The Collaborative National Quality and Efficacy Registry for Scleroderma: association of medication use on gastrointestinal tract symptoms in early disease and the importance of tobacco cessation.

OBJECTIVES: Systemic Sclerosis (SSc) is frequently associated with gastrointestinal tract (GIT) involvement. The Collaborative National Quality and Efficacy Registry (CONQUER) is a US-based collaborative study collecting longitudinal follow up data on SSc patients with less than 5-years disease duration enrolled at Scleroderma centres of excellence. This manuscript presents the GIT natural history and outcomes in relation to other scleroderma manifestations and medication exposures. METHODS: CONQUER participants that had completed a minimum of two serial Scleroderma Clinical Trials Consortium GIT Questionnaires (GIT 2.0) were included in this analysis. Patients were categorised by total GIT 2.0 severity at baseline, and by category change: none-to-mild (0.49); moderate (0.50-1.00), and severe-to-very severe (1.01-3.00) at the subsequent visit. Based on this data, four groups were identified: none-to-mild with no change, moderate-to-severe with no change, improvement, or worsening. Clinical features and medications, categorised as gastrointestinal tract targeted therapy, anti-fibrotic, immunosuppression, or immunomodulatory drugs, were recorded. Analysis included a proportional odds modelaccounting for linear and mixed effects of described variables. RESULTS: 415 enrolled CONQUER participants met project inclusion criteria. Most participants had stable mild GIT symptoms at baseline and were on immunomodulatory and anti-reflux therapy. In most patients, anti-reflux medication and immunosuppression initiation preceded the baseline visit, whereas anti-fibrotic initiation occurred at or after the baseline visit. In the proportional odds model, worsening GIT score at the follow-up visit was associated with current tobacco use (odds ratio: 3.48 (1.22, 9.98, p 0.020). CONCLUSIONS: This report from the CONQUER cohort, suggests that most patients with early SSc have stable and mild GIT disease. Closer follow-up was associated with milder, stable GIT symptoms. There was no clear association between immunosuppression or anti-fibrotic use and severity of GIT symptoms. However, active tobacco use was associated with worse GIT symptoms, highlighting the importance of smoking cessation counselling in this population.

Predictive Significance of Serum Interferon-Inducible Protein Score for Response to Treatment in Systemic Sclerosis-Related Interstitial Lung Disease.

OBJECTIVE: Response to immunosuppression is highly variable in systemic sclerosis (SSc)-related interstitial lung disease (ILD). This study was undertaken to determine whether a composite serum interferon (IFN)-inducible protein score exhibits predictive significance for the response to immunosuppression in SSc-ILD. METHODS: Serum samples collected in the Scleroderma Lung Study II, a randomized controlled trial of mycophenolate mofetil (MMF) versus cyclophosphamide (CYC), were examined. Results were validated in an independent observational cohort receiving active treatment. A composite score of 6 IFN-inducible proteins IFNγ-inducible 10-kd protein, monokine induced by IFNγ, monocyte chemotactic protein 2, ß2 -microglobulin, tumor necrosis factor receptor type II, and macrophage inflammatory protein 3ß) was calculated, and its predictive significance for longitudinal forced vital capacity percent predicted measurements was evaluated. RESULTS: Higher baseline IFN-inducible protein score predicted better response over 3 to 12 months in the MMF arm (point estimate = 0.41, P = 0.001) and CYC arm (point estimate = 0.91, P = 0.009). In contrast, higher baseline C-reactive protein (CRP) levels were predictive of a worse ILD course in both treatment arms. The predictive significance of the IFN-inducible protein score and CRP levels remained after adjustment for baseline demographic and clinical predictors. During the second year of treatment, in which patients in the CYC arm were switched to placebo, a higher IFN-inducible protein score at 12 months showed a trend toward predicting a worse ILD course (point estimate = -0.61, P = 0.068), while it remained predictive of better response to active immunosuppression in the MMF arm (point estimate = 0.28, P = 0.029). The predictive significance of baseline IFN-inducible protein score was replicated in the independent cohort (rs = 0.43, P = 0.028). CONCLUSION: A higher IFN-inducible protein score in SSc-ILD is predictive of better response to immunosuppression and could potentially be used to identify patients who may derive the most benefit from MMF or CYC.

Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile.

OBJECTIVES: Determine global skin transcriptome patterns of early diffuse systemic sclerosis (SSc) and how they differ from later disease. METHODS: Skin biopsy RNA from 48 patients in the Prospective Registry for Early Systemic Sclerosis (PRESS) cohort (mean disease duration 1.3 years) and 33 matched healthy controls was examined by next-generation RNA sequencing. Data were analysed for cell type-specific signatures and compared with similarly obtained data from 55 previously biopsied patients in Genetics versus Environment in Scleroderma Outcomes Study cohort with longer disease duration (mean 7.4 years) and their matched controls. Correlations with histological features and clinical course were also evaluated. RESULTS: SSc patients in PRESS had a high prevalence of M2 (96%) and M1 (94%) macrophage and CD8 T cell (65%), CD4 T cell (60%) and B cell (69%) signatures. Immunohistochemical staining of immune cell markers correlated with the gene expression-based immune cell signatures. The prevalence of immune cell signatures in early diffuse SSc patients was higher than in patients with longer disease duration. In the multivariable model, adaptive immune cell signatures were significantly associated with shorter disease duration, while fibroblast and macrophage cell type signatures were associated with higher modified Rodnan Skin Score (mRSS). Immune cell signatures also correlated with skin thickness progression rate prior to biopsy, but did not predict subsequent mRSS progression. CONCLUSIONS: Skin in early diffuse SSc has prominent innate and adaptive immune cell signatures. As a prominently affected end organ, these signatures reflect the preceding rate of disease progression. These findings could have implications in understanding SSc pathogenesis and clinical trial design.

Abatacept in Early Diffuse Cutaneous Systemic Sclerosis: Results of a Phase II Investigator-Initiated, Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial.

OBJECTIVE: T cells play a key role in the pathogenesis of early systemic sclerosis. This study was undertaken to assess the safety and efficacy of abatacept in patients with diffuse cutaneous systemic sclerosis (dcSSc). METHODS: In this 12-month, randomized, double-blind, placebo-controlled trial, participants were randomized 1:1 to receive either subcutaneous abatacept 125 mg or matching placebo, stratified by duration of dcSSc. Escape therapy was allowed at 6 months for worsening disease. The coprimary end points were change in the modified Rodnan skin thickness score (MRSS) compared to baseline and safety over 12 months. Differences in longitudinal outcomes were assessed according to treatment using linear mixed models, with outcomes censored after initiation of escape therapy. Skin tissue obtained from participants at baseline was classified into intrinsic gene expression subsets. RESULTS: Among 88 participants, the adjusted mean change in the MRSS at 12 months was -6.24 units for those receiving abatacept and -4.49 units for those receiving placebo, with an adjusted mean treatment difference of -1.75 units (P = 0.28). Outcomes for 2 secondary measures (Health Assessment Questionnaire disability index and a composite measure) were clinically and statistically significantly better with abatacept. The proportion of subjects in whom escape therapy was needed was higher in the placebo group relative to the abatacept group (36% versus 16%). In the inflammatory and normal-like skin gene expression subsets, decline in the MRSS over 12 months was clinically and significantly greater in the abatacept group versus the placebo group (P < 0.001 and P = 0.03, respectively). In the abatacept group, adverse events occurred in 35 participants versus 40 participants in the placebo group, including 2 deaths and 1 death, respectively. CONCLUSION: In this phase II trial, abatacept was well-tolerated, but change in the MRSS was not statistically significant. Secondary outcome measures, including gene expression subsets, showed evidence in support of abatacept. These data should be confirmed in a phase III trial.

Review of Current Immunologic Therapies for Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory disease of apocrine gland-bearing skin which affects approximately 1-4% of the population. The disease is more common in women and patients of African American descent and approximately one-third of patients report a family history. Obesity and smoking are known risk factors, but associations with other immune disorders, especially inflammatory bowel disease, are also recognized. The pathogenesis of HS is poorly understood and host innate or adaptive immune response, defective keratinocyte function, and the microbial environment in the hair follicle and apocrine gland have all been postulated to play a role in disease activity. While surgical interventions can be helpful to reduce disease burden, there is a high recurrence rate. Increasingly, data supports targeted immune therapy for HS, and longitudinal studies suggest benefit from these agents, both when used alone and as an adjunct to surgical treatments. The purpose of this review is to outline the current data supporting use of targeted immune therapy in HS management.

Retention rates and benefits of Painless Punctal Plug F(TM) in dry eye patients.

In this article, the authors attempt to determine the retention rate and benefits of Painless Punctal Plug F(TM) placed in patients diagnosed with dry eye. This is a prospective, observational cohort study. Forty patients diagnosed with dry eye underwent Painless Punctal Plug F placement in the inferior puncta (80 puncta) in a private clinic from January 2010 to July 2012. Patients were then followed up monthly for seven months taking note of plug retention, spontaneous plug loss, and complications. Retention rates of patients with mean age of 58.6 years were 100% after one month, 98.75% after two months, 96.25% after three months, 95% after four months, 93.75% after five months, and 92.5% after seven months. In the 80 plugs, three plugs underwent spontaneous punctal plug loss and three plugs were removed due to local discomfort. In total, 74 out of 80 plugs remained intact after seven months of follow-up. Kaplan-Meier analysis showed that there was propensity for spontaneous punctal plug loss or plug removal in the Sjogren group as compared to the non-Sjogren group. No complications were noted such as epiphora, local inflammatory reaction, nor canalicular pyogenic granuloma except for local discomfort. This study showed that Painless Punctal Plug F has a high retention rate with the following benefits, it has one-size, fitted for small to medium puncta; extended round end which made prior dilation unnecessary and once inserted, the soft round bulb fits snugly inside the punctum preventing plug loss.

High-quality genome sequence and description of Chryseobacterium senegalense sp. nov.

Strain FF12(T) was isolated from the mouth of a West African lungfish (Protopterus annectens) in Senegal. MALDI-TOF-MS did not provide any identification. This strain exhibited a 97.97% 16S rRNA sequence identity with Kaistella flava. Using a polyphasic study including phenotypic and genomic analyses, strain FF12(T) is Gram-negative, aero-anaerobic, oxidase-positive, non-motile, non-spore-forming, and exhibited a genome of 4,397,629 bp with a G+C content of 35.1% that coded 4,001 protein-coding and 55 RNA genes. On the basis of these data, we propose the creation of Chryseobacterium senegalense strain FF12(T).

High-quality genome sequence and description of Paenibacillus dakarensis sp. nov.

Strain FF9T was isolated in Dakar (Senegal) from a blood-culture taken from a 16-month-old child. MALDI-TOF analysis did not allow for identification. After sequencing, strain FF9T exhibited 98.18% similarity with the 16SrRNA sequence of Paenibacillus uliginis. A polyphasic study of phenotypic and genomic analyses showed that strain FF9T is Gram variable, catalase-positive, and presents a genome of 4,569,428 bp (one chromosome but no plasmid) with 4,427genes (4,352 protein-coding and 75 RNA genes (including 3 rRNA operons). The G+C content is 45.7%. On the basis of these genomic and phenotypic data analyses, we propose the creation of Paenibacillus dakarensis strain FF9T.

Noncontiguous finished genome sequence and description of Weeksella massiliensis sp. nov.

Strain FF8(T) (= CSUR P860 = DSM 28259) was isolated in Dakar, Senegal, from the urine of a 65-year-old man with acute cystitis. This strain shows a similarity of sequence of 16S rRNA of 98.38% with Weeksella virosa, and its GenBank accession numbers are HG931340 and CCMH00000000. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis had a poor score, ranging from 1.32 to 1.56, that did not allow identification of the bacterium. Using a polyphasic study made of phenotypic and genomic analyses, strain FF8(T) was a Gram-negative, aerobic rod and a member of the family Flavobacteriaceae. The sequenced genome is 2 562 781 bp with one chromosome but no plasmid. It exhibits a G + C content of 35.9% and contains 2390 protein-coding and 56 RNA genes, including a complete rRNA operon. On the basis of these data, we propose the creation of Weeksella massiliensis sp. nov.

Noncontiguous finished genome sequence and description of Necropsobacter massiliensis sp. nov.

Strain FF6(T) was isolated from the cervical abscess of a 4-year-old Senegalese boy, in Dakar, Senegal. MALDI-TOF MS did not provide any identification. This strain exhibited a 95.17% 16S rRNA sequence identity with Necropsobacter rosorum. Using a polyphasic study including phenotypic and genomic analyses, strain FF6(T) was an aero-anaerobic Gram-negative cocobacillus, oxidase positive, and exhibited a genome of 2,493,927 bp (1 chromosome but no plasmid) with a G+C content of 46.2% that coded 2,309 protein-coding and 53 RNA genes. On the basis of these data, we propose the creation of Necropsobacter massiliensis sp. nov.

High-quality genome sequence and description of Bacillus ndiopicus strain FF3(T) sp. nov.

Strain FF3(T) was isolated from the skin-flora of a 39-year-old healthy Senegalese man. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry did not allow any identification. This strain exhibited a 16S rRNA sequence similarity of 96.8% with Bacillus massiliensis, the phylogenetically closest species with standing nomenclature. Using a polyphasic study made of phenotypic and genomic analyses, strain FF3(T) was Gram-positive, aeroanaerobic and rod shaped and exhibited a genome of 4 068 720 bp with a G+C content of 37.03% that coded 3982 protein-coding and 67 RNA genes (including four rRNA operons). On the basis of these data, we propose the creation of Bacillus ndiopicus sp. nov.

[Impact of preoperative breast magnetic resonance imaging on surgical management: experience of two university hospitals]. / Impact de l'IRM mammaire préopératoire sur la prise en charge chirurgicale des cancers du sein: expérience de deux centres hospitaliers universitaires.

OBJECTIVES: Breast magnetic resonance imaging (MRI) has attained a solid position in the diagnosis of breast cancer but its benefit is still to be confirmed in the preoperative staging. The authors assessed the impact of preoperative breast MRI on surgical management of breast cancer in two university hospitals. PATIENTS AND METHODS: This retrospective review was realized in two university hospitals and concerned all patients with breast carcinoma who had a surgical first therapy. We selected 89 patients who underwent preoperative breast MRI in the period between January 2008 and December 2009. RESULTS: The sensitivity of breast MRI for detecting breast tumor was 95%. Fourteen percent of patients had a multifocal disease, 10% a multicentric disease and 2% a synchronous bilateral cancer. The correlation of radiological tumor size with histopathological size was r=0.68 in IRM compared to r=0.45 in conventional imaging (P<0.001). Nineteen additional biopsies were performed and 9.9% of false-positive findings were detected. Retrospectively, planned surgical management was altered in 9% of patients, resulted from use of breast MRI. Six patients had conversion of planned breast conservation to mastectomy and two patients underwent contralateral lumpectomy after discover synchronous bilateral cancer. DISCUSSION AND CONCLUSION: Breast MRI was very sensitive for the detection of breast carcinoma and improved local staging in almost 9% of patients. But, low specificity of this imaging requires a systematically validation of additional lesions by biopsy before surgical planning.

Use of an imaging device after nonablative radiofrequency (Pellevé): treatment of periorbital rhytids.

OBJECTIVE: To use the Canfield Reveal imager in objective photo documentation of the effect of nonablative radiofrequency (Pellevé) treatment on periorbital rhytids. METHODS: This is a prospective cohort study. Twelve patients underwent 1 to 2 sessions of nonablative radiofrequency (Pellevé) treatment over the periorbital region. INCLUSION CRITERIA: aged 30 to 60 years old, minimal tissue laxity, and shallow wrinkle development. Standardized reproducible photographs (left, frontal, right views) with use of the Canfield Reveal imager's superimposition feature were taken of each patient prior, immediately after application, and on 2nd, 4th, 6th, and 8th week follow up. Brow elevation was measured in the pre- and posttreatment photographs with the use of the Canfield Reveal imager and rendered the photographs in 3-dimensional images. RESULTS: Comparison of the pre- and posttreatment photographs taken via the Canfield Reveal imager showed reduction in the wrinkles, smoothening, and tightening of the eyelid and the periorbital tissue. Patients exhibited an average increase of 2.05 mm (p<0.001) of eyebrow lift and 0.98 mm (p<0.001) of superior eyelid crease elevation immediately after treatment. Eight weeks after, average brow elevation was measured at 3.52 mm (p<0.001) and crease elevation at 1.84 mm (p<0.001). The 3-dimensional imaging feature rendered in normal skin tone, and shades of gray showed softening of fine lines and crow's feet after treatment. Furthermore, it also rendered in color relief that highlighted the changes seen with depressions noted to decrease after treatment. CONCLUSION: The Canfield Reveal imager can be used in the objective photodocumentation of subtle and modest effects of nonablative radiofrequency (Pellevé) treatment to the periorbital region.

[Is radical hysterectomy necessary in surgical procedure for early stage cervical cancer?]. / La colpohystérectomie élargie a-t-elle encore une place dans le traitement des cancers du col débutants?

OBJECTIVE: Radical hysterectomy is one of the treatment options for early stage cervical cancer. This surgery results in significant morbidity, especially urinary complications. The objective of the study is to determine the rate and predictive factors of parametrial involvement in early stage cervical cancer and to define a subset of patient at low risk for parametrial disease and potential applicant to less morbid surgery. METHODS: This review reports recent retrospective and prospective studies and we show randomized trial concerning feasibility of no radical surgery. RESULTS: Parametrial involvement rate in tumors <2 cm, without lymphovascular space invasion, with negative lymph nodes and depth of invasion <10mm is between 0 and 1.96%. CONCLUSION: This result, which suggests simple hysterectomy, is maybe adequate in this case. At present, no randomized trial allows to validate this hypothesis and to change present practices. Radical hysterectomy stays standard of surgical treatment of early stage cervical cancer.

[Diagnosis of presumed benign ovarian tumors]. / Stratégies diagnostiques des tumeurs ovariennes présumées bénignes.

Symptoms of presumed benign ovarian tumors (PBOT) are not specific (LE4). Personal or family history of gynecological cancers can guide the diagnostic strategy. Clinical examination is ineffective for positive, topographic and etiologic diagnosis of PBOT (LE4). Signs of hormonal impregnation may refer to certain types of tumors (LE4). For any patient presenting with a pelvic mass, pelvic ultrasound is in the first-line exam (grade A); it can classify most ovarian tumors. In case of pure liquid unilocular mass smaller than 7 cm, ultrasound is sufficient to characterize the mass (grade A). In case of indeterminate or complex ovarian mass on ultrasound, MRI is useful to characterize the mass (LE2). Beyond 7 cm, the diagnostic performance of ultrasound decreases (LE2). When a non-unilocular liquid ovarian formation is characterized using ultrasound as determinate mass, ultrasound scan is the only exam recommended (grade B). MRI is indicated as a second-line scan for indeterminate masses or greater than 7 cm (grade B). Cyst puncture for diagnostic purposes has no place in the diagnostic strategy of ovarian cysts (grade C). In case of PBOT in pre-pubertal period, dosing biomarkers is useful but should not delay care. In adult women with PBOT, the measurement of CA125 is not recommended for first-line diagnosis (grade C). Current literature data are not sufficient to specify the diagnostic strategy for an ovarian tumor discovered incidentally during laparoscopy. In case of discovery of a high CA125 value, pelvic ultrasound is the first-line examination. The literature data are still limited to define a CA125 threshold value requiring further exploration or special monitoring, in case of normal pelvic ultrasound.

Indirect nitrous oxide emissions from surface water bodies in a lowland arable catchment: a significant contribution to agricultural greenhouse gas budgets?

In the UK agriculture is by far the largest source of nitrous oxide (N(2)O) emissions. Direct N(2)O emissions as a result of nitrogen (N) application to soils have been well documented in the UK, whereas indirect emissions produced in surface waters and groundwaters from leached N are much less understood with limited data to support IPCC emission factors. Indirect emissions were studied in surface waters in the Upper Thurne, a lowland drained arable catchment in eastern England. All surface waters were found to have dissolved N(2)O concentrations above that expected if in equilibrium with ambient concentrations, demonstrating all surface waters were acting as a source of N(2)O. The drainage channels represented 86% of the total indirect N(2)O flux, followed by wetland areas, 11%, and the river, 3%. The dense drainage network was found to have the highest dissolved N(2)O concentrations of all the water bodies studied with a combined N(2)O flux of 16 kg N(2)O-N per day in March 2007. Such indirect fluxes are comparable to direct fluxes per hectare and represent a significant proportion of the total N(2)O flux for this catchment. Separate emission factors were established for the three different surface water types within the same catchment, suggesting that the one emission factor used in the Intergovernmental Panel on Climate Change (IPCC) methodology for predicting all indirect N(2)O emissions is inappropriate.

Elevated expression of cav-1 in a subset of SSc fibroblasts contributes to constitutive Alk1/Smad1 activation.

Previous studies have shown that the transforming growth factor (TGF)ß/Alk1/Smad1 signaling pathway is constitutively activated in a subset of systemic sclerosis (SSc) fibroblasts and this pathway is a critical regulator of CCN2 gene expression. Caveolin-1 (cav-1), an integral membrane protein and the main component of caveolae, has also been implicated in SSc pathogenesis. This study was undertaken to evaluate the role of caveolin-1 in Smad1 signaling and CCN2 expression in healthy and SSc dermal fibroblasts. We show that a significant subset of SSc dermal fibroblasts has up-regulated cav-1 expression in vitro, and that cav-1 up-regulation correlates with constitutive Smad1 phosphorylation. In addition, basal levels of phospho-Smad1 were down-regulated after inhibition of cav-1 in SSc dermal fibroblasts. Caveolin-1 formed a protein complex with Alk1 in dermal fibroblasts, and this association was enhanced by TGFß. By using siRNA against cav-1 and adenoviral cav-1 overexpression we demonstrate that activation of Smad1 in response to TGFß requires cav-1 and that cav-1 is sufficient for Smad-1 phosphorylation. We also show that cav-1 is a positive regulator of CCN2 gene expression, and that it is required for the basal and TGFß-induced CCN2 levels. In conclusion, this study has revealed an important role of cav-1 in mediating TGFß/Smad1 signaling and CCN2 gene expression in healthy and SSc dermal fibroblasts.

[Kidney and iodinated and gadolinium-based contrast agents]. / Rein et produits de contraste iodés et gadolinés.

UNLABELLED: In patients with renal failure, iodinated contrast agents may cause acute deterioration of the renal function and gadolinium-based contrast agents (GBCAs) may cause nephrogenic systemic fibrosis (NSF). The administration of a contrast agent must thus be reviewed for each patient and evaluation of renal function is paramount even though its estimation using formulas derived from the creatinine level may fluctuate. For iodinated contrast agents, contrast induced nephropathy is reduced by hydratation, preferably intravenous, when the GFR is less than 60 ml/min. The risk for intravenous injections is less than the risk for arterial injections, and the GFR threshold may be reduced to 45 ml/min. For gadolinium-based contrast agents, patients at risk for NSF are those with end-stage renal disease and patients undergoing dialysis. In such cases, the injection of a gadolinium-based contrast agent is only considered after a risk-benefit analysis has been completed, an alternate linear or macrocyclic agent issued and the dose limited to 0,1 mmol Gd/kg. Recently, recommendations from US and European agencies have converged. LEARNING OBJECTIVES: to be familiar with the risk factors of CIN with iodinated contrast agents; to be familiar with hydration procedures for patients at risk of CIN; to be familiar with the diagnostic criteria of NSF; to be familiar with the classification of GBCA with regards to the risk of NSF; to be familiar with the contraindications of the different groups of GBCA.

Dynamic contrast enhanced optical imaging of capillary leakage.

We studied in vivo the vascular permeability of two fluorescent contrast agents in three types of capillary, using a fibered confocal fluorescence microscopy system. Mice were imaged after injection of a macromolecular (albumin FITC 68,000 daltons) or low-molecular-weight contrast agent (FITC 389 daltons). We studied continuous capillaries in muscles (FITC n = 4, albumin FITC n = 6), fenestrated capillaries in mesenteries (FITC n = 8, albumin FITC n = 10), and discontinuous capillaries in xenografted tumors (FITC n = 2, albumin FITC n = 4). Signal intensity (SI) was measured in capillary and interstitial regions, and time-enhancement curves were drawn. Two-compartment models were constructed to determine quantitative microcirculation parameters. The arrival of the bolus of the two different contrast agents was observed in mesentery and muscle capillaries but not in tumor capillaries. Interstitial leakage of the low-molecular-weight contrast agent was observed almost instantaneously, whereas the macromolecular agent remained within the vessels. Signal intensity declined over the observation period, specifically in the tumor. No quantitative microcirculation parameters could be obtained with either of two bi compartmental models, owing to model instability. This study shows that the microcirculation can be reproducibly observed in different types of capillary in vivo with this fibered fluorescence imaging device. Further work is required to quantify microvascular parameters.