Pinzamiento anterolateral del tobillo: evaluación ecotomográfica / Anterolateral impingement on ankle: echotomographic evaluation

Se realizó una evaluación de la anatomía ultrasonográfica de los ligamentos normales y patológicos de la región lateral del tobillo, con el objeto de determinar su utilidad en pacientes con clínica sugerente de pinzamiento anterolateral. Se estudiaron ambos lados en 15 pacientes sanos y en 14 pacientes referidos por traumatólogo con clínica sugerente. Los ligamentos evaluados fueron los: tibioperoneo anterior (TPA), peroneoastragalino (PA) y peroneocalcáneo. (PC) En pacientes sanos se observan como bandas ecogénicas, rectas, con estructura hipoecoica posterior. En 8 pacientes con sospecha clínia se detectó alteración en 11 ligamentos, observándose aumento de volumen y convexidad de la banda. A cuatro de estos pacientes se les practicó cirugía endoscópica encontrándose una buena correlación con los hallazgos ecotomográficos. En todos se indicó correctamente los ligamentos comprometidos. La ecotomografía de alta resolución puede ser un buen método diagnóstico en el pinzamiento anterolateral del tobillo a nivel de PA y TPA, especialmente si se considera como método alternativo a la RM por su bajo costo y accesibilidad

Isolated mental developmental delay in very low birth weight infants: association with prolonged doxapram therapy for apnea.

OBJECTIVE: We investigated factors associated with isolated mental delay in infants weighing < 1250 g at birth. STUDY DESIGN: With a case-control design, matching variables for 40 cases included gestation, birth weight, sex, grade of intraventricular hemorrhage, and socioeconomic status. Case subjects had a mental developmental index < 70, and controls had a mental developmental index > or = 85, according to the Bayley Scales of Infant Development II at 18 months' corrected age. RESULTS: There were no differences between the case and control subjects for neonatal complications and antenatal or postnatal steroid use. There was a marked difference in the cumulative dosage and duration of doxapram therapy used for apnea of prematurity (total dose 2233 +/- 1927 mg vs 615 +/- 767 mg, P < .001; duration 45.2 +/- 32.5 days vs 19.4 +/- 23.4 days, P < .001 for case subjects and control subjects, respectively). Multivariate analysis did not identify additive predictive variables. CONCLUSION: Isolated mental delay in infants weighing < 1250 g at birth was associated with the total dosage and duration of doxapram therapy for severe apnea. Although this may be a marker for cerebral dysfunction manifesting as apnea of prematurity, possible adverse effects of doxapram or its preservative, benzyl alcohol, on the developing brain deserve further study.

Clinical outcome after early Pseudomonas aeruginosa infection in cystic fibrosis.

OBJECTIVE: To determine the clinical consequences of acquiring Pseudomonas aeruginosa infection during early childhood in children with cystic fibrosis (CF). DESIGN: Prospective, observational cohort study of 56 children with CF identified by newborn screening during 1990-92. Each child underwent an annual bronchial lavage during the first 2 to 3 years of life. Clinical outcome was determined at 7 years of age. RESULTS: P aeruginosa infection was diagnosed in 24 (43%) cohort subjects. Four children died before 7 years of age, all of whom had been infected with a multi-resistant, mucoid strain of P aeruginosa (P =.04). In survivors, P aeruginosa infection was associated with significantly increased morbidity as measured by lower National Institutes of Health scores, greater variability in lung function, increased time in the hospital, and higher rates of recombinant human deoxyribonuclease therapy (P <.01). In this young CF cohort, best forced expiratory volume in 1 second was an insensitive measure of increased morbidity. CONCLUSIONS: Acquisition of P aeruginosa was common by 7 years of age in this CF birth cohort and was associated with increased morbidity and mortality. An improved disease severity score would improve the evaluation and study of early CF lung disease.

Cerebral infarction in the term newborn: clinical presentation and long-term outcome.

OBJECTIVE: We evaluated the long-term neurodevelopmental outcome of cranial computed tomography (CT)-documented cerebral infarction in term neonates to ascertain factors that would help to predict the risk of subsequent neurodevelopmental sequelae in early childhood. STUDY DESIGN: From 1983 to 1997, all surviving neonates from two level III neonatal intensive care units were prospectively identified and subsequently assessed in childhood. Clinical presentation was characterized by retrospective chart review and blinded re-reading of computed tomography (CT) scans. Perinatal events were compared with neurodevelopmental outcome. RESULTS: Forty-six children were followed up for a mean of 42.1 months (range, 18-164 months). Neurodevelopmental outcome was normal in 15 and abnormal in 31. A single disability was present in 8, and multiple disabilities were present in 23. Cerebral palsy was present in 22 and cognitive impairment in 19. Abnormal findings on neurologic examination at discharge and seizures in the neonatal period were associated with the presence of one or more childhood disabilities. The site or laterality of the vascular distribution of the lesion on neonatal CT did not correlate with long-term outcome. CONCLUSION: After cerebral infarction in the neonatal period, one third of term infants have normal long-term development. Neonatal seizure history and the findings on neurologic examination at discharge help in counseling parents about the possible long-term outcome of neonatal stroke.

The Leishmania mexicana proteasome.

As a start to understanding the importance of intracellular proteolysis in the protozoon Leishmania mexicana, the parasite proteasome has been purified and characterised. The L. mexicana proteasome is similar to proteasomes from other eukaryotes. It is soluble, and the 20S form has a mass of around 670 kDa, composed of at least 10 distinct subunits in the 22 to 32 kDa size range. The molecular mass of the L. mexicana proteasome increases to 1200 kDa in the presence of adenosine-5'-triphosphate, consistent with there being a 26S proteasome in the parasite. The purified 20S proteasome has activity towards substrates with hydrophobic, basic and acidic P, residues, and is sensitive to a range of peptide aldehyde inhibitors, as well as the proteasome-specific inhibitor lactacystin. The peptide aldehydes are able to arrest parasite growth in vitro with the same relative effectiveness as against the purified proteasome activity. The parasite population arrests with an increased 4N DNA content, indicating that, in part, the essential nature of the proteasome for L. mexicana proliferation is due to a role in the parasite cell cycle. Surprisingly, lactacystin is a relatively inefficient inhibitor of L. mexicana growth in vitro.

Prolonged use of pancuronium bromide and sensorineural hearing loss in childhood survivors of congenital diaphragmatic hernia.

Sensorineural hearing loss (SNHL) is a significant neurologic morbidity in survivors of neonatal congenital diaphragmatic hernia (CDH), with a reported incidence of up to 60%. In a historical cohort study of 37 neonates with CDH, we investigated the use of pancuronium bromide (PB) and common ototoxic drugs during the neonatal period and their relationship to SNHL in childhood survivors. Survivors with SNHL (n = 23) had significantly higher cumulative dose of PB administered during the neonatal illness than survivors without SNHL (n = 14). The cumulative dose and duration of PB use significantly correlated (r = 0.66-0.81) and independently predicted (adjusted r (2) = 0.42-0.64) the greatest intensity (in decibels) and the widest band (lowest frequency in hertz) loss of SNHL. No differences were identified between survivors with and without SNHL regarding demographic and neonatal characteristics (including oxygenation and ventilation variables and the cumulative dose and duration of therapy with aminoglycosides, vancomycin, and furosemide), although survivors with SNHL had received a modestly higher cumulative dose of ethacrynic acid than survivors without SNHL. Although we show that prolonged administration of PB during the neonatal period is associated with SNHL in childhood survivors of CDH, further multicenter studies are required to investigate the possible etiologies of SNHL in this high-risk population.

The outcome of very low birth weight neonates (

Although inhaled nitric oxide (INO) improves oxygenation in critically ill neonates, the neurodevelopmental outcome of premature neonates with severe hypoxemic respiratory failure treated with INO has not been reported. Mortality and prospective neurodevelopmental assessment in early childhood were studied in a cohort of 24 very low birth weight neonates (

Worldwide variations in prevalence of symptoms of allergic rhinoconjunctivitis in children: the International Study of Asthma and Allergies in Childhood (ISAAC).

BACKGROUND: As part of the International Study of Asthma and Allergies in Childhood (ISAAC), prevalence surveys were conducted among representative samples of school children from locations in Europe, Asia, Africa, Australia, North and South America. SUBJECTS: 257,800 children aged 6-7 years from 91 centres in 38 countries, and 463,801 children aged 13-14 years from 155 centres in 56 countries. METHODS: Written symptom questionnaires were translated from English into the local language for self-completion by the 13-14-year-olds and completion by the parents of the 6-7-year-olds. Rhinitis was described as a problem with sneezing, or a runny, or blocked nose when you (your child) DID NOT have a cold or the flu. Additional questions were asked about rhinitis associated with itchy-watery eyes, interference with activities and a history of hay fever ever. RESULTS: The prevalence of rhinitis with itchy-watery eyes ("rhinoconjunctivitis") in the past year varied across centres from 0.8% to 14.9% in the 6-7-year-olds and from 1.4% to 39.7% in the 13-14-year-olds. Within each age group, the global pattern was broadly consistent across each of the symptom categories. In centres of higher prevalence there was great variability in the proportion of rhinoconjunctivitis labelled as hay fever. The lowest prevalences of rhinoconjunctivitis were found in parts of eastern Europe, south and central Asia. High prevalences were reported from centres in several regions. CONCLUSION: These results suggest substantial worldwide variations in the prevalence and labelling of symptoms of allergic rhinoconjunctivitis which require further study. These differences, if real, may offer important clues to environmental influences on allergy.

One-year outcome in 232 premature infants with birth weights of 750 to 1249 grams and respiratory distress syndrome randomized to rescue treatment with two doses of synthetic surfactant or air placebo. Canadian Exosurf Neonatal Study Group.

A randomized, double-blind, placebo-controlled trial was performed in 13 hospitals in Canada to assess whether two rescue doses of a synthetic surfactant (Exosurf Neonatal) would reduce mortality and morbidity rates in neonates with respiratory distress syndrome who weighed from 750 to 1249 gm. As part of the original trial design, double-blind follow-up evaluations were performed at 1-year adjusted age. A total of 118 patients who received air placebo and 114 patients who received synthetic surfactant were evaluated at 1 year. Growth and development in the two groups were equivalent. Scores on the Bayley Scales of Infant Development were within the normal range for both groups (mental development index, 90 +/- 22 vs 92 +/- 22; psychomotor development index, 81 +/- 19 vs 87 +/- 22 for the air placebo and synthetic surfactant groups, respectively). However, in both groups the proportion of infants with any impairment (air placebo group, 43 of 118 (36%); synthetic surfactant group, 41 of 114 (36%) and severe impairment (air placebo group, 29 of 118 (25%); synthetic surfactant group, 21 of 114 (18%)) was substantial. We conclude that two rescue doses of synthetic surfactant in infants with RDS who weighed 750 to 1249 gm had no detrimental effect on developmental outcome or late morbidity. No long-term benefits to 12-months corrected age were observed with the use of surfactant in this weight class. Larger studies or meta-analyses of existing trials will be required to determine if there are any late outcome advantages associated with rescue use of synthetic surfactant in infants weighing 700 to 1249 gm.

Outcome at 1-year adjusted age of 957 infants weighing more than 1250 grams with respiratory distress syndrome randomized to receive synthetic surfactant or air placebo. American and Canadian Exosurf Neonatal Study Groups.

This study determined outcomes at 12-months adjusted age of 957 infants weighing more than 1250 gm at birth who were subjects in a randomized, double-blind, controlled trial of synthetic surfactant or air placebo administered in a rescue trial at 23 hospitals in the United States and 13 hospitals in Canada. Follow-up results were available for 475 of 563 surviving infants who received air placebo (84%) and 482 of 571 infants who received synthetic surfactant (84%). Developmental outcome was equivalent in the two groups. Morbidity was less in the synthetic surfactant group as assessed by the need for medication for chronic lung disease (52 of 475 (11%) for the air placebo group vs 32 of 482 (7%) for the synthetic surfactant group) or respiratory support (10 of 475 (2%) for the air placebo group vs 1 of 482 (< 1%) for the synthetic surfactant group) at 1-year adjusted age. Bayley Scales of Infant Development (mental development Index: 102 for both the air placebo and synthetic surfactant groups; psychomotor development index: 95 for the air placebo group vs 94 for the synthetic surfactant group) and impairment rates (94 of 475 (20%) for the air placebo group vs 86 of 482 (18%) for the synthetic surfactant group) were similar in the two groups. Infants weighing more than 1250 gm who have respiratory distress syndrome have previously been shown to have improved survival rates and lower neonatal morbidity after treatment with synthetic surfactant. These follow-up data confirm that developmental outcome as determined at 12-months adjusted age is at least as good in those receiving synthetic surfactant.

Analysis of the cysteine proteinases of Leishmania mexicana and Trypanosoma cruzi using specific antisera.

Antisera raised against papain and cysteine proteinases (CPs) purified from Leishmania mexicana and Trypanosoma cruzi have been used to study the proteins in the two parasites. The antisera against the major CP of T. cruzi (cruzipain) not only cross-reacted with known CPs of L. mexicana but also detected stage-specific molecules that may represent previously unrecognised CPs. The binding of the same antisera to extracts of different life cycle stages of T. cruzi suggested that the stages possess different isoforms of cruzipain. The lack of cross-reactivity of anti-papain antiserum against cruzipain suggests that the major immunogenic epitopes of these CPs are different, whereas the detection of the major CPs of L. mexicana with both heterologous antisera shows that the parasite's enzymes share epitopes with the other CPs.

Expression of cysteine proteinases by metacyclic promastigotes of Leishmania mexicana.

The expression of cysteine proteinases by metacyclic promastigotes of Leishmania mexicana was investigated using gelatin polyacrylamide gel electrophoresis. Two prominent bands were detected which distinguished metacyclics from multiplicative promastigotes, lacking detectable cysteine proteinase activity, and amastigotes, with a distinct banding pattern composed of multiple enzymes. A correlation between relative activity of the metacyclic-specific bands and the prevalence of metacyclics was found both during the growth cycle in vitro as metacyclogenesis occurred, and by comparison of stationary phase populations from consecutive subpassages in vitro. Irreversible inhibition of the metacyclic activities using N-benzyloxycarbonyl-phenylalanyl-alanyl diazomethane did not inhibit metacyclic to amastigote transformation in vitro. These activities provide a useful biochemical marker for the metacyclic promastigotes of L. mexicana.

Multiple high activity cysteine proteases of Leishmania mexicana are encoded by the Imcpb gene array.

The interrelationship of the multiple cysteine proteases (CPs) found characteristically at high activity in Leishmania mexicana amastigotes has been investigated. The mature forms of the five enzymes of groups B and C, which have subtly different substrate preferences, are the same size. Enzymically deglycosylated group A CP proteins also have the same molecular mass. Proteases of all three groups are specifically recognized by antisera raised against the group B or group C CPs. In addition, CPs of groups A, B and C have highly similar N-terminal amino acid sequences. The consensus sequence matches that predicted from the sequenced Imcpb gene, which occurs in a tandem array of over ten similar genes. Thus, the results are consistent with the groups A, B and C CPs being products of different Imcpb genes within the array, the different genes encoding CPs with identical N-termini, but with limited amino acid substitutions within the mature enzyme accounting for the different properties of the CPs. Evidence is also presented to indicate membrane-association of proteolytically active but less processed forms of Imcpb products.

Cathepsin B-like cysteine proteases of Leishmania mexicana.

A group of Leishmania mexicana cysteine proteases that differ from those previously found in this protozoon are described. The enzymes characteristically have a preference for peptidyl substrates with a phenylalanyl-valyl-arginyl moiety, do not hydrolyse gelatin in substrate-sodium dodecyl sulphate polyacrylamide gels, are stimulated by thiol-reducing agents and are sensitive to inhibitors specific for cysteine proteases. They have unusual solubility properties that indicate that the enzymes are amphiphilic proteins. Two of the cysteine proteases have been purified from L. mexicana amastigotes and shown to have molecular masses of 31 and 33 kDa. Their N-terminal amino acid sequences are very similar and show high homology to the mammalian cysteine protease, cathepsin B.

International comparison of asthma prevalence in children: Australia, Switzerland, Chile.

The aim of the study was to determine if the prevalence of symptoms suggestive of asthma in school-age children was similar in three countries with differing language and culture. To answer this question, we used the same instrument, translated appropriately, for schoolchildren in Melbourne, Australia, St. Gallen, Switzerland, and La Serena, Chile. A three page respiratory symptoms questionnaire was issued to schools for distribution to children for completion by parents and return to the school. Three age groups were selected for study, based on the average age of the school grade. Grades were used with average ages of 7, 12, and 15 years, respectively. A total of 26,628 questionnaires were issued to parents (Australia, 10,981; Switzerland, 4,464; Chile, 11,183). The response rates for each country were 89% for Australia, 97.5% for Switzerland, and 71% for Chile. The prevalence of wheezing in the last 12 months for 7 year olds was 23.1% in Melbourne, 7.4% in St. Gallen, and 26.5% in La Serena; for 12 year olds it was 20.9% in Melbourne, 6.0% in St. Gallen, and 21.1% in La Serena; for 15 year olds it was 18.6% in Melbourne, 4.5% in St. Gallen, and 17.7% in La Serene. A history of wheezing was more common in boys than girls at age 7 in Melbourne and St. Gallen, but not La Serena. This difference was less at age 12 and was not seen at age 15. Among those who had reported wheezing in the last 12 months, bronchodilator use was reported by 83% (1,611/1,948) from Melbourne, 46% (118/259) from St. Gallen, and 47% (538/1,140) from La Serena.(ABSTRACT TRUNCATED AT 250 WORDS)

Axenic cultivation and characterization of Leishmania mexicana amastigote-like forms.

A new method is described which has made possible the long-term axenic cultivation of Leishmania mexicana amastigote-like forms in Schneider's Drosophila medium supplemented with 20% (v/v) foetal calf serum. Unlike previous methods, it utilizes direct culture of parasites obtained from the lesions of infected animals rather than adaptation of promastigotes in vitro. Ultrastructural (possession of megasomes), biochemical (cysteine proteinase activity and gelatin SDS-PAGE banding pattern) and infectivity (in vivo) data are presented which show the close similarity of the cultured forms to lesion amastigotes. The axenically cultured forms grew optimally at a temperature of 32-33 degrees C, providing further evidence for their amastigote nature. It was found that adjustment of the pH of the growth medium to 5.4 was required in order to retain the amastigote morphology of the cultured parasites. This supports the notion that leishmanial amastigotes are acidophiles.

A developmentally regulated cysteine proteinase gene of Leishmania mexicana.

We have isolated a gene encoding a previously unreported class of trypanosomatid cysteine proteinase (CP) from the protozoan parasite Leishmania mexicana. The single-copy gene (lmcpa) [corrected]. has several unusual features that distinguish it from CP genes cloned from the related species Trypanosoma brucei and Trypanosoma cruzi. These include a shorter C-terminal extension of only 10 amino acids and a three-amino-acid insertion, GlyValMet, close to the predicted N-terminus of the mature protein. Northern blot analysis showed that the gene is expressed in all life-cycle stages but at higher levels in the amastigote stage in the mammal and in stationary phase promastigote cultures which contain the infective metacyclic form of the parasite. A precursor protein of 38 kDa was detected in amastigotes and stationary phase promastigotes with antisera specific to the LmCPa pro-region, but was barely detectable in early log-phase promastigotes. Anti-central domain antisera recognized the 38 kDa precursor and 24 and 27 kDa proteins. The major CPs of L. mexicana amastigotes, previously designated types A, B and C, were not detected with the antisera, suggesting that the gene codes for a previously uncharacterized CP in L. mexicana. The 24 kDa protein detected by the antiserum has no activity towards gelatin but apparently hydrolyses the peptide substrate BzPheValArgAMC. The relative levels of the 24 and 27 kDa proteins vary between the different life-cycle stages. The results indicate that expression of this CP is regulated at both the RNA and protein level.

Stage-specific proteinases of Leishmania mexicana mexicana promastigotes.

Four distinct bands of cysteine proteinase activity were detected when stationary-phase populations of Leishmania mexicana mexicana were subjected to gelatin-SDS-PAGE. The highest mobility band contained at least three isoforms separable by mono Q anion exchange chromatography. These high mobility activities were distinct from all the major amastigote enzymes. Stationary-phase promastigote populations also contained two acid-activable precursor forms of the promastigote-specific band. It is suggested that these promastigote-specific activities occur in the infective metacyclic stage of the parasite and may have a role in parasite survival upon inoculation into a mammal.