Histologic analysis of renal leukocyte infiltration in antineutrophil cytoplasmic antibody-associated vasculitis: importance of monocyte and neutrophil infiltration in tissue damage

OBJECTIVE: The histopathologic lesions in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have been studied extensively, but the exact composition of the cellular infiltrate is unclear. We undertook this study to analyze renal leukocyte infiltration and the cellular distribution within glomeruli and interstitium in 65 renal biopsy samples obtained from patients newly diagnosed as having AAV. METHODS: Renal cellular tissue infiltration was assessed with an immunoperoxidase method. Furthermore, the infiltrating cell types were correlated with clinical and histopathologic data. RESULTS: The predominant interstitial infiltrating cells were T lymphocytes, while monocytes and, to a lesser extent, granulocytes constituted the dominant infiltrating cell types in glomeruli. Interestingly, lymphocyte infiltration was predominantly periglomerular, especially around glomeruli with sclerosis or heavy crescent formation, while interstitial monocyte and neutrophil infiltration was diffusely distributed over the interstitial tissue. A significant correlation was found for the glomerular infiltration of CD68-positive macrophages with the presence of glomerular necrosis as well as with the number of glomeruli with crescents (P < 0.0001 and P = 0.005, respectively). No correlation was found for interstitial fibrosis with the infiltration of any leukocyte subset. Furthermore, a significant correlation was found for the interstitial as well as for the glomerular infiltration of CD68-positive macrophages with serum creatinine concentration at the time of biopsy (P = 0.001 and P = 0.006, respectively). CONCLUSION: These data underscore a major role of monocytes in addition to neutrophils in the tissue damage of AAV.     

Cimetidine effect on dopaminergic modulation of prolactin release in healthy women

The aim of the present study was to test whether cimetidine (Cim) influences PIF (prolactin inhibitory factor), and thereby indirectly affects the release of prolactin (PRL) from the pituitary lactotrophs. For that purpose 10 mg metoclopramide (Met), known for its dopamine-receptor blocking properties, were first given orally to 6 subjects. This raised the PRL level from 13 ± 2 to 97 ± 12 ng/ml in 60 min (p < 0.001). PRL tended to plateau at this level until 120 min. An additional 7 subjects were then injected iv with 400 mg Cim, 90 min after oral administration of placebo. Placebo did not change the basal PRL level, but the subsequent Cim injection raised the PRL level from 14 ± 4 to 66 ± 9 ng/ml (p < 0.01). When, in the same subjects, an oral dose of Met was given (10 mg) PRL increased from 19 ± 4 to 112 ± 10 ng/ml (p < 0.001). A subsequent Cim injection, given on top of the PRL plateau, 90 min after the Met ingestion, however, failed to induce any further increase in PRL. To exclude that this failure was not merely a reflection of a Met-induced depletion of the PRL stores, 25 μg thyrotropin-releasing hormone (TRH) were given iv to an additional 6 subjects, 90 min after ingestion of either placebo or Met. Also in these subjects placebo left basal PRL unaffected. The subsequent TRH injection, however, raised PRL from 10 ± 2 to 55 ± 6 ng/ml (p < 0.001). Met increased PRL from 17 ± 4 to 133 ± 19 ng/ml (p < 0.01) in these subjects, and TRH, subsequently injected, induced a further PRL increase to 174 ± 18 ng/ml (p < 0.01). The observation that Cim fails to elicit an increase in PRL after priming with Met thus indicates that Cim, under normal conditions, stimulates the PRL release via a reduced dopaminergic inhibition of the lactotrophs.     

Lipoprotein particle distribution and size, insulin resistance, and metabolic syndrome in Alaska Eskimos: the GOCADAN study

Background

Metabolic syndrome (MS) is associated with dyslipidemia, and insulin resistance (IR) may be a main determinant of this dyslipidemia.

Objective

To determine how lipoprotein particle concentration and size are related to MS and IR in a population-based sample of Alaska Eskimos.

Design

Participants underwent a physical exam, personal interview, collection of biological specimens, and diagnostic tests.

Setting

This study was conducted in the Norton Sound region of Alaska.

Participants

One thousand one hundred fifty-eight Inupiat Eskimo adults (women = 653, men = 505).

Main outcome measures

Lipoprotein particle profile was evaluated by nuclear magnetic resonance (NMR) and related to presence of MS and level of IR.

Results

Participants with MS had (a) significantly higher concentrations of all VLDLs and a larger VLDL size (women, p = 0.007; men, p = 0.0001); (b) higher concentrations of small LDL (women, p < 0.0001; men, p = 0.09) and lower concentrations of large LDL (women, p < 0.0001), leading to a smaller overall LDL size (women, p < 0.0001; men, p < 0.05); (c) significantly lower concentrations of large HDL (both genders, p < 0.0001) and an increase in intermediate (women, p < 0.05) and small HDL (women, p < 0.0001; men, p < 0.004). Lipoprotein profile with increasing HOMA-IR resembled that of individuals with MS.

Conclusions

In this population MS is characterized by lipoprotein distribution and size abnormalities independent of obesity, age, and other cardiovascular risk factors, including lipid concentration. IR seems the major determinant.     

Value of oxygen-enhanced MRI of the lungs in patients with pulmonary hypertension: a qualitative and quantitative approach

Purpose:

To assess the clinical value of oxygen‐enhanced magnetic resonance imaging (oeMRI) in patients with pulmonary hypertension (PH) by correlation with ventilation/perfusion (V/Q) scintigraphy.

Materials and Methods:

In all, 33 patients with known PH underwent V/Q scintigraphy and oeMRI. oeMRI was used to assess the regional pulmonary function based on relative‐signal‐enhancement (RSE) and cross‐correlation‐coefficient (CCC) maps, evaluating mean RSE (mRSE), fraction of oxygen‐activated pixels (fOAP), and mean CCC (mCCC). Two reviewers, blinded to the results of scintigraphy, performed visual detection of diseased lung areas.

Results:

In 26 of the 33 patients (79%) the image quality of oeMRI reached a diagnostic level. In total, 150 lung areas were analyzed and compared. Sensitivities/specificities of oeMRI for detecting these defects were: RSE vs. ventilation scintigraphy 92%/73%; RSE vs. perfusion scintigraphy 60%/87%; CCC vs. ventilation scintigraphy 89%/81%; CCC vs. perfusion scintigraphy 50%/87%. The number of diseased lung areas in oeMRI correlated significantly with the number in V/Q scintigraphy (P < 0.01). mRSE showed a significant correlation with the number of diseased lung areas in ventilation scintigraphy (P < 0.05).

Conclusion:

oeMRI is feasible in PH patients, yielding an overall moderate agreement between oeMRI and V/Q scans, with a good sensitivity of oeMRI for the detection of ventilation defects as compared with ventilation scintigraphy. J. Magn. Reson. Imaging 2012;35:86‐94. © 2011 Wiley Periodicals, Inc.     

Flow diversion treatment: intra-aneurismal blood flow velocity and WSS reduction are parameters to predict aneurysm thrombosis

Background

To evaluate the haemodynamic changes induced by flow diversion treatment in cerebral aneurysms, resulting in thrombosis or persisting aneurysm patency over time.

Method

Eight patients with aneurysms at the para-ophthalmic segment of the internal carotid artery were treated by flow diversion only. The clinical follow-up ranged between 6?days and 12?months. Computational fluid dynamics (CFD) analysis of pre- and post-treatment conditions was performed in all cases. True geometric models of the flow diverter were created and placed over the neck of the aneurysms by using a virtual stent-deployment technique, and the device was simulated as a true physical barrier. Pre- and post-treatment haemodynamics were compared, including mean and maximal velocities, wall-shear stress (WSS) and intra-aneurysmal flow patterns. The CFD study results were then correlated to angiographic follow-up studies.

Results

Mean intra-aneurysmal flow velocities and WSS were significantly reduced in all aneurysms. Changes in flow patterns were recorded in only one case. Seven of eight aneurysms showed complete occlusion during the follow-up. One aneurysm remaining patent after 1?year showed no change in flow patterns. One aneurysm rupturing 5?days after treatment showed also no change in flow pattern, and no change in the maximal inflow velocity.

Conclusions

Relative flow velocity and WSS reduction in and of itself may result in aneurysm thrombosis in the majority of cases. Flow reductions under aneurysm–specific thresholds may, however, be the reason why some aneurysms remain completely or partially patent after flow diversion.     

Intraoperative MRI and endocrinological outcome of transsphenoidal surgery for non-functioning pituitary adenoma

Background  

Transsphenoidal surgery guided by intraoperative MRI (iMRI) is related to higher rates of tumour resection. The influence of iMRI on endocrinological outcome is still unclear. This study evaluates the endocrinological outcome of iMRI-guided transsphenoidal surgery.     

Adult patients with sporadic polycystic kidney disease: the importance of screening for mutations in the PKD1 and PKD2 genes

Background

ADPKD is one of the most common inherited disorders, with high risk for end-stage renal disease. Numerous patients, however, have no relatives in whom this disorder is known and are unsure whether they may transmit the disease to their offsprings. The aim of this study was to evaluate whether germline mutation analysis adds substantial information to clinical symptoms for diagnosis of ADPKD in these patients.

Methods

Clinical data included renal function and presence of liver or pancreas cysts, heart valve insufficiency, intracranial aneurysms, colonic diverticles, and abdominal hernias. Family history was evaluated regarding ADPKD. Germline mutation screening of the PKD1 and PKD2 genes was performed for intragenic mutations and for large deletions.

Results

A total of 324 adult patients with ADPKD including 30 patients without a family history of ADPKD (sporadic cases) were included. PKD1 mutations were found in 24/30 and PKD2 mutations in 6 patients. Liver cysts were present in 14 patients and intracranial aneurysms in 2 patients. Fourteen patients (45%) had no extrarenal involvement. Compared to the 294 patients with familial ADPKD, the clinical characteristics and the age at the start of dialysis were similar in those with sporadic ADPKD.

Conclusion

The clinical characteristics of patients with sporadic and familial ADPKD are similar, but sporadic ADPKD is often overlooked because of the absence of a family history. Molecular genetic screening for germline mutations in both PKD1 and PKD2 genes is essential for the definitive diagnosis of ADPKD.     

Morphological characteristics of Schatzker type IV tibial plateau fractures: a computer tomography based study

Purpose

The objective of this study was to evaluate the morphological characteristics of Schatzker type IV tibial plateau fractures.

Methods

A retrospective analysis of radiographic and computed tomographic data of tibial plateau Schatzker type IV fractures from January 2010 to December 2011 was conducted in a level 1 trauma centre. The medial fracture angle (MFA), surface area percentage (SAP), and medial fracture height (MFH) were measured on CT images using the Picture Archiving and Communication System.

Results

Based on the location of fracture and the MFA, 75 cases of Schatzker type IV fracture were divided into three subtypes: anteromedial fracture (seven cases, 9.3 %), total medial plateau fracture (36 cases, 48 %), and posteromedial fracture (32 cases, 42.7 %). The anteromedial fracture was located on the anterior part of the medial plateau, the average MFA was positive 47.5°, the SAP was 38.3 % and the MFH was 41.6 mm. The total medial plateau fracture usually involved the entire medial plateau, the mean value of MFA was 81.2°, the SAP was 53.9 % and the MFH was 64.0 mm. The posteromedial fracture was located on the posterior part of the medial plateau, the MFA was negative 42.5°, the SAP was 32.4 % and the MFH was 44.8 mm.

Conclusion

The direction and location of Schatzker type IV fractures are highly variable. Proper operative approach and fixation method should be selected based on the morphological characteristics of individual medial plateau fractures.