Patients with Primary Sjögren's Syndrome Have Alterations in Absolute Quantities of Specific Peripheral Leucocyte Populations.

An accurate dissection of peripheral blood enumeration is lacking in primary Sjögren's syndrome (pSS). The purpose of this study was to quantify different leucocyte populations in peripheral blood of patients with pSS. Numbers of specific leucocyte subsets were determined in 86 pSS patients and 74 healthy donors quantifying 21 distinct subtypes by flow cytometry. Subgroups of pSS patients were stratified based on presence of extraglandular manifestations (EGMs) and SSA/SSB autoantibodies. Overall, pSS patients manifested decreased lymphocyte subpopulations compared to healthy donors. Such decreases were more pronounced in SSA/SSB positive patients and patients with EGM. Granulocyte and monocyte subpopulations were increased in pSS patients compared to healthy donors, with the greatest increases in SSA/SSB positive patients. Unsupervised hierarchal clustering based on cell quantities was used to further subgroup the pSS patients into four clusters. One of the clusters characterized by higher concentrations of NKT cells, CD56hi NK cells, CD20+ CD38- B cells and CD8+ CD38- T cells was associated with weaker clinical symptoms than the other clusters, possibly marking a milder disease phenotype. In conclusion, our analyses indicate significant alterations in the cellular profiles of peripheral blood leucocytes in patients with pSS and may help to stratify the patients according to disease severity.

Bromelain treatment leads to maturation of monocyte-derived dendritic cells but cannot replace PGE2 in a cocktail of IL-1ß, IL-6, TNF-α and PGE2.

Immunotherapy using dendritic cells (DC) has shown promising results. However, the use of an appropriate DC population is critical for the outcome of this treatment, and the search for an optimal DC subset is still ongoing. The DC used in immunotherapy today are usually matured with a cytokine cocktail consisting of TNF-α, IL-1ß, IL-6 and PGE(2). These cells have deficits in their cytokine production, particularly IL-12p70, mainly because of the presence of PGE(2). Bromelain is a pineapple stem extract containing a mixture of proteases that has been used clinically in adjuvant cancer treatment. In this study, we analysed the effect of bromelain on human monocyte-derived DC. We added bromelain to the cytokine cocktail and modified cytokine cocktails with either no PGE(2) or reduced amounts of PGE(2), respectively. Combining bromelain with the cytokine cocktails containing PGE(2) resulted in an increased surface expression of CD83, CD80 and CD86. The chemokine receptor CCR7 was also considerably upregulated in these DC populations compared with DC treated with the cytokine cocktail alone. Removal or reduction of PGE(2) from the cytokine cocktail did not increase the IL-12p70 secretion from stimulated DC, and addition of bromelain to the different cytokine cocktails resulted in only a minor increase in IL-12p70 production. Moreover, combining bromelain with the cytokine cocktails did not improve the T cell stimulatory capacity of the generated DC populations. In conclusion, bromelain treatment of monocyte-derived DC does not improve the functional quality compared with the standard cytokine cocktail.

Role of dendritic cells in Sjögren's syndrome.

Sjögren's syndrome (SS) is a chronic inflammatory and lymphoproliferative autoimmune disease of unknown aetiology. It is characterised by progressive mononuclear cell infiltration of the salivary and lacrimal glands and a decreased glandular secretion, resulting in dryness of the mouth and eyes (xerostomia and keratoconjunctivitis sicca, respectively). Dendritic cells (DC) are considered to be the most potent antigen-presenting cells. Because of their central role in initiating an immune response while maintaining tolerance, impaired function of these cells might lead to the break of peripheral tolerance and initiation of immune responses to self-antigens. This review will focus on the possible role of DC in SS.

[Conventional and virtual simulation in retrobulbar irradiation]. / Konventionelle und virtuelle Simulation bei der Retrobulbärbestrahlung.

BACKGROUND: Radiotherapy is commonly used in Grave's ophthalmopathy. The target volume encompasses the ocular muscles and the orbital tissue. The result of conventional simulation can be examined by means of CT simulation. PATIENTS AND METHODS: Twenty-five planning CTs with Grave's ophthalmopathy were studied. The conventional simulation of 4 x 4 cm2 lateral portals confined anteriorly by the fleshy canthus was performed on a CT-simulator using the observer's eye view (OEV) and digitally reconstructed radiographs (DRR). The coverage of the target volume and sparing of the eye lenses were studied on axial CT slices and multiplanar reconstructions (MPR). The distances between the apex of the orbita and cornea, fleshy canthus, and bony canthus were measured as well as the distance between cornea and posterior face of the lens. RESULTS: The pituitary gland and the ocular lenses were spared in each case (25/25). The orbita was entirely covered in 24 cases (96%). However, anterior parts of the external eye muscles were not completely encompassed in 7 cases (28%). The distance from the apex of the orbita to the cornea was 54.6 mm (53.3 to 55.8 mm, 95% confidence interval), to the fleshy canthus 40.3 mm (39.4 to 41.2 mm), and to the bony canthus 31.4 mm (30.2 to 32.5 mm). The distance between cornea and posterior face of the lens was 8.3 mm (7.9 to 8.7 mm). The distance between cornea and canthus differed significantly from normal eyes while the distance between cornea and posterior face of the lens was very similar to normal eyes. CONCLUSIONS: Conventional simulation of orbital irradiation with lateral fields confined anteriorly by the fleshy canthus ensures protection of the ocular lenses and the pituitary gland. However, anterior parts of the eye muscles may occasionally not completely be covered. The fleshy canthus and the cornea are more reliable landmarks as compared to the bony canthus.

The role of CT simulation in whole-brain irradiation.

PURPOSE: Evidence is growing that incorrect field-shaping is a major cause of treatment failure in whole-brain irradiation (WBI). To evaluate the potential benefits of CT simulation in WBI we compared field-shaping based on 3D CT simulation to conventional 2D simulation. METHODS: CT head scans were obtained from 20 patients. Conventional 2D planning was imitated by drawing the block contours on digitally reconstructed radiographs (DRR) by four radiotherapists. Critical parts of the target and the eye lenses were subsequently marked and planning was repeated using 3D information ("3D planning"). The results of both methods were compared by evaluation of the minimal distance from the field edge according to each site. RESULTS: In conventional planning using DRR, major geographic mismatches (< -3 mm) occurred in the subfrontal region and both eye lenses with 1% each location. Minor mismatches (-3 to 0 mm) predominantly occurred in the contralateral lens (21%), ipsilateral lens (10%), and subfrontal region (9%). Close margins (0-5 mm) were most frequently noted at the contralateral lens (49%), ipsilateral lens (35 %), and the subfrontal region (28%). When 3D planning was used, mismatches were not found. However, close margins were inevitable at the ipsilateral lens (5%), subfrontal region (30%), and contralateral lens (70%). CONCLUSIONS: CT simulation in WBI is significantly superior to conventional simulation with respect to complete coverage of the target volume and protection of the eye lenses. The narrow passage between the ocular lenses and lamina cribrosa represents a serious limitation. These patients are safely identified with CT simulation and can be referred for modified irradiation techniques.

Exfoliative cytology of adenoma malignum (minimal deviation adenocarcinoma) of the uterine cervix.

Cervical scraping smears from two cases of histologically confirmed adenoma malignum of the uterine cervix were reviewed. In one case, several irregular sheets of benign-appearing glandular cells with slightly enlarged nuclei, conspicuous nucleoli, and clear cytoplasm were found. In the other case, in addition to sheets of benign-appearing glandular cells, there were clustered malignant glandular cells with prominent nucleoli. The sheets of benign-appearing glandular cells in both cases displayed wispy cytoplasmic extensions or "tails." Cytologic differential diagnosis with other glandular lesions of the cervix such as clear cell carcinoma, microglandular hyperplasia, diffuse laminar glandular hyperplasia, tubal metaplasia, and well-differentiated invasive or in situ adenocarcinoma is briefly discussed.

Cytology of atypical and malignant meningiomas in intraoperative crush preparations.

Six cases of atypical and malignant meningioma studied by intraoperative crush preparations are reported. Four atypical meningiomas were characterized by large cohesive and dyshesive cell clusters showing slightly pleomorphic nuclei and scant cytoplasm. The papillary meningioma yielded dyshesive groups of pleomorphic cells with variable and well-defined cytoplasm. The malignant meningioma, hemangiopericytic type, showed dyshesive cells with scant, ill-defined cytoplasm and spindle-shaped or vesicular nuclei.

Follicular carcinoma of the thyroid with an adenoid cystic pattern. Report of a case with aspiration biopsy cytology, immunohistochemistry and electron microscopy.

Aspiration biopsy of a histologically confirmed follicular carcinoma of the thyroid with an adenoid cystic pattern revealed numerous epithelial cells with scant cytoplasm and oval or pleomorphic nuclei present singly, in clusters or around round, laminated bodies.

Tamm-Horsfall protein as a marker in interstitial cystitis.

It has been suggested that immunohistochemical staining for Tamm-Horsfall protein in bladder epithelium may be a marker for interstitial cystitis. Of bladder biopsies from 14 interstitial cystitis patients only 3 demonstrated positive staining for Tamm-Horsfall protein within the mucosa, whereas 2 of 11 control biopsies showed positive Tamm-Horsfall protein results. In addition, staining in 4 ureteral specimens from interstitial cystitis patients and 4 controls was negative in all cases. An effort to detect this protein in enterocystoplasty specimens also showed a negative pattern. Our study does not confirm the Tamm-Horsfall protein as permeating either the bladder epithelium in interstitial cystitis or bowel mucosa in enterocystoplasty. This finding does not necessarily mean that these surfaces are not permeable to substances of smaller molecular size, nor does it define whether this is of importance in the etiology of interstitial cystitis. However, it does suggest that this technique does not allow detection of a marker for the disease.

Imaging strategies in the evaluation of soft-tissue hemangiomas of the extremities: correlation of the findings of plain radiography, angiography, CT, MRI, and ultrasonography in 12 histologically proven cases.

Twelve patients with the histologic diagnosis of soft-tissue hemangioma of the extremities (nine intramuscular, two subcutaneous, and one synovial) were evaluated in a retrospective study using plain film radiography (n = 12), angiography (n = 8), computed tomography (CT; n = 4), magnetic resonance imaging (MRI; n = 3), and ultrasonography (US; n = 2). In eight of nine intramuscular lesions, the plain film demonstration of phleboliths suggested the diagnosis, while the plain radiographs were normal in three. Angiograms showed the pathognomonic features of soft-tissue hemangioma in six patients. MRI was characteristic in all three patients: The lesion demonstrated intermediate signal intensity on T1-weighted spin echo images and extremely bright signal on T2-weighting. US showed a hypoechoic soft-tissue mass in one case and a mixed echo pattern in the other. In one case, a central echogenic focus with acoustic shadowing consistent with a calcified phlebolith was identified, and one lesion exhibited increased color flow and low resistance arterial Doppler signal. CT showed a nonspecific mass in one of four cases and a mass with phleboliths in three. If a deep hemangioma is suspected, we recommend initial imaging with plain radiography followed by MRI. US may be useful in confirming the presence of a mass in doubtful cases or if MRI is unavailable. CT offers no distinct advantage over the combined use of plain radiography and MRI. Although angiography demonstrated the pathognomonic features in all six deeply situated lesions, because of its invasiveness it should be reserved chiefly for those patients undergoing surgical resection.

Orthogonal electrode catheter array for mapping of endocardial focal site of ventricular activation.

Precise location of the endocardial site of origin of ventricular tachycardia may facilitate surgical and catheter ablation of this arrhythmia. The endocardial catheter mapping technique can locate the site of ventricular tachycardia within 4-8 cm2 of the earliest site recorded by the catheter. This report describes an orthogonal electrode catheter array (OECA) for mapping and radiofrequency ablation (RFA) of endocardial focal site of origin of a plunge electrode paced model of ventricular activation in dogs. The OECA is an 8 F five pole catheter with four peripheral electrodes and one central electrode (total surface area 0.8 cm2. In eight mongrel dogs, mapping was performed by arbitrarily dividing the left ventricle (LV) into four segments. Each segment was mapped with OECA to find the earliest segment. Bipolar and unipolar electrograms were obtained. The plunge electrode (not visible on fluoroscopy) site was identified by the earliest wave front arrival times of -30 msec or earlier at two or more electrodes (unipolar electrograms) with reference to the earliest recorded surface ECG (I, AVF, and V1). Validation of the proximity of the five electrodes of the OECA to the plunge electrode was performed by digital radiography and RFA. Pathological examination was performed to document the proximity of the OECA to the plunge electrode and also for the width, depth, and microscopic changes of the ablation. To find the segment with the earliest LV activation a total of 10 +/- 3 (mean +/- SD) positions were mapped. Mean arrival times at the two earlier electrodes were -39 +/- 4 msec and -35 +/- 3 msec. Digital radiography showed the plunge electrode to be within the area covered by all five electrodes in all eight dogs. The plunge electrode was within 1 cm2 area of the region of RFA in all eight dogs. The width and depth of ablation were 5 +/- 3.5 and 7 +/- 3.5 mm, respectively. Microscopic changes revealed coagulative necrosis, hemorrhage, and inflammatory changes in all RFAs. In conclusion, the OECA can map the endocardial focal site of origin of paced ventricular activation within 1 cm2 area in a canine model. RFA from the OECA can cause discrete ablations representing all five electrodes or cross-shaped ablation connecting central electrode to all four peripheral electrodes. This catheter holds promise for extending surgical and clinical catheter ablation procedures.