[Etiopathogenesis and treatment of breast capsular contracture]. / Etiopatogenia e Tratamento da Contractura Capsular Mamária.

INTRODUCTION: Capsular contracture is a chronic and the most frequent complication of augmentation mammoplasty with breast implants and the main cause of patient's and surgeon's dissatisfaction. The mammary capsule consists of a fibrous tissue that surrounds the implant that may contract, changing the shape and consistency of the breast. In its advanced stage is accompanied by pronounced deformity, hardness and pain, being indicated for surgical treatment. MATERIAL AND METHODS: All the articles indexed on PubMed through the search 'capsular contracture' (2000 - January 2012) were reviewed and were included the articles of greater interest in terms of etiology, prophylaxis and treatment. Articles referred in relevant publications were also examined. RESULTS: Everything indicates that its etiology is multifactorial; the etiopathology of breast capsular contracture continues being subject of multiple pre-clinical investigations. There are many studies performed in order to prevent the onset of capsular contracture but, although promising results, little is set for its application on clinical practice. The capsulectomy/capsulotomy continues being the gold standard treatment although the future may undergo non invasive techniques, at least in mild stages of disease. CONCLUSION: Although the surgical techniques and the quality of breast implants have been improving drastically in recent years, capsular contracture remains a real complication with great incidence and that continues affecting thousands of women all over the world.

Introdução: A contractura capsular é a complicação crónica mais frequente da mamoplastia de aumento com próteses mamárias e a principal causa de insatisfação da doente e do cirurgião plástico. A cápsula mamária consiste num tecido fibroso que circunda a prótese e que pode contrair, alterando a forma e a consistência da mama. No estádio mais avançado é acompanhada de deformidade acentuada, rigidez e dor, tendo indicação para tratamento cirúrgico.Material e Métodos: Foram revistos todos os artigos indexados na PubMed através da pesquisa 'capsular contracture' (2000 - Janeiro 2012), dos quais foram inseridos os artigos de maior interesse em termos de etiologia, profilaxia e tratamento. Artigos referenciados em publicações relevantes foram também analisados.Resultados: Tudo indica que a sua etiologia é multifactorial; a etiopatogenia da contractura capsular mamária continua a ser alvo de múltipla investigação pré-clínica. Vários são os estudos realizados de forma a prevenir a ocorrência de contractura capsular e, embora os resultados sejam promissores, pouco está definido em termos da sua aplicação na prática clínica. Relativamente ao tratamento a capsulectomia/capsulotomia continua a ser o gold-standard, no entanto o futuro poderá passar por técnicas não invasivas, pelo menos em estádios mais leves da doença.Conclusão: Apesar das técnicas cirúrgicas e a qualidade das próteses mamárias terem vindo a melhorar drasticamente nos últimos anos, a contractura capsular mamária mantém-se uma complicação real, com incidência elevada e que continua a afectar milhares de mulheres no mundo.

Fluctuations in C-reactive protein concentration and neutrophil activation during normal human pregnancy.

OBJECTIVES: To clarify the changes in serum C-reactive protein (CRP) levels and in the neutrophil activation state during normal human pregnancy. MATERIALS AND METHODS: A longitudinal study (n=23) was performed during the three trimesters of pregnancy; a group of non-pregnant women (n=24) was used as control. Total and differential leukocyte count, serum concentration of CRP and plasma levels of granulocyte-macrophage colony stimulating factor (GM-CSF) and of lactoferrin and elastase (two indirect markers of neutrophil activation) were measured. RESULTS: Pregnancy imposed an inflammatory response in the mother, observed by the significant increment in total white blood cell (WBC) and neutrophil counts and in the circulating levels of CRP, GM-CSF and lactoferrin, in all trimesters of gestation compared with non-pregnant controls. Plasma elastase concentration was also significantly higher in pregnant women, but only in the first trimester of gestation. Regarding the ratios of lactoferrin and elastase per neutrophil, they were significantly lower in pregnant women (all trimesters). During gestation, WBC and neutrophil count increased significantly from the first to the second trimester and remained high in the third period. In contrast, the ratios of lactoferrin and elastase per neutrophil decreased significantly from the first to the second trimester, remaining low in the last trimester. Concerning CRP levels, no consistent changes were observed throughout gestation; 12 cases (52.2%) presented fluctuations, whereas 7 (30.4%) showed progressive reductions and 4 (17.4%) progressive increments throughout pregnancy. CONCLUSIONS: Changes in CRP levels vary in a wide manner between subjects along pregnancy, even though median values are consistently elevated throughout pregnancy. Moreover, circulating levels of neutrophil-activation products are higher in normal human gestation.

LDL size, total antioxidant status and oxidised LDL in normal human pregnancy: a longitudinal study.

The aim of our work was to evaluate changes in levels of oxidised low-density lipoprotein (Ox-LDL) during pregnancy and how they correlate with changes in LDL size and serum total antioxidant status (TAS). LDL peak and mean particle diameter (LDL-PPD and LDL-MPD, respectively) and the relative proportion of 3 LDL subfractions were quantified. We evaluated plasma levels of Ox-LDL and serum levels of TAS, total cholesterol (Chol), triglycerides (TG), apolipoprotein A-I (apo A-I), apolipoprotein B (apo B), HDL-cholesterol (HDLc) and LDL-cholesterol (LDLc). A longitudinal study was performed in the three trimesters (T1-T3) of pregnancy in normal pregnant women (n = 23) and a non-pregnant group (n = 18) was used as control. TG levels were significantly elevated whereas LDL-MPD and LDL-PPD were significantly reduced in T1 compared to controls. Ox-LDL, TG, Chol, apo B and LDLc rose markedly throughout pregnancy with significant changes between each trimester; LDL-PPD, LDL-MPD and TAS levels decreased significantly from T1 to T3. Changes in LDL size and in Ox-LDL and TAS levels were more pronounced between T1 and T2 than between T2 and T3. HDLc and apo A-I reached peak concentration in T2 but decreased in T3. TG concentrations correlated inversely with LDL size and positively with Ox-LDL; Ox-LDL was positively and strongly correlated with LDLc. Moreover, relative changes in the levels of Ox-LDL correlated inversely with relative changes in LDL size and TAS between trimesters. In conclusion, during human gestation the change in LDL profile towards smaller species and the decrease in serum TAS are closely associated with increased levels of Ox-LDL. The exact physiological role of the increments in Ox-LDL during pregnancy remains to be clarified.

Apolipoprotein E and cholesteryl ester transfer protein polymorphisms in normal and preeclamptic pregnancies.

OBJECTIVES: To evaluate the association of apolipoprotein (apo) E polymorphism and a cholesteryl ester transfer protein (CETP) polymorphism (CETP/TaqIB) with preeclampsia and with lipid/lipoprotein profile in pregnancy. MATERIALS AND METHODS: A group of 144 normal pregnant women (67 in the third trimester) were compared with 51 cases of preeclampsia in the third trimester of gestation. Apo E and CETP genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. Serum lipids, lipoproteins and apolipoproteins were evaluated using commercially available kits. LDL size was assessed by gradient gel electrophoresis. RESULTS: No differences were found in the distribution of subjects with respect to genotypes, in the apo E and CETP polymorphisms, between control and pathologic groups. In the third trimester of gestation (both control and case groups considered), apo E polymorphism, but not CETP polymorphism, was associated with different lipid and lipoprotein levels. Patients carrying the E2 allele (E2+) presented with significantly lower values of LDL cholesterol (LDLc) compared with carriers of E4 (E4+) and E3/3 individuals. E2+ also presented with the highest triglyceride (TG) level, although this was not statistically significant. On the other hand, HDL cholesterol (HDLc) and apo A-I levels were significantly reduced in E4+, compared with E3/3. Furthermore, E4+ presented with the highest total cholesterol and LDL and therefore LDLc/HDLc and apo B/apo A-I ratios were significantly higher in this group compared with the other two. CONCLUSIONS: Neither of our candidate genes showed association with preeclampsia. However, apo E genotype was associated with changes in lipid and lipoprotein profiles in pregnant women.

Neutrophil activation and C-reactive protein concentration in preeclampsia.

Preeclamptic pregnancies seem to be associated with a higher extent of inflammation compared with normal ones. We intended to test this proposal and also to clarify the contribution of some variables in such inflammatory process. We measured total and differential leukocyte count, serum C-reactive protein (CRP), and plasma levels of lactoferrin, elastase, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Uric acid was also evaluated and used as an indicator of the severity of the disease. A cross-sectional study was performed by evaluating healthy and preeclamptic women in the third trimester of gestation (n = 67 and n = 51, respectively) and 24 to 48 h postpartum (n = 32 and n = 26, respectively). When comparing the third trimester of normal and preeclamptic pregnancies, we found significantly higher levels of uric acid, CRP, and elastase, and a significantly higher elastase to neutrophil ratio in the pathologic group. However, for CRP, statistical significance was lost after adjustment for maternal weight. No significant differences were found in total leukocyte count, plasma levels of GM-CSF, and lactoferrin between groups. In preeclampsia, a significant positive correlation was found between elastase and lactoferrin and these neutrophil activation products correlated positively with uric acid level. Considering the analysis of all variables in the postpartum period, only CRP and uric acid levels were significantly elevated in the pathologic group. However, CRP differences obtained in the puerperium seem to be influenced by the increased number of dystocic deliveries in the preeclamptic group. In conclusion, our data suggest that inflammation is further pronounced in preeclampsia and that the extent of neutrophil activation correlates with the severity of this syndrome.

Elevated tissue plasminogen activator as a potential marker of endothelial dysfunction in pre-eclampsia: correlation with proteinuria.

OBJECTIVE: To clarify the role played by endothelial cell production of fibrinolytic factors in normal pregnancy and pre-eclampsia. DESIGN: A longitudinal study performed during normal pregnancy and a cross sectional study performed in healthy and pre-eclamptic pregnant women in the third trimester of pregnancy. SETTING: Department of Obstetrics and Gynaecology, University Hospital of S. João, Porto, Portugal. POPULATION: Fourteen normal pregnant women followed through the three trimesters of gestation. Two groups of women (normal, n = 56; pre-eclamptic, n = 37) evaluated at the third trimester of gestation. METHODS: Measurement of platelet number, plasma levels of fibrinogen, tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor-1 (PAI-1) activity, and fibrin fragment D-dimer. MAIN OUTCOME MEASURES: Pre-eclampsia, proteinuria. RESULTS: All the substances, except platelet count, increased significantly throughout normal pregnancy. Comparison of the values in the third trimesters of normal and pre-eclamptic pregnancies showed similar values for the fibrinogen and platelet counts, and higher values of t-PA (almost twice normal median value; P < 0.0001), PAI-1 and D-dimer in the pre-eclamptic women. t-PA correlated positively and significantly with the degree of proteinuria in pre-eclamptic women (r = 0.575, P = 0.0002). CONCLUSION: These findings suggest that elevated t-PA antigen may reflect endothelial disturbance in preeclampsia, and may be a potential biomarker of risk.

Band 3 as a marker of erythrocyte changes in pregnancy.

Modifications in the erythrocyte membrane protein band 3 seem to mark the cell for death. A decrease in band 3 high molecular weight aggregates (HMWAg) and a rise in its proteolytic fragments (Pfrag) were described for younger erythrocytes. The aim of this work was to study the band 3 profile as a marker of erythrocyte changes in pregnancy and postpartum. We performed a cross-sectional study in non-pregnant controls (n = 24), in women in the first (n = 64), second (n = 48) and third (n = 67) trimesters of gestation, and also in the puerperium (24-48 h after delivery; n = 32); we also carried out a longitudinal study (n = 23) during the three trimesters of normal pregnancy. We evaluated the band 3 profile (% of band 3 monomer, HMWAg, and Pfrag) and the membrane-bound haemoglobin. Total serum bilirrubin, glutathione peroxidase activity, red blood cell (RBC) count, haematocrit (Ht), haemoglobin (Hb) concentration, the haematimetric indices, and red cell distribution width were also evaluated. Similar results were found in pregnancy in both the cross-sectional and longitudinal studies. We found that the RBC count, Hb, and Ht decreased significantly in pregnancy and in puerperium. Band 3 profile in the first trimester of pregnancy, when compared with controls, presented significantly reduced HMWAg and increased Pfrag. Comparing the first with the third trimester, we found a significant reduction in band 3 and a significant rise in Pfrag. However, between these same periods, HMWAg did not decrease. Our data suggest band 3 profile as a marker of erythrocyte changes in pregnancy, which are independent of the 'physiological anaemia' of pregnancy. These changes suggest an increase in damaged RBCs, but also an increase in younger RBCs in the maternal circulation.

Changes in LDL size and HDL concentration in normal and preeclamptic pregnancies.

The aim of this study was to evaluate changes in lipids, apolipoproteins and lipoproteins in Portuguese pregnant women and their potential involvement in the pathophysiology of preeclampsia. A cross-sectional study was performed by collecting blood samples in the first (n=64), second (n=48) and third (n=67) trimesters and puerperium (n=32) of normal pregnancies. Samples from preeclamptic women were obtained in the third trimester (n=51) and in puerperium (n=26). As normal pregnancy progressed and triglyceride (TG) levels rose there was a decrease in low density lipoprotein (LDL) size, as measured by peak and mean particle diameter (MPD), with an increased proportion of atherogenic small dense LDL. Preeclamptic women exhibited, in the third trimester and puerperium, higher mean serum TG concentration and lower high density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apo A-I) levels compared with healthy pregnant women. In the third trimester, LDL-mean particle diameter (LDL-MPD) and LDL cholesterol-apolipoprotein B (LDLc-apo B) ratio were also significantly reduced in the pathologic group. We conclude that human gestation is associated with an 'atherogenic' lipid profile that is further enhanced in preeclampsia and that this profile may be a potential contributor to endothelial cell dysfunction.