MRI characteristics and histology of bone marrow lesions in dogs with experimentally induced osteoarthritis

Signal changes within the bone marrow adjacent to osteoarthritic joints are commonly seen on magnetic resonance (MR) images in humans and in dogs. The histological nature of these lesions is poorly known. In this study, we describe the MR imaging of bone marrow lesions adjacent to the stifle joints of dogs with experimental osteoarthritis over 13 months. Histology of the proximal tibia at the end of the study was compared with the last MR imaging findings. In five adult dogs, the left cranial cruciate ligament was transected. Post-operatively, MR imaging was performed at 1, 2, 3, 4, 6, 8, and 13 months. Dogs were euthanised after 13 months and histological specimen of the proximal tibia were evaluated. Bone marrow edema like MR imaging signal changes were seen in every MR examination of all dogs in one or more locations of the proximal tibia and the distal femur. Lesions varied in size and location throughout the whole study with the exception of constantly seen lesions in the epiphyseal and metaphyseal region at the level of the tibial eminence. On histology, hematopoiesis and myxomatous transformation of the bone marrow and/or intertrabecular fibrosis without signs of bone marrow edema were consistent findings in the areas corresponding to the MR imaging signal changes. We conclude that within the bone marrow, zones of increased signal intensity on fat suppressed MR images do not necessarily represent edema but can be due to cellular infiltration. Contrary to humans, hematopoiesis is seen in bone marrow edema-like lesions in this canine model of osteoarthritis.

Female patients with atherosclerotic lesions of the lower limbs. Not all are alike

BACKGROUND: Data on female patients with atherosclerotic peripheral arterial disease (PAD) are scarce, and limited primarily to the elderly population with multilevel disease. In this longitudinal observational study we compare female patients below 60 years of age with isolated lesions at the aortic bifurcation or focal superficial femoral artery disease. PATIENTS AND METHODS: Analysis is based on consecutive series of 43 female patients with PAD limited to the aortoiliac bifurcation (n = 28, group I) or an isolated femoral segment at the adductor channel (n = 15, group II) seen in a tertiary referral center between 1998 and 2000. The first assessment provided baseline data, with follow up data obtained at this study. Traditional risk factors, carotid artery disease and clinical outcome (mortality, cardiovascular events, vascular re-intervention rate, PAD progression) were evaluated over an interval of 5 (2 to 8) years. RESULTS: Female patients with aortic disease [group I] were younger (51.8 +/- 7.7 vs. 56.7 +/- 7.6 years in group II; p = 0.048), presented a more masculine phenotype, and smoked significantly more often (82% vs. 40%; p = 0.007). Arterial hypertension and diabetes mellitus were more common in group II, though it missed statistical significance (p = 0.068 and p = 0.085). Cardiovascular and limb outcome were comparable in both groups of female patients, while carotid artery disease was more severe in group I (i.e., carotid plaques in 71 vs. 53%). CONCLUSION: Our data support previous findings that cigarette smoking is a stronger risk factor for aortic disease as compared to femoral disease in younger female patients, with the strongest effect of smoking on a localized region of the aortic bifurcation.

Renal oxygenation changes during acute unilateral ureteral obstruction: assessment with blood oxygen level-dependent mr imaging--initial experience

PURPOSE: To prospectively determine if changes in intrarenal oxygenation during acute unilateral ureteral obstruction can be depicted with blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging. MATERIALS AND METHODS: The study was approved by the local ethics committee, and written informed consent was obtained from all patients. BOLD MR imaging was performed in 10 male patients (mean age, 45 years +/- 17 [standard deviation]; range, 20-73 years) with a distal unilateral ureteral calculus and in 10 healthy age-matched male volunteers to estimate R2*, which is inversely related to tissue Po(2). R2* values were determined in the cortex and medulla of the obstructed and the contralateral nonobstructed kidneys. To reduce external effects on R2*, the R2* ratio between the medulla and cortex was also analyzed. Statistical analysis was performed with nonparametric rank tests. P < .05 was considered to indicate a significant difference. RESULTS: All patients had significantly lower medullary and cortical R2* values in the obstructed kidney (median R2* in medulla, 10.9 sec(-1) [range, 9.1-14.3 sec(-1)]; median R2* in cortex, 10.4 sec(-1) [range, 9.7-11.3 sec(-1)]) than in the nonobstructed kidney (median R2* in medulla, 17.2 sec(-1) [range, 14.6-23.2 sec(-1)], P = .005; median R2* in cortex, 11.7 sec(-1) [range, 11.0-14.0 sec(-1)], P = .005); values in the obstructed kidneys were also significantly lower than values in the kidneys of healthy control subjects (median R2* in medulla, 16.1 sec(-1) [range, 13.9-18.1 sec(-1)], P < .001; median R2* in cortex, 11.6 sec(-1) [range, 10.5-12.9 sec(-1)], P < .001). R2* ratios in the obstructed kidneys (median, 1.06; range, 0.85-1.27) were significantly lower than those in the nonobstructed kidneys (median, 1.49; range, 1.26-1.71; P = .005) and those in the kidneys of healthy control subjects (median, 1.38; range, 1.23-1.47; P < .001). In contrast, R2* ratios in the nonobstructed kidneys of patients were significantly higher than those in kidneys of healthy control subjects (P = .01). CONCLUSION: Increased oxygen content in the renal cortex and medulla occurs with acute unilateral ureteral obstruction, suggesting reduced function of the affected kidney.

[Oral erythroplakia and erythroleukoplakia: red and red-white dysplastic lesions of the oral mucosa--part 2: cytodiagnosis, pathogenesis, therapy, and prognostic aspects]

The second part of the present review article presents and discusses the current literature regarding cytodiagnostic aspects, pathogenesis, therapy, incidence of recurrence, and malignant transformation rate of oral erythroplakia (OE) and oral erythroleukoplakia (OEL). Oral cytopathology, eventually in combination with DNA cytometry, can add valuable information to conventional histopathology, but is not able yet to replace the aforementioned. Numerous molecular genetic variants have been studied in precancerous lesions to gain knowledge about the prognosis of these lesions. Still, there are no evidence-based parameters available to safely detect precursor lesions that will undergo malignant transformation in the future. Excision of OE and OEL should be performed with a margin of safety using the CO2 laser or a scalpel. Data about incidence of recurrence and malignant tranformation rates of OE are mostly based upon case reports or case series. The OEL has a significantly higher risk of malignant transformation than oral leukoplakias.

Elective implantation of sirolimus-eluting stents for bifurcated and non-bifurcated unprotected left main coronary artery lesions: clinical outcomes at one year

AIMS: Recent studies of drug-eluting stents for unprotected left main coronary artery (LMCA) disease have been encouraging. We examined the performance of sirolimus-eluting stents (SES) for this indication. METHODS AND RESULTS: This retrospective study included 228 consecutive patients (mean age = 68 +/- 11 years, 80.6% men, 26.3% diabetics) who underwent implantation of SES for de novo LMCA stenoses. The mean additive and logistic EuroSCOREs were 5.2 +/- 3.9 and 8.2 +/- 13.2, respectively. The main objective of this study was to measure the rate of major adverse cardiac events (MACE), including death, myocardial infarction and target lesion revascularisation (TLR) at 12 months. Other objectives were to measure the rates of in-hospital MACE and 12-month TLR. Outcomes in 143 patients with (BIF+ group), versus 84 patients without (BIF-group) involvement of the bifurcation were compared. The pre-procedural percent diameter stenosis (%DS) was 60.1 +/- 11.2 in the BIF+ versus 54.7 +/- 12.2% in the BIF- group (p=0.008), and decreased to 18.0 +/- 9.7 and 13.9 +/- 11.3%, respectively (ns), after SES implant. The overall in-hospital MACE rate was 3.5%, and similar in both subgroups. The 1-year MACE rate was 14.5% overall, 16.8% in the BIF+ and 10.7% in the BIF- subgroup (ns). CONCLUSIONS: SES implants in high-risk patients with LMCA stenoses were associated with a low 1-year MACE rate. Stenting of the bifurcation was associated with significant increases in neither mortality nor 1-year MACE rate.

Virtopsy -- noninvasive detection of occult bone lesions in postmortem MRI: additional information for traffic accident reconstruction

In traffic accidents with pedestrians, cyclists or motorcyclists, patterned impact injuries as well as marks on clothes can be matched to the injury-causing vehicle structure in order to reconstruct the accident and identify the vehicle which has hit the person. Therefore, the differentiation of the primary impact injuries from other injuries is of great importance. Impact injuries can be identified on the external injuries of the skin, the injured subcutaneous and fat tissue, as well as the fractured bones. Another sign of impact is a bone bruise. The bone bruise, or occult bone lesion, means a bleeding in the subcortical bone marrow, which is presumed to be the result of micro-fractures of the medullar trabeculae. The aim of this study was to prove that bleeding in the subcortical bone marrow of the deceased can be detected using the postmortem noninvasive magnetic resonance imaging. This is demonstrated in five accident cases, four involving pedestrians and one a cyclist, where bone bruises were detected in different bones as a sign of impact occurring in the same location as the external and soft tissue impact injuries.

Verteporfin therapy in occult with no classic CNV due to AMD: results of the Photodynamic Therapy in Occult-Only Lesions study

PURPOSE: To provide further information on verteporfin photodynamic therapy in occult with no classic choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). METHODS: Verteporfin therapy was administered at baseline and then at months 3, 6, and 9, if fluorescein leakage from CNV was evident on angiography. RESULTS: Of 202 patients enrolled, 184 completed 12 months. Each patient was treated in one eye only. All study eyes received verteporfin therapy at baseline, with a progressive decrease in the number treated at subsequent visits (mean 2.5 treatments during 12 months). The mean change in visual acuity letter score from baseline to month 12 was -11.9. At month 12, 164 eyes (82.4%) had lost <30 letters of visual acuity, 123 eyes (61.8%) had lost <15 letters, 78 eyes (39.2%) had lost <5 letters, 31 (15.6%) had >5-letter increase, and 7 (3.5%) had >15-letter improvement. The percentage of eyes with fluorescein leakage from CNV decreased from 75.5% at month 3 to 25.1% at month 12. Adverse events were documented for 54% patients. Few patients had treatment-associated adverse events (7%). Acute severe visual acuity decrease occurred in two eyes (1%), one of which had visual acuity that returned to baseline by the next follow-up visit. CONCLUSIONS: This study provides additional evidence that over 12 months, verteporfin is generally well tolerated and maintains or improves visual acuity in over one-third of eyes containing occult-only CNV. Verteporfin also improved anatomical outcomes by reducing leakage from CNV in at least two-thirds of eyes.

[Unilateral vs. bilateral lung transplantation in obstructive pulmonary disease]

BACKGROUND: The question whether patients suffering from end-stage emphysema who are candidates for lung transplantation should be treated with a single lung or with a double lung transplantation is still unanswered. METHODS: We reviewed 24 consecutive lung transplant procedures, comparing the results of 6 patients with an unilateral and 17 with a bilateral transplantation. PATIENTS AND RESULTS: After bilateral transplantation the patients showed a trend towards better blood gas exchange with shorter time on ventilator and intensive care compared patients after unilateral procedure. Three-year-actuarial survival was higher in the group after bilateral transplantation (83% versus 67%). There was a continuous improvement in pulmonary function in both groups during the first months after transplantation. Vital capacity and forced exspiratory ventilation therapies during the first second were significantly higher in the bilateral transplant group. CONCLUSION: Both unilateral and bilateral transplantation are feasible for patients with end-stage emphysema. Bilateral transplantation results in better pulmonary reserve capacity and faster rehabilitation.

Biolimus-eluting biodegradable polymer versus sirolimus-eluting permanent polymer stent performance in long lesions: results from the LEADERS multicentre trial substudy

AIMS: Lesion length remains a predictor of target lesion revascularisation and results of long lesion stenting remain poor. Sirolimus-eluting stents have been shown to perform better than paclitaxel eluting stents in long lesions. In this substudy of the LEADERS trial, we compared the performance of biolimus biodegradable polymer (BES) and sirolimus permanent polymer stents (SES) in long lesions. METHODS AND RESULTS: A total of 1,707 'all-comer' patients were randomly allocated to treatment with BES and SES. A stratified analysis of angiographic and clinical outcomes at nine months and one year, respectively was performed for vessels with lesion length <20 mm versus >20 mm (as measured by quantitative angiography).Of 1,707 patients, 592 BES patients with 831 lesions and 619 SES patients with 876 lesions had only short lesions treated. One hundred and fifty-three BES patients with 166 lesions and 151 SES patients with 162 lesions had long lesions. There were no significant differences in baseline clinical characteristics, except for higher number of patients with long lesions presenting with acute myocardial infarction in both stent groups. Long lesions tended to have lower MLD and greater percent diameter stenosis at baseline than short lesions. Late loss was greater for long lesions than short lesions. There was no statistically significant difference in late loss between BES and SES stents (0.32+/-0.69 vs 0.24+/-0.57, p=0.59). Binary in-segment restenosis was present in 23.2% versus 13.1% of long lesions treated with BES and SES, respectively (p=0.042). In patients with long lesions, the overall MACE rate was similar for BES and SES (17% vs 14.6%; p=0.62). There was a trend towards higher overall TLR rate with BES (12.4 % vs 6.0%; HR=2.06; p=0.07) and clinically driven TLR (10.5% vs 5.3%: HR 1.94; p=0.13). Rates of definite stent thrombosis were 3.3% in the long lesion group and 1.3-1.7 % in the short lesion group. CONCLUSIONS: BES and SES appear similar with respect to MACE in long lesions in this "all-comer" patient population. However, long lesions tended to have a higher rate of binary in-segment restenosis and TLR following BES than SES treatment.

Ethanol-induced cytochrome P4502E1 causes carcinogenic etheno-DNA lesions in alcoholic liver disease

Oxidative stress is thought to play a major role in the pathogenesis of hepatocellular cancer (HCC), a frequent complication of alcoholic liver disease (ALD). However, the underlying mechanisms are poorly understood. In hepatocytes of ALD patients, we recently detected by immunohistochemistry significantly increased levels of carcinogenic etheno-DNA adducts that are formed by the reaction of the major lipid peroxidation product, 4-hydroxynonenal (4-HNE) with nucleobases. In the current study, we show that protein-bound 4-HNE and etheno-DNA adducts both strongly correlate with cytochrome P450 2E1 (CYP2E1) expression in patients with ALD (r = 0.9, P < 0.01). Increased levels of etheno-DNA adducts were also detected in the liver of alcohol-fed lean (Fa/?) and obese (fa/fa) Zucker rats. The number of nuclei in hepatocytes stained positively for etheno-DNA adducts correlated significantly with CYP2E1 expression (r = 0.6, P = 0.03). To further assess the role of CYP2E1 in the formation of etheno-DNA adducts, HepG2 cells stably transfected with human CYP2E1 were exposed to ethanol with or without chlormethiazole (CMZ), a specific CYP2E1 inhibitor. Ethanol increased etheno-DNA adducts in the nuclei of CYP2E1-transfected HepG2 cells in a concentration-dependent and time-dependent manner, but not in vector mock-transfected control cells. CMZ blocked the generation of etheno-DNA adducts by 70%-90% (P < 0.01). CONCLUSION: Our data support the assumption that ethanol-mediated induction of hepatic CYP2E1 leading inter alia to highly miscoding lipid peroxidation-derived DNA lesions may play a central role in hepatocarcinogenesis in patients with ALD.

Nasolabial esthetics in children with complete unilateral cleft lip and palate after 1- versus 3-stage treatment protocols

PURPOSE: Facial esthetics play an important role in social interactions. However, children with a repaired complete unilateral cleft lip and palate usually show some disfigurement of the nasolabial area. To date, few studies have assessed the nasolabial appearance after different treatment protocols. The aim of the present study was to compare the nasolabial esthetics after 1- and 3-stage treatment protocols. MATERIALS AND METHODS: Four components of the nasolabial appearance (nasal form, nasal deviation, mucocutaneous junction, and profile view) were assessed by 4 raters in 108 consecutively treated children who had undergone either 1-stage closure (Warsaw group, 41 boys and 19 girls, mean age 10.8 years, SD 2.0) or 3-stage (Nijmegen group, 30 boys and 18 girls, mean age 8.9 years, SD 0.7). A 5-grade esthetic index of Asher-McDade was used, in which grade 1 indicates the most esthetic and grade 5 the least esthetic outcome. RESULTS: The nasal form was judged the least esthetic in both groups and graded 3.1 (SD 1.1) and 3.2 (SD 1.1). The nasal deviation, mucocutaneous junction, and profile view were scored from 2.1 (SD 0.8) to 2.3 (SD 1.0) in both groups. The treatment outcome after the Warsaw and Nijmegen protocols was comparable. Neither overall nor any of the 4 components of the nasolabial appearance showed intercenter differences (P > .1). CONCLUSIONS: The nasolabial appearance after the Warsaw (1-stage) and Nijmegen (3-stage) protocols was comparable. The technique of lip repair (triangular flap in Warsaw and Millard rotation advancement in Nijmegen) gave comparable results for the esthetics of the nasolabial area.

Preventive effect of ozone on the development of white spot lesions during multibracket appliance therapy

OBJECTIVE: To test the null hypotheses: (1) there is no difference in the caries protective effect of ozone and Cervitec/Fluor Protector during multibracket (MB) appliance therapy, and (2) DIAGNOdent and quantitative light-induced fluorescence (QLF) are not superior to a visual evaluation of initial caries lesions. MATERIALS AND METHODS: Twenty right-handed patients with a very poor oral hygiene who required full MB appliance therapy were analyzed during 26 months. In a split-mouth-design, the four quadrants of each patient were either treated with ozone, a combination of Cervitec and Fluor Protector, or served as untreated controls. The visible plaque index (VPI) and white spot formation were analyzed clinically. DIAGNOdent and QLF were used for a quantitative assessment of white spot formation. RESULTS: The average VPI in all four dental arch quadrants amounted to 55.6% and was independent of the preventive measure undertaken. In the quadrants treated with Cervitec/Fluor Protector, only 0.7% of the areas developed new, clinically visible white spots. This was significantly (P < .05) less than in the quadrants treated with ozone (3.2%). The lesions detected with QLF only partially corresponded to the clinically detected white spots, while DIAGNOdent proved to be unable to detect any changes at all. CONCLUSIONS: The caries protective effect of Cervitec/Fluor Protector during MB therapy was superior to ozone, and a visual evaluation of initial caries lesions was superior to both DIAGNOdent and QLF.

Visualization of alveolar recruitment in a porcine model of unilateral lung lavage using 3He-MRI

BACKGROUND: In the acute respiratory distress syndrome potentially recruitable lung volume is currently discussed. (3)He-magnetic resonance imaging ((3)He-MRI) offers the possibility to visualize alveolar recruitment directly. METHODS: With the approval of the state animal care committee, unilateral lung damage was induced in seven anesthetized pigs by saline lavage of the right lungs. The left lung served as an intraindividual control (healthy lung). Unilateral lung damage was confirmed by conventional proton MRI and spiral-CT scanning. The total aerated lung volume was determined both at a positive end-expiratory pressure (PEEP) of 0 and 10 mbar from three-dimensionally reconstructed (3)He images, both for healthy and damaged lungs. The fractional increase of aerated volume in damaged and healthy lungs, followed by a PEEP increase from 0 to 10 mbar, was compared. RESULTS: Aerated gas space was visualized with a high spatial resolution in the three-dimensionally reconstructed (3)He-MR images, and aeration defects in the lavaged lung matched the regional distribution of atelectasis in proton MRI. After recruitment and PEEP increase, the aerated volume increased significantly both in healthy lungs from 415 ml [270-445] (median [min-max]) to 481 ml [347-523] and in lavaged lungs from 264 ml [71-424] to 424 ml [129-520]. The fractional increase in lavaged lungs was significantly larger than that in healthy lungs (healthy: 17% [11-38] vs. lavage: 42% [14-90] (P=0.031). CONCLUSION: The (3)He-MRI signal might offer an experimental approach to discriminate atelectatic vs. poor aerated lung areas in a lung damage animal model. Our results confirm the presence of potential recruitable lung volume by either alveolar collapse or alveolar flooding, in accordance with previous reports by computed tomography.

A comparative study of the expression of cytotoxic proteins in allergic contact dermatitis and psoriasis: spongiotic skin lesions in allergic contact dermatitis are highly infiltrated by T cells expressing perforin and granzyme B

Recent reports indicate that cytotoxic T cells are critically involved in contact hypersensitivity reactions in animals. In this study we sought to investigate the in vivo expression of cytotoxic granule proteins in the elicitation phase of allergic contact dermatitis in humans. Skin biopsy specimens were obtained from patients with allergic contact dermatitis (n = 8) and psoriasis (n = 6) and from controls with normal skin (n = 6). Expression of perforin and granzyme B was investigated by in situ hybridization and immunohistochemistry. In contrast to normal skin and psoriasis, a significant enhancement of perforin and granzyme B gene expression and immunoreactivity was observed in the mononuclear cell infiltrate of allergic contact dermatitis. Immunoreactivity for perforin and granzyme B was mainly found in the cytoplasm of lymphocytic cells, which were located in the dense perivascular infiltrate as well as at sites of marked spongiosis in the epidermis. Double immunostaining revealed that both CD4+ and CD8+ T cells are capable of expressing perforin and granzyme B. In conclusion, our data suggest that T-cell-mediated mechanisms involving cytotoxic granule proteins may elicit epidermal cell injury in vivo and thereby strongly contribute to the development of allergic contact dermatitis in humans.