A Vaccine to Prevent Egg Layer Peritonitis in Chickens.

A series of studies was undertaken in specific-pathogen-free white leghorn chickens for the development of a chicken model of avian pathogenic Escherichia coli (APEC) peritonitis. Once established, this model was then used to measure the effectiveness of a siderophore receptor and porin proteins (SRP®) APEC vaccine. Initially, five pilot studies were performed to compare the E. coli serotype, challenge route, and dose of inoculum that resulted in pathologies characteristic of the peritonitis observed in commercial layer facilities, such as widespread organ infection, atrophy, discoloration, corrugation of yolk sacs, and the presence of caseous exudate. Isolates of serotypes O1, O2, and O78 were tested by intravenous, intravaginal, intratracheal, and intraperitoneal routes and were compared at various levels of challenge inoculum. Daily observations of mortality and morbidity were made, and at necropsy, gross lesion scores were collected and bacterial colonization of internal organs determined. Outcomes varied from a complete lack of mortality or detectable pathology and low, or no, organ colonization in the case of intravaginal and intratracheal routes with each E. coli serotype to moderate to high levels of mortality, pathology, and colonization after challenge via the intravenous and intraperitoneal routes with O2 and O78 serotypes, respectively. The O78 serotype was found to result in pathologies consistent with field observations of peritonitis, and therefore, subsequent studies were performed only with O78. In addition to the relative failure with both the intratracheal and intravaginal routes of challenge, the intravenous route was found to be inconsistent and often resulted in lameness not observed with the intraperitoneal route. A final pilot study confirmed that the dose (∼ 8 log 10 CFU) administered by the intraperitoneal route replicated peritonitis, and therefore, all vaccination/challenge studies were conducted in this manner. Five vaccination/challenge studies are reported here in which variables of chicken age, vaccination interval, and vaccination to challenge interval were examined. In all studies, vaccine effectiveness was dramatic and was shown to completely protect against mortality and substantially against tissue colonization and pathology typical of APEC infections. The vaccine elicited a rapid onset of immunity with both narrow and broad vaccination intervals and in both young and mature chickens. Additionally, the vaccine was demonstrated to sustain robust effectiveness against mortality over 3 months. The SRP APEC vaccine should provide effective protection of young and mature chickens from E. coli under broadly flexible conditions of use in commercial operations.

Artíclo regular­Vacuna para prevenir la peritonitis de gallina de postura. Se llevó a cabo una serie de estudios en aves tipo Leghorn blancas libres de patógenos específicos para el desarrollo de un modelo en pollo para la peritonitis causada por Escherichia coli patógena aviar (APEC). Una vez establecido, este modelo se utilizó para medir la eficacia de una vacuna con proteínas del receptor de sideróforo y de porina (SRP®) de E. coli patógena aviar. Inicialmente, se realizaron cinco estudios piloto para comparar el serotipo de E. coli, la ruta de desafío y la dosis de inóculo que resultaron en patologías características de las peritonitis observadas en instalaciones comerciales de ponedoras, como la infección generalizada de órganos, atrofia, decoloración, ondulación de saco vitelino y la presencia de exudado caseoso. Los aislamientos de los serotipos O1, O2 y O78 se analizaron por vías intravenosa, intravaginal, intratraqueal e intraperitoneal y se compararon a varios niveles de inóculo de desafío. Se realizaron observaciones diarias de mortalidad y morbilidad, en la necropsia, se registraron puntuaciones de lesiones macroscópicas y se determinó la colonización bacteriana de los órganos internos. Los resultados variaron desde una ausencia total de mortalidad o patología detectable y una colonización de órganos baja o nula en el caso de las rutas intravaginal e intratraqueal con cada serotipo de E. coli hasta niveles de mortalidad, patología y colonización de moderados a altos después del desafío por vía intravenosa e intraperitoneal con los serotipos O2 y O78, respectivamente. Se encontró que el serotipo O78 dio como resultado patologías consistentes con las observaciones de campo de la peritonitis y por lo tanto, los estudios posteriores se realizaron solo con el serotipo O78. Además del fracaso relativo con las rutas de desafío intratraqueal e intravaginal, se descubrió que la vía intravenosa era inconsistente y a menudo, provocaba cojera que no se observaba con la vía intraperitoneal. Un estudio piloto final confirmó que la dosis (∼8 log10 UFC) administrada por vía intraperitoneal reproducía la peritonitis y por lo tanto, todos los estudios de vacunación/desafío se realizaron de esta manera. En este estudio se reportan cinco estudios de vacunación/desafío en los que se examinaron las variables de edad del pollo, intervalo de vacunación e intervalo de vacunación al desafío. En todos los estudios, la eficacia de la vacuna fue muy evidente y se demostró que protege completamente contra la mortalidad y sustancialmente contra la colonización de tejidos y la patología típica de las infecciones por E. coli patógena aviar. La vacuna provocó un rápido inicio de la inmunidad con intervalos de vacunación tanto estrechos como amplios y tanto en aves jóvenes como maduras. Además, se demostró que la vacuna mantiene una sólida eficacia contra la mortalidad durante tres meses. La vacuna con proteínas del receptor de sideróforo y de porina de E. coli patógena aviar debería proporcionar una protección eficaz de las aves jóvenes y maduras contra E. coli en condiciones de uso ampliamente flexibles en operaciones comerciales.

De novo truncating variants in the intronless IRF2BPL are responsible for developmental epileptic encephalopathy.

PURPOSE: Developmental and epileptic encephalopathies (DEEs) are severe clinical conditions characterized by stagnation or decline of cognitive and behavioral abilities preceded, accompanied or followed by seizures. Because DEEs are clinically and genetically heterogeneous, next-generation sequencing, especially exome sequencing (ES), is becoming a first-tier strategy to identify the molecular etiologies of these disorders. METHODS: We combined ES analysis and international data sharing. RESULTS: We identified 11 unrelated individuals with DEE and de novo heterozygous truncating variants in the interferon regulatory factor 2-binding protein-like gene (IRF2BPL). The 11 individuals allowed for delineation of a consistent neurodevelopmental disorder characterized by mostly normal initial psychomotor development followed by severe global neurological regression and epilepsy with nonspecific electroencephalogram (EEG) abnormalities and variable central nervous system (CNS) anomalies. IRF2BPL, also known as enhanced at puberty protein 1 (EAP1), encodes a transcriptional regulator containing a C-terminal RING-finger domain common to E3 ubiquitin ligases. This domain is required for its repressive and transactivating transcriptional properties. The variants identified are expected to encode a protein lacking the C-terminal RING-finger domain. CONCLUSIONS: These data support the causative role of truncating IRF2BPL variants in pediatric neurodegeneration and expand the spectrum of transcriptional regulators identified as molecular factors implicated in genetic developmental and epileptic encephalopathies.

Phenotype-genotype correlations in patients with Marinesco-Sjögren syndrome.

Marinesco-Sjögren syndrome (MSS; MIM 248800) is an autosomal recessive disorder characterized by congenital cerebellar ataxia, early cataracts, developmental delay, myopathy and short stature. Alterations in the gene SIL1 cause MSS in some patients with typical findings. In this study, molecular investigations including sequencing of the SIL1 gene, western blotting and microscopic investigations in fibroblast cultures were carried out in a cohort of 15 patients from 14 unrelated families, including the large, inbred family reported by Superneau et al., having the clinical features of MSS to provide insights into the pathophysiology of the disorder. A total of seven different mutations were found in eight of the patients from seven families. The mutations caused loss of the BIP-associated protein (BAP) protein in four patients by western blot. Novel clinical features such as dental abnormalities, iris coloboma, eczema and hormonal abnormalities were noticed in some patients, but there was no clear way to distinguish those with and without SIL1 mutations. Cultured fibroblasts contained numerous cytoplasmic inclusion bodies, similar to those identified in the brain of the whoozy mouse in five unrelated patients, three with and two without SIL1 mutations, suggesting some SIL1 negative patients share a common cellular pathogenesis with those who are SIL1 positive.

Penile biometry on prenatal magnetic resonance imaging.

OBJECTIVE: In view of the implementation of magnetic resonance imaging (MRI) as an adjunct to ultrasonography in prenatal diagnosis, this study sought to demonstrate normal penile growth on prenatal MRI. METHODS: This was a retrospective study of MRI of 194 male fetuses (18-34 weeks' gestation) with normal anatomy or minor abnormalities. On sagittal T2-weighted MRI sequences, we measured penile length from the glans tip to the scrotal edge (outer length) and from the glans tip to the symphyseal border (total length). Descriptive statistics, as well as correlation and regression analysis, were used to evaluate penile length in relation to gestation. T-tests were calculated to compare mean outer/total length on MRI with published ultrasound data. RESULTS: Mean length values, including 95% CIs and percentiles, were defined. Penile length as a function of gestational age was expressed by the following regression equations: outer mean length = - 5.514 + 0.622 × gestational age in weeks; total mean length = - 8.865 + 1.312× gestational age in weeks. The correlation coefficients, r = 0.532 and r = 0.751, respectively, were statistically significant (P < 0.001). Comparison of outer penile length on MRI with published ultrasound penile length data showed no significant differences, while total penile length on MRI was significantly greater than ultrasound penile length (P < 0.001). CONCLUSION: Our MRI results provide a reference range of fetal penile length, which, in addition to ultrasonography, may be helpful in the identification of genital anomalies. Outer penile length on MRI is equivalent to penile length measured on ultrasound, whereas total length is significantly greater.

Ehlers-Danlos arthrochalasia type (VIIA-B)--expanding the phenotype: from prenatal life through adulthood.

The Ehlers-Danlos syndromes (EDS) form a clinically and genetically heterogeneous group of inherited connective-tissue disorders characterized by joint hypermobility, tissue fragility and skin abnormalities. Six subtypes have been well characterized based on clinical features and molecular genetic abnormalities. The arthrochalasia type EDS (formerly types VIIA and B) is characterized by severe generalized joint hypermobility with multiple dislocations including congenital bilateral dislocation of the hips, muscular hypotonia and distinct dysmorphic features. The diagnosis of the arthrochalasia type EDS is of importance in the neonatal period because of consequences of physical disability in later life. However, the differential diagnosis may be difficult because of overlap with other hypermobility syndromes. In addition, the significant hypotonia may direct the physician toward various neuromuscular diagnoses. As patients become older, the hypotonia decreases and facial features become less distinct. In this report, we describe seven patients at different ages. Timing of diagnosis varied from prenatal life to adult age. The diagnosis of EDS type VII was confirmed by biochemical studies or mutation analysis showing characteristic mutations in COL1A1 and COL1A2. These mutations result in skipping of exon 6, which leads to defective collagen synthesis. For physicians treating patients with EDS type VII, achieving mobility for the patient is the greatest challenge and it may be impossible because of recurrent dislocations of nearly all joints in severe cases.

Female external genitalia on fetal magnetic resonance imaging.

OBJECTIVES: To characterize the normal development of the female external genitalia on fetal magnetic resonance imaging (MRI). METHODS: This retrospective study included MRI examinations of 191 female fetuses (20-36 gestational weeks) with normal anatomy or minor abnormalities, following suspicion of anomalies on prenatal ultrasound examination. Using a 1.5-Tesla unit, the bilabial diameter was measured on T2-weighted sequences. Statistical description, as well as correlation and regression analyses, was used to evaluate bilabial diameter in relation to gestational age. MRI measurements were compared with published ultrasound data. The morphological appearance and signal intensities of the external genitalia were also assessed. RESULTS: Mean bilabial diameters, with 95% CIs and percentiles, were defined. The bilabial diameter as a function of gestational age was expressed by the regression equation: bilabial diameter = - 11.336 + 0.836 × (gestational age in weeks). The correlation coefficient, r = 0.782, was statistically significant (P < 0.001). Bilabial diameter on MRI was not significantly different from that on ultrasound (P < 0.001). In addition, on MRI we observed changes in morphology of the external genitalia and in signal intensities with increasing gestational age. CONCLUSIONS: We have provided a reference range of fetal bilabial diameter on MRI, which, in addition to ultrasound findings, may be helpful in the identification of genital anomalies.

Abnormalities of the upper extremities on fetal magnetic resonance imaging.

OBJECTIVE: In view of the increasing use of fetal magnetic resonance imaging (MRI) as an adjunct to prenatal ultrasonography, we sought to demonstrate the visualization of upper extremity abnormalities and associated defects on MRI, with regard to fetal outcomes and compared with ultrasound imaging. METHODS: This retrospective study included 29 fetuses with upper extremity abnormalities visualized with fetal MRI following suspicious ultrasound findings and confirmed by postnatal assessment or autopsy. On a 1.5-Tesla unit, dedicated sequences were applied to image the extremities. Central nervous system (CNS) and extra-CNS anomalies were assessed to define extremity abnormalities as isolated or as complex, with associated defects. Fetal outcome was identified from medical records. MRI and ultrasound findings, when available, were compared. RESULTS: Isolated upper extremity abnormalities were found in three (10.3%) fetuses. In 26 (89.7%) fetuses complex abnormalities, including postural extremity disorders (21/26) and structural extremity abnormalities (15/26), were demonstrated. Associated defects involved: face (15/26); musculoskeletal system (14/26); thorax and cardio/pulmonary system (12/26); lower extremities (12/26); brain and skull (10/26); and abdomen (8/26). Of the 29 cases, 18 (62.1%) pregnancies were delivered and 11 (37.9%) were terminated. MRI and US findings were compared in 27/29 cases: the diagnosis was concordant in 14 (51.9%) of these cases, and additional findings were made on MRI in 13/27 (48.1%) cases. CONCLUSIONS: Visualization of upper extremity abnormalities on fetal MRI enables differentiation between isolated defects and complex ones, which may be related to poor fetal prognosis. MRI generally confirms the ultrasound diagnosis, and may provide additional findings in certain cases.

Male sexual development in utero: testicular descent on prenatal magnetic resonance imaging.

OBJECTIVE: To visualize in utero male fetal testicular descent on magnetic resonance imaging (MRI) and to correlate it with gestational age. METHODS: This retrospective study included 202 MRI examination results of 199 male fetuses (17-39 gestational weeks) with normal anatomy or minor congenital abnormalities, following suspicion of anomalies on prenatal ultrasound examination. Using a 1.5-Tesla unit, multiplanar T2-weighted sequences were applied using a standard protocol to image and identify the scrotal content. The relative frequencies of unilateral and bilateral testicular descent were calculated and correlated with gestational age. RESULTS: Between 17 and 25 gestational weeks, neither unilateral nor bilateral testicular descent was visualized on MRI. Testicular descent was first observed at 25 + 4 weeks, in 7.7% of cases. 12.5% of 27-week fetuses showed unilateral descent and 50% showed bilateral descent. Bilateral descent was observed in 95.7% of cases, on average, from 30 to 39 weeks. CONCLUSIONS: Our results chart the time course of testicular descent on prenatal MRI, which may be helpful in the identification of normal male sexual development and in the diagnosis of congenital abnormalities, including the early detection of cryptorchidism.

Clinical experience in the evaluation of 30 patients with a prior diagnosis of FG syndrome.

BACKGROUND: FG syndrome (FGS) is an X-linked disorder characterised by mental retardation, hypotonia, particular dysmorphic facial features, broad thumbs and halluces, anal anomalies, constipation, and abnormalities of the corpus callosum. A behavioural phenotype of hyperactivity, affability, and excessive talkativeness is very frequent. The spectrum of clinical findings attributed to FGS has widened considerably since the initial description of the syndrome by Opitz and Kaveggia in 1974 and has resulted in clinical variability and genetic heterogeneity. In 2007, a recurrent R961W mutation in the MED12 gene at Xq13 was found to cause FGS in six families, including the original family described by Opitz and Kaveggia. The phenotype was highly consistent in all the R961W positive patients. METHODS: In order to determine the prevalence of MED12 mutations in patients clinically diagnosed with FGS and to clarify the phenotypic spectrum of FGS, 30 individuals diagnosed previously with FGS were evaluated clinically and by MED12 sequencing. RESULTS: The R961W mutation was identified in the only patient who had the typical phenotype previously associated with this mutation. The remaining 29 patients displayed a wide variety of features and were shown to be negative for mutations in the entire MED12 gene. A definite or possible alternative diagnosis was identified in 10 of these patients. CONCLUSION: This report illustrates the difficulty in making a clinical diagnosis of FGS given the broad spectrum of signs and symptoms that have been attributed to the syndrome. Individuals with a phenotype consistent with FGS require a thorough genetic evaluation including MED12 mutation analysis. Further genetic testing should be considered in those who test negative for a MED12 mutation to search for an alternative diagnosis.

A comparison of the analgesic efficacy and side-effects of paravertebral vs epidural blockade for thoracotomy--a systematic review and meta-analysis of randomized trials.

Epidural analgesia is considered by many to be the best method of pain relief after major surgery. It is used routinely in many thoracic surgery centres. Although effective, side-effects include hypotension, urinary retention, incomplete (or failed) block, and, in rare cases, paraplegia. Paravertebral block (PVB) is an alternative technique that may offer comparable analgesic effectiveness and a better side-effect profile. We undertook a systematic review and meta-analysis of all relevant randomized trials comparing PVB with epidural analgesia in thoracic surgery. Data were abstracted and verified by both authors. Studies were tested for heterogeneity, and meta-analyses were done with random effects or fixed effects models. Weighted mean difference (WMD) was used for numerical outcomes and odds ratio (OR) for dichotomous outcomes, both with 95% CI. We identified 10 trials that had enrolled 520 thoracic surgery patients. All of the trials were small (n<130) and none were blinded. There was no significant difference between PVB and epidural groups for pain scores at 4-8, 24 or 48 h, WMD 0.37 (95% CI: -0.5, 121), 0.05 (-0.6, 0.7), -0.04 (-0.4, 0.3), respectively. Pulmonary complications occurred less often with PVB, OR 0.36 (0.14, 0.92). Urinary retention, OR 0.23 (0.10, 0.51), nausea and vomiting, OR 0.47 (0.24, 0.53), and hypotension, OR 0.23 (0.11, 0.48), were less common with PVB. Rates of failed block were lower in the PVB group, OR 0.28 (0.2, 0.6). PVB and epidural analgesia provide comparable pain relief after thoracic surgery, but PVB has a better side-effect profile and is associated with a reduction in pulmonary complications. PVB can be recommended for major thoracic surgery.

How we do it: patient participation in cochlear implant selection.

. Involving patients and parents in the choice of their cochlear implant encourages an active role in the process and facilitates 'bonding' and 'ownership' of the device. . The most frequent reasons given by patients for selecting a device included cochlear implant comfort and appearance. . We describe the Implant Programme based at the Royal National Throat, Nose and Ear Hospital, London, and also examine patient satisfaction with the scheme.

A prospective randomized controlled trial evaluating alcohol on loudness perception in cochlear implant users.

AIM: The aim of this study was to determine the effects of alcohol on the psychophysical responses in patients with cochlear implants. This has not been previously studied. It was also hoped to provide information that could suggest possible sites of action of the known effects of alcohol on the auditory pathway. DESIGN: A prospective randomized placebo-controlled trial, with full ethical approval. PARTICIPANTS: Eight successful cochlear implant users were selected, of whom two had bilateral implants which were tested separately. In total 10 cochlear implants were tested. INTERVENTION: Alcohol was given in the form of vodka (50% alcohol, 1 mL/kg body weight) with 500 mL of orange and cranberry juice. The placebo control was given in the form of 500 mL of orange and cranberry juice alone. OUTCOME MEASUREMENT: The 'comfort level' (C level) was recorded before, and 1 h after alcohol or placebo ingestion for each patient's cochlear implant. Blood alcohol concentration was determined prior to alcohol or placebo consumption and then repeated after 45, 60, 90 and 180 min. RESULTS: The mean blood alcohol concentration 1 h after ingestion was 50 mg/dL. In the 'alcohol' arm the mean electrical unit increase in the C level was 19.9 with a standard deviation of 2.2. In the control arm the mean change in C level was 0.10 with a standard deviation of 0.3. CONCLUSIONS: In this first prospective randomized control study of the effect of alcohol on sound perception in cochlear implant users, alcohol significantly increased the upper end of the dynamic range (C levels) in comparison with placebo (P = <0.0001 using paired t-test analysis). This effect is likely to be the result of change in the auditory pathways proximal to the cochlea.

The relationship between oxygenator exhaust P(CO2) and arterial P(CO2) during hypothermic cardiopulmonary bypass.

During cardiopulmonary bypass the partial pressure of carbon dioxide in oxygenator arterial blood (P(a)CO2) can be estimated from the partial pressure of gas exhausting from the oxygenator (P(E)CO2). Our hypothesis is that P(E)CO2 may be used to estimate P(a)CO2 with limits of agreement within 7 mmHg above and below the bias. (This is the reported relationship between arterial and end-tidal carbon dioxide during positive pressure ventilation in supine patients.) During hypothermic (28-32 degrees C) cardiopulmonary bypass using a Terumo Capiox SX membrane oxygenator, 80 oxygenator arterial blood samples were collected from 32 patients during cooling, stable hypothermia, and rewarming as per our usual clinical care. The P(a)CO2 of oxygenator arterial blood at actual patient blood temperature was estimated by temperature correction of the oxygenator arterial blood sample measured in the laboratory at 37 degrees C. P(E)CO2 was measured by connecting a capnograph end-to-side to the oxygenator exhaust outlet. We used an alpha-stat approach to cardiopulmonary bypass management. The mean difference between P(E)CO2 and P(a)CO2 was 0.6 mmHg, with limits of agreement (+/-2 SD) between -5 to +6 mmHg. P(E)CO2 tended to underestimate P(a)CO2 at low arterial temperatures, and overestimate at high arterial temperatures. We have demonstrated that P(E)CO2 can be used to estimate P(a)CO2 during hypothermic cardiopulmonary bypass using a Terumo Capiox SX oxygenator with a degree of accuracy similar to that associated with the use of end-tidal carbon dioxide measurement during positive pressure ventilation in anaesthetized, supine patients.

The adult phenotype in Costello syndrome.

We report clinical findings in 17 adults with Costello syndrome ranging in age from 16 to 40 years. Two patients in this series have had bladder carcinoma, the only malignancy reported to affect adults with Costello syndrome. Benign tumors included multiple ductal papillomata in two women, and a fourth ventricle mass in one man, thought to be a choroid plexus papilloma. Endocrine problems in this series were osteoporosis, central hypogonadism, and delayed puberty. Other health problems were symptomatic Chiari malformations in three patients. Four patients had adult-onset gastro-esophageal reflux, three of whom had Chiari malformations. Fourteen adults had mild to moderate intellectual disability with three individuals having severe intellectual disability; 15 individuals attained some reading and writing skills and 14 showed ongoing acquisition of new skills into adulthood. On the basis of this data, we recommend that neuro-imaging be considered in adults with Costello syndrome if they develop symptoms suggestive of a Chiari malformation. In the event of pubertal delay, endocrine investigations are indicated and hormone treatment may be required. Bone density assessments should be performed in adults with Costello syndrome, particularly in those with pubertal abnormalities. Screening for microscopic hematuria as a marker for bladder carcinoma may be indicated, although this requires further evaluation.

Incidence of meningitis and of death from all causes among users of cochlear implants in the United Kingdom.

BACKGROUND: During 2002, there was an increase in reports of bacterial meningitis among people with cochlear implants in Europe and North America. One model of implant, which included a space-occupying 'positioner', was recalled. Implantation of a positioner was shown to be a risk factor for meningitis among children in the United States. The situation in the United Kingdom was not known. METHODS: We ascertained the cohort of people who had received cochlear implants with intra-cochlear electrodes in UK hospitals prior to 1 October 2002 and were permanently resident in the United Kingdom. We compared the incidence of meningitis, and the causes and incidence of death from all causes, between the cohort and reference populations. RESULTS: Of 1851 children (66 with positioners), none had contracted meningitis. Neither the incidence rate of meningitis, nor the cumulative mortality from all causes, differed significantly between implanted children and values expected for the general population. Of 1779 adults (139 with positioners), five had contracted meningitis with three fatalities. No case of meningitis involved a positioner and four of the cases, including the fatalities, possessed risk factors unrelated to implantation. Although the incidence rate of meningitis was significantly higher in implanted adults than the general population, cumulative mortality from all causes was never higher, and was significantly lower at some time points after implantation. CONCLUSION: Specific evidence of the association between bacterial meningitis and implantation with a positioner that arose in the United States and mainland Europe during 2002 has not been found in the United Kingdom.

Severe uncontrolled pain in buttock in a patient on naltrexone: a diagnostic challenge.

A 26-year-old woman with a history of intravenous drug use was admitted to hospital with worsening pain in the right buttock radiating to the lateral part of the thigh and to the calf with no suspicion of cauda equina compression. Eventually, a diagnosis of sacroiliitis was made and appropriate antibiotics were administered. Provision of analgesia for this patient was difficult. On admission her medications included naltrexone, venlafaxine and tramadol. Initially naltrexone was continued and analgesia provided by epidural local anaesthetic and clonidine, intravenous ketamine and oral agents. After several days, naltrexone was ceased and opioids were used in addition to the other analgesics. The epidural analgesia was only partially effective, perhaps because of inadequate blockade of the L4-S1 nerve roots, which carry sensation from the sacroiliac joint. Naltrexone is a long-acting opioid antagonist. If opioid analgesia is planned, it is necessary to cease naltrexone for 24 to 72 hours. In an emergency, if non-opioid techniques prove ineffective, short-acting opioids can be titrated to effect in a monitored environment.