Outbreak of Salmonella Braenderup infections associated with Roma tomatoes, northeastern United States, 2004: a useful method for subtyping exposures in field investigations.

Salmonella Braenderup is an uncommon serotype in the United States. In July 2004, a multistate outbreak of Salmonella Braenderup diarrhoeal infections occurred, with 125 clinical isolates identified. To investigate, we conducted a case-control study, enrolling 32 cases and 63 matched controls. Cheese, lettuce and tomato eaten at restaurants all appeared to be associated with illness. To further define specific exposures, we conducted a second study and asked managers of restaurants patronized by patients and controls about cheese, lettuce and tomato varieties used in dishes their patrons reported consuming. This information was obtained for 27 cases and 29 controls. Roma tomatoes were the only exposure significantly associated with illness (odds ratio 4.3, 95% confidence interval 1.2-15.9). Roma tomatoes from two restaurants were traced back to a single tomato packing house. The methods used in this field investigation to define specific exposures may be useful for other foodborne outbreaks.

Colposcopy information leaflets: what women want to know and when they want to receive this information.

OBJECTIVES: To evaluate whether the information leaflets produced by UK colposcopy clinics provide women with the information they desire and to determine when they would like to receive this information. DESIGN: Questionnaire study and structured evaluation. SETTING: The colposcopy clinic of a UK cancer centre. PARTICIPANTS: Forty-two women attending a pre-colposcopy counselling session and 100 consecutive women attending the colposcopy clinic. METHODS: Thirty-eight standards derived from the concerns/questions asked by women attending a pre-colposcopy counselling session were used to assess locally produced colposcopy clinic leaflets from UK colposcopy clinics, the leaflets produced by the Royal College of Obstetricians and Gynaecologists and the National Health Service Cervical Screening Programme (NHSCSP), and two "leaflets" obtained from internet sites. The Gunning fog test was used to assess the leaflets' readability. A questionnaire survey of 100 women attending the colposcopy clinic was used to determine when women wanted to receive information about colposcopy. MAIN OUTCOME MEASURES: Percentage of questions answered by a given leaflet and Gunning fog scores for readability. RESULTS: The information leaflets of 128 colposcopy clinics were received and assessed. Thirty-two clinics only sent women the NHSCSP leaflet. No leaflet answered all 38 questions. Less than half (36/100) of the leaflets answered more than 50% of the questions. In addition to the lack of advice given, different leaflets frequently gave conflicting advice. The average Gunning fog score was 9.7 (range 5.5-15.5). The majority of women (70%) wanted to receive information about colposcopy at or prior to the time of receiving their abnormal smear test result, although only 42% of women actually received information at this time. CONCLUSIONS: Many UK colposcopy clinics do not appear to be providing women with the information they require to understand their condition and the procedure that they are about to undergo. Furthermore, this information is often not provided at the appropriate time in the screening process.

Contribution of regions distal to glycine-160 to the anticoagulant activity of tissue factor pathway inhibitor.

The functions of the first two Kunitz domains of tissue factor pathway inhibitor (TFPI) are well defined as active site-directed inhibitors of factor VIIa and factor Xa. The anticoagulant properties of the third Kunitz domain and C-terminal region were probed using altered forms of TFPI. TFPI-160 contains the first two Kunitz domains. K1K2C contains the first two Kunitz domains and the basic C-terminus. Neither TFPI-160 nor K1K2C contains the third Kunitz domain. In amidolytic assays containing calcium, TFPI-160 is a less potent inhibitor of factor Xa than TFPI. However, addition of the C-terminus in K1K2C nearly restores inhibitory activity to that of TFPI, indicating that the third Kunitz domain is not required for direct inhibition of factor Xa. When compared in assays containing phospholipids and factor Va, K1K2C and TFPI-160 are poor inhibitors compared to TFPI, demonstrating that the third Kunitz domain is required for the full anticoagulant activity of TFPI. TFPI was further characterized in amidolytic assays performed with Gla-domainless factor Xa and in prothrombin activation assays using submicellar concentrations of short-chain phospholipids (C6PS). TFPI and K1K2C are worse inhibitors of Gla-domainless factor Xa, compared to wild-type factor Xa, while TFPI-160 inhibits both forms of factor Xa equally, suggesting a C-terminus/Gla domain interaction. TFPI is a potent inhibitor of thrombin generation by prothrombinase assembled with C6PS, while TFPI-160 and K1K2C are not. Conversely, TFPI does not inhibit prothrombin activation by prothrombinase assembled on a two-dimensional lipid bilayer. Together, the data indicate that the region between Gly-160 and the end of the third Kunitz domain contributes to TFPI function by orienting the second Kunitz domain so that it can bind the active site of phospholipid-associated factor Xa prior to prothrombinase assembly and/or by slowing formation of the prothrombinase complex.

Tissue factor pathway inhibitor binds to platelet thrombospondin-1.

Tissue factor pathway inhibitor (TFPI) is a Kunitz-type serine proteinase inhibitor that down-regulates tissue factor-initiated blood coagulation. The most biologically active pool of TFPI is associated with the vascular endothelium, however, the biochemical mechanisms responsible for its cellular binding are not entirely defined. Proposed cellular binding sites for TFPI include nonspecific association with cell surface glycosaminoglycans and binding to glycosyl phosphatidylinositol-anchored proteins. Here, we report that TFPI binds specifically and saturably to thrombospondin-1 (TSP-1) purified from platelet alpha-granules with an apparent K(D) of approximately 7.5 nm. Binding is inhibited by polyclonal antibodies against TFPI and partially inhibited by the B-7 monoclonal anti-TSP-1 antibody. TFPI bound to immobilized TSP-1 remains an active proteinase inhibitor. Additionally, in solution phase assays measuring TFPI inhibition of factor VIIa/tissue factor catalytic activity, the rate of factor Xa generation was decreased 55% in the presence of TSP-1 compared with TFPI alone. Binding experiments done in the presence of heparin and with altered forms of TFPI suggest that the basic C-terminal region of TFPI is required for TSP-1 binding. The data provide a mechanism for the recruitment and localization of TFPI to extravascular surfaces within a bleeding wound, where it can efficiently down-regulate the procoagulant activity of tissue factor and allow subsequent aspects of platelet-mediated healing to proceed.

Solvent/detergent-treated plasma has decreased antitrypsin activity and absent antiplasmin activity.

Solvent/detergent (S/D)-treated plasma is currently marketed by the American Red Cross as a virally inactivated alternative to fresh-frozen plasma (FFP). The serpin-type serine proteinase inhibitors have a flexible reactive site loop (RSL) that can convert from the active conformation to the inactive latent or polymerized conformations when exposed to heat and/or detergents. We have compared the conformational stability and inhibitory activity of 3 plasma serpins-antithrombin, antitrypsin, and antiplasmin-in S/D plasma and FFP. In S/D plasma, virtually 100% of the antiplasmin and approximately 50% of the antitrypsin are in either the latent or polymerized conformation and lack inhibitory activity, while in FFP only the active conformation is present. Interestingly, antithrombin is not affected by S/D treatment and remains fully active. These data demonstrate that S/D plasma is not simply a virally inactivated equivalent of FFP. The lack of antiplasmin activity and decreased antitrypsin activity in S/D plasma suggest that it may not be as effective as FFP for the treatment of bleeding in patients with systemic activation of proteolytic cascades, such as disseminated intravascular coagulation and sepsis, acquired fibrinolytic states, and large-volume transfusion. Although there has been extensive use of S/D plasma in several European countries with no reports of adverse effects, clinical studies directly comparing the efficacy of these 2 plasma products are needed to directly evaluate the relative therapeutic efficacy of FFP and S/D plasma for the treatment of these diseases.

Patient-controlled analgesia: optimizing the experience.

A patient-controlled analgesia (PCA) program was established on a surgical unit with children age 7 years and older. The primary objectives for the PCA program were safety and efficacy. A retrospective evaluation of the first 30 patients enrolled in the program suggested in the program suggested that it was safe and adequately controlled pain for all but 4 patients. A chart review of these patients indicated that the relation between the number of failed administration attempts, the total hourly analgesic intake, and the pain intensity score was key to optimizing the use of PCA. Recommendations to strengthen the PCA program were implemented based on information gained from these 4 patients with poorly controlled pain.

Do women referred for colposcopy receive adequate information from the primary care team?

The objective of this study was to assess whether women had been counselled by their primary health care team and whether or not they had received any information about colposcopy. We also asked where the best information had been obtained. The setting was the colposcopy clinic of a large district general hospital, the design of which was a cross-sectional audit using a questionnaire. The subjects were 100 women attending the colposcopy clinic. The results show that 63% of women were seen by their primary health care team before the colposcopy visit and that counselling was associated with knowledge about colposcopy (P = 0.017). However, 43% of women felt that they knew nothing about colposcopy whilst 19% of women thought that the information they had obtained was not useful. We conclude that there is scope for improving the quality, timing and provision of information for women undergoing colposcopy.

Total sacrectomy for a giant sacral schwannoma. A case report.

Giant sacral schwannomas (GSS) are extremely rare. Complete resection of benign but neurologically devastating tumors has been recommended. A 48-year-old man with GSS had a tumor so large that a total sacrectomy was necessary. A special method of lumbar iliac fixation was devised. Two years and nine months after surgery, the patient was free of pain and ambulating with bilateral orthoses.