Microvascular Density In Patients Research Articles

Inter-eye asymmetry of microvascular density in patients on hydroxychloroquine therapy by optical coherence tomography angiography

AimsTo explore the inter-eye retinal microvascular density asymmetry of patients on hydroxychloroquine (HCQ) therapy through optical coherence tomography angiography (OCTA). Methods40 subjects were enrolled in this cross-sectional study, including 20 systemic lupus erythematasus patients currently treated with HCQ (40 eyes) and 20 age- and sex-matched normal controls (NCs, 40 eyes). OCTA images were obtained to measure macular and peripapillary mircrovasculatures and microstructures, including vessel density, retinal nerver fiber layer thickness, and peripapillary ganglion cell-inner plexiform layer thickness. The absolute values of the difference between right and left eyes were taken as a measure of inter-eye asymmetry. ResultsMacular whole image vessel density (wiVD-M) and perifoveal vessel density (pfVD) of superficial capillary plexus (SCP) were notably reduced in both the right and left eyes of the HCQ treatment group compared with NCs. Specifically, SLE patients treated with HCQ have higher inter-eye asymmetry of wiVD-M of SCP (2.28 ± 1.03 vs 1.27 ± 0.79, p < 0.01) and pfVD of SCP (2.55 ± 1.26 vs 1.78 ± 1.06, p = 0.04) compared with NCs. There were no significant differences in inter-eye asymmetry of structure parameters. Inter-eye asymmetry of wiVD-M of SCP (AUC = 0.80, p < 0.01) and pfVD of SCP (AUC = 0.71, p = 0.02) exhibited greater discrimination power. ConclusionSLE Patients treated with HCQ exhibited a notably higher inter-eye vessel density asymmetry compared to that of NCs. Thus, inter-eye vessel density asymmetry could be used to screen for HCQ retinal toxicity.

Impaired cerebrovascular reactivity correlates with reduced retinal vessel density in patients with carotid artery stenosis: Cross-sectional, single center study.

The cerebral and retinal circulation systems are developmentally, anatomically, and physiologically interconnected. Thus, we hypothesized that hypoperfusion due to atherosclerotic stenosis of the internal carotid artery (ICA) can result in disturbances of both cerebral and retinal microcirculations. We aimed to characterize parameters indicating cerebrovascular reactivity (CVR) and retinal microvascular density in patients with ICA stenosis, and assess if there is correlation between them. In this cross-sectional study the middle cerebral artery (MCA) blood flow velocity was measured by transcranial Doppler (TCD) and, simultaneously, continuous non-invasive arterial blood pressure measurement was performed on the radial artery by applanation tonometry. CVR was assessed based on the response to the common carotid artery compression (CCC) test. The transient hyperemic response ratio (THRR) and cerebral arterial resistance transient hyperemic response ratio (CAR-THRR) were calculated. Optical coherence tomography angiography (OCTA) was used to determine vessel density (VD) on the papilla whole image for all (VDP-WIall) and for small vessels (VDP-WIsmall). The same was done in the peripapillary region: all (VDPPall), and small (VDPPsmall) vessels. The VD of superficial (VDMspf) and deep (VDMdeep) macula was also determined. Significance was accepted when p<0.05. Twenty-four ICA stenotic patients were evaluated. Both CVR and retinal VD were characterized. There was a significant, negative correlation between CAR-THRR (median = -0.40) and VDPPsmall vessels (median = 52%), as well as between VDPPall vessels (median = 58%), and similar correlation between CAR-THRR and VDP-WIsmall (median = 49.5%) and between VDP-WIall (median = 55%). The significant correlation between impaired cerebrovascular reactivity and retinal vessel density in patients with ICA stenosis suggests a common mechanism of action. We propose that the combined use of these diagnostic tools (TCD and OCTA) helps to better identify patients with increased ischemic or other cerebrovascular risks.

Associations between tumor grade, contrast-enhanced ultrasound features, and microvascular density in patients with clear cell renal cell carcinoma: a retrospective study.

Clear cell renal cell carcinoma (ccRCC) comprises 70% of all renal cell carcinomas (RCCs). Currently, the most important prognostic factor for this type of carcinoma is the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade. However, nonsurgical methods are rarely used to determine a tumor's WHO/ISUP grade, thus limiting the development of nonsurgical therapies. Due to variations in microvascular density (MVD) at different stages of tumor growth, contrast-enhanced ultrasound (CEUS) features may provide a noninvasive method for evaluating the WHO/ISUP grade of ccRCC. In this study, we analyzed confirmed cases of ccRCC using CEUS features. We also used CD34 and CD31 antibodies to determine MVD. The heterogeneity of CD34 and CD31 expressions were used to determine different degrees of angiogenesis. When compared to WHO/ISUP grade I/II (G1/G2) tumors, grade III/IV (G3/G4) tumors had reduced peak intensity (PI) (P=0.006), time to peak (TTP) (P<0.001), and relative enhancement percentage index (∆PI%) (P<0.001). However, the frequency of incomplete pseudocapsule (P=0.049) and slow wash-in (P=0.001) was significantly higher in G3/G4 tumors. A cut-off value of ∆PI% <33.15% (P<0.001) allowed identification of G3/G4 tumors with an area under the curve (AUC) of 0.80 [95% confidence interval (CI): 0.70 to 0.91) and a sensitivity of 80%. The mean CD34+ MVD (P<0.001) and CD31+ MVD (P<0.001) were significantly lower in G3/G4 tumors. A positive correlation was revealed between ∆PI% and MVD. There was a statistically significant difference in the density of undifferentiated vessels between the slow wash-in and fast wash-in cases (P<0.001). The features of CEUS are effective for differentiating G3/G4 tumors from G1/G2. There was a positive correlation detected between ∆PI% and MVD, and the density of undifferentiated vessels showed a significant difference between slow wash-in and fast wash-in cases. These findings indicate that CEUS can enable the sonographic visualization of tumor angiogenesis and thus be considered an acceptable method for the nonsurgical assessment of tumor microvascular distribution and grade.

MDS-426: Cardiovascular Disease and Marrow Vascular Markers in Patients with Myeloid Malignancies

Context: The incidence of both myeloid malignancies and cardiovascular disease (CVD) increases with age. We aimed to study whether the presence of CVD is associated with worse outcomes in patients with myeloid malignancies and to delineate a possible mechanism. Objective: Compare overall survival (OS) and marrow vascular density among patients with and without CVD. Design: We retrospectively reviewed 295 previously untreated patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or MDS/myeloproliferative neoplasm (MDS/MPN). CVD included congestive heart failure, coronary artery disease, arrhythmia, peripheral vascular disease, congenital heart disease, and/or cerebrovascular accident. CVD and no-CVD patient characteristics were compared using Fisher’s exact and t-tests. OS was estimated by Kaplan-Meier analysis. Microvascular density (MVD) was determined in CD34-stained bone marrow sections of 20 MDS patients (11 with and 9 without CVD). The mean number of blood vessels was calculated for each sample and compared using the t-test. Setting: University of Maryland Greenebaum Comprehensive Cancer Center, in Baltimore, Maryland. Patients: The study included 228 (77%) patients with AML and 67 (23%) with MDS or MDS/MPN, of whom 92 had CVD (31%) and 203 (69%) did not. Median age at diagnosis was 66 years (range 19–89). Results: For AML patients, 1-, 2- and 3-year OS in CVD vs no-CVD groups was 46% vs 70%, 34% vs 53%, and 26% vs 43%, respectively [HR 1.9, 95% CI = 1.35, 2.67]. For MDS patients, 44% vs 81%, 26% vs 51%, and 26% vs 49% [HR 2.52, 95% CI = 1.27, 5]. In a multivariable regression model accounting for age, performance status, and karyotype, CVD independently predicted worse OS. We hypothesized that treatment response might be affected by MVD, but we did not find a significant difference in MVD in patients with CVD vs no-CVD (mean score 17 vs 22, p=0.4), ever smoker vs never smoker (mean score 19 vs 20, p=0.9), or with vs without diabetes mellitus (mean score 23 vs 13, p=0.1), although the lack of significant difference may be attributed to the small sample size. Conclusions: CVD is a predictor of survival outcomes in patients with AML and MDS. Variability in MVD is a possible mechanism of impaired treatment response in CVD patients, which warrants further evaluation.

Visual Impairments Are Associated With Retinal Microvascular Density in Patients With Parkinson's Disease.

ObjectiveThis study aimed to evaluate retinal microvascular density in patients with Parkinson’s disease (PD) and its correlation with visual impairment.MethodsThis cross-sectional study included 24 eyes of 24 patients with PD and 23 eyes of 23 healthy controls. All participants underwent ophthalmic examination, visual evoked potential (VEP) test, 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25), and optical coherence tomography angiography (OCTA) examination. The correlation between retinal microvascular density and visual parameter was evaluated using Spearman correlation analysis, and the area under receiver operating characteristic curve (AUROC) was calculated.ResultsParkinson’s disease patients had prolonged P100 latency (P = 0.041), worse vision-related quality of life (composite score and 3 of 12 subscales in NEI VFQ-25), and decreased vessel density (VD) in all sectors of 3-mm-diameter region (all P < 0.05) compared with healthy controls. There were no statistical differences in the ganglion cell-inner plexiform layer (GCIPL) thickness and retinal nerve fiber layer (RNFL) thickness between the two groups. A negative correlation was found between P100 latency and nasal and superior sectors of macular VD in a 3-mm-diameter region (r = −0.328, P = 0.030; r = −0.302, and P = 0.047, respectively). Macular VD in a 3-mm-diameter region showed diagnostic capacities to distinguish PD patients from healthy controls (AUROCs, ranging from 0.655 to 0.723).ConclusionThis study demonstrated that decreased retinal microvascular density was correlated with visual impairment in PD patients. Retinal microvasculature change may occur earlier than visual decline and retinal structure change and has the potential to be a promising diagnostic marker for early PD.

Effect of amblyopia treatment on macular microvasculature in children with anisometropic amblyopia using optical coherence tomographic angiography

To measure the retinal microvascular density in patients with anisometropic amblyopia using optical coherence tomographic angiography (OCTA) and to evaluate the effects of successful amblyopia treatment on microvasculature in retina. 59 children (5–12 years old) including 22 newly diagnosed unilateral anisometropic amblyopia, 16 recovered unilateral anisometropic amblyopia, and 21 control children were imaged with OCTA using 6 × 6-mm macular scan pattern. Vessel densities of the superficial capillary plexus (SCP), the deep capillary plexus (DCP), and the overall macular thickness were acquired and compared among the three groups. After adjustment for axial length, the amblyopia group showed lower macular vessel density in the SCP (P = 0.005) and in the DCP (P = 0.004) compared with that of the control group. However, for the recovered amblyopia group, no difference of vessel density was found when compared with the control group in both the SCP (P = 0.548) and the DCP (P = 0.124). No difference of the mean macular thickness was found among three groups (P ≥ 0.15). Children with anisometropic amblyopia have reduced macular vessel density in OCTA, while no difference of macular vessel density was found between the recovered amblyopic and control eyes. Macular thickness showed no difference in anisometropic amblyopia and remained unchanged after amblyopic treatment.

Altered microvascular density in patients with systemic lupus erythematosus treated with hydroxychloroquine\u2014an optical coherence tomography angiography study

PurposeTo evaluate the retinal microvascular density using optical coherence tomography angiography (OCTA) in patients with systemic lupus erythematosus (SLE) treated with hydroxychloroquine (HCQ).MethodsNineteen eyes of 19 patients with SLE (study group) without HCQ retinopathy and 19 eyes of 19 healthy subjects (control group) were included in this study. The study group was divided into patients using HCQ for > 5 years (high-risk group) and < 5 years (low-risk group). The VD data of the 3 × 3 mm OCT angiogram of the superficial capillary plexus (SCP) and the choriocapillaris (VD-CC), the foveal avascular zone (FAZ) area and the central retinal thickness (CRT) were extracted and analyzed.ResultsVD in the en face SCP was significantly reduced in the high-risk group and the low-risk group compared with that in the control group (p < 0.001, p = 0.001) and in the high-risk group compared with the low-risk group (p = 0.007). Correlation analysis between the cumulative dose of HCQ and the VD of the study group revealed a negative correlation, but no statistical significance (p = 0.074). However, a significant positive correlation was observed for the low-risk group (p = 0.035). In patients with SLE, VD-CC was lower (p = 0.042) and the FAZ area larger (p = 0.019). CRT showed no difference between the groups (p = 0.183).ConclusionIn this study, SLE patients showed a reduced VD in both groups. In patients treated with HCQ < 5 years, HCQ might have a protective effect on retinal microvasculature. Analysis of retinal microvascular density using OCTA could be useful in the diagnosis and monitoring of vascular alteration in patients with SLE.

Evaluation of retinal microvascular density in patients affected by systemic lupus erythematosus: an optical coherence tomography angiography study

Retinopathy in systemic lupus erythematosus (SLE) has an incidence of 7%–29% and is suggestive of high disease activity being a marker of poor visual outcome and prognosis for survival.1 Recently,...

Application of optical coherence tomography angiography in evaluation of retinal microvascular changes in patients with obstructive sleep apnea syndrome

Objective: To assess the changes of retinal microvasculature in patients with obstructive sleep apnea syndrome (OSAS) evaluated by optical coherence tomography (OCTA). Methods: Adult OSAS patients who visited Beijing Tongren Hospital from Jan 2016 to Apr 2016 and complained of snoring were included in this study. The patients' general information, results of polysomnography, and OCTA parameters were collected. Patients were divided into three groups according to their apnea hypopnea index (AHI) results: Mild-moderate group, AHI≤30/h; Severe group, 30/h<AHI≤60/h; Extremely severe group, AHI>60/h, and clinical characteristics, polysomnography and OCTA parameters among the three groups were compared. Results: A total of 27 patients were included in this study with 21 males (77.8%) and 6 females (22.2%). Mean age was (41.7±10.0) years, and the mean body mass index was (27.9±4.5) kg/m(2;) Neck circumference was 31-48 cm, mean (39.8±4.3) cm; 8 patients (29.6%) suffered from hypertension that could be controlled; Epworth sleepiness scale scored 1-18 points and mean (8.5±4.4) scores; AHI ranged between 5.5 and 92.1/h with a mean of (46.4±28.6)/h. There were 9 (33.3%), 7 (25.9%), and 11 (40.7%) patients in mild-moderate group, severe group, and extremely severe group, respectively. Compared with severe group, the optic nerve head and radial peripapillary capillaries (RPC) peripapillary vascular density in extremely severe group were significantly decreased (62.4%±1.9% vs 60.3%±1.9%, P=0.041; 64.7%±1.7% vs 62.2%±2.3%, P=0.036). Conclusions: OCTA has rapid, safe, and objective characteristics in assessing the retinal microvascular changes in OSAS patients. Retinal microvascular damage in patients with OSAS is associated with the disease severity. Reduction of retinal microvascular density in patients with OSAS may be associated with intermittent hypoxia.

Microvascular Density as a Parameter of Endometrial Assessment in Infertile Women

Background: A good blood flow towards the endometrium is an essential prerequisite for its development and differentiation, for the implantation of blastocyst and continuation of pregnancy. Diminished endometrial perfusion may be the one of the important reason behind the patients with unexplained infertility. The present study was carried out to estimate the cut-off of microvascular density determinative of good endometrial receptivity. Methods: The study included 60 patients who qualified the exclusion and inclusion criteria. Transvaginal Doppler ultrasonographic examination was performed for all patients prior to the scheduled premenstrual biopsy to determine sub endometrial blood flow. The biopsied endometrial tissue was processed. The blood vessels were identified in endometrial tissue and counted in 5 high power fields/slide. Total area of the field was calculated using stage micrometer. The density of the vessels was calculated as number of vessels/mm 2 of the fields. Results: Three vascular penetration zones based on Doppler ultrasonographic examination were identified as zone 1, zone 2, and zone 3 i.e. poor, intermediate and good vascularity respectively. The endometrial microvascular density in patients with vascularity falling in zone 1, zone 2, and zone 3 were 14.18 ± 4.07 vessels/mm 2 , 24.53 ± 4.65 vessels/mm 2 and 42.3 ± 6.1 vessels/mm 2 respectively. Comparative observation between Doppler and microvascular density revealed that in all patients with zone 3 vascularity, the microvascular density was more than 35 vessels/mm ² . Conclusions: A quantitative parameter was obtained from this study which identifies good endometrial receptivity and predicts the fertility of the patient which can be used as a prognostic marker in infertile patients particularly in developing countries. doi: http://dx.doi.org/10.4021/jcgo168w

The Significance of non Correlation Between Interleukin-8 Serum Levels with Bone Marrow Microvascular Density in Patients with Myeloma Multiple

In multiple myeloma (MM), angiogenesis plays a substantial role in disease progression. Interleukin-8 (IL-8), a pro-inflammatory chemokine with potent pro-angiogenic properties, has been implicated in the pathophysiology of MM. The aim of the study is to measure serum levels of IL-8 in MM patients and to correlate them with markers of angiogenesis, such as circulating levels of platelet derived growth factor-AB (PDGF-AB) and angiogenin (Ang), and bone marrow microvascular density (MVD). Fifty-three newly diagnosed MM patients, 23 of them, who reached plateau phase after effective treatment and 20 healthy controls, were studied. Serum levels of PDGF-AB, Ang and IL-8 were measured by ELISA, whereas bone marrow MVD was estimated by immunohistochemical staining of vessels with anti-CD31. All measured parameters were higher in MM patients compared to controls and in increased disease stages. They all also significantly decreased in plateau phase. IL-8 correlated positively with Ang and PDGF-AB, but not with MVD. The circulating levels of IL-8, PDGF-AB and Ang are elevated in patients with MM. The lack of correlation between IL-8 with MVD suggests that its levels represent the inflammatory element of MM disease and the participation in angiogenesis process is rather complex with multifactorial mechanisms.

Correlation of Cav-1 mRNA, S100A4 mRNA and CD31 expression with prostate cancer tumor metastasis and patient survival rate

Objective To explore the expression of Cav-1 mRNA,S100A4 mRNA and CD31 in prostate cancer (PCa) and their correlation with tumor metastasis and patient survival rate. Methods PCa specimens (n =42) and adjacent tissue specimens ( n =12 ) from radical prostatectomy were obtained from January 2004 to May 2006.The mean age of patient was 71.6 ± 7.6 years ( range 58 - 86 years).According to Gleason scores,prostatectomy specimens were stratified into≤6 (n =17),7 (n =12) and ≥8( n =13 ) groups.Patients were classified as clinical stage T1 ( n =16),stage T2 ( n =9 ),stage T3 ( n =11 )and stage T4 (n =6).Patients were divided into PCa with bone metastasis (n =8 ) and PCa without bone metastasis ( n =34).Preoperative PSA levels of the patients were stratified into three groups: ＜ 4 ( n =4)μg/L,4-10 (n=10)μg/Land ＞10 μg/L (n=28).12 adjacent tissues 1 -2 cm away from tumor or another lobe of prostate were microscopically verified without cancer cells and were tested for comparison.The expression of Cav-1 mRNA and S100A4 mRNA were detected by Situ hybridization in 42 PCa specimens and 12 adjacent tissues and using CD31 for marking vascular endothelial cells,the tumor microvascular density (MVD) was counted.The correlation of Cav-1 mRNA,S100A4 mRNA and CD31 expression was analyzed in combination.with clinical and pathological fcatures including Gleason score,TNM staging,PSA values and bone metastasis. Results The positive expression rate of Cav-1 mRNA in PCa was 35.7％ ( 15/42),while it was 0％ (0/12) in controls,P ＜0.05.The positive expression rate of S100A4 mRNA in PCa was 47.6％ (20/42),while it was 8.3％ (1/12) in controls,P ＜0.05.The positive expression rate of Cav-1 mRNA in PCa was positively correlated with Gleason score,TNM stage and bone metastasis.The positive expression rate of S100A4 mRNA in PCa was positively correlated with TNM stage and bone metastasis.The average MVD in patients of negative expression of Cav-1 mRNA was (62.8 ± 10.4)/mm2,and the average -MVD in patients of positive expression of Cav-1 mRNA was (83.5 ±6.7 )/mm2,P ＜ 0.05.While the average MVD in patients of negative expression of S100A4 mRNA was (63.3 ± 12.0)/mm2,and the average MVD in patients of positive expression of S100A4 mRNA was (77.9 ± 11.0)/mm2,P ＜ 0.05.The 5-year survival rate in patients with positive Cav-1 mRNA expression was significantly lower than that of with negative expression (46.7％ versus 85.2％,P ＜ 0.05 ),while the 5-year survival rate in the patients with positive expression of S100A4 mRNA was significantly lower than that of with negative expression (50.0％ versus 90.9％,P ＜ 0.05 ). Conclusions The positive Cav-1 mRNA and S100A4 mRNA expression,increased MVD are positively correlated with PCa progression and bone metastasis. Furthermore,Cav-1 and S100A4 in PCa may promote angiogenesis and cause tumor cells to bone metastases,which can reduce survival rate of patients. Key words: Prostate cancer; Caveolin-1; S100A4; Situ hybridization

Predictive Value of Intratumoral Microvascular Density in Patients with Advanced Non-small Cell Lung Cancer Receiving Chemotherapy Plus Bevacizumab

The use of bevacizumab combined with chemotherapy represents a recent advance in clinical oncology for significantly improving the survival of patients who have non-small cell lung cancer (NSCLC). There is an unmet need for biomarkers that can predict response to such treatment and identify patients sensitive to it. Our study was designed to investigate the predictive value of intratumoral microvascular density (MVD) in patients with NSCLC treated with bevacizumab. Sixteen patients with NSCLC who underwent chemotherapy combined with bevacizumab were included into this study. Paraffin-embedded tumor samples were sectioned and stained immunohistochemically for the blood vessel markers CD34 and CD31 to characterize the intratumoral vasculature. A computerized image analysis program was used to quantitatively calculate the intratumoral MVD. Treatment response was evaluated by computed tomography scanning. Two types of blood vessels, undifferentiated (CD31*/CD34*) and differentiated (CD34*), were identified. A positive correlation was found between the largest percentage of tumor shrinkage and the MVD of undifferentiated (CD31*/CD34*) vessels, with Spearman correlation coefficient being 0.576 (p = 0.019). No correlation between tumor shrinkage and differentiated vessel MVD (CD34*) was found. Moreover, seven of the eight patients with more undifferentiated vessels showed a partial response, versus only one of the seven patients with fewer undifferentiated vessels (p = 0.009). There are two major types of microvessel in lung cancer vasculature. The MVD of undifferentiated vessels is a favorable predictor for patients with NSCLC treated with a chemotherapy regimen plus bevacizumab, with a higher MVD value correlating with better treatment response. Further studies are needed to verify the predictive role of MVD in treatment of NSCLC with bevacizumab.

Significance of microvascular density (MVD) in cervical cancer recurrence.

The purpose of this retrospective study of 118 patients with squamous cell cervical cancer from January 1990 to December 1993 was to evaluate angiogenesis as predictive factor of recurrence in cervical cancer stages II-III treated with standard radiotherapy. Microvessel density (MVD) was evaluated and correlated with other prognostic factors. MVD was greater than 20 in 67.8% of patients with recurrence (P = 0.002) in comparison to 39% of patients without. Disease-free survival was shorter in stage IIA and MVD >20 (P = 0.0193) as well as for stage IIB (P < 0.05 ), but not for IIIB (P = 0.1613 ). Global survival was significantly shorter when MVD was >20 (P = 0.0316). For stage IIA and MVD >20 survival was shorter (P = 0.0008) for stage IIB (P < 0.05) but not for IIIB (P = 0.14). Patients younger than 40 years and MVD >20 had poorer disease-free interval and survival (P = 0.0029). MVD in patients with squamous cell cervical cancer stage II and age younger than 40 may play a role in predicting recurrence and survival.

Significance of microvascular density (MVD) in cervical cancer recurrence

The purpose of this retrospective study of 118 patients with squamous cell cervical cancer from January 1990 to December 1993 was to evaluate angiogenesis as predictive factor of recurrence in cervical cancer stages II–III treated with standard radiotherapy. Microvessel density (MVD) was evaluated and correlated with other prognostic factors. MVD was greater than 20 in 67.8% of patients with recurrence (P= 0.002) in comparison to 39% of patients without. Disease-free survival was shorter in stage IIA and MVD &gt;20 (P= 0.0193) as well as for stage IIB (P&lt; 0.05), but not for IIIB (P= 0.1613). Global survival was significantly shorter when MVD was &gt;20 (P= 0.0316). For stage IIA and MVD &gt;20 survival was shorter (P= 0.0008) for stage IIB (P&lt; 0.05) but not for IIIB (P= 0.14). Patients younger than 40 years and MVD &gt;20 had poorer disease-free interval and survival (P= 0.0029). MVD in patients with squamous cell cervical cancer stage II and age younger than 40 may play a role in predicting recurrence and survival.

Capillary density of skeletal muscle: A contributing mechanism for exercise intolerance in class II–III chronic heart failure independent of other peripheral alterations

OBJECTIVESThe study was conducted to determine if the capillary density of skeletal muscle is a potential contributor to exercise intolerance in class II–III chronic heart failure (CHF).BACKGROUNDPrevious studies suggest that abnormalities in skeletal muscle histology, contractile protein content and enzymology contribute to exercise intolerance in CHF.METHODSThe present study examined skeletal muscle biopsies from 22 male patients with CHF compared with 10 age-matched normal male control patients. Aerobic capacities, myosin heavy chain (MHC) isoforms, enzymes, and capillary density were measured.RESULTSThe patients with CHF demonstrated a reduced peak oxygen consumption when compared to controls (15.0 ± 2.5 vs. 19.8 ± 5.0 ml·kg−1·min−1, p <0.05). Using cell-specific antibodies to directly assess vascular density, there was a reduction in capillary density in CHF measured as the number of endothelial cells/fiber (1.42 ± 0.28 vs. 1.74 ± 0.35, p = 0.02). In CHF, capillary density was inversely related to maximal oxygen consumption (r = 0.479, p = 0.02). The MHC IIx isoform was found to be higher in patients with CHF versus normal subjects (28.5 ± 13.6 vs. 19.5 ± 9.4, p <0.05).CONCLUSIONSThere was a significant reduction in microvascular density in patients with CHF compared with the control group, without major differences in other usual histologic and biochemical aerobic markers. The inverse relationship with peak oxygen consumption seen in the CHF group suggests that a reduction in microvascular density of skeletal muscle may precede other skeletal muscle alterations and play a critical role in the exercise intolerance characteristic of patients with CHF.