A cluster analysis for threshold perimetry

Cluster analysis in perimetry is a technique used in the evaluation of localised visual field loss. It has previously been applied to suprathreshold data and, unlike the indices currently available to indicate localised loss, it is influenced by the relative positions of individual defects. This paper describes a cluster analysis for use with data from Program 31 of the Octopus perimeter. To demonstrate the technique, sensitivity values of normal 60-year-old subject were altered to simulate localised loss. Illustrative examples of clinical cases are given, showing differing degrees of localised loss that do not influence the corrected loss variance (CLV) but influence the computed cluster parameters. It is hoped that the value of this form of analysis will be demonstrated in clinical follow-up of glaucoma patients.     

Tc-99m(V) DMSA imaging. A new approach to studying metastases from breast carcinoma.

Combined Tc-99m MDP skeletal imaging and Tc-99m(V) DMSA whole body scans to detect metastases were performed during the follow-up of 30 patients who underwent surgery for breast carcinoma. Eight patients had normal Tc-99m MDP and Tc-99m(V) DMSA scans and were declared free of metastatic disease, further confirmed by no change in symptomatology over a 1-year follow-up period. Twenty-two patients had positive Tc-99m MDP scans with varied skeletal involvement. Tc-99m(V) DMSA scans showed matched areas of increased radiotracer concentration in bony metastases in 20 of these patients. Tc-99m(V) DMSA concentration was not seen in traumatic vertebral collapse or in coexistent osteoarthritic disease in vertebral metastatic involvement. Interestingly, Tc-99m(V) DMSA showed increased concentration in brain and liver metastases. Pentavalent Tc-99m(V) DMSA appears useful for detecting skeletal and soft-tissue metastases in breast carcinoma, and can improve the specificity of Tc-99m MDP bone scans in screening for bone metastases.     

Direct detection and identification of Mycobacterium tuberculosis and Mycobacterium bovis in bovine samples by a novel nested PCR assay: correlation with conventional techniques

Mycobacterium tuberculosis and M. bovis infect animals and humans. Their epidemiologies in developed and developing countries differ, owing to differences in the implementation of preventive measures (World Health Organization, 1999). Identification and differentiation of these closely related mycobacterial species would help to determine the source, reservoirs of infection, and disease burden due to diverse mycobacterial pathogens. The utility of the hupB gene (Rv2986c in M.tuberculosis, or Mb3010c in M.bovis) to differentiate M. tuberculosis and M. bovis was evaluated by a PCR-restriction fragment length polymorphism (RFLP) assay with 56 characterized bovine isolates (S. Prabhakar et al., J. Clin. Microbiol. 42:2724-2732, 2004). The degree of concordance between the PCR-RFLP assay and the microbiological characterization was 99.0% (P < 0.001). A nested PCR (N-PCR) assay was developed, replacing the PCR-RFLP assay for direct detection of M. tuberculosis and M. bovis in bovine samples. The N-PCR products of M. tuberculosis and M. bovis corresponded to 116 and 89 bp, respectively. The detection limit of mycobacterial DNA by N-PCR was 50 fg, equivalent to five tubercle bacilli. M. tuberculosis and/or M. bovis was detected in 55.5% (105/189) of the samples by N-PCR, compared to 9.4% (18/189) by culture. The sensitivities of N-PCR and culture were 97.3 and 29.7, respectively, and their specificities were 22.2 and 77.7%, respectively. The percentages of animals or samples identified as infected with M.tuberculosis or M. bovis by N-PCR and culture reflected the clinical categorizations of the cattle (P of <0.05 to <0.01). Mixed infection by N-PCR was detected in 22 animals, whereas by culture mixed infection was detected in 1 animal.     

Over-expression of TATA binding protein (TBP) and p53 and autoantibodies to these antigens are features of systemic sclerosis, systemic lupus erythematosus and overlap syndromes

The aim of this study was to determine the expression levels of p53 and TATA binding protein (TBP) and the presence of autoantibodies to these antigens in Asian Indian patients with systemic sclerosis (SSc), overlap syndromes (OS) and systemic lupus erythematosus (SLE). Fifty patients with SSc, 20 with OS, including mixed connective tissue diseases (MCTD), 20 with SLE, 10 disease controls (DC) and 25 controls (C) were studied. The over-expression of p53 and TBP antigen was determined quantitatively by sandwich enzyme-linked immunosorbent assay (ELISA), varies between four- and sevenfold higher in patients with SSc, OS and SLE, in comparison to DC and C. The expressed protein antigens were not present as free antigens but as immune-complexes. Autoantibodies to p53 were detected by ELISA in 78% subjects with SSc, 100% with OS and 80% with SLE. Autoantibodies to TBP were observed in 28% patients with SSc, 25% with OS and 15% with SLE. In comparison to healthy controls, the titre of antibodies to p53 was significantly higher in patients with SSc (P = 0.00001) than the patients with OS (P = 0.00279) and SLE (P = 0.00289), whereas the titre of antibodies to TBP was higher in patients with OS (P = 0.00185) than the SLE (P = 0.00673) and the SSc (P = 0.00986) patients. Autoantibodies to p53 and TBP were detected in all these patients and the levels of these two autoantibodies showed weak negative correlation with each other. We propose that the over-expression of these antigens might be due to hyperactive regulatory regions in the p53 and TBP gene.     

Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice

Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1^asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1^asj/asj mice on normal chow and to patients with mono- and biallelic ENPP1 mutations, 5-week-old Enpp1^asj/asj mice on the high-phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1^asj/asj mice with recombinant Enpp1-Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Personal exposure to nitrogen dioxide and risk of airflow obstruction in asthmatic children with upper respiratory infection

BACKGROUND: Several studies have linked air pollution by nitrogen dioxide (NO(2)) with increased hospital admissions for asthma in children. Exacerbations of asthma in children are often precipitated by upper respiratory infections. It is therefore possible that NO(2) increases the risk of airways obstruction when asthmatic children develop upper respiratory infections. METHODS: To test this hypothesis a sample of 114 asthmatic children aged 7-12 years were followed for a total of up to 13 months. Probable upper respiratory infections were identified by consensus review of daily symptom diaries, and episodes of airways obstruction from serial records of peak expiratory flow (PEF). Personal exposures to NO(2) were measured with Palmes tubes that were changed weekly. Generalised estimating equations were used to assess the relative risk (RR) of an asthmatic exacerbation starting within seven days of an upper respiratory infection according to estimated NO(2) exposure during the one week period from two days before to four days after the onset of the infection. RESULTS: The children were followed for an average of 34 weeks during which 318 upper respiratory infections and 224 episodes of reduced PEF were diagnosed. PEF episodes were much more likely to occur in the seven days following the onset of an upper respiratory infection than at other times. Estimated exposures to NO(2) at the time of infections were generally low (geometric mean 10.6 microg/m(3)). Compared with exposures of < or = 8 microg/m(3), exposures of >28 microg/m(3) were associated with a RR of 1.9 (95% confidence interval 1.1 to 3.4) for the development of an asthmatic episode within seven days of an infection. CONCLUSIONS: The findings give some support to the hypothesis that NO(2) increases the risk of asthmatic exacerbations following respiratory infections, even at relatively low levels of exposure. Further studies in populations with higher exposures would be useful.