Influenza A H1N1 (2009): clinical spectrum of disease among adult patients admitted to a regional hospital in Singapore.

INTRODUCTION: The worldwide spread of Influenza A H1N1 (2009) has proceeded at an unprecedented rate, with the World Health Organization rapidly raising its influenza pandemic alert to phase six. We describe the disease spectrum of H1N1 (2009) to aid the triaging and identification of patients at risk. METHODS: This is a retrospective chart review of all confirmed H1N1 (2009) cases admitted to our institution between June and September 2009. RESULTS: The disease severity of the 153 patients studied was classified as mild (n is 75), moderate (n is 55) and severe (n is 23). 81 patients were female. The median age was 26 years. While comorbidities were more prevalent among patients with moderate-severe illness, 47.4 percent reported no pre-existing illness. Presenting complaints of breathlessness, tachycardia, low-pulse oximetry, higher leukocyte counts and C-reactive protein with low albumin levels were more commonly noted in moderate-severe illness (p-value less than 0.001). All patients received oseltamivir at a median of four days from illness onset. 18 required intensive care unit admission, with the majority (94.4 percent) within the first 24 hours of hospitalisation. The overall mortality rate was 4.6 percent. Median lengths of hospitalisation were four and nine days for moderate and severe cases, respectively. CONCLUSION: While the majority of H1N1 (2009) patients have mild illness, a subgroup can become critically ill. Prior good health is not necessarily a good discriminator against severe illness. The presence of dyspnoea, tachycardia and desaturation at triage should heighten the index of suspicion for H1N1 (2009)-related complications.

Abdominal manifestations of cystic fibrosis in adults: a review.

Gastrointestinal manifestations of disease are present in most adults with cystic fibrosis. Radiologists are familiar with the classical imaging characteristics of end-stage pulmonary disease and the radiological findings of meconium ileus in neonates. As most patients now live into adulthood, recognition of the imaging appearances of abdominal disease is important to enable prompt diagnosis and treatment. Accordingly, this article presents typical imaging appearances of the adult gastrointestinal manifestations of cystic fibrosis.

Pulmonary nocardiosis re-visited: experience of 35 patients at diagnosis.

Pulmonary infection by Nocardia is an uncommon opportunistic infection in humans. Thirty-five patients with pulmonary nocardiosis were identified in two tertiary referral hospitals. A retrospective review of the patient characteristics, clinical and laboratory features including antimicrobial susceptibility at diagnosis was carried out. Radiological features derived from chest radiographs and CT scans were also documented. In our population, the predominant risk factors were immuno-compromised state, corticosteroid therapy, and underlying pulmonary pathology. The presenting features were similar to those previously described but disseminated infection was not common. The radiological changes were diverse and non-specific. Nocardia asteroides was the commonest species. Most Nocardia isolates were susceptible to imipenem, ceftriaxone, amikacin, and cotrimoxazole. Co-existing microbial agents are common and reflect the underlying complex disorders.

Comparing fasting plasma glucose against two-hour post-load glucose concentrations for the diagnosis of diabetes mellitus and glucose intolerance in Singaporean hospital patients.

INTRODUCTION: Several studies have assessed the impact of the 1997 American Diabetes Association (ADA) recommendation, of using fasting plasma glucose (FPG) concentration, to diagnose diabetes mellitus in population-based cohorts. However, data concerning the impact of this recommendation in the hospital setting are limited. As the performance characteristics of diagnostic tests vary depending on the prevalence of diabetes in the population studied, we have examined the clinical impact of adopting the ADA recommendations in comparison to the traditional 2-hour post-load glucose (2HPG) concentration used by the World Health Organisation (WHO) in diagnosing diabetes and other categories of glucose intolerance in Singaporean hospital patients. MATERIALS AND METHODS: We analysed the results of the standard 75 g oral glucose tolerance test (OGTT) performed on 625 patients in our hospital from 1994 to 1999. RESULTS: The prevalence of diabetes amongst these 625 patients was 36.8% (230) based on the ADA recommendation of using FPG, 42.8% (263) on using the 2HPG and 52.0% (325) on using the full 1998 WHO criteria. The degree of agreement (kappa) in establishing the diagnosis of diabetes between the FPG and 2HPG cut-offs was 0.48. Ninety-five (15.2%) individuals had diabetes based on the 2HPG alone, 62 (9.9%) based on the FPG alone and 168 (26.9%) based on both the FPG and 2HPG. Eighty-six (13.8%) individuals had impaired fasting glucose (IFG) and 123 (19.7%) had impaired glucose tolerance (IGT). The kappa-value between IFG and IGT was 0.08. CONCLUSION: Fasting plasma glucose concentration was an inadequate parameter in diagnosing diabetes and intermediate categories of glucose intolerance in our cohort of subjects. Our findings suggest that the OGTT remains an important diagnostic tool for classifying glucose tolerance in our hospital patients.

Association of clinical, radiological and synovial immunopathological responses to anti-rheumatic treatment in rheumatoid arthritis.

OBJECTIVES: To compare immunohistochemical scoring with clinical scoring and radiology for the assessment of rheumatoid arthritis (RA) disease activity, synovial tissue (ST) biopsied arthroscopically was assessed from 18 patients before and after commencement of disease-modifying anti-rheumatic drug (DMARD) therapy. METHODS: Lymphocytes, macrophages, differentiated dendritic cells (DC), vascularity, tumour necrosis factor (TNF) alpha and interleukin-1beta levels were scored. Clinical status was scored using the American College of Rheumatology (ACR) core set and serial radiographs were scored using the Larsen and Sharp methods. Histopathological evidence of activity included infiltration by lymphocytes, DC, macrophages, tissue vascularity, and expression of lining and sublining TNFalpha. These indices co-varied across the set of ST biopsies and were combined as a synovial activity score for each biopsy. RESULTS: The change in synovial activity with treatment correlated with the ACR clinical response and with decreased radiological progression by the Larsen score. The ACR response to DMARD therapy, the change in synovial activity score and the slowing of radiological progression were each greatest in patients with high initial synovial vascularity. CONCLUSIONS: The data demonstrate an association between clinical, radiological and synovial immunopathological responses to anti-rheumatic treatment in RA. High ST vascularity may predict favourable clinical and radiological responses to treatment.

Successful treatment of rheumatoid arthritis is associated with a reduction in synovial membrane cytokines and cell adhesion molecule expression.

OBJECTIVE: To investigate the change in synovial membrane cytokine content and cell adhesion molecule expression in sequential biopsies from the same knee joint of patients with rheumatoid arthritis, before and following anti-rheumatic drug treatment and to assess the relationship of these changes with clinical responses to the drug treatment. METHODS: A selected group of patients with rheumatoid arthritis, some of whom had achieved a disease remission based on American College of Rheumatology (ACR) criteria, were included in this study. Sequential synovial biopsies obtained before and throughout the treatment period were studied by immunohistochemical labelling techniques for the cellular content, production of a range of pro- and anti-inflammatory cytokines and the expression of cell adhesion molecules. The staining was quantitated using computer-assisted digital image analysis. RESULTS: There was a decrease in tumour necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta) production in the synovial membrane lining and sublining of all patients who responded to treatment. The changes in IL-1 receptor antagonist production were variable. Paradoxically, there was a trend to decreased synovial membrane production of the anti-inflammatory cytokines, IL-10 and transforming growth factor-beta (TGFbeta), while IL-4 was not detectable in any of the synovial membrane biopsies. A significant reduction in the density and total amount of E-selectin expression in the synovial membrane was seen. Similarly, intercellular adhesion molecule-1 (ICAM-1) expression in the lining and sublining was decreased in those patients who had a significant clinical response to drug treatment or attained disease remission. There were no consistent or significant changes seen in the expression of other cell adhesion molecules in the synovial membranes of these patients. CONCLUSIONS: Successful drug treatment of rheumatoid arthritis patients is characterized at the synovial membrane level by a decrease in TNFalpha, IL-10 and TGFbeta production. Some (E-selectin and ICAM-1) but not all (P-selectin, VCAM-1, PECAM-1) cell adhesion molecules are modulated in patients who respond clinically to drug treatment. E-selectin and ICAM-1 may be important targets for the development of future drug treatments for rheumatoid arthritis.

Computed tomography pulmonary angiography with pelvic venography in the evaluation of thrombo-embolic disease.

A prospective study was performed to evaluate the usefulness of CT pelvic venography (CTV) in the detection of pelvic vein thrombosis in patients referred for CT pulmonary angiography (CTPA) for suspected pulmonary embolism. Fifty consecutive patients referred for CTPA had CTV performed at the time of CTPA. All patients had duplex ultrasound (DUS) of the lower limb veins for evaluation of deep venous thrombosis (DVT) within 24 h of the CT study. Twelve (24%) of the 50 patients had pulmonary embolism diagnosed on CTPA. Associated DVT was detected in six of these patients; two cases were detected by CTV alone, while one case was detected by both CTV and DUS. The remaining three cases had DVT diagnosed by DUS alone. In the 38 patients with a negative CTPA, three patients had venous thrombus diagnosed by CTV. Of these three patients, two had a negative DUS study. CTV therefore led to a definitive imaging diagnosis of thrombo-embolic disease in two (4%) more patients. CTV adds little time and cost to the CTPA examination and leads to a moderate increase in definite imaging diagnosis of thrombo-embolic disease.

Treatment-induced remission in rheumatoid arthritis patients is characterized by a reduction in macrophage content of synovial biopsies.

OBJECTIVES: To document the change in synovial membrane macrophage and T-lymphocyte content in rheumatoid arthritis (RA) patients who achieve remission induced by disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Arthroscopic synovial biopsies were taken from four to seven sites around a knee joint in 13 patients with RA before and at regular intervals after commencing treatment with a DMARD. The cellular content of synovial membrane biopsies taken at regular intervals for a period of up to 3 yr after commencing treatment was quantitated by routine histopathology and immunohistochemical labelling with anti-macrophage (CD68) and anti-T lymphocyte (UCHL-1) antibodies. Synovial biopsies were quantitated with a validated semiquantitative scoring system and video image analysis. RESULTS: Nine patients obtained clinical remission, as defined by American College of Rheumatology (ACR) criteria. The changes that occurred in the synovial biopsies included a reduction in lining layer thickness, reduced vascularity and cellular infiltrate. The most significant reduction in cellular infiltrate was in the lining layer macrophages, with less dramatic change in the subintimal macrophage infiltrate. Although there was a reduction in CD45 Ro-positive T lymphocytes in the synovial membranes of patients who attained ACR-defined disease remission, it was less significant than the reduction in macrophage content of the synovial membranes and tended to plateau at a reduced level of T-cell infiltration. CONCLUSIONS: Remission in RA patients is characterized by a predominant reduction in macrophage content of the synovial membrane, suggesting that current DMARDs may target this cell and its inflammatory mediators.

Pulmonary hypertension secondary to left-sided heart disease: a cause for ventilation-perfusion mismatch mimicking pulmonary embolism.

Ventilation-perfusion (V/Q) scans are commonly performed in patients with suspected pulmonary thromboembolism (PE). V/Q mismatch is typically attributed to PE. We describe a case in which a V/Q scan performed on a patient with advanced hypertrophic obstructive cardiomyopathy showed large areas of V/Q mismatch not due to PE. The mismatch was due to pulmonary hypertension secondary to left-sided heart disease. The pathophysiology is briefly reviewed.

Electromagnetic cross sections of double giant dipole resonances in 136Xe and 208Pb within the phonon damping model

The electromagnetic cross sections of the double giant dipole resonances (DGDR) in 136Xe and 208Pb are calculated using the strength functions obtained within the phonon damping model. The parameters of the model have been selected to describe reasonably well the single giant dipole resonance in these nuclei. The results are found in an overall agreement with the recent experimental data for the DGDR cross sections in exclusive measurements at near-relativistic energies.

Effects of singlet oxygen on the extracellular matrix protein collagen: oxidation of the collagen crosslink histidinohydroxylysinonorleucine and histidine.

The reaction of singlet oxygen, a putative agent of skin photodamage, with the dermal collagen crosslink histidinohydroxylysinonorleucine (HHL) and its precursor histidine is reported. Reaction studies were performed with both purified HHL and bovine dermal tissue. We demonstrate that singlet oxygen can selectively oxidize HHL and histidine amino acid residues in dermal tissue and that intermediate oxidation products of histidine lead to new crosslink products. A novel mechanism for crosslink formation was proposed to involve nucleophilic addition to a transient imidazolone intermediate formed from singlet oxygen oxidation of the histidine imidazole moiety. The implication for such adduct formation and histidine oxidation in collagen proteins is the expression of aberrant collagen crosslinks, perturbation of the dermal collagen function, and hence an altered dermal state.

Pulmonary sequestration diagnosed by contrast enhanced three-dimensional MR angiography.

Pulmonary sequestration is a congenital bronchopulmonary foregut malformation in which a segment of lung parenchyma is not connected to the tracheobronchial tree. This abnormal segment receives a blood supply from the systemic circulation. Multiple imaging modalities have been used to demonstrate the vascular anatomy of the sequestration. Different magnetic resonance angiography (MRA) techniques have been employed in the identification of these anomalous vessels. We report a case of pulmonary sequestration diagnosed by MRI with the use of contrast enhanced three-dimensional MRA.

Clinical outcome of micrometastasis in the lung in stage IA persistent gestational trophoblastic disease.

BACKGROUND: Computed tomography (CT) of the thorax can be used in the staging of persistent gestational trophoblastic disease (PGTD). However, the prognostic significance of micrometastasis in the lung detected by CT of the thorax has not been well documented. The aim of the study is to define the effect of micrometastasis on the clinical course of the disease. METHODS: Thirty-five patients who had nonmetastatic GTD underwent CT thorax examination before treatment in the Department of Obstetrics and Gynaecology, University of Hong Kong. All patients had workups which showed no evidence of metastasis and were diagnosed as FIGO stage IA. They all received methotrexate (MTX) infusion therapy. RESULTS: Three groups of patients were identified based on the thorax CT findings. Sixteen patients (45.7%) showed no evidence of micrometastasis on CT thorax. Two of them (12.5%) had poor response to MTX with unsatisfactory fall in serum hCG levels requiring change of chemotherapy to actinomycin D. Nine patients had suspicious micrometastasis and one (11.1%) of them needed change of MTX. Ten patients had micrometastasis and one (10%) of them needed change of MTX. There was only one recurrence and it was in the suspicious micrometastasis group (11.1%). There was no statistically significant difference in the rate of poor drug response or recurrence among the three groups of patients. CONCLUSIONS: Micrometastases in the lung do not affect the clinical outcome of patients with FIGO stage IA disease. CT thorax is not essential in the staging of GTD.

Clinics in diagnostic imaging (16). Lower gastrointestinal bleeding caused by ileal tumour.

A 38-year-old Chinese man presented with melaena and anaemia. Urgent superior mesenteric angiogram showed a well-circumscribed vascular mass in the ileum. A stromal tumour was surgically excised. The radiological approach to lower gastrointestinal bleeding is described, followed by a brief discussion on stromal tumours of the small bowel.

Clinics in diagnostic imaging (3). Acute-on-chronic pancreatitis causing diabetic ketoacidosis.

A 49-year-old man presented with clinical and biochemical features of diabetic ketoacidosis and concomitant acute pancreatitis. Plain radiographs, computerised tomography (CT) and endoscopic retrograde cholangiopancreatogram demonstrated changes of chronic pancreatitis, which was the cause of exocrine pancreatic insufficiency in this patient. Advantages and disadvantages of various imaging modalities in the diagnosis and management of pancreatitis are discussed. Imaging features of acute and chronic pancreatitis, and associated complications, are described.