Gene expression profiling in aggressive digital papillary adenocarcinoma sheds light on the architecture of a rare sweat gland carcinoma.

BACKGROUND: Sweat gland carcinomas are rare cutaneous adnexal malignancies. Aggressive digital papillary adenocarcinoma (ADPA) represents a very rare subentity, thought to arise almost exclusively from the sweat glands of the fingers and toes. The aetiology of sweat gland carcinomas and ADPA is largely unknown. ADPAs are most likely driven by somatic mutations. However, somatic mutation patterns are largely unexplored, creating barriers to the development of effective therapeutic approaches to the treatment of ADPA. OBJECTIVES: To investigate the transcriptome profile of ADPA using a sample of eight formalin-fixed, paraffin-embedded tissue samples of ADPA and healthy control tissue. METHODS: Transcriptome profiling was performed using the Affymetrix PrimeView Human Gene Expression Microarray and findings were validated via reverse transcription of RNA and real-time quantitative polymerase chain reaction. RESULTS: Transcriptome analyses showed increased tumour expression of 2266 genes, with significant involvement of cell cycle, ribosomal and crucial cancer pathways. Our results point to tumour overexpression of FGFR2 (P = 0·001). CONCLUSIONS: The results indicate the involvement of crucial oncogenic driver pathways, highlighting cell cycle and ribosomal pathways in the aetiology of ADPA. Suggested tumour overexpression of FGFR2 raises the hope that targeting the fibroblast growth factor (FGF)/FGF receptor axis might be a promising treatment for ADPA and probably for the overall group of sweat gland carcinomas.

The role of the 595-nm pulsed dye laser in treating superficial basal cell carcinoma: outcome of a double-blind randomized placebo-controlled trial.

BACKGROUND: Pulsed dye laser (PDL) treatments have been suggested to be a safe and effective therapeutic approach for treating basal cell carcinomas (BCCs). However, robust supporting evidence is lacking due to inconsistent design of available studies. OBJECTIVES: To evaluate PDL efficacy and safety in treating superficial BCC (sBCC) at low-risk anatomical sites in an evidence-based study setting. MATERIALS AND METHODS: Thirty-nine patients (27 men and 12 women, 75·9 ± 10 years) with a total of 100 sBCCs were randomized to receive PDL treatment (wavelength 595 nm; fluence 8 J cm(-2) ; pulse duration 0·5 ms; spot size 10 mm) or sham treatment. The primary endpoint was complete clinical and histological remission of the tumour at 6-month follow-up; the secondary endpoints were the evaluation of side-effects and pain as well as patient satisfaction. RESULTS: The primary endpoint showed significant superiority of the laser group to the sham group (P < 0·0001). Complete remission was achieved in 44 of 56 cases (78·6%) in the laser and in two of 44 cases (4·5%) in the sham treatment arm. The main adverse events in the laser group were crusts, hyper- and hypopigmentation. An average of 72% of patients stated at the individual sessions that they were 'satisfied' with the laser treatment, whereas 25% were 'very satisfied'. CONCLUSIONS: PDL is an effective and safe method for treating sBCC. However, the occurrence of persistent dyspigmentation still limits the potential for excellent cosmetic outcomes.

Use of 2-octyl cyanoacrylate together with a self-adhering mesh (Dermabond™ Prineo™) for skin closure following abdominoplasty: an open, prospective, controlled, randomized, clinical study.

BACKGROUND: Abdominoplasty is one of the most commonly performed procedures in plastic surgery. The appearance of the scar is a major factor that contributes to the aesthetic outcome of the procedure and depends largely on the technique of wound closure. The new Prineo™ wound closure system was introduced to combine the effectiveness of 2-octyl cyanoacrylate (Dermabond™) together with a self-adhering mesh. METHODS: Fifty-two women and eight men aged between 21 and 65 years who were scheduled for abdominoplasty were included in the study. The total operating times after abdominoplasty of the traditional wound closure technique and the Prineo™-type wound closure technique were compared. Furthermore, an analysis comparing the cost of the two methods was performed. Two weeks after surgery the wounds were examined and graded using the Hollander Cosmesis Scale. At the 6- and 12-month follow-ups, the aesthetic outcome of the abdominal scar was evaluated using the Vancouver Scar Scale. Twelve months after surgery, the patients were asked to answer their part of the Patient Scar Assessment Scale. RESULTS: The mean total operating time for the new skin closure system was statistically significantly shorter than that of intradermal sutures. The mean price difference per patient was 104.27 (134.79$) in favor of Prineo™. The Hollander Cosmesis Scale indicated a significantly more favorable overall result with Prineo™ at 2 weeks after surgery. The Vancouver Scar Scale demonstrated a better cosmetic outcome in favor of Prineo™ 6 and 12 months after surgery. The Patient Scar Assessment Scale scores 12 months after surgery indicated that the patients noted significantly less pain, thickness, and irregularity with Prineo™. CONCLUSION: Based on our results, we conclude that Prineo™ is a safe and effective substitute for superficial skin closure, with good cosmetic results and no increase in wound complications. The use of Prineo™ decreases operative time and cost and enhances the patient's postoperative comfort. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Protective effects of C5a blockade in sepsis.

Sepsis in humans is a difficult condition to treat and is often associated with a high mortality rate. In this study, we induced sepsis in rats using cecal ligation and puncture (CLP). In rats depleted of the complement factor C3, CLP led to very short survival times (about 4 days). Of the rats that underwent CLP ('CLP rats') that were C3-intact and treated with preimmune IgG, most (92%) were dead by 7 days. Blood neutrophils from these rats contained on their surfaces the powerful complement activation product C5a. This group had high levels of bacteremia, and their blood neutrophils when stimulated in vitro had greatly reduced production of H2O2, which is known to be essential for the bactericidal function of neutrophils. In contrast, when companion CLP rats were treated with IgG antibody against C5a, survival rates were significantly improved, levels of bacteremia were considerably reduced, and the H2O2 response of blood neutrophils was preserved. Bacterial colony-forming units in spleen and liver were very high in CLP rats treated with preimmune IgG and very low in CLP rats treated with IgG antibody against C5a, similar to values obtained in rats that underwent 'sham' operations (without CLP). These data indicate that sepsis causes an excessive production of C5a, which compromises the bactericidal function of neutrophils. Thus, C5a may be a useful target for the treatment of sepsis.

Is there a risk for bacterial transmission from surgical marker pens?

Markers for preoperative skin marking are used several times and bear a risk of transmitting bacteria. Bacterial contamination was assessed by sonication and culture. Antimicrobial susceptibility testing (AST) was performed for facultative pathogens to assess multi-drug resistance (MDR). An accelerated failure time model was applied to assess the statistical relationship between the bacterial contamination and the filling status of markers. Of 45 markers, 13 had a colony count <10 cfu/mL and 32 had counts from 10 to 12,500 cfu/mL. Three markers were colonized by Staphylococcus aureus. No MDR bacteria were found. We recommend single use of markers to reduce transmission risk.

Protective effects of an aptamer inhibitor of neutrophil elastase in lung inflammatory injury.

Neutrophils play an important part in the development of acute inflammatory injury. Human neutrophils contain high levels of the serine protease elastase, which is stored in azurophilic granules and is secreted in response to inflammatory stimuli. Elastase is capable of degrading many components of extracellular matrix [1-4] and has cytotoxic effects on endothelial cells [5-7] and airway epithelial cells. Three types of endogenous protease inhibitors control the activity of neutrophil elastase, including alpha-1 protease inhibitor (alpha-1PI), alpha-2 macroglobulin and secreted leukoproteinase inhibitor (SLPI) [8-10]. A disturbed balance between neutrophil elastase and these inhibitors has been found in various acute clinical conditions (such as adult respiratory syndrome and ischemia-reperfusion injury) and in chronic diseases. We investigated the effect of NX21909, a selected oligonucleotide (aptamer) inhibitor of elastase, in an animal model of acute lung inflammatory disease [11-14]. This inhibitor was previously selected from a hybrid library of randomized DNA and a small-molecule irreversible inhibitor of elastase (a valine diphenyl ester phosphonate, Fig. 1), by the blended SELEX process [15]. We show that NX21909 inhibits lung injury and neutrophil influx in a dose-dependent manner, the first demonstration of efficacy by an aptamer in an animal disease model.

Requirement and role of C5a in acute lung inflammatory injury in rats.

The complement activation product, C5a, may play a key role in the acute inflammatory response. Polyclonal antibody to rat C5a was used to define the requirements for C5a in neutrophil-dependent inflammatory lung injury after systemic activation of complement by cobra venom factor (CVF) or after intrapulmonary deposition of IgG immune complexes. In the CVF model, intravenous infusion (but not intratracheal instillation) of anti-C5a produced a dose-dependent reduction in lung permeability and in lung content of myeloperoxidase. In C6-deficient rats, CVF infusion caused the same level of lung injury (measured by leak of 125I-albumin) as found in C6-sufficient rats. In the IgG immune complex model of lung injury, anti-C5a administered intratracheally (but not intravenously) reduced in a dose-dependent manner both the increase in lung vascular permeability as well as the buildup of lung myeloperoxidase. Treatment with anti-C5a greatly suppressed upregulation of lung vascular intercellular adhesion molecule-1 (ICAM-1). This was correlated with a substantial drop in levels of TNFalpha in bronchoalveolar fluids. These data demonstrate the requirement for C5a in the two models of injury. In the IgG immune complex model, C5a is required for the full production of TNFalpha and the corresponding upregulation of lung vascular ICAM-1.

Epidemiologic and age-dependent data on multiple myeloma in Austria.

The mortality rates for multiple myeloma showed an increasing trend between 1969 and 1979, when multiple myeloma accounted for 6% of the reported cancer deaths in Austria. The median age at diagnosis was relatively high: 68.5 years for males and 69.0 years for females. The age-corrected male:female ratio of 1.23:1 indicated a higher incidence of multiple myeloma in males. Age-standardized (standard population for Europe) incidence rates amounted to 1.5/100,000 male inhabitants and 1.2/100,000 female inhabitants/year. In subsample of patients with multiple myeloma, the paraprotein types as well as the k:lambda ratio resembled the frequency distribution of normal immunoglobulins. There were no age-related differences for the stages of the disease and the poor risk factors at diagnosis for patients 85 years old or younger or for those over 65 years of age at diagnosis. Survival rates were significantly higher for younger patients than for older ones, with a 50% survival time of 45 and 26 months, respectively. The differences resulted solely from the dissimilar general life expectancies in both groups, and survival rates with strict regard to multiple myeloma proved to be identical in younger and older patients.

Role of complement in in vitro and in vivo lung inflammatory reactions.

Complement is one of the integral buttresses of the inflammatory response. In addition to host defense activities, proinflammatory properties of several complement components are described. This overview elucidates the role of complement in inflammatory reactions in vitro and in vivo, focusing on the complement activation products, C5a, and the membrane attack complex, C5b-9. Using several approaches, the impact of these complement components in mechanisms relevant to neutrophil recruitment is emphasized. In addition, the participation of complement in endothelial superoxide generation and its essential requirement for full expression of lung injury is demonstrated, as are the involved intracellular signal transduction pathways. Understanding the mechanisms of complement-induced proinflammatory effects may provide a basis for future therapeutic blockade of complement and/or its activation products.

A Multiple Regression Analysis of Postoperative Complications After Body-Contouring Surgery: a Retrospective Analysis of 205 Patients : Regression Analysis of Complications.

BACKGROUND: As bariatric surgery becomes ever more popular, so does body-contouring surgery to eliminate excess skin after radical weight loss. To date, the literature has described a number of risk factors affecting the postoperative outcome. Our study aimed to define those factors more closely, focusing on abdominoplasty ("tummy tuck") patients who suffered intra- and postoperative complications. METHODS: The study collective included 205 patients over 5 years (2001-2006) who underwent dermolipectomy at our department. The mean follow-up was 5.94 years. Every abdominoplasty was performed under general anesthesia with intraoperative one-dose antibiotic. The analysis included a complete review of all medical records. Statistical analysis was performed with the R-2.5.0 Software for Windows. RESULTS: The overall rate for major complications that required operative revision and/or antibiotics was 10.2 %, including 2.9 % cases of infections. Forty-one percent had minor complications, such as seromas, hematomas, wound healing problems, and wound dehiscences. The logistic regression models demonstrated that smoking combined with the age, a BMI higher than 30 kg/m(2), and the amount of removed tissue (measured in g) lead to significantly more wound healing problems in nearly all age groups. The probability of infections correlated with later drain removal. CONCLUSIONS: Regardless of the amount of tissue removed, no main risk factor for complications could be identified. A complication-free course and good outcome can be best achieved with careful patient selection and preoperative planning.

A pharmacogenetic study of uridine diphosphate-glucuronosyltransferase 2B7 in patients receiving morphine.

We investigated the variation in the uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7) gene in patients receiving patient-controlled analgesia with morphine. UGT2B7 was sequenced in phenotypic extremes (n = 12) of the distribution of morphine-6-glucuronide/morphine plasma ratios. A new -161C/T promoter variant was in complete linkage disequilibrium with the 802C/T variant and was more frequent in low glucuronidators (P =.039). Both variants were genotyped in all patients (n = 86), and complete linkage disequilibrium was confirmed. Trend analysis showed reduced morphine-6-glucuronide/morphine ratios in patients with T/T, C/T, and C/C genotypes (T/T > C/T > C/C) (P =.031). Morphine levels were lower in T/T patients (median, 18 ng/mL [range, 18-1490 ng/mL]) as compared with C/T and C/C patients combined (median, 66 ng/m; range, 18-3995 ng/mL) (P =.04). Morphine-6-glucuronide and morphine-3-glucuronide concentrations were significantly lower in C/C patients (median, 18 ng/mL; range, 0-66 ng/mL; and median, 152 ng/mL; range, 30-434 ng/mL; respectively) compared with C/T and T/T patients combined (median, 43 ng/mL; range, 0-193 ng/mL; and median, 242 ng/mL; range, 33-1381 ng/mL; respectively) (P =.045 and P =.004, respectively). Interindividual differences in morphine glucuronidation may be the result of genetic variation in UGT2B7, and further studies are indicated.

A variable intron distribution in globin genes of Chironomus: evidence for recent intron gain.

The intron positions found in globin genes of plants, protozoa and invertebrates have been interpreted as evidence for a three-intron-four-exon structure of the ancestral globin gene. In particular, the so-called 'central' introns, which are not found in vertebrate globin genes but are present in a variety of invertebrate and plant species, have been used as an argument for an ancestral gene structure featuring three introns. We have analyzed the presence or absence of central introns in the Gb genes 2beta, 9 and 7A of various European and Australasian species of the insect Chironomus. We find unrelated central introns at different positions in some of the species investigated, while other species completely lack introns in these genes. This variable distribution of introns is parsimoniously explained by independent intron additions. Such a gain of introns may occur convergently at identical positions in unrelated taxa. Insertion by gene conversion may be a viable mechanism to explain intron gain.

Lung injury and complement activation: role of neutrophils and xanthine oxidase.

Evidence is presented that oxygen products generated from xanthine oxidase (XO) may also be involved in the pathogenesis of neutrophil-mediate lung injury following intravascular activation of complement with cobra venom factor (CVF). CVF injection in rats resulted in a rapid increase in plasma of both XO activity (but not xanthine dehydrogenase) and its reaction product, uric acid. These changes were greatly attenuated in allopurinol-treated animals. The appearance of XO activity was paralleled by a rise in plasma of histamine. Prevention of histamine release by pretreatment of rats with cromolyn abolished both the rise in plasma histamine and the increase in XO activity. Since we have previously shown that histamine can enhance XO activity in vitro and in vivo (Am. J. Pathol. 135:203, 1989), these observations suggest that the increase in plasma XO activity following CVF injection is related to the appearance in plasma of histamine. Accordingly, pretreatment of rats with xanthine oxidase inhibitors (allopurinol, lodoxamide) or prevention of histamine release by pretreatment with cromolyn significantly attenuated development of lung injury following injection of CVF. Our data support the concept that oxygen radicals derived from both neutrophils and XO are playing a role in the CVF-induced acute lung injury.

Xanthine oxidase and superoxide radicals in portal triad crossclamping-induced microvascular reperfusion injury of the liver.

Although reactive oxygen metabolites may play a pivotal role in mediating microvascular reperfusion injury, the source of these radicals is still a matter of controversy. With the use of spectrophotometry and intravital microscopy we studied the role of xanthine oxidase and superoxide radicals in portal triad crossclamping-induced microvascular injury in rats. After 20 min of global hepatic ischemia and splanchnic vascular congestion, followed by 40 min of reperfusion (n = 8), xanthine oxidase activities in hepatic venous (26.9 +/- 4.7 nmol/ml x min) and systemic arterial blood (16.3 +/- 2.5 nmol/ml x min) were found significantly (p < .01) increased when compared with sham-operated controls (6.8 +/- 0.9 and 6.0 +/- 0.8 nmol/ml x min, n = 8). The increase of xanthine oxidase activity was accompanied by oxygen radical-mediated intravascular hemolysis. Intravital microscopy (n = 6) revealed accumulation of leukocytes within the postischemic hepatic microvasculature with stasis in sinusoids (75.9 +/- 8.9 per liver lobule) and adherence to the endothelial lining of postsinusoidal venules (534.7 +/- 125.3 per mm2 endothelial surface). Concomitantly, compromised microvascular reperfusion was characterized by perfusion deficits of individual sinusoids (25.6 +/- 4.0% nonperfused sinusoids). The xanthine oxidase inhibitor allopurinol (50 mg/kg b.wt., orally, n = 6) and the radical scavenger superoxide dismutase (60000 IU/kg b.wt., IV, n = 6) effectively (p < .01) inhibited both sinusoidal leukostasis (16.1 +/- 2.6 and 32.1 +/- 3.1 cells/lobule) and venular leukocyte adherence (247.6 +/- 7.9 and 205.0 +/- 38.0 cells/mm2), and, hence, reduced microcirculatory deteriorations, indicated by the attenuation of sinusoidal perfusion failure (2.8 +/- 0.8 and 9.0 +/- 3.1%). Our results support the hypothesis that portal triad crossclamping-induced microvascular reperfusion injury is triggered by superoxide radicals derived from the xanthine oxidase system.

Cigarette smoke elicits leukocyte adhesion to endothelium in hamsters: inhibition by CuZn-SOD.

Although cigarette smoking has been identified as a major risk factor for cardiovascular diseases, the underlying pathomechanism is largely unknown. Using a dorsal skinfold chamber model in Syrian golden hamsters for intravital microscopy on striated muscle microcirculation, we investigated whether cigarette smoke (CS) affects the adhesion of circulating leukocytes to the endothelium, a constant feature of early atherogenesis and a hallmark of ischemia-reperfusion injury. Awake hamsters were exposed for 5 min to the mainstream smoke of one cigarette (2R1 research cigarette), inducing nicotine, cotinine, and carboxyhemoglobin plasma levels comparable to levels found in human smokers. In control animals (n = 7), CS exposure elicited the rolling and subsequent adhesion of fluorescently stained leukocytes to the endothelium of arterioles and postcapillary venules. Leukocyte/endothelium interaction was preceded by an early rise in xanthine oxidase activity and intravascular hemolysis. Leukocyte adhesion and xanthine oxidase (XO) activation were significantly attenuated in hamsters pretreated with superoxide dismutase (5 mg/kg, 10 min prior to CS, n = 7), suggesting a key role of superoxide in this event. These in vivo results suggest a novel pathomechanism of CS-induced cardiovascular pathology.

Incidence of cancer of the respiratory and upper digestive tract in urban and rural eastern Austria.

The incidence of head and neck, oesophagus and lung cancer between 1981 and 1985 was studied in Eastern Austria for an urban-rural division. In males, rural rates of oral cavity, oropharynx and oesophagus tumours were higher than urban rates. For lung tumours, urban rates slightly exceeded rural rates. In females, the incidence of oral cavity, oropharynx, larynx, hypopharynx, oesophagus and lung cancer showed an urban predominance, steepest for head and neck and oesophagus cancers. Cancer of the oral cavity, pharynx, larynx, oesophagus and lung had a high male preponderance.

Childhood leukaemia following the Chernobyl accident: the European Childhood Leukaemia-Lymphoma Incidence Study (ECLIS).

The objective of the European Childhood Leukaemia-Lymphoma Incidence Study (ECLIS) is to investigate trends in incidence rates of childhood leukaemia and lymphoma in Europe, in relation to the exposure to radiation which resulted from the accident at the Chernobyl nuclear power plant in April 1986. In this first report, the incidence of leukaemia in children aged 0-14 is presented from cancer registries in 20 European countries for the period 1980-1988. Risk of leukaemia in 1987-1988 (8-32 months post-accident) relative to that before 1986, is compared with estimated average dose of radiation received by the population in 30 geographic areas. The observed changes in incidence do not relate to exposure. The period of follow-up is so far rather brief, and the study is planned to continue for at least 10 years.

Requirement for C5a in lung vascular injury following thermal trauma to rat skin.

Previous studies in rats have shown that deep second degree dermal burns, involving 28-30% of total body surface area, result in systemic complement activation, appearance in plasma of chemotactic activity, sequestration of blood neutrophils in lung capillaries, and development of neutrophil-dependent dermal vascular and lung vascular injury. Although blockade of complement activation or depletion of complement before skin burns has resulted in significant attenuation of tissue injury both locally and distally (in lung), a role for C5a in these events is unclear. In the following studies, we demonstrate the presence of C5a and neutrophil chemotactic activity in serum and in lung homogenates after thermal injury. C5a has also been found in bronchoalveolar lavage fluids of thermally injured animals. Treatment of animals with a polyclonal neutralizing rabbit antibody to rat C5a was lung protective. The protective effects of the antibody (anti-C5a) were associated with diminished vascular permeability changes, as well as reduced tissue build-up of myeloperoxidase. Anti-C5a also prevented up-regulation of lung vascular ICAM-1 (intercellular adhesion molecule-1) in skin-burned rats. These observations indicate that C5a is essential for development of neutrophil accumulation and vascular permeability increases in distant (lung) organs after thermal trauma to skin. The protective effects of anti-C5a in lung, appear to be related to prevention of up-regulation of vascular ICAM-1. Accordingly, C5a may represent a target for clinical approaches in the treatment of organ injury following thermal trauma.

Tobacco-related cancer in relation to prevalence of drinking and smoking in eastern Austria.

Eastern Austrian regional mortality patterns of oral cancer (oral cavity, pharynx and larynx) and oesophageal, lung and urinary bladder cancer were compared to smoker rates and to liver cirrhosis mortality by type of residence: Vienna (1.7 x 10(6) inhabitants), middle towns (50,000-100,000 and 10,000-50,000 inhabitants), small towns (2000-10,000 inhabitants) and rural areas categorized by agrarian quota less than or equal to 10%, 10%-20% and greater than 20%. The study area (Vienna, Lower Austria and Burgenland) covers 23,600 km2 with 3.23 x 10(6) inhabitants. In men, liver cirrhosis correlated negatively with smoker rates (r = 0.74, P = 0.1). Deaths from oral cancer and oesophageal cancer correlated significantly with deaths from liver cirrhosis (r = 0.81, P = 0.03; r = 0.78, P = 0.04, respectively) but not with smoker rates; lung cancer and bladder cancer correlated significantly with smoker rates (r = 0.91, P = 0.01; r0.83, P = 0.04, respectively), but not with liver cirrhosis. In women, similar urban-rural gradients for all parameters resulted in a positive correlation between liver cirrhosis and smoker rates (r = 0.59, P = 0.22) and a significant correlation of lung cancer with liver cirrhosis (r = 0.75, P = 0.05). Oral cancer correlated significantly with liver cirrhosis (r = 0.83, P = 0.02), but not with smoker rates; lung cancer correlated more significantly with smoker rates (r = 0.92, P = 0.01) than with liver cirrhosis; bladder cancer correlated positively with smoker rates (r = 0.70, P = 0.12). Geographical distribution of oral and oesophageal cancer in Eastern Austria seems thus to be highly subject to the prevalence of heavy drinking. Sociocultural influences upon the occurrence of these cancers seem to be mediated through drinking habits rather than through smoking habits alone.

Insulin receptor binding to erythrocytes in the first half of pregnancy is increased in healthy pregnant women as compared with non-pregnant or gestational diabetic women.

Insulin binding to erythrocytes was measured longitudinally by a competitive radioreceptor assay in 21 healthy pregnant (HP) and 20 well-controlled gestational diabetic women (GD) in 4-week intervals throughout pregnancy and at day 4 post-partum. Maximum insulin binding (maxbdg) at weeks 8-14 was increased (P < 0.001) in HP (median: 6.0%) but not in GD (median: 2.7%) as compared with non-pregnant control subjects (C) (median: 3.6%; previously reported: Clin. Chim. Acta 1992;207:57-71) due to an increased number of high-affinity insulin receptors. Throughout gestation the binding decreased continuously, to reach at term the levels found in C. In GD maxbdg remained close to the level of C throughout pregnancy. Binding differences between HP and GD were independent of the body mass index. Maxbdg did not differ between diet- and insulin-treated patients. It was higher in women whose offspring had low umbilical cord insulin levels (< 10 mu units/ml). The findings suggest that (a) higher insulin binding in HP could contribute to the improved glucose tolerance in early pregnancy and (b) the lack of increase in insulin binding during early pregnancy in gestational diabetes might be one factor leading to the manifestation of the disease in late pregnancy. However, it must be kept in mind that insulin receptors on erythrocytes do not necessarily resemble those on the major target tissues of insulin.