Pregnancy loss, tissue factor pathway inhibitor deficiency and resistance to activated protein C.
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Biomedical subjects
Publications and source records attributed to C Gardiner.
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OBJECTIVES: Recent work has shown that human bone marrow contains mesenchymal stem cells (MSCs). However, little is known about their presence in peripheral blood. Since these cells are potentially responsible for tissue repair after injury, their number should be increased during these situations. To demonstrate their number during these situations, we measured MSCs in the peripheral blood of healthy donors and burn patients. MATERIALS AND METHODS: Blood samples were obtained from 15 acute burn patients and 15 healthy donors. We performed flow cytometric analysis, using a large monoclonal antibody panel: CD44, CD45, CD14, DR, CD34, CD19, CD13, CD29, CD105, CD1a, CD90, CD38, CD25. MSC phenotype was considered positive for CD44, CD13, CD29, CD90, and CD105, and negative for the other monoclonals. The testing was performed on day 3 after injury. We correlated the results with the age, sex, and size and type of burns. RESULTS: Cells expressing the MSC phenotype were detected in the peripheral blood of both groups. Noteworthy, compared with samples from healthy donors (0.0078 +/- 0.0044), blood obtained from burn patients showed a higher MSC percentage (0.1643 +/- 0.115; P < .001). The percentage of MSCs correlated with the size and severity of the burn. Increased values were also observed among younger patients. CONCLUSIONS: MSCs have an important role in regenerative processes of human tissues. We found cells phenotypically identical to MSCs circulating in physiological number in normal subjects, but in significantly higher amounts during acute large burns. Therefore, they may represent a previously unrecognized circulatory component to the process of skin regeneration.
We report a feasibility study of patient self-testing telemedicine for anticoagulant management using TOPCARE (Telematic Homecare Platform in Cooperative Health Care Provider Networks, developed by the European Commission for a user-friendly information society). TOPCARE comprises a Home Telematic Box (TOPCARE BOX), a central database held on a remote server and secure computer terminals in the anticoagulant clinic. The TOPCARE BOX transmits encrypted International Normalized Ratio (INR) results from the CoaguChek S monitor (Roche Diagnostics) via the patient's telephone line to the database, which is accessed by health-care professionals via the Internet. The database displays the patient's anticoagulant record, highlighting out of range results, overdue tests and quality control results. The database can also send information back to the TOPCARE box, although currently only the next test date can be transmitted. 23 patients, on long-term oral anticoagulation were recruited from the hospital anticoagulant clinic. After completing a nurse-led training course, patients tested their INR weekly on a CoaguChek S and transmitted their results via the TOPCARE BOX. The nurse specialist accessed the patient's results, electronically entered the date of the next test. Changes in warfarin dose were telephoned. Four patients dropped out early in the study and 19 patients received TOPCARE BOXs of which nine were fully functional. Unintentional software misconfiguration meant that remaining 10 TOPCARE BOXs were nonfunctional (these were later reconfigured but not reintroduced into the study). Patients successfully transmitted 222 results over a 5-month period using the TOPCARE system. Early server problems were resolved, but intermittent problems with database access persisted and five results were not received by the server. Although concerns were raised regarding technical problems, feedback from patients and staff was favourable and the system thought to be user-friendly. In conclusion, this pilot study showed that telemedicine is a feasible option for anticoagulant management, but that the technology requires thorough testing prior to installation.
BACKGROUND: Disseminated cutaneous herpes zoster in healthy persons is uncommon, though it has been described in immunocompromised patients. CASE PRESENTATION: We describe a case of disseminated cutaneous herpes zoster in an elderly man with no apparent immunosuppressive condition. The patient was treated successfully with intravenous Acyclovir. CONCLUSION: We suggest that disseminated zoster can occur in an immunocompetent host and should be promptly recognized and treated to prevent serious complications.
There is a limited evidence base for self-testing and -management for oral anticoagulation management. Available data suggest that these are credible models for a significant minority of patients if underpinned by structured training and follow-up. The guidelines presented are necessarily consensual and outline procedures for patient selection, training, product procurement, product maintenance, quality assurance procedures, dosage adjustment and clinical supervision. The cost-effectiveness of these models remains to be elucidated within the UK. Further data on both health economic and clinical outcomes are required from UK based studies before widespread implementation of self-testing and management can be recommended on a wider scale.
BACKGROUND AND OBJECTIVE: We tested the hypothesis that disturbances of the visual pathway following sevoflurane general anaesthesia (a) exist and persist even after clinical discharge criteria have been met and (b) are associated with decreased contrast sensitivity. METHODS: We performed pattern and full-field flash electroretinograms (ERG) in 10 unpremedicated ASA I patients who underwent nitrous oxide/sevoflurane anaesthesia. ERG and contrast sensitivity were recorded preoperatively, immediately after discharge from the recovery room and 2 h after discontinuation of sevoflurane. The time at which the Post Anaesthesia Discharge Score first exceeded 9 was also noted. Data were analysed using paired, one-tailed t-tests and Pearson's correlation coefficient. RESULTS: On the full-field photopic ERG, b-wave latency was greater at each postoperative time point (31.6+/-1.1 and 30.8+/-1.1 ms) compared to preoperatively (30.1+/-1.1 ms, P < 0.001 and P = 0.03, respectively). Oscillatory potential latencies were greater on discharge from the recovery room compared with preanaesthetic values (23.1+/-3.1 vs. 22.4+/-3.3 ms, P = 0.01) and returned to baseline by 2 h after emergence from anaesthesia. Also at 2 h after emergence from anaesthesia: (a) P50 latency on the pattern ERG was greater than at baseline (81.5+/-17.9 vs. 51.15+/-22.6ms, P = 0.004); (b) N95 amplitude was less compared to preanaesthetic values (2.6+/-0.5 vs. 3.3+/-0.4 microV, P = 0.003) and (c) contrast sensitivity was less compared to baseline values (349+/-153 vs. 404+/-140, P = 0.048). A positive correlation was demonstrated between contrast sensitivity and both N95 amplitude and b-wave latency (r = 0.99 and r = -0.55 at significance levels of P < 0.005 and P < 0.05, respectively). CONCLUSIONS: Postoperative ERG abnormalities and associated decreases in contrast sensitivity are consistently present in patients who have undergone nitrous oxide/sevoflurane anaesthesia. These abnormalities persist beyond the time at which standard clinical discharge criteria have been met.
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We describe two cases of a unilateral fixed dilated pupil secondary to the ocular instillation of nebulised ipratropium bromide. In one patient there was no other neurological abnormality. The second patient was unconscious following a cardiac arrest. While a fixed dilated pupil is an alarming sign, if it is caused by ocular instillation of ipratropium bromide the condition will resolve, although it may take up to 24 hours. The differential diagnosis of a unilateral dilated pupil includes partial third nerve palsy, tonic pupil, direct trauma to the eye and pharmacological mydriasis. The diagnosis can often be determined using pilocarpine eye drops.
A comparative evaluation of four commercial coagulation test kits for screening the protein C pathway kits was performed at two centres. The tests were Acticlot V-OUT (V-OUT), the PCA test (PCA), the GradiThrom PCP test (PCP) and ProC Global (ProC). Reference ranges were established in 40 normal subjects and, with the exception of V-OUT and ProC, significant differences were observed between males and females. Consequently, sex-specific normal cut-off values (fifth percentile) were used that led to greatly improved sensitivity when compared with the manufacturers' recommended cut-off values. Plasma from patients with factor V Leiden (n = 23), congenital protein S deficiency (n = 19), congenital protein C deficiency (n = 11), lupus anticoagulant (n = 17) and thrombophilia with no demonstrable protein C pathway defect (n = 20) were tested. All kits showed 100% sensitivity to factor V Leiden, but sensitivity was variable for protein C deficiency (27-73%), and poor for protein S deficiency (29-35%). The lupus anticoagulant affected all kits to some degree, with 29-35% giving values below the fifth percentile of normal, whereas all kits gave 1/20 unexpected abnormal results in the thrombophilia group, with the same sample accounting for the abnormal results in three of the four kits. Overall sensitivity and specificity, respectively, for defects in the protein C pathway were: V-OUT, 60 and 91%; PCA, 70 and 86%; PCP 75 and 94%; and ProC, 66 and 88%. We conclude that all four kits lack the sensitivity and specificity required for routine laboratory screening for defects in the protein C pathway and cannot replace assays for the individual proteins of this system.
Three commercial dilute Russell's viper venom time (DRVVT) kits were evaluated at four UK centres experienced at performing lupus anticoagulant (LA) tests. Each centre established a normal reference range for the DRVVT ratio calculated against local pooled normal plasma from 20 healthy normal subjects. Plasma from LA-positive patients and LA-negative thrombophilia patients was also tested. DRVVT ratios and the degree of correction were assessed in a variety of ways to reflect not only the UK national Guidelines, but also the manufacturers' recommendations. The reference range data showed a normal distribution in each case, but considerable variation in the mean and SD between the centres and reagents, with the mean +2SD value ranging from 1.06 to 1.19. The use of an arbitrary DRVVT ratio of < 1.1 as the cut-off value for normality, which is applied in many laboratories, is therefore inappropriate. Although no single kit had a clear overall advantage in terms of sensitivity and specificity, the way in which the screen and confirmation data were analysed had a major impact on the interpretation of the results. A data analysis method employing a mean plus two standard deviations (SDs) cut-off for normality, and judgement regarding confirmation of LA based on a percentage correction of DRVVT ratio, was the simplest and most consistent, with overall sensitivity and specificity values of 81% and 94%, respectively, for uncomplicated LA-positive and LA-negative thrombophilia samples. We conclude that the 1991 BSCH Guidelines are in need of revision, each laboratory should establish its own normal reference range for the DRVVT ratio and a common method should be used for calculating the degree of correction with confirmation reagents, so that LA results can be correctly interpreted between laboratories. Standardizing DRVVT interpretation in this way should improve the consistency of LA detection.
Mast cells are thought to play an important role in atherogenesis and plaque rupture, but their role in the subsequent platelet activation and thrombus formation is unclear. Tryptase positive cells (KU812T+) were established from the KU812 cell line as an in vitro model of human mast cells and used to study the effect of mast cell activation on human platelets. Overnight incubation of KU812T+ with IgE and subsequent challenge with anti-IgE caused the release of heparinoid substances which inhibited 1 microg/ml collagen-induced platelet aggregation. KU812T+ challenged with compound 48/80 produced a releasate that had no apparent heparinoid content but caused full platelet aggregation. These findings showed that, although activation of KU812T+ via FcepsilonR1 partially abrogated collagen-induced platelet aggregation, activation of the C5a receptor signalling pathway, by compound 48/80, caused the release of potent platelet-activating substances. This cell culture model offers a unique insight into the role of platelet-mast cell interactions in arterial thrombogenesis.
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The measurement of protein S is essential in the investigation of thrombophilia. Protein S forms a complex with C4b binding protein which exists in equilibrium with the free form but only the free form has anticoagulant cofactor activity. The accurate measurement of protein S has previously proved problematical. We have investigated the use of an ELISA method for protein S, using monoclonal antibodies directed against the free form, which can be used in parallel with polyclonal antibodies for the simultaneous assay of total protein S. The total protein S measurement was based on a well established method while the monoclonal antibody free protein S assay (mAb PS) was less complex than previous assays with no requirement for prior PEG precipitation and showed improved precision (intra-assay CV = 4.8% and 7.1%, between assay CV = 7.1% and 8.6% respectively). The mAb assay compared well with the conventional PEG precipitation ELISA for free protein S and a functional protein S assay based on the prothrombin time, in normal subjects, patients with thrombophilia, congenital protein S deficient patients or out-patients stabilized on oral anticoagulants. This assay overcomes many of the problems associated with protein S measurement and is a useful tool in the investigation of thrombophilia.
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A randomized treatment trial of travelers' diarrhea was carried out among U.S. military personnel participating in routine exercises in several port cities in South America and West Africa. A 5-day, twice daily course of either norfloxacin (400 mg) or trimethoprim/sulfamethoxazole (TMP/SMX, 160/800 mg) was given to 142 volunteers. At the end of 5 days of treatment, diarrhea had resolved in 100% of 73 patients receiving norfloxacin and 97.1% (67/69) receiving TMP/SMX. A probable bacterial pathogen was determined in 44% of 142 subjects: 49% of the norfloxacin group and 39% of the TMP/SMX group. The most common pathogens detected were enterotoxigenic Escherichia coli in 20% of cases and rotavirus in 15%. Resistance to TMP/SMX was present in 20 (27%) bacterial isolates, while no resistance to norfloxacin was found. Eight of 10 patients in the TMP/SMX treatment group who had TMP/SMX-resistant bacterial enteropathogens improved clinically. Both norfloxacin and TMP/SMX were clinically effective in the treatment of travelers' diarrhea in this military population.
Two outbreaks of photosensitivity and jaundice in sheep grazing the grass, Brachiaria decumbens. In West Java in 1983 and 1983 and 1990 are described. Aggregates of acicular clefts and crystals were present in bile canaliculi, bile ducts, Kupffer cells, hepatocytes and in kidney tubules. The number of crystals increased with the length of exposure to the plant and sheep that died had the largest accumulations. These crystalline structures have been reported before in this syndrome, but are similar to those seen in Tribulus terrestris and Panicum spp toxicities.