Endoscopic mucosal resection of large rectal adenomas in the era of centralization: Results of a multicenter collaboration.

BACKGROUND AND OBJECTIVE: Endoscopic mucosal resection (EMR) of large rectal adenomas is largely being centralized. We assessed the safety and effectiveness of EMR in the rectum in a collaboration of 15 Dutch hospitals. METHODS: Prospective, observational study of patients with rectal adenomas >3 cm, resected by piecemeal EMR. Endoscopic treatment of adenoma remnants at 3 months was considered part of the intervention strategy. Outcomes included recurrence after 6, 12 and 24 months and morbidity. RESULTS: Sixty-four patients (50% male, age 69 ± 11, 96% ASA 1/2) presented with 65 adenomas (diameter 46 ± 17 mm, distance ab ano 4.5 cm (IQR 1-8), 6% recurrent lesion). Sixty-two procedures (97%) were technically successful. Histopathology revealed invasive carcinoma in three patients (5%), who were excluded from effectiveness analyses. At 3 months' follow-up, 10 patients showed adenoma remnants. Recurrence was diagnosed in 16 patients during follow-up (recurrence rate 25%). Fifteen of 64 patients (23%) experienced 17 postprocedural complications. CONCLUSION: In a multicenter collaboration, EMR was feasible in 97% of patients. Recurrence and postprocedural morbidity rates were 25% and 23%. Our results demonstrate the outcomes of EMR in the absence of tertiary referral centers.

The epidemiology of life-threatening complications associated with reproductive process in public hospitals in Argentina.

OBJECTIVE: To analyse life-threatening obstetric complications that occurred in public hospitals in Argentina. DESIGN: Multicentre collaborative cross-sectional study. SETTING: Twenty-five hospitals included in the Perinatal Network of Buenos Aires Metropolitan Area. POPULATION: Women giving birth in participating hospitals during a 1-year period. METHODS: All cases of severe maternal morbidity (SMM) and maternal mortality (MM) during pregnancy (including miscarriage and induced abortion), labour and puerperium were included. Data were collected prospectively. MAIN OUTCOME MEASURES: Identification criteria, main causes and incidence of SMM; case-fatality rates, morbidity-mortality index and effective intervention's use rate. RESULTS: A total of 552 women with life-threatening conditions were identified: 518 with SMM, 34 with MM. Identification criteria for SMM were case-management (48.9%), organ dysfunction (15.2%) and mixed criteria (35.9%). Incidence of SMM was 0.8% (95% confidence interval [95% CI] 0.73-0.87%) and hospital maternal death ratio was 52.3 per 100 000 live births (95% CI 35.5-69.1). Main causes of MM were abortion complications and puerperal sepsis; main causes of SMM were postpartum haemorrhage and hypertension. Overall case-fatality rate was 6.2% (95% CI 4.4-8.6): the highest due to sepsis (14.8%) and abortion complications (13.3%). Morbidity-mortality index was 15:1 (95% CI 7.5-30.8). Use rate of known effective interventions to prevent or treat main causes of MM and SMM was 52.3% (95% CI 46.9-57.7). CONCLUSIONS: This study describes the importance of life-threatening obstetric complications that took place in public hospitals with comprehensive obstetric care and the low utilisation of known effective interventions that may decrease rates of SMM and MM. It also provides arguments that justify the need to develop a surveillance system for SMM.

LIN28B fosters colon cancer migration, invasion and transformation through let-7-dependent and -independent mechanisms.

Lin28b is an RNA-binding protein that inhibits biogenesis of let-7 microRNAs. LIN28B is overexpressed in diverse cancers, yet a specific role in the molecular pathogenesis of colon cancer has to be elucidated. We have determined that human colon tumors exhibit decreased levels of mature let-7 isoforms and increased expression of LIN28B. To determine LIN28B's mechanistic role in colon cancer, we expressed LIN28B in immortalized colonic epithelial cells and human colon cancer cell lines. We found that LIN28B promotes cell migration, invasion and transforms immortalized colonic epithelial cells. In addition, constitutive LIN28B expression increases expression of intestinal stem cell markers LGR5 and PROM1 in the presence of let-7 restoration. This may occur as a result of Lin28b protein binding LGR5 and PROM1 mRNA, suggesting that a subset of LIN28B functions is independent of its ability to repress let-7. Our findings establish a new role for LIN28B in human colon cancer pathogenesis, and suggest LIN28B post-transcriptionally regulates LGR5 and PROM1 through a let-7-independent mechanism.

Laparoscopic-monitored colonoscopic polypectomy: a multimodality method to avoid segmental colon resection.

AIM: In some patients with adenoma, snare polypectomy may be technically impossible owing to angulation of the colon or after previous surgery. This may result in a segmental colonic resection, if malignant invasion is thought to be likely. Laparoscopic mobilization of the colon to enable a simultaneous colonoscopy can avoid this difficulty. METHOD: A feasibility study was performed in 11 patients for whom endoscopic removal was technically impossible due to fibrosis after previous surgery or to anatomical difficulty. In 10, adenoma (histologically benign) had been diagnosed during diagnostic colonoscopy and in the remaining patient the indication was rectal bleeding. RESULTS: It was possible to perform a full colonoscopy after laparoscopic mobilization in all cases. In nine of the 10 patients with adenoma 11 tubulovillous adenomas were removed endoscopically, and in one the tumour was too large for endoscopic resection even after full mobilization. A laparoscopic segmental resection was performed in this case. In the patient with rectal bleeding, colonoscopy revealed an angiodysplasia of the caecum, also treated by resection. Apart from the two patients having resection, all patients were discharged within 24 h of the procedure. During endoscopic follow up (4-27 months) there were no recurrences. CONCLUSIONS: Combined laparoscopy and endoscopy enabled removal of adenomas otherwise inaccessible for endoscopic techniques. Thus, segmental colon resections can be avoided in most of these patients.

Computer-aided classification of colorectal polyps based on vascular patterns: a pilot study.

BACKGROUND AND STUDY AIMS: Recent studies have shown that narrow-band imaging (NBI) is a powerful diagnostic tool for differentiating between neoplastic and nonneoplastic colorectal polyps. The aim of the present study was to develop and evaluate a computer-based method for automated classification of colorectal polyps on the basis of vascularization features. PATIENTS AND METHODS: In a prospective pilot study with 128 patients who were undergoing zoom NBI colonoscopy, 209 detected polyps were visualized and subsequently removed for histological analysis. The proposed computer-based method consists of image preprocessing, vessel segmentation, feature extraction, and classification. The results of the automated classification were compared to those of human observers blinded to the histological gold standard. RESULTS: Consensus decision between the human observers resulted in a sensitivity of 93.8 % and a specificity of 85.7 %. A "safe" decision, i. e., classifying polyps as neoplastic in cases when there was interobserver discrepancy, yielded a sensitivity of 96.9 % and a specificity of 71.4 %. The overall correct classification rates were 91.9 % for the consensus decision and 90.9 % for the safe decision. With ideal settings the computer-based approach achieved a sensitivity of approximately 90 % and a specificity of approximately 70 %, while the overall correct classification rate was 85.3 %. The computer-based classification showed a specificity of 61.2 % when a sensitivity of 93.8 % was selected, and a 53.1 % specificity with a sensitivity of 96.9 %. CONCLUSIONS: Automated classification of colonic polyps on the basis of NBI vascularization features is feasible, but classification by observers is still superior. Further research is needed to clarify whether the performance of the automated classification system can be improved.

Value of magnifying endoscopy in classifying colorectal polyps based on vascular pattern.

BACKGROUND AND STUDY AIMS: Narrow-band imaging (NBI) has been developed as a new technique to differentiate tissue patterns in vivo. The aim of this study was to evaluate the diagnostic accuracy of NBI endoscopy with and without high magnification for the differentiation of neoplastic from non-neoplastic colorectal polyps. PATIENTS AND METHODS: Among 200 colorectal polyps from 131 patients, 100 lesions were classified according to vascular patterns by NBI endoscopy with high optical magnification and 100 lesions by high-definition endoscopy without high magnification. Additionally, the clarity of the vessel network was assessed. Histologic analysis was performed on all lesions. RESULTS: NBI endoscopy with high magnification resulted in a sensitivity of 92.1 % and a specificity of 89.2 % for the differentiation of neoplastic versus non-neoplastic lesions. This performance was statistically comparable to high-definition NBI endoscopy without high magnification, which showed a sensitivity of 87.9 % and specificity of 90.5 %. However, vessel network was significantly better visualized by NBI endoscopy with optical magnification compared with high-definition NBI endoscopy without high magnification. In comparison with NBI endoscopy, white-light endoscopy, with or without magnification, resulted in inferior discrimination between neoplastic and non-neoplastic polyps. CONCLUSION: The results demonstrate that the superior visibility of capillary vessels by the NBI technique allows the evaluation of colorectal lesions - based on the vascular patterns - with high diagnostic accuracy. In clinical routine, high-definition NBI endoscopy without high magnification may be used to sufficiently predict colorectal polyp histology, and high magnification can additionally facilitate visualization of vascular networks.

[The value of duodenal biopsy within routine upper endoscopy: a prospective study in 1000 patients]. / Die Wertigkeit der tiefen Duodenalbiopsie im Rahmen der Routineendoskopie: Eine prospektive Studie mit 1000 Patienten.

BACKGROUND AND AIM: Several gastrointestinal diseases are localised in the small bowel and are confirmed by duodenal biopsies upon upper gastrointestinal endoscopy. However, the clinical value of routine duodenal biopsies during endoscopy has not been satisfactorily defined and was assessed in the current study. METHODS: In 1000 consecutive patients duodenal biopsies were performed during routine upper gastrointestinal endoscopy. Endoscopic diagnoses, symptoms and the prevalence of anaemia were correlated with the histological diagnoses. RESULTS: Coeliac disease and giardiasis was diagnosed in 18 and two patients, respectively (2.0 % of all cases). In 11 (55 %) patients the diagnosis was already made macroscopically during endoscopy. The sensitivity for endoscopic diagnosis of coeliac disease MARSH III was 84.6 %. There was no correlation between clinical symptoms, the prevalence of anaemia and the diagnosis of coeliac disease or giardiasis in our cohort. CONCLUSION: Endoscopic diagnosis of advanced celiac disease (MARSH III) can be made with high sensitivity and specifity. Nevertheless, duodenal biopsy is necessary for the diagnosis of early coeliac disease or giardiasis. However, the routine duodenal sampling of normal mucosa during gastrointestinal endoscopy cannot be recommended.

Value of magnifying chromoendoscopy and narrow band imaging (NBI) in classifying colorectal polyps: a prospective controlled study.

BACKGROUND AND STUDY AIMS: Chromoendoscopy in combination with magnifying endoscopy is useful in distinguishing neoplastic from non-neoplastic colorectal polyps. Narrow band imaging (NBI) has been developed as a new technique to differentiate tissue patterns in vivo. The aim of the present study was to directly compare the diagnostic values of chromoendoscopy and NBI for the differentiation of neoplastic from non-neoplastic colorectal polyps. PATIENTS AND METHODS: In total, 200 colorectal polyps from 99 patients were distributed in a 1 : 1 ratio in order to analyze the surface according to the pit pattern classification and vascular patterns by either magnifying chromoendoscopy or NBI magnification. Histologic analysis was performed on all lesions. RESULTS: Using the Kudo classification of mucosal patterns, NBI with magnification resulted in a sensitivity of 90.5 % and a specificity of 89.2 % for the differentiation of neoplastic vs. non-neoplastic lesions. This performance was comparable to magnifying chromoendoscopy with a sensitivity of 91.7 % and a specificity of 90 %, respectively. Using vascular patterns for differentiation, NBI with magnification correctly identified 93.7 % of neoplastic polyps and 89.2 % of non-neoplastic colorectal lesions, whereas magnifying chromoendoscopy had a specificity of 95 % but a sensitivity of only 66.7 %. CONCLUSION: NBI in combination with magnifying endoscopy is a promising tool for the differentiation of neoplastic from non-neoplastic colorectal polyps in vivo without the necessity of using dye. The detection of capillary vessels with NBI allows the evaluation of colorectal lesions based on the vascular patterns with high diagnostic accuracy.

The interleukin-6 (IL6)-174 G/C promoter genotype is associated with the presence of septic shock and the ex vivo secretion of IL6.

Septic shock is associated with a high mortality and an excessive activation of immune cascades. Interleukin (IL)-6 has been found to be a key cytokine in the pathogenesis of severe sepsis, but the importance of a regulatory polymorphism within the IL6 promoter has been controversial in these patients. The aim of the study was therefore to systematically investigate the IL6-174 G/C promoter genotype with regard to the presence of shock in patients with sepsis, the IL6 serum levels, and the ex vivo secretion of IL6, respectively. Overall, 112 consecutive subjects with severe sepsis and septic shock according to consensus criteria were enrolled. The ex vivo secretion of IL6 after stimulation with lipopolysaccharide (LPS) in a whole blood assay and the IL6 serum concentrations were determined after admission of the patients. Among the 112 subjects with severe sepsis, 85 patients fulfilled the criteria of septic shock. In these patients, the frequency of the mutated C-allele of the IL6 promoter polymorphism was significantly (P = 0.04) higher compared to that in individuals without shock. IL6 serum concentrations were highest in patients with the GG genotype (mean 2209 pg mL(-1)), followed by CG genotype (mean 1113 pg mL(-1)), and lowest in individuals with the CC genotype (mean 256 pg mL(-1)). Interestingly, a significantly (P = 0.005) higher ex vivo secretion of IL6 is detected in heterozygote individuals (535 pg mL(-1)) and patients with the IL6 CC genotype (555 pg mL(-1)) compared to patients with the -174 GG genotype (276 pg mL(-1)). In conclusion, the IL6-174 G/C promoter genotype is associated with shock in patients with sepsis. Functionally, the mutated C-allele is correlated with low IL6 serum concentrations, but a high ex vivo secretion after LPS stimulation. These results further indicate a complex regulation of the expression of IL6 during infection and have implications for the design of immune intervention trials.

[Elevated concentrations of fecal calprotectin in patients with liver cirrhosis]. / Erhöhte Konzentrationen von fäkalem Calprotectin bei Patienten mit Leberzirrhose.

UNLABELLED: BACKGROUND AND OBJECTION: Bacterial translocation from the gut lumen is considered to play an important role in the development of infectious complications in patients with liver cirrhosis. This translocation might be increased by inflammation of the gut mucosa. Calprotectin is a cytoplasmatic protein of neutrophilic granulocytes and is an established marker for the assessment of localized intestinal inflammation. It was the aim of the current study to systematically evaluate a localized intestinal inflammation in patients with liver cirrhosis by means of fecal calprotectin concentrations. PATIENTS AND METHODS: Fecal calprotectin concentrations were determined in 53 consecutive patients with liver cirrhosis and in 18 subjects without intestinal or liver diseases, who were comparable with respect to age and gender. Patients with diarrhoea, inflammatory bowel disease and a positive stool test for occult blood were excluded from the study. Fecal calprotectin concentrations were measured by a sandwich ELISA. The systemic inflammatory reaction of the patients was assessed by C-reactive protein, white blood cells counts and the serum concentrations of the cytokines IL-6, IL-8 and IL-10. RESULTS: Fecal calprotectin concentrations were significantly increased in patients with liver cirrhosis (median 37.0 mg/kg) compared to controls patients (median 2.2, P < 0.0001). There were no significant correlations of calprotectin concentrations with systemic inflammatory parameters, like CRP, white blood cell count or serum cytokines. However, fecal calprotectin concentrations were significantly associated with the stage of liver cirrhosis as expressed by the Child-Pugh score ( P < 0.001). A trend towards higher concentrations of calprotectin was found in patients with alcoholic liver cirrhosis ( P = 0.1). CONCLUSIONS: Patients with liver cirrhosis display elevated fecal calprotectin concentrations as a potential sign of intestinal inflammation. Further studies are warranted to establish a role of calprotectin for the risk assessment of infectious complications secondary to bacterial translocation in patients with liver cirrhosis.

Relationship between bolus transit and LES-relaxation studied with concurrent impedance and manometry.

BACKGROUND/AIMS: Neuromuscular mechanisms regulating esophageal bolus transport are well studied. However, detailed data about the relationship between bolus transit and lower esophageal sphincter (LES)-relaxation during conventional motility testing are still lacking. METHODOLOGY: We performed systematic studies in 25 normal subjects, employing a catheter that integrates the two techniques impedancometry and manometry in a single instrument for simultaneous recording and analysis of the relationship between bolus transit and LES relaxation after swallowing saline or yogurt. RESULTS: 195 swallows were analyzed. LES relaxation occurred frequently later than UES relaxation. The mean latency between bolus entry into the esophagus and LES relaxation was 3.6 +0.2 sec. Two types of swallow-induced LES relaxation were observed: (a) LES relaxation preceding bolus transit (46 cases or 24%) and (b) LES relaxation occurring during bolus transit (149 cases or 76%). In the later case, during 114 (76%) cases of this deglutition, the position of the bolus was very close to the LES. CONCLUSIONS: During deglutition, LES relaxation seems to be modulated by bolus transit and occurs predominantly upon arrival of the bolus in the distal esophagus.

Impedance characteristics of esophageal motor function in achalasia.

Detailed data on patterns of esophageal bolus transport in patients with achalasia are still lacking. To study these we applied the novel technique of multichannel intraluminal impedance measurements. Ten patients with achalasia were studied using a 16 channel system. Liquid and semisolid boluses of 10 mL were applied with the patients in a supine position. Patterns of bolus transport were determined and analyzed as compared to results obtained from 20 healthy subjects. The healthy subjects featured a unique typical primary peristalsis pattern independent of bolus viscosity. In contrast, achalasia patients demonstrated different impedance characteristics, including: (i) significantly lower baseline esophageal impedance during the resting state as compared with healthy volunteers (999 omega +/- 108 versus 2749 omega +/- 113); (ii) failed bolus transport through the esophagus in all cases; (iii) impedance evidence of luminal content regurgitation in 35% of the swallows (iv) impedance evidence of pathological air movement within the proximal esophagus during deglutition in 38% of the swallows, so called air trapping. Thus, impedance characteristics of achalasia have been defined and can be attributed to known symptoms of achalasia. They can be used as basic findings for further classification of pathological bolus transports in other esophageal motility disorders.

Effect of glutathione depletion and hydrophilic bile acids on hepatic acute phase reaction in rats with extrahepatic cholestasis.

BACKGROUND: Extrahepatic cholestasis by biliary obstruction induces an acute phase reaction in the liver. It is a complex process involving cytokines, hormones and growth factors. To determine whether the regulation of acute phase proteins (APP) in cholestasis depends on glutathione (GSH), the effect of buthionine sulfoximine-induced (BSO-induced) GSH depletion on the expression of various APP was studied. In addition, we determined the influence of hepatoprotective bile acids on hepatic APP and underlying cytokine events. METHODS: Liver samples of bile-duct-ligated or sham-operated rats were examined. mRNA expression was quantified by densitometric analysis of Northern blots. RESULTS: Expression of APP increased 2-5-fold in bile-duct-ligated rats as compared to sham-operated controls. This acute phase reaction remained similar independently of whether cholestasis occurred for 5 days or 3 weeks. In contrast to alpha2-macroglobulin and tissue inhibitor of metalloproteinases-1 (TIMP-1), mRNA levels of both beta-fibrinogen and haptoglobin were significantly up-regulated after GSH depletion by BSO in cholestasis. Feeding of ursodeoxycholic and iso-ursodeoxycholic acid markedly down-regulated alpha2-macroglobulin and TIMP-1 expression in cholestasis but did not affect overexpression of beta-fibrinogen and haptoglobin. Cholestasis leads to an increased APP expression accompanied by an increased expression of inflammatory cytokines (IL-6, TNF-alpha). After feeding of hydrophilic bile acids, increases in inflammatory cytokines were abrogated. CONCLUSIONS: We show that GSH is involved in the acute phase reaction during obstructive cholestasis. In addition, bile acids might selectively ameliorate the acute phase response by reducing expression of the APP not affected by GSH depletion (alpha2-macroglobulin and TIMP-1).

Tratamiento conservador de embarazo ectópico cervical / Cervical Ectopic Pregnancy Conservative Treatment

El tratamiento conservador de embarazo cervical es poible en centros de tercer nivl de complejidad donde se cuente con servicios de Obstetricia, Imágenes, Hemodinamia y UTI. Presenta una tasa de fracasos del 8 al 20 porciento determinada fundamentalmente por la edad gestacional al momento del diagnóstico

Tratamiento conservador de embarazo ectópico cervical / Cervical Ectopic Pregnancy Conservative Treatment

El tratamiento conservador de embarazo cervical es poible en centros de tercer nivl de complejidad donde se cuente con servicios de Obstetricia, Imágenes, Hemodinamia y UTI. Presenta una tasa de fracasos del 8 al 20 porciento determinada fundamentalmente por la edad gestacional al momento del diagnóstico

Activity and cellular origin of gelatinases in patients with colon and rectal carcinoma differential activity of matrix metalloproteinase-9.

BACKGROUND: Expression and enzymatic activity of gelatinases were examined in biopsy specimens from patients with colon and rectal neoplasms. The objective of this study was to determine whether the activity of these enzymes is altered between tumor areas compared with areas of noninvolved, normal mucosa and between colon and rectal carcinoma. METHODS: Matrix metalloproteinase (MMP) production was analyzed by Western immunoblot analysis and gelatin zymography. mRNA was determined by quantitative, real-time polymerase chain reaction analysis. RESULTS: Patients with colon carcinoma (n = 20 patients) showed a significant increase in levels of MMP-9 (92 kDa and 88 kDa) and MMP-2 (72 kDa and 62 kDa) in tumor areas compared with noninvolved regions. In contrast, patients with rectal carcinoma (n = 10 patients) had revealed the same high activity of MMP-9 in tumor regions and corresponding healthy tissue. Confirming activity measurements, in colon tumors, but not in rectal tumors, there was significant up-regulation of MMP-9 transcription compared with healthy tissue in the same patients. There were no significant changes in the tissue inhibitor of metalloproteinase-1 protein when colon and rectal tumor tissues were compared with the corresponding noninvolved regions. Cell culture experiments revealed fibroblasts as the cellular origin of MMPs. The findings showed that the secretion and activation of gelatinases depend on soluble factors secreted by tumor cells and are influenced by extracellular matrix components. CONCLUSIONS: This is the first report showing differences in MMP-9 activity between rectal carcinoma and colon carcinoma. Previous results indicating an active involvement of stromal cells in the generation of MMPs during tumor invasion are extended. Because the abundance of gelatinases increases in colorectal carcinoma, inhibitors of these proteases may be of therapeutic value.

Metabolism and effects on cholestasis of isoursodeoxycholic and ursodeoxycholic acids in bile duct ligated rats.

Isoursodeoxycholic acid (isoUDCA), the 3 beta-epimer of ursodeoxycholic acid (UDCA), may have pharmaceutical potential because of its similar hydrophilicity and in vitro cytoprotection as compared with UDCA. We compared metabolism and effects on cholestasis of UDCA and isoUDCA in experimental cholestasis in rats. Cholestasis was induced by bile duct ligation. For bile flow and biliary bile acid analysis, UDCA or isoUDCA were infused intraduodenally. For the study of chronic effects, chow was supplemented with 2.5 g/kg UDCA or isoUDCA for 3 weeks. Sham-operated animals served as controls. IsoUDCA became completely converted to UDCA in the liver. Choleresis and biliary bile acids were the same after the intraduodenal administration of either compound. Oral administration of UDCA or isoUDCA significantly improved liver biochemistry but not clinical and histological parameters in chronic cholestasis. The decrease of serum cholic acid in control animals was more pronounced after isoUDCA (-93%) than after UDCA (-76%). Only after UDCA, this decrease was compensated by increases of UDCA, beta-muricholic acid (MCA), and Delta(22)-beta-MCA. Our results show that isoUDCA has the same effect on choleresis and liver biochemistry as UDCA. IsoUDCA features pro-drug characteristics of UDCA and causes compared to the latter lower serum bile acid concentrations in non-cholestatic animals.

Increased TIMP-1 activity results in increased expression of gelatinases and altered cell motility.

Matrix metalloproteinases are proteolytic enzymes which play a major role in resorption of collagen and other components of the extracellular matrix. They are controlled by specific inhibitors, so-called tissue inhibitors of metalloproteinases (TIMPs). The balance between matrix metalloproteinases and TIMPs seems to play a major role in controlling extracellular matrix homeostasis and cell migration. The influence of TIMP-1 on migration behaviour was explored in human hepatoma cells transiently and stably transfected with mouse TIMP-1, and incubated with biologically active TIMP-1. Transfection and biosynthesis were verified by Northern blotting, Western blotting, metabolic labeling, and reverse zymography. Overexpression of and incubation with TIMP-1 resulted in suppressed migration and seemed to enhance cell-cell contact. Using gelatin zymography and Western blotting we measured a significant increase of matrix metalloproteinases-2 and matrix metalloproteinases-9 in cells transfected with TIMP-1. This new phenomenon may be of important physiological significance in modulating TIMP and MMP expression. Our results indicate a functional involvement of TIMP-1 in matrix homeostasis and some automatic control in matrix turnover.