagnosed with HCU in Brazil are late diagnosed, express a severe phenotype, and poor metabolic control. Milder forms of HCU are likely underrepresented due to underdiagnosis.

Analysis of the genetic ancestry of patients with oral clefts from South American admixed populations.

Increased susceptibility to cleft lip, with or without cleft palate (CL±P) has been observed in South America, as related to Amerindian ancestry, using epidemiological data, uniparental markers, and blood groups. In this study, it was evaluated whether this increased risk remains when Amerindian ancestry is estimated using autosomal markers and considered in the predictive model. Ancestry was estimated through genotyping 62 insertion and deletion (INDEL) markers in sample sets of patients with CL±P, patients with cleft palate (CP), and controls, from Patagonia in southern Argentina and Belém in northern Brazil. The Amerindian ancestry in patients from Patagonia with CL±P was greater than in controls although it did not reach statistical significance. The European ancestry in patients with CL±P from Belém and in patients with CP from Belém and Patagonia was higher than in controls and statistically significant for patients with CP who were from Belém. This high contribution of European genetic ancestry among patients with CP who were from Belém has not been previously observed in American populations. Our results do not corroborate the currently accepted risks for CL±P and CP estimated by epidemiological studies in the North American populations and probably reflect the higher admixture found in South American ethnic groups when compared with the same ethnic groups from the North American populations.

Mucopolysaccharidoses in northern Brazil: Targeted mutation screening and urinary glycosaminoglycan excretion in patients undergoing enzyme replacement therapy.

Mucopolysaccharidoses (MPS) are rare lysosomal disorders caused by the deficiency of specific lysosomal enzymes responsible for glycosaminoglycan (GAG) degradation. Enzyme Replacement Therapy (ERT) has been shown to reduce accumulation and urinary excretion of GAG, and to improve some of the patients' clinical signs. We studied biochemical and molecular characteristics of nine MPS patients (two MPS I, four MPS II and three MPS VI) undergoing ERT in northern Brazil. The responsiveness of ERT was evaluated through urinary GAG excretion measurements. Patients were screened for eight common MPS mutations, using PCR, restriction enzyme tests and direct sequencing. Two MPS I patients had the previously reported mutation p.P533R. In the MPS II patients, mutation analysis identified the mutation p.R468W, and in the MPS VI patients, polymorphisms p.V358M and p.V376M were also found. After 48 weeks of ERT, biochemical analysis showed a significantly decreased total urinary GAG excretion in patients with MPS I (p < 0.01) and MPS VI (p < 0.01). Our findings demonstrate the effect of ERT on urinary GAG excretion and suggest the adoption of a screening strategy for genotyping MPS patients living far from the main reference centers.

Tetrahydrobiopterin responsiveness of patients with phenylalanine hydroxylase deficiency.

OBJECTIVE: To identify patients responsive to tetrahydrobiopterin (BH4) in a sample of Brazilians with hyperphenylalaninemia due to phenylalanine hydroxylase deficiency (HPA-PAH). METHODS: Interventional study, convenience sampling. The inclusion criteria were: diagnosis of HPA-PAH; age ≥ 7 years; phenylalanine-restricted diet and phenylalanine (Phe) levels ≥ 6 mg/dL in all blood tests 1 year before inclusion. Blood samples were obtained the day before (day 1) and at 0, 4, 8 (day 2) and 24 h (day 3) after BH4 intake. Phe levels were measured using tandem mass spectrometry. The criteria used to define responsiveness to BH4 were: criterion 1- Phe reduction ≥ 30% 8 h after BH4 administration; criterion 2 - Phe reduction ≥ 30% 24 h after BH4 administration. RESULTS: Eighteen patients were enrolled (median age, 14 years; 12 boys). Five patients were responsive to BH4, 3 according to both criteria (one classical PKU, two mild PKU); and two according to criterion 2 (one classical PKU; one indefinite PKU type). There were no differences between Phe serum levels on day 1 and at the other time points (p = 0.523). However, Phe levels on days 1 and 2 were significantly different (p = 0.006). The analysis of the phenotype-genotype association confirmed its multifactorial character. CONCLUSION: A relevant number of Brazilian patients with HPA-PAH are responsive to BH4, in agreement with other studies in the literature.

Responsividade à tetrahidrobiopterina em pacientes com deficiência de fenilalanina hidroxilase / Tetrahydrobiopterin responsiveness of patients with phenylalanine hydroxylase deficiency

OBJETIVO: Identificar indivíduos responsivos à tetrahibrobiopterina (BH4) em uma amostra de pacientes brasileiros com hiperfenilalaninemia por deficiência de fenilalanina-hidroxilase (HPA-PAH). MÉTODOS: Estudo intervencional, amostragem por conveniência. Para serem incluídos no estudo, os pacientes deveriam: possuir diagnóstico bioquímico de HPA-PAH; ter idade > 7 anos; estar em tratamento dietético; e apresentar níveis de fenilalanina (Phe) > 6 mg/dL em todas as medidas realizadas no ano anterior à inclusão no estudo. Os níveis de Phe foram determinados por meio de espectrometria de massas in tandem no dia anterior (dia 1) e nos pontos de hora 0, 4 e 8 h (dia 2) e 24 h (dia 3) após ingestão de BH4. Os critérios utilizados para definir responsividade ao BH4 foram: critério 1-redução > 30 por cento de Phe após 8 h da administração de BH4; e critério 2-redução > 30 por cento de Phe após 24 h da administração. RESULTADOS: Dezoito pacientes foram incluídos no estudo (mediana de idade = 14 anos, sexo masculino = 12). Cinco pacientes foram responsivos ao BH4, sendo três (forma clássica: um; forma leve: dois) de acordo com ambos os critérios, e dois (forma clássica: um; forma não definida: um) de acordo com o critério 2. Os níveis de Phe plasmáticos do dia 1 não demonstraram variação nos pontos de hora (p = 0,523). Entretanto, quando comparamos os níveis de Phe nos pontos de hora dos dias 1 e 2, encontramos uma variação significativa (p = 0,006). A análise da associação genótipo-fenótipo confirmou o caráter multifatorial da responsividade ao BH4. CONCLUSÃO: Os nossos achados estão de acordo com a literatura e indicam que um número relevante de pacientes brasileiros com HPA-PAH é responsivo à BH4.

OBJECTIVE: To identify patients responsive to tetrahydrobiopterin (BH4) in a sample of Brazilians with hyperphenylalaninemia due to phenylalanine hydroxylase deficiency (HPA-PAH). METHODS: Interventional study, convenience sampling. The inclusion criteria were: diagnosis of HPA-PAH; age > 7 years; phenylalanine-restricted diet and phenylalanine (Phe) levels > 6 mg/dL in all blood tests 1 year before inclusion. Blood samples were obtained the day before (day 1) and at 0, 4, 8 (day 2) and 24 h (day 3) after BH4 intake. Phe levels were measured using tandem mass spectrometry. The criteria used to define responsiveness to BH4 were: criterion 1- Phe reduction > 30 percent 8 h after BH4 administration; criterion 2 - Phe reduction > 30 percent 24 h after BH4 administration. RESULTS: Eighteen patients were enrolled (median age, 14 years; 12 boys). Five patients were responsive to BH4, 3 according to both criteria (one classical PKU, two mild PKU); and two according to criterion 2 (one classical PKU; one indefinite PKU type). There were no differences between Phe serum levels on day 1 and at the other time points (p = 0.523). However, Phe levels on days 1 and 2 were significantly different (p = 0.006). The analysis of the phenotype-genotype association confirmed its multifactorial character. CONCLUSION: A relevant number of Brazilian patients with HPA-PAH are responsive to BH4, in agreement with other studies in the literature.

Ethical issues related to the access to orphan drugs in Brazil: the case of mucopolysaccharidosis type I.

BACKGROUND/AIMS: Mucopolysaccharidosis type I (MPS I) is a rare lysosomal storage disorder treated with bone marrow transplantation or enzyme replacement therapy with laronidase, a high-cost orphan drug. Laronidase was approved by the US Food and Drug Administration and the European Medicines Agency in 2003 and by the Brazilian National Health Surveillance Agency in 2005. Many Brazilian MPS I patients have been receiving laronidase despite the absence of a governmental policy regulating access to the drug. Epidemiological and treatment data concerning MPS I are scarce. This study aims to present a demographic profile of Brazilian patients with MPS I, describe the routes of access to laronidase in Brazil, and discuss associated ethical issues relating to public funding of orphan drugs. METHODS: In this cross-sectional observational study, data were collected nationwide between January and September 2008 from physicians, public institutions and non-governmental organisations involved with diagnosis and treatment of MPS I, using two data collection instruments specifically designed for this purpose. RESULTS: The minimum prevalence of MPS I in Brazil was estimated at 1/2,700,000. Most patients (69.8%) were younger than 15 years; 60 (88.2%) received laronidase. The most common route of access to the drug was through lawsuits (86.6%). CONCLUSIONS: In Brazil, MPS I is predominantly a paediatric illness. Even though the cost of laronidase treatment is not officially covered by the Brazilian government, most MPS I patients receive the drug, usually through litigation. This gives rise to major ethical conflicts concerning drug access in a low-resource context. The Brazilian health policy framework lacks evidence-based clinical protocols for the distribution of orphan drugs.

Mucopolysaccharidoses in northern Brazil: Targeted mutation screening and urinary glycosaminoglycan excretion in patients undergoing enzyme replacement therapy

Mucopolysaccharidoses (MPS) are rare lysosomal disorders caused by the deficiency of specific lysosomal enzymes responsible for glycosaminoglycan (GAG) degradation. Enzyme Replacement Therapy (ERT) has been shown to reduce accumulation and urinary excretion of GAG, and to improve some of the patients' clinical signs. We studied biochemical and molecular characteristics of nine MPS patients (two MPS I, four MPS II and three MPS VI) undergoing ERT in northern Brazil. The responsiveness of ERT was evaluated through urinary GAG excretion measurements. Patients were screened for eight common MPS mutations, using PCR, restriction enzyme tests and direct sequencing. Two MPS I patients had the previously reported mutation p.P533R. In the MPS II patients, mutation analysis identified the mutation p.R468W, and in the MPS VI patients, polymorphisms p.V358M and p.V376M were also found. After 48 weeks of ERT, biochemical analysis showed a significantly decreased total urinary GAG excretion in patients with MPS I (p < 0.01) and MPS VI (p < 0.01). Our findings demonstrate the effect of ERT on urinary GAG excretion and suggest the adoption of a screening strategy for genotyping MPS patients living far from the main reference centers.

High frequency of D727E polymorphisms in exon 10 of the TSHR gene in Brazilian patients with congenital hypothyroidism.

Congenital Hypothyroidism affects between 1:3000 and 1:4000 newborn infants in iodine-sufficient regions. Some studies have shown that mutations and polymorphisms in the TSH receptor gene are responsible for this disease. In the present study, mutations of exon 10 of the TSH receptor gene were investigated in Congenital Hypothyroidism patients. In the present study a sample of 90 Brazilian patients with primary congenital hypothyroidism was analyzed. Genomic DNA was isolated from peripheric blood samples. Exon 10 of the TSH receptor gene was amplified by PCR, and amplicons were automatically sequenced. Three nucleotide alterations were identified: c.1377G>A (A459A), c.1935G>A (L645L), and c.2181C>G (D727E). A459A polymorphism was also described previously in patients with thyroid cancer. The nucleotide alteration L645L was found in a single patient. This is the first time the L645L mutation has been described. D727E polymorphism showed high frequency (allele frequency 10%) in present study when compared to others reports.

Effects of chronic exposure to crack cocaine on the respiratory tract of mice.

Smoked cocaine (crack cocaine) causes several forms of injury to the respiratory tract, including asthma exacerbations, lung edema and hemorrhage, and nasal mucosal alterations. Few studies, however, have assessed respiratory tract pathology in habitual users of crack cocaine. Here, we describe the histological alterations in the respiratory tract of mice caused by chronic inhalation of crack cocaine. Twenty 2-month-old BALB/c mice were exposed to the smoke of 5 g crack cocaine in an inhalation chamber once a day for two months and compared to controls (n = 10). We then morphometrically analyzed nose and bronchiolar epithelial alterations, bronchiolar and alveolar macrophage cell density, alveolar hemosiderin content, and in addition determined the vasoconstriction index and the wall thickness of pulmonary arteries. The serum cocaine level was 212.5 ng/mL after a single inhalation. The mucus content of the nasal epithelium increased in crack-exposed animals, and the nasal and bronchial epithelium thickness decreased significantly. The alveolar hemosiderin content and the alveolar and bronchiolar macrophage cell density increased in animals exposed to crack. The vasoconstriction index increased in the pulmonary arteries of the exposed group. Chronic crack cocaine inhalation causes extensive histological changes along the entire respiratory tract.

Hepatitis B virus infection in Haemodialysis Centres from Santa Catarina State, Southern Brazil. Predictive risk factors for infection and molecular epidemiology.

BACKGROUND: Patients under haemodialysis are considered at high risk to acquire hepatitis B virus (HBV) infection. Since few data are reported from Brazil, our aim was to assess the frequency and risk factors for HBV infection in haemodialysis patients from 22 Dialysis Centres from Santa Catarina State, south of Brazil. METHODS: This study includes 813 patients, 149 haemodialysis workers and 772 healthy controls matched by sex and age. Serum samples were assayed for HBV markers and viraemia was detected by nested PCR. HBV was genotyped by partial S gene sequencing. Univariate and multivariate statistical analyses with stepwise logistic regression analysis were carried out to analyse the relationship between HBV infection and the characteristics of patients and their Dialysis Units. RESULTS: Frequency of HBV infection was 10.0%, 2.7% and 2.7% among patients, haemodialysis workers and controls, respectively. Amidst patients, the most frequent HBV genotypes were A (30.6%), D (57.1%) and F (12.2%). Univariate analysis showed association between HBV infection and total time in haemodialysis, type of dialysis equipment, hygiene and sterilization of equipment, number of times reusing the dialysis lines and filters, number of patients per care-worker and current HCV infection. The logistic regression model showed that total time in haemodialysis, number of times of reusing the dialysis lines and filters, and number of patients per worker were significantly related to HBV infection. CONCLUSIONS: Frequency of HBV infection among haemodialysis patients at Santa Catarina state is very high. The most frequent HBV genotypes were A, D and F. The risk for a patient to become HBV positive increase 1.47 times each month of haemodialysis; 1.96 times if the dialysis unit reuses the lines and filters > or = 10 times compared with haemodialysis units which reuse < 10 times; 3.42 times if the number of patients per worker is more than five. Sequence similarity among the HBV S gene from isolates of different patients pointed out to nosocomial transmission.

Prevalence of TTV in blood donors and patients with acute viral hepatitis and genotyping by phylogenetic analysis

O objetivo desse estudo foi avaliar a prevalência da infecção pelo TTV em pacientes com hepatite aguda A e B e genotipar os isolados do TTV através de análise filogenética. Foram avaliados soros de 82 pacientes que apresentaram hepatite aguda A(N = 40) e B (N = 42)e 71 doadores de sangue. O TTV foi determinado atraváes nested-PCR, e a análise filogenetica foi realizada utilizando o metódo neighbor-Joining". O TTV foi detectado em 23por cento dos pacientes com hepatite aguda e em 31 por cento dos doadores. Os níveis médiosde aminotransferases foram semelhantes em pacientes TTV positivos e pacientes TTV negativos. Uma árvore filogenética foi construída e mostrou isolados do TTV dos genótipos1,2,3 e 4. Em conclusão, a infecção pelo TTV foi mais frequente entre doadores de sangue do que em pacientes com hepatite aguda A ou B, em Salvdor-Bahia. O TTV não aumentou a gravidade da atividade necroinflamatória dos pacientes com hepatite aguda A ou B. Através de análise filogenétiaca foram encontrados isolados do TTV dos genótipos 1,2,3 e 4 na população estudada