Fibrinopeptide A and the phosphate content of fibrinogen in venous thromboembolism and disseminated intravascular coagulation

Concentrations of plasma fibrinopeptide A (FPA) were measured by radioimmunoassay in 50 patients with venous thromboembolism or disseminated intravascular coagulation or both. A consistent discrepancy was observed in values obtained with two anti-FPA antisera. Analysis of extracts from plasma of these patients by high-performance liquid chromatography (HPLC) revealed the presence of a phosphorylated and an unphosphorylated form of the A peptide. Differences in concentrations of FPA measured with the two antisera could be accounted for by their different reactivity with phosphorylated FPA (FPA-P). The differences were abolished by treatment with alkaline phosphatase. A good correlation was observed between the FPA-P content of free A- peptide material and of fibrinogen in plasma as determined by HPLC (r = .88, P less than .001, n = 11). In patients with elevated FPA levels, the mean FPA-P content of fibrinogen was significantly higher (P less than .002, n = 13) than in patients with normal FPA levels (n = 8) and in healthy controls (n = 14). Phosphorus in fibrinogen did not correlate with fibrinogen degradation products or fibrinogen levels and became normal on adequate anticoagulation. Therefore, blood-clotting activation may lead to a high phosphate content of fibrinogen and of free FPA in plasma.     

Spinal metastases mimicking low back pain of mechanical origin: a case report

Spinal malignancies are an essential consideration when a patient presents to a chiropractic office with back pain. This single case report exemplifies the importance of patient presentation and physical examination findings. We must also consider the rationale for x-raying patients on an individual case basis. Textbook cases do not always exist and special diagnostic tests do not always provide a definitive diagnosis of underlying pathology. Even though history and examination findings suggest a routine diagnosis, continual re-evaluation and recognition of the need to change the diagnosis on occasion is extremely important. The patient should not only be thoroughly evaluated upon initial presentation, but also each time they present for treatment. The decision to x-ray a patient is considered important. X-ray examination can be used to confirm a diagnosis or to rule out potential pathologies, and not necessarily done as a routine screening procedure.A case report is presented in which the pathologic signs were not evident on plain film x-rays upon initial presentation.     

Optic disc haemorrhages and vascular abnormalities in a glaucoma population

Purpose: To retrospectively examine the optic disc photographs of a glaucoma population for optic disc haemorrhages, vascular occlusions and vascular abnormalities. Methods: The optic disc photographs of 906 eyes of glaucoma and suspect glaucoma patients were examined. Optic disc photographs were taken annually, where possible, with the follow-up period varying between 1 and 14 years duration (mean, 2.89). Glaucoma patients are regularly reviewed every 4–6 months and glaucoma suspects every 1–2 years, depending on the ophthalmologist. Low-tension glaucoma patients were reviewed more frequently (mean, every 2.6 months). The results of the findings were compared to a control group of 39 subjects with a mean follow-up period of 7 years, using Fisher's exact test. Results: It was found that during the period under review, 7.4% (n= 67) of eyes had optic disc haemorrhages. The highest frequency of optic disc haemorrhages (37.5%) was found in the low tension glaucoma group (P= 0.0001) followed by 11.4% of primary open-angle glaucoma eyes (P= 0.03). In the normal group there were three eyes with optic disc haemorrhages and one with a disc collateral, which constitutes 5.1% vascular changes in this sub-group. Of the study eyes 2.8% had central retinal vein occlusions, 1.3% branch vein occlusion, 1.2% disc vessel abnormalities (loops) and 1.1% disc collaterals. Discrete nerve fibre layer haemorrhages and microaneurysms were found in 0.8% and 1.8% of eyes, respectively. Conclusions: A total of 16.8% of the eyes observed in this study had either disc haemorrhages or vascular changes. The underlying trend of vascular and haemorrhagic changes in glaucoma are demonstrated in this sample, which is in general agreement with previous studies. The high percentage of optic disc haemorrhages in low tension glaucoma is highlighted. The presence of microaneurysms and nerve fibre layer haemorrhages is interesting but of unknown significance.     

Characterisation of the solution conformation of a cyclic RGD peptide analogue by NMR spectroscopy allied with a genetic algorithm approach and constrained molecular dynamics

The solution conformation of a cyclic RGD peptide analogue, cyclo-(S,S)-2-merrcaptobenzoate-arginine-glycine-aspartate -2-mercaptoanilide, has been determined via two independent approaches for the searching of conformational space and identification of conformations consistent with NMR and CD spectroscopic data: (i) the use of a binary genetic algorithm and (ii) a molecular dynamics simulation. Inter-proton distances were obtained via analysis of cross-peak volumes from a two-dimensional ROESY NMR spectroscopy experiment at 600 MHz and were used as constraints for the computational calculations. The mercaptoanilide amide proton resonance chemical shift had a very small temperature coefficient, indicating that this proton was hydrogen-bonded. Circular diehroism data showed that, in solution, the torsion angle about the disulfide bond was negative, consistent with one of the distinct conformations around this bond in the 200 ps molecular dynamics simulation. The backbone conformations of the structures resulting from the two different approaches were very similar.     

Causal association in pharmacovigilance and pharmacoepidemiology: thoughts on the application of the Austin Bradford-Hill criteria.

The methods used for the evaluation of drug safety signals (including major signals leading to withdrawal of products from the market) are inconsistent and sometimes of poor quality. While the assessment of the safety of medicines needs to consider specific issues such as drug interactions and variation in compliance, the general principles, which are used to study environmental hazards, can be applied for this purpose. The criteria proposed by Sir Austin Bradford-Hill more than 35 years ago for attributing disease causation to environmental factors have been used widely in epidemiology, are applicable to pharmacovigilance and pharmacoepidemiology. The Austin Bradford-Hill criteria include strength, consistency, specificity, temporality, biological gradient, plausibility, coherence, experimental evidence and analogy. The paper reviews each of these criteria with emphasis on pharmacovigilance and pharmacoepidemiology and with some examples. The application of the Austin Bradford-Hill criteria to the evaluation of causal association in pharmacovigilance and pharmacoepidemiology is very useful. However, it requires understanding of the limitations of the data, such as, under-reporting, poor quality of information from third parties and misclassification. Further work is required to develop strategies to handle these limitations.     

Extended wear disposable soft contact lenses as an alternative to photorefractive keratectomy: Report of 4 years experience

Purpose: To establish whether; in a well-informed population, the use of extended wear disposable soft contact lenses (EWDSCL) poses an unacceptable risk to vision and corneal health due to complications associated with their use. Methods: A 4 year retrospective review of EWDSCL, involving 371 patients in Melbourne from a single general ophthalmology practice. The important aspects of this group were that all patients were given written instructions about the methods of ensuring initial and ongoing cleanliness of lenses, no lenses were cleaned and reinserted, and no solutions other than the saline in the original packaging, and comfort drops, were used. Two types of EWDSCL were used, in powers from - 9.0 to + 6.0 D, and with an initial aim of 4 weeks uninterrupted extended wear. Follow-up was from 2 to 52 months, with an average of 24 months. Results: Of the 354 patients followed up, 236 (66%) regularly wore them on an extended overnight basis, and of these 180 (76%) wore them for the suggested 4 week period before renewal of lenses. In the 471 eyes of 236 patients, adverse reactions occurred at the following rates: marginal infiltrates (12 cases, 2.5%); corneal oedema (10 cases, 2%); peripheral corneal vascularization (2 cases, 0.4%); and presumed infective keratitis (1 case, 0.2%). No eyes lost one or more lines of Snellen acuity. Conclusions: When disposable soft contact lenses do not come into contact with cleaning solutions, saline from bottles or aerosol cans, or storage cases, their use on an extended wear basis (up to 4 weeks continuous) appears to be associated with a low risk of minor or major complications. The results of this review indicate that controlled usage of EWDSCL is safer than previous reports have indicated.     

Mupirocin resistance among consecutive isolates of oxacillin-resistant and borderline oxacillin-resistant Staphylococcus aureus at a university hospital.

Mupirocin resistance was determined in consecutive oxacillin-resistant and borderline oxacillin-resistant Staphylococcus aureus clinical isolates collected over 14 months at a university hospital during 1991 and 1992. Twenty of 86 (23%) oxacillin-resistant and borderline oxacillin-resistant S. aureus isolates were mupirocin resistant; 80% were high-level resistant. Prior mupirocin use was a significant risk factor (relative risk, 6.08; 95% confidence interval, 3.7 to 9.99). Seven of 20 resistant isolates were distinct strains, as determined by pulsed-field gel electrophoresis typing. Two instances of clonal dissemination of a single strain occurred, but several other distinct mupirocin-resistant strains were documented. Mupirocin resistance was unexpectedly common among these isolates.