Comparison of two-dimensional measurement with three-dimensional volume rendering for the assessment of loss of domain in incisional hernia patients.

PURPOSE: We aimed to compare simple two-dimensional (2D) measurement with comprehensive three-dimensional (3D) volume rendering to determine loss of domain (LOD), a clinically important decision-making feature for incisional hernia repair. METHODS: In this single-center retrospective study, we analyzed the CT scans of a consecutive cohort of adult patients with a midline incisional hernia. The hernia sac- and abdominal cavity volumes were obtained by two different methods. The 2D method estimated the volumes using the corresponding height, width, and depth. The 3D method comprised of a volume rendering tool. For both methods, LOD was calculated according to the Sabbagh ratio (hernia sac volume / (hernia sac volume + abdominal cavity volume)). Taking the 3D method as the reference standard, the performance of the 2D method was expressed as positive predictive value (PPV) and negative predictive value (NPV) for LOD of more than- and less than 20%. The agreement between both methods was expressed as Cohen's kappa coefficient (kappa). RESULTS: We analyzed 92 CT scans. Agreement between both methods was high (kappa = 0.854, p = 0.0001); all 67 measurements for which the 2D method assessed LOD to be less than 20% were correctly classified (NPV = 100%), and 20 of 25 measurements for which the 2D method assessed LOD to be more than 20% were correctly classified (PPV = 80%). CONCLUSIONS: The 2D method can exclude patients from perioperative actions needed for a more complex hernia. Since this method is easy to use and less time-consuming, it seems useful for the routine radiological assessment of LOD in clinical practice.

A computed tomography study investigating the effects of botulinum toxin injections prior to complex abdominal wall reconstruction.

OBJECTIVE: To explore how intramuscular injection of botulinum toxin A (BTA) affects the lateral abdominal wall (LAW) musculature, abdominal- and hernia dimensions, and muscle structure on computed tomography (CT) in patients scheduled for complex abdominal wall reconstruction (CAWR). METHODS: Retrospective analysis of prospectively registered patients who received bilateral intramuscular BTA injections into all three muscles of the LAW. Only patients for which a CT was available before and 3-6 weeks after BTA treatment prior to surgery were analyzed. RESULTS: Fifty-two patients were analyzed. Median hernia width in all patients decreased with 0.4 cm (IQR - 2.1;0.6) (p = 0.023). Median intra-abdominal transverse diameter increased with 0.9 cm (IQR - 0.2;3.3) (p = 0.001) and the intra-abdominal anterior-posterior diameter decreased with 0.5 cm (IQR - 1.3;0.5) (p = 0.017), making the abdomen more oval. Median LAW muscle length increased with 0.9 cm (IQR 0.0;2.4) per side (p < 0.001), muscle thickness decreased with 0.5 cm (IQR - 0.8;- 0.2) (- 25.0%) per side (p < 0.001), and muscle mass decreased with 3.9 cm2 (IQR - 6.4;-1.5) (- 15.8%) per side (p < 0.001). Median HU of the psoas muscles (density) increased with 4.8 HU (IQR 0.4;9.7) (10.3%) per side (p < 0.001). Effects of BTA were more pronounced in patients with a loss of domain (LoD) ≥ 20%. CONCLUSIONS: The main effect of BTA injections is elongation and thinning of the LAW muscles, more than a decrease in hernia width. Concomitantly, the abdomen becomes more oval. An increase of psoas muscles density is seen, associated with offloading of the LAW muscles. Patients with large LoD have a proportionally higher effect of BTA.

Electronic structure of spatially aligned graphene nanoribbons on Au(788).

We report on a bottom-up approach of the selective and precise growth of subnanometer wide straight and chevron-type armchair nanoribbons (GNRs) on a stepped Au(788) surface using different specific molecular precursors. This process creates spatially well-aligned GNRs, as characterized by STM. High-resolution direct and inverse photoemission spectroscopy of occupied and unoccupied states allows the determination of the energetic position and momentum dispersion of electronic states revealing the existence of band gaps of several electron volts for straight 7-armchair, 13-armchair, and chevron-type GNRs in the electronic structure.

Outcomes of mid-term and long-term degradable biosynthetic meshes in single-stage open complex abdominal wall reconstruction.

OBJECTIVE: To assess clinical outcomes in patients that underwent open single-stage complex abdominal wall reconstruction (CAWR) with biosynthetic mesh. METHODS: Retrospective observational study of two prospectively registered series of consecutive patients undergoing CAWR with either long-term degradable (LTD) Phasix™ or mid-term degradable (MTD) BIO-A® biosynthetic mesh in a single institution between June 2016 and December 2019. RESULTS: From 169 patients with CAWR, 70 consecutive patients were identified who underwent CAWR with either LTD or MTD biosynthetic mesh. More than 85% of patients had an incisional hernia that could be classified as moderately complex to major complex due to a previous wound infection (67%), one or more complicating comorbidities (87.1%), one or more complicating hernia characteristics (75.7%) or contaminated or dirty defects (37.1%). Concomitant component separation was performed in 43 of 70 patients (61.4%). Overall surgical site infection (SSI) rate in these CAWR patients was 45.7%. Seventeen of 70 patients (24.3%) had computed tomography (CT) - and culture-confirmed SSI in direct contact of mesh, suspicious of mesh infection. Mesh removal for persistent local infection occurred in 10% (7 of 70) after a median of 229 days since surgery. Salvage rate of mesh after direct contact with infection was 58.8%. All removed meshes were in the LTD group. Seven patients (10%) had a recurrence; four patients in the LTD group (10%) had a recurrence at a median follow-up of 35 months and three patients in the MTD group (10%) at a median follow-up of 11 months. Three of the seven recurrences occurred in patients with SSI in persistent and direct contact with mesh. CONCLUSIONS: Comorbid patients undergoing open complex abdominal wall reconstruction are at high risk of postoperative wound complications regardless of which type of biosynthetic mesh is used. When in persistent and direct contact with infection, long-term biodegradable biosynthetic meshes may need to be removed, whereas mid-term biodegradable biosynthetic meshes can be salvaged.

A systematic review and meta-analysis of technical aspects and clinical outcomes of botulinum toxin prior to abdominal wall reconstruction.

PURPOSE: To systematically review technical aspects and treatment regimens of botulinum toxin A (BTA) injections in the lateral abdominal wall musculature. We also investigated the effect of BTA on abdominal muscle- and hernia dimensions, and clinical outcome. METHODS: PubMed, EMBASE, CENTRAL, and CINAHL were searched for studies that investigate the injection of BTA in the lateral abdominal wall muscles. Study characteristics, BTA treatment regimens, surgical procedures, and clinical outcomes are presented descriptively. The effect of BTA on muscle- and hernia dimensions is analyzed using random-effects meta-analyses, and exclusively for studies that investigate ventral incisional hernia patients. RESULTS: We identified 23 studies, comprising 995 patients. Generally, either 500 units of Dysport® or 200-300 units of Botox® are injected at 3-5 locations bilaterally in all three muscles of the lateral abdominal wall, about 4 weeks prior to surgery. No major procedural complications are reported. Meta-analyses show that BTA provides significant elongation of the lateral abdominal wall of 3.2 cm per side (95% CI 2.0-4.3, I2 = 0%, p < 0.001); 6.3 cm total elongation, and a significant but heterogeneous decrease in transverse hernia width (95% CI 0.2-6.8, I2 = 94%, p = 0.04). Furthermore, meta-analysis shows that BTA pretreatment in ventral hernia patients significantly increases the fascial closure rate [RR 1.08 (95% CI 1.02-1.16, I2 = 0%, p = 0.02)]. CONCLUSION: The injection technique and treatment regimens of botulinum toxin A as well as patient selection require standardization. Bilateral pretreatment in hernia patients significantly elongates the lateral abdominal wall muscles, making fascial closure during surgical hernia repair more likely. STUDY REGISTRATION: A review protocol for this meta-analysis was registered at PROSPERO (CRD42020198246).

Reporting of prognostic studies of tumour markers: a review of published articles in relation to REMARK guidelines.

BACKGROUND: Poor reporting compromises the reliability and clinical value of prognostic tumour marker studies. We review articles to assess the reporting of patients and events using REMARK guidelines, at the time of guideline publication. METHODS: We sampled 50 prognostic tumour marker studies from higher impact cancer journals between 2006 and 2007. The inclusion criteria were cancer; focus on single biological tumour marker; survival analysis; multivariable analysis; and not gene array or proteomic data. Articles were assessed for the REMARK profile and other REMARK guideline items. We propose a reporting aid, the REMARK profile, motivated by the CONSORT flowchart. RESULTS: In 50 studies assessed for the REMARK profile, the number of eligible patients (56% of articles), excluded patients (54%) and patients in analyses (98%) was reported. Only 50% of articles reported the number of outcome events. In multivariable analyses, 54% and 30% of articles reported patient and event numbers for all variables. Of the studies, 66% used archival samples, indicating a potentially biased patient selection. Only 36% of studies reported clearly defined outcomes. CONCLUSIONS: Good reporting is critical for the interpretability and clinical applicability of prognostic studies. Current reporting of key information, such as the number of outcome events in all patients and subgroups, is poor. Use of the REMARK profile would greatly improve reporting and enhance prognostic research.

ADAM17 upregulation in human renal disease: a role in modulating TGF-alpha availability?

A disintegrin and metalloproteinase (ADAM)17 sheds growth factors from the cell membrane, including epidermal growth factor receptor (EGFR) ligand transforming growth factor (TGF)-alpha. In mice, angiotensin II infusion induces renal fibrosis via ADAM17-mediated TGF-alpha shedding and subsequent EGFR activation. Pharmacological ADAM17 inhibition reduced renal fibrotic lesions and improved renal function, positioning ADAM17 as a promising target of intervention in renal disease. We studied ADAM17 expression in the human kidney. ADAM17 mRNA was constitutively expressed in normal adult kidneys, with highest expression in distal tubules. In human renal disease, ADAM17 was de novo expressed in proximal tubules, peritubular capillaries, and glomerular mesangium and upregulated in podocytes. Glomerular mesangial and endothelial ADAM17 were associated with mesangial matrix expansion, focal glomerulosclerosis, and glomerular macrophage infiltration (P < 0.01). Peritubular capillary and proximal tubular ADAM17 were associated with interstitial fibrosis and interstitial macrophage infiltration (P < 0.05). Both glomerular and interstitial ADAM17 were associated with decreased renal function (P < 0.05). In renal fibrosis, ADAM17 colocalized with TGF-alpha. Moreover, in cultured human podocytes and proximal tubular cells, pharmacological ADAM17 inhibition reduced constitutive TGF-alpha shedding by 78% (P < 0.005) and 100% (P < 0.05), respectively, and phorbol ester-induced TGF-alpha shedding by 84% (P < 0.005) and 92% (P = 0.005), respectively. Finally, ADAM17 inhibition reduced cellular proliferation. In conclusion, the ADAM17 expression pattern and its role in shedding TGF-alpha from cultured human kidney cells suggest a role in the development of fibrosis. Since EGFR signaling is implicated in renal fibrosis, targeting ADAM17 to reduce availability of EGFR ligand TGF-alpha may represent a promising way of intervention in human renal disease.

S3-guideline "helicobacter pylori and gastroduodenal ulcer disease" of the German society for digestive and metabolic diseases (DGVS) in cooperation with the German society for hygiene and microbiology, society for pediatric gastroenterology and nutrition e. V., German society for rheumatology, AWMF-registration-no. 021 / 001.

This guideline updates a prior consensus recommendation of the German Society for Digestive and Metabolic Diseases (DGVS) from 1996. It was developed by an interdisciplinary cooperation with representatives of the German Society for Hygiene and Microbiology, the Society for Pediatric Gastroenterology and Nutrition (GPGE), and the German Society for Rheumatology. The guideline is methodologically based on recommendations of the Association of the Scientific Medical Societies in Germany (AWMF) for providing a systematic evidence-based S 3 level consensus guideline and has also implemented grading criteria according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) process. Clinical applicability of study results as well as specifics for Germany in terms of epidemiology, antibiotic resistance status, diagnostics, and therapy were taken into account.

A placental cause of intra-uterine fetal death depends on the perinatal mortality classification system used.

Different classification systems for the cause of intra-uterine fetal death (IUFD) are used internationally. About two thirds of these deaths are reported as unexplained and placental causes are often not addressed. Differences between systems could have consequences for the validity of vital statistics, for targeting preventive strategies and for counselling parents on recurrence risks. Our objective was to compare use of the Tulip classification with other currently used classification systems for causes of IUFD. We selected the extended Wigglesworth classification, modified Aberdeen and the classifications by Hey, Hovatta, de Galan-Roosen and Morrison. We also selected the ReCoDe system for relevant conditions, comparable to contributing factors in the Tulip classification. Panel classification for 485 IUFD cases in the different systems was performed by assessors after individual investigation of structured patient information. Distribution of cases into cause of death groups for the different systems varied, most of all for the placental and unknown groups. Systems with a high percentage of cases with an unknown cause of death and death groups consisting of clinical manifestations only are not discriminatory. Our largest cause of death group was placental pathology and classification systems without placental cause of death groups or minimal subdivision of this group are not useful in modern perinatal audit as loss of information occurs. The most frequent contributing factor was growth restriction. This illustrates the vital role of the placenta in determination of optimal fetal development. In the Tulip classification, mother, fetus and placenta are addressed together. The system has a clear defined subclassification of the placenta group, a low percentage of unknown causes and is easily applied by a multidisciplinary team. A useful classification aids future research into placental causes of IUFD.

Expression and cellular localisation of chloride intracellular channel 3 in human placenta and fetal membranes.

Chloride channels regulate the movement of a major cellular anion and are involved in fundamental processes that are critical for cell viability. Regulation of intracellular chloride is achieved by multiple classes of channel proteins. One class of putative channels are the chloride intracellular channel (CLIC) family. Evidence suggests that several CLICs are expressed in human placenta, although their roles in this tissue are not certain. Northern blot analysis has shown that CLIC3 is highly expressed in placenta relative to other human tissues; however, its cellular distribution is not known. This study used microarray expression profiling to clarify which CLICs are expressed in human placenta and RT-PCR, Western blot and immunohistochemistry to determine the expression pattern of CLIC3 in human placenta and fetal membranes. Placentas and fetal membranes were obtained from term pregnancies after delivery and placental tissue was obtained from first trimester following either chorionic villous sampling or elective pregnancy termination. Trophoblast cells were isolated from first trimester and term placentas and placental endothelial cells were isolated from term placentas. Microarray expression profiling identified high expression of mRNA for CLICs 1, 3 and 4 in the isolated first trimester and term trophoblast cells. High mRNA expression in the isolated endothelial cells was also found for CLICs 1 and 4, but not CLIC3. Low expression was found for CLIC5 in all three types of isolated cells. RT-PCR confirmed that CLIC3 mRNA was expressed in trophoblast cells at both gestational ages, but was not present in endothelial cells. CLIC3 mRNA was also identified in whole placental extracts at both gestational ages and in term amnion and choriodecidua. Immunohistochemistry using a chicken anti-human CLIC3 antibody localised strong CLIC3-specific staining to the syncytiotrophoblast and villous cytotrophoblast cells in both first trimester and term placentas, and weaker staining in extravillous trophoblast cells in first trimester. In fetal membranes at term strong CLIC3-specific staining was localised to chorionic trophoblast cells, with weaker staining in amniotic epithelial and decidual cells. It was previously shown that chloride uptake was increased into cells that had been transfected with CLIC3. CLIC3 may facilitate chloride ion movement and the regulation of cellular processes associated with the movement of chloride in the placental and fetal membrane cells in which it is expressed.

Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis.

BACKGROUND: Maintenance of remission is a major issue in inflammatory bowel disease. In ulcerative colitis, the evidence for the effectiveness of azathioprine and 6-mercaptopurine for the maintenance of remission is still controversial. OBJECTIVES: To assess the effectiveness and safety of azathioprine and 6-mercaptopurine for maintaining remission of ulcerative colitis. SEARCH STRATEGY: The MEDLINE database was used to search literature from 1966 to 2006. A manual search was also performed using references from these articles as well as review articles, proceedings from major gastrointestinal meetings and data available from the Cochrane Collaboration database. Authors of maintenance trials were asked about unpublished studies. SELECTION CRITERIA: Randomized controlled trials of at least 12 months duration that compared azathioprine or 6-mercaptopurine with placebo or standard maintenance therapy (mesalamine) were included. DATA COLLECTION AND ANALYSIS: Data were extracted by two raters using standard forms. Disagreements were solved by informal consent, including a third rater. Jadad scores were applied to assess study quality. Analyses were performed separately by type of control (placebo, or active comparator). Pooled odds ratios were calculated based on the fixed effects model unless heterogeneity was shown. MAIN RESULTS: Six studies were identified including 286 patients with ulcerative colitis. The study quality was mostly poor. Azathioprine was shown to be superior for the maintenance of remission as compared to placebo based on four trials (failure to maintain remission: OR 0.41; 95% CI 0.24 to 0.70). Two trials that compared 6-mercaptopurine to mesalazine, or azathioprine to sulfasalazine showed significant heterogeneity. Both studies using active comparators were open label. Adverse effects occurred in 11 of 127 patients receiving azathioprine, including acute pancreatitis (3 cases) and significant bone marrow suppression (5 cases). AUTHORS' CONCLUSIONS: Azathioprine may be an effective maintenance therapy for patients who have failed or cannot tolerate mesalazine or sulfasalazine and for patients who require repeated courses of steroids. More research is needed to evaluate superiority over standard maintenance therapy, especially in the light of a potential for adverse events from azathioprine.

Identification of bacterial invasion in necrotizing enterocolitis specimens using fluorescent in situ hybridization.

OBJECTIVE: Investigation of bacterial invasion into the intestinal wall in necrotizing enterocolitis (NEC) specimens. STUDY DESIGN: We compared 43 surgical NEC specimens with 43 age-matched controls. We used fluorescent in situ hybridization (FISH), a universal bacterial probe together with species-specific probes for Clostridium spp., Enterobacteriaceae, bacteroides and enterococci/lactobacilli. We used a FISH scoring system to reveal invasion of the intestinal wall, in which 1 represented no colonies and 4 invasion of the intestinal wall. RESULTS: We observed invasion of the intestinal wall in 22/43 of the most affected NEC tissue samples as compared with 16/43 in the least affected NEC tissue samples (P=0.03). A FISH score of 4 was reached in 7/43 control cases. Enterobacteriaceae dominated the NEC specimens. Clostridium spp. were detected occasionally in NEC samples. CONCLUSION: Bacterial invasion of the intestinal wall is more present in most affected NEC tissue samples compared with least affected NEC tissue samples or controls. Enterobacteriaceae are prevalent in advanced NEC.

cis-diamminedichloroplatinum(ii) resistance in vitro and in vivo in human embryonal carcinoma cells.

In the embryonal carcinoma cell line Tera and its 3.7-fold cis-diamminedichloroplatinum(II) (CDDP)-resistant subline, Tera-CP, parameters were studied that might have changed in relation to induction of CDDP resistance. Phenotypes of both lines were embryonal carcinoma. Karyotypes were related with a decreased mean number of chromosomes and fewer copies of the short arm of chromosome 12 in Tera-CP. Tera-CP showed cross-resistance for melphalan and 4-hydroperoxycyclophosphamide and had an 1.4-fold increased glutathione (GSH) level, a 1.5-fold increased glutathione S-transferase (GST) activity, and a 1.4-fold increased GST pi expression compared to Tera. Tera-CP was cross-resistant to 5-fluorouracil, but thymidylate synthase activity was not increased. Topoisomerase I and II activities and c-myc RNA and protein expression were the same in both lines. Platinum accumulation was equal in both lines, and platinum-DNA binding was lower in Tera-CP than in Tera. Both cell lines were xenografted into nude mice and tumors showed marked differentiation. Tera-CP tumors were 2.8-fold resistant to CDDP compared to Tera tumors. In new cell lines derived from xenografts of Tera and Tera-CP CDDP sensitivity, GST activity and GSH level corresponded with their sensitivity and resistant origin. Tera-CP is a model of in vitro and in vivo CDDP resistance with the GSH/GST detoxifying system as an important mechanism. CDDP resistance could be induced without a concomitant increase in differentiation.

Good Medicine and Good Healthcare Demand Good Information (Systems).

The demand for evidence-based health informatics and benchmarking of 'good' information systems in health care gives an opportunity to continue reporting on recent papers in the German journal GMS Medical Informatics, Biometry and Epidemiology (MIBE) here. The publications in focus deal with a comparison of benchmarking initiatives in German-speaking countries, use of communication standards in telemonitoring scenarios, the estimation of national cancer incidence rates and modifications of parametric tests. Furthermore papers in this issue of MIM are introduced which originally have been presented at the Annual Conference of the German Society of Medical Informatics, Biometry and Epidemiology. They deal as well with evidence and evaluation of 'good' information systems but also with data harmonization, surveillance in obstetrics, adaptive designs and parametrical testing in statistical analysis, patient registries and signal processing.

Intestinal fatty acid-binding protein levels in Necrotizing Enterocolitis correlate with extent of necrotic bowel: results from a multicenter study.

BACKGROUND: Intestinal fatty acid-binding protein (I-FABP) is considered as a specific marker for enterocyte damage in necrotizing enterocolitis (NEC). OBJECTIVE: The purpose of this study was to evaluate the association of plasma and urinary I-FABP levels with the extent of macroscopic intestinal necrosis in surgical NEC. METHODS: We combined data from prospective trials from two large academic pediatric surgical centers. Nine and 10 infants with surgical NEC were included, respectively. Plasma and urinary of I-FABP at disease onset were correlated with the length of intestinal resection during laparotomy. RESULTS: Median length of bowel resection was 10cm (range 2.5-50) and 17cm (range 0-51), respectively. Median I-FABP levels were 53ng/mL (range 6.3-370) and 4.2ng/mL (range 1.1-15.4) in plasma in cohort 1 respectively cohort 2 and 611ng/mL (range 3-23,336) in urine. The length of bowel resection significantly correlated with I-FABP levels in plasma (Rho 0.68; p=0.04 and Rho 0.66;p=0.04) and in urine (Rho 0.92; p=0.001). CONCLUSION: This 'proof of concept' study demonstrates that plasma and urine I-FABP levels at disease onset was strongly associated with the length of intestinal resection in surgical NEC. This offers further evidence that I-FABP levels are a promising biomarker for assessing intestinal necrosis in infants with advanced NEC.

Formation by diethylnitrosamine and persistence of O4-ethylthymidine in rat liver DNA in vivo.

The formation by diethylnitrosamine (DEN) and persistence of O4-ethylthymidine in rat liver DNA in vivo has been studied using enzymic hydrolysis of DNA, cation exchange column chromatography and thin-layer chromatography (TLC). The amount of O4-ethylthymidine represented about 1% of the total ethylation; its half-life in vivo was 19 (range 16--24) days, the same value as obtained for O2-ethylthymidine. The persistence of O2- and O4-ethylthymidine, rather than the rapid removal of O6-ethylguanine, favours the former miscoding base adducts as relevant molecular lesions in rat liver carcinogenesis.

Time trends in the incidence and disease location of Crohn's disease 1980-1995: a prospective analysis in an urban population in Germany.

To determine the incidence and clinical pattern of Crohn's Disease in a defined area in Germany, a prospective, population-based study was carried out from 1980 to 1984 and again from 1991 to 1995. All patients newly diagnosed with Crohn's disease within the respective study period who were resident in the study area were included in the study. The results from both study periods were then compared to detect time trends. Altogether 288 (156 and 132, respectively) incident cases were identified yielding an almost unchanged incidence over the years (1980-84: 4.9/10(5); 1991-95 5.2/10(5)). While the peak of incidence is still in the 15-24-year-old group, 1 out of 5 incident patients is now age 50 years and older. Median age at onset of symptoms increased to 30 years (20 years in the former period). Time from onset of symptoms was reduced from a median of 20 months in the 1980s to 5 months. Symptoms did not change significantly, although there seems to be less complicated disease recently. Distal migration of the inflammation in the intestinal tract was observed with significantly more involvement of the sigmoid and rectum in the recent period.

Uterine artery Doppler flow and uteroplacental vascular pathology in normal pregnancies and pregnancies complicated by pre-eclampsia and small for gestational age fetuses.

This study was conducted to investigate the association between uterine artery Doppler flow patterns and uteroplacental vascular pathology in normal and complicated pregnancies in view of the recently described concept of heterogeneous causes of hypertensive pregnancy complications. Forty-three women whose pregnancies were complicated by pre-eclampsia, the HELLP (Haemolysis, Elevated Liver enzymes, Low Platelets) syndrome and/or small for gestational age (SGA) fetuses and 27 women with normal pregnancies undergoing elective caesarean section were included. We obtained uterine artery Doppler waveforms at a mean of 4 days before delivery. Placental bed biopsies were obtained at caesarean section and analysed for physiological changes and pathological changes. We found that abnormal uterine artery Doppler flow was strongly associated with pregnancy complications. Absence of physiological changes was seen in 58 per cent of complicated pregnancies and 40 per cent of normal pregnancies. Pathological changes were seen in 58 per cent of complicated pregnancies and 53 per cent of normal pregnancies; they occurred in spiral arteries with and without physiological changes, and there was no significant correlation to Doppler results. In conclusion, absence of physiological changes is associated with abnormal uterine artery Doppler flow and pregnancy complications. However, there is a gradient in the severity of uteroplacental vascular pathology and the correlation with pregnancy complications is not as strong as previously thought. There is also a significant degree of uteroplacental vascular pathology in normal pregnancies with normal uterine artery Doppler flow. This variation may be partly due to sampling error, as a typical biopsy contains only one or two spiral arteries. We hypothesize that additional factors might be necessary to induce the clinical syndrome of pre-eclampsia.