The impact of reclassification of C3 predominant glomerulopathies on diagnostic accuracy, outcome and prognosis in patients with C3 glomerulonephritis.

BACKGROUND: C3 glomerulonephritis is a recently described entity with heterogeneous histopathological features. This study was conducted to assess the effect of reclassification of C3 glomerulopathies on renal outcomes, mortality, and response to therapy. METHODS: We undertook a retrospective analysis of 857 renal biopsies collected at The Canberra Hospital. Samples with predominant C3 staining were reviewed by a renal histopathologist. Of 31 biopsies with predominant C3 staining, 10 fulfilled histological criteria for C3 glomerulonephritis, while the remaining 21 cases were used as C3 Controls. RESULTS: Aside from a higher incidence of C3 glomerulonephritis in Torres Strait islanders (40% vs 5% C3 Controls, p = 0.04), presentation demographics were similar between the two groups. Median creatinine at diagnosis was higher in patients with C3 glomerulonephritis (253 umol/L IQR 103-333 vs 127 umol/L C3 Controls, IQR 105-182, p = 0.01). Prior to reclassification, a majority of C3 glomerulonephritis cases were diagnosed as membranoproliferative glomerulonephritis (60% vs 5% (C3 Controls) p < 0.01). Electron microscopy demonstrated all C3 glomerulonephritis patients had C3 deposition (100% vs 38% p = 0.02), these deposits were amorphous in nature (50% vs 5% respectively p = 0.007). C3 glomerulonephritis patients had shorter median follow-up (405 days IQR 203-1197 vs 1822 days respectively, IQR 1243-3948, p = 0.02). Mortality was higher in C3 glomerulonephritis patients (30% vs 14% in C3 Controls (log rank p = 0.02)). CONCLUSION: We have devised a diagnostic and treatment algorithm based on the results of literature review and our current study. Further prospective assessment is required to review diagnostic and treatment outcomes for this disease in Australian centres.

Nursery pig growth performance and tissue accretion modulation due to porcine epidemic diarrhea virus or porcine deltacoronavirus challenge.

Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) are both members of the family which induce clinical signs of diarrhea, dehydration, and in some circumstances, mortality. Most research has been focused on isolation, genome sequencing, pathogenicity, and virulence of these viruses, but there is little information on long-term growth performance and tissue accretion of pigs inoculated with PEDV or PDCoV. Therefore, our objective was to determine the effect of PEDV or PDCoV infection on growth performance and tissue accretion over 42 d following inoculation. A total of 75 Choice Genetics Large White Pureline barrows and gilts (BW = 10.81 ± 0.81 kg) at approximately 2 wk post-wean and naïve for PEDV and PDCoV were selected. Pigs were allotted based on BW and sex, stratified across 3 treatments with 8 pens per treatment. Treatments were: 1) Control ( = 8); 2) PEDV inoculated ( = 8); and 3) PDCoV inoculated ( = 8). On day post inoculation (dpi) 2, 5, 7, and 14 pigs were euthanized for tissue collection and analyses from these tissues are discussed elsewhere. Pen feed intake and BW were recorded on dpi 2, 5, 7, and weekly thereafter until dpi 42. On 1 designated pig per pen, initial and final body composition was determined using dual-energy X-ray absorptiometry (DXA) and tissue accretion rates were calculated over 6 wk test period. Peak PEDV infection was noted at 3 dpi compared with 4 dpi for PDCoV pigs as determined by fecal swab quantitative real-time PCR (RT-PCR). Control pigs remained negative for PEDV and PDCoV throughout the experiment. Overall, Control and PDCoV pigs did not differ in ADG, ADFI or G:F ( > 0.05). Compared to Control and PDCoV pigs, the overall 42 d ADFI was reduced in the challenged PEDV pigs ( < 0.05) by 19 and 27%, respectively. PEDV did not significantly reduce the overall ADG or G:F compared with Control and PDCoV pigs; however, the biggest reduction in ADG and ADFI for PEDV pigs was within 14 dpi compared to the Control pigs ( < 0.05). Whole body tissue accretion was altered due to PED, with fat, lean, protein, and bone mineral accretion reductions by 24, 20, 21, and 42%, respectively ( < 0.05) compared with Control pigs. Overall, nursery pig performance was greatly impacted by PEDV challenge. Surprisingly, the PDCoV challenge did not negatively influence nursery pig performance. This study provides further insight into the longitudinal impact swine enteric coronaviruses have on growing pigs.

An evidence-based approach to laboratory tests in usual care of patients with rheumatoid arthritis.

Laboratory tests often are regarded as the most important information in clinical care by patients and doctors, and dominate clinical decisions in many chronic diseases such as diabetes and hyperlipidemia. Most patients with rheumatoid arthritis (RA) have a positive test for rheumatoid factor or anti-cyclic citrullinated peptide antibodies (ACPA), or an elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). However, about a third of RA patients, have negative tests for rheumatoid factor or ACPA, and more than 40% have a normal ESR or CRP at presentation ('false-negative' results). Furthermore, many normal people have a positive test for rheumatoid factor or ACPA but do not have RA, even among those with extensive musculoskeletal pain ('false-positive' results). Abnormal laboratory tests are the most significant predictor of high levels of radiographic progression, and therefore regarded as indicators of 'poor prognosis RA'. By contrast, laboratory tests are far less predictive of severe long-term outcomes such as work disability and premature mortality than functional difficulties reported on a patient questionnaire. A patient questionnaire score is abnormal in 89% of RA patients at presentation, and therefore more useful than ESR or CRP to document subsequent clinical improvement or deterioration. In clinical practice, patient questionnaire scores and RAPID3, an index of physical function, pain, and patient global estimate of status, identify incomplete responses to methotrexate more effectively than ESR. Improved understanding of the limitations of laboratory tests in diagnosis and management of individual patients with RA (and all rheumatic diseases) could improve patient care and outcomes.

Deglacial pulses of deep-ocean silicate into the subtropical North Atlantic Ocean.

Growing evidence suggests that the low atmospheric CO2 concentration of the ice ages resulted from enhanced storage of CO2 in the ocean interior, largely as a result of changes in the Southern Ocean. Early in the most recent deglaciation, a reduction in North Atlantic overturning circulation seems to have driven CO2 release from the Southern Ocean, but the mechanism connecting the North Atlantic and the Southern Ocean remains unclear. Biogenic opal export in the low-latitude ocean relies on silicate from the underlying thermocline, the concentration of which is affected by the circulation of the ocean interior. Here we report a record of biogenic opal export from a coastal upwelling system off the coast of northwest Africa that shows pronounced opal maxima during each glacial termination over the past 550,000 years. These opal peaks are consistent with a strong deglacial reduction in the formation of silicate-poor glacial North Atlantic intermediate water (GNAIW). The loss of GNAIW allowed mixing with underlying silicate-rich deep water to increase the silicate supply to the surface ocean. An increase in westerly-wind-driven upwelling in the Southern Ocean in response to the North Atlantic change has been proposed to drive the deglacial rise in atmospheric CO2 (refs 3, 4). However, such a circulation change would have accelerated the formation of Antarctic intermediate water and sub-Antarctic mode water, which today have as little silicate as North Atlantic Deep Water and would have thus maintained low silicate concentrations in the Atlantic thermocline. The deglacial opal maxima reported here suggest an alternative mechanism for the deglacial CO2 release. Just as the reduction in GNAIW led to upward silicate transport, it should also have allowed the downward mixing of warm, low-density surface water to reach into the deep ocean. The resulting decrease in the density of the deep Atlantic relative to the Southern Ocean surface promoted Antarctic overturning, which released CO2 to the atmosphere.

Acute gout management during hospitalization: a need for a protocol.

AIM: To review systematically the management of acute gout during hospitalization. METHODS: Case-file review of all episodes of acute gout occurring in a large tertiary hospital over a 20-month period. RESULTS: Of 134 acute gout episodes identified, the large majority (118) occurred in patients not admitted under the rheumatology unit. Baseline anti-gout medications were frequently ceased on admission and in 9% of episodes, no pharmacotherapy was prescribed. Delays in initiation of treatment occurred in up to 29% of patients. Acute management included anti-inflammatory monotherapy, or combinations of colchicine, non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids. Of patients prescribed colchicine, 26% received >1.5 mg/day and a strong correlation was found between colchicine dose and the occurrence of diarrhoea. NSAIDs were prescribed in 29% of patients with pre-existing renal impairment. Overall, 25% of patients received inappropriate pharmacological management. In patients not under the direct care of the rheumatology unit, in-hospital rheumatology consultation was sought by the treating unit in 34% of episodes. Consultation was sought more frequently in patients with multiple joint involvement, but there were no other obvious differences in baseline clinical characteristics between cases with or without rheumatology involvement. In cases with rheumatology involvement, patients were investigated more frequently, they received more pharmacotherapeutic intervention, in particular combination anti-inflammatory therapy, and they achieved better symptomatic relief and long-term follow up. CONCLUSION: Acute gout episodes in hospital are variably investigated and treated with frequent suboptimal management. We recommend establishment of a hospital-wide protocol to support decision-making regarding investigations, treatment and follow up.

Long-term outcomes of vertebroplasty for osteoporotic compression fractures.

INTRODUCTION: This study aimed to determine outcomes of percutaneous vertebroplasty for osteoporotic vertebral compression fractures (VCFs). METHODS: Prospective assessment of short-term (

Expression of the alphaEbeta7 integrin by mast cells in rheumatoid synovium.

OBJECTIVE: Rheumatoid synovitis is characterized by a mast cell response in which tryptase containing mast cells (MCT) associate with T lymphocyte infiltration, and tryptase and chymase containing mast cells (MCTC) correlate more closely with tissue damage or repair events. We investigated expression of the alphaEbeta7 integrin and its ligand E-cadherin in rheumatoid and normal synovium and compared this expression to synovial mast cell responses. METHODS: Immunohistochemical analysis was used to determine the expression of alphaEbeta7 and E-cadherin in rheumatoid (n = 17) and normal (n = 6) synovium. The density of MCT and MCTC mast cell subsets was compared to the density of alphaEbeta7 positive mast cells. RESULTS: The mean density of alphaEbeta7 positive cells in rheumatoid synovia was 25.2 cells/mm2 (range 0.3-102.9), of which 26.7% (range 0-68.6%) were mast cells. A mean of 11.9% (range 0-30.4%) of rheumatoid synovial mast cells expressed alphaEbeta7 compared to 0% in normal synovium (p < 0.0001). There was a strong correlation between the density of alphaEbeta7 positive cells and the total mast cell density in rheumatoid synovium (r2= 0.74). alphaEbeta7 positive mast cell density correlated significantly with the MCT subset density (r2 = 0.5, p = 0.014), but not with the MCTC subset density. E-cadherin expression was increased in rheumatoid compared with normal synovium, but did not colocalize or correlate with alphaEbeta7 expression. CONCLUSION: These results indicate a role for alphaEbeta7 in the mast cell response that occurs in rheumatoid synovitis, in particular the MCT mast cell subset expansion associated with inflammatory events and interactions with infiltrating lymphocytes.

Coincidence Counting in Time-of-Flight Mass Spectrometry: A Test for Chemical Microhomogeneity.

Coincidence counting techniques have been combined with time-of-flight mass spectrometry in the examination of surfaces for chemical microhomogeneity. A mathematical formalism was developed to describe the principles underlying this coincidence counting technique and was used to produce a quantitative method for handling the data obtained. This technique of testing for chemical homogeneity has been demonstrated with a sample that consists of a physical mixture of polystyrene and crystals of NaF which were tenths of micrometers in diameter. Ultimately this approach is expected to be useful for the routine testing of surfaces for chemical homogeneity at the level of tens of nanometers.