The performance of two rapid quantitative D-dimer assays in 287 patients with clinically suspected pulmonary embolism

Context: Objective tests are necessary for the diagnosis of pulmonary embolism (PE). D-dimer assays have been suggested as useful screening tests to exclude this diagnosis. Objective: To compare the diagnostic accuracy of two rapid quantitative D-dimers in patients with suspected pulmonary embolism. Design: Plasma D-dimer levels were measured using two commercially available assays (Tinaquant® and Vidas®). A strict imaging protocol was used to arrive at a final diagnosis of PE or deep venous thrombosis (DVT). Setting: Multicenter study in six Dutch referral centers. Patients: A total of 287 in- and outpatients with clinically suspected pulmonary embolism. Main outcome measures: Diagnostic accuracy indices for the two assays were calculated and additional receiver-operated characteristics (ROC) analysis was performed. Results: Using the manufacturer's advised cutoff values, the sensitivity and specificity were 88% and 52% for Vidas and 82% and 61% for Tinaquant, respectively. These differences were statistically significant (McNemar, P<0.0001). However, no statistical differences were found between the two assays using ROC analysis (AUC=0.78 for both assays). Conclusions: Both quantitative D-dimer tests had similar diagnostic accuracy; however, at the manufacturer's advised cutoff level, Vidas performed significantly better. Nevertheless, to safely exclude pulmonary embolism, D-dimer assays should be combined with other diagnostic tests.     

Somatostatin and somatostatin analogues: diagnostic and therapeutic uses.

Somatostatin and its octapeptide analogues exert their effects through interaction with somatostatin receptor (sst) subtypes 1 through 5 (sst 1-5 ). Somatostatin binds with high affinity to all sst subtypes, whereas the currently commercially available octapeptide analogues bind only with a high affinity to sst 2 and sst 5. Pituitary tumors, endocrine pancreatic tumors, and carcinoid tumors express multiple sst subtypes, but sst 2 predominance is found in 90% of carcinoids and 80% of endocrine pancreatic tumors. Sst 2 and sst 5 predominance is found in growth hormone-secreting pituitary tumors. In patients harboring sst 2 - or sst 5 -positive neuroendocrine tumors, clinical symptomatology can be controlled by the chronic administration of one of the currently commercially available octapeptide somatostatin analogues. Tumors and metastases that bear sst 2 or sst 5 can be visualized in vivo after injection of radiolabeled octapeptide analogues. Radiolabeled octapeptide analogues can also be used for radiotherapy of sst 2 - and sst 5 -positive advanced or metastatic neuroendocrine tumors.     

Frequent detection of human papillomavirus 16 E2-specific T-helper immunity in healthy subjects.

The incidence of genital human papillomavirus (HPV) infections is high in young, sexually active individuals. Most infections are cleared within 1 year after infection. The targets for the cellular immune response in this process of viral clearance remain to be identified, but the expression pattern of the E2 protein in early infection and low-grade cervical intraepithelial neoplasia renders this early protein a candidate antigen. Therefore, we studied the HPV16 E2-specific T-cell responses in more detail. Very strong proliferative responses against one or more peptide-epitopes derived from this antigen can be found in peripheral blood mononuclear cell cultures of approximately half of the healthy donors. Additional analysis revealed that at least a majority of these responses represent reactivity by memory CD4(+) T-helper (Th) 1-type cells capable of secreting IFN-gamma on antigenic stimulation. Interestingly, all of the E2 peptides against which strong responses were detected are clustered in the key functional domains of the E2 protein, which are conserved to considerable extent between HPV types. This suggests that HPV16 E2-specific Th memory may be installed through encounter with HPV types other than HPV16. Indeed, one HPV16 E2-specific Th clone was found to cross-react against homologuous peptides from other HPV types, but three other Th clones failed to show similar cross-reactivity. Therefore, part of the HPV16 E2-specific Th memory may relate to previous encounter of other HPV types, whereas the majority of the immune repertoire concerned is most likely established through infection with HPV16 itself. Our data are the first to reveal that the T-cell repertoire of healthy donors can contain particularly high frequencies of E2-specific memory Th cells and suggest that boosting of this immunity can be used for preventive and therapeutic vaccination against HPV-induced lesions.     

Nonpharmacological treatment of reflex syncope

Clinical Autonomic Research - Reflex syncope is a common medical problem. Vasovagal reflex syncope is the most frequent form. Although the prognosis of the disorder is excellent, it may impose...     

Simultaneous kidney-pancreas transplantation: The preferred option for patients with type I diabetes mellitus and approaching end-stage renal disease

Diabetes mellitus is a chronic disease often leading to disabling microvascular and macrovascular complications. Intensive treatment with insulin can only delay the progression of these complications. Normalization of the glucose homeostasis will reduce the cardiovascular morbidity and mortality. At this time, whole-pancreas transplantation is the only option to achieve long-term insulin independence, resulting in an improvement or stabilization of the microvascular and, at least partly, the macrovascular lesions. Therefore, simultaneous kidney-pancreas transplantation has become the preferred treatment option for selected patients with type I diabetes mellitus and approaching end-stage renal disease. With the improving results of isolated pancreas transplantation, this procedure may be offered with increasing frequency to diabetics with a good functioning kidney transplant or to diabetics with overt diabetic nephropathy but preserved renal function. In this review we describe recipient and donor selection criteria, some surgical techniques, survival rates, and the currently used immunosuppressive protocols, and at the end we propose a treatment strategy.     

Unipolarity of fibroblasts in rodent periodontal ligament

In order to investigate whether fibroblasts in rodent periodontal ligament have a structural polarity, the position of the Golgi apparatus or the centriolar region in the cells was studied using light and electron microscopy. It appeared that, in the periodontal ligament of continuously erupting mouse and rat incisors, centrioles in fibroblasts on the tooth side of the ligament are preferably located in the anterior (occlusally directed) part of the cytoplasm. Polarity of fibroblasts in a single direction was less pronounced or absent on the bone side of the tissue. In the mouse, fibroblasts in the connective tissue adjacent to the incisor also contained an extensive system of cytoplasmic microtubules, whereas in the fibroblasts on the bone side of the ligament microtubules were less frequent. Unipolarity of fibroblasts was also observed in the periodontal ligament of the rat maxillary first molar, which is characterized by a limited eruption. Here, the Golgi region was usually situated in that pole of the cells that was directed towards the alveolar wall and the occlusal plane. It is suggested that structural polarity of fibroblasts in the periodontal ligament of rodent teeth is associated with orientation of functional activities of the cells, such as unidirectional movement or unidirectional deposition or phagocytosis of collagen.     

Presentation and diagnosis of imported schistosomiasis: relevance of eosinophilia, microscopy for ova, and serology

BACKGROUND: In nonendemic countries a steady rise in cases of imported schistosomiasis has been observed. The objective of this study was to describe the presentation of patients diagnosed with schistosomiasis in the Outpatient Department (OPD) for Tropical Diseases in the Academic Medical Center, Amsterdam, the Netherlands. METHODS: In a retrospective study, patients with schistosomiasis from our OPD (1997-1999), including a subgroup of persons asking for screening for schistosomiasis and found positive, were analyzed. Diagnosis was based on freshwater exposure in an endemic area and positive serology for schistosomal antibodies. The following data were recorded: age, gender, country of birth, travel destination, symptoms, eosinophil count, and results of serology and stool and urine microscopy. RESULTS: Seventy-eight patients (42 travelers, 16 expatriates, and 20 immigrants) were diagnosed with schistosomiasis; 47% were infected in southern Africa. Twenty-four percent had specific symptoms, 57% had eosinophilia, and in 17 patients (22%) Schistosoma ova were found. Eleven travelers suffered from Katayama syndrome. Of the subgroup of 42 persons screened for schistosomiasis, 15 (36%) had schistosomal antibodies; the majority of these persons (10/15 [67%]) were infected in southern Africa. CONCLUSION: In our OPD schistosomiasis was diagnosed in about 26 patients per year, 3% of all new presentations. Infections were almost exclusively acquired in Africa. In travelers high eosinophilia was due to acute schistosomiasis; in immigrants it was due to concomitant helminthic infections. One of three people asking to be screened for schistosomiasis had schistosomal antibodies. Eosinophilia was indicative but an insufficient screening tool, and stool and urine microscopy for ova were not sensitive. Screening by serology is easy and reliable and the method of choice in asymptomatic persons with a history of freshwater exposure in a high-risk area.     

Less invasive anterior column reconstruction in thoracolumbar fractures

Posterior short-segment pedicle screw constructs are commonly used for reduction and fixation of traumatic thoracolumbar spine fractures. Although this technique is usually simple and effective, complications such as loss of fixation or recurrence of deformity are common because of the insufficiency of the damaged anterior column. Anterior approaches to address this deficiency are associated with high morbidity and complications. We have developed a technique to reduce and support the fractured anterior column through a transpedicular approach. Balloon-assisted-endplate-reduction (BAER) followed by vertebroplasty (VTP) with calcium phosphate cement in combination with short segment pedicle screw construct seem to be a safe and effective technique to reconstruct the anterior column in a less invasive manner. In this article, the rationale behind this technique, experimental studies, and the first clinical results are discussed.     

Dermal exposure to cyclophosphamide in hospitals during preparation, nursing and cleaning activities

Objectives: To determine levels of potential and actual dermal exposure to cyclophosphamide (CP) during performance of oncology-related tasks in hospitals and to investigate the relationship with potential sources and surface contamination levels of CP. Methods: Dermal exposure to CP was determined for tasks with potential exposure to CP: preparation of CP, decanting of patients urine, washing of the patient, removal of bed sheets of treated patients and cleaning of patients toilets on oncology wards. Exposure was assessed by the collection of nitrile and latex protective medical gloves (potential exposure), washing of hands (actual exposure), from cotton pads attached to (un)covered forearms (potential or actual exposure) and a wipe sample of the forehead (actual exposure). Bulk samples (i.e. application fluids and patients excreta) and possible contact surfaces were monitored to assess the amount of CP available for dermal exposure. Results: Pharmacy technicians, oncology nurses and cleaning personnel showed actual and potential dermal exposure to CP during performance of their daily duties. Exposure occurred predominantly on the hands and sporadically on the forehead and forearms. Although all nurses used gloves during handling of patients urine and sometimes during the other nursing tasks, skin underneath gloves was repeatedly contaminated. Results of tests on bulk and surface contamination samples confirmed that patients intravenously treated with CP excrete the unmetabolised drug, which could subsequently lead to dermal exposure of hospital personnel. A clear relationship was found between dermal exposure levels and direct sources of exposure for all tasks, except for handling patients urine. Conclusions: We demonstrated for the first time that actual dermal exposure to CP is common among oncology nurses working with patients treated with this anti-neoplastic drug. Pharmacy technicians and cleaning personnel, on the other hand, are potentially exposed to CP, and protection provided by gloves seemed to be sufficient.