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The article draws attention to the problem of the presence of metals: germanium (Ge), tellurium (Te), thallium (Tl), and others (Cd, Ba, Co, Mn, Cr, Cu, Ni, Pb, Sr, and Zn) in selected waste of electrical and electronic equipment (WEEE). As a result of the growing demand for new technologies, the global consumption of TECs has also been increasing. Thus, the amount of metals in circulation, of which the impacts on the environment have not yet been fully understood, is constantly increasing. Due to the low content of these metals in WEEE, they are usually ignored during e-waste analyses. The main aim of this study was to determine the distribution of Ge, Te, and Tl (and other elements) in ground sieve fractions (1.0, 0.5, 0.2, and 0.1 mm) of selected electronic components (solar lamps, solar cell, LED TV screens, LCD screens, photoresistors, photodiodes, phototransistors) and to determine the possible tendency of the concentrations of these metals in fractions. This problem is particularly important because WEEE recycling processes (crushing, grinding, and even collection and transport operations) can lead to dispersion and migration of TCE pollutants into the environment. The quantitative composition of e-waste was identified and confirmed by ICP-MS, ICP-OES and SEM-EDS, and XRD analyses. It was found that Ge, Te, and Tl are concentrated in the finest fractions of ground e-waste, together with Cd and Cr, which may favor the migration of these pollutants in the form of dust during storage and processing of e-waste.

Background: The Micra leadless pacemaker (MLP) has proven to be an effective alternative to a traditional transvenous pacemaker (TVP). However, there has been concern about using the MLP in frail elderly patients because of the size of the implant sheath and perceived risk of perforation., Objectives: The objectives of this study were to report the safety of the MLP and compare MPLs with TVPs in the very elderly., Methods: All patients 85 years and older who received an MLP or a single-chamber TVP across 6 hospitals in the Northwell Health system from December 2015 to November 2019 were included. Demographic characteristics, procedural details, and procedure-related complications were reviewed., Results: Over 4 years, 564 patients underwent MLP implantation. During this time, 183 MLPs and 119 TVPs were implanted in patients 85 years and older. The mean age was 89.7 ± 3.4 years, and 47.4% were men. MLP implantation was successful in all but 3 patients (98.4% success rate). There was no difference in procedure-related complications (3.3% vs 5.9%; P = .276). Complications included 5 (2.7%) access site hematomas in the MLP group, 3 (2.5%) in the TVP group, 1 (0.5 vs 0.8%) pericardial effusion in each group, and 3 (2.5%) acute lead dislodgments (<24 hours) in the TVP group. MLP implantation resulted in a significantly shorter mean procedure time (35.7 ± 23.0 minutes vs 62.3 ± 31.5 minutes, P < .001)., Conclusion: In a large multicenter study of patients 85 years and older, MLP implantation (1) was successful in 98.4% of patients, (2) was safe with no difference in procedure-related complications compared to the TVP group, and (3) resulted in significantly shorter procedure times., (Published by Elsevier Inc.)

Background: Idiopathic ventricular arrhythmias (IVAs) from the left ventricular (LV) summit may be successfully ablated from the distal great cardiac vein (dGCV). Using a 12-lead electrocardiogram (ECG) to localize IVAs that can be ablated from the dGCV is valuable for ablation planning., Objective: To determine if a "w" wave, a notch in the Q wave in lead I, and other ECG features can identify IVAs that can be successfully ablated from the dGCV., Methods: We reviewed outflow tract premature ventricular contraction (PVC) ablations performed at two centers between September 2010 and June 2018. Successful PVC ablations, in which the PVCs were mapped from the right ventricular outflow tract, coronary cusps, commissures, endocardial LV, and the coronary venous system including the dGCV were included. ECG characteristics were compared between patients with successful ablations in the dGCV and non-dGCV sites., Results: Of the 120 patients (age 56.8 ± 13.8 years, 45% female) that met the inclusion criteria, the dGCV was the successful ablation site in 18 patients (15%). Multivariate analysis with binary logistic regression showed that a "w" in lead I in combination with an early precordial pattern break and a maximum deflection index (MDI) ≥ 0.5 had sensitivity and specificity for a successful ablation in the dGCV of 94.4% and 96.1%, respectively., Conclusion: Combining a "w" wave in lead I with an early precordial pattern break and an MDI ≥ 0.5 is highly sensitive and specific for identifying the dGCV as a successful ablation site for PVCs., (© 2020 Wiley Periodicals LLC.)

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040. 1 ., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

The implantable loop recorder (ILR) is a valuable tool used in the evaluation of syncope, arrhythmia, and cryptogenic stroke. In the inpatient setting, ILRs are routinely implanted in the electrophysiology (EP) lab despite the low complication rate. The purpose of this study was to evaluate the safety, feasibility, and cost of implanting ILRs at the patient's bedside by both electrophysiologists and advanced practice providers (APPs). This was a single center, retrospective study of consecutive ILR implantations performed from February 2018 to May 2019. We examined 3 groups: implantations in the EP lab by electrophysiologists (EP Lab/MD), implantations at the bedside by electrophysiologists (Floor/MD), and implantations at the bedside by APPs (Floor/APP). Over 15 months, 152 patients underwent ILR implantation: 48 in the EP Lab/MD group, 57 in the Floor/MD group, and 47 in the Floor/APP group. The procedure duration was longer in the Floor/APP group (14.2 ± 5.9 minutes) compared with the EP Lab/MD and Floor/MD groups (6.8 ± 4.3 minutes, 9.1 ± 4.9 minutes, p <0.001). The overall complication rate was low (2.6%) with no differences between the groups (p = 0.83). The calculated costs per implant for the EP Lab/MD group, Floor/MD group, and Floor/APP group were $482.05, $162.82, and $73.08, respectively., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is responsible for the global coronavirus disease 2019 pandemic. Small studies have shown a potential benefit of chloroquine/hydroxychloroquine±azithromycin for the treatment of coronavirus disease 2019. Use of these medications alone, or in combination, can lead to a prolongation of the QT interval, possibly increasing the risk of Torsade de pointes and sudden cardiac death., Methods: Hospitalized patients treated with chloroquine/hydroxychloroquine±azithromycin from March 1 to the 23 at 3 hospitals within the Northwell Health system were included in this prospective, observational study. Serial assessments of the QT interval were performed. The primary outcome was QT prolongation resulting in Torsade de pointes. Secondary outcomes included QT prolongation, the need to prematurely discontinue any of the medications due to QT prolongation, and arrhythmogenic death., Results: Two hundred one patients were treated for coronavirus disease 2019 with chloroquine/hydroxychloroquine. Ten patients (5.0%) received chloroquine, 191 (95.0%) received hydroxychloroquine, and 119 (59.2%) also received azithromycin. The primary outcome of torsade de pointes was not observed in the entire population. Baseline corrected QT interval intervals did not differ between patients treated with chloroquine/hydroxychloroquine (monotherapy group) versus those treated with combination group (chloroquine/hydroxychloroquine and azithromycin; 440.6±24.9 versus 439.9±24.7 ms, P =0.834). The maximum corrected QT interval during treatment was significantly longer in the combination group versus the monotherapy group (470.4±45.0 ms versus 453.3±37.0 ms, P =0.004). Seven patients (3.5%) required discontinuation of these medications due to corrected QT interval prolongation. No arrhythmogenic deaths were reported., Conclusions: In the largest reported cohort of coronavirus disease 2019 patients to date treated with chloroquine/hydroxychloroquine±azithromycin, no instances of Torsade de pointes, or arrhythmogenic death were reported. Although use of these medications resulted in QT prolongation, clinicians seldomly needed to discontinue therapy. Further study of the need for QT interval monitoring is needed before final recommendations can be made.

Introduction: The need for transvenous lead extractions due to cardiac implantable electronic device (CIED)-related infections continues to rise. Current guidelines recommend complete device removal in the setting of an active infection, which can be challenging in pacemaker-dependent patients., Methods: We retrospectively reviewed all leadless pacemaker implants between January 2018 and November 2019 and identified a subset of patients who had undergone a concomitant CIED extraction in the setting of an active infection. Baseline characteristics, procedural details, and clinical follow-ups were recorded., Results: Seventeen patients received a leadless pacemaker during the same procedure as the CIED extraction. There were no procedural complications. All patients were being treated for an active CIED infection at the time of the procedure. Fourteen patients (82.4%) were completely pacemaker-dependent and four patients (23.5%) had positive blood cultures at the time of the leadless pacemaker implantation. During a median follow-up of 143 days (interquartile range: 57, 181 days), there were no recurrent infections., Conclusion: Simultaneous leadless pacemaker implantation and CIED extraction are safe and feasible in the setting of an active infection. This strategy may be particularly useful in patients that are pacemaker-dependent., (© 2020 Wiley Periodicals, Inc.)

Escape mapping is a novel technique that can be used to locate sites of persistent conduction and achieve exit block during an atrial fibrillation ablation. This method allows for mapping solely with the ablation catheter in the left atrium by annotating to a catheter in the coronary sinus. We illustrate the utility escape mapping during an atrial fibrillation ablation where entrance block is achieved without exit block. We further expand upon this technique by describing the first reported case of escape mapping being used to achieve bidirectional block during an atrial flutter ablation., (© 2018 Wiley Periodicals, Inc.)

Purpose of Review: A variety of complex vascular pathologies arise following the implantation of electronic cardiac devices. Pacemaker and defibrillator lead insertion may cause proximal venous obstruction, resulting in symptomatic venous congestion and the compromise of potential future access sites for cardiac rhythm lead management., Recent Findings: Various innovative techniques to recanalize the vein and establish alternate venous access have been pioneered over the past few years. A collaborative team of electrophysiologists and vascular specialists strategically integrate the patient's vascular disease into the planning of electrophysiology procedures. When vascular complications occur after device implantation, the same team effectively manages both the resulting vascular sequelae and related cardiac rhythm device challenges. This review will outline the various vascular challenges related to device therapy and offer an effective strategy for their management.

Purpose: Paroxysmal supraventricular tachycardia (PSVT) ablation can result in injury to the atrioventricular (AV) node causing complete heart block requiring permanent pacemaker (PPM) implantation. Few studies have examined the impact of hospital PSVT ablation volume and PPM implantation rates post ablation., Methods: We included adult patients from the Nationwide Inpatient Sample (NIS) database, from 1998 to 2011, using ICD-9 diagnoses codes 427.0 and 427.89 for PSVT and ICD-9 procedure code 37.34 for ablation. Patients with concomitant arrhythmias, prior pacemaker/defibrillator implants, or pre-existing sinus node dysfunction were excluded. Multivariate logistic regression analysis was performed to identify predictors of PPM implantation., Results: There were 119,938 PSVT ablations from 1998 to 2011 with a mean age of 54.6 ± 17.5 years and 64.1% females. The overall PPM implantation rate was 3.2%. PPM implantation rates in the first (1-14 ablations/year), second (15-32 ablations/year), and third (> 32/ablations/year) tertiles of annual PSVT ablation volume were respectively 4.4, 3.3, and 1.9% (p < 0.001). Increasing age, female gender, bifascicular, or trifascicular block and teaching hospital status were independent predictors of PPM implantation. The adjusted odds ratio for PPM implantation in hospitals performing > 32 PSVT ablations/year compared to hospitals performing ≤ 14 PSVT ablations/year was 0.54 (95% confidence interval 0.3-0.9, p = 0.026)., Conclusions: PPM implantation rates are significantly lower in hospitals performing > 32 PSVT ablations/year, indicating that hospital experience is an important determinant of outcomes after PSVT ablation.

Atrial fibrillation is the most common sustained cardiac arrhythmia and is associated with a high risk of stroke and thromboembolism. Increasing evidence suggests that the thrombogenic tendency inherent to atrial fibrillation is related to several underlying pathophysiological mechanisms, including reduced flow in the left atrium, changes in vessel walls, and changes in blood constituents. This article reviews the mechanisms of stroke, available risk stratification tools and therapies available for prevention of stroke in patients with atrial fibrillation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Choroideremia is an X-linked recessive disorder characterized by vision loss with progressive atrophy of the retinal photoreceptors, retinal pigment epithelium (RPE), and choriocapillaris. Ectodermal dysplasia is a heterogeneous group of disorders characterized by a deficiency of two or more ectodermal derivatives. We report on the phenotypic and genetic characteristics of a 29-year-old woman with both choroideremia and ectodermal dysplasia., Materials and Methods: Observational case report with physical and ophthalmic examination, fluorescein angiography (FA), visual field testing, electroretinography, and cytogenetic analysis. This study adhered to the tenets of the Declaration of Helsinki and The New York Eye and Ear Infirmary Institutional Review Board guidelines., Results: Physical and ocular examination revealed hypotrichosis, hypohidrosis, full dentures, meibomian gland hypoplasia, and a decrease in corneal tear film. Visual acuity was hand motions in the right eye and 20/50 in the left eye. Fundus examination and fluorescein angiography were consistent with advanced choroideremia and revealed diffuse bilateral RPE and chorioretinal atrophy with sparing of the fovea. Visual field testing had less than 10-degree central islands in both eyes. Scotopic electroretinogram (ERG) was flat with a small flicker response. Cytogenetic analysis showed a complex translocation involving chromosomes X, 1, and 3: 46,X,t(X;1;3)(q13;q24;q21),inv(9)(p11q13). Selective inactivation of the normal X chromosome was present in blood and skin. Chromosomal analyses of the proband's family (mother and two brothers) were normal., Conclusion: An X-autosome chromosomal translocation combined with non-random inactivation of the normal X-chromosome in a woman resulted in the phenotypic findings of choroideremia and ectodermal dysplasia.

The polyp hydra is ubiquitous in freshwater and is highly variable, with many species names assigned to different strains. Types of hydra do fall into four morphologically recognizable groups but many of the species determinations are confusing. To assess the diversity of hydra we collected 101 strains from six continents and built a phylogeny using three genetic markers. Each of the four well-defined groups of species represents a clade in our phylogeny. The green hydra group diverged first, followed by the braueri group and finally the sister groups vulgaris and oligactis. Each of eight species easily definable by morphological criteria represents a distinct clade in our phylogeny. Hydra of two clades, the green and the vulgaris hydra, are found on all continents (except Antarctica) and many islands, whereas hydra of the other two groups (braueri and oligactis) are restricted to the Northern Hemisphere. Our best estimate of the time of origin of hydra is about 60 Ma, long after the breakage of Pangea into northern and southern landmasses. Hydra appear to have diversified in the Northern Hemisphere, and their current diversity is greatest here. Two species were then able to disperse to the Southern Hemisphere, perhaps due to their thermal tolerance., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: To compare local control, disease-free survival and overall survival after postoperative radiochemotherapy with or without total mesorectal excision (TME) in a retrospective analysis., Patients and Methods: Between 1993 and 2002, 103 patients with UICC stage II and III rectal cancer were treated by surgery and postoperative chemoradiation. Group B (n = 50; 1993-1998) were operated before TME era without using TME and group A (n = 53; 1998-2002) with TME; both groups received identical radiochemotherapy to a total dose of 50.4 Gy (median) and two courses of continuous 5-fluorouracil infusion., Results: Patients in group A (TME) showed a significant improvement in 5-year disease-free survival (71.1%; 46.8%) and freedom from distant metastases (76.3%; 46.9%) and a marked improvement of local control (85.2%; 62.5%). Acute and late toxicity were significantly less frequent in group A., Conclusion: Radiochemotherapy cannot compensate an insufficient surgical procedure. These data confirm that TME is the standard. High outcome quality can be achieved in daily practice compared to results of randomized studies without patient selection.

Objective: Cholecystectomy is the standard treatment for acute cholecystitis, but in high-risk patients with serious comorbidity and in patients of advanced age there is substantial morbidity and mortality associated with the intervention. In these selected patients, percutaneous cholecystostomy (PCS) is an alternative mode of management. The aim of the present study was to evaluate the outcome of PCS in selected patients with acute cholecystitis., Material and Methods: Thirty-five patients, representing 0.6% of all acute cholecystitis patients managed during the period 1994-2003, were subjected to PCS. Patients' charts were reviewed retrospectively for age, gender, comorbidity, hospital stay, procedure, complications and final outcome, including requirement of additional interventions., Results: PCS was considered successful in 34/35 patients, 26 of whom responded within 3 days. Two patients required additional cholecystectomy 3 days and 20 months, respectively, after the PCS procedure. Two patients underwent endoscopic retrograde cholangiopancreatography (ERCP) and one patient underwent rotation lithotripsy. Four patients suffered recurrent biliary complaints after the acute episode of cholecystitis, while the only serious procedure-related complication was bile leakage from the gallbladder in one patient, which necessitated cholecystectomy., Conclusions: PCS is a comparatively safe and efficient procedure in the treatment of acute cholecystitis in high-risk patients with serious comorbidity and in elderly patients, contraindicating the general anaesthesia required for laparoscopic or open cholecystectomy.

Objective: To assess the value and adverse effects of an ultrasound-guided renal biopsy technique in women with normal and pathologic pregnancies., Method: Biopsy samples were taken from 36 women with hypertensive disease (28 with pre-eclampsia) and 18 healthy pregnant women using a thin needle and an ultrasound-guided biopsy device., Results: Glomerular endotheliosis, a structural change typical of pre-eclampsia, was found in all hypertensive women, but it was more pronounced in the 28 pre-eclamptic women than in the 8 women with nonproteinuric hypertension. A similar change, however, was seen in 11 of the 18 controls. One serious adverse event occurred, retroperitoneal hematoma, in the woman with the most severe pre-eclampsia., Conclusion: Glomerular endotheliosis is not to be considered pathognomonic for pre-eclampsia. Few complications followed renal biopsy in this study, but complications arose in the sickest patient. It is probably not advisable to perform antepartum renal biopsies in pregnant women with a rapidly deteriorating renal function and swollen kidneys. In these women, the biopsy does not facilitate diagnosis and is hazardous.

Purpose: A patterns-of-care study of radiotherapy (RT) in prostate cancer was performed in Northern Bavaria, Germany, to characterize patient selection, treatment strategies and outcome for the time period 1998-2000., Material and Methods: Patients who received curative-intent radical or postoperative RT were identified from the databases of six centers (one university, five teaching/regional hospitals). Two centers treated < 20 patients and were excluded from further analysis. At the remaining four centers, 148 patients receiving radical RT and 134 undergoing postoperative RT were analyzed for pretreatment and RT characteristics and actuarial biochemical control (BC; ASTRO definition)., Results: All patients were treated with three-dimensional conformal external-beam techniques. In radical RT patients, cT- and cN-stages as well as the frequency of (neo)adjuvant hormonal therapy (53-91%) and RT to pelvic nodes (2-97%) and the mean total RT dose (64.8-71.0 Gy) varied significantly between centers. In postoperative RT, centers differed significantly in R-status, initial prostate-specific antigen (PSA) and nodal RT frequency (2-89%), whereas total RT doses were similar (62.3-64.8 Gy). After radical RT, 5-year BC was 68.6% and differed significantly between centers on univariate analysis. In a multivariate model, only total RT dose showed a trend toward an effect on BC. In postoperative RT patients, overall 5-year BC was 82.1%, and age and initial PSA were associated with BC on multivariate analysis., Conclusion: From 1998 to 2000, radical RT for prostate cancer at the Northern Bavarian centers now studied was performed with three-dimensional conformal technique to conservative total doses and selection criteria for postoperative RT were highly variable.

We evaluated alterations in p53, PIK3CA, PTEN, CTNNB1 (beta-catenin), MLH1, and BRAF among common histological subsets of epithelial ovarian tumors to characterize patterns of alterations of different molecular pathways. There were 12 clear cell, 26 endometrioid, and 51 serous carcinomas evaluated by direct DNA sequencing for mutations in p53, PIK3CA, PTEN, BRAF, and CTNNB1. Methylation-specific polymerase chain reaction (PCR) assessed MLH1 promoter methylation status. Quantitative PCR identified PIK3CA amplification in 22 EC/CC and 94 SC. p53 mutations were identified in 25 (49%) of 51 SC, 11 (42%) of 26 EC, and 1 (8.3%) of 12 CC neoplasms and were more common in grade 3 EC (P = .045) and advanced-stage EC/CC (P = .007). PIK3CA mutations were identified in 3 (25%) of 12 CC, 3 (12%) of 26 EC, and 0 of 51 SC. PTEN mutations were significantly more common in EC (8/26, 31%) compared with CC (0/12; P = .04) and SC (2/51, 4%; P = .002). CTNNB1 mutations were identified, 6 (23%) EC and no CC or SC (P = .008). Both PTEN and CTNNB1 mutations were more common in low-grade EC/CC, whereas PIK3CA mutations occurred only in grade 3 cancers. PTEN and PIK3CA mutations were more common in p53 wild-type tumors (P = .003). PIK3CA amplification occurred in fewer EC/CC (0/22) versus SC (19/94, 20%; P = 0.02) and were slightly more common in p53 wild-type compared with p53 mutant SC (P = .08). Of 26 EC, 22 (85%) had a mutation in one of the genes studied compared with 4 33% of 12 CC (P = .003). Women with EC/CC had significantly better overall survival (P = .0008), and this remained significant after accounting for stage (P=.04). Mutations in p53 or in PTEN/PIK3CA are alternative pathways in ovarian carcinogenesis. Activation of PIK3CA occurs by gene amplification in SC but via somatic mutation of PIK3CA or PTEN in EC and CC. PIK3CA mutations are associated with high-grade tumors, whereas PTEN and CTNNB1 mutations are associated with low-grade tumors. Mutations in p53, PIK3CA, PTEN, and CTNNB1 account for most EC tumors; most CC remain unexplained. EC/CC histology is a favorable prognostic factor.

The importance of somatic TP53 mutations and germline TP53 codon 72 genotype in the survival of women with epithelial ovarian cancer is controversial. Recent data suggest that a promoter polymorphism in the MDM2 gene may influence age of cancer onset in a gender-specific fashion. We sought to determine the relationship between somatic TP53 mutations, germline genotypes at TP53 codon 72 and MDM2 SNP309, and overall survival and response to chemotherapy in a large series of patients with ovarian and peritoneal carcinomas. Of the 188 cancers, 103 (54.8%) had a TP53 mutation, of which 71% were missense mutations and 29% were null mutations. TP53 mutation status and mutation type (null vs. missense) did not influence response to therapy or overall survival. Women with the codon 72 Pro/Pro had a decreased overall survival (median, 29 months) compared with women with one or two arginine alleles (median, 49 months; P=0.04). Somatic mutation or deletion was equally common for either codon 72 allele. Age of diagnosis was not influenced by codon 72 but showed a trend for younger age in women with somatic TP53 mutations and the MDM2 G/G genotype., (Copyright (c) 2006 Wiley-Liss, Inc.)

Purpose: Radiation enteritis is the main acute side-effect during pelvic irradiation. The aim of this study was to quantify the dose-volume relationship between irradiated bowel volumes and acute enteritis during combined chemoradiotherapy for rectal cancer., Material and Methods: Twenty-eight patients with locally advanced rectal cancer received chemoradiotherapy. The radiation therapy was given with a traditional multi-field technique to a total dose of 50 Gy, with concurrent 5-Fluorouracil (5-FU) and oxaliplatin (OXA) based chemotherapy. All patients underwent three-dimensional CT-based treatment planning. Individual loops of small and large bowel as well as a volume defined as "whole abdomen" were systematically contoured on each CT slice, and dose-volume histograms were generated. Diarrhea during treatment was scored retrospectively according to the NCR common Toxicity Criteria scale., Results: There was strong correlation between the occurrence of grade 2 + diarrhea and irradiated small bowel volume, most notably at dose > 15 Gy. Neither irradiated large bowel volume, nor irradiated "whole abdomen" volume correlated significantly with diarrhea. Clinical or treatment related factors such as age, gender, hypertension, previous surgery, enterostomy, or dose fractionation (1.8 vs. 2.0 Gy/fraction) did not correlate with grade 2 + diarrhea., Discussion: This study indicates a strong dose-volume relationship between small bowel volume and radiation enteritis during 5-FU-OXA-based chemoradiotherapy. These findings support the application of maneuvers to minimize small bowel irradiation, such as using a "belly board" or the use of IMRT technique aiming at keeping the small bowel volume receiving more than 15 Gy under 150 cc.

Evidence that NMDA receptors contribute to synaptic plasticity in the hippocampus has stimulated research on their role in behavioral learning and memory. Recent studies indicate that NMDA antagonists decrease use of place strategies by rats in a T-maze task that can be solved using either a "place" or "response" strategy. In the present study, rats were given MK-801 before maze exposure and/or training on this redundant strategy T-maze task. MK-801 did not impair rats' ability to learn the task, but did change the strategies they used on a probe trial administered after learning. MK-801 decreased use of place strategies only when administered before both maze exposure and training; rats given MK-801 only before maze exposure or only before training tended to use place strategies on the probe trial. These results show that MK-801 does not prevent rats from utilizing previously acquired spatial information, but does appear to impair the acquisition of spatial information needed for place strategies.

Purpose: The aim of this study was to examine whether, after preceding induction chemotherapy, simultaneous chemoradiotherapy is superior to radiotherapy alone., Patients and Methods: Patients with non-small-cell lung cancer in inoperable stage IIIA or IIIB received induction chemotherapy with two cycles of paclitaxel 200 mg/m2 and carboplatin area under the curve 6 every 3 weeks. Patients without progression at restaging after induction chemotherapy were randomly assigned to radiotherapy (60 Gy) or chemoradiotherapy (paclitaxel 60 mg/m2 weekly). The primary end point was overall survival; secondary end points were time to progression, response, and toxicity., Results: Three hundred three patients entered the study, and 276 completed induction chemotherapy. Two hundred fourteen patients were randomly assigned (radiotherapy alone: n = 113; simultaneous chemoradiotherapy: n = 101). Median follow-up time of all randomly assigned patients was 13.6 months (interquartile range [IQR], 6.4 to 29.0 months), and median follow-up time of the subgroup of censored patients (n = 52) was 37.4 months (IQR, 5.9 to 57.0 months; maximum, 76.1 months). Toxicities during the induction phase were mild. During radiotherapy, overall toxicity rates were not significantly different between the two arms. Median survival times in the radiotherapy group and chemoradiotherapy group were 14.1 months (95% CI, 11.8 to 16.3 months) and 18.7 months (95% CI, 14.1 to 23.3 months; difference not statistically significant, P = .091). Median time to progression significantly favored simultaneous chemoradiotherapy (11.5 months; 95% CI, 8.3 to 14.7 months) versus radiotherapy alone (6.3 months; 95% CI, 5.0 to 7.6 months; P < .001, log-rank test)., Conclusion: Induction chemotherapy followed by chemoradiotherapy with weekly paclitaxel is feasible. Response, time to progression, and survival favor chemoradiotherapy compared with radiotherapy alone.

Objective: Pancreatic pseudocyst is a common complication of both acute and chronic pancreatitis. The aim of the present study was to evaluate the efficacy and complications of different treatment regimens., Material and Methods: All patients > or =15 years of age admitted to Lund University Hospital from 1994 to 2003 with pancreatic pseudocysts were analysed retrospectively. Pseudocysts were defined according to the Atlanta classification., Results: Forty-four patients (29 M (66%), mean age 55+/-14 years) were included in the study, and all were subjected to treatment on 88 occasions. Mean size of pseudocysts at diagnosis was 9.6+/-6.8 cm (1.5-40 cm). Recurrence after treatment was 1.0+/-1.1 times (range 0-4). No difference was found in recurrence rate or pseudocyst size when comparing conservative versus interventional treatment, but patient weight was higher (p=0.013) and acute pancreatitis was more frequent (p=0.046) in conservatively treated patients. Surgical treatment tended to be associated with a lower recurrence rate as compared with percutaneous treatments. The rate of hospital admissions was a median 3 (0-16) and median length of stay (LOS) was 12 days (0-141 days). Six patients (14%) had complications and 3 died (7%). Pseudocysts > or =8 cm did not differ significantly from smaller pseudocysts regarding the choice of conservative treatment, LOS, recurrence and gastrointestinal obstruction, but there was a trend towards more complications in the group with larger pseudocysts (5 versus 1)., Conclusions: Patients with pancreatic pseudocysts require frequent hospital admissions and repeated treatments. Larger pseudocysts do not imply more recurrences. The lowest recurrence rate overall was seen after open surgery.

Hypoxia-inducible factor-1alpha (HIF-1alpha) is both a potential endogenous marker of tumor hypoxia and therapeutic target, and elevated HIF-1alpha protein levels have been shown to be associated with increased hypoxic radiation resistance in FaDu human pharyngeal carcinoma cells in vitro. Here, we found that in FaDu xenografts, no significant HIF-1alpha protein accumulation was detectable by either flow cytometry or Western blot, despite the presence of hypoxic (pimonidazole-positive, radiation resistant) cells. To investigate the effect of different tumor microenvironment conditions on hypoxic HIF-1alpha accumulation, we performed in vitro hypoxia experiments (0.1% O2, 24 h) with manipulation of pH (7.4 vs. 6.7), glucose (0-5.5 mM) and serum (0 or 10%) availability in FaDu and HT 1080 human fibrosarcoma cells. Hypoxic induction of HIF-1alpha protein was strongly dependent on glucose availability and largely abolished at 0.55 mM glucose or less in both cell lines. This glucose effect was confirmed in a hypoxia-responsive-element (HRE)/enhanced-green-fluorescent-protein (EGFP) reporter assay in transfected HT 1080 cells and possibly explains a lack of HIF-1alpha protein in hypoxic tumor cells.

Objective: To define the clinical, radiologic, and genetic features of periventricular heterotopia (PH) with Ehlers-Danlos syndrome (EDS)., Methods: Exonic sequencing and single stranded conformational polymorphism (SSCP) analysis was performed on affected individuals. Linkage analysis using microsatellite markers on the X-chromosome was performed on a single pedigree. Western blotting evaluated for loss of filamin A (FLNA) protein and Southern blotting assessed for any potential chromosome rearrangement in this region., Results: The authors report two familial cases and nine additional sporadic cases of the EDS-variant form of PH, which is characterized by nodular brain heterotopia, joint hypermobility, and development of aortic dilatation in early adulthood. MRI typically demonstrated bilateral nodular PH, indistinguishable from PH due to FLNA mutations. Exonic sequencing or SSCP analyses of FLNA revealed a 2762 delG single base pair deletion in one affected female. Another affected female harbored a C116 single point mutation, resulting in an A39G change. A third affected female had a 4147 delG single base pair deletion. One pedigree with no detectable exonic mutation demonstrated positive linkage to the FLNA locus Xq28, an affected individual in this family also had no detectable FLNA protein, but no chromosomal rearrangement was detected., Conclusion: These results suggest that the Ehlers-Danlos variant of periventricular heterotopia (PH), in part, represents an overlapping syndrome with X-linked dominant PH due to filamin A mutations.

Background/aims: To investigate possible relationships between ambulatory blood pressure (BP) and renal structure and function in type 2 diabetic patients., Methods: Renal biopsies were performed on 39 patients with urine albumin concentrations above 100 mg/l. BP was investigated with a 24-h, automated, portable BP device., Results: None of the patients in the study had signs of other renal disease than nephrosclerosis or diabetic nephropathy. Ten patients had slight, 13 intermediate, and 6 severe diabetic nephropathy on the renal biopsy. Among the remaining patients, 4 had normal microscopy findings and 6 had nephrosclerosis. The degree of albuminuria correlated to the systolic BP during the day (r = .43; P < .01) and night (r = .49; P < .01). The glomerular filtration rate (GFR) was associated with the systolic BP daytime (r = -.32; P < .05) and nighttime (r = -.47; P < .01). Neither degree of albuminuria nor GFR was associated with the diastolic BP levels. The degree of the glomerular pathology correlated to the systolic BP during daytime (P < .05), whereas the degree of interstitial fibrosis did not correlate to the BP levels., Conclusions: We have demonstrated that degree of albuminuria and GFR was significantly associated with daytime and nocturnal BP and glomerular structure with daytime BP. Furthermore, no renal disease other than diabetic nephropathy was found.

Prognostic factors and the role of post-operative radiotherapy (PORT) in patients with pN1 nodal stage following surgery for NSCLC were identified. The clinical course of 211 patients with pN1 nodal involvement following thoracic surgery were reviewed, 97 of them received PORT. Multi-variate survival analysis with respect to prognostic factors (including treatment) was performed. The most frequent site of recurrence was the ipsilateral bronchus-stump or hilus (63% of recurrences). The 5-year rate of intercurrent deaths for PORT was 1% vs 6% in the group without PORT. The 5-year rate of locoregional recurrence was similar (24% vs 19%) for PORT vs no PORT (p=0.97). PORT patients had a higher rate of distant metastases (p=0.04). The 5-year rate of overall survival was 45% without PORT and 25% with PORT (p=0.003). Multivariate survival analysis identified 4 prognostic factors associated with decreased survival rate: age, extended pneumectomy, number of involved nodes and PORT dose. A PORT dose of 50 Gy corresponds to an increase in relative risk of death in the range of 1.5. Patients with PORT do not have an increased rate of intercurrent deaths. However in this cohort, PORT in pN1 patients was associated with a decreased survival rate due to distant metastases. Even after correction with respect to accepted prognostic factors in multivariate survival analysis, PORT was not able to improve or equalize prognosis of these negatively selected patients. The main site of recurrence is the bronchial stump and hilus. If PORT is applied in pN1 patients, a reduction of the target volume should be discussed since local control in high-risk patients may be of relevance.

Background and Purpose: Recommendations for radiation ports in adjuvant radiation therapy for rectal cancer are mainly based on analysis of recurrence patterns. To evaluate whether changes in surgical technique have influenced this pattern of recurrence, a multicenter retrospective analysis was carried out on a patient population treated recently., Patients and Methods: 123 patients were evaluated with the help of a CT-based self-developed 3-D data file system and an extensive questionnaire. Major inclusion criteria (one sufficient) for eligibility were: histological confirmation, clear bone destruction, and a positive PET scan, or at least three minor criteria: progressive soft tissue mass, invasion of adjacent organs on follow-up CT or MRI, rising tumor markers, and typical appearance in cross-sectional imaging. Clinical or serologic signs of inflammation were exclusion criteria., Results: Initially, 54% of the evaluated patients were N0; in the remainder, N1 and N2 were distributed evenly. Initial T-category was T1 in 2%, T2 in 24%, T3 in 60%, and T4 in 13%, the male-to-female ratio was 2:1. Recurrent tumors were mainly situated in the posterior part of the bony pelvis as displayed in the figures. When abdominoperineal resection was compared to low anterior resection as primary operation, there was a significant difference in extension of recurrent tumors in the inferior parts of the pelvis (p<0.025 in all statistical tests applied), whereas no significant difference was found in the superior parts of the pelvis., Conclusion: Based on these results, a modest field size reduction in adjuvant radiotherapy for rectal cancer seems feasible, offering the perspective of a reduction in acute and late side effects.

Objective: To investigate the proportion of women with findings characteristic for pre-eclampsia, as opposed to renal disease, in a controlled study of hypertensive pregnant women undergoing antepartum renal biopsy., Design: An observational prospective controlled study., Setting: University Hospital of Lund, Sweden., Sample: Thirty-six previously healthy women with hypertensive disease in pregnancy, consecutively admitted to the antenatal ward at onset of disease during a 20 month period and giving informed consent, as well as 12 voluntary healthy pregnant controls., Methods: Renal biopsy samples were obtained from all participants and evaluated by light microscopy, electron microscopy and immunofluorescence techniques., Main Outcome Measures: Presence and degree of glomerular endotheliosis., Results: Glomerular endotheliosis was present in all women with pre-eclampsia and gestational hypertension, and in 5 of the 12 controls, although significant differences in the degree of endotheliosis were found between the groups. Clinically undetected renal disease was not diagnosed in any of the women., Conclusion: Glomerular endotheliosis was found in women with normal pregnancy as well as in both non-proteinuric and proteinuric hypertension and is consequently not, as earlier believed, pathognomonic for pre-eclampsia. The transition between normal term pregnancy, gestational hypertension and pre-eclampsia appears to be a continuous process, perhaps of increasing adaptation to pregnancy. Pre-eclampsia may be the extreme of the adaptational process, rather than a separate abnormal condition. Clinically undetected renal disease could be a rare cause of hypertension in pregnancy.

Objective: To study the correlation between serum cystatin C levels and renal structural changes in normal, hypertensive and pre-eclamptic pregnancy to evaluate it as a marker of the degree of renal involvement in pre-eclampsia., Design: An observational prospective study., Setting: University Hospital of Lund, Sweden., Sample: Thirty-six women with hypertensive disease in pregnancy and 12 healthy pregnant women in the third trimester recruited from maternal health care centres in the catchment area of the hospital., Methods: Renal biopsy samples were obtained from all participants and the degree of endotheliosis as well as the mean glomerular volume was evaluated by light microscopy in silver methenamin-stained sections. Serum cystatin C levels were measured and correlated to the structural changes., Main Outcome Measures: Correlation among degree of glomerular endotheliosis, glomerular volume and serum cystatin C., Results: Serum cystatin C levels differed between the different degrees of endotheliosis, showing a highly significant increasing linear trend. They also correlated significantly with glomerular volume (r = 0.60, P < 0.001). Mean serum urate and creatinine levels also increased with the degree of endotheliosis, but not above the reference interval for normal term pregnancy, even in pre-eclamptic women., Conclusion: Serum cystatin C may be used as a marker, not only for impaired renal function, but also for the degree of glomerular endotheliosis and increase in glomerular volume in pregnancy. It may be of value in the monitoring of pregnancies complicated by pre-eclampsia.

Surface electromyography (sEMG) is an important tool to estimate muscular activity at work. There is, however, a great inter-individual variation, even in carefully standardized work tasks. The sEMG signal is attenuated in the subcutaneous tissues, differently for each subject, which requires normalization. This is commonly made in relation to a reference contraction, which by itself, however, introduces a variance. A normalization method that is independent of individual motivation, motor control and pain inhibition would be desirable. The aim of the study was to explore the influence of the subcutaneous tissue thickness on sEMG amplitude. Ultrasound measurements of the muscle to skin surface distance were made bilaterally over the trapezius muscle in 12 females. Skinfold caliper measurements from these sites, as well as from four other sites, were made, body mass index (BMI) was recorded, and sEMG was recorded at maximal and submaximal contractions. The muscle-electrode distance, as measured by ultrasound, explained 33% and 31% (on the dominant and non-dominant sides respectively) of the variance of the sEMG activity at a standardized submaximal contraction (average between the sides, 46%); for maximal contractions the explained variance was 21%. Trapezius skinfold measurements showed poor correlations with sEMG. Instead, the mean of skinfold measurements from other sites explained as much as 68% (submaximal contraction). The corresponding figure for BMI was 67%. In conclusion, skinfold thickness explains a major part of the inter-individual variance in sEMG amplitude, and normalization to this measure is a possibility worth further evaluation.

Background: To evaluate the effect of paclitaxel/cisplatin induction chemotherapy (ICHT) and CT-based radiotherapy (RT) on larynx preservation, tumor control, and survival in patients with larynx/hypopharynx carcinoma eligible for total laryngectomy (TL) or TL plus partial pharyngectomy (TLPP)., Patients and Methods: Fifty patients eligible for TL or TLPP were enrolled onto a prospective study and treated with ICHT (200 mg/m(2) paclitaxel, 100 mg/m(2) cisplatin; day 1, 22). In patients with complete or partial tumor response RT (69.9 Gy in 5.5 weeks at the gross tumor, 50.4 Gy in the lymphatic drainage; single dose: 1.8 Gy, concomitant boost: 1.5 Gy) was applied. Non-responders had TL/TLPP and RT with total doses adapted to the radicality of tumor resection (56-70 Gy)., Results: The response rate to ICHT was 88% (10% complete, 78% partial response). At a median follow-up period of 25 months the larynx preservation rate was 84%. The 2-year local-regional control rate was 91% and the 2-year overall survival rate was 72.3%. The 3-year estimate to survive with functional larynx is 60%., Conclusion: In a large portion of patients eligible for TL or TLPP the larynx was preserved by paclitaxel/cisplatin ICHT and 3D RT.

Purpose: To determine whether a little dose to a large normal lung volume or a high dose to a small lung volume is more critical for induction of clinical pneumonitis. The second question is if dose-volume histogram (DVH) parameters are more reliable, if the lungs are analyzed as separate organs or as a whole organ., Patients and Methods: We analyzed the clinical and DVH data from 49 patients treated for a thoracic malignancy using 3-D conformal treatment plans. 18 patients had developed a clinical pneumonitis (CTC II or III). The majority of patients (n = 48) received radiochemotherapy for non-small-cell lung cancer (NSCLC) with a combination of paclitaxel and carboplatin. Patients were generally treated 5 fx/week, single dose 2 Gy, using a two-series approach (shrinking field) up to a total dose of 60-70 Gy. For every individual patient, the overall dose distribution was recalculated in the Helax-TMS by means of adding dose plans according to the total dose applied in each series. The lungs were defined both as separate organs and as a whole organ. Low-dose volume (< or = 10 Gy, Vlow), moderate-dose volume (> 10-40 Gy, Vmod) and high-dose volume (> 40 Gy, Vhigh), as well as V10-V40 and mean lung dose (MLD) were defined from the cumulative DVH. Dose-effect relationships were fitted with a logistic regression model., Results: Manifestation of clinical pneumonitis was within 3 months from termination of irradiation in all cases. For the ipsilateral lung, the incidence of pneumonitis was closely correlated to Vhigh. The pneumonitis rate increased from 13% up to 60%. By contrast, with increasing Vlow the pneumonitis rate dropped to < 10%. A similar but less pronounced effect was seen for the total lung. The lung volumes Vlow, Vmod and Vhigh of the ipsilateral, contralateral and whole lung were significantly correlated to the corresponding MLD. The incidence of pneumonitis increased with increasing MLD for the ipsilateral lung with a D50 of 32 Gy and a gamma 50 of 0.98. For the whole lung, the observed increase was less steep. MLD showed a close correlation to NTCP calculated by the Kutcher model. However, NTCP calculation overestimated the pneumonitis risk for the ipsilateral lung and underestimated the risk for the whole lung due to the steeper gradient. The logistic regression curve for the DVH parameters V10-V40 showed an increase of steepness toward higher doses. From the logistic regression curves, a DVH template indicating critical borders of V10-V40 was generated for the ipsilateral as well as for the total lung., Conclusion: Our data indicate that it is reasonable to disperse the dose outside the target volume over large areas in order to reduce the volumes of lung receiving > 40 Gy. Reducing the high-dose volume reduces the pneumonitis rate more than a corresponding reduction in the low-dose regions of the DVH. Landmarks for DVH optimization as defined in this analysis may serve as a basis for DVH contrains in IMRT planning. Separate organ analysis produced more reliable results and should be preferred to whole-organ analysis, if techniques mainly involving one side of the lung are applied. Further validation of these constraints is necessary prior to general recommendation.

Purpose: Type II cells and the surfactant system have been proposed to play a central role in pathogenesis of radiation pneumonitis. We analyzed the secretory function and proliferation parameters of alveolar type II cells in the early (until 24 h) and late phase (1-5 weeks) after irradiation (RT) in vitro and in vivo., Methods and Materials: Type II cells were isolated from rats according to the method of Dobbs. Stimulation of secretion was induced with terbutaline, adenosine triphosphate (ATP), and 12-O-tetradecanoylphorbol-13-acetate (TPA) for a 2-h period. Determination of secretion was performed using (3)H-labeled phosphatidylcholine. For the early-phase analysis, freshly isolated and adherent type II cells were irradiated in vitro with 9-21 Gy (stepwise increase of 3 Gy). Secretion stimulation was initiated 1, 6, 24, and 48 h after RT. For late-phase analysis, type II cells were isolated 1-5 weeks after 18 Gy whole lung or sham RT. Each experiment was repeated at least fivefold. Flow cytometry was used to determine cell cycle distribution and proliferating cell nuclear antigen index., Results: During the early-phase (in vitro) analysis, we found a normal stimulation of surfactant secretion in irradiated, as well as unirradiated, cells. No change in basal secretion and no dose effect were seen. During the late phase, 1-5 weeks after whole lung RT, we observed enhanced secretory activity for all secretagogues and a small increase in basal secretion in Weeks 3 and 4 (pneumonitis phase) compared with controls. The total number of isolated type II cells, as well as the rate of viable cells, decreased after the second post-RT week. Cell cycle alterations suggesting an irreversible G(2)/M block occurred in the second post-RT week and did not resolve during the observation period. The proliferating cell nuclear antigen index of type II cells from irradiated rats did not differ from that of controls., Conclusion: In contrast to literature data, we observed no direct effect of radiation on secretory activity in the early phase after RT. In our study of isolated type II cells, as well as in intact animals, RT did not result in an impaired surfactant secretion up to 5 weeks after RT. Our in vivo experiments even showed an increased response of phosphatidylcholine secretion to all known secretagogues at Weeks 3 and 4 after whole lung RT, possibly due to inflammatory cytokines. Cell cycle alterations with G(2)/M block and cell loss in the late post-RT period may contribute more to the manifestation of radiation-induced lung damage than functional impairment in type II cells.

Single deletions of mitochondrial DNA (mtDNA) are associated with three major clinical conditions: Kearns-Sayre syndrome, a multisystem disorder; Pearson syndrome (PS), a disorder of the hematopoietic system; and progressive external ophthalmoplegia (PEO), primarily affecting the ocular muscles. Typically, single mtDNA deletions are sporadic events, since the mothers, siblings, and offspring of affected individuals are unaffected. We studied a woman who presented with PEO, ptosis, and weakness of pharyngeal, facial, neck, and limb muscles. She had two unaffected children, but another of her children, an infant son, had sideroblastic anemia, was diagnosed with PS, and died at age 1 year. Morphological analysis of a muscle biopsy sample from the mother showed cytochrome c oxidase-negative ragged-red fibers-a typical pattern in patients with mtDNA deletions. Southern blot analysis using multiple restriction endonucleases and probed with multiple mtDNA fragments showed that both the mother and her infant son harbored an identical 5,355-bp single deletion in mtDNA, without flanking direct repeats. The deletion was the only abnormal species of mtDNA identified in both patients, and there was no evidence for duplications. We conclude that, although the vast majority of single large-scale deletions in mtDNA are sporadic, in rare cases, single deletions can be transmitted through the germline.

Background: To evaluate the influence of total dose and tumor volume on local control and survival in primary radiotherapy of non-small-cell lung cancer (NSCLC)., Methods and Materials: We retrospectively analyzed the clinical course and CT-derived pre- and post-therapeutic tumor volume data of 135 patients with NSCLC undergoing primary radiotherapy at our department between 1989 and 1996. Among these, a total of 192 spatially separated tumor volumes (135 primary tumors, 1 additional intrapulmonary tumor, and 56 involved lymph nodes) were available for analysis. In all patients, treatment was planned using CT-based three-dimensional treatment planning. The dose to each tumor volume was derived from the individual dose plans. Mean total dose was 59.9 Gy (range: 30-80 Gy). All but 3 patients were followed until death. For local control analysis, each tumor was analyzed separately, and its remission status was determined in serial follow-up CT scans. A total of 784 CT scans were analyzed. Actuarial local control analysis was performed for the 192 separated tumor volumes, and survival analysis was performed for the 135 patients. Tumor control probability was calculated using a Poisson statistical model., Results: Overall 1- and 2-year local control rate was 50% and 37%, respectively. The 2-year local control rate for tumors <50 ccm, 50-200 ccm, and >200 ccm was 51%, 22%, and 10%, respectively (p = 0.02). The 2-year local control rate for dose levels < or = 60 Gy and >60 Gy was 28% and 43% (p < 0.001). For the subgroup of 147 tumors smaller than 100 ccm, the local control rate increased up to 70% (1 year) and 51% (2 years) with doses of more than 60 Gy. For tumors larger than 100 ccm, no dose effect was seen. Only 2 of 45 tumors >100 ccm were controlled more than 2 years. Multivariate analysis revealed tumor volume, total dose, histopathologic type, and grading as significant and independent prognostic factors for local control. The number of delay days by split course (if used) and application of chemotherapy was not found to influence local control. Overall 1- and 2-year survival rate was 42% and 13%. Total radiation dose, chemotherapy, and T and N stage---but not tumor volume---were found to be independent and significant prognostic factors for survival in multivariate analysis., Conclusion: Tumor volume is an important predictor of local control in NSCLC. We found a clear dose effect for local control and survival in NSCLC. Long-term local control for a significant proportion of patients seems possible for small tumors only (<100 ccm, i.e., maximum diameter 6 cm) with doses of 70 Gy and more. Tumors of > or = 100 ccm are unlikely to be controlled long term by conventional doses up to 70 Gy. These results support dose escalation in patients with NSCLC.

Renal biopsies were obtained from type 2 diabetic patients with elevated albumin excretion. The aim was to obtain quantitative structural data to correlate with clinical findings. Biopsies from 27 diabetic patients and 12 non-diabetic cases were analysed. Stereological methods were applied by light- and electron microscopy. Diabetic patients showed quantitatively markedly expressed diabetic glomerulopathy, but also an increase in glomerular volume, in prevalence of new-vessel formation at the vascular pole, prevalence of glomerular occlusion and in interstitial volume fraction. A significant correlation was not observed between the degree of interstitial and glomerular involvement. The glomerular hypertrophy is interpreted as a compensatory phenomenon, leading to preservation of filtration surface in the open glomeruli. Close correlation was seen between glomerulopathy and glomerular function, and also with the stage of retinopathy. New vessel formation at the vascular pole was most frequent in patients with proliferative retinopathy. Signs of non-diabetic glomerulopathy were not observed, but various atypical ultrastructural changes accompanying the advanced stages are illustrated. Our present findings correspond to data from type I diabetic patients. It is emphasised that all compartments of the kidney are affected by the diabetic state. It is suggested that the interstitial and glomerular lesions are influenced by different factors.