Outcome of infection of C57BL/6 IL-10(-/-) mice with Campylobacter jejuni strains is correlated with genome content of open reading frames up- and down-regulated in vivo.

Human Campylobacter jejuni infection can result in an asymptomatic carrier state, watery or bloody diarrhea, bacteremia, meningitis, or autoimmune neurological sequelae. Infection outcomes of C57BL/6 IL-10(-/-) mice orally infected with twenty-two phylogenetically diverse C. jejuni strains were evaluated to correlate colonization and disease phenotypes with genetic composition of the strains. Variation between strains was observed in colonization, timing of development of clinical signs, and occurrence of enteric lesions. Five pathotypes of C. jejuni in C57BL/6 IL-10(-/-) mice were delineated: little or no colonization, colonization without disease, colonization with enteritis, colonization with hemorrhagic enteritis, and colonization with neurological signs with or without enteritis. Virulence gene content of ten sequenced strains was compared in silico; virulence gene content of twelve additional strains was compared using a C. jejuni pan-genome microarray. Neither total nor virulence gene content predicted pathotype; nor was pathotype correlated with multilocus sequence type. Each strain was unique with regard to absences of known virulence-related loci and/or possession of point mutations and indels, including phase variation, in virulence-related genes. An experiment in C. jejuni 11168-infected germ-free mice showed that expression levels of ninety open reading frames (ORFs) were significantly up- or down-regulated in the mouse cecum at least two-fold compared to in vitro growth. Genomic content of these ninety C. jejuni 11168 ORFs was significantly correlated with the capacity to colonize and cause enteritis in C57BL/6 IL-10(-/-) mice. Differences in gene expression levels and patterns are thus an important determinant of pathotype in C. jejuni strains in this mouse model.

Prevalence of referable, sight-threatening retinopathy in type 1 diabetes and its relationship to diabetes duration and systemic risk factors.

PurposeThe purpose of the study was to provide contemporary estimates for diabetic retinopathy (DR) prevalence in a well-defined UK cohort of patients with type 1 diabetes (T1DM) and investigate potential risk factors for proliferative diabetic retinopathy (PDR) and diabetic maculopathy.Patients and MethodsFour hundred and sixty four T1DM patients in North Hampshire had T1DM duration, demographic and systemic risk factor data evaluated retrospectively alongside their DR status in 2010 using logistic regression analysis.ResultsOverall prevalence of any retinopathy, PDR, and maculopathy was 71.5%, 6.5%, and 10.8%, respectively. PDR and maculopathy prevalence were 0 and 0.7% for <10 years T1DM duration. PDR prevalence was 4%, 8%, and 16% for 10-19.9 years, 20-29.9, years and ≥30 years duration, respectively. Maculopathy prevalence was 15.6%, 18%, and 11% for 10-19.9 years, 20-29.9 years, and ≥30 years duration, respectively. In univariate analysis, PDR was associated with T1DM duration (odds ratio (OR) 1.07/year), age (OR 1.03/year), systolic blood pressure (OR 1.03/mmHg), and antihypertensive therapy (OR 10.63), while maculopathy was associated with duration (OR 1.03/year) and statin therapy (OR 2.83). In multivariate analysis, disease duration (OR 1.07/year) and antihypertensive therapy (OR 6.87) remained significantly associated with PDR, and maculopathy with statin therapy (OR 2.27).ConclusionThis study confirms T1DM duration is a strong risk factor for sight-threatening DR. Maculopathy and PDR prevalence within 10 years of T1DM diagnosis is very low. PDR prevalence at 10-20 years was 4% and then doubled for every 10-year interval thereafter up to 16% with ≥30 years duration. Antihypertensive therapy and statin therapy were strongly associated with PDR and maculopathy, respectively.

Magnetic resonance imaging in idiopathic retroperitoneal fibrosis: measurement of T1 relaxation time.

Magnetic resonance imaging at 0.08 Tesla was performed in nine patients with proven idiopathic retroperitoneal fibrosis. A total of 11 scans was performed. Three patients were scanned before diagnosis; one of these also had two follow-up scans. A further six patients were scanned a variable time after diagnosis and treatment. On each scan, a periaortic soft-tissue mass was readily identified, the distribution corresponding to that seen on computed tomography. There was no difference in the mean T1 relaxation time of the mass between patients scanned before diagnosis and those scanned after treatment. However, the patient followed with serial scans showed a progressive reduction in the T1 value of the mass with time. Comparison with results obtained in patients with lymphoma suggests that the T1 values in retroperitoneal fibrosis are lower than in lymphoma, particularly non-Hodgkin's lymphoma.

Non-invasive assessment of diffuse liver disease by in vivo measurement of proton nuclear magnetic resonance relaxation times at 0.08 T.

44 patients with a range of parenchymal liver diseases diagnosed by biopsy or laboratory investigations underwent proton nuclear magnetic resonance (NMR) relaxometry of the liver at 0.08 T. T1 maps were produced using an interleaved saturation recovery and inversion recovery sequence and T2 maps using a four echo Carr-Purcell-Meiboom-Gill sequence. Significantly raised relaxation times compared with a previously studied group of 42 normal volunteers were found in groups of patients with alcoholic cirrhosis (p < 0.001 for T1 and T2), chronic active hepatitis (CAH) (p < 0.01 for T1 and T2) and minor liver abnormalities (p < 0.01, T2 only). T1 was significantly higher in cirrhotics than in patients with CAH (p < 0.002) and minor abnormalities (p < 0.001). This suggests a role for relaxometry in the confirmation of the presence of cirrhosis (sensitivity = 75%, specificity approximately 97%, taking T1 > 266 ms as a positivity criterion). Reduced T2 values were found in patients with liver iron overload prior to venesection (p < 0.001 versus normals, p < 0.02 versus venesected patients). Although this latter test has relatively low sensitivity and specificity, it may have a role in the monitoring of treatment for iron overload.

Sickle cell disease and silent avascular necrosis of the hip.

We reviewed the prevalence of avascular necrosis (AVN) in a series of patients with sickle cell disease, using radiography and magnetic resonance imaging. We found AVN of at least one hip in 11 of 27 patients (41%). This is a significantly greater prevalence than reported. MRI was not as helpful in patients with sickle cell disease as it is in patients with AVN from other causes; it detected no more cases than radiography.

Abnormal vascular reflexes in Charcot-Marie-Tooth disease.

Vascular reflexes were assessed in 17 adult patients with Charcot-Marie-Tooth disease using the Valsalva manoeuvre, and the pulse rate and systolic blood pressure responses to standing. Six patients showed abnormalities consistent with an autonomic neuropathy. One patient had giant nerve fibre bundles in the myenteric plexus of bowel resected for co-existent Crohn's disease, indicating histological involvement of these autonomic neurones. Other evidence of an autonomic component to the peripheral neuropathy of Charcot-Marie-Tooth disease is reviewed.

Establishing a statewide primary care network: the PrimaryOne experience.

To insure that patients receive the highest quality, cost-effective health care in the future, primary care physicians must become the leaders in the reform. The future of medicine belongs in physicians' hands. Physicians have the opportunity to bring about the greatest reform to the largest industry in the world, and do it in such a fashion that patient care is not compromised. The following article describes the purpose, objectives, organizational structure, accomplishments, philosophy, goals, results, and future of PrimaryOne and its HMO, PrimeONE.

Computed tomography of the chest in the trauma patient.

Thirty-six (1.5%) of 2340 patients admitted to the Trauma Unit at UCSD Medical Center over a 26-month period had 46 chest CT scans. A retrospective review of these cases showed that CT was useful in the diagnosis and management of suspected post-traumatic infective complications, assessment of suspected sternoclavicular joint dislocation, and localisation of bullet fragments. Other unsuspected abnormalities (pneumothoraces, misplaced endotracheal tube, intraperitoneal air, and axillary vein disruption) were also well demonstrated. However, CT failed to demonstrate some skeletal injuries, in particular, manubriosternal joint dislocation and vertebral fracture. Our experience supports a role for chest CT in certain limited clinical situations following trauma.

A family with diaphyseal aclasis and peripheral dysostosis.

Autosomal dominant inheritance of a type of peripheral dysostosis occurred in a family with diaphyseal aclasis. The features of their type of peripheral dysostosis were short limbed short stature, normal intelligence, very stubby fingers, flat face and nose, shortened metacarpals and terminal phalanges, thickened beaten-copper skull vault, and advanced skeletal maturation.

The incidence of Duchenne muscular dystrophy in the South East of Scotland.

In a survey carried out to determine the incidence of Duchenne muscular dystrophy in the South East of Scotland, 47 cases were ascertained among 177,413 live male births for the years 1953 to 1968. The overall incidence is 1 case in 3,775 live male births (26.5 +/- 3.2 X 10(-5)). This incidence figure has been compared with those reported in nine other studies, and any differences appear likely to be due to varying degrees of ascertainment. So far there is no evidence of any decrease in incidence of the disease in S.E. Scotland as a result of genetic counselling and antenatal foetal sexing.

A family study of Charcot-Marie-Tooth disease.

Forty-seven cases of Charcot-Marie-Tooth peripheral neuropathy were seen in 18 families within a defined area, with a disease prevalence of 1 in 16 400. Maximum motor nerve conduction velocity (MNCV) measurement divided off two types of neuropathy (MNCV less than 30 ms-1 and greater than 40 ms-1), but did not distinguish clinically affected from normal in families whose probands had median nerve MNCV greater than 40 ms-1. In the neuronal type of neuropathy ((MNCV greater than 40 ms-1) two genotypes were seen, autosomal dominant (ADN) and autosomal recessive (ARN). Most cases with the demyelinating type (MNCV less than 30 ms-1) had an autosomal dominant genotype (ADD) but one family had possible X linked recessive inheritance (XRD). In one autosomal dominant family a father and son had different electrophysiological types of neuropathy. Peroneal muscle weakness was progressive with age in the ADD genotype and certain patterns of phenotypic features were associated with the major genotypes. Age of onset was not found to be reliable in distinguishing genotypes. Care is needed when counselling isolated male cases because of asymptomatic affected females in the autosomal dominant genotypes, and the possibility of ill defined X linked forms.

Diaphragmatic (Bochdalek) hernias simulating pulmonary metastases on computed tomography.

Three patients with known primary malignancy and a normal chest radiograph are presented. Computed tomographic scans viewed on 'lung' settings showed a solitary mass lesion simulating a neoplastic mass in the posterior costophrenic recess in each patient. These lesions in fact were small herniations of abdominal fat into the chest through diaphragmatic defects.

Computed tomography in the diagnosis of traumatic rupture of the thoracic aorta.

Over a 26-month period, 25 patients admitted to the Trauma Unit at UCSD Medical Center following blunt trauma were investigated for suspected traumatic rupture of the thoracic aorta by computed tomography (CT) of the chest. A retrospective review of these patients was performed. Twenty-one (84%) also had CT of other body areas, most commonly the head or abdomen. Nine of the 25 patients subsequently had aortography; in 15 patients the CT findings were felt at the time to exclude rupture, and one patient was not investigated further because of severe head injuries. In general, if CT failed to show a mediastinal haematoma, aortography was not performed. However, five patients with CT evidence of a haematoma, including two with vertebral fractures, were not investigated by aortography. Two of the 25 patients (8%) had angiographically proven aortic ruptures; in both CT had shown not only a haematoma but also an abnormal outline of the aorta on contrast-enhanced scans. The haematoma was large in one patient and small in the other. Although 10 of the 25 patients had unenhanced scans, no case of aortic rupture is known to have been missed. During the same study period, 47 patients were investigated for suspected aortic rupture solely by aortography. Four patients (8% of this group) had aortic rupture, and two had subclavian or innominate artery ruptures. Only a minority (approximately one-quarter) also had CT of the head or abdomen. The role of CT in the diagnosis of traumatic rupture of the aorta is critically assessed in the light of our experience and a review of the literature.

Changes in glycosylated haemoglobin after poor control in insulin-dependent diabetics.

Glycosylated haemoglobin (HbA1) was measured in seven insulin-dependent diabetic patients before, during, and after a seven-day period of monitored poor control. There was considerable individual variation in the pattern and degree of change in HbA1 concentration induced by poor control and the time when it occurred. Greater increases in HbA1 were seen during the period of metabolic derangement than in the subsequent two months. More information is required before HbA1 estimations are widely used clinically to monitor control in individual diabetics.

Aortic displacement on computed tomography of idiopathic retroperitoneal fibrosis.

We present two cases of proven idiopathic retroperitoneal fibrosis in which displacement of the aorta from the spine (caused by the presence of tissue posterior to the aorta) was demonstrated on computed tomography, an appearance which has not been reported previously.