Brucella suis in three dogs: presentation, diagnosis and clinical management.

Brucella suis is an emerging, zoonotic disease predominantly affecting dogs and humans that engage in feral pig hunting in Australia and other countries. Although B. suis infection in dogs shares some clinical similarities to the host-adapted species (B. canis), B. suis remains an incompletely understood pathogen in dogs with limited published data on its pathogenesis and clinical features. This case series describes the presentations, diagnosis, and clinical management of B. suis infection in three dogs: (1) a bitch with dystocia, abortion and mastitis; (2) an entire male dog with septic arthritis and presumptive osteomyelitis; and (3) a castrated male dog with lymphadenitis. Unique features of these cases are reported including the first documented detection of B. suis from milk and isolation from lymph nodes of canine patients, as well as the follow-up of pups born to a B. suis-infected bitch. Consistent with previous reports, all three dogs showed a favourable clinical response to combination antibiotic therapy with rifampicin and doxycycline. Individually tailored drug regimens were required based on the clinical presentation and other factors, including owner expectations and compliance with therapy as well as a zoonotic risk assessment (generally considered low, except around time of whelping). The authors include their recommendations for the clinical management of dogs that are at-risk or seropositive for B. suis with or without clinical signs or laboratory-confirmed infection.

The FXR agonist obeticholic acid inhibits the cancerogenic potential of human cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive cancer with high resistance to chemotherapeutics. CCA is enriched in cancer stem cells, which correlate with aggressiveness and prognosis. FXR, a member of the metabolic nuclear receptor family, is markedly down-regulated in human CCA. Our aim was to evaluate, in primary cultures of human intrahepatic CCA (iCCA), the effects of the FXR agonist obeticholic acid (OCA), a semisynthetic bile acid derivative, on their cancerogenic potential. Primary human iCCA cell cultures were prepared from surgical specimens of mucinous or mixed iCCA subtypes. Increasing concentrations (0-2.5 µM) of OCA were added to culture media and, after 3-10 days, effects on proliferation (MTS assay, cell population doubling time), apoptosis (annexin V-FITC/propidium iodide), cell migration and invasion (wound healing response and Matrigel invasion assay), and cancerogenic potential (spheroid formation, clonogenic assay, colony formation capacity) were evaluated. Results: FXR gene expression was downregulated (RT-qPCR) in iCCA cells vs normal human biliary tree stem cells (p < 0.05) and in mucinous iCCA vs mixed iCCA cells (p < 0.05) but was upregulated by addition of OCA. OCA significantly (p < 0.05) inhibited proliferation of both mucinous and mixed iCCA cells, starting at a concentration as low as 0.05 µM. Also, CDCA (but not UDCA) inhibited cell proliferation, although to a much lower extent than OCA, consistent with its different affinity for FXR. OCA significantly induced apoptosis of both iCCA subtypes and decreased their in vitro cancerogenic potential, as evaluated by impairment of colony and spheroid formation capacity and delayed wound healing and Matrigel invasion. In general, these effects were more evident in mixed than mucinous iCCA cells. When tested together with Gemcitabine and Cisplatin, OCA potentiated the anti-proliferative and pro-apoptotic effects of these chemotherapeutics, but mainly in mixed iCCA cells. OCA abolished the capacity of both mucinous and mixed iCCA cells to form colonies when administered together with Gemcitabine and Cisplatin. In subcutaneous xenografts of mixed iCCA cells, OCA alone or combined with Gemcitabine or Cisplatin markedly reduced the tumor size after 5 weeks of treatment by inducing necrosis of tumor mass and inhibiting cell proliferation. In conclusion, FXR is down-regulated in iCCA cells, and its activation by OCA results in anti-cancerogenic effects against mucinous and mixed iCCA cells, both in vitro and in vivo. The effects of OCA predominated in mixed iCCA cells, consistent with the lower aggressiveness and the higher FXR expression in this CCA subtype. These results, showing the FXR-mediated capacity of OCA to inhibit cholangiocarcinogenesis, represent the basis for testing OCA in clinical trials of CCA patients.

Transcriptomic analysis and mutational status of IDH1 in paired primary-recurrent intrahepatic cholangiocarcinoma.

BACKGROUND: Effective target therapies for intrahepatic cholangiocarcinoma (ICC) have not been identified so far. One of the reasons may be the genetic evolution from primary (PR) to recurrent (REC) tumors. We aim to identify peculiar characteristics and to select potential targets specific for recurrent tumors. Eighteen ICC paired PR and REC tumors were collected from 5 Italian Centers. Eleven pairs were analyzed for gene expression profiling and 16 for mutational status of IDH1. For one pair, deep mutational analysis by Next Generation Sequencing was also carried out. An independent cohort of patients was used for validation. RESULTS: Two class-paired comparison yielded 315 differentially expressed genes between REC and PR tumors. Up-regulated genes in RECs are involved in RNA/DNA processing, cell cycle, epithelial to mesenchymal transition (EMT), resistance to apoptosis, and cytoskeleton remodeling. Down-regulated genes participate to epithelial cell differentiation, proteolysis, apoptotic, immune response, and inflammatory processes. A 24 gene signature is able to discriminate RECs from PRs in an independent cohort; FANCG is statistically associated with survival in the chol-TCGA dataset. IDH1 was mutated in the RECs of five patients; 4 of them displayed the mutation only in RECs. Deep sequencing performed in one patient confirmed the IDH1 mutation in REC. CONCLUSIONS: RECs are enriched for genes involved in EMT, resistance to apoptosis, and cytoskeleton remodeling. Key players of these pathways might be considered druggable targets in RECs. IDH1 is mutated in 30% of RECs, becoming both a marker of progression and a target for therapy.

Clinical safety of percutaneous ultrasound-guided fine-needle aspiration of adrenal gland lesions in 19 dogs.

OBJECTIVE: To evaluate the safety of fine-needle aspiration of adrenal gland lesions in dogs and to characterise the risks in a subset of patients with cytologically or histopathologically diagnosed phaeochromocytoma. MATERIALS AND METHODS: Retrospective review of medical records of dogs that underwent percutaneous ultrasound-guided fine-needle aspiration of adrenal gland lesions between August 2014 and December 2016. Nineteen dogs were identified, with three undergoing bilateral adrenal gland aspiration and one dog undergoing aspiration twice, yielding 23 cytology samples in total. Data collected included signalment, concurrent medical conditions, current medications, blood pressure and heart rate before adrenal fine-needle aspiration, imaging characteristics of the adrenal gland lesions and any clinically apparent procedure-related complications. RESULTS: Phaeochromocytoma was diagnosed in nine of 19 dogs, including one dog with bilateral phaeochromocytoma. One dog developed ventricular tachycardia following aspiration of an adrenal gland lesion cytologically consistent with a phaeochromocytoma. CLINICAL SIGNIFICANCE: Percutaneous ultrasound-guided fine-needle aspiration of adrenal gland lesions appears to be relatively safe, even in phaeochromocytoma, but further data are required to lend more weight to this finding. Minimally invasive aspirates could be considered as part of the diagnostic algorithm in the investigation of an incidentally detected adrenal gland lesion of uncertain clinical significance.

MSR1 repeats modulate gene expression and affect risk of breast and prostate cancer.

Background: MSR1 repeats are a 36-38 bp minisatellite element that have recently been implicated in the regulation of gene expression, through copy number variation (CNV). Patients and methods: Bioinformatic and experimental methods were used to assess the distribution of MSR1 across the genome, evaluate the regulatory potential of such elements and explore the role of MSR1 elements in cancer, particularly non-familial breast cancer and prostate cancer. Results: MSR1s are predominately located at chromosome 19 and are functionally enriched in regulatory regions of the genome, particularly regions implicated in short-range regulatory activities (H3K27ac, H3K4me1 and H3K4me3). MSR1-regulated genes were found to have specific molecular roles, such as serine-protease activity (P = 4.80 × 10-7) and ion channel activity (P = 2.7 × 10-4). The kallikrein locus was found to contain a large number of MSR1 clusters, and at least six of these showed CNV. An MSR1 cluster was identified within KLK14, with 9 and 11 copies being normal variants. A significant association with the 9-copy allele and non-familial breast cancer was found in two independent populations (P = 0.004; P = 0.03). In the white British population, the minor allele conferred an increased risk of 1.21-3.51 times for all non-familial disease, or 1.7-5.3 times in early-onset disease. The 9-copy allele was also found to be associated with increased risk of prostate cancer in an independent population (odds ratio = 1.27-1.56; P =0.009). Conclusions: MSR1 repeats act as molecular switches that modulate gene expression. It is likely that CNV of MSR1 will affect risk of development of various forms of cancer, including that of breast and prostate. The MSR1 cluster at KLK14 represents the strongest risk factor identified to date in non-familial breast cancer and a significant risk factor for prostate cancer. Analysis of MSR1 genotype will allow development of precise stratification of disease risk and provide a novel target for therapeutic agents.

Thigh burns from exploding e-cigarette lithium ion batteries: First case series.

E-cigarette (EC) use has risen meteorically over the last decade. The majority of these devices are powered by re-chargeable lithium ion batteries, which can represent a fire hazard if damaged, over-heated, over-charged or stored inappropriately. There are currently no reports in the medical literature of lithium ion battery burns related to EC use and no guidance on the appropriate management of lithium ion battery associated injuries. We report two individual cases of burn resulting from explosion of EC re-chargeable lithium ion batteries. Both patients required in-patient surgical management. We provide evidence that lithium ion battery explosions can be associated with mixed thermal and alkali chemical burns, resulting from the significant discharge of thermal energy and the dispersal of corrosive lithium ion compounds. We would recommend, as with other elemental metal exposures, caution in exposing lithium ion battery burns to water irrigation. Early and thorough cleaning and debridement of such burns, to remove residual lithium contamination, may limit the risk of burn wound extension and potentially improve outcomes.

Variant haploinsufficiency and phenotypic non-penetrance in PRPF31-associated retinitis pigmentosa.

Retinitis pigmentosa (RP) is a genetically heterogenous group of inherited disorders, characterized by death of the retinal photoreceptor cells, leading to progressive visual impairment. One form of RP is caused by mutations in the ubiquitously expressed splicing factor, PRPF31, this form being known as RP11. An intriguing feature of RP11 is the presence of non-penetrance, which has been observed in the majority of PRPF31 mutation-carrying families. In contrast to variable expressivity, which is highly pervasive, true non-penetrance is a very rare phenomenon in Mendelian disorders. In this article, the molecular mechanisms underlying phenotypic non-penetrance in RP11 are explored. It is an elegant example of how our understanding of monogenic disorders has evolved from studying only the disease gene, to considering a mutation on the genetic background of the individual - the logical evolution in this genomic era.

Diverse clinical phenotypes associated with a nonsense mutation in FAM161A.

PURPOSE: Mutations in the FAM161A gene have been reported in association with autosomal recessive retinitis pigmentosa (arRP) in several ethnic populations. This study aimed to assess the prevalence of FAM161A-related retinopathy in a British cohort and to characterise the phenotype associated with mutations in this gene. METHODS: The FAM161A coding region and intron-exon boundaries were screened by Sanger sequencing in 120 retinitis pigmentosa (RP) patients (with likely autosomal recessive inheritance) in whom mutations in other known major RP genes have been ruled out by commercially available testing. Homozygosity mapping was performed in one consanguineous family, and high-throughput sequencing of candidate genes was performed to identify disease-associated changes. Clinical assessment of affected individuals included perimetry testing, fundus autofluorescence imaging, and optical coherence tomography. RESULTS: Two patients of British origin with a homozygous mutation in FAM161A (c.1309A>T, p.Arg437*) were identified by Sanger sequencing. Homozygosity mapping and subsequent high-throughput sequencing analysis identified a further family of Pakistani origin with the same genotype. Clinical examination of affected members of these families revealed that this mutation was associated with a diverse clinical phenotype, ranging from mild disease with preservation of central acuity to severe visual impairment. CONCLUSIONS: Homozygosity for the c.1309A>T, p.Arg437* variant in FAM161A is a relatively common cause of arRP. The mutation occurs in diverse ethnic populations, associated with typical retinitis pigmentosa with disease onset usually in the second or third decade of life.

Lymphoepithelial cyst of the pancreas: case report and review of the literature.

BACKGROUND AND STUDY AIMS: Lymphoepithelial cyst of the pancreas (LCP) is a rare, benign cyst mimicking pseudocyst or cystic neoplasm. Literature describing LCP is limited to case or brief series reports, and the natural history of this condition is largely unknown. A literature review was carried out in order to elucidate the clinical, pathological and biochemical features of LCP. The aim of this study was to define diagnostic criteria and treatment. METHODS: A Medline and Pubmed search was conducted by using the key-words "lymphoepithelial cyst" and "pancreas". The articles found were accurately examined and all details regarding clinical and pathological features were included in a data-base. Furthermore, a case recently observed in our unit was added to the review. RESULTS: Ninety-two cases of LCP were found in the worldwide literature, including the case that we observed. LCP occurs more frequently in males (M:F=5.5:1), its preferred site is the tail of the pancreas, and its size ranges between 2 and 10centimetres. Histologically, it is a true cyst delineated by a keratinizing squamous epithelium surrounded by lymphoid tissue. LCP is asymptomatic in the majority of cases and preoperative diagnosis is complicated by a lack of specific radiological features of the disease. An accurate preoperative diagnosis can only be made by obtaining cytological specimens and placing them in the hands of a pathologist who is familiar with the cytological appearances of the disease. CONCLUSIONS: LCP is a rare lesion worldwide, without any prevalence in different countries or in different ethnic groups. Understanding the features of LCP, making an accurate diagnosis and differentiating it from cystic neoplasm preoperatively is vital, as when it is diagnosed certainly, a conservative treatment is justified. Otherwise, radical surgery in the form of pancreatic resection is required to exclude the diagnosis of pancreatic cystic neoplasm.

Liver resection for intrahepatic stones in congenital bile duct dilatation.

OBJECTIVE: This study reports our clinical experience with liver resection for congenital dilatation of the intrahepatic bile duct and intrahepatic gallstones to evaluate results and define indications for treatment. PATIENTS AND METHODS: We studied the clinical data of patients who underwent hepatic resection for intrahepatic lithiasis from January 1992 to December 2008 and assessed the immediate and long-term results of these interventions. RESULTS: Of 49 treated patients, 47 underwent liver resection. In the majority of cases, the disease was limited to the left lobe and left hepatectomy was the most commonly performed surgical procedure. The operative mortality was zero with morbidity in 24.5% of patients. Cholangiocarcinoma was diagnosed in six cases (12.2%). In 91.6% of cases the long-term results were good or satisfactory. CONCLUSION: Treatment goals in all cases should be the elimination of intrahepatic stones, the prevention of recurrent lithiasis, and prevention or cure of cholangiocarcinoma. Surgical excision is the best possible treatment for symptomatic patients with localized disease and atrophy of the affected liver.

Adherence to National Burn Care Review referral criteria in a paediatric Emergency Department.

INTRODUCTION: The National Burn Care Review (NBCR) gives guidance on the recognition of potentially complex burns requiring assessment and management in a burn unit. This guidance provides a referral framework for those initiating assessment and management of burns. The effect of close adherence to NBCR guidance on workload is at present unknown. OBJECTIVES: To audit referral patterns of burns in our paediatric Emergency Department (ED) in comparison to NBCR referral criteria. To identify the type of injuries not referred despite meeting criteria, and their outcomes, to assess whether these patients come to any harm short-term. To estimate the effect that closer adherence would have on workload and how our unit proposes to work with the ED to improve its distribution and our patients care. METHODS: A retrospective case-note audit of patients presenting to a paediatric ED with a triage diagnosis of "burn/scald" over a 6-month period between 1st April and 29th September 2008. RESULTS: 190 patients presented with burns during this period, of which 126 (66%) had potentially complex burns. Of these, 93 (74%) were not referred to the burns unit i.e. were "under-referred". In this group burns to specialized areas in patients under 5 years of age were particularly prevalent. 78 (84%) were reviewed in the ED and received no specialist input. Seven patients suffered minor complications. Only three of these patients (3.2%) required subsequent referral to the burns unit for opinion. None required any further specialist intervention. CONCLUSION: Strict adherence to NBCR referral criteria could result in a significant increase in workload for regional burn units with as yet unquantifiable benefit in patient outcomes. Many minor injuries appear to be safely managed in the ED with little adverse outcome. Even small improvements in practice could result in a considerable workload increase for a burns unit. Further prospective research is required, particularly looking at longer-term outcomes. We are hoping to improve educational and clinical links between our EDs and burn unit to improve patient care and distribution of clinical workload. Further national guidance maybe necessary.

Gas in portal circulation and pneumatosis cystoides intestinalis during chemotherapy for advanced rectal cancer.

OBJECTIVES: Acute abdominal symptoms with CT scan evidence of intramural gas in bowel walls (pneumatosis cystoides intestinalis, PCI) and of gas in the portal venous blood (PBG) in patients undergoing chemotherapy may represent a worrisome picture, suggestive of bowel necrosis. This picture remains a major clinical clue and the reporting of new cases may help to share awareness and experience on management. We describe a patient with acute abdominal symptoms and evidence of PCI with PBG under cetuximab, oxaliplatin, tegafur-uracil and folinic acid chemotherapy for metastatic adenocarcinoma of the rectosigmoid junction. METHODS: After admission for mucositis with diarrhea and profound dehydration, and subsequent emergency laparotomy for derotation of an intestinal volvulus, on the tenth postoperative day the patient developed fever and abdominal pain, with CT scan evidence of PCI with PBG. The exam of the abdomen did not suggest major problems requiring emergency surgery, and antibiotic treatment with close monitoring were performed, followed by rapid improvement. RESULTS: Twelve days later, after resumption of oral diet, the patient unexpectedly suffered a spontaneous jejunal microperforation, requiring emergency laparotomy and bowel resection. Pathology showed that the perforation was within an area of ulceration involving the inner superficial layer of the bowel. Subsequently recovery was normal and at present, after 15 months, the patient is well and continuing chemotherapy. CONCLUSIONS: This is probably the first report of PCI with PBG related to intestinal toxicity during cetuximab, oxaliplatin, tegafur-uracil and folinic acid chemotherapy in a patient with advanced rectal carcinoma, followed by delayed small bowel perforation. It provides an example of the challenges involved in the management of this type of patient.

Total gastrectomy for type 1 gastric carcinoid: an unusual surgical indication?

Gastric carcinoid is a relatively rare neoplasm with peculiar features which differentiate it from the intestinal and pulmonary carcinoid and, obviously, from gastric adenocarcinoma. Gastric carcinoids are divided into three different types: Type 1, associated with gastric atrophy and megaloblastic anemia; Type 2, associated with Zollinger-Ellison syndrome within a type 1 multiple endocrine neoplasia (MEN); and Type 3, sporadic tumor not associated with other lesions, particularly invasive and with poor prognosis. Type 1 carcinoid is usually asymptomatic and casually detected at endoscopy due to aspecific symptoms or to screening in patients with atrophic gastritis. It is generally small, multifocal and located in the gastric fundus, has no tendency for vascular invasion and is associated with a benign course. Therefore, the recommended treatment, for lesions < 10 mm and in a number < 5, is endoscopic resection with strict follow-up. We report a case of a woman with a type 1 gastric carcinoid in which, for the presence of an extended micro-polyposis of the fundus a total gastrectomy was necessary for treatment. Pathology revealed vascular invasion at the level of the major lesion of 8 mm of diameter. In conclusion this finding, unknown before surgery, emphasizes the need for careful assessment also in the presence of apparently less important gastric carcinoid lesions.

Caenorhabditis elegans dpy-5 is a cuticle procollagen processed by a proprotein convertase.

Genetic analysis of the nematode Caenorhabditis elegans reveals that all dpy-5 alleles are dominant suppressors of bli-4 blistering. Molecular cloning of dpy-5 establishes that it encodes a cuticle procollagen, defects in which are responsible for the short-body, dumpy phenotype. The null mutation, e907 removes the entire coding region, whereas the dpy-5 reference allele, e61, contains a nonsense substitution. RT-PCR analysis and a dpy-5::gfp fusion show that dpy-5 is expressed only in hypodermal cells at all post-embryonic life-cycle stages. Variable expression of dpy-5 in V lineage-derived seam cells suggests an alternative regulatory mechanism in these cells. The dpy-5 gene product contains an Arg-X-X-Arg cleavage motif that could be recognized by a proprotein convertase, such as BLI-4. Mutation of this site cause a dominant dumpy phenotype suggesting Dpy-5 procollagen requires processing for normal cuticle production.

High sensitivity and specificity of the Pastorex latex agglutination test for Neisseria meningitidis serogroup A during a clinical trial in Niger.

There is a great need for a rapid diagnostic test to guide vaccine choice during outbreaks of meningococcal meningitis in resource-poor countries. During a randomised clinical trial conducted during an epidemic of Neisseria meningitidis serogroup A in Niger in 2003, the sensitivity and specificity of the Pastorex latex agglutination test for this serogroup under optimal field conditions were assessed, using culture and/or PCR as the gold standard. Results from 484 samples showed a sensitivity of 88% (95% CI 85-91%) and a specificity of 93% (95% CI 90-95%). Pastorex could be a good alternative to current methods, as it can be performed in a local laboratory with rapid results and is highly specific. Sensitivity can be improved with prior microscopy where feasible. A study specifically to evaluate the Pastorex test under epidemic conditions, using laboratories with limited resources, is recommended.

A decade of change: tuberculosis in England and Wales 1988-98.

Tuberculosis cases in children (aged under 15 years) in the National Surveys rose from 308 (rate: 3.3 per 100,000) in 1988 to 408 (4.2 per 100,000) in 1993 and then fell to 364 (3.6 per 100,000) in 1998. The rates in white children were 1.6, 2.0, and 1.1 per 100,000 respectively; in Indian subcontinent children, the rates were unchanged between 1988 and 1993 at around 33 per 100,000 but fell to 23 per 100,000 in 1998. In black African children, the rates were 15, 34, and 71 per 100,000 respectively. From 1988 to 1998, the proportion of cases resident in London more than doubled to 49% (rate: 11.9 per 100,000) and the proportion of cases in children born abroad increased from 13% to 27% in the country as a whole. Although the overall rate of tuberculosis in children in England and Wales has changed little between 1988 and 1998, the distribution of disease has changed in line with the change in adults. Services for the diagnosis and treatment of tuberculosis in children should be adapted to the changing pattern of disease in this group. Continuous enhanced tuberculosis surveillance will enable more detailed and timely scrutiny of trends in tuberculosis in the future.

Patterns of Puumala virus infection in Finland.

Puumala hantavirus infection is prevalent throughout most of Europe, and in endemic areas it may be the most common cause of acute renal failure. To evaluate trends in incidence of Puumala virus infections in Finland, we analysed national surveillance data in 12-month periods from March 1995 to February 2002. During this time, 8184 laboratory-confirmed cases were notified to the National Infectious Disease Register. Three epidemic periods were identified, for which the number of cases was more than 1400 (there were approximately 600-900 cases per non-epidemic period). The incidence of Puumala hantavirus infection varied by geographic region during the study period, and the overall number of cases may be increasing.

An estimate of the contribution of HIV infection to the recent rise in tuberculosis in England and Wales.

BACKGROUND: The number of patients with tuberculosis has been increasing slowly in England and Wales since the late 1980s. HIV infection has been a contributory factor to increases in tuberculosis in a number of comparable industrialised countries. This study investigated the extent of tuberculosis and HIV co-infection in England and Wales in 1993 and 1998, and estimated its contribution to the increase in tuberculosis observed during this period. METHODS: Patients aged 16-54 years old at diagnosis on the 1993 and 1998 National Tuberculosis Survey databases were matched with those on the HIV/AIDS patient database. A coded process maintained patient confidentiality. Primary outcome measures were the increase between 1993 and 1998 in the numbers with both infections reported and an estimate of the proportion of the increase in tuberculosis during this period attributable to HIV co-infection. RESULTS: In 1993 61 (2.2%) tuberculosis patients aged 16-54 years matched with patients reported to the HIV database, increasing to 112 (3.3%) in 1998 (p=0.08; OR 1.35; 95% CI 0.97 to 1.87). Patients co-infected with HIV contributed an estimated 8.5% of the increase in number of tuberculosis patients between 1993 and 1998 nationwide (11% in London). In both years prevalence of co-infection was greatest in London and in patients of white and black African ethnic groups. CONCLUSIONS: In 1998 the number of tuberculosis patients co-infected with HIV in England and Wales, though still small, had nearly doubled since 1993, with most of the increase occurring in London. As HIV infection may be undiagnosed in patients with tuberculosis, and tuberculosis may be unreported in patients with diagnosed HIV infection, the true extent of co-infection will have been underestimated by this study. In addition, constraints in coded matching make it inevitable that some reported co-infections are missed. Routine HIV testing of all patients with tuberculosis should now be considered, particularly in patients of white or black African ethnic origin under 55 years of age.